Vitamin D: extrarenal 1-alpha-hydroxylase: practice question

A Biochemistry question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Biochemistry · Vitamin D: extrarenal 1-alpha-hydroxylase

Sample item

A 40-year-old woman with bilateral hilar lymphadenopathy and non-caseating granulomas on biopsy has serum calcium 12.4 mg/dL, low PTH, normal 25-hydroxyvitamin D and raised 1,25-dihydroxyvitamin D. Which mechanism explains the hypercalcaemia?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

A. Unregulated 1-alpha-hydroxylase activity in granuloma macrophages

Activated macrophages in sarcoid granulomas express 1-alpha-hydroxylase and convert 25-hydroxyvitamin D to calcitriol without the negative feedback from calcium and PTH that restrains the renal enzyme. Raised calcitriol increases gut calcium absorption and bone resorption, suppressing PTH. Glucocorticoids reduce macrophage activation and calcitriol production.

Option by option

  • A. Unregulated 1-alpha-hydroxylase activity in granuloma macrophages (correct)

    Correct. Macrophage 1-alpha-hydroxylase escapes feedback and overproduces calcitriol.

  • B. Excess PTH from a parathyroid adenoma

    A parathyroid adenoma would raise PTH rather than suppress it.

  • C. Osteolysis by metastatic deposits in bone

    Metastatic osteolysis suppresses PTH but does not explain the raised calcitriol level.

  • D. Autonomous secretion of PTH-related peptide by the lymph nodes

    PTHrP secretion would give low calcitriol, not a raised level, and is typical of solid tumours and some lymphomas.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is A, Unregulated 1-alpha-hydroxylase activity in granuloma macrophages. Activated macrophages in sarcoid granulomas express 1-alpha-hydroxylase and convert 25-hydroxyvitamin D to calcitriol without the negative feedback from calcium and PTH that restrains the renal enzyme.

Why is "Excess PTH from a parathyroid adenoma" not the answer?

A parathyroid adenoma would raise PTH rather than suppress it.

Why is "Osteolysis by metastatic deposits in bone" not the answer?

Metastatic osteolysis suppresses PTH but does not explain the raised calcitriol level.

Why is "Autonomous secretion of PTH-related peptide by the lymph nodes" not the answer?

PTHrP secretion would give low calcitriol, not a raised level, and is typical of solid tumours and some lymphomas.

What concept does this question test?

It tests Vitamin D: extrarenal 1-alpha-hydroxylase in Biochemistry. Raised calcitriol increases gut calcium absorption and bone resorption, suppressing PTH. Glucocorticoids reduce macrophage activation and calcitriol production.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Vitamin D: extrarenal 1-alpha-hydroxylase?

Build one table of enzyme deficiency, disease, inheritance and key finding, then revise it by spaced recall. Then use the flashcards and the other Biochemistry questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.