vitamin-d-deficiency — Viva

Q1: Metabolism and what to measure (2 min)^[1]

Examiner: Walk me through vitamin D metabolism. Which metabolite do you measure to diagnose deficiency, and why?^[1]

Expected answer:^[1]

• Vitamin D3 is made in skin when UVB converts 7-dehydrocholesterol to previtamin D3; D2 and D3 also come from the diet.
• The LIVER 25-hydroxylates it (CYP2R1) to CALCIDIOL (25-OH-D) — the storage form and the metabolite MEASURED, because this step is unregulated and reflects total-body status.^[1]
• The KIDNEY 1-alpha-hydroxylates it (CYP27B1, stimulated by PTH and low phosphate) to CALCITRIOL (1,25-diOH-D), the active hormone acting via the vitamin D receptor on gut and bone.
• Measure 25-OH-D, NOT calcitriol: calcitriol can be normal in deficiency because secondary hyperparathyroidism drives its production.
• Severe deficiency is under 12 ng/mL (30 nmol/L); deficiency under 20 ng/mL (50 nmol/L); 50 nmol/L or above is the treatment goal.

Q2: Clinical features and biochemistry (3 min)^[1]

Examiner: How do rickets and osteomalacia differ clinically, and what is the classical biochemical pattern?^[1]

Expected answer:^[1]

• RICKETS (children, growing skeleton): bowing of legs (genu varum), enlarged wrists, rachitic rosary, frontal bossing, delayed fontanelle closure, dental defects, short stature; severe infant disease can cause hypocalcaemic seizures and cardiomyopathy. X-rays show cupped, frayed metaphyses.
• OSTEOMALACIA (adults, mature skeleton): diffuse bone pain, PROXIMAL MYOPATHY with difficulty rising from a chair or climbing stairs, waddling gait, pathological fractures; X-rays show LOOSER ZONES (pseudofractures).
• Classical biochemistry: LOW or NORMAL calcium, LOW phosphate, HIGH PTH (secondary hyperparathyroidism), HIGH ALP.
• Pathophysiology: low calcitriol reduces gut calcium absorption -> hypocalcaemia -> PTH rises -> phosphaturia (low phosphate) and bone resorption (high ALP), alongside defective mineralisation.

Q3: Causes and treatment (3 min)^[1]

Examiner:^[3] List the causes and describe the treatment.

Expected answer:

• Causes: inadequate sun, dark skin, exclusive breastfeeding, malabsorption (coeliac, IBD, post-bariatric), CKD, liver disease, obesity, enzyme-inducing drugs (anticonvulsants, rifampicin).
• Treatment: CHOLECALCIFEROL (or ergocalciferol) — validated regimens: oral 50,000 IU weekly for 8 weeks, oral 200,000 IU monthly, or IM 600,000 IU monthly, then maintenance 50,000 IU monthly or bimonthly.^[3] PLUS adequate calcium (1000 to 1200 mg/day).
• In CKD or liver failure use ACTIVE vitamin D — CALCITRIOL or alfacalcidol — because 1-alpha-hydroxylation is impaired.
• Obesity needs roughly two-thirds higher intake (dose-response slope 0.398 vs 0.66 nmol/L per microgram/day); malabsorption needs higher doses.
• Treat the underlying cause and monitor 25-OH-D, calcium, phosphate, PTH and ALP.

Q4: Special populations and pearls (2 min)^[1]

Examiner:^[1] What preventive advice do you give, and what emergency must you not miss?

Expected answer:

• ALL infants should receive 400 IU/day vitamin D from birth, especially exclusively breastfed babies (breast milk is vitamin D poor) — 400 IU daily achieves 25-OH-D over 50 nmol/L.^[1]tamin D poor).
• Screen and supplement high-risk groups: dark skin, elderly, housebound, veiled, obese, malabsorption, CKD.
• Symptomatic HYPOCALCAEMIA in severe infantile rickets (seizures, laryngospasm, cardiomyopathy) is an EMERGENCY — give IV calcium gluconate with cardiac monitoring, then vitamin D.
• Response is rapid: pain and weakness improve within weeks, biochemistry within months; residual bowing may persist if treatment is delayed.
• The two exam traps: measure 25-OH-D not calcitriol, and CKD needs calcitriol not cholecalciferol.

References4ShowHide

1. [1]Munns CF, Shaw N, Kiely M, et al. Global Consensus Recommendations on Prevention and Management of Nutritional Rickets J Clin Endocrinol Metab, 2016.PMID 26745253
2. [2]Amrein K, Scherkl M, Hoffmann M, et al. Vitamin D deficiency 2.0: an update on the current status worldwide Eur J Clin Nutr, 2020.PMID 31959942
3. [3]Hassan AB, Hozayen RF, Alotaibi RA, et al. Therapeutic and maintenance regimens of vitamin D3 supplementation in healthy adults: A systematic review Cell Mol Biol (Noisy-le-grand), 2018.PMID 30511630
4. [4]Sanders KM, Stuart AL, Williamson EJ, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial JAMA, 2010.PMID 20460620