Hyperparathyroidism in hereditary syndromes: Special expressions and special managements

Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892-1802, USA.
Journal of Bone and Mineral Research (Impact Factor: 6.83). 12/2002; 17 Suppl 2:N37-43.
Source: PubMed


Hyperparathyroidism (HPT) in its hereditary variants assumes special forms, has special associations, and requires special managements. Familial hypocalciuric hypercalcemia (FHH or FBHH) and neonatal severe primary hyperparathyroidism (NSHPT) reflect heterozygous or homozygous mutations, respectively, in the calcium-sensing receptor. FHH and NSHPT represent the mildest and severest variants of HPT. Both cause hypercalcemia from birth and atypical HPT that always and uniquely persists after subtotal parathyroidectomy. Their HPT is likely polyclonal and nonneoplastic. In contrast, mono- or oligo-clonal parathyroid neoplasia underlays most other HPT variants: multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and hyperparathyroidism-jaw tumor syndrome (HPT-JT). Familial-isolated HPT combines several diagnoses, including occult forms of the above syndromes. Each neoplastic variant has tumors in multiple parathyroids and a delayed, but still early age of onset for HPT (average age, 25-35 years). Each justifies special and similar approaches to parathyroidectomy: typically, identification of four glands, subtotal parathyroidectomy, rapid intraoperative parathyroid hormone (PTH) assays, and parathyroid cryopreservation. Outcomes of parathyroidectomy remain suboptimal in each. Each syndrome of parathyroid neoplasia associates with characteristic cancer(s): enteropancreatic neuroendocrine or foregut carcinoid tissues (MEN1), thyroidal C cells (MEN2A), or parathyroid (HPT-JT). HPT has promoted gene discovery more through its rare hereditary variants than through common adenoma; the main genes causing four of six hereditary variants are known. The RET mutation test became essential in management of MEN2A. The MEN1 test is less urgent, because it rarely guides a major patient benefit. The CASR test, perhaps least urgent, has largely been unavailable. Further progress in molecular genetics will enhance understandings, diagnosis, and therapy of HPT.

17 Reads
  • Source
    • "Clinical features that differentiate between patients with sporadic PHPT and MEN-related PHPT are: age of onset, female to male ratio, severity of bone involvement, family history and related endocrine neoplasias [7-9]. Once PHPT and its setting are diagnosed, the course of the disease and its treatment will change the perspective for both surgeon and patient considerably. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Primary hyperparathyroidism (PHPT) is most commonly sporadic (sPHPT). However, sometimes PHPT develops as part of multiple endocrine neoplasia (MEN) type 1 or 2A. In all, parathyroidectomy is the only curative treatment. Nevertheless, there are important differences in clinical expression and treatment. We analyzed a consecutive cohort of patients treated for sporadic, MEN1-related, and MEN2A-related PHPT and compared them regarding clinical and biochemical parameters, differences in preoperative workup, operative strategies, findings, and outcome. A total of 467 patients with sPHPT, 52 with MEN1- and 16 with MEN2A-related PHPT were analyzed. Patients with sPHPT were older, more often female and had higher preoperative calcium and parathyroid hormone levels, when compared with MEN1 and MEN2A patients. Minimally invasive parathyroidectomy (MIP) was performed in 367 of 467 sPHPT patients (79%). One abnormal parathyroid was found in 426 patients (91%). Two or more in 35 patients (7%). In six patients (1%) no abnormal parathyroid gland was retrieved. Of 52 MEN1 patients, eight (15%) underwent a MIP and 44 patients (85%) underwent conventional neck exploration (CNE); with resection of fewer than 3½ enlarged glands in 21 patients (40%), subtotal parathyroidectomy (SPTX, 3-3½ glands) in seventeen (33%) and total parathyroidectomy with autotransplantation (TPTX) in six (12%). Eleven patients (21%) had persistent disease, 29 (56%) recurrent PHPT and nine (17%) permanent hypoparathyroidism, mostly after TPTX. Of 16 MEN2A patients, six (38%) underwent MIP, four (25%) CNE and six (38%) selective resection of the enlarged gland(s) during total thyroidectomy. Three patients (19%) suffered from persistent PHPT and two (13%) developed recurrent disease. Sporadic PHPT, MEN1- and MEN2A-related PHPT are three distinct entities as is reflected preoperatively by differences in gender, age at diagnosis and calcium and PTH levels. MEN2A patients are very similar to sPHPT with respect to operative approach and findings. MIP is the treatment of choice for both. MIP has low rates of persistent and recurrent PHPT and a low complication rate. The percentage of multiglandular disease and recurrences are significantly higher in MEN1 patients, demonstrating the need for a different approach. We advocate treating these patients with CNE and SPTX.
    Orphanet Journal of Rare Diseases 04/2013; 8(1):50. DOI:10.1186/1750-1172-8-50 · 3.36 Impact Factor
  • Source
    • "Primary hyperparathyroidism (PHPT) is a condition caused by hyperfunction of the parathyroid tissue, usually involving only one gland. However, it is often multiglandular when expressed within complex hereditary syndromes, such as multiple endocrine neoplasia type 1 (MEN1), MEN2A, familial isolated hyperparathyroidism, autosomal dominant mild hyperparathyroidism, neonatal severe hyperparathyroidism, familial hypocalciuric hypercalcemia, and the hyperparathyroidism–jaw tumor syndrome (1),(2). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Primary hyperparathyroidism is a common endocrinological disorder. In rare circumstances, it is associated with familial syndromes, such as multiple endocrine neoplasia type 1. This syndrome is caused by a germline mutation in the multiple endocrine neoplasia type 1 gene encoding the tumor-suppressor protein menin. Usually, primary hyperparathyroidism is the initial clinical expression in carriers of multiple endocrine neoplasia type 1 mutations, occurring in more than 90% of patients and appearing at a young age (20-25 years). Multiple endocrine neoplasia type 1/primary hyperparathyroidism is generally accompanied by multiglandular disease, clinically manifesting with hypercalcemia, although it can remain asymptomatic for a long time and consequently not always be recognized early. Surgery is the recommended treatment. The goal of this short review is to discuss the timing of surgery in patients when primary hyperparathyroidism is associated with multiple endocrine neoplasia type 1.
    Clinics (São Paulo, Brazil) 04/2012; 67 Suppl 1(Suppl 1):141-4. DOI:10.6061/clinics/2012(Sup01)23 · 1.19 Impact Factor
  • Source
    • "HPT occurs predominantly as a sporadic disease in 95% of cases; the remaining 5% of cases are hereditary forms of the disease (2)–(6). It is worth noting that subtotal or total parathyroidectomy (PTx) is usually recommended for the treatment of inherited HPT cases, whereas adenomectomy is indicated for the vast majority of sporadic HPT cases (6)–(8). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Primary hyperparathyroidism associated with multiple endocrine neoplasia type I (hyperparathyroidism/multiple endocrine neoplasia type 1) differs in many aspects from sporadic hyperparathyroidism, which is the most frequently occurring form of hyperparathyroidism. Bone mineral density has frequently been studied in sporadic hyperparathyroidism but it has very rarely been examined in cases of hyperparathyroidism/multiple endocrine neoplasia type 1. Cortical bone mineral density in hyperparathyroidism/multiple endocrine neoplasia type 1 cases has only recently been examined, and early, severe and frequent bone mineral losses have been documented at this site. Early bone mineral losses are highly prevalent in the trabecular bone of patients with hyperparathyroidism/multiple endocrine neoplasia type 1. In summary, bone mineral disease in multiple endocrine neoplasia type 1 related hyperparathyroidism is an early, frequent and severe disturbance, occurring in both the cortical and trabecular bones. In addition, renal complications secondary to sporadic hyperparathyroidism are often studied, but very little work has been done on this issue in hyperparathyroidism/multiple endocrine neoplasia type 1. It has been recently verified that early, frequent, and severe renal lesions occur in patients with hyperparathyroidism/multiple endocrine neoplasia type 1, which may lead to increased morbidity and mortality. In this article we review the few available studies on bone mineral and renal disturbances in the setting of hyperparathyroidism/multiple endocrine neoplasia type 1. We performed a meta-analysis of the available data on bone mineral and renal disease in cases of multiple endocrine neoplasia type 1-related hyperparathyroidism.
    Clinics (São Paulo, Brazil) 04/2012; 67 Suppl 1(Suppl 1):99-108. DOI:10.6061/clinics/2012(Sup01)17 · 1.19 Impact Factor
Show more