This document provides information on thyroid hormone metabolism and thyroid function. It discusses iodine uptake and transport by the thyroid gland, thyroglobulin synthesis and storage, hormone release, and thyroid hormone actions in the body. It also covers abnormalities of thyroid function including hyperthyroidism, hypothyroidism, and goiter. Common causes, signs, symptoms and diagnostic tests for different thyroid disorders are described.

1. M. ARAVIND
MBBS I YEAR
DSMCH PERAMBALUR

2.  Iodine metabolism
 Thyroid hormone metabolism
 Function of thyroid hormone
 Abnormalities of thyroid function
 Hyperthyroidism
 Hypothyroidism
 Goiter
 Thyroid function tests

3.  SOURCES: drinking water, fish, cereals,
vegetables, iodinated salt
 Commercial: sea weeds
 RDA: 150-200 microgram/day
 DISTRIBUTION:
 Total body content:25-30mg (found in all cells)
 80%- thyroid gland
 Blood- 5-10 microgram/dL
 FUNCTION: formation of T3 & T4

4.  GOITROUS BELTS:
 In most parts of the world, iodine is a scarce
component of the soil. Upper regions of the
mountains contain less iodine
 GOITROGENS:
 Ingredients in food stuffs, which prevent utilization
of iodine
 Seen in cassava, maize millet, bamboo shoots, sweet
potatoes, beans
 Cabbage & tapioca (thiocynate- inhibits iodine
uptake)
 Mustard seed (thiourea – iodination of
thyroglobulin)

5.  STEP 1: UPTAKE OF IODINE BY THYROID
GLAND
 Inhibited by thiocynate & perchlorate which
compete for carrier mechanism
 Stimulated by TSH
 Rx congenital iodine trapping defect- large
doses of iodine

6.  Stimulated by TSH
 Inhibited by antithyroid drugs (thiourea,
thiouracil, methimazole)
 Rx- inborn error of iodine oxidation defect- T4
administration
 From the follicular cells, iodine is transported
into the follicular cavity by an iodine chloride
pump called pendrin

8.  Tgb – SYNTHESIS- thyroid follicles
(endoplasmic reticulum & Golgi apparatus)
 Large protein about 5000 aas (600kD)
 10% carbohydrates
 115 tyrosine residues (35 – iodinated)
 Stored in follicle
 3- monoiodotyrosine & 3,5 diiodotyrosine are
produced

9.  Tyrosine + I = MIT
 MIT + I = DIT
 DIT + MIT = T3 (formed by de-iodination of outer ring
of T4 by 5’ deiodinase) (1 molecule of thyroxine for
every 10 molecules) (peripheral cells)
 MIT + DIT = reverse T3 (1% - negligible biological
activity)(formed b inner ring deiodination by
5deiodinase)
 DIT +DIT = T4 (99%)
 Attached to Tgb
 Rx – inborn error give T4

11.  Thyroid- only endocrine gland to store
appreciable amounts of hormone
 Tgb 8 T4 residues per molecule
 Thyroid acini
 Several months (4)
 Signs & symptoms of thyroid hormone
deficiency donot occur for 4 months

12.  Follicular cell sends foot-like extensions called
pseudopods, which close around the
thyroglobulin-hormone complex. This process
is mediated by a receptor-like substance called
megalin, which is present in the membrane of
the follicular cell.
 Psudopods convert thyroglobulin-hormone
complex into small pinocytic vesicles.
(pinocytosis)

13.  Lysosomes fuse with these vesicles
 Proteinases digest Tgb (proteolysis) & release
thyroid hormones
 Stimulated by TSH
 Inhibited by iodide(KI is used as an adjuvant in
hyperthyroidism)
 In a genetic disorder abnormal Tgb is
produced, resulting in deficient proteolysis and
deficiency of thyroxine

14.  When the dietary level of iodine is moderate,
the blood level of thyroid hormones is normal.
 However, when iodine intake is high, the
enzymes necessary for synthesis of thyroid
hormones are inhibited by iodine itself,
resulting in suppression of hormone synthesis
 This effect of iodide is called Wolff-Chaikoff
effect

15.  Diffuse through base of the follicular cell and
enter the blood stream

16.  MIT & DIT are not released into blood
 These iodotyrosine residues are deiodinated by
an enzyme iodotyrosine deiodinase, resulting
in the release of iodine
 The iodine is reutilized by follicular cells for
further synthesis of thyroid hormones
 During congenital absence of iodotyrosine
deiodinase, MIT & DIT are excreted in urine &
the symptoms of iodine def develop
 Rx- give iodine

17.  3 types of proteins
 total protein bound iodine (PBI) is 10
microgram/dL out of which T4 constitutes 8
microgram/dL
 THYROXINE BINDING GLOBULIN: (one
third) 80%- T4, 60%- T3
 Transthyretin(TTR) or thyroxine binding
prealbumin: one fourth
 Albumin: one tenth

18.  HALF LIFE:
 T4- 4-7 days (is a prohormone which is
deiodinated to T3)
 T3- 1 day (biologically more active)
 Deiodination takes place in the peripheral
tissues by deiodinase (Se containing enz)
 Conjugated with glucoronic acid – excreted
through bile
 Lesser extent through urine
 Deamination: T4 – tetraiodothyroacetic
acid(Tetrac), T3- triiodothyroacetic acid (triac)
 These are only one fourth as active as parent
compound

19. increase in transcription rate
Receptor hormone complex binds to DNA
T3 receptor complex binding sequence-
Thyroid responsive element
Nuclear receptors

21.  Acts on almost all the tissues
 BMR- increases
 CALORIGENIC EFFECT OR
THERMOGENESIS: 1 mg of T4 produce 1000
kcal by uncoupling oxidative phosphorylation.
 Body temp increases called thyroid hormone
induced thermogenesis
 Normal functioning of CNS
 Erythropoietic activity
 It causes the muscle to work with more vigour

22.  PROTEIN MET: increased RNA synthesis-
increased protein synthesis. Higher
concentration of T3 causes protein catabolism
and negative nitrogen balance
 CARBOHYDRATE MET:
 Increased gluconeogenesis, glycogenolysis,
glucose uptake. Glucose tolerance test shows
rapid absorption
 FAT MET: mobilize fat from adipose tissue
increases FFA level in blood. Decreases plasma
cholesterol, phospholipids, triglyceride levels
(increasing its excretion from liver into bile)

24.  CAUSES:
 Graves disease
 Thyroid adenoma
 Pituitary adenoma
 Excessive intake of thyroid hormones
 Increased affinity of binding protein
 Increase in binding protein
 T4 toxicosis (T4 increase, T3 low)

25.  PRIMARY HYPERTHYROIDISM: due to
diseases of thyroid gland (Grave’s disease,
adenoma, functioning metastatic thyroid
carcinoma, TSH receptor mutation, excess
iodine)
 SECONDARY HYPERTHYROIDISM: due to
diseases of pituitary or hypothalamus (TSH
secreting pituitary adenoma)

26.  Exophthalmus
 Increased rate of metabolism
 Intolerance to heat
 Weight loss
 Sweating
 Fine tremors emotional disturbances
 Anxiety/ excess worries / paranoid thoughts
 diarrhoea

29.  MYXEDEMA- in adults characterised by
generalised edematous appearance
 CAUSE:
 Deficiency of iodine
 Deficiency of TSH/ TRH
 Diseases of thyroid gland
 Iodine deficiency
 Hashimoto’s thyroiditis(autoimmune
thyroiditis)

30.  Swelling of the face
 Bagginess under the eyes
 Non pitting type of edema
 Atherosclerosis (inc cholestrol)
 Arteriosclerosis
 Hypertension
 Increase in body weight
 Fatigue and muscular sluggishness
 Mental sluggishness
 Cold intolerance
 Constipation
 Anemia

31. anaemic

33.  Hypothyroidism in children characterised by
stunted growth
 CAUSE
 Congenital absence of thyroid gland
 Lack of iodine in the diet
 Genetic defect
 CONGENITAL HPOTHYROIDISM
 (incidence: 1:4000)

34.  Sluggish movements and croaking sound
 Skeletal growth is affected
 Tongue becomes so big and hangs down with
dribbling saliva
 Big tongue obstructs swallowing and breathing
 Guttural breathing-sometimes choke the baby
 Mental retardation
 Different parts of the body are
disproportionate
 Reproductive functions are affected
 sleepiness

37.  CAUSE: iodine def
 CHARACTERISTICS:
 Raised TSH level would produce continued
stimulation of gland leading to hyperplasia &
goiter
 Hormone levels

38.  In acutely ill patients, T3,T4, TSH are found to
be lowered
 It is advisable to postpone the thyroid function
in acutely ill patients till they recover
completely in order to get a correct picture of
the functional status of the thyroid gland

39.  Enlargement of the thyroid gland
 Goiter in hyperthyroidism- toxic goiter
 Inc secretion of thyroid hormone caused by tumour
 Goiter in hypothyroidism- nontoxic goiter
 (hypothyroid goiter) enlargement of thyroid gland
without increase in hormone secretion
 ENDEMIC COLLOID GOITER- iodine def
 IDIOPATHIC NON-TOXIC GOITER- goitrogens,
def of enz- peroxidase, iodinase, deiodinase

41.  ASSAY OF HORMONES T3 & T4
 Radio immuno assay (RIA)
 Enzyme linked immuno sorbent assay (ELISA)
 Chemiluminescent immunoassay (CLIA)
 Fluorescent immuno assay (FIA)
 HYPERTHYROIDISM- T3,T4 TSH
 HYPOTHYROIDISM- T3,T4 TSH
 Due to hypothalamic/ pituitary defect-
T3,T4,TSH

42.  Free hormones are active forms which can be
measured accurately by CLIA / FIA
 fT4- 0.35% fT3-0.3%
 Variations in binding proteins donot affect the
free hormone levels therefore more reliable in
diagnosing true hyper & hypofunction

43.  P hypothyroidism- TSH
 S hypothyroidism- TSH (T3, T4)
 P hyperthyroidism- (T3,T4 )TSH
 S hyperthyroidism- (T3, T4) TSH

44.  Since sensitive and accurate tests are there to
measure free T3 and T4, this test is only of
historical importance

45.  HYPERTHYROIDISM: negative feedback effect
of high T4 overpowers the stimulant effect of
TRH. TSH T3,T4
 P HYPOTHYROIDISM: TSH (exaggerated
response)
 HYPOPITUITARISM: TSH,T3,T4

46.  HYPOTHYROIDISM- increased cholesterol
level(cholesterol carrying lipoprotein
degradation is decreased)
 It is not diagnostic, because
hypercholesterolinemia is also seen in
DM,obstructive jaundice, hypertension,
nephrotic syndrome
 It is useful in monitoring the effectiveness of
the therapy

47.  Dose of 131I is given
intravenously, after few hours,
the patient is monitored at the
neck region by a movable
gamma-ray counter.
 NORMAL VALUES- 25% within
2 hours, 50% within 24 hours
 HYPERTHYROIDISM- increased
uptake
 HYPOTHYROIDSM- decreased
uptake

48.  24 hours after administering the dose of 131I
intravenously, the patient is placed under the
scanner, which detects the radioactive
emissions from the neck region.
 Approximate size & shape of the thyroid gland
is produced
 Hyperthyroidism- heavily shaded areas
 Thyroid cancer- silent nodule (iodine uptake is
defective)

49.  In Grave’s disease, thyroid stimulating
immunoglobulin (TSIg) also known as long
acting thyroid stimulator (LATS) is seen in
circulation
 They bind to TSH receptor which is not under
feed back control
 It is significant because the prevalence of
autoimmune disease is on the increase
 In thyroid cancer- antithyroglobulin antibodies