TOPLINE:

First-degree relatives of patients with primary hyperparathyroidism (PHPT) had nearly threefold higher odds of developing the condition than relatives of matched control individuals from the general population, with markedly higher odds among patients with early-onset PHPT. Although certain cancers were slightly overrepresented in relatives, the associations were weak.

METHODOLOGY:

• PHPT occurs in both sporadic and inherited forms, with familial clustering in certain genetic syndromes. Although patients appear to have an elevated risk for malignancies, whether this risk extends to their first-degree relatives remains uncertain.
• Researchers in Sweden conducted a retrospective case-control analysis and a prospective cohort analysis to assess familial aggregation of PHPT and malignancies among first-degree relatives of affected patients.
• They included 6693 patients who underwent parathyroidectomy for PHPT from 2008 to 2017 and 33,393 control individuals matched on the basis of year of parathyroidectomy, age, sex, and address.
• A total of 36,386 first-degree relatives of patients and 182,343 first-degree relatives of control individuals were identified; first-degree relatives were biological parents, full siblings, or children.
• The primary endpoint was diagnosis of PHPT in first-degree relatives, and secondary endpoints were diagnoses of site-specific malignancies and endocrine organ neoplasia among first-degree relatives.

TAKEAWAY:

• In the case-control analysis, first-degree relatives of patients with PHPT had nearly threefold higher odds of PHPT than first-degree relatives of control individuals (odds ratio [OR], 2.65; 95% CI, 2.33-3.02); the association was strongest when the index patient was aged 40 years or younger at diagnosis (OR, 9.07; 95% CI, 5.46-15.08).
• Patients had markedly higher odds of having first-degree relatives diagnosed with both PHPT and a neuroendocrine tumor than control individuals (OR, 7.67; 95% CI, 3.59-16.37).
• Malignancies — specifically prostate cancer, nonmedullary thyroid cancer, and hematologic malignancies — in first-degree relatives were modestly more common in patients with PHPT than in control individuals (OR, 1.07; 95% CI, 1.01-1.13).
• In the prospective analysis, no increased risk for malignancies was observed in first-degree relatives.

IN PRACTICE:

“The results underscore the importance of family history, genetic screening, and counseling in selected patients with PHPT, particularly those diagnosed at or before age 40 years, to identify a potential hereditary form of the disease,” the authors of the study wrote.

SOURCE:

The study was led by David Thorsteinsson, Karolinska University Hospital, Stockholm, Sweden. It was published online in the Journal of the Endocrine Society.

LIMITATIONS:

The inclusion of only patients who underwent parathyroidectomy likely introduced detection bias and limited generalizability to the general PHPT population. Because coverage of tertiary care visits in the National Patient Register was incomplete before 2001, PHPT among relatives was probably underreported. Additionally, because PHPT diagnosis relies on laboratory testing and health-seeking behavior, which may run in families, this could have resulted in earlier detection and overrepresentation of malignancies among relatives of these patients.

DISCLOSURES:

The study was supported by Region Stockholm and the Karolinska Institutet. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.