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. 2023 Apr 2;15(7):2125.
doi: 10.3390/cancers15072125.

Primary Hyperparathyroidism in Multiple Endocrine Neoplasia Type 2A in Denmark 1930–2021: A Nationwide Population-Based Retrospective Study

Magnus Holm  1 , Peter Vestergaard  2 , Morten Møller Poulsen  3 , Åse Krogh Rasmussen  4 , Ulla Feldt-Rasmussen  4   5 , Mette Bay  1 , Lars Rolighed  6 , Stefano Londero  6 , Henrik Baymler Pedersen  7 , Christoffer Holst Hahn  8 , Klara Bay Rask  8 , Heidi Hvid Nielsen  9 , Mette Gaustadnes  10 , Maria Caroline Rossing  4   11 , Anne Pernille Hermann  12 , Christian Godballe  1   13 , Jes Sloth Mathiesen  1   13
Affiliations

Primary Hyperparathyroidism in Multiple Endocrine Neoplasia Type 2A in Denmark 1930–2021: A Nationwide Population-Based Retrospective Study

Magnus Holm et al. Cancers (Basel). .

Abstract

Studies of primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia type 2A (MEN 2A) shows divergence in frequency, disease definition, reporting of clinical characteristics and traces of selection bias. This is a nationwide population-based retrospective study of PHPT in MEN 2A, suggesting a representative frequency, with complete reporting and a strict PHPT definition. The Danish MEN 2A cohort 1930-2021 was used. Of 204 MEN 2A cases, 16 had PHPT, resulting in a frequency of 8% (CI, 5-12). Age-related penetrance at 50 years was 8% (CI, 4-15). PHPT was seen in the American Thyroid Association moderate (ATA-MOD) and high (ATA-H) risk groups in 62% and 38% of carriers, respectively. Median age at PHPT diagnosis was 45 years (range, 21-79). A total of 75% were asymptomatic and 25% were symptomatic. Thirteen underwent parathyroid surgery, resulting in a cure of 69%, persistence in 8% and recurrence in 23%. In this first study with a clear PHPT definition and no selection bias, we found a lower frequency of PHPT and age-related penetrance, but a higher age at PHPT diagnosis than often cited. This might be affected by the Danish RET p.Cys611Tyr founder effect. Our study corroborates that PHPT in MEN 2A is often mild, asymptomatic and is associated with both ATA-MOD and ATA-H variants. Likelihood of cure is high, but recurrence is not infrequent and can occur decades after surgery.

Keywords: Denmark; REarranged during Transfection; hypercalcemia; multiple endocrine neoplasia type 2A; national cohort; primary hyperparathyroidism.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart showing identification of the Danish MEN 2A cohort 1930–2021. Abbreviations: MEN 2, multiple endocrine neoplasia type 2; RET, REarranged during Transfection; PHPT, primary hyperparathyroidism.
Figure 2
Figure 2
Age-related penetrance of PHPT in the Danish MEN 2A cohort 1930–2021. Abbreviations: PHPT, primary hyperparathyroidism; MEN 2A, multiple endocrine neoplasia type 2A.
Figure 3
Figure 3
Status after surgery for PHPT in the Danish MEN 2A cohort 1930–2021. Abbreviations: PHPT, primary hyperparathyroidism; MEN 2A, multiple endocrine neoplasia type 2A.
See this image and copyright information in PMC

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