Distinguishing hyperparathyroidism from insulin-like growth factor I–driven calcium–phosphate metabolism changes in acromegaly
Abstract
OBJECTIVES: Acromegaly is frequently associated with disturbances in calcium-phosphate metabolism, including mild hypercalcemia. Hypercalcemia may also reflect primary hyperparathyroidism (PHPT), which can occur with or without variants in MEN1 or the related genes. Distinguishing PHPT from insulin-like growth factor I (IGF-I)-related alterations in mineral metabolism remains challenging. We aimed to assess the prevalence and characteristics of PHPT in patients with acromegaly and explore biochemical approaches for identifying parathyroid autonomy. DESIGN: We conducted a retrospective study at 2 French university hospitals, including adults with acromegaly who had at least 1 serum calcium measurement obtained during uncontrolled disease. Three diagnostic approaches based on serum calcium and phosphate levels were evaluated: a threshold-based decision rule, logistic regression, and a support vector machine model. RESULTS: Among 393 patients (54% women; median age 43 years [interquatile range 33-55]), 23 (5.9%) had concomitant PHPT. In isolated acromegaly, hyperphosphatemia occurred in 37.3% and mild hypercalcemia in 3.2% of patients; both resolved after acromegaly treatment. Patients with PHPT had persistent mild hypercalcemia (median calcium 2.72 mmol/L [interquatile range 2.66-2.86]), elevated PTH, and low-to-normal phosphate levels, these abnormalities resolved after parathyroid surgery in the 10 operated patients. No pathogenic variants were identified in the tested genes. A threshold-based rule combining calcium >2.60 mmol/L and phosphate <1.46 mmol/L showed excellent diagnostic performance for identifying parathyroid autonomy, with bootstrap 0.632+ corrected sensitivity and specificity of 0.940 and 0.993, respectively, and was preferred because of its simplicity. CONCLUSIONS: PHPT may be more frequent in acromegaly than in the general population. In patients with acromegaly and hypercalcemia, a nonelevated phosphate level strongly suggests concomitant PHPT, whereas an elevated phosphate level favors IGF-I-related mineral disturbances.
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BibTeX
@article{laure2026distinguishing,
title = {{Distinguishing hyperparathyroidism from insulin-like growth factor I–driven calcium–phosphate metabolism changes in acromegaly}},
author = {Cécilia Laure and Adrien Lecoeuvre and Benoit Cochet and Marie Verdoux and Maureen Lopez and Margot Dupeux and Anne-Lise Lecoq and Sylvie Salenave and Luigi Maione and Fanny Chasseloup and Pauline Romanet and Séverine Trabado and Jacques Young and Isabelle Raingeard and Philippe Chanson and Peter Kamenický},
journal = {European Journal of Endocrinology},
year = {2026},
month = sep,
doi = {10.1093/ejendo/lvag169},
url = {https://hal.science/hal-05768444v1},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Distinguishing hyperparathyroidism from insulin-like growth factor I–driven calcium–phosphate metabolism changes in acromegaly
AU - Cécilia Laure
AU - Adrien Lecoeuvre
AU - Benoit Cochet
AU - Marie Verdoux
AU - Maureen Lopez
AU - Margot Dupeux
AU - Anne-Lise Lecoq
AU - Sylvie Salenave
AU - Luigi Maione
AU - Fanny Chasseloup
AU - Pauline Romanet
AU - Séverine Trabado
AU - Jacques Young
AU - Isabelle Raingeard
AU - Philippe Chanson
AU - Peter Kamenický
PY - 2026
DA - 2026/09/28
JO - European Journal of Endocrinology
DO - 10.1093/ejendo/lvag169
UR - https://hal.science/hal-05768444v1
AB - OBJECTIVES: Acromegaly is frequently associated with disturbances in calcium-phosphate metabolism, including mild hypercalcemia. Hypercalcemia may also reflect primary hyperparathyroidism (PHPT), which can occur with or without variants in MEN1 or the related genes. Distinguishing PHPT from insulin-like growth factor I (IGF-I)-related alterations in mineral metabolism remains challenging. We aimed to assess the prevalence and characteristics of PHPT in patients with acromegaly and explore biochemical approaches for identifying parathyroid autonomy. DESIGN: We conducted a retrospective study at 2 French university hospitals, including adults with acromegaly who had at least 1 serum calcium measurement obtained during uncontrolled disease. Three diagnostic approaches based on serum calcium and phosphate levels were evaluated: a threshold-based decision rule, logistic regression, and a support vector machine model. RESULTS: Among 393 patients (54% women; median age 43 years [interquatile range 33-55]), 23 (5.9%) had concomitant PHPT. In isolated acromegaly, hyperphosphatemia occurred in 37.3% and mild hypercalcemia in 3.2% of patients; both resolved after acromegaly treatment. Patients with PHPT had persistent mild hypercalcemia (median calcium 2.72 mmol/L [interquatile range 2.66-2.86]), elevated PTH, and low-to-normal phosphate levels, these abnormalities resolved after parathyroid surgery in the 10 operated patients. No pathogenic variants were identified in the tested genes. A threshold-based rule combining calcium >2.60 mmol/L and phosphate <1.46 mmol/L showed excellent diagnostic performance for identifying parathyroid autonomy, with bootstrap 0.632+ corrected sensitivity and specificity of 0.940 and 0.993, respectively, and was preferred because of its simplicity. CONCLUSIONS: PHPT may be more frequent in acromegaly than in the general population. In patients with acromegaly and hypercalcemia, a nonelevated phosphate level strongly suggests concomitant PHPT, whereas an elevated phosphate level favors IGF-I-related mineral disturbances.
SN - 0804-4643
SN - 1479-683X
ER -