# Pathology

Pathology

The underlying aetiology of  PHPT is usually a solitary parathyroid adenoma; however, in a small number of  patients (2–4%) there are double adenomas. It may occur in a sporadic fashion or it can be familial (approximately 10%) (MEN type 1, type 4, type 2A or hyperparathyroidism–jaw tumour syndrome [HPT-JT]) in nature. John L Doppman , 1928–2000, radiologist, National Institutes of  Health, USA, developed the technique of  selective venous sampling for parathyroid localisation. is a history of  prior neck irradiation. The underlying genetic pathogenesis of  PHPT remains unclear. However, genes r egulating the cell cycle, such as MEN1 and CCND1 , have been recognised as playing an important role owing to the clonal nature of  adenomas. Somatic mutations in MEN1 , which encodes menin, occur in 12–35% of  sporadic cases and rearrangements or overexpression of CCND1 , which encodes cyclin D1, have been demonstrated in 20–40% of  patients. Upregulation of cyclin D may lead to a clonal proliferation within the parathyroid glands. This does not alter the set point of  calcium but the hyperplasic nature of  the parathyroid cells - themselves causes excessive secretion of  PTH. Multigland disease is less common, occurring in approxi - mately 15% of  patients. No clinical features di ff erentiate single from multigland disease, although multigland disease is more commonly associated with familial syndromes such as MEN types 1 and 2A, as well as the chronic ingestion of  lithium. Pathology

The underlying aetiology of  PHPT is usually a solitary parathyroid adenoma; however, in a small number of  patients (2–4%) there are double adenomas. It may occur in a sporadic fashion or it can be familial (approximately 10%) (MEN type 1, type 4, type 2A or hyperparathyroidism–jaw tumour syndrome [HPT-JT]) in nature. John L Doppman , 1928–2000, radiologist, National Institutes of  Health, USA, developed the technique of  selective venous sampling for parathyroid localisation. is a history of  prior neck irradiation. The underlying genetic pathogenesis of  PHPT remains unclear. However, genes r egulating the cell cycle, such as MEN1 and CCND1 , have been recognised as playing an important role owing to the clonal nature of  adenomas. Somatic mutations in MEN1 , which encodes menin, occur in 12–35% of  sporadic cases and rearrangements or overexpression of CCND1 , which encodes cyclin D1, have been demonstrated in 20–40% of  patients. Upregulation of cyclin D may lead to a clonal proliferation within the parathyroid glands. This does not alter the set point of  calcium but the hyperplasic nature of  the parathyroid cells - themselves causes excessive secretion of  PTH. Multigland disease is less common, occurring in approxi - mately 15% of  patients. No clinical features di ff erentiate single from multigland disease, although multigland disease is more commonly associated with familial syndromes such as MEN types 1 and 2A, as well as the chronic ingestion of  lithium.