Sie sind auf Seite 1von 98

HYPOTHALAMUS

DIABETES INSIPIDUS
SIADH
TRUE PRECOCIOUS PUBERTY
DELAYED PUBERTY
AMENORRHEA
 impossibility of the kidney to concentrate urine

  the free water (without electrolytes) will be


eliminated in excess.
Causes

 partial or total ADH deficit (central DI)

 renal unresponsiveness to physiologic actions of


ADH (nephrogenic DI)

!!! ADH levels are normal or elevated.


 rare disease:1-2 cases/100.000 persons,

 F:M = 1:1.
 onset – sudden

 occurs at any age (rarely in suckling)

 Polyuria:
 may be > 10 liters/day
 urine is diluted, discoloured, inodorous, insipidus

 Polydipsia
 thirst has imperative character
 ingestion of big amounts of liquid/24 hours,

 It exceeds polyuria :

 due to an associated “potophillic index”

 conditioned protective reflex


(the patient drinks to “cover” in advance his
needs!).
 Potophillia - associated to psychiatric disorders:
 anxiety
 insomnia
 weakness

 Potomania - primary morphologic alteration of thirst


center.
 liquid loss > liquid ingestion
Patients present:
 more frequent in:
•skin and mucosal
 older patients,
dryness,
 patients given anesthesia, •constipation,
 cerebro-vascular accidents, •weight loss,
 children under 4 years of •confusion and
age. •even death.
 opto-chiasmatic compression syndrome –
tumoral syndrome
 headache
 hypothalamic functional disorders :
 polyfagia,
 heat or cold intolerance,
 behavior modifications.
1.Hypothalamic osmo- receptors destruction

2. ADH synthesis defect

3. Inadequate ADH secretion  inefficient ADH

4. Absence of renal receptors


Imaging studies

Congenital abnormality – Lesions after neonatal hipoxic


absence of retrohypophysis encephalopaty
1. Central diabetes insipidus
 Acquired
 Hereditary
 Idiopathic

2. Nephrogenic diabetes insipidus


 Hereditary
 Acquired
a) Acquired:
 Tumors

 Trauma

 Granulomatous infiltration

 Post-infectious status

 Vascular causes (trombosis,hemorrhage,


necrosis,cerebral aneurisms)
b) Hereditary:
 dominant
 recesive
Could be:
 Familial - usually partial ADH deficit
 Congenital - associated to other disorders:
 Laurence-Moon-Bardet-Biedl syndrome (obesity, retinitis
pigmentosa  blindness, polydactyly, hypogonadism)
 D.I.D.M.O.A.D. syndrome (diabetes insipidus,diabetes
mellitus, optic atrophy, deafness).
c) Idiopatic:

 more frequent in adult: 67 % of cases

 normal duration of life


2 forms:
Hereditary: Acquired - more frequent:
- drug-induced: lithium, vinblastine
- renal diseases:
- Dominant X transmission chronic renal failure,
hyperaldosteronism,
- manifest only in boys amiloidosis,
sarcoidosis
- hypercalcemia:
hyperparathyroidism,
bone tumors,
Hodgkin disease,
sarcoidosis,
hypervitaminosis D.
1. Partial diabetes insipidus:

 small amounts of ADH,

 urinary volume - not very increased,

 urinary density may reach 1010-1014.


2. Diabetes insipidus with
- hypodipsia and
- essential hypernatremia – by dehydration:
 severe form of diabetes insipidus,
 lesions that affect thirst mechanism,
 ADH secretion - delayed.
 diuresis - unchanged
 hypernatremia -160 mEq/l -mortality 75%.
 neuronal dehydration with:
 convulsions and coma.
3. Diabetes insipidus in children < 4 years old:

 growth deficit and

 impared mental development.


4. Diabetes insipidus in pregnant women:

 during the last trimester - vasopressinasis occur

 needs in ADH dosis are increased.

 risk to develop diabetes insipidus during the last


months of pregnancy.
1. ADH measurement by RIA:

 low level,

 not a specific method.


2. Urine volume - very increased.

3. Urine density:
- very low - about 1000 (water-like).
- could be higher, but below normal values
(partial forms).
4. Seric and urinary ionogram:

 hypernatremia in dehydration

 hyponatremia in dilution
5. Urine and plasma osmolality -low.
a) Water deprivation test :
based on osmo-and volume-receptors
stimulation
With mild polyuria, water deprivation can begin
the night before the test.
With severe polyuria, water restriction is carried
out during the day (to allow close observation)
The extent of deprivation is limited by the
patient’s thirst, drop in BP, dehydration
urine - collected every hour (volume +density).
Results

In normal persons:
 urinary volume- decreases and
 urinary density and osmolality increase.

Central diabetes insipidus:


 inability to concentrate urine.
urine density may reach 1010 - partial forms.
b) ADH test:
- performed at the end of thirst test,
- synthetic ADH is administered;.

Urine density
- in normal persons – increment < 9% .
- central diabetes insipidus – increment > 20 %.
- nephrogenic diabetes insipidus- no response.
c) Endogenous ADH reserves - explored with:

 nicotine

 hypertonic saline solution

 clorpropamide.
1. Diabetes mellitus:

 polyuria

 glycosuria

 increased urine density.


2. Hyperthyroidism:

 Polyuria
- thyroxine effect on renal tubes,

- effect accentuated by adrenergic


stimulation.

 Betablokers improve the symptoms.


3. Hypercalcemia

4. Psychogenic polydipsia:

 with secondary polyuria -disappears with


hydric restriction.
5. Renal diseases:

 chronic renal failure,

 congenital or acquired tubulopathy.


1. Central diabetes insipidus:
1. desmopressin acetate- synthetic analogue of vasopressin:
 intranasally.
 not oxytocic effects and
 not develops antibodies.
2. vasopressin tannate- i.m.:
 effects for 24-72 hours
 side effects:abdominal pain,angina
3. aqueous vasopressin- s.c.,i.m.:
 short effect,- 3-6 hours;
 useful in comatous patients
4. lisin –vasopressin-intranasally:
 short effect-3-6 hours;
 side effect –vasopressor effect
!!!ADH must be given ONLY when the patient feels
thirsty

ADH overdose leads to water intoxication :

 symptoms due to hyponatremia:


 weakness,
 loss of apetite,
 loss of thirst,
 nausea,
 vomiting,
 constipation,
 somnolence,
 convulsions/ even coma.
2. Nephrogenic diabetes insipidus
Treatment:
 Directed towards the underlying disorder

 In familial forms therapy must be given as soon as possible in


infants due to particular susceptibility to neurologic damage due
to dehydration.

 Diuretics (Amilorid;Triamteren) - with dietary salt restriction

 NSAIDs (Ibuprofen, Indomethacin): inhibit the PGs synthesis 


reduce the delivery of solute to distal tubules  reduce urine
volume and increase osmolality
SIADH

SYNDROME OF
INAPPROPRIATE ADH
SECRETION
SIADH could be caused by:

a) Hypothalamic ADH hypersecretion

b) Ectopic ADH production

c) Drugs that stimulate ADH release and


effectiveness
due to:
 inflammations

 tumors

 vascular causes

 local thrombosis
 bronchogenic carcinoma

 pancreas carcinoma

 duodenum carcinoma
 Clofibrate

 Clorpropamide

 Carbamazepine

 Cyclophosphamide
ADH excess- leads to :

 hydric retention with:

 haemodilution
 hyponatremia

 hypernatriuria.
 fluid restriction

 Diuretics

 Lithium carbonate and


Demeclocycline – blockers of
renal ADH receptor.
Puberty represents a step of the continuing
process of

growth

development
 starts at 10 years - girls and
12 years - boys

 is dominated by GH secretion

 LH and FSH secretion occurs


 LH, FSH secretion- continues to increase

 sexual maturation processes

 menarche (first menstruation) and

 semenarche
 It lasts until:
 epiphyseal fusion and
 wisdom tooth occur

 dominated by thyroid secretion


Dezvoltarea pilozităţiii pubiene
Dezvoltarea sânilor
feminine
Pubertal stages – according to Tanner
Puberty in boys
(Tanner)
1. Precocious puberty

2. Delayed puberty
• secondary sexual development
before:

8 yrs - girls

9-10 yrs - boys


a) premature activation – hypothalamo-hypophysea
axis
= complete (true) precocious puberty.

b) autonomous sex steroid secretion occurs:


= incomplete precocious puberty
 isosexual- according to the patient’s gender
 heterosexual –opposite to patient’s gender.
 in girls - usually idiopathic

 in boys- often a tumor


Precocious puberty at a pacient 9 years age (left); together with
his brother 11 years (right)
 idiopathic or familial

 CNS disorders:

 congenital or acquired hydrocephaly


 glyomas
 neurofibromatosis
 meningitis,encephalitis
 hamartomas
 secondary to endocrine disorders:

 hypothyroidism:
- increase in both TRH and LH/FSH secretion.
- the onely form of true precocious puberty with
delayed bone age !!!

 congenital adrenal hyperplasia (CAH):


- incomplete precocious puberty,
- true precocious puberty- if adrenal hyperplasia is
controlled by glucocorticoid therapy
 marked growth spurt -rate 1 cm /month
 bone age- advanced maturation
 stature:
 tall - early phases,
 shorter than normal- finally ( early epiphyseal fusion)
 secondary sex characters- rapid and complete
development
 menstruation, spermatogenesis
 serum and urinary gonadotrops and sex hormones -
elevated
 characterized by:
 absence of gonadotropins secretion.

 either iso- or heterosexual.

! LESS COMMON THAN THE CENTRAL


TYPE
 isosexual
- harmonizes to

 heterosexual patient’s gender


- not harmonize to
 adrenal:
 congenital hyperplasia

 tumors secreting sex steroids (estrogens or androgens)

 gonadal tumors:
 in boys-leydigiomas, teratomas

 in girls-luteomas,follicular cysts,tecomas
 paraneoplasic secretion:

 chorioepitelioma,

 lung carcinoma,

 hepatoblastoma

 Iatrogenic (estrogens,androgens)
 Premature menarche:
 menstruate at an early age,
 without other signs of estrogens effects;

In most subjects:
- menses stop within 1-6 months and
- normal pubertal progression occurs
thereafter.
 Premature telarche:
 uni-or bilateral breast enlargement

 without other signs of estrogen secretion

 caused by brief episodes of estrogen


secretion from ovarian cysts.

 bone age - normal.


 Premature adrenarche:

 pubic or axillary hair

 without other signs of virilisation or puberty

 bone age is normal.


Treatment
- directed toward:

 the underlying tumor or


 abnormality
If the primary cause is controlled
–> signs of sexual development :

 will be halted in progression or

 may even regress.


 Inhibition of hypothalamo-hypophyseal axis

 in order to slow down the sexualization process:


 GnRH analogues- preferred treatment- :
decrease in
 gonadotropins and sex steroids
 stopping the progression of signs of
sexual precocity

 medroxyprogesterone acetate,30 mg/day,orally

 cyproterone acetate - antiandrogenic and


antigonadotropic
 Danazole - antigonadotropic drug

 Tamoxifen inhibits estrogen receptors

 Ketoconazole - antifungal agent:

 inhibits testosterone synthesis;

 the treatment of choice in testotoxicosis


No signs of pubertal development:

 girl - 13years or

 boy -14 years


 constitutional delay in
 growth and
 adolescence
 undeveloped fat tissue

 excessive exercise

 chronic stress

 iatrogenic
 urinary gonadotropins-
decreased to
undetectable

 gonadal sex steroids- decreased

 GnRH stimulating tests:

positive -hypothalamic origin


negative -hypophyseal origin
 genital hypoplasia:
 morphological deficit of external genitalia

 before the age of normal sex development

 genital infantilism:

 absence of secondary sex characters after


- 18 years in boys and

- 17 in girls.
 micromastia due to:

 lack of ovarian hormones,

 lack of breast receptors for estrogens and


progesterone,

 poor development of breast fat tissue


In hypothalamic forms:

 synthetic GnRH (pulsatile pumps)

 Clomiphene citrate :

 inhibits the action of strong estrogens and, thus,

 stimulates the secretion of gonadotropins.


In hypophyseal forms:

 HCG (human chorionic gonadotropin):


 LH-like efect
 5000 units/week

 HMG (human menopausal gonadotropin):


 FSH-like efect
 75 units x 3/week.

 psychological support
Amenorrhea:

 Primary:
 absence of first menstruation
 secondary sex characters could be present / not;

 Secondary
 absence of menstrual cycles >6 months
 secondary sex characters could be:
 normal
 involuated
 intricated (virilisation).
 Evaluation of associated disorders:
hypophyseal,adrenal,thyroid,

 secondary sex characters

 signs of virilisation,

 malformation,

 Gynecologic examination –important to diagnose


amenorrhea of utero-vaginal cause
 Presence of galactorrhea.
1. hypothalamo-hypophyseal axis:

 LH, FSH
 Tests with GnRH, clomiphene

2. ovaries:

 estrogens

 plasma progesterone and

 stimulating tests (HCG,HMG).


3. Investigation of peripheral receptors:

 cervical mucus

 vaginal epithelium

 endometrial biopsy

4. Hysterography
5. Hormone measurements :
 PRL,
 TSH, T3, T4,
 cortisole,
 testosterone,
 17 keto-steroids

6. Sex chromatine (Barr’s test).


Group I :

 amenorrheic women
 without endogenous estrogen production,
 normal PRL level,
 no hypothalamo-hypophyseal tumors;
 may respond to pulsatile GnRH;
 cause - functional.
Group II:

 women with menstrual disorders,


 progesterone insufficiency,
 anovulatory cycles,
 normal levels: estrogens,PRL and FSH;
 may respond to:
 progesterone or clomiphene- stimulates LH and
corpus luteum.
Group III:

 primary amenorrhea - framework of


ovarian dysgenesis;

 LH and FSH -elevated.


Group IV:

 amenorrhea of genital tract cause:

 absence of uterus-Rokitansky’s syndrome

 imperforate hymen

 endometrial distruction
Group V:

 hyper-PRL and

 hypothalamo-hypophyseal tumors:

 prolactinoma

 therapy-see Prolactinoma.
Group VI:

 hyper-PRL,

 without hypothalamo-hypophyseal
organic lesions,

 treatment with Bromocriptine / Cabergoline.


Group VII:

 hypothalamo-hypophyseal tumors

 normal PRL level.


 absence of vagina:

 malformation,

 Intersexuality

 imperforate hymen

 presence of vagina- establish


if uterus is present.
Sex chromatin (Barr’s test):
a) negative Barr’s test:
 testicular feminisation, incomplete form
 true hermaphroditism
 other forms of hermaphroditism - without malformation
of external genitalia

b) positive Barr’s test should measure:


Gonadotrops:
 elevated level- ovarian cause
 decreased level- central cause
 normal level- genital tract cause
Sex chromatin (Barr’s test):

a) negative Barr’s test:


 testicular feminisation- complete form

b) positive Barr’s test:


 malformative syndrome (Rokitansky’s syndrome)