Granulomatous inflammation: sarcoid hypercalcaemia: practice question

A Pathology 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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Pathology · Granulomatous inflammation: sarcoid hypercalcaemia

Sample item

A 32-year-old woman has cough and bilateral hilar lymphadenopathy. Serum calcium is 11.8 mg/dL, PTH is suppressed, 25-hydroxyvitamin D is normal and 1,25-dihydroxyvitamin D is raised. 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 feedback control that limits the renal enzyme. The resulting excess calcitriol raises gut calcium absorption and causes hypercalcaemia with a suppressed PTH. Sun exposure and vitamin D supplements can worsen it, and steroids lower calcitriol production.

Option by option

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

    Raised calcitriol from granuloma 1-alpha-hydroxylase with low PTH fits this picture.

  • B. Secretion of PTH-related peptide by the tumour cells

    PTHrP hypercalcaemia also suppresses PTH but is a paraneoplastic effect, with low rather than raised 1,25-dihydroxyvitamin D.

  • C. Osteolytic metastases releasing calcium from bone

    Osteolytic metastases suppress PTH but give bone pain and lesions, with normal or low calcitriol.

  • D. Autonomous hypersecretion of PTH by a parathyroid adenoma

    A parathyroid adenoma raises PTH, which is suppressed here.

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 Pathology question

What is the answer to this Pathology 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 feedback control that limits the renal enzyme.

Why is "Secretion of PTH-related peptide by the tumour cells" not the answer?

PTHrP hypercalcaemia also suppresses PTH but is a paraneoplastic effect, with low rather than raised 1,25-dihydroxyvitamin D.

Why is "Osteolytic metastases releasing calcium from bone" not the answer?

Osteolytic metastases suppress PTH but give bone pain and lesions, with normal or low calcitriol.

Why is "Autonomous hypersecretion of PTH by a parathyroid adenoma" not the answer?

A parathyroid adenoma raises PTH, which is suppressed here.

What concept does this question test?

It tests Granulomatous inflammation: sarcoid hypercalcaemia in Pathology. The resulting excess calcitriol raises gut calcium absorption and causes hypercalcaemia with a suppressed PTH. Sun exposure and vitamin D supplements can worsen it, and steroids lower 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 Granulomatous inflammation: sarcoid hypercalcaemia?

Learn each disease as a bundle: cause, key histology, markers, and the clinical hallmark. Then use the flashcards and the other Pathology 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.