Primary Hyperparathyroidism With Negative Localisation

She meets several guideline criteria for surgery: symptomatic hypercalcaemia (stones, fatigue), a serum calcium above the upper limit of normal by more than 1 mg/dL, a T-score below −2.5, and age under 50. Her eGFR of 48 is reduced and would ordinarily support rather than argue against intervention, although the perioperative and anaesthetic risk of CKD needs assessment.

The thiazide is the first thing to address. Thiazides reduce renal calcium excretion and can unmask or worsen primary hyperparathyroidism, and occasionally produce hypercalcaemia with a mildly raised PTH. The correct step is to stop the thiazide, substitute another antihypertensive, and repeat calcium, PTH and a 24-hour urine calcium after 2–4 weeks. Even so, a PTH of 142 pg/mL with calcium 11.9 mg/dL in the presence of hypercalciuria is very likely genuine primary hyperparathyroidism.

Familial hypocalciuric hypercalcaemia must be excluded before surgery: a 24-hour urine calcium of 380 mg is not low, and a calcium-to-creatinine clearance ratio above 0.01 argues against FHH. Family history and genetics are relevant if the calcium persists after stopping the thiazide.

Negative imaging does not preclude curative surgery; it changes the operation from a focused approach to a bilateral neck exploration by an experienced parathyroid surgeon, which achieves cure rates around 95% in that setting.

Plan:

• Counsel her explicitly that the operation is a full exploration, not a small targeted incision, and that the incision will be a standard collar incision.
• At surgery, identify all four glands. If one is enlarged and the other three are normal, remove it and confirm with intraoperative PTH.
• Use the Miami criterion: a fall of more than 50% from the highest pre-excision level at 10 minutes after excision. If it is not met, search the usual ectopic sites - tracheo-oesophageal groove, retro-oesophageal, carotid sheath, thymus, and intrathyroidal - and consider a thymectomy and, if a gland is still missing, a thyroid lobectomy on that side.
• If four normal-looking glands are found in a patient with proven disease, consider hyperplasia, and consider whether the diagnosis is wrong; blind resection is not justified.
• If the gland cannot be found after a thorough exploration, abort rather than perform a blind resection, and arrange selective venous sampling before a reoperation.

Document the plan and the discussion of persistent hyperparathyroidism and the small risk of recurrent laryngeal nerve injury.

This is hungry bone syndrome - rapid recalcification of a skeleton that has been demineralised, common after removal of a large adenoma in a patient with a low T-score and a high alkaline phosphatase. It is the expected cause of symptomatic hypocalcaemia on day 1, but magnesium must be checked and replaced, and a neck haematoma must be excluded first because it can present with stridor rather than tingling.

Management:

• If symptoms are mild and the ECG shows only QT prolongation, start oral calcium carbonate or citrate 1–2 g of elemental calcium daily in divided doses plus calcitriol 0.25–1 µg daily, and check calcium every 6–12 hours.
• If she develops carpopedal spasm, seizures or a markedly prolonged QT, give intravenous calcium gluconate by slow infusion and monitor for extravasation.
• Correct magnesium, since hypomagnesaemia makes hypocalcaemia refractory to treatment.
• Avoid overcorrection into hypercalcaemia; taper when calcium stabilises above the lower limit of normal.

Predictors in this patient: the pre-existing T-score of −2.9, likely vitamin D deficiency, a large adenoma and a high bone turnover state. Vitamin D should be repleted before elective surgery in similar patients to reduce the severity of this complication.