Thyroid gland

T3 & T4
 The thyroid gland is a butterfly-shaped gland in the
middle of the neck, located below the larynx and above
the clavicles. It produces 2 hormones , the
triiodothyronine ( T3) and the thyroxine (T4) that
regulate the bodys metabolism. Thyroid function is
controlled by the pituitary gland that produces thyroid
stimulating hormone (TSH or thyrotropin), which
stimulates the thyroid to produce T3 and T4. At the
time of parturition, a physiologic TSH surge in response
to neonatal (cold) extrauterine exposure is apparent,
with blood levels peaking at a mean concentration of
approximately 70 mU/L at 30 mins and may remain
elevated for 3 to 5 days of birth. TSH production in
turn is stimulated by the thyrotropin releasing
hormone (TRH) produced by the hypothalamus.
Hypothalamus TRH

Anterior
TSH
Pituitary
gland

Thyroid gland

T3 & T4
 Thyroid hormone production
1) Iodide
Absorption
Thyroidal COLLOID
peroxidase
MIT/DIT Lysosomal
I I Tgb T4 (T3)
2) ATP 3) Peptidases
Na 5)
I T3/T4

4)
Thyroglobulin Tyrosyl residues
 The thyroid gland concentrate iodide from the blood and
return it to the peripheral tissues in a hormonally active
form. Major substrates of thyroid hormone synthesis
are iodide which is the rate limiting substrate and
tyrosine. Iodide is trapped through the the Na- Iodide
symporter. It undergoes oxidation by the thyroidal
peroxidase and organification by the same enzyme
through iodination of tyrosyl residues from thyroglobulin
forming monoodotyrosine( MIT) and diiodotyrosine
(DIT). One molecule of MIT plus DIT form T3 and two
molecules of DIT form a molecule of T4. Once formed
these hormones are stored as thyroglobulin in the lumen
of the folicle until ready to be distributed to body cells.
T4 and T3 are liberated from the thyroglobulin by
activation of proteases and peptidases.
 T4 - produced primarily by thyroid gland
T3 10-30% secreted by thyroid gland
- remainder- peripheral conversion
of T4
- primary mediator of thyroid
hormone effects
- 3 to 4x metabolic potency
 Functions of thyroid hormones
increase oxygenation consumption
& heat production
stimulate protein synthesis
influence growth & differentiation
affect carbohydrate, lipid and vitamin
metabolism
CNS maturation
 Upon admission

pediatric endocrinologist
CBC: anemia CBC1
 Upon admission
Peripheral blood smear:
- RBCsdimished in number,
hypochromic & microcytic
 Upon admission
Chest Xray: Pneumonia in both lung
fields with hyperaeration
CXR

Cefuroxime IVTT
Salbutamol nebulization
newborn screening: elevated TSH
SERUM FREE T4 (0.3 pmol/L)
(NV: 13.9 - 26.1 )

SERUM TSH (100 uIU/L)

(NV: 1.36 8.8)

LEVOTHYROXINE SODIUM
37.5 mcg/D
 Serum free T4 ; TSH

Transient Hypothalamic- Thyroid

Pituitary TSH Thyroid
hypothyroidism Dysgenesis
Deficiency Dyshormogenesis
(10%) (75%)
(5%) (10%)
 Since my patient has been confirmed as a case
of CH evidenced by a low serum free T4 and
an elevated serum TSH, Levothyroxine sodium
was then started at 37.5 mcg/D. It is not
enough to diagnose a patient with CH but the
etiology of the condition should be
determined.
We dnt stop at the dx
 Transient hypothyroidism

causes goitrogenic agents

TSH receptor-blocking
maternal autoantibodies
iodine deficiency
 (Transient hypothyroidism may occur if the
mother took goitrogenic agents and symptoms
may last up to 2 weeks. TSH receptor blocking
maternal autoantibodies may last up from 1 to 4
months). Considering that my patient is still
symptomatic at this time and that there is
absence of maternal goitrogenic intake (eg
antithyroid drugs and maternal iodine). Mother
had no history of autommune thyroid disease
where we may suspect a TSH receptor blocking
autoantibodies nor is she a resident of an area
endemic with iron deficiency.
 Serum free T4 ; TSH

Transient Hypothalamic- Thyroid

Pituitary TSH Thyroid
hypothyroidism Dysgenesis
Deficiency Dyshormogenesis
(10%) (75%)
(5%) (10%)
 Central CH (hypothalamic-
pituitary TSH deficiency)
Divided to:
Secondary pituitary gland
Tertiary hypothalamus
organic TSH deficiency
(low to normal TSH)
not detected by newborn screening
Serum free T4 ; TSH

Hypothalamic- Thyroid
Pituitary TSH Thyroid
Dyshormogenesis Dysgenesis
Deficiency (75%)
(5%) (10%)
 2nd hospital day
Thyroid scan: scan

- abnormal pertechnetate scan

- congenitally absent thyroid gland
Packed RBC secured
 3rd hospital day
Thyroid ultrasound:
- no demonstrable thyroid tissue
Packed RBC transfused
Rpt CBC: increase in Hct CBC2
Serum free T4 ; TSH

Thyroid Thyroid
Dyshormogenesis Dysgenesis
(10%) (75%)
 4th hospital day
Levothyroxine (LT4) increased
to 50 mcg/D
Cefuroxime shifted to p.o.
 6th hospital day
Discharged
Home medications:
1. Levothyroxine 50 mcg/D
2. Cefuroxime p.o.
3. NaCl nasal spray
4. Zinc & Iron p.o.
 FINAL DIAGNOSES
1. Pediatric Community Acquired
Pneumonia C
2. Congenital hypothyroidism
secondary to thyroid agenesis
 Congenital
Hypothyroidism
 NEWBORN SCREENING
widely used screening for CH
Prevalence of positive CH in the Phils:
Year Screened Confirmed

2004 1:3065 130

2005 1:3172 169

2006 1:3431 210

2007 1:3369 293

Newborn Screening Reference Center (December 2007). Retrieved July 7,2008

from http://www.nsrc.nih.org.ph/quicklinks/prevalence update07.pdf
Congenital Hypothyroidism
Majority: Sporadic
most commonly caused by
thyroid dysgenesis
Minority: Familial
autosomal recessive
thyroid dyshormogenesis
 Thyroid dysgenesis

- agenesis
- hypoplasia
- ectopic
 Thyroid dysgenesis
mutations in homeobox genes
( TTF-1, TTF-2 or PAX 8)
mechanism: obscure
prevalent in females (2:1)
 Positive newborn screening
Serum T4, free T4 and TSH

Normal Abnormal

Thyroid scan

Normal Absent Uptake Ectopic

TBA Measurement Ultrasound

Normal gland No thyroid tissue

(-) (+)
TBA Measurement
Tgb Measurement

Normal or Absent (-) (+)

TH Synthetic TSH receptor Ectopic

Transient
Defect or Tgb TH Synthetic defect Transient Thyroid Thyroid
CH
Drug defect Synthetic OR CH Agenesis Gland
Defect Iodine blockade
 Clinical manifestations
normal birthweight & length
head size may be slightly increased
prolonged physiologic jaundice
feeding difficulties
choking spells during nursing
poor feeding and weight gain
small stature
 Clinical manifestations
good babies
somnolence
hypotonia
respiratory difficulties due to large tongue
- apneic episodes
- noisy respirations
nasal obstruction
constipation
 Clinical manifestations
retarded development
lethargic
hoarse voice
unable to talk
delayed sexual maturation
 Physical exam
growth stunted
head size: normal or increased
Scalp: thickened
Hair: coarse, brittle & scanty
Hairline reaches down the
forehead
skin: dry, general pallor, scaly, cold
 Physical exam
anterior & posterior fontanels
open widely
hypertelorism
narrow palpebral fissures
swollen eyelids
broad nasal bridge
 Physical exam
mouth open and thick
macroglossia
delayed dentition
neck: short & thick
hands: broad & short fingers
short extremities
large abdomen w/ umbilical hernia
 Physical exam
edema of genitals and extremities
slow pulse
heart murmurs, cardiomegaly and
asymptomatic pericardial effusion
10% of CH - cardiac anomalies
- nervous system anomalies
- eye anomalies
 Diagnostics
anemia
Knee Xray: absence of osseous
development at distal femoral
epiphysis at birth
xray
 Treatment
thyroxine preferred treatment
tablet form
not mixed with soy or iron containing milk
formula
Lifelong treatment
 Thyroxine dosing
PO
AGE mcg/kg/dose mcg/Day
< 6 months 8 -10 mcg/kg/d 25 - 50 mcg/D
6-12 months 6-8 mcg/kg/d 50-75 mcg/D
1 to 5 yrs 5 to 6 mcg/kg/d 75-100 mcg/D
IV/IM:
6-12 years50-75% PO
4-5 dose
mcg/kg/d 100-150 mcg/D
>12 yo 2-3 mcg/kg/d 150 mcg/D
 Thyroid hormone monitoring
serum free T4: maintained at upper half
of normal range
(NV : 12-28 pmol/L)
total T4 : 130-206 nmol/L
(10-16 ug/dl)
< 6 months : every 1 to 2 months
6 months to 3 yrs: every 3 to 4 months
 Prognosis

Early diagnosis & treatment

- prevent severe mental
retardation and other neurologic
complications
 Salerno, et al..
study on growth & intellectual outcome of
4 year old children with CH on screening
Conclusion: Group 3
- 10.1 to 15 mcg/kg/D LT4 replacement
- had higher IQ (98 +/- 9)
- both free T4 and TSH were normalized
- group 1 (6-8 mcg/kg/D)
- group 2 (8.1-10 mcg/kg/D)
Salerno, M. et al. Thyroid ( January 1,2002), 12 (1) 45-52.
 12 year old children with CH on screening
mean IQ scores: 88.4 +/- 13.1
(within normal for control population)
low IQ scores:
- severe hypothyroidism
- inadequate compliance to therapy
- poor parental pedagogic attitude

Salerno, et al. European Journal of Endocrinology

(1999 August) 141 (2) 101-104.
 Some cases with early treatment
-mild delays in reading comprehension
and arithmetic in the third grade but with
catch up by the sixth grade
Adolescence
- some cognitive problems may persist
- visuospatial, memory & attention
problems

Rovet, J. & Ehrlich, R. (2000) Psychoeducational Outcome in

children with Early-treated Congenital hypothyroidism. Pediatrics
( 2000); 105;515-522. Retrieved July 21,2008 from
http//www.pediatrics.org/cgi/content/full/105/3/515
Early adequate therapy

Physical growth &

development normalized
bone age normalized in 1
to 2 years
SUMMARY
 NEWBORN SCREENING
RA 9288: Newborn screening Act of 2004
2006 :
- 11 % of total number of DOH accredited
facilities in the Philippines
- 5% of annual livebirths were newborn
screened in region VII

National Reference Center (2006). Newborn screening

statistics. Retrieved July 2008 from www.nsrc-
nih.org.ph/quicklinks/regionperformance06.htm
 Follow-up.
LT4 dose: 50 mcg/D
weight post therapy:
- 2 weeks - 7 kg (-4 SD)
- 2 months (1 yo) - 9kg (p10)
length post therapy:
- 2 weeks - 63.5 cm (-7 SD)
- 2 months (1 yo) - 68.5 cm (-5 SD)
 Follow-up.
Chronological age : 1 year old
Developmental age: 6 months
2 months post therapy (1 yo)
- TSH : 17.4 uIU/ml (NV: 1.7-9.1)
- free T4 : 18 pmol/L (NV: 13.9-26.1)
Dose: increased to 62.5 mcg/D
 At present.
active
eyelids not swollen
umbilical hernia resolved
stool output: soft, three times a day
sleeping time: 10 hours per day
 At present.
1 year & 2 months old
Developmental age:
8 months