Faculty Collaboration Database

The Role of Demographic and Clinical Factors in Germline Mutation Testing for Patients with Primary Hyperparathyroidism. Ann Surg Oncol 2024 Jun;31(6):3964-3971

Date

03/09/2024

Pubmed ID

38459417

DOI

10.1245/s10434-024-15104-3

Scopus ID

2-s2.0-85187140833 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

INTRODUCTION: Guidelines recommending genetic counseling in primary hyperparathyroidism (PHPT) vary. To further delineate current recommendations, this study examined genetic counseling referral patterns and rates of mutations in surgical patients with PHPT.

PATIENTS AND METHODS: A single-institution review was performed of adult patients who underwent parathyroidectomy for presumed sporadic PHPT. Genetic testing indications of hypercalcemia onset ≤ 40 years, multigland disease (MGD), family history (FHx) of PHPT, or other clinical indications suspicious for a PHPT-related endocrinopathy were examined by demographics and mutation detection rates.

RESULTS: Genetic counseling was performed in 237 (37.9%) of 625 patients. Counseling was discussed but not performed in 121 (19.4%) patients. No evidence was noted of genetic referral discussion in the remaining 267 (42.7%). Of these groups, patients who received genetic counseling were youngest, p < 0.001 [median age 55.3 (IQR 43.2, 66.7) years]. The majority of patients with indications of age ≤ 40 years (65.7%), FHx (78.0%), and other clinical indications (70.7%) underwent genetic counseling, while most with MGD (57.0%) did not. Eight mutations were detected in 227 patients (3.5%). Mutations included: MEN1 (n = 2), CDC-73 (n = 4), and CASR (n = 2). Detection was most common in patients with FHx (4/71, 5.6%), then age ≤ 40 years (3/66, 4.5%), and other clinical indications (3/80, 3.8%). No mutations were identified in 48 patients tested solely for MGD.

CONCLUSIONS: Most patients with onset of hypercalcemia age ≤ 40 years, positive FHx, or other clinical concerns underwent genetic counseling, while most with MGD did not. As no germline mutations were identified in patients with MGD alone, further investigation of MGD as a sole indication for genetic counseling may be warranted.

Author List

Hangge PT, Dream S, Yen TWF, Doffek K, Stachowiak SM, Shaker J, Evans DB, Wang TS

Authors

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin
Joseph L. Shaker MD Professor in the Medicine department at Medical College of Wisconsin
Tracy S. Wang MD, MPH Professor in the Surgery department at Medical College of Wisconsin
Tina W F Yen MD, MS Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Female
Follow-Up Studies
Genetic Counseling
Genetic Testing
Germ-Line Mutation
Humans
Hypercalcemia
Hyperparathyroidism, Primary
Male
Middle Aged
Parathyroidectomy
Prognosis
Proto-Oncogene Proteins
Retrospective Studies
Tumor Suppressor Proteins