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PH7.1-9 | Endocrine Pharmacology — Practice Quiz
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A 52-year-old man with Type 2 diabetes mellitus (T2DM) and BMI 28 kg/m² presents to the OPD with an HbA1c of 9.2% despite metformin 2 g/day for 6 months. He has no heart failure or CKD (eGFR 78 mL/min). Which drug is the most appropriate add-on to metformin based on current evidence for cardiovascular risk reduction?
Correct. In a T2DM patient with established cardiovascular risk or multiple risk factors and eGFR ≥45, adding an SGLT2 inhibitor (empagliflozin, canagliflozin) to metformin is recommended by ADA/EASD 2023 guidelines for cardiovascular and renal benefit beyond glucose lowering.
SGLT2 inhibitors have a dual threshold: eGFR ≥45 for glycaemic benefit; eGFR ≥20–25 (drug-specific) for cardio-renal benefit. Do not withhold them solely for borderline eGFR when the indication is HFrEF or CKD albuminuria.
Incorrect. While glibenclamide lowers HbA1c, it carries hypoglycaemia risk and no cardiovascular benefit. Acarbose has modest efficacy. Pioglitazone increases weight and heart failure risk. Empagliflozin (SGLT2i) has proven CV mortality reduction in EMPA-REG OUTCOME and is the preferred add-on here.
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A 28-year-old woman with newly diagnosed Type 1 diabetes presents with HbA1c 11.4%. She is started on a basal-bolus insulin regimen. Which insulin analogue is most appropriate as the basal (background) component?
Correct. Insulin glargine (and detemir/degludec) are long-acting analogues with a peakless, flat profile lasting 20–24 hours — ideal as a once-daily basal insulin, closely mimicking the physiological basal secretion.
Insulin classification by onset/peak/duration: rapid (lispro/aspart/glulisine) → 5-15 min; short/regular → 30-60 min; intermediate (NPH) → peak 6-10 hr; long (glargine/detemir) → peakless, 20-24 hr.
Incorrect. Regular insulin (30–60 min onset, 6–8 hr duration) and lispro (5–15 min onset, 3–4 hr duration) are short/rapid-acting and are used as bolus insulins to cover meals, not as basal. NPH has a peak at 6–10 hours and variable absorption, making it inferior to analogues for basal coverage.
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A 65-year-old man with T2DM and eGFR 35 mL/min/1.73 m² is currently on metformin 500 mg/day. His physician is considering dose adjustment. What is the correct action regarding metformin?
Correct. Metformin is contraindicated when eGFR falls below 30 and should be used with caution and dose reduction at eGFR 30–45. Accumulated metformin in renal failure causes lactic acidosis — stop at eGFR <45 per current MIMS India/BNF guidance (some guidelines say <30; the safer threshold accepted in Indian NMC context is <45).
Metformin lactic acidosis threshold: stop at eGFR <45; absolute contraindication at eGFR <30. SGLT2 inhibitors have a SEPARATE dual threshold: glycaemic benefit lost at eGFR ~45; cardio-renal benefit (HFrEF/CKD) preserved down to eGFR ~20.
Incorrect. Metformin is renally eliminated; reduced eGFR leads to accumulation and life-threatening lactic acidosis. SGLT2 inhibitors have reduced glycaemic efficacy at eGFR <45 (insufficient SGLT2 in proximal tubule) — they should also not be started at eGFR <45 for glucose lowering.
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A 35-year-old woman in the first trimester of pregnancy is diagnosed with hyperthyroidism (Graves' disease). Her free T4 is markedly elevated. Which drug should be initiated?
Correct. PTU is the preferred antithyroid drug in the first trimester because carbimazole carries a teratogenicity risk (aplasia cutis, choanal atresia). From the second trimester, the switch back to carbimazole is recommended because PTU's hepatotoxicity risk increases with prolonged use.
The pregnancy antithyroid switch rule: PTU in T1 (carbimazole teratogenic) → switch to carbimazole from T2 (PTU hepatotoxic long-term). Both cross the placenta — use the minimum effective dose and monitor fetal thyroid.
Incorrect. Carbimazole is teratogenic (risk of aplasia cutis and embryopathy) in the first trimester. Radioiodine is absolutely contraindicated in pregnancy. Lugol's iodine provides only temporary control (Wolff-Chaikoff effect) and is not a standalone therapy for Graves' disease in pregnancy.
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A 55-year-old woman on long-term prednisolone 15 mg/day for rheumatoid arthritis is to undergo elective knee surgery. Pre-operatively, her surgeon asks about steroid management. What is the most important instruction regarding her prednisolone?
Correct. Patients on long-term corticosteroids (≥3 weeks) have HPA axis suppression and cannot mount an adequate cortisol stress response. Abrupt cessation risks Addisonian crisis (hypotension, hyponatraemia, hyperkalaemia, hypoglycaemia). The correct management is to continue the baseline dose and give supplemental IV hydrocortisone (100 mg q8h perioperatively) during the surgical stress.
Two corticosteroid disasters: (1) never stop abruptly after ≥3 weeks — taper slowly (7-10 days minimum); (2) supplement perioperatively with IV hydrocortisone to cover the cortisol demand of surgical stress.
Incorrect. Abruptly stopping corticosteroids causes acute adrenal insufficiency during surgical stress. Halving the dose or switching to dexamethasone (no mineralocorticoid activity) without adding supplemental glucocorticoid leaves the patient dangerously undersupported. The key intervention is supplemental IV hydrocortisone.
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A 68-year-old postmenopausal woman is diagnosed with osteoporosis (T-score −3.2, one prior vertebral fracture, eGFR 42 mL/min). She cannot tolerate oral bisphosphonates due to severe GORD. Which agent is the most appropriate first-line treatment?
Correct. Denosumab (RANK-L monoclonal antibody) is the agent of choice when oral bisphosphonates are not tolerated. Importantly, unlike bisphosphonates (renally eliminated; avoid at eGFR <35), denosumab does not require dose adjustment for renal function and can be used at any eGFR. It is given as SC injection every 6 months, bypassing the GI route.
Denosumab vs bisphosphonates: denosumab has no renal contraindication (unlike bisphosphonates which require eGFR ≥35); after stopping denosumab, must transition to a bisphosphonate to prevent rebound bone loss (the 'denosumab holiday' trap).
Incorrect. Alendronate is contraindicated in severe GORD and requires eGFR ≥35. Teriparatide (anabolic) is reserved for severe osteoporosis (T-score ≤−3.0 + multiple fractures or prior anti-resorptive failure) — not first-line. Raloxifene (SERM) reduces vertebral fractures only and has no benefit for non-vertebral fractures; also not first-line in high-risk disease.
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A 30-year-old woman presents with Graves' hyperthyroidism. Free T3 and T4 are elevated, TSH is suppressed. Propranolol 40 mg BD is started alongside carbimazole. What is the primary pharmacological rationale for propranolol in hyperthyroidism?
Correct. Propranolol (a non-selective beta-blocker) provides two benefits in hyperthyroidism: (1) rapidly controls adrenergic symptoms (palpitations, tremor, sweating, anxiety) — these are mediated by increased sensitivity to catecholamines in thyrotoxicosis; (2) at high doses, propranolol inhibits the 5'-deiodinase enzyme that converts T4 to the active T3 peripherally, providing additional symptomatic control.
Propranolol dual action in thyrotoxicosis: (1) symptom control via beta-blockade (adrenergic hypersensitivity); (2) blocks peripheral T4→T3 conversion via 5'-deiodinase inhibition — making it valuable in thyroid storm as an adjunct.
Incorrect. Beta-blockers have no effect on thyroid hormone synthesis (that is carbimazole/PTU's job) and no direct effect on iodide uptake (that is the Na/I symporter, blocked by competitive iodide loading) or TSH receptor antibodies (TSI — targeted by immunosuppressants, not beta-blockers).
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Assertion (A): Long-term oral prednisolone use can cause osteoporosis. Reason (R): Glucocorticoids increase RANK-L expression in osteoblasts and decrease OPG, tipping the balance toward osteoclast-mediated bone resorption.
Correct. Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary form of osteoporosis. The mechanism — upregulation of RANK-L and downregulation of OPG by osteoblasts — directly explains both decreased bone formation and increased resorption, making R the correct explanation of A.
GIOP mechanism: glucocorticoids → ↑RANK-L + ↓OPG → ↑osteoclastogenesis + ↓osteoblast lifespan + ↓Ca absorption. Prevention: calcium 1–1.5 g/day + vitamin D 800 IU + bisphosphonate (alendronate/risedronate) for any patient on ≥7.5 mg/day prednisolone for >3 months.
Incorrect. Both the assertion and reason are factually correct, and the mechanism described in R (RANK-L/OPG imbalance) directly explains the bone loss described in A. This is therefore option A.
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A 26-year-old breastfeeding woman (4 months postpartum) requests a reversible contraceptive. She is otherwise healthy. What is the most appropriate hormonal contraceptive option?
Correct. Oestrogen in COCs suppresses lactation (reduces prolactin efficacy) and is categorised WHO MEC 4 (absolute contraindication) in breastfeeding women <6 weeks postpartum, and WHO MEC 3 (relative contraindication) between 6 weeks and 6 months postpartum. The progestogen-only pill (POP) does not affect milk supply and is safe from day 21 postpartum.
Breastfeeding contraception: COC = WHO MEC 3–4 (oestrogen reduces milk supply) → use POP, progestogen-only injectable (DMPA), or copper IUD instead. POP is the preferred oral option — safe from day 21 postpartum.
Incorrect. COCs are contraindicated in breastfeeding women because oestrogen inhibits prolactin-driven lactation. Combined injectables also contain oestrogen. Emergency contraception (levonorgestrel) is for post-coital use only, not ongoing contraception.
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A 40-year-old woman is prescribed levothyroxine 75 mcg/day for hypothyroidism. She is also taking ferrous sulphate 200 mg daily and calcium carbonate 500 mg BD. Despite adequate doses, her TSH remains elevated at 8 mIU/L. What is the most likely cause of inadequate response?
Correct. Levothyroxine absorption (70–80% when fasting) is significantly reduced by chelating agents taken simultaneously: ferrous sulphate, calcium salts, antacids (aluminium/magnesium), and sucralfate all bind levothyroxine in the gut, forming insoluble complexes. The standard instruction is to take levothyroxine 30–60 minutes before breakfast and separate it by at least 4 hours from iron, calcium, or antacids.
Levothyroxine absorption rule: take fasting, at least 30 minutes before food; separate from iron, calcium, antacids, sucralfate by ≥4 hours. Failure to counsel on this is the most common cause of 'refractory hypothyroidism'.
Incorrect. At 75 mcg/day for a 40-year-old woman, the dose may be adequate if absorbed properly. The key issue here is drug-drug interaction: iron and calcium chelate levothyroxine in the GI tract. T4→T3 conversion by deiodinase is not blocked by iron, and TSH secretion is not directly influenced by calcium supplements.
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A 55-year-old man with acromegaly undergoes transsphenoidal surgery but post-operative GH and IGF-1 remain elevated. He is started on medical therapy. Which drug class is the first-line medical treatment after failed surgery in acromegaly?
Correct. Long-acting somatostatin analogues (octreotide LAR monthly, lanreotide depot) are the first-line medical therapy for residual/recurrent acromegaly after surgery. They suppress GH secretion and reduce IGF-1 in ~50-60% of patients. Cabergoline is adjunctive (for mildly elevated levels). Pegvisomant is reserved for SSA-refractory cases.
Acromegaly medical sequence: SSA (octreotide LAR/lanreotide) first → add cabergoline if mildly elevated → switch to pegvisomant if SSA-refractory. Pegvisomant monitoring: IGF-1 (not GH, as GH rises on this drug by design).
Incorrect. Cabergoline (dopamine agonist) is adjunctive — it lowers GH in acromegaly but less effectively than SSAs, used only when GH/IGF-1 are mildly elevated. Pegvisomant (GH receptor antagonist) blocks GH action but does not lower GH itself; it is reserved for SSA-refractory cases. Recombinant GH (somatropin) is for GH deficiency — it would worsen acromegaly.
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A 32-year-old woman presents with primary infertility due to PCOS-associated anovulation. She has failed 3 cycles of clomiphene citrate at 150 mg. Her BMI is 31 kg/m². What is the most appropriate next drug for ovulation induction?
Correct. Letrozole (aromatase inhibitor) is now the first-line ovulation inducer for PCOS anovulation, having dethroned clomiphene after the PCOSACT trial (NEJM 2014) demonstrated higher live birth rates (27.5% vs 19.1%) and fewer multiple gestations. It transiently reduces oestrogen, increasing FSH — without clomiphene's anti-oestrogenic endometrial effect. After 3 failed clomiphene cycles at maximum dose, letrozole is the logical next step before gonadotropins.
PCOS anovulation treatment ladder: Letrozole (preferred first-line per PCOSACT) ± metformin (adjunct in obese) → gonadotropins (with monitoring) → IVF. Letrozole's advantage: no anti-oestrogenic endometrial effect; lower multiple gestation rate than gonadotropins.
Incorrect. Clomiphene 150 mg is already at the effective ceiling; 200 mg is not a standard dose and would not improve outcomes. Gonadotropins are used after both clomiphene and letrozole fail — they require intensive monitoring for OHSS. GnRH agonists are not used for ovulation induction in PCOS; they suppress the axis and are used for down-regulation before IVF.
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