Hypercalcaemia and hyperparathyroidism — branching viva

Station opening

Examiner: "Tell me the single test that frames every child with a high serum calcium, and why it matters." [1]

Strong candidate (must-hit)

• The test is the intact parathyroid hormone, drawn with the calcium. When the calcium is high, a normal axis switches the hormone off, so a hormone that is high or inappropriately normal means the parathyroid is driving the calcium — primary hyperparathyroidism or familial hypocalciuric hypercalcaemia. A hormone that is suppressed means the calcium is coming from elsewhere — malignancy, vitamin D, bone, a drug. Holding that fork turns a long differential into two short lists and a clear plan, and it decides the next test. [1]

Weak candidate

• "I would check the vitamin D level and a bone density scan." [1]

Branch A — The adolescent with stones and bone pain

Examiner: "A 14-year-old boy has a calcium of 2.9 mmol per litre, an inappropriately normal parathyroid hormone, and a urine calcium-to-creatinine clearance ratio of 0.02. Name the test that separates familial hypocalciuric hypercalcaemia from primary hyperparathyroidism and its cut-off." [5]

Strong

• The test is the urine calcium-to-creatinine clearance ratio, calculated from paired serum and urine calcium and creatinine. A ratio below 0.01 means familial hypocalciuric hypercalcaemia, which is benign and must not be operated on; a ratio above 0.01 means primary hyperparathyroidism, which is cured by parathyroidectomy. This child's ratio of 0.02 points to primary hyperparathyroidism. The distinction matters because the two conditions are managed in opposite directions, and operating on familial hypocalciuric hypercalcaemia recurs and causes permanent hypocalcaemia. [5]

Weak

• "I would order a calcium-sensing receptor gene test to decide." [5]

Branch B — The child with a family history

Examiner: "An asymptomatic girl has a calcium of 2.7, a mother and grandfather with lifelong hypercalcaemia, and a clearance ratio of 0.008. What is the diagnosis and what is the cardinal error?" [5]

Strong

• The diagnosis is familial hypocalciuric hypercalcaemia, a calcium-sensing receptor loss-of-function mutation. The cardinal error is parathyroidectomy. The condition is benign and lifelong, with a stable, asymptomatic calcium. The parathyroid glands are set to a higher set-point rather than being autonomous, so removing tissue does not cure it: the calcium recurs, or the child is rendered permanently hypocalcaemic and dependent on calcium and calcitriol. The correct management is to confirm with a calcium-sensing receptor gene test, document it, reassure the family, and screen relatives. [5]

Weak

• "She needs the parathyroid gland removed to cure the calcium." [5]

Branch C — The hypotonic hypercalcaemic neonate

Examiner: "A neonate has a calcium of 4.2 mmol per litre, hypotonia, respiratory distress and fractures. What is the likely diagnosis, the genetic basis, and the usual definitive treatment?" [4]

Strong

• The likely diagnosis is neonatal severe hyperparathyroidism, the homozygous or compound-heterozygous form of the calcium-sensing receptor defect. The profoundly high calcium, hypotonia, respiratory distress and fractures are its hallmark. Medical therapy with a calcimimetic, calcitonin and a bisphosphonate may buy time, but the disease is often life-threatening and a total parathyroidectomy with lifelong calcium and calcitriol replacement is usually needed. This is the severe homozygous end of the same spectrum as the benign heterozygous familial hypocalciuric hypercalcaemia. [4] [5]

Weak

• "It is probably vitamin D intoxication — stop the supplement." [4]

Branch D — Hypercalcaemic crisis

Examiner: "A child arrives with a calcium of 3.8 mmol per litre, dehydration, vomiting and confusion. What is the first intervention and what three drugs follow it?" [2]

Strong

• This is hypercalcaemic crisis. The first intervention is aggressive isotonic saline at ten to twenty millilitres per kilogram per hour, titrated to euvolaemia, because the child is volume-depleted from nephrogenic diabetes insipidus and vomiting, and the dehydration itself worsens the calcium. Once euvolaemic, add calcitonin at four units per kilogram subcutaneously or intravenously every twelve hours for rapid but transient calcium lowering, then a bisphosphonate such as pamidronate or zoledronic acid for a slower but durable fall. Glucocorticoids are added only if vitamin D is the driver, because they block the one-alpha-hydroxylation of vitamin D. [2] [6]

Weak

• "I would start a bisphosphonate immediately." [2]

Branch E — The postoperative collapse

Examiner: "A child is on the ward the day after a successful parathyroidectomy for an adenoma. Her calcium has fallen to 1.7 mmol per litre and she is twitchy. What is happening and what do you do?" [3]

Strong

• She has hungry bone syndrome. The sudden removal of parathyroid hormone lets calcium flood into the demineralised skeleton, so the serum calcium falls rapidly and she becomes symptomatic. The low calcium is the sign that the operation worked, not that it failed. Treat with intravenous calcium for the acute symptomatic fall, then oral calcium and calcitriol, and monitor the calcium every six to twelve hours, tapering the replacement as the skeleton remineralises over weeks. Chvostek or Trousseau signs warrant urgent intravenous calcium. [3]

Weak

• "The operation has failed — she needs re-exploration." [3]

Close

Examiner: "Summarise your approach to paediatric hypercalcaemia in one sentence." [1]

Strong

• "I measure the parathyroid hormone first to split parathyroid-driven from non-parathyroid causes, use the urine calcium-to-creatinine clearance ratio to separate familial hypocalciuric hypercalcaemia below 0.01 from primary hyperparathyroidism above it, treat crisis with saline before drugs, and remember that glucocorticoids only work when vitamin D is the driver." [1] [2]