Journal of the Endocrine Society · 2025
Familial Aggregation of Primary Hyperparathyroidism and Malignancy-Nationwide Case-Control and Cohort Study.
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Thorsteinsson David, Granath Fredrik, Bränström Robert, Zedenius Jan, Nilsson Inga-Lena
Аннотация
CONTEXT: Primary hyperparathyroidism (PHPT) presents both in sporadic and hereditary forms, with familial clustering observed in certain genetic syndromes. While emerging research suggests an increased malignancy risk in patients, the extent to which this association extends to their first-degree relatives remains unclear. Understanding familial aggregation of PHPT and malignancies could reveal underlying genetic risk factors and guide clinical management.
OBJECTIVE: This work aimed to assess familial clustering of PHPT and malignancies among first-degree relatives of affected patients.
METHODS: A nationwide register-based case-control and cohort study was conducted including all patients with PHPT who underwent parathyroidectomy between 2008 and 2017, with matched controls and their first-degree relatives. This Swedish, nationwide, population-based register study included 6693 patients born in Sweden after 1932 who were matched with 33 393 controls. Main outcome measures included diagnoses of PHPT and malignancies among first-degree relatives.
RESULTS: A total of 218 729 first-degree relatives were identified. Relatives of patients had statistically significantly higher odds of PHPT, particularly if diagnosed at age 45 years or younger (odds ratio [OR] 7.7; 95% CI, 5.23-11.34; P < .001). The risk of malignancy was slightly increased (OR 1.07; 95% CI, 1.01-1.13; P = .017), due to prostate, nonmedullary thyroid, and hematologic malignancies. In prospective analysis, no increased risk of malignancy in relatives was observed.
CONCLUSION: This study highlights a significant familial aggregation of PHPT, particularly in early-onset cases. Although a modest overrepresentation of a family history of malignancy was observed, this may reflect multiple comparisons and surveillance bias rather than a true causal link between PHPT and cancer.
OBJECTIVE: This work aimed to assess familial clustering of PHPT and malignancies among first-degree relatives of affected patients.
METHODS: A nationwide register-based case-control and cohort study was conducted including all patients with PHPT who underwent parathyroidectomy between 2008 and 2017, with matched controls and their first-degree relatives. This Swedish, nationwide, population-based register study included 6693 patients born in Sweden after 1932 who were matched with 33 393 controls. Main outcome measures included diagnoses of PHPT and malignancies among first-degree relatives.
RESULTS: A total of 218 729 first-degree relatives were identified. Relatives of patients had statistically significantly higher odds of PHPT, particularly if diagnosed at age 45 years or younger (odds ratio [OR] 7.7; 95% CI, 5.23-11.34; P < .001). The risk of malignancy was slightly increased (OR 1.07; 95% CI, 1.01-1.13; P = .017), due to prostate, nonmedullary thyroid, and hematologic malignancies. In prospective analysis, no increased risk of malignancy in relatives was observed.
CONCLUSION: This study highlights a significant familial aggregation of PHPT, particularly in early-onset cases. Although a modest overrepresentation of a family history of malignancy was observed, this may reflect multiple comparisons and surveillance bias rather than a true causal link between PHPT and cancer.