Clinicopathological correlates of primary hyperparathyroidism
| Diagnosis | Parathyroid hyperplasia (multigland disease) | Parathyroid adenoma (single-gland disease)* | Parathyroid carcinoma (single-gland disease)* |
|---|---|---|---|
| Frequency | ∼10–15% | ∼80–85% | <1–5% |
| Onset | Variable, but in familial forms earlier than single-gland disease | Usually after age 50 | Usually after age 50, except in HPT-JT or familial isolated HPT |
| Clinical features | Variable 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 features | Variable 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 adenomas | Severe hypercalcaemia with marked elevations of PTH |
| Radiological features | Multigland 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 scan | Single-gland disease, ±distant metastasis or local invasion |
| Treatment | Four gland parathyroid exploration followed by total or subtotal parathyroidectomy | Minimally invasive parathyroidectomy with intraoperative PTH measurements | Oncological surgical approach, including at least ‘en bloc’ resection |
| Special considerations | Genetic testing should be considered, unless identifiable cause such as chronic kidney disease | True single-gland disease is usually sporadic | Consider genetic testing, in carcinomas with loss of parafibromin |
| Prognosis | Risk of recurrent and/or persistent disease after surgery, especially in individuals with FHH-1 | Often cured after surgery | High 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.