2. Thyroid hormones: Introduction
Hormone Source Remarks
Triiodothyroxine T3
Thyroid follicles Referred as thyroid hormones
Tetraiodothyroxine, T4,
Also known as thyroxine
Calcitonin Parafollicular C cells
Considered along with
Parathormone
Regulates Calcium metabolism
9. Thyroid Hormones: Actions
Normal Hyperthyroidis
m
Hypothyroidism/Deficiency States
Intermediary Lipid: indirectly enhances lipolysis; Hypercholesterol
Metabolism elevated plasma free fatty acid; emia
Lipogenesis also stimulated
Carbohydrate: metabolism stimulated; Hyperglycaemia,
tissue utilization of sugar increased; diabetic like
glycogenolysis and gluconeogenesis stale, insulin
increased, faster absorption of glucose resistance
from intestine
Protein: overall catabolic, prolong action: Weight loss
negative nitrogen balance and tissue
wasting.
10. Normal Hyperthyroidism Hypothyroidism/Deficiency
states
Calorigenesis Increase BMR; Metabolic rates
in brain, gonads, uterus, spleen,
lymph nodes, not significantly
affected.
Cardiovascular
System
Hyperdynamic state of
circulation due: increased
peripheral demand, direct
cardiac actions.
Fast bounding pulse
Atrial fibrillation, arrhythmias
Congestive Heart Failure,
angina
Reduced Myocardial O2
demand
Nervous System Profound functional effects Anxious, nervous, excitable,
tremors, hyperreflexia
Mental Retardation
(Cretinism)
Sluggishness, behavioural
symptoms (Myxedema)
Skeletal Muscle Increased Muscle tone, tremor,
weakness due to myopathy
Flabby and weak
(Myxedema)
Gastrointestinal Increases propulsive activity Diarrhoea Constipation
Thyroid Hormones: Actions
11. Normal Hyperthyroidism Hypothyroidism/Deficiency State
Reproduction Indirect effect on Reproduction
Maintenance of pregnancy and
lactation
Impaired female fertility
Oligomenorrhoea
Kidney No diuresis in euthyroid
patients
Diuresis in myxedematous pts on
treatment with T3 & T4
Hematopoiesis Facilitates erythropoiesis Anaemia
Growth and
Development
Maturation of nervous system • Congenital deficiency leading to
Cretinism
• Delayed developmental
milestones
• Retardation and nervous deficit
• Adult: Impaired intelligence and
slow movements
Thyroid Hormones: Actions
12. Thyroid Hormones
• Mechanism of Action:
• Penetrates cells by active transport binds to
nuclear thyroid hormone receptor bound to the
thyroid hormone response element (TRE)
conformation changes occur
(heterodimerization of receptor with retinoid X
receptor (RXR)) releases coreporessor and
binding of coactivator occurs gene
transcription induced production of specific
mRNA and protein synthesis metabolic and
anatomic effects.
• Sensitization of adrenergic receptors to
catecholamines tachycardia, arrhythmia,
raised BP, tremor, hypoglycaemia
13. Thyroid Hormones: Uses
• Cretinism
• Adult Hypothyroidism
• Myxoedema coma
• Nontoxic Goiter
• Thyroid Nodule
• Papillary carcinoma of thyroid
• Emperical use
16. Antithyroid Drugs
• Mechanism of Action:
• Binds to the Thyroid Peroxidase and prevent oxidation of
iodide/iodotyrosil residues thereby:
• Inhibit iodination of tyrosine residues in thyroglobulin
• Inhibit coupling of iodotyrosine residues to for T3 and T4
• Thyroid colloid is depleted over time and blood levels of thyroid
hormones are progressively lowered.
• Additionally for Propylthiouracil: inhibits peripheral conversion of
T4 to T3 by Deiodinase (D1)
Propylthiouracil, Methimazole,
Carbimazole
17. Thioamides: Pharmacokinetics
• Well absorbed orally
• Widely distributed (enters milk and placenta)
• Higher concentration in thyroid, longer intrathyroid half life
• Metabolised in liver
• Excreted in urine
18. Thioamides: Adverse Effects
• Due to Overtreatment:
• Hypothyroidism, goiter
• Important side effects:
• Gastrointestinal intolerance, skin rashes, joint pain
• Infrequent side effects:
• Loss or graying of hair, loss of taste, fever, liver damage
• Rare but serious:
• Agranulocytosis
19. Thioamides: Uses
• Control Thyrotoxicosis in:
• Grave’s Disease
• Toxic Nodular Goiter
• Can be used as:
• Definitive therapy
• Preoperatively
• Along with 131I
20. Ionic Inhibitors
• Mechanism of Action
• Inhibits iodide trapping by NIS into the thyroid T3 and T4 not synthesised
• Toxic and not clinically used these days
Thiocyanates, Perchlorates, Nitrates
21. Iodine and Iodides
• Fastest acting thyroid inhibitor
• Peak effects seen after 10-15 days followed by “thyroid escape”
• Seen more in multinodular goiter
• Mechanism of Action (not clear):
• Inhibition of hormone release- termed as ‘thyroid constipation’
• Endocytosis of colloid and proteolysis of thyroglobulin comes to halt.
• Excess of iodine inhibits its own transport by interfering with expression of
NIS
• Attenuates TSH and cAMP induced thyroid stimulation
• Rapid and brief intereference with iodination of tyrosil and thyronil residues
of Thyroglobulin
22. Iodine and Iodides: Uses
• Preoperative preparation
• Thyroid storm
• Prophylaxis of endemic goiter
• As antiseptic
23. Iodine and Iodide: Adverse Effects
• Acute Reaction
• Chronic overdose (iodism)
• Long term use of high doses:
• Hypothyroidism and goitre
• Flaring of acne in adolscents
• Pregnancy/Lactating mothers:
• Foetal/infantile goitre and hypothyroidism
• Aggravation of thyrotoxicosis in multinodular goitre
24. Radioactive Iodine
•131I emits X-rays and β-particles
• X-rays: tracer studies
• β-particles: destructive effect on thyroid tissues
• Mechanism of Action:
• Concentrated by thyroid, incorporated into colloid emits
radiation from within the follicle undergo pyknosis and necrosis
followed by fibrosis
• Partial ablation can be achieved
25. Radioactive Iodine
• Administered as sodium salt of 131I dissolved in water and taken orally.
• Use:
• Diagnostic: 25-100 mcCurie is given: no damage to thyroid cells occur at this
dose
• Therapeutic:
• Hyperthyroidism due to Grave’s disease or Toxic nodular goitre
• Average Dose: 3-6 mCurie; higher dose for toxic multinodular goitre
