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