Primary hyperparathyroidism

Q: Susie, 43, presents with headaches and fatigue. Her biochemistry results include: albumin 49 g/L (38-55 g/L), calcium 3.14 mmol/L (2.10-2.60 mmol/L), corrected calcium 2.96 mmol/L (2.10-2.60 mmol/L) and intact parathyroid hormone 8.9 pmol/L (1.6-6.9 pmol/L). Discuss the diagnosis, further investigations and management.

A: In this case, the total corrected calcium indicates the presence of hypercalcaemia. Hypercalcaemia is PTH-dependent as indicated by the elevated intact PTH result.

The differential diagnosis includes primary hyperparathyroidism (PHPT) due to parathyroid adenoma, parathyroid hyperplasia, lithium therapy or familial hypocalciuric hypercalcaemia (FHH).

Parathyroid cancer is extremely rare and characterised by either a palpable neck mass or markedly elevated intact PTH result.

The typical patient with PHPT is asymptomatic or reports non-specific symptoms as in this case.

About one in five patients with PHPT have classical symptoms with kidney stones or overt bone disease.

A review of medications and assessment of serum creatinine and eGFR along with either fasting urine calcium excretion (CaE) or 24-hour urine calcium/creatinine clearance ratio are required.

Assessment of 25 hydroxyvitamin D is also advisable as vitamin D deficiency may often co-exist with primary hyperparathyroidism.

In FHH the fasting CaE is typically less than 30 umol/L GFR¹ and the 24-hour calcium creatinine clearance ratio is characteristically less than 0.01.²

The importance of recognising FHH is to avoid unnecessary surgical neck exploration, as this disorder is due to a mutation in the calcium-sensing receptor, rarely associated with pathology and cannot be cured by parathyroidectomy.

If the patient is taking lithium and it is safe to cease medication, withdrawal and retesting in three months is advised.

In PHPT, investigation of bone mineral density is advisable to assess fracture risk.

Based on consensus recommendations, surgical treatment for PHPT could be offered if the patient is young (< 50 years old), serum corrected calcium is high (> 3 mmol/L), 24-hour urine calcium excretion is increased (> 7.5 mmol/d), creatinine clearance is reduced (by > 30%), bone density is low (T score < -2.5 at hip, spine or forearm) or medical surveillance is not desirable or possible.

In patients who decline surgery or do not meet these criteria, opt for routine surveillance with six-monthly serum calcium, creatinine and eGFR, annual bone mineral density plus consideration of abdominal ultrasound surveillance to detect nephrocalcinosis.

Medical management options include encouraging sufficient dietary calcium intake, supplementation with cholecalciferol if vitamin D is less than 50 nmol/L, and consideration of bisphosphonates or raloxifene if fracture risk is increased.

1. CaE (umol/L) = urinary calcium (mmol/L) x plasma creatinine (umol/L)/urine creatinine (mmol/L). Collect spot urine and plasma samples fasting.

2. 24-hour Ca/Cr clearance ratio = urine calcium (mmol/L) x plasma creatinine (umol/L) x 0.001/(plasma calcium (mmol/L) x urine creatinine (mmol/L).