Lucan · Conditions

Primary hyperparathyroidism

Australian guidance: eTG Endocrinology — Hypercalcaemia and hyperparathyroidism

Authoring note: this prose was synthesised from general clinical knowledge plus the references above, without a provided source PDF. Verify cutoffs and surgical criteria against current eTG Endocrinology before stamping any derived card or SBA.

1. Definition and epidemiology

Primary hyperparathyroidism (PHPT) is a disorder of autonomous, excessive secretion of parathyroid hormone (PTH) from one or more parathyroid glands, producing hypercalcaemia with an inappropriately raised or non-suppressed PTH. It is the commonest cause of hypercalcaemia in the community and ambulatory setting, whereas malignancy is the commonest cause in hospital inpatients. Prevalence rises with age and is roughly two to three times higher in women, peaking in the postmenopausal decades. Most cases in Australia are now detected incidentally as mild asymptomatic hypercalcaemia on routine biochemistry rather than as classic symptomatic bone and stone disease.

2. Pathophysiology

A single benign parathyroid adenoma accounts for approximately 80 to 85 percent of cases. Four-gland hyperplasia accounts for around 10 to 15 percent and is the pattern seen in the multiple endocrine neoplasia (MEN) syndromes. Parathyroid carcinoma is rare (under 1 percent) but should be suspected with very high calcium, very high PTH, and a palpable neck mass. Excess PTH acts through three mechanisms that raise serum calcium: it stimulates osteoclastic bone resorption (releasing calcium and phosphate), it increases renal tubular reabsorption of calcium while promoting phosphate excretion, and it upregulates renal 1-alpha-hydroxylase, raising calcitriol (active vitamin D) and thereby increasing gut calcium absorption. The net biochemical signature is hypercalcaemia with hypophosphataemia. Loss of normal calcium-sensing receptor (CaSR) feedback restraint on the autonomous gland is the central defect. Hereditary forms occur in MEN1 (parathyroid, pancreatic islet, and pituitary tumours) and MEN2A (parathyroid, medullary thyroid carcinoma, and phaeochromocytoma).

3. Clinical presentation and diagnostic criteria

Most patients are asymptomatic. When symptomatic, features follow the classic mnemonic of "stones, bones, abdominal groans, and psychiatric moans": renal calculi and nephrocalcinosis; bone pain, osteoporosis, and the now-rare osteitis fibrosa cystica with brown tumours; abdominal pain, constipation, peptic ulcer disease, and pancreatitis; and fatigue, depression, poor concentration, and cognitive slowing. Polyuria and polydipsia occur because hypercalcaemia impairs renal concentrating ability. Severe acute hypercalcaemia (a hypercalcaemic crisis) presents with dehydration, vomiting, confusion, and cardiac arrhythmia.

Diagnostic criteria: PHPT is confirmed by hypercalcaemia (corrected for albumin) together with a PTH that is frankly elevated or inappropriately within the normal range. A fully suppressed PTH points instead to a non-parathyroid cause such as malignancy. The key benign mimic to exclude is familial hypocalciuric hypercalcaemia (FHH), a CaSR loss-of-function condition that produces lifelong mild hypercalcaemia with a low urinary calcium and does not benefit from surgery.

4. Investigations and AU-specific cutoffs

Confirmatory biochemistry: measure serum calcium corrected for albumin, PTH, and phosphate. Raised or inappropriately normal PTH with hypercalcaemia and a low or low-normal phosphate is diagnostic of PHPT. Always check 25-hydroxyvitamin D, because concurrent vitamin D deficiency lowers calcium and can mask the diagnosis or, once repleted, unmask frank hypercalcaemia.

Distinguishing FHH from PHPT: calculate the calcium to creatinine clearance ratio from a paired serum and 24-hour urine sample. A ratio below 0.01 suggests FHH (do not operate); a ratio above 0.02 supports PHPT. Family history and genetic testing for a CaSR mutation help when the ratio is intermediate.

End-organ assessment: renal function (eGFR), a 24-hour urinary calcium, imaging for renal stones or nephrocalcinosis (ultrasound or CT), and bone mineral density by DXA. In PHPT the distal one-third of the radius (cortical bone) is preferentially affected, so it should always be included in the DXA scan.

Localisation (only once surgery is decided, not for diagnosis): neck ultrasound and a technetium-99m sestamibi scan are first-line, with four-dimensional CT reserved for discordant or negative studies. Localisation guides whether a minimally invasive single-gland resection is possible.

5. Management

Parathyroidectomy is the only curative treatment and is definitively indicated for symptomatic disease (renal stones, fragility fracture, symptomatic hypercalcaemia). For asymptomatic disease, surgery is recommended when any of the following criteria are met, adapted from the Fourth International Workshop:

• Serum calcium more than 0.25 mmol/L above the upper limit of normal.
• Osteoporosis on DXA (T-score of -2.5 or below at any site) or a vertebral fracture on imaging.
• eGFR below 60 mL/min, a 24-hour urinary calcium above 10 mmol/day with increased stone risk, or nephrolithiasis or nephrocalcinosis on imaging.
• Age under 50 years.

Patients who do not meet criteria, or who are unfit or unwilling for surgery, are monitored with periodic serum calcium, renal function, and DXA, and are advised to maintain hydration, keep a moderate calcium intake, replete vitamin D cautiously, and avoid thiazide diuretics and lithium, which raise calcium.

Acute severe hypercalcaemia (for example calcium above 3.5 mmol/L or symptomatic) is managed first with intravenous normal saline rehydration to restore volume and promote calciuresis, followed by an intravenous bisphosphonate (zoledronic acid) for a sustained effect. Calcitonin gives a rapid but short-lived additional fall while the bisphosphonate takes effect. Loop diuretics are used only after full rehydration and if fluid overload develops, not as routine calcium-lowering therapy.

6. Pharmacology and AU PBS notes

Cinacalcet is a calcimimetic that allosterically activates the calcium-sensing receptor on the parathyroid gland, lowering PTH and calcium. It is used in PHPT for patients who meet surgical criteria but are unfit or decline operation, and in parathyroid carcinoma. Typical starting dose is 30 mg daily, titrated against calcium. PBS listing is restricted; confirm the current authority indication at the time of prescribing. AU brand: Sensipar.

Zoledronic acid (and pamidronate) are intravenous bisphosphonates used for hypercalcaemia and to protect bone; they inhibit osteoclastic resorption. Monitor renal function and calcium, and ensure vitamin D repletion to avoid hypocalcaemia.

Vitamin D (colecalciferol) is repleted when deficient, because uncorrected deficiency drives secondary PTH rise and worsens bone disease; repletion is done cautiously with calcium monitoring in PHPT.

Drugs to avoid or review: thiazide diuretics reduce urinary calcium excretion and raise serum calcium, and lithium raises the PTH set-point; both can unmask or worsen hypercalcaemia and should be reviewed.

7. Complications and monitoring

Untreated PHPT risks progressive osteoporosis and fragility fracture, nephrolithiasis, nephrocalcinosis and chronic kidney disease, and, uncommonly, hypercalcaemic crisis. There is an association with hypertension and vascular calcification.

Post-operative complications include transient hypocalcaemia, hungry bone syndrome (profound, prolonged hypocalcaemia after removing a long-standing high-turnover stimulus, needing calcium and calcitriol), recurrent laryngeal nerve injury, and permanent hypoparathyroidism if too much parathyroid tissue is removed. Persistent or recurrent hypercalcaemia after surgery suggests a missed gland, multi-gland disease, or, rarely, carcinoma.

Monitoring: after successful surgery, confirm cure with serum calcium and PTH at follow-up and reassess bone density, which typically improves. In conservatively managed patients, monitor serum calcium and renal function at least annually and DXA every one to two years, with a low threshold to reconsider surgery if criteria develop.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.