Table 2

Clinicopathological correlates of primary hyperparathyroidism

DiagnosisParathyroid hyperplasia (multigland disease)Parathyroid adenoma (single-gland disease)*Parathyroid carcinoma (single-gland disease)*
OnsetVariable, but in familial forms earlier than single-gland diseaseUsually after age 50Usually after age 50, except in HPT-JT or familial isolated HPT
Clinical featuresVariable symptoms†, depending on the familial syndrome (25% of cases). Consider family history of hypercalcaemia (FHH) and/or other familial endocrine disorders (MEN)Often asymptomatic, Although large adenomas can present with overt HPT symptoms†Severe HPT symptoms†, palpable neck mass, jaw tumour (HPT-JT) and/or hypercalcemic crisis with neurological manifestations
Biochemical featuresVariable biochemistry profile (mild-to-severe hypercalcaemia and HPT) depending on the genetic syndrome.
In hypocalciuria, consider FHH
Often mild hypercalcaemia with mild-to-moderate HPT, although more severe features are seen in large adenomasSevere hypercalcaemia with marked elevations of PTH
Radiological featuresMultigland disease may be detected with imaging but usually localising studies are more helpful in the setting of recurrent disease after most of the abnormal parathyroid tissue has already been removed.Single-gland disease on sestamibi, US and/or CT scanSingle-gland disease, ±distant metastasis or local invasion
TreatmentFour gland parathyroid exploration followed by total or subtotal parathyroidectomyMinimally invasive parathyroidectomy with intraoperative PTH measurementsOncological surgical approach, including at least ‘en bloc’ resection
Special considerationsGenetic testing should be considered, unless identifiable cause such as chronic kidney diseaseTrue single-gland disease is usually sporadicConsider genetic testing, in carcinomas with loss of parafibromin
PrognosisRisk of recurrent and/or persistent disease after surgery, especially in individuals with FHH-1Often cured after surgeryHigh risk of locoregional recurrence and/or distant metastasis, especially in tumours with angioinvasion
  • *Rare exceptions include case reports of parathyroid ‘double adenomas’ and carcinoma arising from a background of parathyroid hyperplasia.

  • †Symptoms of hyperparathyroidism include bone pain, renal colic (nephrolithiasis) and neurocognitive symptoms related to hypercalcaemia (weakness, easy fatigability, anxiety, depression, altered cognition).

  • FHH, familial hypocalciuric hypercalcaemia syndrome; HPT, hyperparathyroidism; HPT-JT, hyperparathyroidism-jaw tumour syndrome; MEN, multiple endocrine neoplasia syndromes; PTH, parathyroid hormone; US, ultrasound.