Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 105, Issue 6, Pages E2271-E2281Publisher
ENDOCRINE SOC
DOI: 10.1210/clinem/dgaa142
Keywords
acromegaly; hyperparathyroidism; multiple endocrine neoplasia type 1 (MEN-1); MEN-1 phenocopy
Categories
Funding
- Ipsen
- Wellcome Investigator Award
- National Institute for Health Research (NIHR) Senior Investigator Award
- NIHR Oxford Biomedical Research Centre Programme
Ask authors/readers for more resources
Context: Clinical multiple endocrine neoplasia type 1 (MEN-1) is diagnosed by the presence of at least 2 MEN-1-associated tumors. Many patients with acromegaly and clinical MEN-1 yield negative testing for MEN1 mutations. While cases of acromegaly and primary hyperparathyroidism (PHP) with negative genetic testing have been reported, its prevalence among patients with acromegaly is undetermined, and the clinical presentation has not been well characterized. Objectives: The main goals of this study are: (1) To determine the prevalence of clinical MEN-1 with PHP in patients with acromegaly and characterize their clinical features; and (2) to evaluate the genetic basis for the coexistence of acromegaly and PHP. Design: Retrospective record review and genetic analysis. Setting: Clinical Research Centers. Participants: 414 patients with acromegaly. Interventions: Clinical evaluation and DNA sequencing for MEN1, CDKN1A, CDKN1B, CDKN2B, CDKN2C, and A/P genes. Main outcome measurements: Clinical and genetic analysis. Results: Among patients with acromegaly, clinical MEN-1, as defined by the presence of at least one other MEN-1-associated tumor, was present in 6.6%. PHP occurred in 6.1%; more than half had parathyroid hyperplasia. DNA sequencing was unrevealing for genetic mutations, except for 1 case of a CDC73 mutation. Acromegaly was diagnosed at an older age with a higher prevalence of malignancies (specifically breast and thyroid) in patients with coexisting PHP than those with isolated acromegaly. Conclusions: A distinct phenotype is described in patients with clinical MEN-1 and negative genetic testing for mutations previously associated with this syndrome. Further studies are needed to identify other genes that may explain the association between PHP and acromegaly.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available