Top

Published in:

08-03-2024 | Hyperparathyroidism | Endocrine Tumors

The Role of Demographic and Clinical Factors in Germline Mutation Testing for Patients with Primary Hyperparathyroidism

Authors: Patrick T. Hangge, MD, Sophie Dream, MD, Tina W. F. Yen, MD, MS, Kara Doffek, BS, Samantha M. Stachowiak, MS, CGC, Joseph Shaker, MD, Douglas B. Evans, MD, Tracy S. Wang, MD, MPH

Published in: Annals of Surgical Oncology | Issue 6/2024

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.

Available only for authorised users

Iacobone M, Carnaille B, Palazzo FF, Vriens M. Hereditary hyperparathyroidism—A consensus report of the European society of endocrine surgeons (ESES). Langenbeck’s Arch Surg. 2015;400(8):867–86. https://doi.org/10.1007/s00423-015-1342-7.CrossRef

Simonds WF. Genetics of hyperparathyroidism, including parathyroid cancer. Endocrinol Metab Clin North Am. 2017;46(2):405–18. https://doi.org/10.1016/j.ecl.2017.01.006.CrossRefPubMedPubMedCentral

Lee JY, Shoback DM. Familial hypocalciuric hypercalcemia and related disorders. Best Pract Res Clin Endocrinol Metab. 2018;32(5):609–19. https://doi.org/10.1016/j.beem.2018.05.004.CrossRefPubMedPubMedCentral

Bilezikian JP, Khan AA, Silverberg SJ, et al. Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the fifth international workshop. J Bone Miner Res. 2022;37(11):2293–314. https://doi.org/10.1002/jbmr.4677.CrossRefPubMed

Bollerslev J, Rejnmark L, Zahn A, et al. European expert consensus on practical management of specific aspects of parathyroid disorders in adults and in pregnancy: recommendations of the ESE Educational Program of Parathyroid Disorders (PARAT 2021). European J Endocrinol. 2022;186(2):R33–63. https://doi.org/10.1530/eje-21-1044.CrossRef

Wilhelm SM, Wang TS, Ruan DT, et al. The American association of endocrine surgeons guidelines for definitive management of primary hyperparathyroidism. JAMA Surg. 2016;151(10):959–68. https://doi.org/10.1001/jamasurg.2016.2310.CrossRefPubMed

Eastell R, Brandi ML, Costa AG, D’Amour P, Shoback DM, Thakker RV. Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the Fourth international workshop. J Clin Endocrinol Metab. 2014;99(10):3570–9. https://doi.org/10.1210/jc.2014-1414.CrossRefPubMed

Lassen T, Friis-Hansen L, Rasmussen ÅK, Knigge U, Feldt-Rasmussen U. Primary hyperparathyroidism in young people. When should we perform genetic testing for multiple endocrine neoplasia 1 (MEN-1)? J Clin Endocrinol Metab. 2014;99(11):983–3987. https://doi.org/10.1210/jc.2013-4491.CrossRef

Bricaire L, Odou M-F, Cardot-Bauters C, et al. Frequent large germline HRPT2 deletions in a French national cohort of patients with primary hyperparathyroidism. J Clin Endocrinol Metab. 2013;98(2):E403–8. https://doi.org/10.1210/jc.2012-2789.CrossRefPubMed

10.

Hayden S, Mange S, Duquette D, Petrucelli N, Raymond VM. Large, prospective analysis of the reasons patients do not pursue BRCA genetic testing following genetic counseling. J Genet Couns. 2017;26(4):859–65. https://doi.org/10.1007/s10897-016-0064-5.CrossRefPubMed

11.

Lin GA, Trosman JR, Douglas MP, et al. Influence of payer coverage and out-of-pocket costs on ordering of NGS panel tests for hereditary cancer in diverse settings. J Genet Couns. 2022;31(1):130–9. https://doi.org/10.1002/jgc4.1459.CrossRefPubMed

12.

El Lakis M, Nockel P, Gaitanidis A, et al. Probability of positive genetic testing results in patients with family history of primary hyperparathyroidism. J Am Coll Surg. 2018;226(5):933–8. https://doi.org/10.1016/j.jamcollsurg.2018.01.007.CrossRefPubMedPubMedCentral

13.

Falchetti A. Genetic screening for multiple endocrine neoplasia syndrome type 1 (MEN-1): when and how. F1000 Med Rep. 2010. https://doi.org/10.3410/m2-14.CrossRefPubMedPubMedCentral

14.

Ellard S, Hattersley A, Brewer C, Vaidya B. Detection of an MEN1 gene mutation depends on clinical features and supports current referral criteria for diagnostic molecular genetic testing. Clin Endocrinol. 2005;62(2):169–75.CrossRef

15.

Tham E, Grandell U, Lindgren E, Gr T, Skogseid B, Nordenskjöld M. Clinical testing for mutations in the MEN1 gene in Sweden: a report on 200 unrelated cases. J Clin Endocrinol Metab. 2007;92(9):3389–95. https://doi.org/10.1210/jc.2007-0476.CrossRefPubMed

16.

Mariathasan S, Andrews KA, Thompson E, et al. Genetic testing for hereditary hyperparathyroidism and familial hypocalciuric hypercalcaemia in a large UK cohort. Clin Endocrinol. 2020;93(4):409–18. https://doi.org/10.1111/cen.14254.CrossRef

17.

Starker LF, Akerström T, Long WD, et al. Frequent germ-line mutations of the MEN1, CASR, and HRPT2/CDC73 genes in young patients with clinically non-familial primary hyperparathyroidism. Horm Cancer. 2012;3(1–2):44–51. https://doi.org/10.1007/s12672-011-0100-8.CrossRefPubMed

18.

Park HS, Lee YH, Hong N, Won D, Rhee Y. Germline mutations related to primary hyperparathyroidism identified by next-generation sequencing. Front Endocrinol (Lausanne). 2022;13:853171. https://doi.org/10.3389/fendo.2022.853171.CrossRefPubMedPubMedCentral

19.

Dershem R, Gorvin CM, Metpally RPR, et al. Familial hypocalciuric hypercalcemia type 1 and autosomal-dominant hypocalcemia type 1: prevalence in a large healthcare population. Am J Hum Genet. 2020;106(6):734–47. https://doi.org/10.1016/j.ajhg.2020.04.006.CrossRefPubMedPubMedCentral

Title: The Role of Demographic and Clinical Factors in Germline Mutation Testing for Patients with Primary Hyperparathyroidism
Authors: Patrick T. Hangge, MD
Sophie Dream, MD
Tina W. F. Yen, MD, MS
Kara Doffek, BS
Samantha M. Stachowiak, MS, CGC
Joseph Shaker, MD
Douglas B. Evans, MD
Tracy S. Wang, MD, MPH
Publication date: 08-03-2024
Publisher: Springer International Publishing
Keywords: Hyperparathyroidism
Hypercalcemia
Parathyroidectomy
Parathyroidectomy
Published in: Annals of Surgical Oncology / Issue 6/2024
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-024-15104-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The Role of Demographic and Clinical Factors in Germline Mutation Testing for Patients with Primary Hyperparathyroidism

Abstract

Introduction

Patients and Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Patients and Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 6/2024

ASO Visual Abstract: Contemporary Analysis of Re-Excision and Conversion to Mastectomy Rates and Associated Health Care Costs for Women Undergoing Breast-Conserving Surgery

Lessons from Dr. Norton

ASO Author Reflections: Addressing Hospital-Based Disparities in Access to Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) and Survival in Patients with Isolated Colorectal Peritoneal Metastases

Unfolding the Art of Methodical Approach for Total Sacrectomy

ASO Visual Abstract: Effect of Hospital Cancer Designation on Use of Multimodal Therapy and Survival of Patients with Metastatic Colorectal Cancer: A State-Wide Analysis

Optimizing Postoperative Pain Management After Cytoreductive Surgery: Time to Break Old Habits and Usher in More Interdisciplinary Collaboration