The document details the biosynthesis, function, and disorders related to thyroid hormones, including hyperthyroidism and hypothyroidism. It explains the causes, symptoms, and clinical features of these conditions as well as their treatment options, emphasizing the importance of iodine in thyroid hormone production. Recommendations for iodine intake and the classification of related diseases are also discussed.

1. HYPERTHYROIDISM

2. THYROID HORMONE
• Iodine is the main substrate for the formation of thyroid hormones.
• After active transport (the thyroid to serum concentration ratio is 25)
into the thyroid follicular cells, it is organified, forming the
iodotyrosines, mono- and diiodo-tyrosines (MIT and DIT).
• This is followed by coupling, which leads to the formation of
triiodothyronine (T3) and thyroxine (T4).
• Further, polypeptide chains and carbohydrate moieties combine to
form thyroglobulin, the storage form of thyroid hormone.
• This iodinated thyroglobulin molecule is secreted in the colloid of the
follicles and acts as the primary intrathyroid storage form of thyroid
hormone.
• Entry into the circulation is by exocytosis and is followed by proteolysis
of thyroglobulin, releasing T4 and T3.
• Deiodination at the peripheral tissue level brings out the functionality
of the thyroid hormone

3. ACTIONS
• Thyroid hormones increase protein synthesis
in all cells. The second important effect is
increase in oxygen consumption.
• Both T3 and T4 are active but T3 is three times
more potent

4. IODINE DEFICIENCY DISORDERS
• These may be characterised by
– a) Goitre at all ages
– b) Endemic cretinism with associated mental
retardation, deaf-mutism, spastic diplegia and
lesser degree of neurological deficit
– c) Impaired mental function in children and adults
– d) Increased rates of abortion, stillbirth, and
perinatal and infant mortality

5. GOITRE
• Goitre may be due to iodine deficiency

6. IODINE DEFICIENCY GOITRE
• The thyroid follicles are hyperplastic.
• In more advanced stages, nodule formation
ensues and vesicles become distended with
flattening of epithelium.
• Nodules may undergo degeneration, and
fibrosis of varying degree may ensue.
• Rarely, this may be followed by calcification.

7. TREATMENT
• For the management of iodine deficiency, an average
daily intake of 150 µg of Iodine has to be ensured.
Salt can be easily iodinated.
• The recommended concentration of iodine of 25
ppm in common salt ensures optimum iodine supply.
• Lugol’s iodine has 5% iodine and 10% potassium
iodide; this contains 126 µg of iodine per ml.
• A saturated solution of potassium iodide contains
250 µg of iodine in 5 drops

8. HYPERTHYROIDISM
• Hyperthyroidism or thyrotoxicosis refers to a state where
there is an excess of circulating thyroid hormones, T4 or
T3
• Thyrotoxicosis is designated primary when the gland is
diffusely enlarged and there are signs of hypermetabolic
state; eye signs may or may not be present (Grave’s
disease).
• Thyrotoxicosis is designated as secondary where the
patient had previously abnormal gland, i.e. nodular
goitre (single or multiple), and now assumes
hyperfunctional status (Plummer’s disease).

9. HYPERTHYROIDISM
• The hyperthyroidism of Grave’s disease results from
the presence in the serum of IgG antibodies directed
against the TSH receptor of the thyroid follicular
cells.
• These antibodies are unique in that, once bound to
the TSH receptor, they stimulate thyroid hormone
production via the adenyl cyclase cAMP system in a
manner similar to TSH.
• They are termed thyroid stimulating antibodies
(TSAb).

10. CAUSES OF HYPERTHYROIDISM
• Thyroid source
• 1) Grave’s disease
• 2) Toxic multinodular goitre
• 3) Solitary toxic nodule / adenoma
• 4) Acute thyroiditis
– viral , autoimmune, post-irradiation

11. CAUSES OF HYPERTHYROIDISM
• Extrathyroidal source
– 1) Thyrotoxicosis factitia
– 2) Exogenous iodine intake
– 3) Drugs (e.g. amiodarone)
– 4) Hyperfunctioning ovarian teratoma (struma
ovaril)

12. CAUSES OF HYPERTHYROIDISM
• Increase in TSH
– 1) TSH secreting tumours (e.g. pituitary)
– 2) HCG producing tumours

13. Clinical features could be broadly
stated as follows
a) Evidence of hyperkinesis
b) Objective evidence of hypermetabolic state
(weight loss, catabolic state)
c) Presence of goitre, with or without
ophthalmopathy

14. FEATURES
• Symptoms General Demour of anxiety,
tremulousness, generalised weakness, heat
intolerance, skin tanning, pruritus
• Signs Restlessness, inability to keep still,
objective weight loss, excessive sweating, hair
thinning and straightening

15. FEATURES (SYSTEMIC)
• CVS Symptoms: Palpitation, irregular
beats, shortness of breath
• Signs: Tachycardia, increased pulse pressure,
ectopic beats, atrial fibrillation, sick sinus
syndrome, cardiac failure
• CNS: Hyperactivity, muscle weakness, apathy in
older age
• Signs: Fine tremors, hyperreflexia, proximal
muscle weakness, periodic paralysis

16. FEATURES (SYSTEMIC)
• GIT: Diarrhoea (non-infective)
• Signs: Rapid bowel transit time, steatorrhoea
• Reproductive system: Oligomenorrhoea or
amenorrhoea, impotence
• Signs: Gynaecomastia, infertility
• Thyroid: Enlargement in anterior, neck pressure
symptoms
• Signs: Diffuse or nodular goitre, bruit, thrill

17. FEATURES (SYSTEMIC)
• Ophthalmic Stare, gritty sensation, increased
lacrimal secretion, diplopia, diminished visual
acuity
• Signs: Lid retraction, lid lag, chemosis,
infiltrative ophthalmopathy, ocular muscle
paresis, exposure keratitis

18. Classification of the eye signs of
Grave’s disease
• Class Definition
• 0 No signs or symptoms
• 1 Only signs, no symptoms (signs
limited to upper lid retraction, stare, lid lag)
• 2 Soft tissue involvement (symptoms
and signs)
• 3 Proptosis more than 20 mm
(measured by Hertel exophthalmometer)
• 4 Extra-ocular muscle involvement
• 5 Corneal involvement

19. The diagnosis is based on
• a) Abnormal Free hormone and TSH levels in
blood
• b) TS Ab for the immunological basis for
Grave’s disease
• c) Assessment of end-organ involvement

20. HYPOTHYROIDISM
• Clinical manifestations due to lack of thyroid
hormone are designated as hypothyroidism.
• The presentation varies depending on
(a) the age of the patient,
(b) the cause of the disorder, i.e. primary or
secondary, and
(c) pre-existing health status.

21. CAUSES OF HYPOTHYROIDISM
• 1.Idiopathic atrophic, seen in middle-aged women with insidious thyroid
deficiency state; it is probably the commonest form of primary hypothyroidism.
• 2. Post-ablative surgical or radioactive 131l therapy; the incidence increases with
the time lapse after treatment and figures vary from 5-50% in 10-20 years’ follow
up.
• 3. Autoimmune thyroiditis (Hashimoto’s thyroiditis), the commonest cause of
goitrous hypothyroidism; 35-45 years are the most often affected. This may be in
association with manifestations of autoimmune involvement in other systems.
• 4. Drug-induced, e.g. iodide, lithium carbonate, amiodarone. Such agents affect
hormone synthesis or release or its peripheral deiodination.
• 5. Secondary to pituitary disease due to deficiency of TSH; manifestations include
lack of other pituitary hormones, e.g. growth hormone and/or gonadotrophin;
ACTH is probably the last to be affected.
• 6. Congenital, in childhood. Hypothyroidism may be due to (a) environmental l2
deficiency, (b) hormonal biosynthetic defect or (c) maldevelopment, i.e.
cryptothyroidism (maldescent).

22. Symptoms Signs
• General features
Blunting of features, generalised slowing Periorbital puffiness, psychomotor retardation
• Skin
Dryness, itching Dry, rough, flaky skin; non-pitting oedema; carotenaemia
• Hair
Hair loss Coarse and brittle; selective areas of alopecia
• CVS
Shortness of breath Bradycardia
Angina pectoris Ischaemic heart disease
Congestive cardiac failure Pericardial effusion
• CNS
Muscle aches and pains Delayed relaxation of
Slowing of motor function tendon reflexes
Deafness Myotonia and myoedema
Somnolence Carpal tunnel syndrome
Nerve conduction deafness
Slowing of cerebration
• GIT
Constipation lleus
Ascites
• Reproductive system
Menses irregular , menorrhagia High FSH/LH
Infertility Hyperprolactinaemia
Galactorrhoea
• Haematological
Pallor Dimorphic anaemia

23. FEATURES SUMMARISED AS FOLOWS
• a) Hypokinesis: slowing of physical as well as
mental functions.
• b) i) Infiltration of body tissues by
mucopolysaccharide, hyaluronic acid, and
chondroitin sulphate (‘myxoedema’ implies
mucous swelling).
• ii) Functional alterations in end-organs.
• c) Thyroid gland status: goitrous or atrophic.

24. INVESTIGATIONS
• The diagnosis of hypothyroidism can be confirmed
by:
• a) Level of thyroid hormones in circulation (T4, T3)
• b) Value of TSH and its response to TRH
• c) Indirect tests:
– i) Photomotogram
– ii) Serum enzymes (Creatine phosphokinase, LDH)
– iii) ECG
• d) Thyroid antibody tests

25. TREATMENT
• Replacement with thyroxine is adequate in a
majority of instances of hypothyroidism.
• There is a peripheral conversion of T4 to T3 so as
to be available at the tissue level.
• The usual replacement dose of thyroxine is 1.5-
2.5 µg/kg.
• The normal adult with ideal body weight requires
a maintenance dose of 150-200 µg/day.
• The dose is adjusted to achieve serum TSH and
T3, T4 levels in the normal range

26. COMPLICATIONS
• MYXOEDEMA COMA
• Cardinal features of myxoedema coma are:
a) Hypothermia
b) Altered consciousness
c) Hypoventilation
• Extreme cold weather; use of narcotics,
phenothiazines or anaesthetic agents;
intercurrent infections or situations that can
cause hypotension, may be the precipitating
events for myxoedema coma.