Parathyroid adenomas are known to cause 75–85% of cases of primary hyperparathyroidism (pHPT). Parathyroid chief-cell hyperplasia was described in 1958, and has been reported to occur in 15–25% of pHPT patients. Hyperplasia has remained a problem in parathyroid surgery, as results are inferior if multigland involvement is not recognized. Adenomas and hyperplastic glands are often indistinguishable from one another by histopathological examination, and many physicians have preferred to classify hyperplasia as multigland disease (MGD). Nodular hyperplasia is common, and individual nodules often represent monoclonal lesions, which may grow to occupy an entire gland and appear as adenomas. In sporadic pHPT, causes of stimulation often are not identified, in contrast to HPT that is secondary to uremia or long-term lithium therapy. The hyperplasia or MGD in sporadic cases occurs more frequently in patients with mild hypercalcemia, especially in postmenopausal women with vitamin D deficiency, slight renal impairment, or both. It is also common in young patients who have been diagnosed early with renal stone disease . MGD is the common disease entity in familial pHPT, as all parathyroid cells harbor the germline genetic alteration. About 5% or more of pHPT patients have familial HPT related to the multiple endocrine neoplasia (MEN) syndromes, most frequently MEN1 (due to mutations of the MEN1 gene, encoding the menin protein). In this syndrome, 95% of probands have developed HPT by the age of 45 years, whereas in MEN2A (due to RET oncogene mutations), HPT affects only 20–30% of patients. In the recently discovered, very rare MEN4 syndrome (due to CDKN1B mutations), both single adenomas and MGD have been reported . Hereditary disease also occurs as familial isolated HPT, including patients with MEN1 gene mutations, where other endocrinopathies have not been expressed. In the rare HPT-jaw-tumor syndrome (HPT-JT, due to mutation of the HRPT2/CDC73 parafibromin gene), patients may have single or multiple adenomas, and parathyroid carcinoma occurs in 10–15% of patients. Patients with familial hypocalciuric hypercalcemia (FHH), caused by heterozygous mutation in the calcium sensing receptor (CASR) gene, need to be differentiated from those with other syndromes because they generally should not be subjected to parathyroid operations. Homozygous CASR gene mutations cause neonatal severe pHPT with marked four-gland hyperplasia, and urgent parathyroidectomy may need to be performed in infancy.
- Subtotal parathyroidectomy
- Parathyroid hyperplasia
- Sporadic primary hyperparathyroidism
- Familial primary hyperparathyroidism