Endocrinology: PTH resistance: practice question

A Physiology 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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Physiology · Endocrinology: PTH resistance

Sample item

A 12-year-old with short stature, a round face and short fourth metacarpals has low serum calcium, high phosphate and a high PTH. Infused PTH causes no rise in urinary cAMP or phosphate excretion. What is the basic defect?

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

The answer and the reasoning

C. Target-cell resistance to PTH from defective Gs-alpha coupling of its receptor

In pseudohypoparathyroidism the PTH receptor cannot signal through Gs-alpha, so cAMP does not rise and the kidney and bone do not respond. The glands secrete abundant PTH but calcium stays low and phosphate high. The unresponsiveness to infused PTH separates it from true hypoparathyroidism.

Option by option

  • A. Deficient 1-alpha-hydroxylation of vitamin D in the kidney

    Poor vitamin D activation would give low calcium, but the cAMP and phosphaturic response to PTH would be normal.

  • B. Inactivating mutation of the calcium-sensing receptor

    An inactivating calcium-sensing receptor mutation causes hypercalcaemia with a raised PTH rather than hypocalcaemia.

  • C. Target-cell resistance to PTH from defective Gs-alpha coupling of its receptor (correct)

    Correct. Failed Gs-alpha signalling means PTH is high but the tissues do not respond.

  • D. Destruction of parathyroid tissue after neck surgery

    Destroyed glands would give a low PTH, and infused PTH would still raise cAMP and phosphaturia.

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 Physiology question

What is the answer to this Physiology question?

The best answer is C, Target-cell resistance to PTH from defective Gs-alpha coupling of its receptor. In pseudohypoparathyroidism the PTH receptor cannot signal through Gs-alpha, so cAMP does not rise and the kidney and bone do not respond.

Why is "Deficient 1-alpha-hydroxylation of vitamin D in the kidney" not the answer?

Poor vitamin D activation would give low calcium, but the cAMP and phosphaturic response to PTH would be normal.

Why is "Inactivating mutation of the calcium-sensing receptor" not the answer?

An inactivating calcium-sensing receptor mutation causes hypercalcaemia with a raised PTH rather than hypocalcaemia.

Why is "Destruction of parathyroid tissue after neck surgery" not the answer?

Destroyed glands would give a low PTH, and infused PTH would still raise cAMP and phosphaturia.

What concept does this question test?

It tests Endocrinology: PTH resistance in Physiology. The glands secrete abundant PTH but calcium stays low and phosphate high. The unresponsiveness to infused PTH separates it from true hypoparathyroidism.

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 Endocrinology: PTH resistance?

For each system, sketch the key graph (pressure–volume loop, oxygen dissociation curve, nephron handling) and explain it aloud. Then use the flashcards and the other Physiology 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.