Evolution of Our Understanding of the Hyperparathyroid Syndromes: A Historical Perspective.

We review advancing and overlapping stages for our understanding of the expressions of six hyperparathyroid (HPT) syndromes: multiple endocrine neoplasia type 1 (MEN1) or type 4, multiple endocrine neoplasia type 2A (MEN2A), hyperparathyroidism-jaw tumor syndrome, familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism, and familial isolated hyperparathyroidism. During stage 1 (1903 to 1967), the introduction of robust measurement of serum calcium was a milestone that uncovered hypercalcemia as the first sign of dysfunction in many HPT subjects, and inheritability was reported in each syndrome. The earliest reports of HPT syndromes were biased toward severe or striking manifestations. During stage 2 (1959 to 1985), the early formulations of a syndrome were improved. Radioimmunoassays (parathyroid hormone [PTH], gastrin, insulin, prolactin, calcitonin) were breakthroughs. They could identify a syndrome carrier, indicate an emerging tumor, characterize a tumor, or monitor a tumor. During stage 3 (1981 to 2006), the assembly of many cases enabled recognition of further details. For example, hormone non-secreting skin lesions were discovered in MEN1 and MEN2A. During stage 4 (1985 to the present), new genomic tools were a revolution for gene identification. Four principal genes ("principal" implies mutated or deleted in 50% or more probands for its syndrome) (MEN1, RET, CASR, CDC73) were identified for five syndromes. During stage 5 (1993 to the present), seven syndromal genes other than a principal gene were identified (CDKN1B, CDKN2B, CDKN2C, CDKN1A, GNA11, AP2S1, GCM2). Identification of AP2S1 and GCM2 became possible because of whole-exome sequencing. During stages 4 and 5, the newly identified genes enabled many studies, including robust assignment of the carriers and non-carriers of a mutation. Furthermore, molecular pathways of RET and the calcium-sensing receptor were elaborated, thereby facilitating developments in pharmacotherapy. Current findings hold the promise that more genes for HPT syndromes will be identified and studied in the near future. © 2018 American Society for Bone and Mineral Research.

Parathyroid surgery: from inception to the modern day.

Parathyroid surgery has undergone great changes since its inception less than a century ago. It is still the only definitive option available to cure primary or tertiary hyperparathyroidism. This review details the development of parathyroid surgery, our understanding of hyperparathyroidism and the treatment options available. It also discusses the technological advances that have enabled parathyroid localization and prediction of surgical success.

[Primary hyperparathyroidism. History]. / L'hyperparathyroïdie primaire. Historique.

The term primary hyperparathyroidism currently refers to the clinical and biological manifestations resulting from the hypersecretion of parathyroid hormone by one or several parathyroid adenomas. This entity is a recent one since it goes back to 1925. The clinical picture resulting from this anomaly, were first described as Recklinghausen's fibrous osteitis, which was not justified since Recklinghausen had not established the relationship between the clinical manifestations and the adenoma discovered by Mandl, then under the name of parathyroid osteosis. This term was justified at a time when the disease presented only bony manifestations with biological evidence. Primary hyperthyroidism is the current appellation, demonstrating that the disease is now a biological disease, often discovered systematically, with therapeutic progress, progress in biological identification and possibility of medical forms without mandatory surgical outcome. Bibliographic references accompany the various stages of this historical reminder.