Thyroid Hormone

Hypothyroidism

Sidarti Soehita SFHS

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Thyroid Hormone synthesis, storage and
release :

 Iodide trapping by active thyrotrophin-dependent

pump mechanism
 Iodide oxidized by thyroidal peroxidase enzyme
(TPO)
 Iodine reacting with thyrosine amino-acid in
thyroglobulin (thyroidal protein) mono/di-iodo
thyrosyl
 Coupling iodinated thyrosyls  tri/tetra iodinated
thyronine (T3/T4) and stored in the follicles as
colloid
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Thyroid Hormone synthesis, storage and
release :

 Adenohypophysial hormone thyrotrophin (thyroid

stimulating hormone= TSH) stimulate follicles 
colloid endocytosis  release the hormone into
general circulation
 T3 is biologically more active than T4 (20-100x)
 T3 concentration in blood < T4
 T4 has a longer half life than T3

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 HYPOTHALAMUS

TRH

ANTERIOR PITUITARY

TSH

NEGATIVE
FEEDBACK THYROID

T3 rT3 T4
IODIUM

DEIODINATION
DEAMINATION
CONJUGATION
THYROID HORMONE DISORDER

 PRIMARY : thyroid gld

TSH negatively correlated with T3/T4
CENTRAL : hypothalamus or anterior pituitary
TSH positively correlated with T3/T4
SECONDARY:anterior pituitary
TERTIARY:hypothalamus

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Thyroid Hormone Actions
 Associated with cellular metabolism  increase
in basal metabolic rate (BMR)
 Excess hormone: BMR up to 100%
 Severe hypothyroidism: BMR 50-60%
Carbohydrate metabolism
Increase of glucose absorption in g.i.tract
Increase of glucose uptake by muscle/adiposum
Enhance glycolysis,gluconeogenesis

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Fat metabolism
 Stimulate lipolysisfree fatty acid
increase
 Stimulate synthesis,mobilization and
degradation of lipids
 Degradation is more prominent
 Excess hormonedecrease in body
weight,lipid concentration↓(cholesterol etc)
 Hypothyroidismincrease in body weight,
lipid concentration↑(cholesterol etc)
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Protein Metabolism
 Stimulate protein anabolism,catabolism
 Excess hormone:protein deficiency due to
excessive catabolismamino acid increase
liver gluconeogenesis
 Hypothyroidism:decreased protein anabolism
 Important to growth and development
 Hypothyroidism in childcretinism
 Hyperthyroidism in child:accelerated growth at
first,stop at earlier age(epiphyses closed)
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Vitamin Metabolism
 Metabolic effectvitamins requirement
increase
 Hyperthyroidismvitamin deficiency
 Stimulate vitamin A synthesis from
carotene in the liver
 Hypothyroidismvitamin A deficiency and
yellowish skin

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Cardiovascular Effects
 Potentiate circulating catecholamine effect
heart contraction
 Hormone slightly increaseincrease of
force of contraction
Hormone excessdecrease the strength
of the heart beats due to increased protein
catabolism in this tissue
 Hypothyroidismbradycardia
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CNS Effects

 Important to mental development

 Absence of hormone from birth to puberty
mentally and physically retarded
(cretinism) due to hypoplasia of cortical
neuron and delayed myelination
 Hypothyroidism in adultlack of memory
and psychological changes

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ENDEMIC GOITER
(GAKI:Gangguan akibat kekurangan iodium)

Hypothyroidism most common in Indonesia

Etiology : iodide deficiency
Clinical Findings:
fatigue, bradycardia, weight gain, anemia,
menorrhagia, impotence, hair loss

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ENDEMIC GOITER

 LABORATORY FINDINGS
 T3 / T4 ↓
 TSH ↑
 Hypercholesterolemia
 Hemoglobin ↓

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HASHIMOTO THYROIDITIS

 Hypothyroidism
 Etiology : auto-immune process
 Prognosis : not good
 Lab. findings:
 T3/T4 decreased
 TSH increased
 anti-thyroid Ab positive

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GRAVES’ DISEASE(MORBUS
BASEDOW)
 Hyperthyroidism
 Etiology: auto immune process
 Clinical findings:
weight loss
heat intolerant
tachycardia, arrhytmia  cardiac failure
exophthalmos, diplopia
nervous / tremor, hyperhydrosis
amenorrhoea, osteoporosis 15
GRAVES’ DISEASE

 In severe condition could occured THYROID

CRISIS (fever,unconscious,arrhythmiaheart
block)
 LAB.FINDINGS
T3/T4 increaased
TSH decreased
anti-thyroid Ab positive

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THYROID HORMONE

 Unbound (Free): FT3/ FT4 (biologically active)

 Bound to protein (TBG:thyroid binding globulin,
TBPA:thyroid binding prealbumin=transthyretin)
 TBG increased:
pregnancy
estrogen user
THYROGLOBULIN:protein synthesized by thyroid
gld.Increased in thyroid carcinoma relaps.

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THYROID AUTOIMMUNITY

Auto antigen:
thyroglobulin
TSH receptor
thyroidal peroxydase (TPO/microsomal Ag)
G-4 kDa protein Ag (thyroid gld/orbita)
AUTO ANTIBODIES
anti-thyroglobulin Ab, anti microsomal Ab
anti=TSH receptor Ab(blocking & stimulating)
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HYPOTHYROIDISM
 Clinical syndrome resulting of thyroid hormone
deficiency,results decreament of metabolic
process
 Hypothyroidism in infant/childrenslowing
of growth and development,mental retardation
Hypothyroidism in adultslowing down the
organism with deposition of glycosaminoglycans
in intracellular spaces esp.muscle and skin
producing myxedema
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Etiology of Hypothyroidism
 Primary (thyroid failure)
1.Hashimoto Thyroiditis
a.with goiter
b.”idiopathic”thyroid atrophy,presumably
end stage of autoimmune thyroid dis.
(Grave’s/Hashimoto)
c.neonatal hypothyroidism due to
placental transmission of TSH-R blocking
antibodies
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Etiology of Hypothyroidism (2)
 2.Radioactive iodine therapy for Grave’s
disease
3.Subtotal thyroidectomy
4.Excessive iodide intake(radiocontrast
dyes,iodide containing cough prep.)
5.Subacute thyroiditis
6.Iodide deficiency(common in developing
countries,Indonesia:GAKI)
7.Goitrogens:lithium,antithyroid (PTU)
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Etiology of Hypothyroidism (3)
 Secondary(to pituitary TSH deficit)
Hypothyroidism due to pituitary adenoma,
pituitary ablative therapy/destruction
Tertiary:due to hypothalamic deficiency of
TRH (rare)
Peripheral resistance to the action of
thyroid hormone

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Clinical Findings
 A.Newborn Infants (cretinism)
Incidence 1: 5000.
Symptoms:respiratory difficulty,cyanosis,
jaundice,poor feeding,hoarse cry,umbilical
hernia,marked retardation of bone
maturation(absence of proximal tibial/distal
femoral epiphysis)
Early diagnosis:TSH>30 μU/ml,T4<6 μg/dl
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Clinical Findings (2)
 B.Children
 Retarded growth and mental retardation
 Adolescent: precocious puberty,
enlargement of sella tursica in addition to
short stature(pituitary hypertrophy due to
excessive TSH production)

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Clinical Findings (3)
 C.Adults
Fatigue,coldness,weight gain,constipation,
menstrual irregularities,muscle cramps,
cool/rough/dry skin,puffy face and hands,
hoarse/husky voice,slow reflexes,
yellowish skin

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Clinical Findings (4)
 Cardiovascular signs:bradycardia,cardiac
enlargement,ECG:low voltage of QRS
complexes,P and T waves, pericardial
effusion
 Pulmonary function: shallow, slow
respiration,respiratory failure
 Intestinal peristalsis: slow, chronic
constipation, ileus
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Clinical Findings (5)
 Renal function:decreased glomerular
filtration rate
 Anemia: due to impaired hemoglobin
synthesis,menorrhagia,impaired intestinal
iron absorption,folate/vit.B12 defficiency
 Neuromuscular system:muscle cramps,
paresthesias,muscle weakness

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Clinical Findings (6)
 CNS symptoms: fatigue, lethargy,inability
to concentrate,depression.
Hypothyroidism impairs conversion of
estrogen precursors to estrogen resulting
anovulatory cycles and infertility, severe
menorrhagia

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Diagnosis
 Primary Hypothyroidism: low FT4 and
elevated TSH
 Hashimoto thyroiditis: thyroid antibodies
positive (TPO/Tg/TSH-R Ab)
 Pituitary myxedema: low FT4 but TSH not
elevated, absence of TSH response to
TRH

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Diagnosis (2)
 Thyroid Hormone Measurement
Total T4/T3 = FT4/FT3 + Protein bound T4/T3
Free T4/T3 (FT4/FT3) biologic active
Protein bound T4/T3 inactive
Thyroid Binding Protein (TBP) increase in
estrogen administration  protein bound
T4/T3 increase

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Diagnosis (3)
 High protein bound T4/T3 in normal total
T4/T3 cause low FT4/FT3Hypothyroid
though the total T4/T3 is normal
 FT4/FT3 is more recommended than total
T4/T3 in diagnosis hyper/hypothyroid

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Diagnosis (4)
 TRH Test
 Indication: Secondary hypothyroidism
(hypothalamic-pituitary failure)
 TRH(200-500 μg)i.v. rise inTSH(normal)
 TSH response measured at 20 & 60 mnt
 TSH no response in hypopituitarism
 TSH exaggregated response in
hypothalamic-based pituitary hypothyroid
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Diagnosis (5)
 Thyroid Autoantibodies
1.Anti Thyroglobulin (Tg) Ab
2.Anti Thyroid Peroxidase (TPO) Ab,
formerly microsomal Ab
3.Anti TSH Receptor (TSH-R) Ab
Anti TSH-R stim Ab : Grave’s dis.
Anti TSH-R block Ab : Hashimoto dis.
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Diagnosis (6)

 Other Laboratory Findings

 1. Hypercholesterol
 2. Anemia

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THANK YOU

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