Endocrinology

ENDOCRINOLOGY
D r. R . S i lve r
Jo d i e B u rto n an d Am i sh P ari kh , e d i to rs
E yal C o h e n , asso ci ate e d i to r
DISORDERS OF GLUCOSE METABOLISM. . . . . 2
D iab e te s M e llitu s
C o m p licatio n s o f D iab e te s
Tre atm e n t o f D iab e te s
D iab e tic K e to acid o sis
H yp e ro sm o lar N o n ke to tic H yp e rglyce m ic S yn d ro m e
H yp o glyce m ia
S yn d ro m e X - In su lin R e sistan ce S yn d ro m e
DYSLIPIDEMIAS . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
L ip o p ro te in P h ysio lo gy
S e co n d ary C au se o f H yp e rlip id e m ias
Ap p ro ach to D yslip id e m ias
Tre atm e n t o f D yslip id e m ias
OBESITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
OVERVIEW OF HORMONES. . . . . . . . . . . . . . . . . . 15
PITUITARY GLAND . . . . . .. . . . . . . . . . . . . . . . . . . . 15
G ro wth H o rm o n e
P ro lactin
L H an d F S H
An tid iu re tic H o rm o n e
O xyto cin
P itu itary Tu m o u rs
H yp o p itu itarism
THYROID. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
T S H
T h yro id H o rm o n e s
Te sts o f T h yro id F u n ctio n
Te sts o f T h yro id S tru ctu re
H yp e rth yro id ism
A. G rave s D ise ase
B . S u b acu te T h yro id itis
C . To xic N o d u lar G o itre
D . P o stp artu m T h yro id itis
E . T h yro to xic S to rm
H yp o th yro id ism
A. C o n ge n ital H yp o th yro id ism
B . H ash im o to s T h yro id itis
C . R ie d e l s S tru m a
D . M yxe d e m a C o m a
E . S ick E u th yro id S yn d ro m e
N o n -to xic G o itre
T h yro id N o d u le s
T h yro id M align an cie s
M C C Q E 2000 R e vi e w N o te s an d L e ctu re S e ri e s E n d o cri n o lo gy 1
ADRENAL CORTEX . . . . . . . . . . . . . . . . . . . . . 28
AC T H
C o rtical H o rm o n e s
Te sts o f Ad re n o co rtical F u n ctio n
H yp e rald o ste ro n ism
C u sh in g s S yn d ro m e
C o n ge n ital Ad re n al H yp e rp lasia
H irsu tism an d Virilizatio n
Ad re n o co rtical In su fficie n cy
ADRENAL MEDULLA. . . . . . . . . . . . . . . . . . . . 36
P h e o ch ro m o cyto m a
MULTIPLE ENDOCRINE NEOPLASIA. . . . . 37
CALCIUM DISORDERS. . . . . . . . . . . . . . . . . . . 37
C alciu m H o m e o stasis
H yp e rcalce m ia
H yp o calce m ia
METABOLIC BONE DISEASE . . . . . . . . . . . . 42
O ste o p o ro sis
O ste o m alacia an d R icke ts
R e n al O ste o d ystro p h y
P age t s D ise ase o f B o n e
REPRODUCTIVE ENDOCRINOLOGY. . . . . . 46
Te sts o f Te sticu lar F u n ctio n
M ale G o n ad al D iso rd e rs
A. M ale H yp o go n ad ism
B . M ale In fe rtility
C . E re ctile D ysfu n ctio n
D . G yn e co m astia
Ab n o rm alitie s o f P u b e rty
COMMON MEDICATIONS USED IN . . . . . . . 49
ENDOCRINOLOGY
E n d o cri n o lo gy 2 M C C Q E 2000 R e vi e w N o te s an d L e ctu re S e ri e s
N o te s
DISORDERS OF GLUCOSE
METABOLISM
DIABETES MELLITUS
J d iagn o sis co n firm with te st o n an o th e r d ay)
sym p to m s o f d iab e te s p o lyu ria, p o lyd ip sia, we igh t lo ss,
n o ctu ria, p o lyp h agia, b lu rry visio n ) p lu s ran d o m p lasm a
glu co se 1 1 .1 m m o l/L O R
F B S 7.0 m m o l/L O R
p lasm a glu co se valu e 1 1 .1 d u rin g two h o u r O G T T
Clas s ification of Diabe te s Me llitus
Table 1. Comparis on of Type 1 and Type 2 Diabe te s
1. Type 1 Diabe te s 2. Type 2 Diabe te s
Etiology id io p ath ic ge n e tically-lin ke d
au to -im m u n e
Ons e t u su ally b e fo re age 40 u su ally afte r age 40
Body Habitus typ ically n o rm al to waste d typ ically o ve rwe igh t
Ris k Factors p e rso n al h isto ry o f au to im m u n e d ise ase s o b e sity
in cre ase s like lih o o d o f d e ve lo p in g D M fam ily h isto ry
race - H isp an ic, B lack an d N ative Am e rican
p rio r ab n o rm al glu co se to le ran ce
h yp e rte n sio n
h yp e rlip id e m ia
G D M
Ge ne tics asso ciate d with H L A D R 3, gre ate r h e ritab ility th an Typ e 1
D R 4 an d D Q alle le s 80-1 00% co n co rd an ce in m o n o zygo tic twin s
40% co n co rd an ce in m o n o zygo tic twin s
Pathophys iology co m p le te ly in su lin d e ficie n t ab n o rm al in su lin se cre tio n
in cre ase d in su lin re sistan ce in targe t tissu e s,
like ly d u e to re ce p to r an d p o st re ce p to r ab n o rm alitie s
in cre ase d h e p atic glu co n e o ge n e sis
Pharmacological in su lin re q u ire d co m b in atio n o f o ral h yp o glyce m ic age n ts in su lin
the rapy
Othe r p ro n e to ke to acid o sis n o t p ro n e to ke to acid o sis b u t p ro n e to
h yp e ro sm o lar co m a
3. Diabe te s Se condary to Spe cific Etiologie s
J ge n e tic d e fe cts/ syn d ro m e s
D o wn S yn d ro m e , Tu rn e r S yn d ro m e , H u n tin gto n d ise ase ,
ge n e tic d e fe cts in b e ta-ce ll fu n ctio n an d in su lin actio n
J d ise ase s o f th e e n d o crin e /e xo crin e p an cre as
p an cre atitis, n e o p lasia, cystic fib ro sis, h e m o ch ro m ato sis b ro n ze d d iab e te s)
J e n d o crin o p ath ie s
acro m e galy, C u sh in g's S yn d ro m e , glu cago n o m a, h yp e rth yro id ism
J d ru g-in d u ce d
b e ta-ago n ists, glu co co rtico id s, th iazid e s, p h e n yto in
J in fe ctio n s
cyto m e galo viru s, co n ge n ital ru b e lla
4. Ge s tational Diabe te s (GDM)
J D e fin itio n - glu co se in to le ran ce th at d e ve lo p s d u rin g p re gn an cy
J in cid e n ce
2-4% o f all p re gn an cie s
J risk facto rs
age > 25 m e m b e r o f h igh risk e th n ic gro u p
o b e sity p re vio u s G D M
1 re lative with D M p re vio u s m acro so m ic b ab y > 4 kg)
J scre e n in g an d d iagn o sis
an y p re gn an t wo m an with o n e o r m o re risk facto rs sh o u ld b e
scre e n e d at b e gin n in g o f th ird trim e ste r we e k 28)
N o te s
METABOLISM . . . CONT.
50 g glu co se ch alle n ge te st, m e asu rin g glu co se o n e h o u r late r
if ab n o rm al 7.8 m m o l/L ) , th e n 75 g o ral glu co se to le ran ce te st O G T T )
sh o u ld b e d o n e ; if an y two o f th e fo llo win g th re e valu e s are
m e t o r e xce e d e d , a d iagn o sis o f G D M is e stab lish e d :
fastin g glu co se 5.3 m m o l/L
1 h r valu e 1 0.6 m m o l/L
2 h r 8.9 m m o l/L
Fe tus
J m ate rn al h yp e rglyce m ia in d u ce s h yp e rin su lin e m ia in fe tu s
J re su lts in m acro so m ia in su lin acts as a gro wth facto r
J p ro n e to re sp irato ry d istre ss, n e o n atal h yp o glyce m ia,
h yp o calce m ia, h yp e rb iliru b in e m ia, p o lycyth e m ia, IU G R , sacral
age n e sis, card iac stru ctu ral d e fe cts, p re m atu rity
J p ro n e to co n ge n ital m alfo rm atio n if d iab e te s p re -d ate s p re gn an cy
Mothe r
J in cre ase d risk o f d e ve lo p in g su b se q u e n t Typ e 2 D M
J p ro gre ssio n o f d iab e tic re tin o p ath y an d n e p h ro p ath y
J m an age m e n t
p re co n ce p tio n care to n o rm alize H b A1 c
tigh t glu co se co n tro l sh o wn to d e cre ase b o th fe tal an d
m ate rn al co m p licatio n s)
o ral h yp o glyce m ics co n train d icate d
in su lin to m ain tain tigh t glyce m ic co n tro l if d ie t in ad e q u ate
fe tu s m u st b e m o n ito re d care fu lly
5. Impaire d Glucos e Tole rance (IGT) and Impaire d
Fas ting Glucos e (IFG)
J IF G is b e twe e n 6.1 an d 6.9 m m o l/L
J IG T is a 2 h o u r p o st-p ran d ial b e twe e n 7.8 an d 1 1 .1 afte r O G T T
with a fastin g glu co se o f < 7 m m o l/L
J 1 -5% p e r ye ar d e ve lo p D M
J 50-80% re ve rt to n o rm al glu co se to le ran ce
J we igh t lo ss m ay im p ro ve glu co se to le ran ce
J asso ciate d with p ro gre ssive ly gre ate r risk o f d e ve lo p in g m icro vascu lar an d
m acro vascu lar co m p licatio n s
COMPLICATIONS OF DIABETES
J th e m ajo rity o f co m p licatio n s in vo lve th e vascu lar syste m
m acro an gio p ath y an d m icro an gio p ath y
J aggravatin g facto rs: p o o r glyce m ic co n tro l, in ad e q u ate co n tro l o f
h yp e rte n sio n an d ch o le ste ro l, sm o kin g, h igh fat d ie t
Macroangiopathy
J acce le rate d ath e ro scle ro sis le ad in g to
co ro n ary arte ry d ise ase
stro ke
p e rip h e ral vascu lar d ise ase
J m o st co m m o n cau se o f d e ath in Typ e 2 D M
Microangiopathy
J m ajo r ch ro n ic co m p licatio n o f Typ e 1 an d Typ e 2 D M
J p ath o gn o m o n ic le sio n is b ase m e n t m e m b ran e th icke n in g
J classically cau se s re tin o p ath y, n e p h ro p ath y an d n e u ro p ath y
J can in vo lve m an y o th e r o rgan s, in clu d in g h e art an d skin
1. Re tinopathy se e O p h th alm o lo gy N o te s)
J e p id e m io lo gy
p re se n t in 50% o f p atie n ts afte r 1 0 ye ars with D M
o n e o f th e le ad in g cau se s o f b lin d n e ss in N o rth Am e rica
J typ e s
n o n -p ro life rative b ackgro u n d )
ge n e rally n o sym p to m s b u t m ay affe ct m acu la an d im p air visio n
m icro an e u rysm s, h ard e xu d ate s, d o t an d b lo t h e m o rrh age s
N o te s
p re -p ro life rative
1 0-40% p ro gre ss to p ro life rative with in o n e ye ar
m acu lar e d e m a, ve n o u s sh u n ts an d b e ad in g, n e rve
fib re laye r m icro in farcts co tto n wo o l sp o ts)
p ro life rative (s e e Color Atlas H13)
gre at risk fo r lo ss o f visio n
n e o vascu larizatio n , fib ro u s scarrin g, vitre al
d e tach m e n t, re tin al d e tach m e n t
J p re se n tatio n
asym p to m atic to co m p le te lo ss o f visio n
J p re ve n tio n an d m an age m e n t
tigh t glyce m ic co n tro l
p h o to co agu latio n
vitre cto m y
fre q u e n t fo llo w-u p visits with an o p h th alm o lo gist im m e d iate
re fe rral afte r d iagn o sis o f Typ e 2 D M )
2. Ne phropathy
d iab e te s-in d u ce d re n al failu re is th e m o st co m m o n cau se o f
re n al failu re in N o rth Am e rica
40% o f p e rso n s with Typ e 1 D M an d 4-20% with Typ e 2 D M
h ave p ro gre ssive n e p h ro p ath y
J p re se n tatio n
in itial ch an ge s in clu d e : in cre ase d G F R u p to 1 40%) , e n large d
kid n e ys, an d m icro alb u m in u ria
o ve r 1 5 ye ars, p ro gre sse s to cau se h yp e rte n sio n , p e rsiste n t
p ro te in u ria m acro alb u m in u ria) , n e p h ro tic syn d ro m e , re n al failu re
tigh t glu co se co n tro l
tigh t b lo o d p re ssu re co n tro l AC E in h ib ito rs sh o wn to
re d u ce n e p h ro p ath ic co m p licatio n s) an d calciu m ch an n e l b lo cke rs
lim it u se o f n e p h ro to xic d ru gs an d d ye s
p ro te in re strictio n co n tro ve rsial)
3. Ne uropathy
co m m o n in b o th Typ e 1 an d 2 D M
J p ath o p h ysio lo gy
m e tab o lic d e fe ct th o u gh t to b e in cre ase d so rb ito l o r
d e cre ase d m yo in o sito l
J typ e s
d istal sym m e tric glo ve an d sto ckin g p o lyn e u ro p ath y
au to n o m ic d ysfu n ctio n e .g. gastro p are sis)
m o n o n e u ro p ath y e .g. C arp al Tu n n e l S yn d ro m e )
J p re se n tatio n
p are sth e sias o r n e u ro p ath ic p ain
m o to r d e ficits in clu d in g cran ial n e rve s)
o rth o static h yp o te n sio n
im p o te n ce
vo id in g d ifficu ltie s
fo o t u lce rs
tigh t glu co se co n tro l
an ti-d e p re ssan ts e .g. am itrip tylin e ) , cap saicin , an d
an ti-e p ile p tics e .g. Te gre to l) fo r p ain fu l n e u ro p ath ic syn d ro m e s
e ryth ro m ycin , d o m p e rid o n e an d cisap rid e fo r gastro p are sis
Othe r
J o th e r co m p licatio n s o f D M in clu d e
skin d ise ase
b o n e an d jo in t d ise ase
cataracts
im p aire d wo u n d h e alin g
N o te s
TREATMENT OF DIABETES
J D iab e te s C o m p licatio n s C o n tro l Trial 1 993) d e m o n strate d a
50-70% d e cre ase in m icro vascu lar co m p licatio n s in Typ e 1 D M in
an in te n sive ly tre ate d gro u p as co m p are d to a co n ve n tio n ally
tre ate d gro u p
J U n ite d K in gd o m P ro sp e ctive D iab e te s S tu d y 1 998) - a stu d y o f
glyce m ic an d b lo o d p re ssu re co n tro l in Typ e 2 D M b e twe e n
in te n sive an d co n ve n tio n al tre atm e n t gro u p s
F in d in gs: d e cre ase in d iab e te s co m p licatio n s in in te n sive ly tre ate d
gro u p ; m arke d d e cre ase in vascu lar co m p licatio n s in th o se with
we ll co n tro lle d b lo o d p re ssu re
Die t
J e n e rgy in take to ach ie ve an d m ain tain d e sirab le we igh t
J o th e r re co m m e n d atio n s as p e r C an ad a's F o o d G u id e
Life s tyle
J re gu lar p h ysical e xe rcise can im p ro ve in su lin se n sitivity an d lo we r
lip id co n ce n tratio n s an d b lo o d p re ssu re
J sto p sm o kin g an d d e cre ase alco h o l co n su m p tio n
Oral Hypoglyce mic Age nts (OHA)
J m ain ly in Typ e 2 D M
Table 2. Oral Hypoglyce mics
Me dication Me chanis m of Action Side Effe cts Contraindications
Sulfonylure as stim u late re le ase o f e n d o ge n o u s in su lin h yp o glyce m ia h e p atic o r re n al
glyb u rid e D iab e ta) n au se a im p airm e n t
G I d isco m fo rt
Me glitimide s stim u late s re le ase o f e n d o ge n o u s in su lin h yp o glyce m ia
re p aglitim id e rap id actin g, b e tte r p o st-p ran d ial glu co se le ss fre q u e n t th an
G lu co n o rm ) co n tro l) S u lfo n ylu re as)
Biguanide s re d u ce s glu co n e o ge n e sis G I an o re xia, h e p atic o r re n al
m e tfo rm in n au se a, im p airm e n t
G lu co p h age ) d iarrh e a alco h o lism
d isco m fo rt) ad van ce d age
Thiazolidine dione s in su lin se n sitize r h e p ato to xicity
tro glitazo n e R e zu lin )
-Glucos idas e d e cre ase s th e ab so rp tio n o f carb o h yd rate s flatu le n ce
Inhibitors th u s d e cre ase s p o stp ran d ial rise o f glu co se ) ab d o m in al cram p in g
acarb o se P ran d ase ) d iarrh e a
Clinical Pe arl
J Sulfonyure as and Me glitimide s s que e ze e ndoge nous ins ulin from the pancre as
J Biguanide s and Thiazolidine dione s act primarily in pe riphe ral tis s ue s re mote from
the pancre as
Ins ulin se e Tab le 3 an d F igu re 1 )
J d o se s ad ju ste d fo r in d ivid u al p atie n t n e e d s to m e e t targe t glyce m ic co n tro l
J ad m in istratio n
su b cu tan e o u s in je ctio n s
co n tin u o u s su b cu tan e o u s in su lin in fu sio n p u m p
IV in fu sio n re gu lar in su lin o n ly)
J p re p aratio n s
u ltra-rap id H u m alo g)
rap id o r re gu lar To ro n to )
in te rm e d iate N o r N P H )
lo n g-actin g U o r U ltrale n te )
N o te s
J m u ltip le in je ctio n s o f m ixe d in su lin s u su ally n e ce ssary fo r o p tim al
glu co se co n tro l
J e stim ate o f to tal d aily in su lin re q u ire m e n t wh e n startin g an ad u lt
Typ e 1 d iab e te s p atie n t o n in su lin = 0.5 - 0.6 u n its/kg
Table 3. Kine tics of Diffe re nt Ins ulins
Ins ulin Duration Ons e t Pe ak Us ual Effe ctive Duration of
(hours ) (hours ) Action (hours )
Humalog v. sh o rt 5-1 0 m in 30-40 m in 2-3
re gular sh o rt 1 /2-1 1 -3 5-7
NPH/le nte in te rm e d iate 2-4 8-1 0 1 8-24
ultrale nte lo n g 4-5 25-36
Figure 1. Duration of Activity of Diffe re nt Ins ulins
Glucos e Monitoring
J fre q u e n t se lf-m o n ito rin g an d re co rd in g o f b lo o d glu co se is n o w
stan d ard m an age m e n t
Table 4. Laboratory Indicators of Glucos e Control
Se rum Glucos e Se rum Fructos amine Se rum HbA1c
Tim e S p an Im m e d iate 2-3 we e ks 3 m o n th s
R e fle cte d b y M e asu re m e n t se co n d s-m in u te s)
DIABETIC KETOACIDOSIS (DKA)
Pathophys iology
J in su lin d e ficie n cy co m b in e d with in cre ase d co u n te r-re gu lato ry
h o rm o n e s i.e . glu cago n , co rtiso l, G H , cate ch o lam in e s
J clin ically in vo lve s two facto rs: lack o f in su lin n o n -co m p lian ce ,
in ad e q u ate d o se , in itial p re se n tatio n o f D M ) an d /o r p re cip itan t
su rge ry, in fe ctio n , e m o tio n al stre ss)
J u n re stricte d h e p atic glu co se p ro d u ctio n > h yp e rglyce m ia
J lip o lysis re su ltin g in fre e fatty acid s > ke to acid s > acid o sis
J o sm o tic d iu re sis cau se s d e h yd ratio n an d e le ctro lyte ab n o rm alitie s
Clinical Fe ature s
J typ ical p atie n t: yo u n g Typ e 1 D M
J p re se n tatio n p re ce d e d b y p o lyu ria an d p o lyd ip sia
J L O C m ay b e d e cre ase d with h igh se ru m o sm o lality > 330 m o sm )
J d e h yd rate d an d ke to acid o tic
an o re xia, n au se a, vo m itin g, fatigu e
ab d o m in al p ain e sp e cially in ch ild re n )
K u ssm au l s re sp iratio n s rap id d e e p b re ath in g)
acti vi ty
h u m alo g
b re akfast lu n ch d i n n e r b e d
re gu lar
le n te an d N P H
ultralente
N o te s
Inve s tigations and Laboratory Findings
J p lasm a glu co se , e le ctro lyte s, cre atin in e , B U N , ke to n e s
J u rin e glu co se an d ke to n e s
J h yp e rglyce m ia an d ke to n e m ia
b lo o d glu co se e le vate d
ke to n e s in ran ge o f 1 5 m m o l/L
J wid e an io n gap m e tab o lic acid o sis p H 7.3 an d /o r H C O 3 1 5) p lu s
p o ssib le se co n d ary re sp irato ry alkalo sis d u e to K u ssm au l s re sp iratio n s;
can also h ave m e tab o lic alkalo sis fro m vo m itin g an d d e h yd ratio n
Tre atme nt
J rap id d iagn o sis an d clo se m e d ical su p e rvisio n are e sse n tial
J in ge n e ral, m o n ito r d e gre e o f ke to acid o sis with an io n gap , n o t
b lo o d glu co se o r ke to n e le ve l
J re h yd ratio n
critical in o rd e r to m ain tain ad e q u ate card iac o u tp u t an d
re n al fu n ctio n
b o lu s o f n o rm al salin e in itially fo llo we d b y h igh rate n o rm al
salin e in fu sio n
ab o u t 400 m E q N a
+
is lo st in th e u rin e d u e to b u ffe rin g o f
ke to n e acid an io n s, h yp e rglu cago n e m ia an d h yp o in su lin e m ia
le ad in g to d ire ct re n al e xcre tio n , an d to a le sse r e xte n t as p art
o f th e o sm o tic d iu re sis in d u ce d b y glyco su ria
J in su lin
in itial b o lu s o f 5-1 0 U o r 0.1 U /kg) IV in ad u lts
fo llo we d b y co n tin u o u s in fu sio n at 5-1 0 U o r 0.1 U /kg) p e r h o u r
wh e n b lo o d glu co se 1 5 m m o l/L ad d D 5W
J p o tassiu m
avo id h yp o kale m ia
K
+
lo st fro m ce lls d u e to in su lin d e ficie n cy an d ge n e ral catab o lic state
b lo o d le ve ls d o n o t re fle ct to tal b o d y lo sse s wh ich m ay b e
400-500 m E q
K
+
falls d u rin g tre atm e n t d u e to re h yd ratio n an d in su lin
actio n d rive s K
+
in to ce lls)
n o rm al o r lo w K
+
le ve l in itially in d icate s se ve re d e ficie n cy
an d re q u ire s card iac m o n ito rin g
re p lace as p o tassiu m ch lo rid e
J b icarb o n ate
avo id givin g u n le ss situ atio n is life -th re ate n in g an d /o r sh o ck
co rre ct o n ly p artially e .g. 1 to 2 am p o u le s)
J tre atm e n t o f p re cip itatin g cau se with p atie n t e d u catio n to p re ve n t
fu rth e r e p iso d e s o f D K A
J o th e r
fo r th e d e ve lo p m e n t o f ce re b ral e d e m a, tre at with m an n ito l
Prognos is
J 2-5% m o rtality in d e ve lo p e d co u n trie s
J se rio u s m o rb id ity an d m o rtality o fte n re su lt fro m
se p sis
p u lm o n ary an d card io vascu lar co m p licatio n s
th ro m b o e m b o lic co m p licatio n s
ce re b ral e d e m a
HYPEROSMOLAR NONKETOTIC HYPERGLYCEMIC
SYNDROME
Etiology
J u su ally co m p licatio n o f Typ e 2 D M
J p ro fo u n d d e h yd ratio n re su ltin g fro m h yp e rglyce m ia
J p re cip itatin g e ve n ts: in fe ctio n , stro ke , M I, trau m a, d ru gs glu co co rtico id s,
im m u n o su p p re ssive s, d iu re tics) , m e d ical p ro ce d u re s d ialysis) , b u rn s
Clinical Fe ature s
J e xtre m e h yp e rglyce m ia, h yp e ro sm o lality, vo lu m e d e p le tio n an d C N S sign s
N o te s
Lab Findings
J h igh u rin e glu co se , n e gative o r lo w ke to n e s
J B G o fte n > 55 m m o l/L , b u t n o t a go o d in d icato r o f se ve rity
J u rin e n e gative fo r ke to n e s; b lo o d ke to n e s re fle ct o n ly starvatio n
ke to sis
J h igh se ru m o sm o lality
J e le ctro lyte s m ay sh o w sp u rio u s h yp o n atre m ia d e cre ase in
3 m E q /L N a
+
fo r e ve ry 1 0 m m o l/L in cre ase in glu co se )
J n o n ke to tic m ixe d m e tab o lic acid o sis m ay b e p re se n t d u e to o th e r
acu te u n d e rlyin g co n d itio n s se p sis, re n al failu re , lactic acid o sis)
Tre atme nt
J re h yd ratio n with N S to re sto re in travascu lar vo lu m e , th e n 1 /2 N S
J id e n tify an d tre at p re cip itatin g cau se s)
J in su lin 0.1 U /kg/h o u r m ay o r m ay n o t b e n e ce ssary
J ce re b ral e d e m a m ay re su lt if o sm o lality is tre ate d to o aggre ssive ly
J o ve rall m o rtality h igh > 50%)
HYPOGLYCEMIA
De finition
J fastin g se ru m glu co se b e lo w a ce rtain le ve l se e b e lo w) P L U S
n e u ro glyco p e n ic sym p to m s O R
ad re n e rgic sym p to m s au to n o m ic re sp o n se )
J typ ical crite ria fo r fastin g se ru m glu co se is
< 2.8 m m o l/L in m ale s
< 2.3 m m o l/L in fe m ale s
Clinical Fe ature s of Hypoglyce mia
J ad re n e rgic sym p to m s typ ically o ccu r first)
p alp itatio n s, swe atin g, an xie ty, h u n ge r, tre m o u rs, tach ycard ia
J n e u ro glyco p e n ic sym p to m s
h e ad ach e , m e n tal d u lln e ss, fatigu e , co n fu sio n , am n e sia,
se izu re s, co m a
Type s
Pos tprandial (Re active ) Hypoglyce mia
J o ccu rs 1 .5-6 h o u rs afte r a m e al an d re co ve rs sp o n tan e o u sly
J m an ife ste d p rim arily as ad re n e rgic sym p to m s d u e to au to n o m ic d isch arge
J th o u gh t to b e o ve r-d iagn o se d an d o ve r-tre ate d
e tio lo gy
alim e n tary h yp e rin su lin ism
J p o st G I su rge ry gastre cto m y, p ylo ro p lasty, vago to m y)
m ay also b e in d u ce d b y galacto se m ia an d fru cto se in to le ran ce
tre atm e n t
fre q u e n t, sm all fe e d s
we igh t lo ss
Fas ting Hypoglyce mia
J im b alan ce b e twe e n p ro d u ctio n o f glu co se b y live r an d
u tilizatio n in p e rip h e ral tissu e s
im p lie s
d e fe ctive glu co n e o ge n e sis
d e fe ctive glyco ge n o lysis with in ab ility to m ain tain
glu co se co n ce n tratio n if fo o d is with h e ld
e xce ssive u tilizatio n o f glu co se
e tio lo gy
im p aire d p ro d u ctio n o f glu co se
h o rm o n e d e ficie n cie s h yp o p itu itarism , ad re n al
in su fficie n cy, in ad e q u ate cate ch o lam in e s, glu cago n )
e n zym e d e fe cts
su b strate d e ficie n cy
live r d ise ase cirrh o sis, u re m ia)
d ru gs e th an o l, p ro p ran o lo l, salicylate s)
N o te s
J o ve r-u tilizatio n o f glu co se
h yp e rin su lin ism in su lin o m a, su lfo n ylu re a, e xo ge n o u s
in su lin , se p sis)
ap p ro p riate in su lin le ve ls e xtrap an cre atic tu m o u rs)
tre at u n d e rlyin g cau se
SYNDROME X - INSULIN RESISTANCE SYNDROME
J p o stu late d syn d ro m e re late d to in su lin re sistan ce
asso ciatio n b e twe e n glu co se in to le ran ce , h yp e rin su lin e m ia,
h yp e rte n sio n , ce n tral o b e sity, an d d yslip id e m ia e le vate d
L D L -ch o l, VL D L -ch o l an d T G s an d re d u ce d H D L -ch o l)
J Typ e 2 D M is o n ly o n e m an ife statio n o f th e o ve rall syn d ro m e
J o b e sity aggravate s e xte n t o f in su lin re sistan ce
J co m p licatio n s in clu d e ath e ro scle ro sis, co ro n ary arte ry d ise ase ,
stro ke an d m yo card ial in farctio n
DYSLIPIDEMIAS
J m e tab o lic d iso rd e rs ch aracte rize d b y e le vatio n s o f fastin g p lasm a
ch o le ste ro l an d /o r triglyce rid e s T G s) , an d /o r lo w H D L ch o le ste ro l
LIPOPROTEIN PHYSIOLOGY
Exoge nous Pathway
J ch ylo m icro n s carry d ie tary so u rce o f trigylce rid e s T G ) an d are
h yd ro lyze d b y lip o p ro te in lip ase L P L ) re le asin g fatty acid s,
ap o p ro te in s, an d ch o le ste ro l
J re m ain in g ch ylo m icro n re m n an t d e live rs ch o le ste ro l to live r
fo r b ile acid
Endoge nous Pathway
J ve ry lo w d e n sity lip o p ro te in s VL D L ) carry T G syn th e size d fro m
glu co se an d d ie tary sh o rt-ch ain fre e fatty acid s F FA)
J VL D L are h yd ro lyze d b y L P L to VL D L re m n an t, re le asin g F FA,
p h o sp h o lip id s, ap o p ro te in s, an d ch o le ste ro l
J VL D L re m n an t is fu rth e r h yd ro lyze d b y h e p atic lip ase H L ) to ID L ,
th e n L D L
J L D L is take n u p b y live r an d o th e r tissu e s an d is th e m ajo r so u rce
o f ch o le ste ro l to e xtrah e p atic tissu e s
High De ns ity Lipoprote in (HDL)
J acce p ts ch o le ste ro l fro m ce lls an d ab o ve lip o p ro te in s
J h e lp s m ain tain ch o le ste ro l b alan ce an d is th e m ain e ffe cto r o f
ch o le ste ro l tran sp o rt o u t o f ce lls
E n d o cri n o lo gy 1 0 M C C Q E 2000 R e vi e w N o te s an d L e ctu re S e ri e s
N o te s
DYSLIPIDEMIAS . . . CONT.
Figure 2. Lipid Inte rconve rs ions
Reprintedwith permission fromIsselbacher, K.J. HarrisonsPrinciplesof Internal Medicine. 13th edition. McGraw-Hill Inc. 1994.
Table 5. Abnormal Lipid Value s (mmol/L)
LDL TG HDL
mild 3.4-4.1 2.3-4.0 0.6-0.95
mode rate 4.1 -4.9 4.0-1 0.0
marke d > 4.9 > 1 0.0 < 0.6
Table 6. Hype rlipide mias
Hype rlipide mia Lipid Abnormalitie s Clinical Outcome s
1.Hype rchole s te re mias
a) F am ilial H yp e rch o le ste re m ia IIa 8L D L se co n d ary to - h o m o zygo te s m an ife st C AD
- au to so m al d o m in an t L D L re ce p to r d e fe cts an d o th e r vascu lar d ise ase in
8to tal ch o le ste ro l ch ild h o o d an d d ie
- h e te ro zygo te s d e ve lo p C AD an d 50%
ch an ce M I b y 30 in m e n 1 0-20%)
- te n d o n o u s xan th o m ata,
xan th e lasm as, co rn e al arcu s
b ) P o lyge n ic h yp e rch o le ste re m ia IIa 8L D L - asym p to m atic u n til vascu lar
8to tal ch o le ste ro l d ise ase d e ve lo p s
2.Hype rtriglycide mias
a) F am ilial H yp e rtriglyce rid e m ia IV 8VL D L - 8risk p re m atu re ath e ro scle ro sis
8T G - e xp re sse d in e arly ad u lth o o d , triad o f
o b e sity, h yp e rtriglyce rid e m ia, an d
h yp e rin su lin e m ia, also h yp e ru rice m ia
b ) F am ilial L ip o p ro te in L ip ase I, V 8ch ylo m icro n s - asso ciate d with h e p ato sp le n o m e galy,
D e ficie n cy 8T G lip e m ia re tin alis, e ru p tive xan th o m ata,
p an cre atitis o r can b e asyp to m atic
3. Combine d Dis orde rs
a) F am ilial C o m b in e d IIb 8VL D L , 8L D L - iso late d T G o r ch o l in cre ase
H yp e rlip id e m ia 8ch o le ste ro l, 8T G - C AD an d o th e r vascu lar p ro b le m s
b u t o th e rwise asym p to m atic
b ) D ysb e talip o p ro te in e m ia III 8VL D L , 8ID L - p alm ar o r tu b e ro u s xan th o m ata se e n
8ch o le ste ro l, 8T G - can b e we ll u n til vascu lar d ise ase h its
M C C Q E 2000 R e vi e w N o te s an d L e ctu re S e ri e s E n d o cri n o lo gy 1 1
N o te s
SECONDARY CAUSES OF HYPERLIPIDEMIAS
1.Hype rchole s te re mia
J d ie t
J h yp o th yro id ism
J re n al d ise ase n e p h ro tic syn d ro m e )
J live r d ise ase ch o le static)
J d ru gs cyclo sp o rin )
J d iab e te s
J p arap ro te in e m ia
2.Hype rtriglycide mia
J o b e sity
J alco h o l
J d iab e te s
J d ru gs -b lo cke rs with o u t IS A, b irth co n tro l p ill,
h yd ro ch lo ro th iazid e , re tin o ic acid , glu co co rtico id )
J re n al d ise ase u re m ia)
J live r d ise ase acu te h e p atitis)
APPROACH TO DYSLIPIDEMIAS
J o n ce d yslip id e m ia d e te cte d e stab lish wh e th e r p rim ary vs.
se co n d ary p re ve n tio n b ase d o n h isto ry o f C AD , P VD , C VD
J e stab lish p re se n ce o f C AD risk facto rs o u tlin e d
b e lo w fo r p u rp o se o f risk stratificatio n
His tory Sugge s tive of Primary Dys lipide mia
J m arke d h yp e rlip id e m ia se e Tab le 2)
J p e rso n al an d /o r fam ily h isto ry o f p re m atu re C AD < 40 an d
re sistan ce to co n ve n tio n al th e rap y
J xan th o m ata, xan th e lasm a, arcu s in yo u n g p e rso n
Scre e ning and Inve s tigation
J in cre ase d L D L ch o le ste ro l a m ajo r risk facto r fo r ath e ro scle ro sis,
e sp e cially co ro n ary h e art d ise ase
J lo we rin g L D L ch o le ste ro l asso ciate d with d e cre ase d C VD risk, an d
d e cre ase d to tal m o rtality
J in cre ase d H D L asso ciate d with d e cre ase d C VD risk
J h yp e rtriglyce rid e m ia is an in d e p e n d e n t risk facto r fo r C AD in
p e o p le with d iab e te s an d p o stm e n o p au sal wo m e n
J scre e n in g re co m m e n d e d fo r th o se with
C AD
fam ily h isto ry o f h yp e rlip id e m ia o r p re m atu re C AD
o th e r risk facto rs e .g. h yp e rte n sio n , re n al failu re , o b e sity,
sm o ke rs, d iab e te s)
J go o d e vid e n ce fo r b o th p rim ary an d se co n d ary in te rve n tio n
Ris k Factors for CAD Modifie d from National Chole s te rol
Education Program
J p o sitive
age : m ale s 45; fe m ale s 55, o r p re m atu re m e n o p au se
with o u t e stro ge n re p lace m e n t th e rap y
fam ily h isto ry o f C H D : M I o r su d d e n d e ath < 55 age in
fath e r o r o th e r first d e gre e m ale re lative , o r < 65 age in
m o th e r o r o th e r first d e gre e fe m ale re lative
cu rre n t sm o ke r
h yp e rte n sio n as B P 1 40/90 o r o n an ti-h yp e rte n sive m e d icatio n s
lo w H D L -ch o le ste ro l < 0.90)
d iab e te s m e llitu s o r im p aire d glu co se to le ran ce
h yp e rtriglyce rid e m ia 2.3)
ab d o m in al o b e sity B M I 27 an d waist:h ip 0.9 in M , 0.8 in F )
J n e gative
h igh H D L -ch o le ste ro l
N o te s
Table 7. Ris k Stratification for CAD in Individuals with Ele vate d LDL
CAD Ris k Clas s ification %ove r 10 ye ars Profile
ve ry lo w < 5% m ale s < 35
p re m e n o p au sal fe m ale s
n o o th e r risk facto rs
lo w < 1 0% m ale s < 35
p o stm e n o p au sal fe m ale s
< 2 o th e r risk facto rs
in te rm e d iate 1 0-20% m ale s > 35
2-3 risk facto rs with n o clin ical m acro vascu lar d ise ase
h igh > 20% m ale s > 35
> 3 risk facto rs o r m arke d h yp e rlip id e m ia with n o
clin ical m acro vascu lar d isaase
ve ry h igh > 40% clin ical m acro vascu lar d ise ase
TREATMENT OF DYSLIPIDEMIAS
Hype rchole s te role mia
J co n se rvative fo r 4-6 m o n th s
P h ase I d ie t 30% calo rie s fro m fat with < 1 0% satu rate d )
sm o kin g ce ssatio n
lim it alco h o l co n su m p tio n e sp e cially if e le vate d T G )
ae ro b ic e xe rcise e sp e cially if o b e se , Typ e 2 D M )
ch an ge m e d icatio n s wh e re ap p ro p riate
tre at se co n d ary cau se s
H R T
J lip id lo we rin g age n ts se e b e lo w)
Table 8. Initiation and Targe t LDL Le ve l (mmol/L)
by Ris k Group
Ris k Group Initiate Rx Targe t LDL
Ve ry lo w 5.7 3.4
L o w 4.9 3.4
In te rm e d iate 4.1 3.4
H igh 3.4 3.4
Ve ry h igh 2.6 2.6
Hype rtriglyce ride mia
J co n se rvative m e asu re s u su ally e ffe ctive , tre at afte r 4-6 m o n th s if:
T G > 1 0 m m o l/L to p re ve n t p an cre atitis)
m ild -m o d e rate T G wh e n :
ve ry h igh C AD risk
h igh risk > 3 R F )
D M
asso ciate d lo w H D L p lu s o th e r risk facto rs
co m b in e d h yp e rlip id e m ia
Is olate d low HDL
J n o e vid e n ce su p p o rtin g tre atm e n t
J can ju stify tre atm e n t if ve ry h igh risk p atie n t o r fam ily h isto ry o f p re m atu re C AD
N o te s
Drug The rapy
Table 9. Anti-Lipide mic Pharmacothe rapie s
HMG Co-A Fibric Acid Niacin Bile Acid Othe r
Re ductae De rivative s Re s ins
Inibitors
G e n e ric lo vastatin ge m fib ro zil n ico tin ic Acid ch o le stryam in e p ro b u co l
N am e s sim vastatin fe n o fib rate
p ravastatin
ato rvastatin
ce re vo statin
Trad e M e vaco r L o p id Q u e stran L o re lco
N am e s Z o co r L ip id il
P ravach o l
L ip ito r
B ayco l
M e ch an ism d e cre ase s d e cre ase s VL D L d e cre ase s VL D L ab so rb s/b in d s d e cre ase s
ch o le ste ro l in cre ase s H D L syn th e sis b ile acid s wh ich are L D L
syn th e sis in cre ase s H D L e xcre te d , th e re b y an ti-o xid an t
in cre asin g e n te ro h e p atic
circu latio n
In d icatio n s 8to tal 8T G m u ltip le 8L D L 8L D L
8L D L 8ch ylo m icro n s m ixe d
M ain S id e G I u p se t G I u p se t flu sh in g co n stip atio n 9H D L
E ffe cts rash gallsto n e s p ru ritu s n au se a d iarrh e a
p ru ritu s 8L F Ts flatu le n ce flatu le n ce
8L F Ts 9glu co se b lo atin g ab d o p ain
m yo sitis to le ran ce n au se a
h yp e rte n sio n vo m itin g
C o n tra- live r d ise ase s h e p atic & re n al h yp e rse n sitivity b iliary o b stru ctio n
in d icatio n s 8AS T /ALT d ysfu n ctio n h e p atic p re gn an cy lactatio n
d ysfu n ctio n
active P U D
o ve rt D M
8u ric acid
Follow-Up
J q 4-6 m o n th s fo r lip id p ro file s an d L F Ts
J ch e ck C K b ase lin e an d again if p atie n t co m p lain s o f m yalgia
J in cre ase d o se an d ad d se co n d age n t to ach ie ve targe t go als
OBESITY
De finitions
J 20% o r gre ate r ab o ve id e al b o d y we igh t
M e t. L ife In s. tab le s) ; 1 70% is m o rb id o b e sity
J m o st p ractical in d e x is B M I b o d y m ass in d e x) = we igh t/h e igh t
2
kg/m
2
)
B M I < 20 o r > 27 le ad s to in cre ase d h e alth risk
Epide miology
J affe cts 1 5-25% o f N o rth Am e rican ad u lts
Pathophys iology
J p o sitive e n e rgy b alan ce wh e re e n e rgy in p u t > e n e rgy o u tp u t
Pos s ible Contributing Factors
J in cre asin g age
J ge n e tic - variatio n s in e n e rgy e xp e n d itu re , u n d e r stu d y p re se n tly
J b e h avio u r/life style - d ie t an d e xe rcise
J se co n d ary cau se s e .g. e n d o crin e d ise ase su ch as C u sh in g s, P C O D ;
d ru gs su ch as an tid e p re ssan ts an d an tie p ile p tics)
J h yp o th alam ic in ju ry trau m a, su rgical, le sio n s in ve n tro m e d ial o r
p arave n tricu lar m e d ian n u cle u s)
N o te s
OBESITY . . . CONT.
Table 10. Pote ntial Complications of Obe s ity
Sys te m Pos s ible Complications
C ard io vascu lar h yp e rte n sio n
co ro n ary arte ry d ise ase
varico se ve in s
co n ge stive h e art failu re
su d d e n d e ath fro m arrh yth m ia
R e sp irato ry d ysp n e a
sle e p Ap n e a
p u lm o n ary e m b o lu s
in fe ctio n s
G astro in te stin al gallb lad d e r d ise ase
gastro e so p h age al re flu x
fatty live r
M u scu lo ske le tal o ste o arth ritis
E n d o crin e -M e tab o lic IG T to D M Typ e 2
h yp e ru rice m ia
h yp e rlip id e m ia
P C O D
h irsu tism
irre gu lar m e n se s
in fe rtility
N e o p lastic D ise ase s e n d o m e trial
p o st-m e n o p au sal b re ast
p ro state
co lo re ctal
Tre atme nt
J ge n e ral re co m m e n d atio n s
tre atm e n t sh o u ld b e b ase d o n m e d ical risk
safe st an d b e st th e rap y is a co m p re h e n sive ap p ro ach in clu d in g
calo ric re strictio n , in cre ase d p h ysical activity an d b e h avio u r
m o d ificatio n
J d ie t
calo ric re strictio n with a b alan ce d d ie t with re d u ce d fat,
su gar an d alco h o l
J e xe rcise
J b e h avio u r m o d ificatio n
in d ivid u al o r gro u p th e rap y
se lf-m o n ito rin g, stim u lu s co n tro l, stre ss m an age m e n t
re in fo rce m e n t, co gn itive ch an ge , crisis in te rve n tio n
J d ru g th e rap y
th e se ro to n e rgic ap p e tite su p p re ssan ts fe n flu ram in e -p h e n te rm in e
F e n -P h e n ) we re fo u n d to cau se valvu lar h e art d ise ase an d p u lm o n ary
h yp e rte n sio n an d h ave b e e n with d rawn fro m th e m arke t
m o re re ce n t o f O rlistat an ti-lip ase ) fo u n d to b e m ild to m o d e rate ly e ffe ctive
J su rgical th e rap y
gastro p lasty o n e o f se ve ral co n tro ve rsial su rgical p ro ce d u re s
sto m ach stap lin g ) m ay b e u se d as tre atm e n t o f last re so rt
N o te s
OVERVIEW OF HORMONES
Hypothalamic Control of Pituitary
J tro p h ic an d in h ib ito ry facto rs co n tro l th e re le ase o f p itu itary h o rm o n e s
J m o st h o rm o n e s are p rim arily u n d e r tro p h ic stim u latio n e xce p t
p ro lactin wh ich is p rim arily u n d e r in h ib ito ry co n tro l
J tran se ctio n o f th e p itu itary stalk i.e . d isso ciatio n o f h yp o th alam u s
an d p itu itary) le ad s to p itu itary h yp e rse cre tio n o f p ro lactin an d
h yp o se cre tio n o f all re m ain in g h o rm o n e s
Clinical Pe arl
GH, LH, FSH, TSH, ACTH, PRL
J A compre s s ive ade noma in the pituitary will impair hormone
production in this orde r (i.e . GH-s e cre ting ce lls are mos t
s e ns itive to compre s s ion)
J Mne monic: Go Look For The Ade noma Ple as e
PITUITARY GLAND
Ante rior Pituitary Hormone s
J G H , P ro lactin , AC T H , T S H , L H an d F S H
Hypothalamic Hormone s
J an tid iu re tic h o rm o n e AD H ) an d o xyto cin
J p e p tid e s syn th e size d in th e su p rao p tic an d p arave n tricu lar n u cle i
o f th e h yp o th alam u s. AD H sto re d an d re le ase d fro m th e p o ste rio r
p itu itary
GROWTH HORMONE
J p o lyp e p tid e , se cre te d in b u rsts
Phys iology
J se ru m G H u n d e te ctab le m u ch o f th e d ay, su p p re sse d afte r m e als
p articu larly h igh in glu co se , su stain e d rise d u rin g sle e p
J n e ce ssary fo r n o rm al lin e ar gro wth
J acts in d ire ctly th ro u gh se ru m facto rs syn th e size d in live r
in su lin -like gro wth facto rs IG F )
p re vio u sly re fe rre d to as so m ato m e d in s
J IG F sh are s so m e in su lin -like actio n s an d th u s stim u late s gro wth o f
b o n e an d cartilage
Re gulation
J stim u late d b y G H R H , sle e p , e xe rcise , in su lin , h yp o glyce m ia,
argin in e , L -d o p a, p ro p ran o lo l, clo n id in e
J in h ib ite d b y so m ato statin se cre te d b y h yp o th alam u s, D ce lls o f p an cre as)
J lo n g lo o p n e gative fe e d b ack b y IG F -1 so m ato m e d in C )
Pathology
J d e cre ase d G H
n o t ve ry sign ifican t in ad u lts
in n e o n ate s p re se n ts with h yp o glyce m ia an d m icro p e n is; in
ch ild re n o n e can se e sh o rt statu re , fro n tal b o ssin g,
ce n tral o b e sity
re p lace m e n t co n sid e re d if G H d e ficie n cy co n firm e d b y two
p h arm aco lo gic an d o n e p h ysio lo gic stim u latio n te sts
se e P e d iatrics N o te s)
tre atm e n t: re co m b in an t h u m an gro wth h o rm o n e
J in cre ase d G H
gigan tism o r acro m e galy in h yp e rse cre tio n
clin ically se e n as gro wth o f so ft tissu e s h e e l p ad s) , th ick skin , swe atin g,
large b o n e s, co arse fe atu re s, d iab e te s, carp al tu n n e l syn d ro m e ,
o ste o arth ritis, h yp e rte n sio n , an d in cre ase d risk o f co lo n can ce r
d e fin itive d iagn o sis: in cre ase in G H with glu co se to le ran ce te st
p itu itary ad e n o m as m o st co m m o n cau se
o ccasio n ally p itu itary ad e n o m a p ro d u ce s b o th p ro lactin an d G H
rare ly carcin o id tu m o u rs an d p an cre atic isle t tu m o u rs m ake G H R H
tre atm e n t: su rge ry, rad iatio n , d ru gs b ro m o crip tin e ) , so m ato statin an alo gu e
o ctre o tid e )
N o te s
PITUITARY GLAND . . . CONT.
PROLACTIN
J p o lyp e p tid e
Phys iology
J p ro m o te s m ilk p ro d u ctio n
J an tago n ize s se x ste ro id s p e rip h e rally
Re gulation
J stim u latio n
p h ysio lo gic: sle e p , stre ss, p re gn an cy, h yp o glyce m ia,
m id -m e n stru al cycle , b re ast fe e d in g, T R H , se xu al activity
p h arm aco lo gic: d o p am in e an tago n ists, p h e n o th iazin e s,
m e to clo p ram id e , e stro ge n s, m o rp h in e , alp h a m e th yld o p a,
re se rp in e , ve rap am il, d o m p e rid o n e , cim e tid in e
p ath o lo gic: vario u s h yp o th alam ic-p itu itary cau se s
e .g. p itu itary m icro ad e n o m a, p itu itary stalk tran se ctio n ) , p rim ary
h yp o th yro id ism in cre ase d T R H ) , ch ro n ic re n al failu re
se co n d ary to re d u ce d cle aran ce ) , cirrh o sis
J in h ib itio n
p h ysio lo gic: to n ic in h ib itio n b y d o p am in e
p h arm aco lo gic: d o p am in e ago n ists e .g. b ro m o crip tin e )
Pathology
J h yp o p ro lactin e m ia
in ab ility to lactate
m ay b e th e first sign o f S h e e h an syn d ro m e p o st-p artu m
p itu itary h e m o rrh age )
J h yp e rp ro lactin e m ia
galacto rrh e a, in fe rtility, h yp o go n ad ism wo m e n an d m e n )
p ro lactin -se cre tin g tu m o u rs m ay b e in d u ce d b y e stro ge n s
an d m ay gro w d u rin g p re gn an cy
se ru m p ro lactin le ve ls > 300 m icro gram s/L virtu ally d iagn o stic
o f p ro lactin o m a
tre atm e n t in clu d e s b ro m o crip tin e , su rge ry +/ rad iatio n
th e se tu m o u rs are ve ry slo w gro win g an d so m e tim e s re q u ire n o tre atm e n t
LH AND FSH
J glyco p ro te in s with sam e alp h a su b u n it as T S H an d h C G
J p o ssib ly se cre te d b y th e sam e ce lls
Phys iology
J b o th re le ase d in p u lsatile fash io n , b u t F S H h as a lo n ge r h alf-life
3-4 h o u rs vs. 50 m in u te s fo r L H ) an d th u s flu ctu ate s le ss
th ro u gh o u t th e d ay
J go n ad o tro p in s - stim u late go n ad s o varie s an d te sticle s) via cAM P
J in th e o vary
L H stim u late s o varian th e ca ce lls to p ro d u ce an d ro ge n s
an d ro ge n s co n ve rte d to e stro ge n s in gran u lo sa ce lls
p o st-o vu latio n , co n trib u te s to co rp u s lu te u m fo rm atio n
F S H stim u late s gro wth o f gran u lo sa ce lls in o varian fo llicle
co n tro ls e stro ge n fo rm atio n
su p p re sse d b y se x ste ro id s
J in th e te stis
L H co n tro ls te sticu lar p ro d u ctio n o f te sto ste ro n e in L e yd ig ce lls
F S H , to ge th e r with in tra-te sticu lar te sto ste ro n e , stim u late s
S e rto li ce lls tu b u le s to p ro d u ce sp e rm
su p p re sse d b y te sticu lar in h ib in
Re gulation
J G n R H stim u late s b o th F S H an d L H
J in h ib itio n
fe m ale : e stro ge n an d p ro ge ste ro n e
m ale : te sto ste ro n e an d in h ib in
Pathology
J se co n d ary h yp e rse cre tio n in go n ad al failu re
N o te s
J d e cre ase d go n ad o tro p in s se e G yn e co lo gy N o te s)
h yp o go n ad ism
am e n o rrh e a
im p o te n ce
lo ss o f b o d y h air
fin e skin
te sticu lar atro p h y
failu re o f p u b e rtal d e ve lo p m e n t
tre ate d with P e rgo n al an d h C G , o r L H R H an alo gu e if fe rtility
d e sire d ; o th e rwise tre at with e stro ge n /te sto ste ro n e
ANTIDIURETIC HORMONE (VASOPRESSIN)
J o ctap e p tid e syn th e size d in su p rao p tic n u cle i o f h yp o th alam u s an d
se cre te d d o wn p itu itary stalk to p o ste rio r lo b e o f p itu itary
Phys iology
J m ajo r actio n is via cAM P in re n al co lle ctin g d u cts; alte rs
p e rm e ab ility o f m e m b ran e to wate r
J allo ws re so rp tio n o f wate r th e re b y in cre asin g u rin e co n ce n tratio n
Re gulation
J m ajo r se cre to ry stim u lu s is se ru m o sm o tic p re ssu re d e te cte d b y
o sm o re ce p to rs in h yp o th alam u s
J h yp o vo le m ia, stre ss, fe ve r, p ain m ay also stim u late AD H
J co n tracte d p lasm a vo lu m e is a m o re p o te n t stim u lato r o f wate r
re te n tio n th an o sm o lality ch an ge m e d iate d th ro u gh re n in
an gio te n sin syste m )
Dis e as e State s
Diabe te s Ins ipidus (DI)
J d e fin itio n : p assage o f large vo lu m e o f d ilu te u rin e
J ce n tral vs. n e p h ro ge n ic
ce n tral D I: in su fficie n t AD H d u e to d ysfu n ctio n o f
h yp o th alam ic n u cle i e .g. tu m o u rs, h yd ro ce p h alu s,
h istio cyto sis, trau m a)
n e p h ro ge n ic D I: co lle ctin g tu b u le s in kid n e ys re sistan t to
AD H e .g. d ru gs in clu d in g lith iu m , h yp e rcalce m ia, h yp o kale m ia)
p sych o ge n ic p o lyd ip sia m u st b e ru le d o u t
J d iagn o sis
flu id d e p rivatio n will d iffe re n tiate tru e D I h igh u rin e o u tp u t
p e rsists, u rin e o sm o lality < p lasm a o sm .) fro m p sych o ge n ic D I
re sp o n se to e xo ge n o u s AD H will d istin gu ish ce n tral fro m
n e p h ro ge n ic D I
J tre atm e n t
D D AVP fo r to tal D I
D D AVP o r ch lo rp ro p am id e , clo fib rate , carb am aze p in e fo r p artial D I
n e p h ro ge n ic D I tre ate d with so lu te re strictio n an d th iazid e s
Syndrome of Inappropriate ADH s e cre tion (SIADH)
J AD H e xce ss asso ciate d with h yp o n atre m ia with o u t e d e m a;
m u st ru le o u t o th e r cau se s o f e xce ss AD H e .g. h yp o vo le m ic
ad re n o co rtical in su fficie n cy) , e d e m ato u s h yp o th yro id ism )
an d h yp e rte n sive re n o vascu lar ste n o sis) state s
J cau se s
m align an cy lu n g, p an cre as, lym p h o m a)
C N S d ise ase in flam m ato ry, h e m o rrh age , tu m o u r,
G u illan -B arre S yn d ro m e )
ch e st d ise ase T B , p n e u m o n ia, e m p ye m a)
d ru gs vin cristin e , ch lo rp ro p am id e , cyclo p h o sp h am id e ,
carb am aze p in e , n ico tin e , m o rp h in e )
stre ss p o st-su rgical)
J d iagn o sis
in ap p ro p riate ly co n ce n trate d u rin e with a failu re to
m axim ally d ilu te in th e face o f e u vo le m ic
h yp o n atre m ia an d n o rm al th yro id , ad re n al an d re n al fu n ctio n s
N o te s
J tre atm e n t
tre at u n d e rlyin g cau se , flu id re strictio n , d e m e clo cyclin e
an tib io tic with an ti-AD H e ffe cts)
OXYTOCIN se e O b ste trics/G yn e co lo gy N o te s)
PITUITARY TUMOURS
Clinical Fe ature s
J re late d to size an d lo catio n
J visu al fie ld d e fe cts u su ally b ite m p o ral h e m ian o p sia) , o ccu lo m o to r p alsie s,
in cre ase d in tracran ial p re ssu re m ay h ave h e ad ach e s)
sku ll rad io grap h : d o u b le flo o r large se lla o r e ro sio n ) ,
calcificatio n e sp e cially cran io p h aryn gio m a)
C T an d M R I far m o re se n sitive fo r d iagn o sis
J re late d to d e stru ctio n o f glan d
h yp o p itu itarism
J re late d to in cre ase d h o rm o n e se cre tio n
P R L
p ro lactin o m a is m o st co m m o n p itu itary tu m o u r
galacto rrh e a
G H
acro m e galy in ad u lts, gigan tism in ch ild re n
AC T H
C u sh in g s d ise ase = C u sh in g s syn d ro m e cau se d b y a
p itu itary tu m o u r
tu m o u rs se cre tin g L H , F S H an d T S H are rare
Craniopharyngioma
J m o st fre q u e n t in ch ild re n an d ad o le sce n ts
J re m n an t o f R ath ke s p o u ch
J calcificatio n o n x-ray
J m ay h ave sign s o f in cre ase d IC P d u e to h yd ro ce p h alu s in clu d in g
h e ad ach e , vo m itin g an d p ap ille d e m a
J o th e r sign s m ay in clu d e visu al ab n o rm alitie s, re tard e d b o n e age
an d d e laye d se xu al d e ve lo p m e n t d u e to h yp o go n ad o tro p ism
Empty Se lla Syndrome
J se lla tu rcica ap p e ars e n large d o n x-ray b e cau se p itu itary glan d is d isto rte d
J ge n e rally e u p itu itary - n o tre atm e n t n e ce ssary
Pituitary Apople xy
J acu te h e m o rrh age /in farctio n o f p itu itary tu m o u r
J su d d e n se ve re h e ad ach e
J alte re d L O C
J o cu lar sym p to m s
J n o te : o p h th alm o p le gia with p itu itary tu m o u r like ly in d icate s
ap o p le xy sin ce tu m o u r rare ly ge ts b ig e n o u gh to e n cro ach o n
cran ial n e rve s
J n e u ro su rgical e m e rge n cy- acu te d e co m p re ssio n o f p itu itary via
tran ssp h e n o id al ro u te
HYPOPITUITARISM
Etiology
J p o st-p itu itary su rge ry
J tu m o u r
J in filtrative o r d e stru ctive d ise ase e .g. sarco id o sis, h istio cyto sis)
J trau m a, p o st-rad iatio n
J in farctio n
J in fe ctio n e .g. syp h ilis, T B )
J co n ge n ital m id lin e d e fe cts
Clinical Fe ature s
J typ ical clin ical p ro gre ssio n in p an h yp o p itu itarism
J fall in G H , clin ically n o t ap p are n t
N o te s
fall in P R L is variab le , b u t m ay p re se n t as d e cre ase d lactatio n
go n ad o tro p in in su fficie n cy th e n cau se s e re ctile d ysfu n ctio n
in m e n , an d am e n o rrh e a o r in fe rtility in wo m e n
T S H d e ficie n cy p ro d u ce s clin ical h yp o th yro id ism
fin ally, AC T H d e ficie n cy le ad s to ad re n al in su fficie n cy
Diagnos is by Triple Bolus Te s t
J stim u late s re le ase o f all an te rio r p itu itary h o rm o n e s in n o rm al in d ivid u als
J rap id se q u e n ce IV in fu sio n o f in su lin , L H R H an d T R H
J in su lin > h yp o glyce m ia > in cre ase d G H an d AC T H
J L H R H > in cre ase d L H an d F S H
J T R H > in cre ase d T S H an d P R L
Table 11. The Ante rior Pituitary Hormone s
Hormone Inhibitory Stimulus Se cre tory Stimulus
PRL d o p am in e d o p am in e an tago n ists
D 2-re ce p to r ago n ists T R H
b ro m o crip tin e )
ACTH d e xam e th aso n e C R H
co rtiso l m e tyrap o n e
1 1 --h yd ro xylase in h ib ito r
in su lin -in d u ce d h yp o glyce m ia
fe ve r, p ain
TSH circu latin g th yro id h o rm o n e s T R H
GH glu co se ch alle n ge in su lin -in d u ce d h yp o glyce m ia
so m ato statin e xe rcise , R E M sle e p
d o p am in e ago n ists argin in e , clo n id in e ,
IG F -1 p ro p ran o lo l, L -d o p a
G H R H
LH/FSH e stro ge n G n R H in b o lu se s
te sto ste ro n e
co n tin u o u s G n R H in fu sio n
THYROID
TSH
J glyco p ro te in
J a su b u n it sim ilar to th o se in F S H , L H , h C G , b u t all h ave u n iq u e su b u n its
J stim u late s gro wth o f th yro id an d se cre tio n o f T 4 an d T 3 via cAM P
J re gu latio n
stim u late d b y h yp o th alam ic T R H
in h ib ite d b y circu latin g T 4, in trap itu itary T 3, o p iate s, d o p am in e
THYROID HORMONES
Bioche mis try
J fre e T 4 0.03%) an d fre e T 3 0.3%) re p re se n t th e h o rm o n ally active fractio n
th e re m ain d e r is h o rm o n ally in active , m ain ly b o u n d to
th yro xin e b in d in g glo b u lin T B G ) an d alb u m in
J T 3 is m o re b io lo gically active th an T 4
J so m e T 4 is co n ve rte d to T 3 in p e rip h e ral tissu e s b y 5 -d e io d in ase
J m e tab o lize d b y m o st tissu e s; m e tab o lite s re ach live r an d are e xcre te d in b ile
Re gulation of Thyroid Function
J e xtrath yro id
stim u latio n o f th yro id b y T S H , e p in e p h rin e , p ro staglan d in s
cAM P stim u lato rs)
N o te s
THYROID . . . CONT.
J in trath yro id au to re gu latio n )
re sp o n se to io d id e - with in cre asin g io d id e su p p ly,
in h ib itio n o f io d id e o rgan ificatio n o ccu rs an d th u s h o rm o n e
syn th e sis d e cre ase s Wo lff-C h aiko ff e ffe ct)
varyin g th yro id se n sitivity to T S H in re sp o n se to io d id e availab ility
in cre ase d ratio o f T 3 to T 4 in io d id e d e ficie n cy
TESTS OF THYROID FUNCTION
Me as ure me nt of Circulating Thyroid Hormone s
J to tal T 3 an d T 4 le ve ls d e p e n d o n am o u n t o f th yro id b in d in g glo b u lin T B G )
J T B G in cre ase s with : p re gn an cy, O C P u se , acu te in fe ctio u s h e p atitis,
b iliary cirrh o sis; it d e cre ase s with an d ro ge n s, glu co co rtico id s, cirrh o sis,
h yp o n atre m ia, p h e n yto in , AS A, N S AID S , n e p h ro tic syn d ro m e , se ve re syste m ic illn e ss
J stan d ard asse ssm e n t o f th yro id fu n ctio n in clu d e s T S H an d if
n e ce ssary, fre e T 4 an d fre e T 3
TSH
J in p rim ary h yp e rth yro id ism , T S H is lo w an d d o e s n o t rise in
re sp o n se to T R H
J in cre ase d T S H in se co n d ary h yp e rth yro id ism
J in cre ase d T S H is th e m o st se n sitive te st fo r p rim ary h yp o th yro id ism
J in se co n d ary h yp o th yro id ism , T S H is lo w with variab le re sp o n se to
T R H d e p e n d in g o n th e site o f th e le sio n p itu itary o r h yp o th alam ic)
Iodine Kine tics
J R ad io active Io d in e U p take R AIU ) is h igh in G rave s d ise ase an d
lo w in su b acu te th yro id itis
J u se d to d iffe re n tiate th e se co m m o n cau se s o f th yro to xico sis
Te s ts of Effe cts of Thyroid Hormone s on Pe riphe ral Tis s ue s
J se x h o rm o n e b in d in g glo b u lin n o n -sp e cific)
live r in cre ase s p ro d u ctio n in h yp e rth yro id ism , d e cre ase s
p ro d u ctio n in h yp o th yro id ism
J p re -e je ctio n p e rio d / le ft ve n tricu lar e je ctio n tim e is a m e asu re o f
th e e ffe ct o f th yro id h o rm o n e s o n th e h e art
J b asal m e tab o lic rate
TESTS OF THYROID STRUCTURE
Thyroid Anatomy
J n o rm al glan d size 1 5-20 g e stim ate d b y p alp atio n )
J th yro id U /S fo r size o f glan d , so lid vs. cystic n o d u le
J fin e n e e d le asp iratio n fo r cyto lo gy
J th yro id scan
1 23
I,
1 31
I o r Te ch n e tiu m
99
) fo r h o t vs. co ld n o d u le s
Mis ce llane ous Te s ts
J th yro id an tib o d ie s
an tith yro glo b u lin an tib o d ie s, m icro so m al an tib o d ie s
H ash im o to s)
J T S H re ce p to r an tib o d ie s T S I o r T S Ab )
in cre ase d in G rave s D ise ase
J p lasm a th yro glo b u lin le ve l
u se d to m o n ito r th yro id carcin o m a activity
HYPERTHYROIDISM
J h yp e rth yro id ism : e xce ss p ro d u ctio n o f th yro id h o rm o n e
J th yro to xico sis: d e n o te s clin ical, p h ysio lo gical an d b io ch e m ical
fin d in gs in re sp o n se to e le vate d th yro id h o rm o n e
J su b acu te th yro id itis can p ro d u ce th yro to xico sis b y h o rm o n e
re le ase ; G rave s d ise ase is an e xam p le o f h yp e rth yro id ism
N o te s
THYROID . . . CONT.
Diffe re ntial Diagnos is
Table 12.
Dis orde r/Dis e as e Inve s tigations
TSH T4/T3 Thyroid antibodie s RAIU Othe r
1 . G rave s D ise ase 9 8 T S I Ab s 8
2. To xic n o d u lar G o itre 9 8 n o n e 8
3. To xic N o d u le 9 8 n o n e 8
4. S u b acu te T h yro id itis
a) classical S AT 9 8 u p to 50% o f tim e 9 E S R 8
b ) sile n t S AT 9 8 u p to 50% o f tim e 9 E S R 8
c) p o st-p artu m th yro id itis 9 8 u p to 50% o f tim e 9 E S R 8
5. M cC u n e Alb righ t S yn d ro m e 9 8 n o n e
6. Jo d B ase d o w 9 8 n o n e 9
7. E xtra-th yro id al so u rce s o f 9 8 n o n e 9
th yro id h o rm o n e
a) e n d o ge n o u s:
stru m a o variae
o varian te rato m a
m e ts fro m fo llicu lar ca
b ) e xo ge n o u s d ru gs
8. E xce ssive T h yro id stim u latio n
a) p itu itary th yro tro p h o m a 8 8 n o n e 8
b ) p itu itary th yro id h o rm o n e 8 8 n o n e 8
re ce p to r re sistan ce
c) 8h C G e .g. m o lar p re gn an cy) 9 8 n o n e 8
Clinical Fe ature s (thyrotoxicos is and hype rthyroidis m)
J ge n e ral: fatigu e , h e at in to le ran ce , irritab ility, fin e tre m o u r
J C VS : tach ycard ia, atrial fib rillatio n , p alp itatio n s
e ld e rly p atie n ts m ay h ave o n ly C VS sym p to m s, co m m o n ly
n e w o n se t atrial fib rillatio n
J G I: we igh t lo ss with in cre ase d ap p e tite , th irst, in cre ase d fre q u e n cy
o f b o we l m o ve m e n ts
J n e u ro : p ro xim al m u scle we akn e ss, h yp o kale m ic p e rio d ic p aralysis
p atie n ts o f O rie n tal o rigin )
J G U : scan t m e n se s, d e cre ase d fe rtility
J in te gu m e n t: fin e h air, skin m o ist an d warm , vitiligo , so ft n ails with
o n ych o lysis P lu m m e rs n ails )
J M S K rare ) : d e cre ase d b o n e m ass, h yp e rcalce m ia
J h e m ato lo gic: le u ko p e n ia, lym p h o cyto sis, sp le n o m e galy,
lym p h ad e n o p ath y o ccasio n ally in G rave s )
A. GRAVES DISEASE
J triad o f h yp e rth yro id ism with d iffu se go ite r, o p h th alm o p ath y,
d e rm o p ath y n e e d n o t ap p e ar to ge th e r
Epide miology
J re lative ly co m m o n , o ccu rs at an y age with p e ak in 3rd an d 4th d e cad e
J ru n s in fam ilie s
J F > M
J asso ciatio n with H L A B 8 an d D R 3
J m ay b e asso ciate d with o th e r au to im m u n e d iso rd e rs in fam ily
e .g. p e rn icio u s an e m ia, H ash im o to s d ise ase )
N o te s
THYROID . . . CONT.
Etiology and Pathoge ne s is
J au to im m u n e d iso rd e r d u e to a d e fe ct in T-su p p re sso r ce lls
J B -lym p h o cyte s p ro d u ce th yro id stim u latin g im m u n o glo b u lin s T S I)
d ire cte d again st T S H re ce p to r th at m e d iate th yro id stim u latio n
J cau se o f o p h th alm o p ath y u n ce rtain an d m ay b e
an tib o d ie s again st e xtrao cu lar m u scle an tige n s fib ro b lasts
im p licate d ) with lym p h o cytic in filtratio n
glyco sam in o glycan d e p o sitio n
J d e rm o p ath y m ay b e re late d to cu tan e o u s glyco sam in o glycan d e p o sitio n
Additional Clinical Fe ature s
J d iffu se go ite r +/ b ru it
J o p h th alm o p ath y: p ro p to sis, lid lag, lid re tractio n , d ip lo p ia,
ch aracte ristic stare , co n ju n ctival in je ctio n
N O S P E C S se e O p h th alm o lo gy N o te s)
J d e rm o p ath y rare ) : p re tib ial m yxe d e m a th icke n in g o f d e rm is)
J acro p ach y: clu b b in g an d th icke n in g o f d istal p h alan ge s
Diagnos is
J in cre ase d F T 4 o r in cre ase d fre e T 4 an d T 3)
J p o sitive fo r T h yro id S tim u latin g Im m u n o glo b u lin T S I) , a T S H
re ce p to r an tib o d y
J T R H stim u latio n te st flat T S H re sp o n se ) is d iagn o stic if sT S H an d
fre e T 4 are in co n clu sive
Tre atme nt
J p ro p ylth io u racil P T U ) o r m e th im azo le M M I)
m ajo r sid e e ffe cts o f b o th age n ts: rash , h e p atitis an d agran u lo cyto sis
J sym p to m atic tre atm e n t with b e ta ad re n e rgic an tago n ists
J th yro id ab latio n with rad io active
1 31
I if P T U o r M M I trial d o e s n o t
p ro d u ce d ise ase re m issio n
J su b to tal th yro id e cto m y in d icate d rare ly fo r large go itre s)
risks in clu d e h yp o p arath yro id ism an d vo cal co rd p alsy
J b o th M M I an d
1 31
I are co n train d icate d in p re gn an cy
J 1 /3 o f case s ach ie ve lo n g-te rm re m issio n o n d ru g th e rap y alo n e
J sm all go itre an d re ce n t o n se t are go o d in d icato rs fo r lo n g-te rm
re m issio n with m e d ical th e rap y
J h igh in cid e n ce o f h yp o th yro id ism afte r
1 31
I, re q u irin g life lo n g
th yro id h o rm o n e re p lace m e n t
J o p h th alm o p ath y: p re ve n t d ryin g
h igh d o se p re d n iso n e in se ve re case s
o rb ital rad iatio n , su rgical d e co m p re ssio n
B. SUBACUTE THYROIDITIS
(Thyrotoxic Phas e )
Etiology and Pathoge ne s is
J acu te in flam m atio n o f th e th yro id , p ro b ab ly viral in o rigin ,
ch aracte rize d b y gian t ce lls an d lym p h o cyte s
J o fte n p re ce d e d b y U R T I
J d isru p tio n o f th yro id fo llicle s b y in flam m ato ry p ro ce ss re su lts in
th e re le ase o f sto re d h o rm o n e
Clinical Fe ature s
J b e gin s with fe ve r, m alaise , so re n e ss in n e ck
J glan d b e co m e s e n large d
J two fo rm s
p ain fu l D e Q u e rvain s ) o ve r th yro id , e ars, jaw an d o ccip u t
p ain le ss S ile n t )
J u su ally tran sie n t th yro to xico sis with a su b se q u e n t h yp o th yro id ism
p h ase d u e to d e p le tio n o f sto re d h o rm o n e , fin ally re so lvin g in a
e u th yro id state o ve r a p e rio d o f m o n th s
Laboratory
J e le vate d T 4, T 3
J rad io active io d in e u p take R AIU ) m arke d ly re d u ce d
J m arke d e le vatio n o f E S R in p ain fu l varie ty o n ly
J as d ise ase p ro gre sse s, valu e s co n siste n t with h yp o th yro id ism m ay
ap p e ar; a rise in R AIU re fle cts glan d re co ve ry
N o te s
THYROID . . . CONT.
Tre atme nt
J AS A can b e u se d fo r p ain fu l fo rm
J if se ve re p ain , fe ve r, an d m alaise are p re se n t m ay re q u ire p re d n iso n e
J b e ta-ad re n e rgic b lo ckad e is u su ally e ffe ctive in re ve rsin g m o st o f
th e h yp e rm e tab o lic an d card iac sym p to m s
J if sym p to m atically h yp o th yro id m ay tre at sh o rt-te rm with th yro xin e
Prognos is
J fu ll re co ve ry in m o st case s, b u t p e rm an e n t h yp o th yro id ism in 1 0%
o f p ain le ss th yro id itis
C. TOXIC NODULAR GOITRE
J au to n o m o u s th yro id h o rm o n e p ro d u ctio n , m ay arise fro m a n o d u le
in a n o n to xic m u ltin o d u lar go itre
J m ay b e sin gu lar o r m u ltip le
J m u ltin o d u lar go itre also kn o wn as P lu m m e rs D ise ase
Clinical Fe ature s
J go itre with ad e n o m ato u s ch an ge s
J o ccu rs m o re fre q u e n tly in e ld e rly p e o p le
J atrial fib rillatio n is a co m m o n p re se n tatio n in th e e ld e rly
Diagnos is
J th yro id scan with in cre ase d u p take in n o d u le s) , an d su p p re ssio n
o f th e re m ain d e r o f th e glan d
Tre atme nt
J h igh d o se rad io active io d in e is tre atm e n t o f ch o ice
J in itiate th e rap y with an tith yro id m e d icatio n s to attain e u th yro id
state in o rd e r to avo id rad iatio n th yro id itis
J p ro p ran o lo l o fte n n e ce ssary fo r sym p to m atic tre atm e n t p rio r to
d e fin itive th e rap y
D. POSTPARTUM THYROIDITIS
J a typ e o f p ain le ss th yro id itis
J au to im m u n e m e d iate d
J typ ical p re se n tatio n in clu d e s th yro to xico sis 2-3 m o n th s p o stp artu m
with a h yp o th yro id p h ase at th e 4-8 m o n th m ark ; u su ally re so lve s
sp o n tan e o u sly with o u t n e e d fo r su p p le m e n tatio n
J m ay b e m istake n ly d iagn o se d as p o stp artu m d e p re ssio n
J m ay re cu r with su b se q u e n t p re gn an cie s
J tre at as p e r p ain le ss th yro id itis
E. THYROTOXIC STORM
J a se ve re state o f u n co n tro lle d h yp e rth yro id ism , e xtre m e fe ve r,
tach ycard ia, vo m itin g, d iarrh e a an d vascu lar co llap se an d
co n fu sio n
J o fte n p re cip itate d b y in fe ctio n , trau m a, o r su rge ry in h yp e rth yro id p atie n t
Clinical Fe ature s
J h yp e rth yro id ism
J h yp e rth e rm ia, o fte n with d ry skin
J arrh yth m ia > C H F
J m e n tal statu s ch an ge s ran gin g fro m d e liriu m to co m a
Tre atme nt
J h igh d o se P T U , L u go l s io d in e , co rtico ste ro id s b lo ck co n ve rsio n o f T 4 to T 3)
J in trave n o u s h yd ratio n , glu co se , salin e an d vitam in B co m p le x
J p ro p ran o lo l to h e lp stab ilize card iac statu s
J tre at fe ve r b u t n o t with AS A wh ich in cre ase s T 3; AS A in cre ase s
p e rip h e ral co n ve rsio n an d co m p e te s fo r T B G )
J tre at p re cip itan t
Prognos is
J 50% m o rtality rate
N o te s
THYROID . . . CONT.
HYPOTHYROIDISM
1. Primary Dis e as e s of the Thyroid (90%)
J iatro ge n ic: p o st-ab lative
1 31
I o r su rgical th yro id e cto m y)
J au to im m u n e : H ash im o to s th yro id itis
J h yp o th yro id p h ase o f su b acu te th yro id itis
J d ru gs: go itro ge n s io d in e ) , P T U , M M I, lith iu m
J in filtrative d ise ase p ro gre ssive syste m ic scle ro sis, am ylo id )
J io d in e d e ficie n cy
J co n ge n ital 1 /4000 b irth s)
glan d h yp o p lasia/ap lasia
e n zym atic d e fe cts o f th yro id h o rm o n e syn th e sis
2. Pituitary Hypothyroidis m
J in su fficie n cy o f p itu itary T S H
3. Hypothalamic Hypothyroidis m
J d e cre ase d T R H fro m h yp o th alam u s rare )
4. Pe riphe ral Tis s ue Re s is tance to Thyroid Hormone
J rare
Clinical Fe ature s of Hypothyroidis m
J ge n e ral: fatigu e , co ld in to le ran ce , slo win g o f m e n tal an d p h ysical
p e rfo rm an ce , h o arse n e ss, e n large d to n gu e
J C VS : slo w p u lse , ge n e ralize d ath e ro scle ro sis in cre ase d se ru m
ch o le ste ro l an d triglyce rid e s) , p e ricard ial e ffu sio n
J G I: an o re xia, we igh t gain , co n stip atio n , p o o r ap p e tite
J N e u ro : p are sth e sia, slo w sp e e ch , m u scle cram p s, d e lay in
re laxatio n p h ase o f d e e p te n d o n re fle xe s h u n g re fle xe s )
J G U : m e n o rrh agia, am e n o rrh e a, an o vu lato ry cycle s
J d e rm ato lo gical: p u ffin e ss o f face , p e rio rb ital e d e m a, co o l, d ry an d
ro u gh skin , h air d ry an d co arse , e ye b ro ws th in n e d late ral 1 /3)
J h e m ato lo gic: an e m ia
Laboratory
J se n sitive T S H sT S H ) m o st se n sitive te st fo r p rim ary h yp o th yro id ism
J m u st m e asu re T S H to ru le o u t se co n d ary o r te rtiary cau se s
Tre atme nt
J L -th yro xin e d o se ran ge u su ally 0.05 to 0.2 m g/d ay)
J e ld e rly p atie n ts an d th o se with co ro n ary arte ry d ise ase : start at
0.025 m g d aily an d in cre ase grad u ally
J m o n ito r sT S H
J at th e o p tim al re p lace m e n t d o sage , T S H is in th e m id d le o f its n o rm al ran ge ;
can also m o n ito r fre e T 4, p articu larly in p itu itary h yp o th yro id ism
A. CONGENITAL HYPOTHYROIDISM se e P e d iatrics N o te s)
B. HASHIMOTOS THYROIDITIS
J two varian ts
go itro u s: p re se n ts with a e u th yro id o r h yp o th yro id go itre
atro p h ic: p re se n ts in itially with h yp o th yro id state an d atro p h ic glan d
Etiology and Epide miology
J d e fe ct in clo n e o f T-su p p re sso rs le ad s to ce ll-m e d iate d d e stru ctio n
o f th yro id fo llicle s
J B -lym p h o cyte s p ro d u ce an tith yro glo b u lin an tib o d y an d
an tith yro id p e ro xid ase an ti T P O o r an tim icro so m al an tib o d y)
J asso ciate d with H L A B 8 an d D R 3, an d o th e r au to im m u n e d ise ase s
e .g. S j gre n s syn d ro m e , S L E , R A, p e rn icio u s an e m ia, ad re n al in su fficie n cy)
J m o re co m m o n in fe m ale s o f m id d le age an d is th e m o st co m m o n
cau se o f sp o rad ic go ite r in ch ild re n
N o te s
THYROID . . . CONT.
Clinical Fe ature s
J go itro u s varian t u su ally p re se n ts with a ru b b e ry go itre an d
e u th yro id ism , th e n h yp o th yro id ism b e co m e s e vid e n t
J atro p h ic varian t p atie n ts are h yp o th yro id fro m th e start
J asso ciatio n with th yro id lym p h o m a
Laboratory
J th yro id fu n ctio n te st re ve als h yp o th yro id ism , o r a e u th yro id state
with a co m p e n sato ry in cre ase in T S H ; fo llo we d b y d e cre ase d fre e
T 4 an d e ve n tu ally d e cre ase d fre e T 3
J an tim icro so m al an d an ti-th yro glo b u lin an tib o d ie s
Tre atme nt
J if h yp o th yro id , re p lace with L -th yro xin e
J if e u th yro id , also tre at with L -th yro xin e if sign ifican t an ti-th yro id
an tib o d y p re se n t
C. RIEDELS STRUMA
J a rare typ e o f ch ro n ic th yro id itis
J a fib ro tic in flam m ato ry p ro ce ss th at e xte n d s fro m th e th yro id in to
su rro u n d in g tissu e s
Clinical Fe ature s
J ill-d e fin e d , firm m ass with p o ssib le co m p re ssive sym p to m s o f
d ysp h agia, strid o r, h o arse n e ss, p ain
J ch ie f im p o rtan ce is d iffe re n tiatio n fro m m align an cy
Tre atme nt
J su rgical we d ge re se ctio n o f th e isth m u s to p re ve n t trach e al co m p re ssio n )
D. MYXEDEMA COMA
J a se rio u s state o f h yp o th yro id ism co m p o u n d e d b y a se co n d
illn e ss e .g. p n e u m o n ia
J an e n d o crin e e m e rge n cy
Clinical Fe ature s
J h yp o th yro id ism , stu p o r, h yp o ve n tilatio n , h yp o th e rm ia
Tre atme nt
J AB C s
J n o active re -warm in g, b u t avo id co o lin g
J N G tu b e sin ce ile u s o fte n p re se n t
J co rtico ste ro id s d u e to th e p o ssib ility o f co n co m itan t ad re n al in su fficie n cy)
J L -th yro xin e 0.5 m g IV lo ad in g d o se th e n sm alle r d o se s P O
J tre at p re cip itan t
E. SICK EUTHYROID SYNDROME (SES)
J se rio u s illn e ss, trau m a, o r stre ss can in d u ce ch an ge s in
circu latin g le ve ls o f th yro id h o rm o n e s
J n o t d u e to in trin sic th yro id o r p itu itary d ise ase
J th e ab n o rm alitie s in S E S in clu d e alte ratio n s in
p e rip h e ral tran sp o rt an d m e tab o lism o f th yro id h o rm o n e
re gu latio n o f T S H se cre tio n
th yro id fu n ctio n itse lf
J se ve ral varian ts e xist
J n o rm al-T 4 varian t
ch aracte rize d b y lo w T 3, n o rm al T 4
p ro p o se d m e ch an ism in vo lve s in h ib itio n o f p e rip h e ral
5 m o n o d e io d in atio n o f T 4 to T 3
d iffe re n tiate d fro m p rim ary h yp o th yro id ism b y a n o rm al T S H
J lo w-T 4 varian t
ch aracte rize d b y lo w T 3, lo w T 4
lo w T 4 like ly d u e to in h ib ite d T 4 b in d in g to se ru m p ro te in s
an d acce le rate d m e tab o lic cle aran ce
d iffe re n tiate d fro m p rim ary h yp o th yro id ism with n o rm al o r lo w T S H
p o o re r p ro gn o sis
N o te s
THYROID . . . CONT.
J tre at th e u n d e rlyin g d ise ase
J th yro id h o rm o n e re p lace m e n t wo rse n s th e o u tco m e
NON-TOXIC GOITRE
J ge n e ralize d e n large m e n t o f th e th yro id glan d in a e u th yro id in d ivid u al
th at d o e s n o t re su lt fro m in flam m ato ry o r n e o p lastic p ro ce ss
J ap p e aran ce o f a go itre is m o re like ly d u rin g ad o le sce n ce , p re gn an cy,
an d lactatio n b e cau se o f in cre ase d th yro id h o rm o n e re q u ire m e n ts
go itre in th is se ttin g is u su ally d iffu se
d u e to asym m e tric gro wth , are as o f isch e m ia, h e m o rrh age ,
an d fib ro sis, n o d u le an d cyst fo rm atio n can o ccu r
Etiology
J io d in e d e ficie n cy o r e xce ss
J go itro ge n s: b rassica ve ge tab le s tu rn ip , cassava)
J d ru gs: io d in e , lith iu m , p ara-am in o salicylic acid
J an y d iso rd e r o f h o rm o n e syn th e sis with co m p e n sato ry gro wth
J p e rip h e ral re sistan ce to th yro id h o rm o n e
Complications
J co m p re ssio n o f n e ck stru ctu re s, cau sin g strid o r, d ysp h agia, p ain ,
an d h o arse n e ss
J m u ltin o d u lar go itre m ay b e co m e au to n o m o u s le ad in g to to xic
m u ltin o d u lar go itre an d h yp e rth yro id ism
Tre atme nt
J re m o ve go itro ge n s
J su p p re ssio n with L -th yro xin e m ay b e e ffe ctive in an y
T S H -d e p e n d e n t go itre
J su rge ry m ay b e n e ce ssary fo r se ve re co m p re ssive sym p to m s
THYROID NODULES
J cle arly d e fin e d d iscre te m ass, se p arate d fro m th e th yro id p are n ch ym a
Etiology
J b e n ign tu m o u rs e .g. fo llicu lar ad e n o m a)
J th yro id can ce r
J h yp e rp lastic are a in a m u ltin o d u lar go itre
J cyst: tru e th yro id cyst, are a o f cystic d e ge n e ratio n in a m u ltin o d u lar go itre
Inve s tigations
J fin e n e e d le asp iratio n
u se fu l o n ly if p o sitive fo r m align an cy sp e cific, n o t se n sitive )
J th yro id fu n ctio n te sts
J th yro id scan
1 5-20% o f co ld n o d u le s m in im al
1 31
I u p take in to n o d u le )
are m align an t, ve ry lo w m align an t p o te n tial if warm o r
h o t sign ifican t
1 31
I u p take in to n o d u le )
J th yro id U /S
N o te s
THYROID . . . CONT.
T S H
D e te ctab le U n d e te ctab le
- o b se rve if e u th yro id
- R AI o r su rge ry if h yp e rth yro id
F in e N e e d le Asp iratio n B io p sy
F N A)
B e n ign In co n clu sive M align an t
trial o f L -th yro xin e re p e at F N A su rge ry ad ju van t
su p p re ssio n x 6m o s th e rap y
sm alle r large r still in co n clu sive :
trial o f L -th yro xin e
su p p re ssio n
o b se rve su rge ry
sm alle r u n ch an ge d large r
o b se rve re p e at F N A su rge ry
Figure 3. Workup of Thyroid Nodule
THYROID MALIGNANCIES
Ris k Factors for Thyroid Malignancy
J h isto ry
h e ad o r n e ck irrad iatio n e .g. acn e th e rap y)
fam ily h isto ry e sp e cially o f m e d u llary carcin o m a)
rap id gro wth an d failu re to sh rin k o n L -th yro xin e )
o n se t < 30 ye ars o f age
m ale ge n d e r th yro id n o d u le s m o re co m m o n in fe m ale s,
m align an cy m o re co m m o n in m ale s)
co m p re ssive sym p to m s e .g. p ain , d ysp h agia, strid o r, h o arse n e ss)
ce rvical lym p h ad e n o p ath y
n o d u le in p atie n t with H ash im o to s m u st ru le o u t lym p h o m a)
J p h ysical
h ard n e ss o f n o d u le
su rro u n d in g tissu e in vo lve m e n t
re gio n al lym p h ad e n o p ath y
J in ve stigatio n s
fin e n e e d le asp iratio n se e F igu re 3)
Clas s ification
1. Papillary (50-70%)
J co n sid e re d a we ll-d iffe re n tiate d n e o p lasm
J se e n m o re co m m o n ly in yo u n ge r p atie n ts
J m ay b e in d u ce d b y rad iatio n
J m u ltice n tric, sh o w so m e fo llicu lar co m p o n e n ts h isto lo gically
J u su ally m e tastasize s to re gio n al lym p h n o d e s first
J life sp an n o t affe cte d if co n fin e d to o n e lo b e an d < 2 cm
2. Follicular (10-15%)
J also co n sid e re d a we ll-d iffe re n tiate d n e o p lasm , b u t m o re
aggre ssive th an p ap illary
J n o t asso ciate d with rad iatio n e xp o su re
J te n d s to b e an gio in vasive , sp re ad in g to lu n g, b o n e s an d d istan t
site s with o u t lym p h n o d e in vo lve m e n t
J m o st im p o rtan t p ro gn o stic facto r is in vasio n , n o t p rim ary tu m o u r size
3. Anaplas tic Carcinoma (10%)
J o ccu rs m o st co m m o n ly in e ld e rly p atie n ts
J rap id ly p ro gre ssive
J p o o r p ro gn o sis
N o te s
THYROID . . . CONT.
4. Me dullary Carcinoma (1-2%)
J h igh fam ilial aggre gatio n , asso ciate d with M E N IIa o r IIb
J m ay p ro d u ce calcito n in , p ro staglan d in s, AC T H , se ro to n in m ay
p ro d u ce d iarrh e a) , kallikre in , b rad ykin in
th e se su b stan ce s can b e u se d as tu m o u r m arke rs
J wo rse p ro gn o sis th an p ap illary o r fo llicu lar can ce r
J n e e d to scre e n asym p to m atic re lative s
in ap p ro p riate rise in calcito n in with th e ad m in istratio n o f
calciu m an d p e n tagastrin
5. Lymphoma (< 1%)
J se e n in th e co n te xt o f a n o d u le o r an e n largin g go itre in a p atie n t
with H ash im o to s th yro id itis
Tre atme nt
J lo b e cto m y fo r sm all, we ll-d iffe re n tiate d p ap illary C A with n o
e vid e n ce o f aggre ssive b e h avio u r o r m e tastase s
J n e ar-to tal th yro id e cto m y fo r large tu m o u rs with m arke d
an gio in vasio n o r cap su lar in vasio n
J n o d al d isse ctio n re q u ire d o n ly if n o d e s p re se n t
J ge n e rally fo llo w with large d o se o f ab lative rad io active io d in e fo r
large , we ll-d iffe re n tiate d tu m o u rs
J th yro id m align an cie s m ay b e d e p e n d e n t o n T S H an d m ay re gre ss
with L -th yro xin e su p p re ssio n
J fo llo w th yro glo b u lin p ap illary, fo llicu lar , calcito n in m e d u llary)
J in ap p ro p riate se ru m th yro glo b u lin le ve l p o st su rge ry/ab latio n m ay
in d icate m e tastase s
to tal b o d y
1 31
I scan will id e n tify m e tastase s
tre atm e n t b y h igh d o se rad io active io d in e
ADRENAL CORTEX
ACTH
J p o lyp e p tid e
J p art o f lo n g p ro h o rm o n e p ro -o p io m e lan o co rtico tro p in , P O M C )
wh ich co n tain s alp h a, b e ta an d gam m a M S H , b e ta-e n d o rp h in , an d
lip o tro p in as we ll as AC T H
Phys iology
J se cre tio n is b o th p u lsatile an d d iu rn ally varie d , p e akin g at
0200-0400 h o u rs, lo we st at 1 800-2400 h o u rs
J stim u late s gro wth o f ad re n al co rte x an d se cre tio n o f its h o rm o n e s
via cAM P
stim u late s glu co co rtico id s, an d ro ge n s an d , to a lim ite d
e xte n t, m in e ralo co rtico id s
J m ay h ave so m e m e lan o cyte stim u latin g activity
Re gulation
J p rim ary co n tro l b y C R H
J fe e d b ack in h ib itio n b y co rtiso l o n p itu itary, h yp o th alam u s an d
C N S ; also re gu late d b y stre ss, sle e p -wake cycle an d stre ss
p yro ge n s, su rge ry, h yp o glyce m ia, e xe rcise , se ve re e m o tio n al
trau m a)
CORTICAL HORMONES
J all d e rive d fro m ch o le ste ro l se e F igu re 4)
J m in e ralo co rtico id s ald o ste ro n e ) fro m zo n a glo m e ru lo sa
o u te rm o st laye r
J glu co co rtico id s co rtiso l) fro m zo n a fascicu lata m id d le laye r
J an d ro ge n s fro m zo n a re ticu laris in n e rm o st laye r
N o te s
ADRENAL CORTEX . . . CONT.
ch o le ste ro l
p re gn e n alo n e
2 1
p ro ge ste ro n e 1 7-O H -p re gn e n alo n e D H E A-S
3 1 2 2
1 1 -d e o xyco rtico ste ro n e 1 7-O H -p ro ge ste ro n e an d ro ste n e d io n e
4 3 5
co rtico ste ro n e 1 1 -d e o xyco rtiso l te sto ste ro n e
8 4 6 7
ald o ste ro n e co rtiso l e strad io l d ih yd ro te sto ste ro n e
M in e ralo co rtico id s G lu co co rtico id s S e x S te ro id s
zo n a glo m e ru lo sa) zo n a fascicu lata) zo n a re ticu laris)
1 1 7-h yd ro xylase 2 3--d e h yd ro ge n ase 3 21 -h yd ro xylase
4 1 1 -h yd ro xylase 5 1 7--d e h yd ro ge n ase 6 aro m atase
7 5--re d u ctase 8 1 8-h yd ro xylase
Figure 4. Pathways of Major Ste roid Synthe s is in the
Adre nal Gland and The ir Enzyme s
Aldos te rone
J re gu late s E C F vo lu m e at le ve l o f th e co lle ctin g tu b u le s an d K
+
m e tab o lism
J ald o ste ro n e re gu late d p rin cip ally b y th e re n in -an gio te n sin -ald o ste ro n e syste m
se e F igu re 5)
J n e gative fe e d b ack to ju xtaglo m e ru lar ap p aratu s b y lo n g lo o p
ald o ste ro n e via vo lu m e e xp an sio n ) an d sh o rt lo o p an gio te n sin II
via p e rip h e ral vaso co n strictio n )
vo lu m e d e p le tio n vo lu m e e xp an sio n
d e cre ase d arte rial p re ssu re in cre ase d arte rial p re ssu re
d e cre ase d N a d e live ry to m acu la d e n sa d o p am in e
P G s, Vaso p re ssin re n al N a re te n tio n
sym p ath e tic stim u latio n
stim u latio n o f JG A in h ib itio n o f JG A
R E N IN AC E
An gio te n sin o ge n An gio te n sin I An gio te n sin II*
with n e gative fe e d b ack to in h ib it JG A)
Ald o ste ro n e An gio te n sin III*
re le ase * *
* an gio te n sin II in cre ase s p e rip h e ral arte rial re sistan ce , raisin g B P
an gio te n sin III le ss b io lo gically active th an an gio te n sin II
* * cau se s N a re te n tio n , h e n ce E C F V e xp an sio n
JG A - ju xtaglo m e ru lar ap p aratu s AC E - an gio te n sin co n ve rtin g e n zym e
Figure 5. Re nin-Angiote ns in-Aldos te rone Axis
N o te s
Glucocorticoids
J se cre tio n re gu late d b y
d iu rn al variatio n o f AC T H h igh e r in a.m . th an p .m ., with
p e ak aro u n d 0200 h o u rs)
in h ib its b o th AC T H an d C R F re le ase n e gative fe e d b ack)
stre ss e .g. fe ve r, p ain , h yp o glyce m ia) , in ad d itio n to
stim u latin g AC T H re le ase , d ire ctly stim u late s C R H re le ase ,
o ve r-rid in g first two facto rs
J 1 0% fre e in p lasm a, 90% b o u n d to tran sco rtin in active )
J p h ysio lo gic e ffe cts
stim u late s h e p atic glu co se p ro d u ctio n glu co n e o ge n e sis)
in cre ase s in su lin re sistan ce in p e rip h e ral tissu e s
in cre ase s p ro te in catab o lism
stim u late s le u ko cyto sis an d lym p h o p e n ia
e n h an ce s b o n e re so rp tio n
an ti-in flam m ato ry, im p airs ce ll m e d iate d im m u n ity
re gu late d e xtrace llu lar flu id vo lu m e , p ro m o te s re n al
so lu te -fre e wate r cle aran ce
Androge ns
J p rin cip al ad re n al an d ro ge n s are d ih yd ro e p ian d ro ste ro n e D H E A) ,
an d ro ste n e d io n e an d 1 1 -h yd ro xyan d ro ste n e d io n e
J p e ak co n ce n tratio n s in p u b e rty
J p ro p o rtio n o f to tal an d ro ge n s ad re n al to go n ad al) in cre ase s in o ld age
J p rim arily re sp o n sib le fo r ad re n arch e p u b ic an d axillary h air
J ad re n al an d ro ge n fo rm atio n is re gu late d b y AC T H n o t L H )
TESTS OF ADRENOCORTICAL FUNCTION
Plas ma Cortis ol
J d iu rn al variatio n is o f d u b io u s d iagn o stic valu e
J its re sp o n se to stim u latio n o r su p p re ssio n is m o re in fo rm ative
Urinary Fre e Cortis ol
J co rre late s we ll with se cre to ry rate s
J sin ce it re fle cts se cre tio n o f fre e co rtiso l, it is a go o d te st fo r
ad re n al h yp e rfu n ctio n
Se rum ACTH
J h igh in p rim ary ad re n al in su fficie n cy
J lo w in se co n d ary ad re n al in su fficie n cy
Se rum DHEA-S
J th e m ain ad re n al an d ro ge n
Cortros yn Stimulation Te s t
J co rtro syn is an AC T H an alo gu e
J fo r d iagn o sin g ad re n al in su fficie n cy
Short Cortros yn Stimulation Te s t
J 25 U o f co rtro syn IM , m e asu re se ru m co rtiso l at b ase lin e an d 60 m in u te s
J P O S IT IVE re sp o n se : in cre ase in p lasm a co rtiso l le ve l b y > 200 n m o l/L
an d an ab so lu te le ve l o f > 500 n m o l/L ) ru le s o u t p rim ary ad re n al in su fficie n cy
J N E G AT IVE re sp o n se m ay b e d u e to lack o f stim u latio n > p ro ce e d
to lo n g co rtro syn te st
Long Cortros yn Stimulation Te s t
J to d e te rm in e p rim ary vs. se co n d ary ad re n al in su fficie n cy
J 25 U o f syn th e tic AC T H in fu se d fo r 8h o n 3 co n se cu tive d ays,
co rtiso l m e asu re d q a.m .
J P O S IT IVE re sp o n se ru le s o u t p rim ary b u t n o t n e ce ssarily
se co n d ary ad re n al in su fficie n cy
J N E G AT IVE re sp o n se ru le s in p rim ary ad re n al in su fficie n cy
Me tyrapone Te s t
J o n e o f b e st te sts o f in te grity o f p itu itary-ad re n al axis
J u se fu l in d iagn o sin g su sp e cte d se co n d ary ad re n al in su fficie n cy
N o te s
J 750 m g p o q 4h x 24 h , m e asu re se ru m co rtiso l, 1 1 -d e o xyco rtiso l,
an d AC T H
J b lo cks 1 1 -h yd ro xylase , th e fin al ste p o f co rtiso l syn th e sis, cau sin g
e le vate d le ve l o f th e co rtiso l p re cu rso r, 1 1 -d e o xyco rtiso l an d
d e cre ase d se ru m co rtiso l le ve ls
J n o rm al re sp o n se is re d u ce d co rtiso l, e le vate d 1 1 -d e o xyco rtiso l
an d e le vate d AC T H re sp o n se o f h yp o th alam u s to d e cre ase d co rtiso l)
De xame thas one (DXM) Suppre s s ion Te s t
J go ld stan d ard fo r h yp e rco rtiso lism
J D XM is a p o te n t glu co co rtico id
J te sts in te grity o f n e gative fe e d b ack m e ch an ism o f glu co co rtico id s
o n AC T H se cre tio n i.e . p o sitive te st fails to su p p re ss AC T H
p ro d u ctio n )
J o ve rn igh t te st - go o d scre e n in g te st fo r C u sh in g syn d ro m e
J false ly p o sitive in o b e sity, d e p re ssio n , stre ss
J m e asu re p lasm a co rtiso l le ve l at 0800 fo llo win g ad m in istratio n o f
d e xam e th aso n e 1 m g p o at 2300 n igh t b e fo re
J lo w d o se te st- co n firm s C u sh in g syn d ro m e if ab n o rm al re sp o n se
J h igh d o se te st- co n firm s C u sh in g d ise ase p ath o lo gy o f th e p itu itary)
HYPERALDOSTERONISM
J state o f h yp e rse cre tio n o f th e m in e ralo co rtico id ald o ste ro n e
Primary Hype raldos te ronis m
J d iagn o stice crite ria: d iasto lic h yp e rte n sio n with o u t e d e m a,
d e cre ase d re n in an d in cre ase d ald o ste ro n e se cre tio n b o th
u n re sp o n sive to in cre ase s in vo lu m e
J ald o ste ro n e -p ro d u cin g ad re n al ad e n o m a C o n n S yn d ro m e )
J id io p ath ic b ilate ral ad re n al h yp e rp lasia
J ad re n al carcin o m a rare )
Clinical Fe ature s
J h yp e rte n sio n u n co n tro lle d b y stan d ard th e rap y
J h yp o kale m ia O F F d iu re tics
J o th e r sym p to m s m ay in clu d e
p o lyu ria, p o lyd ip sia, n o ctu ria
we akn e ss, p are sth e sia
C H O in to le ran ce
Lab Findings
J h yp o kale m ia
J h igh n o rm al N a
+
J m e tab o lic alkalo sis
J h igh 24 h o u r u rin ary o r p lasm a ald o ste ro n e
J salt lo ad in g te st: u n su p p re sse d ald o ste ro n e afte r 3 d ays o f salt lo ad in g
Tre atme nt
J m e d ical: sp iro n o lacto n e o r am ilo rid e fo r ad re n al h yp e rp lasia
J su rgical: re m o val o f ad e n o m a is cu rative
Se condary Hype raldos te ronis m
J in cre ase in ald o ste ro n e in re sp o n se to activatio n o f re n in -an gio te n sin syste m
J o ve rp ro d u ctio n o f re n in e .g. p rim ary re n in ism fro m
re n in -p ro d u cin g tu m o u r - rare )
J se co n d ary h yp e rre n in ism - d u e to h yp o p e rfu sio n o f kid n e ys
e .g. re n al arte ry ste n o sis) , o r e d e m ato u s state s C H F, live r
cirrh o sis) , wh e re arte rial h yp o vo le m ia an d /o r h yp o te n sio n is
stim u lu s fo r ald o ste ro n e se cre tio n
B artte rs S yn d ro m e - se ve re se co n d ary h yp e rald o ste ro n ism
with o u t e d e m a o r h yp e rte n sio n d u e to JG A h yp e rp lasia)
CUSHINGS SYNDROME
J re gard le ss o f e tio lo gy, all case s o f e n d o ge n o u s C u sh in g syn d ro m e
are d u e to an in cre ase d p ro d u ctio n o f co rtiso l b y th e ad re n al
Etiology
J AC T H -d e p e n d e n t - b ilate ral ad re n al h yp e rp lasia se co n d ary to
p itu itary AC T H tu m o u r C u sh in g d ise ase )
e cto p ic AC T H se cre tin g tu m o u r e .g. sm all ce ll lu n g C A, b ro n ch ial carcin o id )
N o te s
J AC T H -in d e p e n d e n t
p ro lo n ge d u se o f e xo ge n o u s glu co co rtico id s m o st co m m o n
cau se o f C u sh in g syn d ro m e )
p rim ary ad re n o co rtical h yp e rfu n ctio n : ad re n al ad e n o m a an d carcin o m a
b ilate ral ad re n al n o d u lar h yp e rp lasia
Clinical Fe ature s se e F i gu re 6)
J tru n cal ce n trip e tal) o b e sity, th in n in g o f e xtre m itie s
J su p raclavicu lar fat p ad s, p o ste rio r ce rvical fat b u ffalo h u m p ) , m o o n facie s
J h irsu tism
J o ligo m e n o rrh e a in wo m e n , im p o te n ce in m e n
J h yp e rte n sio n
J p ro xim al m u scle we akn e ss
J skin m an ife statio n s: th in skin , p u rp le striae , e asy b ru isin g, p o o r
wo u n d h e alin g, m u co cu tan e o u s can d id iasis, acn e
J p sych iatric d istu rb an ce s d e p re ssio n , co n fu sio n , fran k p sych o sis)
J o ste o p o ro sis
J im p aire d glu co se in to le ran ce co m m o n , b u t fran k d iab e te s n o t ve ry co m m o n
J le u ko cyto sis
J n o te : in e cto p ic AC T H , ge n e rally d o n o t lo o k C u sh in go id , b u t
ch aracte rize d b y se ve re h yp o kale m ic m e tab o lic alkalo sis an d a
rap id catab o lic co u rse with h yp e rp igm e n tatio n an d m u scle wastin g
Figure 6. Cus hings Dis e as e
Inve s tigations
J lo ss o f d iu rn al p lasm a co rtiso l variatio n an e arly fin d in g
se e F igu re 7)
p o o r wo u n d h e ali n g
large ab d o m e n
stri ae
m o o n face
re d ch e e ks
b u ffalo h u m p
th i n ski n
th i n arm s an d le gs
N o te s
clin ical fe atu re s su sp icio u s fo r h yp e rco rtiso lism
24 h o u r u rin ary fre e co rtiso l
n o rm al < 4X in cre ase > 4X in cre ase
n o p ro ce e d to lo w d o se D S T d iagn o sis o f C u sh in g
C u sh in g 5m g D XM q 6h x 48h rs) syn d ro m e e stab lish e d
syn d ro m e to co n firm d iagn o sis
m e asu re AC T H
AC T H in cre ase d AC T H d e cre ase d
in fe rio r p e tro sal sin u s h igh d o se D S T
sam p lin g, p itu itary im agin g 2.0m g q 6h x 48 h rs)
to co n firm d iagn o sis o f
ad re n al C u sh in g s
D XM - d e xam e th aso n e
D S T - D XM su p p re ssio n te st
Figure 7. Hype rcortis olis m: Algorithm for Diagnos is
Tre atme nt
J p itu itary
tran ssp h e n o id al re se ctio n , with glu co co rtico id su p p le m e n t
p e ri- an d p o st-o p e rative
irrad iatio n : o n ly 50% e ffe ctive , with sign ifican t risk o f h yp o p itu itarism
J ad re n al
su rgical re m o val fo r cu re if ad e n o m a; fo r p alliatio n if carcin o m a ve ry p o o r
p ro gn o sis b e cau se o f fre q u e n t m e ts, an d ad ju n ctive ch e m o o fte n n o t u se fu l
J e cto p ic AC T H tu m o u r - u su ally b ro n ch o ge n ic can ce r a p aran e o p lastic syn d ro m e )
ch e m o th e rap y/rad iatio n fo r p rim ary tu m o u r
ad re n al b lo ckin g age n ts: m e tyrap o n e o r ke to co n azo le
p o o r p ro gn o sis
CONGENITAL ADRENAL HYPERPLASIA (CAH)
Pathophys iology
J au to so m al re ce ssive p atte rn o f tran sm issio n , le ad in g to e n zym e
d e fe cts, wh ich can ran ge fro m p artial to to tal
J 21 -h yd ro xylase d e ficie n cy is th e m o st co m m o n fo rm
J re su lts in d e cre ase d co rtiso l an d ald o ste ro n e with sh u n tin g to ward
ad re n al an d ro ge n p ath way se e F igu re 5)
J d e ficie n cy o f co rtiso l le ad s to e le vate d AC T H , wh ich in cre ase s
le ve ls o f u n affe cte d ste ro id s an d cau se s b ilate ral ad re n al h yp e rp lasia
Clinical Fe ature s
J d e p e n d s o n th e d e gre e an d th e sp e cific d e ficie n cy
J in fan ts m ay p re se n t as failu re to th rive , salt-wastin g ad re n al crisis
d u e to lack o f ald o ste ro n e ) , clito ral h yp e rtro p h y, fu se d lab ia o r
su stain e d h yp e rte n sio n se e P e d iatrics N o te s)
J ad u lt o n se t 1 1 -h yd ro xylase varian t) m o re in sid io u s, m ay p re se n t
as h irsu tism
J fe m ale
am b igu o u s ge n italia to co m p le te virilizatio n
am e n o rrh e a
J p re co cio u s p u b e rty, with e arly ad re n arch e
J acce le rate d lin e ar b o n e gro wth in e arly ye ars, b u t p re m atu re
e p ip h yse al clo su re d u e to h igh te sto ste ro n e , re su ltin g in sh o rt statu re
J p o ssib le Ad d iso n ian p ictu re ad re n al in su fficie n cy) if ad re n al o u tp u t o f
co rtiso l se ve re ly co m p ro m ise d
N o te s
Lab Findings
J lo w N a, h igh K , lo w co rtiso l, h igh AC T H if b o th glu co co rtico id an d
m in e ralo co rtico id d e ficie n cy
J in cre ase d se ru m 1 7-O H -p ro ge ste ro n e su b strate fo r 21 -h yd ro xylase )
J in cre ase d te sto ste ro n e
J in cre ase d D H E A-S
J in cre ase d u rin ary 1 7-ke to ste ro id s
J b o n e age in ch ild re n
Tre atme nt
J glu co co rtico id s re p lace m e n t to lo we r AC T H , an d th e re fo re re d u ce
ad re n al an d ro ge n p ro d u ctio n ,
J d iagn o se an d tre at b e fo re e p ip h yse al clo su re to p re ve n t sh o rt statu re
J su rgical re p air o f virilize d fe m ale e xte rn al ge n italia
HIRSUTISM AND VIRILIZATION
J b o th te rm s re fe r to state s o f an d ro ge n e xce ss
J h irsu tism
m ale p atte rn o f h air gro wth in wo m e n : b ack, ch e st, u p p e r ab d o m e n
J virilizatio n
h irsu tism , fro n tal b ald in g
clito ral e n large m e n t
d e e p e n in g o f vo ice
acn e
in cre ase in m u scu latu re
J d e fe m in izatio n
am e n o rrh e a
d e cre ase d b re ast size
Etiology
J co n stitu tio n al
m o st co m m o n
ask fo r fam ily h isto ry, e th n ic b ackgro u n d e .g. m e d ite rran e an )
J m e d icatio n s
an d ro ge n -m e d iate d : AC T H , an ab o lic ste ro id s, an d ro ge n s,
p ro ge statio n al age n ts
n o n -an d ro ge n m e d iate d h yp e rtrich o sis) : p h e n yto in ,
d iazo xid e , cyclo sp o rin , m in o xid il
J o varian
p o lycystic o varian syn d ro m e P C O )
tu m o u rs
J ad re n al
co n ge n ital h yp e rp lasia C AH , ad u lt-o n se t C AH )
tu m o u rs
J C u sh in g d ise ase - h igh AC T H
Inve s tigations
J in cre ase d te sto ste ro n e
J D H E A-S as m e asu re o f ad re n al an d ro ge n p ro d u ctio n
J in cre ase d L H /F S H , se e n co m m o n ly in P C O as ratio > 2.5
Tre atme nt
J co sm e tic th e rap y
J d isco n tin u e cau sative m e d icatio n s
J o ral co n trace p tive s
J lo w d o se glu co co rtico id
J sp iro n o lacto n e - acts as p e rip h e ral an d ro ge n an tago n ist
J cyp ro te ro n e ace tate - b lo cks an d ro ge n re ce p to r b in d in g
n o t co m m o n ly u se d in C an ad a)
ADRENOCORTICAL INSUFFICIENCY
Primary (Addis on Dis e as e )
J ad re n al p ath o lo gy
J m o st case s are id io p ath ic
like ly au to im m u n e d e stru ctio n o f ad re n als sin ce 50% o f
p atie n ts h ave circu latin g ad re n al an tib o d ie s
h igh asso ciatio n with o th e r au to im m u n e d ise ase s e .g. ch ro n ic
lym p h o cytic th yro id itis, typ e I D M , h yp e rth yro id ism , p e rn icio u s an e m ia)
N o te s
J m e tastatic tu m o u r - se co n d co m m o n e st cau se
J h e m o rrh agic in farctio n - co agu lo p ath y in ad u lts o r
Wate rh o u se -F rid e rich se n syn d ro m e in ch ild re n m e n in go co ccal
o r P se u d o m o n as se p tice m ia)
J ad re n ale cto m y
J gran u lo m ato u s d ise ase e .g. T B , sarco id o sis)
J in fe ctio n - p articu larly AID S
Se condary
J h yp o p itu itarism d u e to h yp o th alam ic-p itu itary d ise ase
J su p p re ssio n o f h yp o th alam ic-p itu itary axis b y e xo ge n o u s ste ro id s
o r e n d o ge n o u s ste ro id s fro m tu m o u r se e H yp o p itu itarism S e ctio n )
Clinical Fe ature s
J b o th p rim ary an d se co n d ary
we akn e ss an d fatigu e
p o stu ral h yp o te n sio n
n au se a/vo m itin g, d iarrh e a, an o re xia an d we igh t lo ss
ab d o m in al, m u scle , jo in t p ain
ad re n al crisis - in tractab le sym p to m s with circu lato ry
co llap se , L O C an d o fte n with a p re cip itatin g facto r
J p rim ary
h yp e rp igm e n tatio n , o f skin an d m u co u s m e m b ran e s
e .g. p alm ar cre ase s an d b u ccal m u co sa)
h yp e rkale m ia
d e h yd ratio n , salt cravin g
J se co n d ary
u su ally m o re ch ro n ic th an p rim ary
n o rm al p igm e n tatio n , p o tassiu m an d h yd ratio n
Lab Findings
J h yp o n atre m ia, h yp e rkale m ia, e le vate d B U N /cre atin in e
J ch ro n ic an e m ia n o rm o ch ro m ic n o rm o cytic)
J p rim ary
lo w co rtiso l u n re sp o n sive to e xo ge n o u s AC T H
h igh AC T H
ad re n al an tib o d ie s if au to im m u n e e tio lo gy
J se co n d ary
lo w AC T H
u su ally fin d n o rm al K
+
, B U N /cre atin in e
Tre atme nt
J acu te co n d itio n - can b e life th re ate n in g
IV N S o r D 5W/N S in large vo lu m e s
h yd ro co rtiso n e 1 00 m g IV q 6-8h fo r 24h , th e n rap id tap e rin g
su p p o rtive m e asu re s
J m ain te n an ce
p re d n iso n e 5 m g P O q a.m . an d 2.5 m g q p .m .
flo rin e f syn th e tic m in e ralo co rtico id ) 0.05-0.2 m g P O d aily if
m in e ralo co rtico id d e ficie n t
in cre ase d o se o f ste ro id in tim e s o f illn e ss o r fo r su rge ry
N o te s
ADRENAL MEDULLA
Cate cholamine Me tabolis m
J cate ch o lam in e s syn th e size d fro m tyro sin e in p o stgan glio n ic
sym p ath e tic n e rve s an d ch ro m affin ce lls o f ad re n al m e d u lla
J p re d o m in an t ad re n al cate ch o lam in e = e p in e p h rin e ad re n alin e )
J p re d o m in an t p e rip h e ral cate ch o lam in e = n o re p in e p h rin e
n o rad re n alin e )
PHEOCHROMOCYTOMA
Pathophys iology
J a tu m o u r arisin g fro m ch ro m affin ce lls o f sym p ath e tic syste m
J m o st co m m o n ly a sin gle tu m o u r o f ad re n al m e d u lla
J 1 0% e xtra-ad re n al, 1 0% m u ltip le tu m o u rs, 1 0% m align an t,1 0% fam ilial
J tu m o u r n o t in n e rvate d b u t via u n kn o wn m e ch an ism , ab le to
syn th e size an d re le ase cate ch o lam in e s
J case s sp o rad ic o r p art o f m u ltip le e n d o crin e n e o p lasia se e b e lo w)
J rare cau se o f h yp e rte n sio n < 0.1 % o f all h yp e rte n sive s)
J cu rab le if re co gn ize d an d p ro p e rly tre ate d , b u t fatal if n o t
Clinical Fe ature s
J sym p to m s o fte n p aro xysm al
J h e ad ach e - th e m o st co m m o n sym p to m o f an attack
J o th e rs: swe atin g, p alp itatio n s, flu sh in g, ch e st o r ab d o p ain ,
ap p re h e n sio n o r an xie ty
J se ve re h yp e rte n sio n d u rin g e p iso d e s; tach ycard ia
J su stain e d h yp e rte n sio n is m o re co m m o n an d p re se n t b e twe e n
attacks in 60% o f p atie n ts
Lab Findings
J in cre ase d u rin ary cate ch o lam in e s u su ally su fficie n t to
co n firm d iagn o sis
J e le vate d p lasm a e p in e p h rin e u n su p p re sse d b y clo n id in e
J p o sitive ad re n al C T scan
J m e ta-io d o -b e n zo gu an id in e M IB G ) u p take b y tu m o u r site d u rin g
scan ; u se fu l to lo cate tu m o u r fo r su rge ry
Tre atme nt
J ad e q u ate p re -o p e rative p re p aratio n
alp h a b lo ckad e - p o p h e n o xyb e n zam in e p re -o p ) , IV
p h e n to lam in e p e ri-o p e rative )
b e ta b lo ckad e - p ro p ran o lo l
vo lu m e re sto ratio n with vigo ro u s salt-lo ad in g
J su rgical re m o val o f tu m o u r with care fu l p re -o p e rative an d
p o sto p e rative IC U m o n ito rin g
J re scre e n u rin e o n e m o n th p o st-o p e rative
N o te s
MULTIPLE ENDOCRINE NEOPLASIA
J n e o p lastic syn d ro m e s in vo lvin g m u ltip le e n d o crin e glan d s
J tu m o u rs o f n e u ro e cto d e rm al o rigin AP U D am in e p re cu rso r u p take
an d d e carb o xylatio n ) ce lls
J au to so m al d o m in an t in h e ritan ce with co n sid e rab le variab ility in
p e n e tran ce an d in sp e cific tu m o u r in cid e n ce s am o n g kin d re d
J ge n e tic scre e n in g m e th o d s b e co m in g m o re availab le
Table 13.
MEN Type Chromos ome Implicate d Tis s ue s Involve d Clinical Fe ature s
I 1 1 syn d ro m e can e vo lve o ve r 30-40 ye ars
1 . P itu itary - an t. p itu itary ad e n o m as, o fte n n o n se cre tin g
b u t m ay se cre te G H an d P R L
2. P arath yro id - p rim ary h yp e rp arath yro id ism fro m h yp e rp lasia
3. P an cre as - p an cre atic isle t ce ll tu m o u rs
- gastrin o m a p e p tic u lce rs)
- in su lin o m as h yp o glyce m ia)
- VIP o m as se cre to ry d iarrh e a)
IIa 1 0 1 . T th yro id - m e d u llary th yro id can ce r
2. P arath yro id - p rim ary h yp e rp arath yro id ism fro m h yp e rp lasia
3. Ad re n al m e d u lla - p h e o ch ro m o cyto m a
IIb 1 . T h yro id - m e d u llary th yro id can ce r
2. Ad re n al m e d u lla - p h e o ch ro m o cyto m a
- O th e r: m u co sal n e u ro m as, M arfan o id fe atu re s
CALCIUM DISORDERS
CALCIUM HOMEOSTASIS
J se ru m C a is ab o u t 50% p ro te in b o u n d m o stly alb u m in ) an d n o t
e xch an ge ab le
J alte ratio n s in p ro te in co n te n t o f th e b lo o d fo r an y n u m b e r o f re aso n s
m ay affe ct th e to tal se ru m calciu m with o u t alte rin g th e io n ize d fo rm
J n o rm al to tal se ru m calciu m ran ge is 2.25-2.62 m m o l/L
J to co rre ct fo r ch an ge s in alb u m in : fo r e ve ry 1 0 g/L d e cre ase in alb u m in
fro m a n o rm al o f 40 g/L ) , ad d 0.25 m m o l/L to th e to tal calciu m re su lt
e .g. a calciu m o f 2.00 m m o l/L with an alb u m in o f 30 g/L is
2.25 co rre cte d
J io n ic C a le ve ls are m ain tain e d with in n arro w lim its 1 .1 5-1 .31 u m o l/L )
J so u rce s o f E C F C a: d ie t, re so rp tio n fro m b o n e
J lo ss o f C a fro m E C F sp ace via: G I lo sse s, re n al e xcre tio n , d e p o sitio n
in b o n e m atrix
J re gu late d m ain ly b y two facto rs: p arath yro id h o rm o n e P T H ) an d Vitam in D
J actio n s m ain ly o n th re e o rgan s: G I tract, b o n e , an d kid n e y
Parathyroid Hormone
J se cre tio n in cre ase d b y lo w se ru m C a an d in h ib ite d b y lo w se ru m M g
n o t in flu e n ce d d ire ctly b y P O 4 e xce p t b y P O 4 e ffe ct o n th e
io n ic calciu m le ve ls)
J m ajo r actio n s
in cre ase d o ste o clast activity > in cre ase d C a an d
in cre ase d P O 4
in cre ase d re n al tu b u lar C a an d M g) re so rp tio n
in h ib its re n al tu b u lar re so rp tio n o f P O 4 an d H C O 3)
in cre ase d 1 -a-h yd ro xylase activity > vitam in D >
in cre ase d C a an d P O 4 fro m gu t
N E T E F F E C T: in cre ase d se ru m C a > in cre ase d vit D ,
d e cre ase d P O 4
Vitamin D
J n e ce ssary fo r C a an d P O 4 ab so rp tio n fro m G I tract
J ch o le calcife ro l fo rm e d in th e skin b y th e actio n o f U V ligh t
J co n ve rte d to 25 O H ) -vit D b y th e live r
J co n ve rte d to 1 ,25 O H ) 2-vit D in th e kid n e y
J p ro d u ctio n o f 1 ,25 O H ) 2-vit D is e n h an ce d b y P T H an d lo w P O 4 le ve ls
N o te s
CALCIUM DISORDERS . . . CONT.
J P T H an d lo w se ru m P O are stim u lato rs o f p ro d u ctio n
J if a P T H d e ficie n cy e xists, m e tab o lism is sh u n te d in to th e
p ro d u ctio n o f re lative ly in e rt 24,25- o r 25,26 O H ) 2-vit D
J m ajo r actio n s
in cre ase d C a an d in cre ase d P O 4 ab so rp tio n fro m gu t
in cre ase d b o n e re so rp tio n
in cre ase d o ste o clasts
in cre ase d re n al C a re so rp tio n
N E T E F F E C T: in cre ase d se ru m C a an d P O 4
Calcitonin
J p o lyp e p tid e se cre te d b y th yro id C ce lls
J se cre tio n e n h an ce d b y C a, G I h o rm o n e s, p e n tagastrin
J m ajo r actio n s
d e cre ase d o ste o clastic b o n e re so rp tio n
in cre ase d re n al p h o sp h ate an d so d iu m cle aran ce
AC U T E N E T E F F E C T: d e cre ase d se ru m C a wh e n give n in
p h arm aco lo gic d o se s
Magne s ium
J m ajo r in trace llu lar d ivale n t catio n
J C a is re so rb e d fro m th e kid n e y with M g, an d th u s C a b alan ce is
d ifficu lt to m ain tain in M g d e ficie n cy
Phos phorus
J fo u n d in all tissu e s an d n e ce ssary fo r m o st b io ch e m ical p ro ce sse s
as we ll as b o n e fo rm atio n
Table 14. Summary of Effe cts
Hormone Ne t Effe ct
P arath yro id H o rm o n e P T H ) in cre ase d C a
in cre ase d vit D
d e cre ase d P O 4
Vitam in D in cre ase d C a
in cre ase d P O 4
C alcito n in d e cre ase d C a
in p h arm aco lo gic d o se s)
HYPERCALCEMIA
De finition
J to tal se ru m C a > 2.62 m m o l/L co rre cte d ) O R io n ize d C a > 1 .35 u m o l/L
J a m e d ical e m e rge n cy
vo lu m e d e p le tio n
arrh yth m ias
Pathophys iology
J in cre ase d b o n e re so rp tio n
J in cre ase d gastro in te stin al ab so rp tio n
J d e cre ase d re n al e xcre tio n
Clinical Fe ature s
J sym p to m s d e p e n d e n t o n th e ab so lu te C a valu e an d th e rate o f its
rise m ay b e asym p to m atic)
N o te s
Table 15. Symptoms of Hype rcalce mia
Cardiovas cular Gas trointe s tinal Re nal Ne urologic MSK Ps ychiatric
(groans )
h yp e rte n sio n an o re xia p o lyu ria h yp o to n ia b o n e p ain co gn itive ch an ge s
8d igo xin to xicity n au se a p o lyd ip sia h yp o re fle xia (bone s ) 8ale rtn e ss
arrh yth m ia vo m itin g n e p h ro ge n ic D I m yo p ath y p sych o sis (moans )
9Q T in te rval P U D n e p h ro lith iasis p are sis
p an cre atitis (s tone s )
re n al failu re
Clinical Pe arl
J The s ymptoms and s igns of hype rcalce mia are :
Bone s , Stone s , ps ychos is -bas e d Moans , and abdominal Groans
Endocrine Dis orde rs
1.Parathyroid Dis e as e
a) Primary Hype rparathyroidis m
J m ajo r cau se o f h yp e rcalce m ia
J P T H h yp e rse cre tio n cau se s in cre ase C a an d b o n e
m e tab o lism /tu rn o ve r wh ile d e cre asin g P O 4
J in clu d e s so litary ad e n o m a m o st co m m o n , 81 %) , h yp e rp lasia 1 5%) ,
carcin o m a 4%) , M E N I an d IIa
J p re se n tatio n : 50% asyp to m atic, re n al calcu li, n e u ro m u scu lar
d ise ase , d e cre ase d b o n e d e n sity an d asso ciate d co n se q u e n ce s
J in ve stigatio n s: se ru m C a, P O 4, P T H , d iagn o stic im agin g fo r re n al
calcu li an d o ste o p e n ia
J tre atm e n t: co n tin u e d su rve illan ce vs. su rge ry
b) Se condary Hype rparathyroidis m
J asso ciate d with re n al failu re
2. Malignancy
J so lid tu m o u r e .g. b re ast) with b o n e m e tastase s m e d iate d b y
o ste o clast activatin g facto r O AF ) an d vario u s cyto kin e s
J so lid tu m o u rs with h u m o ral m e d iatio n o f h yp e rcalce m ia se co n d ary
to p ro d u ctio n o f P T H -re late d p e p tid e s P T H rp ) as se e n in lu n g an d
kid n e y can ce rs
J h e m ato lo gical m align an cy e .g. m u ltip le m ye lo m a, lym p h o m a, le u ke m ia)
3. Vitamin D Re late d
J vit D in to xicatio n
J gran u lo m ato u s d ise ase s e .g. sarco id o sis)
4. High Bone Turnove r
J h yp e rth yro id ism
J P age t's
J vit A e xce ss
5. Drugs
J th iazid e s
J lith iu m
J C a C arb o n ate
6. Re nal Failure Bas e d
J m ilk-alkali syn d ro m e h yp e rcalce m ia with alkalo sis an d re n al failu re )
J alu m in u m in to xicatio n
N o te s
7. Familial Hypocalciuric Hypocalce mia
J au to so m al d o m in an t
J m u tatio n in C a se n sin g re ce p to r ge n e le ad s to ab n o rm al se n sin g
calciu m b y p arath yro id glan d s an d re n al tu b u le s cau sin g
in ap p ro p riate se cre tio n o f P T H an d e xce ssive tu b al re ab so rp tio n
o f calciu m
Tre atme nt of Hype rcalce mia
J tre atm e n t d e p e n d s o n th e C a le ve l an d th e sym p to m s
J tre at acu te , sym p to m atic h yp e rcalce m ia aggre ssive ly
J re h yd ratio n
IV N S in fu sio n
o n ly afte r ad e q u ate ly re h yd rate d , p ro m o te calciu re sis with a
lo o p d iu re tic, i.e . fu ro se m id e
J in h ib it b o n e re so rp tio n
J b isp h o sp h o n ate s
in h ib ito r o f o ste o clast activity
in d icate d in m align an cy-re late d h yp e rcalce m ia
p am id ro n ate is m o st co m m o n ly u se d
IV ro u te sin ce p o o rly ab so rb e d fro m th e G I tract
se ve ral d ays u n til fu ll e ffe ct b u t lastin g e ffe ct
J m ith ram ycin
e ffe ctive wh e n p atie n t can n o t to le rate large flu id lo ad
d an ge ro u s - h e m ato to xic an d h e p ato to xic)
J calcito n in
in h ib its o ste o clastic b o n e re so rp tio n an d p ro m o te s re n al
e xcre tio n o f calciu m
acts rap id ly b u t n o rm al C a le ve l se ld o m ach ie ve d
tach yp h ylaxis m ay o ccu r
J in cre ase u rin ary C a e xcre tio n
J ste ro id s
an ti-tu m o u r e ffe cts
u se fu l in vit D -re late d h yp e rcalce m ia in clu d in g sarco id o sis)
an d h e m ato ge n o u s m align an cie s m ye lo m a, lym p h o m a)
J su rgical tre atm e n t if in d icate d
J o th e r
p ro staglan d in in h ib ito rs
J avo id im m o b ilizatio n
HYPOCALCEMIA
De finition
J to tal se ru m C a < 2.25 co rre cte d )
Clinical Fe ature s
J m o st ch aracte ristic sym p to m is te tan y
J d iffe re n tial d iagn o sis o f te tan y
m e tab o lic alkalo sis with h yp e rve n tilatio n )
h yp o kale m ia
h yp o m agn e se m ia
Table 16. Symptoms of Hypocalce mia
Acute Hypocalce mia Chronic Hypocalce mia
p arasth e sias C N S : le th argy, se izu re s, p sych o sis, b asal gan glia calcificatio n
h yp e rre fle xia e xtrap yram id al e ffe cts, p ap ille d e m a, p se u d o tu m o u r ce re b ri
te tan y C VS : p ro lo n ge d Q T in te rval
laryn go sp asm with strid o r G I: m alab so rp tio n , d iarrh e a
co n fu sio n S kin : d ry, scalin g, alo p e cia, b rittle an d fissu re d n ails,
C h o vste k s sign tap C N V) m o n iliasis, ab n o rm al d e n titio n
Tro u sse au s sign carp al sp asm ) O cu lar: cataracts, p ap ille d e m a
N o te s
1. De ficie nt PTH Action (Hypoparathyroidis m)
J d e cre ase d b o n e re so rp tio n
J d e cre ase d in te stin al C a ab so rp tio n
J in cre ase d re n al C a e xcre tio n
J iatro ge n ic p o st-th yro id e cto m y/
1 31
I ab latio n )
J id io p ath ic/au to im m u n e
co n ge n ital D iG e o rge syn d ro m e ) - d ysge n e sis o f th ym u s
an d p arath yro id glan d s
acq u ire d p o lyglan d u lar au to im m u n e d ise ase -
h yp o p arath yro id ism ad re n al in su fficie n cy go n ad al
failu re h yp o th yro id ism an d rare ly h yp o p itu itarism , D I,
Typ e 1 D M )
J h e m o ch ro m ato sis
J p se u d o h yp o p arath yro id ism
P T H re sistan ce se co n d ary to G s p ro te in d e ficie n cy
J se ve re h yp o m agn e se m ia
n o rm ally lo w M g le ve l stim u late s P T H se cre tio n , b u t ch ro n ic
h yp o m agn e se m ia is p arad o xically asso ciate d with im p aire d
P T H se cre tio n
J lo w M g le ve ls also im p air p e rip h e ral re sp o n sive n e ss to P T H
De cre as e d Intake or Abs orption
2. De ficie nt Vitamin D Action
J d e cre ase d in te stin al m alab so rp tio n
J vitam in D d e ficie n cy
J re ce p to r d e fe ct vitam in D -d e p e n d e n t ricke ts typ e II)
J h yd ro xylatio n d e fe cts
co n ge n ital: Typ e I ricke ts
acq u ire d : C R F, h e p atic failu re
Incre as e d Los s
3. Re nal Dis e as e
J m o st co m m o n cau se o f h yp o calce m ia
J C R F, n e p h ro tic syn d ro m e , AR F
4. Drugs
J p h o sp h ate
J calcito n in
J am in o glyco sid e s
J an tin e o p lastic d ru gs cisp latin , m ith ram ycin )
J lo o p d iu re tics
5. Alcoholis m
Phys iological Caus e s
6. Acute Pancre atitis
J sap o n ificatio n o f C a b y lip id s
7. Pre gnancy
J lo w to tal C a d u e to h yp o alb u m in e m ia) b u t n o rm al io n ize d le ve l
Tre atme nt of Hypocalce mia
J co rre ct u n d e rlyin g d iso rd e r
J acu te /se ve re h yp o calce m ia
calciu m glu co n ate ge n e rally re q u ire s co n tin u o u s in fu sio n )
go al is to raise C a to lo w n o rm al ran ge to p re ve n t sym p to m s
b u t allo w m axim u m
stim u latio n o f P T H
J if P T H re co ve ry n o t e xp e cte d , re q u ire s lo n g-te rm th e rap y with
vitam in D an d calciu m
N o te s
METABOLIC BONE DISEASE
OSTEOPOROSIS
De finition
J an age -re late d co n d itio n ch aracte rize d b y d e cre ase d b o n e m ass
an d m icro arch ite ctu ral d e te rio ratio n o f b o n e tissu e with a co n se q u e n t
in cre ase in b o n e fragility an d su sce p tib ility to b o n e fractu re
Pathophys iology
J b o n e re so rp tio n > b o n e fo rm atio n /re m o d e llin g
Ris k Factors
J lo w p e ak b o n e m ass
sm all C au casian o r Asian fe m ale
fam ily h isto ry
J e stro ge n -re late d b o n e m ass
e arly m e n o p au se
o o p h o re cto m y
am e n o rrh e a
J age
J se co n d ary to m e d ical d ise ase se e b e lo w)
J o th e r
d ie t
sm o kin g
alco h o l
caffe in e
m in im al we igh t-b e arin g p h ysical activity
Clas s ification
1. Primary Os te oporos is
Table 17. Type s of Primary Os te oporos is
Pos t-me nopaus al Se nile
S e x m ain ly wo m e n wo m e n an d m e n
Age with in 20 ye ars fo llo win g m e n o p au se with in cre asin g age
B o n e Affe cte d trab e cu lar b o n e trab e cu lar an d co rtical b o n e
2. Se condary Os te oporos is
J e n d o crin o p ath ie s
h yp e rp arath yro id ism
h yp e rth yro id ism
p re m atu re m e n o p au se
d iab e te s
J m align an cy
m u ltip le m ye lo m a
J gastro in te stin al d ise ase
m alab so rp tio n
live r d ise ase
J d ru gs
d ilan tin
ste ro id s
J o th e r
rh e u m ato id arth ritis
re n al d ise ase
p o o r n u tritio n
Fe ature s
J co m m o n ly asym p to m atic
J p ain , e sp e cially b ackach e
J co llap se d ve rte b rae > h e igh t lo ss
J fractu re s - h ip , ve rte b rae , h u m e ru s, an d wrists m o st co m m o n ;
D o wage rs h u m p = co llap se fractu re o f ve rte b ral b o d ie s in
m id -d o rsal re gio n
N o te s
METABOLIC BONE DISEASE . . . CONT.
Inve s tigations
J lab o rato ry
u su ally n o rm al se ru m C a, P O 4, alkalin e p h o sp h atase
J d e n sito m e try
sin gle -e n e rgy x-ray ab so rp tio m e try, d u al-e n e rgy x-ray
ab so rp tio m e try m o st u se fu l) , q u an titative C T, u ltraso n o grap h y
lu m b ar sp in e an d vie ws o f fe m u r
co m p are d to co n tro ls
Tre atme nt
J n o t ve ry satisfacto ry
J p re ve n tio n an d life style m o d ificatio n
e xe rcise
C a su p p le m e n tatio n
vitam in D
lim it sm o kin g an d alco h o l u se
J m e asu re s to d e cre ase fu rth e r b o n e lo ss/b o n e re so rp tio n
p o stm e n o p au sal e stro ge n re p lace m e n t
C a su p p le m e n tatio n
b isp h o sp h o n ate s - in h ib ito rs o f o ste o clast b in d in g
calcito n in - o ste o clast re ce p to r b in d in g
th iazid e d iu re tics fo r h yp e rcalcu ria)
J m e asu re s to in cre ase b o n e m ass
flu o rid e - stim u late o ste o b lasts fo r b o n e fo rm atio n
p arath yro id h o rm o n e
OSTEOMALACIA AND RICKETS
De finitions
J ab n o rm al co n ce n tratio n o f io n s le ad s to h igh e r p ro p o rtio n o f
o ste o id u n m in e ralize d ) tissu e
J d ise ase p rio r to e p ip h yse al clo su re in ch ild h o o d ) = ricke ts
J d ise ase afte r e p ip h yse al clo su re in ad u lth o o d ) = o ste o m alacia
Etiology
J vitam in d iso rd e rs
d e cre ase d availab ility o f vitam in D
in su fficie n t su n ligh t e xp o su re
n u tritio n al d e ficie n cy
m alab so rp tio n
h yd ro xylatio n d e fe cts
n e p h ro tic syn d ro m e
live r d ise ase
ch ro n ic re n al failu re
an tico n vu lsan t th e rap y
J m in e ral d e ficie n cie s
calciu m d e ficie n cy
p h o sp h ate d e ficie n cy
d e cre ase d G I ab so rp tio n
in cre ase d re n al lo ss
J d iso rd e rs o f b o n e m atrix
J in h ib ito rs o f m in e ralizatio n
alu m in u m
b isp h o sp h o n ate s
Table 18. Clinical Pre s e ntations of Ricke ts and Os te omalacia
Ricke ts Os te omalacia
ske le tal d e fo rm itie s, b o wle gs n o t as d ram atic
fractu re su sce p tib ililty d iffu se ske le tal p ain
we akn e ss an d h yp o to n ia b o n e te n d e rn e ss
d istu rb e d gro wth fractu re s
rach itic ro sary gait d istu rb an ce s
p ro m in e n t co sto ch o n d ral ju n ctio n s) p ro xim al m u scle we akn e ss
H arriso n s gro o ve
in d e n tatio n lo we r rib s)
h yp o calce m ia
N o te s
Inve s tigations
J lab o rato ry
d e cre ase d se ru m C a
d e cre ase d se ru m p h o sp h o ru s
in cre ase d se ru m alkalin e p h o sp h atase
d e cre ase d u rin ary C a
J rad io lo gic fin d in gs
p se u d o fractu re s th o u gh t to b e h e ale d m icro fractu re s
rad io lu ce n t b an d in g o f sp in e
J b o n e b io p sy
u su ally n o t n e ce ssary b u t co n sid e re d th e go ld stan d ard fo r d iagn o sis
Tre atme nt
J d e p e n d s o n th e u n d e rlyin g cau se
J vitam in D su p p le m e n tatio n
J P O 4 su p p le m e n ts if lo w se ru m P O 4 is p re se n t
J o ral C a fo r iso late d calciu m d e ficie n cy
J H C O 3 if ch ro n ic acid o sis
RENAL OSTEODYSTROPHY
Pathophys iology
J m e tab o lic b o n e d ise ase se co n d ary to ch ro n ic re n al failu re
J co m b in atio n o f h yp e rp h o sp h ate m ia in h ib its 1 ,25 O H ) 2-vit D
syn th e sis) an d lo ss o f re n al m ass re d u ce d 1 --h yd ro xylase )
Type s
J p ro d u ce s a m ixtu re o f fo u r typ e s o f b o n e d ise ase
o ste o m alacia - fro m acid o sis an d re te n tio n o f to xic m e tab o lite s
o ste o p o ro sis - m e tab o lic acid o sis d isso lu tio n o f b o n e b u ffe rs
o ste itis fib ro sa cystica - fro m in cre ase d P T H
o ste o scle ro sis - fro m in cre ase d P T H
J m e tastatic calcificatio n se co n d ary to h yp e rp h o sp h ate m ia m ay o ccu r
Clinical Fe ature s
J so ft tissu e calcificatio n s > with n e cro tic skin le sio n s if ve sse ls in vo lve d
J o ste o d ystro p h y > b o n e p ain an d fractu re s
J p ru ritu s
J n e u ro m u scu lar irritab ility an d te tan y m ay o ccu r
J rad io lo gic fe atu re s o f o ste itis fib ro sa cystica, o ste o m alacia,
o ste o scle ro sis, o ste o p o ro sis
Tre atme nt
J p re ve n tio n
m ain tain n o rm al se ru m C a an d P O 4 b y re strictin g P O 4 in take
to 1 g/d ay
C a su p p le m e n ts
P O 4 b in d in g age n ts
p ro p h ylactic u se o f vitam in D with clo se m o n ito rin g to avo id
h yp e rcalce m ia an d m e tastatic calcificatio n
PAGETS DISEASE OF BONE
De finition
J a m e tab o lic d ise ase ch aracte rize d b y e xce ssive b o n e d e stru ctio n an d re p air
Epide miology
J a co m m o n d ise ase : 5% o f th e p o p u latio n , 1 0% o f p o p u latio n > 80 ye ars o ld
Etiology
J p o stu late d to b e re late d to a slo w viral in fe ctio n o f o ste o clasts,
p o ssib ly p aram yxo viru s
J stro n g fam ilial in cid e n ce
N o te s
Pathophys iology
J in itiate d b y in cre ase d o ste o clastic activity le ad in g to in cre ase d
b o n e re so rp tio n ; o ste o b lastic activity in cre ase s in re sp o n se to
p ro d u ce n e w b o n e th at is stru ctu rally ab n o rm al an d fragile
Clinical Fe ature s
J u su ally asym p to m atic ro u tin e x-ray fin d in g o r e le vate d alkalin e
p h o sp h atase )
J se ve re b o n e p ain e .g. p e lvis, fe m u r, tib ia) , o fte n th e p re se n tin g
co m p lain t
J ske le tal d e fo rm itie s b o we d tib ias, kyp h o sis, fre q u e n t fractu re s
J sku ll in vo lve m e n t h e ad ach e s, in cre ase d h at size , d e afn e ss
J in cre ase d warm th o ve r in vo lve d b o n e s d u e to in cre ase d vascu larity
Inve s tigations
J lab o rato ry
se ru m alkalin e p h o sp h atase is u su ally ve ry h igh
n o rm al o r in cre ase d se ru m C a
n o rm al se ru m P O 4
in cre ase d u rin ary h yd ro xyp ro lin e in d icate s re so rp tio n )
J im agin g
e valu ate th e e xte n t o f d ise ase with b o n e scan
in itial le sio n m ay b e d e stru ctive an d rad io lu ce n t
in vo lve d b o n e s are e xp an d e d an d d e n se r th an n o rm al
m u ltip le fissu re fractu re s in lo n g b o n e s
J p rim ary b o n e le sio n s
o ste o ge n ic sarco m a
m u ltip le m ye lo m a
fib ro u s d ysp lasia
J se co n d ary b o n e le sio n s
o ste itis fib ro sa cystica
m e tastase s
Complications
J fractu re s
J h yp e rcalce m ia an d n e p h ro lith iasis
J cran ial n e rve co m p re ssio n an d p alsie s, i.e . d e afn e ss
J sp in al co rd co m p re ssio n
J o ste o sarco m a/sarco m ato u s ch an ge
1 -3%
in d icate d b y m arke d b o n e p ain , n e w lytic le sio n s an d
su d d e n in cre ase d alkalin e p h o sp h atase
J h igh o u tp u t co n ge stive h e art failu re d u e to in cre ase d vascu larity
J o ste o arth ritis
Tre atme nt
J sym p to m atic th e rap y
J calcito n in
re d u ce o ste o clastic activity
J b isp h o sp h o n ate s, i.e . ale n d ro n ate
in h ib it o ste o clast-m e d iate d b o n e re so rp tio n
N o te s
REPRODUCTIVE ENDOCRINOLOGY
J fe m ale go n ad al d iso rd e rs an d th e e n d o crin o lo gy o f p re gn an cy are
d iscu sse d in th e G yn e co lo gy N o te s
Androge n Re gulation
J b o th p o sitive an d n e gative fe e d b ack m ay o ccu r b y an d ro ge n
d ire ctly o r afte r co n ve rsio n to e stro ge n
J te sto ste ro n e fro m th e L e yd ig ce ll) p rim arily in vo lve d in n e gative
fe e d b ack o n L H , wh e re as in h ib in fro m th e S e rto li ce ll) su p p re sse s
F S H se cre tio n
TESTS OF TESTICULAR FUNCTION
J te sticu lar size lo we r lim it = 4 x 2.5 cm )
J se ru m L H , F S H , te sto ste ro n e
J h C G stim u latio n te st
asse sse s ab ility o f L e yd ig ce ll to re sp o n d to go n ad o tro p in
J se m e n an alysis
se m e n vo lu m e
sp e rm co u n t, m o rp h o lo gy an d m o tility
J te sticu lar b io p sy
in d icate d in th e co n te xt o f n o rm al F S H an d azo o sp e rm ia/o ligo sp e rm ia
MALE GONADAL DISORDERS
A. MALE HYPOGONADISM
De finition
J d e ficie n cie s in gam e to ge n e sis o r th e se cre tio n o f go n ad al h o rm o n e s
Etiology
1. Hype rgonadotropic Hypogonadis m/Primary Te s ticular
Failure (incre as e d LH/FSH)
J co n ge n ital
ch ro m o so m al d e fe cts, i.e . K lin e fe lte rs syn d ro m e , N o o n an s syn d ro m e )
cryp to rch id ism
m ale p se u d o h e rm ap h ro d itism
b ilate ral an o rch ia
J ge rm ce ll d e fe cts
S e rto li ce ll o n ly syn d ro m e arre st o f sp e rm d e ve lo p m e n t)
L e yd ig ce ll ap lasia/failu re
J in flam m atio n
o rch itis m u m p s, tu b e rcu lo sis, lym p h o m a, le p ro sy
ge n ital tract in fe ctio n
J p h ysical facto rs
trau m a, h e at, irrad iatio n
J d ru gs
m ariju an a, alco h o l, ch e m o th e rap e u tic age n ts
J m yo to n ic d ystro p h y
J d e fe cts in an d ro ge n b io syn th e sis
J id io p ath ic
2. Hypogonadotropic Hypogonadis m/Hypothalamic
Pituitary Failure (de cre as e d or normal LH)
J co n ge n ital - K allm an , P rad e r-Willi
J co n stitu tio n al d e lay
J C u sh in g syn d ro m e
J h yp o th yro id ism
J h yp o p itu itarism - p itu itary tu m o u rs, h yp o th alam ic le sio n s,
h e m o ch ro m ato sis
J d ru gs - alco h o l, m ariju an a, sp iro n o lacto n e , ke to co n azo le
G n R H ago n ists, p rio r an d ro ge n s
J e stro ge n se cre tin g tu m o u rs - te sticu lar, ad re n al
J ch ro n ic illn e ss
J m aln o u rish m e n t
J id io p ath ic
N o te s
REPRODUCTIVE ENDOCRINOLOGY . . . CONT.
3. De fe cts in Androge n Action
J co m p le te an d ro ge n in se n sitivity te sticu lar fe m in izatio n )
J in co m p le te an d ro ge n in se n sitivity
5--re d u ctase d e ficie n cy
Clinical Pre s e ntation
J d e p e n d s o n age o f o n se t
J fe tal life
am b igu o u s ge n italia an d m ale p se u d o h e rm ap h ro d itism
J p re p u b e rtal
p o o r se co n d ary se xu al d e ve lo p m e n t, p o o r m u scle d e ve lo p m e n t
e u n u ch o id ske le tal p ro p o rtio n s u p p e r/lo we r se gm e n t ratio
< 1 ; arm sp an /h e igh t ratio > 1 )
J p o stp u b e rtal
d e cre ase d lib id o
e re ctile d ysfu n ctio n
in fe rtility
d e cre ase d facial an d b o d y h air if ve ry sign ifican t an d ro ge n
d e ficie n cy ve ry lo w le ve ls re q u ire d to m ain tain se xu al h air
fin e wrin kle s in th e co rn e rs o f m o u th an d e ye s
o ste o p o ro sis with lo n gstan d in g h yp o go n ad ism
Tre atme nt
J co n sid e r te sto ste ro n e re p lace m e n t
B. MALE INFERTILITY
J m ajo rity o f in fe rtile m ale s h ave n o e n d o crin e d ise ase
J ab o u t 90% h ave o ligo sp e rm ia o r azo o sp e rm ia an d 1 0% h ave
n o rm al se m in al flu id
1. Endocrine
J cau se s o f h yp o go n ad ism as ab o ve
J h yp e rth yro id ism /h yp o th yro id ism
J ad re n al in su fficie n cy
J co n ge n ital ad re n al h yp e rp lasia
2. Sys te mic Illne s s
3. De fe cts in Spe rmatoge ne s is
J im m o tile cilia syn d ro m e K artage n e r syn d ro m e )
J d ru g-in d u ce d
J se m in ife ro u s tu b u le failu re
J h e at e xp o su re
4. Ductal Obs truction se e U ro lo gy N o te s)
5. Se minal Ve s icle and Pros tatic Dis e as e
6. Varicoce le
7. Re trograde Ejaculation
8. Antibodie s to Spe rm or Se minal Plas ma
9. Ps ychoge nic
10. Anatomical De fe cts
11. Cryptorchidis m
J d e sce n t m ay b e stim u late d b y h C G , o r if th is fails, b y su rge ry
J u n d e sce n d e d te ste s h ave in cre ase d in cid e n ce 20-50 tim e s) o f
n e o p lasia
N o te s
REPRODUCTIVE ENDOCRINOLOGY . . . CONT.
Inve s tigations
J h isto ry an d p h ysical
J se m e n an alysis
J b lo o d te sts L H , F S H , te sto ste ro n e , p ro lactin , th yro id fu n ctio n )
J karyo typ e
J te sticu lar b io p sy if n o rm al size d te ste s, n o rm al h o rm o n al
p aram e te rs an d azo o sp e rm ia
C. ERECTILE DYSFUNCTION (IMPOTENCE) se e U ro lo gy N o te s)
D. GYNECOMASTIA
De finition
J p ro life ratio n o f th e glan d u lar co m p o n e n t o f th e m ale b re ast
Pathophys iology
J e stro ge n /an d ro ge n im b alan ce - in cre ase d e stro ge n /an d ro ge n ratio
J p h ysio lo gic se e b e lo w)
J p ath o lo gic se e b e lo w)
Etiology
J p h ysio lo gic
n e o n atal m ate rn al h o rm o n e )
p u b e rty
agin g
J p ath o lo gic
e n d o crin o p ath ie s - p rim ary h yp o go n ad ism , h yp e rth yro id ism
e xtre m e h yp e rp ro lactin e m ia, ad re n al d ise ase
tu m o u rs - p itu itary, ad re n al, te sticu lar, b re ast
ch ro n ic d ise ase s - live r, re n al, m aln u tritio n , o th e r
d ru gs - sp iro n o lacto n e , cim e tid in e , ch e m o th e rap y,
m ariju an a
co n ge n ital/ge n e tic - K lin e fe lte rs
o th e r - id io p ath ic, fam ilial
Inve s tigations
J h isto ry
age , o n se t, d u ratio n , p ain , fam ily h isto ry, ch ro n ic d ise ase s, d ru gs
J p h ysical e xam in atio n
ge n e ral h e alth , fe m in izatio n , th yro id /ad re n al/live r/te sticu lar
J in ve stigatio n s
lab o rato ry - se ru m T S H , P R L , L H , fre e te sto ste ro n e
Tre atme nt
J m e d ical
co rre ct th e u n d e rlyin g d iso rd e r, d isco n tin u e re sp o n sib le
d ru g
an d ro ge n s fo r h yp o go n ad ism
an tie stro ge n s - tam o xife n , clo m ip h e n e
J su rgical
u su ally re q u ire d if gyn e co m astia p re se n t fo r > 1 ye ar
re d u ctio n m am m o p lasty
ABNORMALITIES OF PUBERTY
(Male and Fe male ) se e P e d iatrics N o te s)
N o te s
COMMON MEDICATIONS USED
IN ENDOCRINOLOGY
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5

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m
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e
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.

d
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D
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.
7
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m
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i
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f
l
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m
m
a
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n

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