Thyroid

Question 1

Lugol’s Iodine – mechanism, beneficial effects, limitations, indications & precautions

Answer 1

• Mechanismofaction(MOA): Produces a rapid ‘thyroid‑constipation’ by blocking multiple steps – inhibits Na⁺/I⁻ symporter expression, interferes with oxidation/iodination (Wolff–Chaikoff effect), arrests endocytosis of thyroglobulin and proteolysis → immediate fall in T₃/T₄ release fileciteturn0file0turn0file11
• Beneficial/therapeutic effects
– Fastest inhibitor: clinical response within 24 h; peak 10–15 days fileciteturn0file0
– Shrinks, firms and devascularises gland → easier surgery fileciteturn0file4
– Falls peripheral T₄→T₃ conversion (useful in storm) fileciteturn0file4
• Indications
1. Pre‑operative preparation in Graves’ disease (5–10 drops × 10 days)
2. Thyroid storm (6–10 drops oral or iodinated contrast)
3. Prophylaxis of endemic goitre (iodised salt)
4. Topical antiseptic forms (tincture, povidone‑iodine) fileciteturn0file4
• Limitations & adverse effects
– ‘Thyroid‑escape’ after 14 d → rebound thyrotoxicosis, esp. multinodular goitre fileciteturn0file0
– Acute allergy (angio‑oedema) or chronic ‘iodism’ (rhinitis, metallic taste, acne) fileciteturn0file5
– Long‑term use → hypothyroidism/goitre; may flare acne; aggravate multinodular toxic goitre
• Precautions/contra‑indications
– Avoid >14 d continuous therapy; donot use in pregnancy/lactation (foetal goitre, cretinism)
– Screen for iodine sensitivity; discontinue at first sign of iodism

Question 2

Carbimazole – mechanism, beneficial effects, limitations, indications & precautions

Answer 2

• MOA: Converted to methimazole; binds thyroid peroxidase → blocks iodination & coupling of MIT/DIT; no effect on hormone release or peripheral T₄→T₃ conversion fileciteturn0file9
• Pharmacokinetics: Well‑absorbed; t½ 6–10 h; single daily dose usually adequate; crosses placenta & milk more than PTU fileciteturn0file2
• Therapeutic advantages
– First‑line for Graves’, children, young adults; high potency (≈5× PTU)
– Reversible hypothyroidism; non‑invasive alternative to surgery/¹³¹I fileciteturn0file14
• Indications
1. Definitive therapy in Graves’ disease (12–24 mo)
2. Pre‑operative euthyroid preparation
3. Short‑term control before/after ¹³¹I
• Limitations/adverse effects
– Latent onset (2–3 wk); relapse ≈50 % on withdrawal fileciteturn0file14
– Common: GI upset, pruritic rash, arthralgia; Serious: agranulocytosis (1 : 500‑1000) fileciteturn0file2
• Precautions
– Avoid high dose in late pregnancy (foetal hypothyroidism); monitor CBC & LFTs; switch to PTU if intolerance

Question 3

Propylthiouracil (PTU) – mechanism, benefits, limitations, indications & precautions

Answer 3

• MOA: Same TPO inhibition as carbimazole + uniquely blocks peripheral 5’-deiodinase (T₄→T₃) conversion fileciteturn0file2
• PK: Highly protein‑bound; t½ 1–2 h ➜ needs 8‑hourly dosing; does not form active metabolite fileciteturn0file2
• Therapeutic advantages
– Preferred in 1st‑trimester pregnancy (less placental transfer) & thyroid storm (double mechanism) fileciteturn0file2
– Safe in children; reversible effects
• Indications
1. Acute thyroid storm (250 mg PO q4–6 h)
2. Early pregnancy hyperthyroidism
3. Intolerance to carbimazole/methimazole
• Limitations & adverse effects
– Hepatotoxicity (rare fulminant hepatitis), agranulocytosis, vasculitis; latent response 2‑3 wk
– Multiple daily dosing affects compliance
• Precautions
– Baseline & periodic liver functions, CBC; instruct patients to report sore throat/jaundice

Question 4

Radioactive Iodine (¹³¹I) – mechanism, benefits, limitations, indications & precautions

Answer 4

• MOA: ¹³¹I⁻ concentrates in follicle; β‑particles (0.5–2 mm) induce selective necrosis & fibrosis; γ‑rays useful diagnostically fileciteturn0file6
• Therapeutic protocol: Oral Na¹³¹I, 3–6 mCi; response starts 2 wk, peaks ≈ 3 mo; repeat doses in 20–40 % fileciteturn0file6
• Advantages
– Simple outpatient procedure, inexpensive, no surgery risk or scar fileciteturn0file6
– Permanent cure for Graves’ / toxic nodular goitre; can be titrated
• Limitations / adverse effects
– Progressive hypothyroidism: 5–10 % per year in Graves’ (lifelong T₄) fileciteturn0file16
– Latent onset; contraindicated in pregnancy & children; not preferred in young adults (<25 y)
– Neck soreness, radiation safety logistics
• Indications
1. Hyperthyroidism due to Graves’ or toxic multinodular goitre, esp. >35 y or surgery‑unfit
2. Relapse after surgery or drug therapy
3. Palliative for metastatic follicular/papillary carcinoma (higher dose with TSH priming) fileciteturn0file6
• Precautions
– Stop antithyroid drugs 5–7 d pre‑dose, restart later; avoid pregnancy conception for ≥6 mo

Question 5

Enumerate the uses of thyroid hormones (levothyroxine/liothyronine)

Answer 5

• Replacement therapy (T₄ 100–150 µg/d in adults)
1. Cretinism – 8–12 µg/kg/d, start early to prevent irreversible neuro‑deficit fileciteturn0file10
2. Adult hypothyroidism (myxoedema) – lifelong; start low if >50 y or cardiac disease fileciteturn0file10
3. Sub‑clinical hypothyroidism with TSH >10 mIU/L
• Myxoedema coma – IV T₄ 200–500 µg + low‑dose IV T₃ fileciteturn0file3
• Non‑toxic goitre with iodine deficiency – suppressive T₄
• Post‑thyroidectomy for differentiated carcinoma – TSH‑suppressive doses fileciteturn0file3
• Benign TSH‑responsive thyroid nodule (trial of suppression) fileciteturn0file19
• Empirical/adjunctive: refractory anaemia, infertility, chronic ulcers (limited evidence) fileciteturn0file19

Question 6

Why is Lugol’s iodine given ~10 days before thyroid surgery?

Answer 6

It rapidly blocks hormone release and shrinks, firms and devascularises the gland, making it easier and safer to handle during subtotal thyroidectomy; effect appears within days and is additive to prior carbimazole therapy fileciteturn0file4

Question 7

Why is Propylthiouracil preferred in hyperthyroid pregnancy / thyroid storm?

Answer 7

Because besides inhibiting hormone synthesis it blocks peripheral T₄→T₃ conversion, giving faster fall in active hormone, and its high protein‑binding limits placental transfer, reducing foetal hypothyroid risk; hence used 1st trimester and in thyroid storm fileciteturn0file2

Question 8

Why is Carbimazole drug of choice in Graves’ disease?

Answer 8

High potency with once‑daily dosing, good long‑term remission rates, well tolerated, suitable for young/children; reversibility and avoidance of surgery or radiation make it first‑line definitive therapy in Graves’ disease fileciteturn0file14

Question 9

Why is Propranolol co‑administered in thyrotoxicosis?

Answer 9

Non‑selective β‑blockade rapidly controls sympathomimetic features (palpitations, tremor) and, at higher doses, inhibits peripheral T₄→T₃ conversion, providing quick biochemical/clinical improvement while awaiting response to antithyroid therapy or ¹³¹I; also vital in thyroid storm and pre‑op preparation fileciteturn0file16

Question 10

Why must antithyroid drugs be started 2 h before iodides in thyroid storm?

Answer 10

Giving PTU first blocks new hormone synthesis and T₄→T₃ conversion; waiting 1–2 h before Lugol’s prevents the iodine from being utilised for new hormone synthesis (avoids Jod‑Basedow) while still allowing its benefit of inhibiting hormone release.

Question 11

Classify antithyroid drugs & outline pharmacotherapy of thyrotoxicosis

Answer 11

• Classification (major therapeutic groups)
1. Synthesis (TPO) inhibitors – Propylthiouracil, Carbimazole, Methimazole
2. Iodide trapping inhibitors – Perchlorate, Thiocyanate (not used clinically)
3. Hormone release inhibitors – High‑dose iodide, Lugol’s, iodinated contrast
4. Follicle‑destroying – Radioactive iodine (¹³¹I)
5. Symptomatic – β‑blockers (Propranolol) fileciteturn0file3
• Step‑wise pharmacotherapy of Graves’ / diffuse thyrotoxicosis
1. Initiate carbimazole 15–30 mg/d (or PTU 100 mg TDS) ➜ taper to maintenance by 12–24 mo
2. Add propranolol 40–60 mg QID for immediate symptom relief
3. If large gland/poor drug tolerance → subtotal thyroidectomy after euthyroid & 10 d Lugol’s
4. Alternative in adults >35 y or relapse → ¹³¹I ablation; control with carbimazole ± β‑blocker during latent period fileciteturn0file14

Question 12

Pharmacotherapy algorithm for toxic nodular goitre

Answer 12

• Definitive therapy – ¹³¹I ablation (higher dose than Graves’) is preferred in older patients; surgery if nodules large, symptomatic or suspicious of malignancy fileciteturn0file6
• Antithyroid drugs (carbimazole/PTU) provide only temporary control; useful pre‑op or where ¹³¹I contraindicated/unavailable fileciteturn0file14
• β‑blocker for prompt symptom relief; Lugol’s for short pre‑op preparation
• Lifelong T₄ supplementation may be needed if post‑therapy hypothyroidism develops.

Question 13

Lugol’s Iodine – mechanism, beneficial effects, limitations, indications & precautions

Answer 13

• Mechanismofaction(MOA): Produces a rapid ‘thyroid‑constipation’ by blocking multiple steps – inhibits Na⁺/I⁻ symporter expression, interferes with oxidation/iodination (Wolff–Chaikoff effect), arrests endocytosis of thyroglobulin and proteolysis → immediate fall in T₃/T₄ release fileciteturn0file0turn0file11
• Beneficial/therapeutic effects
– Fastest inhibitor: clinical response within 24 h; peak 10–15 days fileciteturn0file0
– Shrinks, firms and devascularises gland → easier surgery fileciteturn0file4
– Falls peripheral T₄→T₃ conversion (useful in storm) fileciteturn0file4
• Indications
1. Pre‑operative preparation in Graves’ disease (5–10 drops × 10 days)
2. Thyroid storm (6–10 drops oral or iodinated contrast)
3. Prophylaxis of endemic goitre (iodised salt)
4. Topical antiseptic forms (tincture, povidone‑iodine) fileciteturn0file4
• Limitations & adverse effects
– ‘Thyroid‑escape’ after 14 d → rebound thyrotoxicosis, esp. multinodular goitre fileciteturn0file0
– Acute allergy (angio‑oedema) or chronic ‘iodism’ (rhinitis, metallic taste, acne) fileciteturn0file5
– Long‑term use → hypothyroidism/goitre; may flare acne; aggravate multinodular toxic goitre
• Precautions/contra‑indications
– Avoid >14 d continuous therapy; donot use in pregnancy/lactation (foetal goitre, cretinism)
– Screen for iodine sensitivity; discontinue at first sign of iodism

Question 14

Carbimazole – mechanism, beneficial effects, limitations, indications & precautions

Answer 14

• MOA: Converted to methimazole; binds thyroid peroxidase → blocks iodination & coupling of MIT/DIT; no effect on hormone release or peripheral T₄→T₃ conversion fileciteturn0file9
• Pharmacokinetics: Well‑absorbed; t½ 6–10 h; single daily dose usually adequate; crosses placenta & milk more than PTU fileciteturn0file2
• Therapeutic advantages
– First‑line for Graves’, children, young adults; high potency (≈5× PTU)
– Reversible hypothyroidism; non‑invasive alternative to surgery/¹³¹I fileciteturn0file14
• Indications
1. Definitive therapy in Graves’ disease (12–24 mo)
2. Pre‑operative euthyroid preparation
3. Short‑term control before/after ¹³¹I
• Limitations/adverse effects
– Latent onset (2–3 wk); relapse ≈50 % on withdrawal fileciteturn0file14
– Common: GI upset, pruritic rash, arthralgia; Serious: agranulocytosis (1 : 500‑1000) fileciteturn0file2
• Precautions
– Avoid high dose in late pregnancy (foetal hypothyroidism); monitor CBC & LFTs; switch to PTU if intolerance

Question 15

Propylthiouracil (PTU) – mechanism, benefits, limitations, indications & precautions

Answer 15

• MOA: Same TPO inhibition as carbimazole + uniquely blocks peripheral 5’-deiodinase (T₄→T₃) conversion fileciteturn0file2
• PK: Highly protein‑bound; t½ 1–2 h ➜ needs 8‑hourly dosing; does not form active metabolite fileciteturn0file2
• Therapeutic advantages
– Preferred in 1st‑trimester pregnancy (less placental transfer) & thyroid storm (double mechanism) fileciteturn0file2
– Safe in children; reversible effects
• Indications
1. Acute thyroid storm (250 mg PO q4–6 h)
2. Early pregnancy hyperthyroidism
3. Intolerance to carbimazole/methimazole
• Limitations & adverse effects
– Hepatotoxicity (rare fulminant hepatitis), agranulocytosis, vasculitis; latent response 2‑3 wk
– Multiple daily dosing affects compliance
• Precautions
– Baseline & periodic liver functions, CBC; instruct patients to report sore throat/jaundice

Question 16

Radioactive Iodine (¹³¹I) – mechanism, benefits, limitations, indications & precautions

Answer 16

• MOA: ¹³¹I⁻ concentrates in follicle; β‑particles (0.5–2 mm) induce selective necrosis & fibrosis; γ‑rays useful diagnostically fileciteturn0file6
• Therapeutic protocol: Oral Na¹³¹I, 3–6 mCi; response starts 2 wk, peaks ≈ 3 mo; repeat doses in 20–40 % fileciteturn0file6
• Advantages
– Simple outpatient procedure, inexpensive, no surgery risk or scar fileciteturn0file6
– Permanent cure for Graves’ / toxic nodular goitre; can be titrated
• Limitations / adverse effects
– Progressive hypothyroidism: 5–10 % per year in Graves’ (lifelong T₄) fileciteturn0file16
– Latent onset; contraindicated in pregnancy & children; not preferred in young adults (<25 y)
– Neck soreness, radiation safety logistics
• Indications
1. Hyperthyroidism due to Graves’ or toxic multinodular goitre, esp. >35 y or surgery‑unfit
2. Relapse after surgery or drug therapy
3. Palliative for metastatic follicular/papillary carcinoma (higher dose with TSH priming) fileciteturn0file6
• Precautions
– Stop antithyroid drugs 5–7 d pre‑dose, restart later; avoid pregnancy conception for ≥6 mo

Question 17

Enumerate the uses of thyroid hormones (levothyroxine/liothyronine)

Answer 17

• Replacement therapy (T₄ 100–150 µg/d in adults)
1. Cretinism – 8–12 µg/kg/d, start early to prevent irreversible neuro‑deficit fileciteturn0file10
2. Adult hypothyroidism (myxoedema) – lifelong; start low if >50 y or cardiac disease fileciteturn0file10
3. Sub‑clinical hypothyroidism with TSH >10 mIU/L
• Myxoedema coma – IV T₄ 200–500 µg + low‑dose IV T₃ fileciteturn0file3
• Non‑toxic goitre with iodine deficiency – suppressive T₄
• Post‑thyroidectomy for differentiated carcinoma – TSH‑suppressive doses fileciteturn0file3
• Benign TSH‑responsive thyroid nodule (trial of suppression) fileciteturn0file19
• Empirical/adjunctive: refractory anaemia, infertility, chronic ulcers (limited evidence) fileciteturn0file19

Question 18

Why is Lugol’s iodine given ~10 days before thyroid surgery?

Answer 18

It rapidly blocks hormone release and shrinks, firms and devascularises the gland, making it easier and safer to handle during subtotal thyroidectomy; effect appears within days and is additive to prior carbimazole therapy fileciteturn0file4

Question 19

Why is Propylthiouracil preferred in hyperthyroid pregnancy / thyroid storm?

Answer 19

Because besides inhibiting hormone synthesis it blocks peripheral T₄→T₃ conversion, giving faster fall in active hormone, and its high protein‑binding limits placental transfer, reducing foetal hypothyroid risk; hence used 1st trimester and in thyroid storm fileciteturn0file2

Question 20

Why is Carbimazole drug of choice in Graves’ disease?

Answer 20

High potency with once‑daily dosing, good long‑term remission rates, well tolerated, suitable for young/children; reversibility and avoidance of surgery or radiation make it first‑line definitive therapy in Graves’ disease fileciteturn0file14

Question 21

Why is Propranolol co‑administered in thyrotoxicosis?

Answer 21

Non‑selective β‑blockade rapidly controls sympathomimetic features (palpitations, tremor) and, at higher doses, inhibits peripheral T₄→T₃ conversion, providing quick biochemical/clinical improvement while awaiting response to antithyroid therapy or ¹³¹I; also vital in thyroid storm and pre‑op preparation fileciteturn0file16

Question 22

Why must antithyroid drugs be started 2 h before iodides in thyroid storm?

Answer 22

Giving PTU first blocks new hormone synthesis and T₄→T₃ conversion; waiting 1–2 h before Lugol’s prevents the iodine from being utilised for new hormone synthesis (avoids Jod‑Basedow) while still allowing its benefit of inhibiting hormone release.

Question 23

Classify antithyroid drugs & outline pharmacotherapy of thyrotoxicosis

Answer 23

• Classification (major therapeutic groups)
1. Synthesis (TPO) inhibitors – Propylthiouracil, Carbimazole, Methimazole
2. Iodide trapping inhibitors – Perchlorate, Thiocyanate (not used clinically)
3. Hormone release inhibitors – High‑dose iodide, Lugol’s, iodinated contrast
4. Follicle‑destroying – Radioactive iodine (¹³¹I)
5. Symptomatic – β‑blockers (Propranolol) fileciteturn0file3
• Step‑wise pharmacotherapy of Graves’ / diffuse thyrotoxicosis
1. Initiate carbimazole 15–30 mg/d (or PTU 100 mg TDS) ➜ taper to maintenance by 12–24 mo
2. Add propranolol 40–60 mg QID for immediate symptom relief
3. If large gland/poor drug tolerance → subtotal thyroidectomy after euthyroid & 10 d Lugol’s
4. Alternative in adults >35 y or relapse → ¹³¹I ablation; control with carbimazole ± β‑blocker during latent period fileciteturn0file14

Question 24

Pharmacotherapy algorithm for toxic nodular goitre

Answer 24

• Definitive therapy – ¹³¹I ablation (higher dose than Graves’) is preferred in older patients; surgery if nodules large, symptomatic or suspicious of malignancy fileciteturn0file6
• Antithyroid drugs (carbimazole/PTU) provide only temporary control; useful pre‑op or where ¹³¹I contraindicated/unavailable fileciteturn0file14
• β‑blocker for prompt symptom relief; Lugol’s for short pre‑op preparation
• Lifelong T₄ supplementation may be needed if post‑therapy hypothyroidism develops.