Oral Board Case: Hyperparathyroidism

This patient is referred for hypercalcemia. What is your differential and how do you confirm the diagnosis?

Expected answer

The differential for hypercalcemia includes primary hyperparathyroidism, malignancy (PTH-related peptide, bony metastases), medications (thiazides, lithium, bisphosphonates, excess vitamin D/calcium), familial hypocalciuric hypercalcemia (FHH), sarcoidosis and other granulomatous disease, and other endocrinopathies. The diagnosis of pHPT is biochemical: I would obtain concomitant serum calcium and intact PTH. Classic pHPT shows elevation of BOTH calcium and PTH — as in this patient. I would also check 25-hydroxyvitamin D to identify correctable deficiency, and a 24-hour urine calcium to rule out FHH (where urine calcium is typically <50 mg/24h). A Cl/PO4 ratio >33 also supports pHPT.

Why is the 24-hour urine calcium so important before you take this patient to surgery?

Expected answer

To exclude familial hypocalciuric hypercalcemia (FHH), an autosomal dominant disorder of the renal calcium-sensing receptor that mimics pHPT with high calcium and inappropriately normal/high PTH. FHH patients have low urine calcium (<50 mg/24h) and do NOT benefit from parathyroidectomy — operating on them is a needless, non-curative neck exploration. This patient's recurrent stones make true hypercalciuria/pHPT far more likely, but FHH must still be formally excluded.

Is this patient a surgical candidate? Justify your answer.

Expected answer

Yes. She is symptomatic with objective nephrolithiasis (recurrent kidney stones), which alone is an indication for parathyroidectomy. She also has fatigue, myalgias, weakness, and polyuria. Parathyroidectomy is recommended for all patients with objective symptoms such as nephrolithiasis or fragility fractures. Even if she were asymptomatic, surgery would be indicated if she met NIH criteria: age <50, calcium >1 mg/dL above the upper reference limit, 24-hr urine calcium >400 mg, renal insufficiency (CrCl reduced ~30%), osteoporosis (spine T-score <-2.5), or patient preference.

What imaging do you order and what is its purpose?

Expected answer

Imaging is for operative planning/localization — NOT to confirm or exclude the diagnosis, which is purely biochemical. I would start with neck ultrasound: noninvasive, least costly, and it also evaluates for concomitant thyroid pathology that may need to be addressed at the same operation. If ultrasound is inconclusive, I would obtain a Tc-99m sestamibi scan or 4D-CT of the neck/upper chest depending on institutional preference.

The ultrasound and sestamibi localize a single right inferior adenoma. Describe your operative approach.

Expected answer

With concordant localization of a single adenoma, I would perform a focused/unilateral parathyroidectomy with intraoperative PTH monitoring (IOPM). I draw a baseline PTH before excision, excise the abnormal gland, and send it for frozen section to confirm parathyroid tissue. A repeat PTH is drawn 10 minutes after excision — a drop of at least 50% from baseline AND into the normal range predicts cure/postoperative eucalcemia. If the PTH fails to drop adequately, hypersecreting tissue remains and I convert to bilateral neck exploration.

What if imaging is negative or discordant — the adenoma does not localize?

Expected answer

I would plan a bilateral neck exploration. All four parathyroid glands are identified, and the abnormal or enlarged gland(s) are removed. IOPM may be used as an adjunct to confirm cure, and all specimens are sent for frozen section to confirm parathyroid tissue. Failure to localize never excludes pHPT — the diagnosis is biochemical, and a non-localized study is an indication for four-gland exploration by an experienced parathyroid surgeon.

You excise the gland but the 10-minute PTH only drops 30%. What do you do?

Expected answer

An inadequate PTH drop means hypersecreting tissue remains — likely a second adenoma, double adenoma, or four-gland hyperplasia. I would proceed to bilateral neck exploration, identify and evaluate all four glands, and remove additional abnormal glands. I would not close assuming cure. I would also consider ectopic locations (intrathyroidal, thymic/mediastinal, carotid sheath) for a missing gland.

What are your key postoperative management and follow-up steps?

Expected answer

I give oral calcium supplementation for about 2 weeks postoperatively to prevent symptomatic transient hypocalcemia, and replace vitamin D if deficient. I monitor for symptomatic hypocalcemia (perioral numbness, Chvostek/Trousseau) and for hungry bone syndrome in patients with severe bone disease. I counsel on the risks of recurrent laryngeal nerve injury and persistent/recurrent disease. Serum calcium, PTH, and vitamin D are rechecked at 6 months to assess for cure versus persistent disease.

How does management differ in secondary and tertiary hyperparathyroidism?

Expected answer

Secondary HPT occurs with chronic renal failure: low calcium drives elevated PTH with four-gland hyperplasia (elevated PTH, low/normal calcium). Tertiary HPT occurs in renal transplant patients with autonomous glands and BOTH elevated PTH and calcium. Surgical treatment for both is subtotal (3.5-gland) parathyroidectomy or four-gland resection with autotransplantation, rather than removal of a single adenoma as in primary disease.