Primary hyperparathyroidism

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, such as renal stones, impaired kidney 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 85% of cases, over-production of PTH is due to a single parathyroid adenoma and, less commonly, multi-gland involvement may occur.[1]Bilezikian JP, Khan AA, Silverberg SJ, et al. Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the fifth International Workshop. J Bone Miner Res. 2022 Nov;37(11):2293-314. https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4677 http://www.ncbi.nlm.nih.gov/pubmed/36245251?tool=bestpractice.com ​ An elevated serum calcium level with a raised or inappropriately normal (i.e., non-suppressed) plasma PTH level confirms a diagnosis of PHPT.[1]Bilezikian JP, Khan AA, Silverberg SJ, et al. Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the fifth International Workshop. J Bone Miner Res. 2022 Nov;37(11):2293-314. https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4677 http://www.ncbi.nlm.nih.gov/pubmed/36245251?tool=bestpractice.com ​[2]Wilhelm SM, Wang TS, Ruan DT, et al. The American Association of Endocrine Surgeons guidelines for definitive management of primary hyperparathyroidism. JAMA Surg. 2016 Oct 1;151(10):959-68. http://jamanetwork.com/journals/jamasurgery/fullarticle/2542667 http://www.ncbi.nlm.nih.gov/pubmed/27532368?tool=bestpractice.com ​​​​​ Inherited forms, affecting a minority of patients, lead to hyperfunctioning parathyroid glands. Importantly, hyperparathyroidism is rarely caused by parathyroid cancer characterised by severe hypercalcaemia.[3]Fingeret AL. Contemporary evaluation and management of parathyroid carcinoma. JCO Oncol Pract. 2021 Jan;17(1):17-21. https://ascopubs.org/doi/10.1200/JOP.19.00540 http://www.ncbi.nlm.nih.gov/pubmed/32040373?tool=bestpractice.com ​​

Normocalcaemic PHPT is recognised as a variant of PHPT. It is characterised by persistently high levels of parathyroid hormone in the setting of normal serum and ionised calcium levels, after secondary causes of PTH elevation have been excluded.[1]Bilezikian JP, Khan AA, Silverberg SJ, et al. Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the fifth International Workshop. J Bone Miner Res. 2022 Nov;37(11):2293-314. https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4677 http://www.ncbi.nlm.nih.gov/pubmed/36245251?tool=bestpractice.com ​ The clinical features of normocalcaemic PHPT can be similar to the classical form, including nephrolithiasis and low bone mineral density.[1]Bilezikian JP, Khan AA, Silverberg SJ, et al. Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the fifth International Workshop. J Bone Miner Res. 2022 Nov;37(11):2293-314. https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4677 http://www.ncbi.nlm.nih.gov/pubmed/36245251?tool=bestpractice.com [4]Hollowoa BR, Spencer HJ 3rd, Stack BC Jr. Normocalcemic and normohormonal primary hyperparathyroidism: laboratory values and end-organ effects. Otolaryngol Head Neck Surg. 2021 Sep;165(3):387-97. https://aao-hnsfjournals.onlinelibrary.wiley.com/doi/10.1177/0194599820983728 http://www.ncbi.nlm.nih.gov/pubmed/33461421?tool=bestpractice.com ​ Some, but not all, patients will go on to develop PHPT.​​[1]Bilezikian JP, Khan AA, Silverberg SJ, et al. Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the fifth International Workshop. J Bone Miner Res. 2022 Nov;37(11):2293-314. https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4677 http://www.ncbi.nlm.nih.gov/pubmed/36245251?tool=bestpractice.com ​​