Hypercalcaemia and hyperparathyroidism — formative SAQs

SAQ 1 — The adolescent with stones and bone pain (20 marks, ~15 minutes)

A 14-year-old boy presents with renal colic, bone pain and fatigue over six months. His corrected calcium is 2.9 mmol per litre, his phosphate is low, and his intact parathyroid hormone is inappropriately normal rather than suppressed. A spot urine calcium-to-creatinine clearance ratio is 0.02. A sestamibi scan shows a single focus of uptake at the lower left pole of the thyroid. [4]

Questions

1. Give the most likely diagnosis and explain why the parathyroid hormone is inappropriately normal rather than suppressed. (4 marks) [4]
2. Outline the confirmatory and localising work-up, naming the test that separates this condition from familial hypocalciuric hypercalcaemia and its cut-off. (5 marks) [2]
3. Describe the definitive treatment and the intraoperative monitoring that confirms cure. (5 marks) [1]
4. State the complication you must anticipate in the first days after surgery and how you manage it. (6 marks) [4]

Model answer (must-hit)

1. This is primary hyperparathyroidism from a single parathyroid adenoma. The calcium is high, yet the parathyroid hormone is not suppressed, because the autonomous adenoma secretes hormone regardless of the calcium level — the feedback brake is broken, so the hormone is inappropriately normal or high. The low phosphate reflects the phosphaturic effect of the parathyroid hormone on the renal tubule. [4]
2. Confirm the calcium with an albumin correction or ionised value, then measure intact parathyroid hormone (inappropriately normal confirms PTH-dependent disease). The test that separates this from familial hypocalciuric hypercalcaemia is the urine calcium-to-creatinine clearance ratio: above 0.01 means primary hyperparathyroidism, below 0.01 means familial hypocalciuric hypercalcaemia. This child's ratio of 0.02 points to primary hyperparathyroidism. Localise the gland with a sestamibi single-photon emission computed tomography scan and a neck ultrasound, correct any vitamin D deficiency, and screen for the multiple endocrine neoplasia genes. [2]
3. The definitive treatment is a focused parathyroidectomy to remove the adenoma, guided by preoperative localisation and intraoperative parathyroid hormone monitoring. A hormone fall of more than fifty percent into the normal range at ten minutes after excision confirms cure. Screen the family for multiple endocrine neoplasia because multigland hyperplasia needs a subtotal or total parathyroidectomy rather than a focused removal. [1]
4. Anticipate hungry bone syndrome. The sudden removal of parathyroid hormone lets calcium flood into the demineralised skeleton, producing severe and sometimes symptomatic hypocalcaemia within hours to days. Monitor the calcium every six to twelve hours, give oral calcium and calcitriol prophylactically, and have intravenous calcium ready. The low calcium is the sign that the operation worked, not that it failed. [4]

SAQ 2 — The child with a family history of high calcium (20 marks, ~15 minutes)

An asymptomatic 9-year-old girl is found to have a corrected calcium of 2.7 mmol per litre on a blood test taken for an unrelated reason. Her mother and maternal grandfather have lifelong hypercalcaemia that "runs in the family" and neither has had surgery. Her intact parathyroid hormone is inappropriately normal. Her urine calcium-to-creatinine clearance ratio is 0.008. [6]

Questions

1. Give the most likely diagnosis and the single test result that confirms it. (4 marks) [6]
2. Explain why parathyroidectomy is the wrong treatment for this child, and what happens if she is operated on. (5 marks) [6]
3. Contrast her urine calcium-to-creatinine clearance ratio with that of a child who has primary hyperparathyroidism, and explain the difference mechanistically. (5 marks) [2]
4. Describe the management and counselling you would give the family. (6 marks) [6]

Model answer (must-hit)

1. This is familial hypocalciuric hypercalcaemia, a calcium-sensing receptor loss-of-function mutation. The single test result that confirms it is the urine calcium-to-creatinine clearance ratio of 0.008, which is below the 0.01 cut-off, combined with the family history of lifelong asymptomatic hypercalcaemia in an autosomal dominant pattern. A calcium-sensing receptor gene test confirms the diagnosis. [6]
2. Parathyroidectomy is the wrong treatment because the condition is benign and lifelong, with a stable calcium that is usually asymptomatic. The parathyroid glands are not autonomous — they are set to a higher calcium set-point — so removing tissue does not cure the condition: the calcium recurs, or the child is rendered permanently hypocalcaemic and dependent on lifelong calcium and calcitriol replacement. The correct management is recognition and reassurance, not surgery. [6]
3. In familial hypocalciuric hypercalcaemia the ratio is below 0.01 (this child's is 0.008), while in primary hyperparathyroidism it is above 0.01. The difference is mechanistic: in familial hypocalciuric hypercalcaemia the defective calcium-sensing receptor is expressed in both the parathyroid and the kidney tubule, so the kidney over-reabsorbs calcium and the urine calcium is low despite a high serum calcium. In primary hyperparathyroidism the high parathyroid hormone drives a higher filtered load and the urinary calcium is higher. [2]
4. Counsel the family that the condition is benign, lifelong and stable, that the calcium does not need treatment, and that the most important intervention is to avoid unnecessary parathyroid surgery. Confirm the diagnosis with a calcium-sensing receptor gene test, document it clearly in the medical record, and screen first-degree relatives — including the mother and grandfather — so that they too are protected from unnecessary surgery. Reassure that the child can lead a normal life with routine monitoring of the calcium and renal function. [6]