# Determinants of QTc Interval Prolongation in Patients with Hypopituitarism and Other Pituitary Disorders

**Authors:** Valentina Gasco, Daniela Cuboni, Sergio Siclari, Francesca Mocellini, Michela Sibilla, Silvia Grottoli, Ezio Ghigo, Mauro Maccario

PMC · DOI: 10.3390/biomedicines13112676 · 2025-10-31

## TL;DR

This study finds that age and certain brain lesions are linked to prolonged QTc intervals in patients with pituitary disorders, which may increase heart risks.

## Contribution

The study identifies new predictors of QTc prolongation in pituitary disease patients beyond prior case reports.

## Key findings

- Age was a significant predictor of QTc prolongation in most models.
- Expansive lesions other than pituitary adenomas were strongly associated with QTc prolongation.
- Low potassium and calcium levels showed borderline associations with QTc prolongation.

## Abstract

Background: Long QT syndrome (LQTS) is characterized by delayed myocardial repolarization, predisposing to malignant arrhythmias such as torsades de pointes, ventricular fibrillation, and cardiac arrest. Recent reports suggest that acquired LQTS (aLQTS) may represent an early manifestation of hypopituitarism, potentially contributing to its increased cardiovascular mortality, although evidence remains limited to 16 published case reports. Objective: The objective was to investigate the relationship between hypopituitarism and corrected QT (QTc) interval. Methods: We retrospectively analyzed data from 185 patients (121 males) with hypothalamic–pituitary disorders who underwent a 12-lead electrocardiogram between April 2023 and September 2024. Clinical characteristics, hormone replacement therapy, and same-day laboratory parameters (electrolytes, fT3, fT4, IGF-I, testosterone) were recorded. QTc was calculated using Bazett’s formula. Multivariate logistic regression identified predictors of QTc prolongation. Results: Age (OR 1.07–1.09, p = 0.02) was a significant predictor in 5 of 8 models. The presence of expansive lesions other than pituitary adenomas, craniopharyngiomas, and Rathke’s cleft cysts was also associated with QTc prolongation (OR 8.35–17.73, p < 0.05 and p = 0.03). Potassium (OR 0.14–0.17, p = 0.09) and albumin-corrected calcium levels (OR 0.0003, p = 0.06) showed consistent, though borderline, associations. Conclusions: Age and the presence of expansive lesions other than pituitary adenomas, craniopharyngiomas, and Rathke’s cleft cysts are the main predictors of QTc duration in patients with hypothalamic–pituitary disease. Electrolyte imbalances—particularly low potassium and albumin-corrected calcium—may further contribute. The influence of specific pituitary deficiencies remains uncertain, likely due to adequate replacement therapy in most patients.

## Linked entities

- **Chemicals:** potassium (PubChem CID 813)
- **Diseases:** hypopituitarism (MONDO:0005152), Long QT syndrome (MONDO:0002442), torsades de pointes (MONDO:0005478), ventricular fibrillation (MONDO:0000190), cardiac arrest (MONDO:0000745)

## Full-text entities

- **Genes:** IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}
- **Diseases:** hypothalamic-pituitary disease (MESH:D007029), malignant arrhythmias (MESH:D001145), Pituitary Disorders (MESH:D010900), ventricular fibrillation (MESH:D014693), Hypopituitarism (MESH:D007018), aLQTS (MESH:D000163), Rathke's cleft cysts (MESH:D020863), cardiac arrest (MESH:D006323), QTc Interval Prolongation (MESH:D008133), pituitary adenomas (MESH:D010911), craniopharyngiomas (MESH:D003397), LQTS (MESH:D000094024), torsades de pointes (MESH:D016171)
- **Chemicals:** Potassium (MESH:D011188), testosterone (MESH:D013739), calcium (MESH:D002118), fT3 (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12649990/full.md

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Source: https://tomesphere.com/paper/PMC12649990