Diagnosis of primary hyperparathyroidism is confirmed biochemically with synchronous elevation of serum calcium and inappropriate elevation of parathyroid hormone (PTH).
Normal serum intact PTH in the setting of hypercalcaemia does not rule out disease.
Depression, cognitive changes, change in sleep pattern, fatigue, and myalgia or muscle weakness are non-specific subjective complaints. There may be a history of nephrolithiasis or low bone mineral density.
Physical examination is usually normal, but examination of the neck is essential to look for a hard, dense mass, suggestive of parathyroid carcinoma.
Parathyroidectomy is the only definitive cure. Monitoring is an option for patients who have mild hypercalcaemia without surgical indications, which include lack of ensured follow-up, renal stones, impaired renal function, or osteoporosis.
Primary hyperparathyroidism (PHPT) is an endocrine disorder in which autonomous overproduction of parathyroid hormone (PTH) results in derangement of calcium metabolism. In approximately 80% of cases, over-production of PTH is due to a single parathyroid adenoma and, less commonly, multi-gland involvement may occur. Diagnosis occurs through testing for a concurrent elevated serum calcium level with a raised or inappropriately normal (i.e., non-suppressed) plasma PTH level. Inherited forms, affecting a minority of patients, lead to hyperfunctioning parathyroid glands. Importantly, hyperparathyroidism is rarely caused by parathyroid cancer characterised by severe hypercalcaemia.
Normocalcaemic PHPT is recognised as a variant of PHPT, and has yet to be thoroughly characterised. It presents with high levels of parathyroid hormone in the setting of normal serum and ionised calcium levels, after secondary causes of PTH elevation have been excluded. It is sometimes detected during the evaluation of patients with low bone mineral density. Some, but not all, patients will go on to develop PHPT.
History and exam
Key diagnostic factors
- incidental finding on biochemical testing
- history of osteoporosis or osteopenia
- family history of hyperparathyroidism or features suggestive of hypercalcaemia
Other diagnostic factors
- poor sleep
- memory loss
- overt neuromuscular dysfunction
- cardiovascular and metabolic dysfunction
- features suggestive of hypercalcaemia
- hard and dense neck mass
- female sex
- age ≥50-60 years
- family history of PHPT
- multiple endocrine neoplasia (MEN) 1, 2A, or 4
- current or historical lithium treatment
- hyperparathyroidism-jaw tumour syndrome
- history of head and neck irradiation
1st investigations to order
- serum calcium
- serum intact PTH with immunoradiometric or immunochemical assay
Investigations to consider
- 25-hydroxyvitamin D level
- serum alkaline phosphatase
- serum phosphorus
- 24-hour urinary calcium
- dual-energy x-ray absorptiometry (DXA) scan
- trabecular bone score
- Tc-99m sestamibi scanning and ultrasonography
- single photon emission CT + sestamibi scanning
- CT neck
- 4-Dimensional (4D) CT neck
- MRI neck
- radiolabelled choline PET
asymptomatic with surgical indications or symptomatic
asymptomatic with no surgical indications
- Familial hypocalciuric hypercalaemia (FHH)
- Humoral hypercalcaemia of malignancy
- Multiple myeloma
- The EANM practice guidelines for parathyroid imaging
- ACR–SPR Practice Parameter for the Performance of Parathyroid Scintigraphy
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