Clinicopathological correlates of hyperparathyroidism

Abstract

Hyperparathyroidism is a common endocrine disorder with potential complications on the skeletal, renal, neurocognitive and cardiovascular systems. While most cases (95%) occur sporadically, about 5% are associated with a hereditary syndrome: multiple endocrine neoplasia syndromes (MEN-1, MEN-2A, MEN-4), hyperparathyroidism-jaw tumour syndrome (HPT-JT), familial hypocalciuric hypercalcaemia (FHH-1, FHH-2, FHH-3), familial hypercalciuric hypercalcaemia, neonatal severe hyperparathyroidism and isolated familial hyperparathyroidism. Recently, molecular mechanisms underlying possible tumour suppressor genes (MEN1, CDC73/HRPT2, CDKIs, APC, SFRPs, GSK3β, RASSF1A, HIC1, RIZ1, WT1, CaSR, GNA11, AP2S1) and proto-oncogenes (CCND1/PRAD1, RET, ZFX, CTNNB1, EZH2) have been uncovered in the pathogenesis of hyperparathyroidism. While bi-allelic inactivation of CDC73/HRPT2 seems unique to parathyroid malignancy, aberrant activation of cyclin D1 and Wnt/β-catenin signalling has been reported in benign and malignant parathyroid tumours. Clinicopathological correlates of primary hyperparathyroidism include parathyroid adenoma (80–85%), hyperplasia (10–15%) and carcinoma (<1–5%). Secondary hyperparathyroidism generally presents with diffuse parathyroid hyperplasia, whereas tertiary hyperparathyroidism reflects the emergence of autonomous parathyroid hormone (PTH)-producing neoplasm(s) from secondary parathyroid hyperplasia. Surgical resection of abnormal parathyroid tissue remains the only curative treatment in primary hyperparathyroidism, and parathyroidectomy specimens are frequently encountered in this setting. Clinical and biochemical features, including intraoperative PTH levels, number, weight and size of the affected parathyroid gland(s), are crucial parameters to consider when rendering an accurate diagnosis of parathyroid proliferations. This review provides an update on the expanding knowledge of hyperparathyroidism and highlights the clinicopathological correlations of this prevalent disease.

Efficacy and its predictor in microwave ablation for severe secondary hyperparathyroidism in patients undergoing haemodialysis

“…Parathyroid cells will show increased endocrine function if the iPTH level is high [28][29][30]. It is likely that some parathyroid tissue and cells remained after MWA.…”

Diagnostic accuracy of planar, SPECT, and SPECT/CT parathyroid scintigraphy protocols in patients with hyperparathyroidism

“…The incidence of primary hyperparathyroidism ranges from 34 to 120 per 100,000 in women and 13 to 36 per 100,000 in men [1] and may be caused by parathyroid adenoma, hyperplasia, or rarely, parathyroid carcinoma [2]. Secondary and tertiary hyperparathyroidism are mostly found in patients with chronic kidney disease with prevalence inversely proportional to renal function [3].…”

Identification and Functional Characterization of a Calcium-Sensing Receptor Mutation in an Infant with Familial Hypocalciuric Hypercalcemia

“…The majority of cases of HPT are sporadic (95%), while only 5% are associated with a hereditary syndrome. Inheritable disorders include NSHPT, isolated familial HPT, multiple endocrine neoplasia syndromes (MEN-1, MEN-2A, MEN-4), HPT-jaw tumor syndrome, familial hypercalciuric hypercalcemia, and FHH (20). In the past years, patients with FHH misdiagnosed as primary HPT had inappropriately undergone parathyroidectomy without resolution of their symptoms (21).…”