Phenotypic Profiling and Molecular Mechanisms in Hyperparathyroidism-jaw Tumor Syndrome.

J Clin Endocrinol Metab

Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Published: November 2023

Context: Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a heritable form of primary hyperparathyroidism caused by germline inactivating mutations in CDC73 encoding parafibromin and is associated with an increased risk of parathyroid cancer. There is little evidence to guide the management of patients with the disease.

Objective: (1) Characterize the natural history of HPT-JT, (2) correlate genotype and histology of parathyroid tumors with parafibromin immunostaining, (3) understand molecular changes downstream to CDC73 loss.

Design: Retrospective study of patients with HPT-JT syndrome (genetically confirmed or affected first-degree relatives). Independent review of uterine tumor from 2 patients and staining for parafibromin on parathyroid tumors from 19 patients (13 adenomas, 6 carcinomas) was performed. RNA-sequencing was performed in 21 parathyroid samples (8 HPT-JT-related adenomas, 6 HPT-JT-related carcinomas, and 7 sporadic carcinomas with wild-type CDC73).

Results: We identified 68 patients from 29 kindreds with HPT-JT with median age at last follow-up of 39 [interquartile range, 29-53] years. A total of 55/68 (81%) developed primary hyperparathyroidism; 17/55 (31%) had parathyroid carcinoma. Twelve of 32 (38%) females developed uterine tumors. Of the 11 patients who had surgical resection for uterine tumors, 12/24 (50%) tumors were rare mixed epithelial mesenchymal polypoid lesions. Four of 68 patients (6%) developed solid kidney tumors; 3/4 had a CDC73 variant at p.M1 residue. Parafibromin staining of parathyroid tumors did not correlate with tumor histology or genotype. RNA-sequencing showed a significant association of HPT-JT-related parathyroid tumors with transmembrane receptor protein tyrosine kinase signaling pathway, mesodermal commitment pathway, and cell-cell adhesion.

Conclusions: Multiple, recurrent atypical adenomyomatous uterine polyps appear to be enriched in women with HPT-JT and appear characteristic of the disease. Patients with CDC73 variants at p.M1 residue appear predisposed to kidney tumors.

Clinical Trial Number: NCT04969926.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10655532PMC
http://dx.doi.org/10.1210/clinem/dgad368DOI Listing

Publication Analysis

Top Keywords

parathyroid tumors
16
hyperparathyroidism-jaw tumor
8
hpt-jt syndrome
8
primary hyperparathyroidism
8
patients
8
tumors
8
tumors patients
8
uterine tumors
8
pm1 residue
8
parathyroid
7

Similar Publications

Impact of adipocytes on ultrasound evaluation of parathyroid adenomas.

J Med Ultrason (2001)

December 2024

Department of Internal Medicine, Kuma Hospital, Kobe, Hyogo, 650-0011, Japan.

Purpose: Parathyroid lipoadenomas are difficult to recognize preoperatively; hence, they may remain undetected. Difficulty in recognition is thought to be due to the adipocytes present in the tumor. This study aimed to clarify the impact of adipocytes as a component of parathyroid adenomas on ultrasound evaluation.

View Article and Find Full Text PDF

Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant disorder, accompanied by multiple endocrine neoplasms of the parathyroid, pancreas, pituitary, and other neoplasms in the adrenal glands. However, in some cases, patients clinically diagnosed with MEN1 may be genotype-negative.

Case Presentation: A 56-year-old female was diagnosed with MEN1 based on a macroprolactinoma (19 mm in diameter), primary hyperparathyroidism, and a cortisol-producing adrenal adenoma, without a family history.

View Article and Find Full Text PDF

Background: Surgery is the preferred treatment for primary hyperparathyroidism. Minimally invasive parathyroidectomy is only feasible with accurate preoperative localisation. Virtual 3D anatomical models can be constructed from patient-specific CT scans using segmentation software.

View Article and Find Full Text PDF

Purpose: Primary hyperparathyroidism (PHPT) is associated with long-term implications on many aspects of general health and has been linked to various tumor types. This retrospective monocentric study aimed to evaluate the prevalence of primary hyperparathyroidism in a cohort of thyroid cancer patients and its impact on their general prognosis.

Methods: The prevalence of primary hyperparathyroidism (concomitant or subsequent) was retrospectively evaluated in a cohort of 450 patients with a diagnosis of differentiated thyroid cancer.

View Article and Find Full Text PDF

Defining the Thyroid-RLN Entry Triangle for Enhanced Recurrent Laryngeal Nerve Exposure in TOETVA: A Retrospective Study.

J Otolaryngol Head Neck Surg

December 2024

Department of Thyroid Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, P.R. China.

Background: Injury to the recurrent laryngeal nerve (RLN) and parathyroid glands (PGs) are the most common and serious complications during the transoral endoscopic thyroidectomy vestibular approach (TOETVA), and their exposure and protection are the most important factors affecting the operation time. Here, we report a novel anatomical landmark and surgical method to shorten the operative time and reduce the chance of injury to the RLN and PGs.

Methods: According to the different exposure methods of the RLN, patients were divided into the experimental group (from top to bottom, E-group) and the comparison group (from outside to inside, C-group), and 1:1 propensity score-matching (PSM) was performed.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!