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Cited by 1Cardiac electrophysiology and arrhythmiasPituitary Gland Disorders and TreatmentsHormonal and reproductive studies

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

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Gasco, Valentina, Cuboni, Daniela, Siclari, Sergio, Mocellini, Francesca, Sibilla, Michela, Grottoli, Silvia, Ghigo, Ezio, Maccario, Mauro·2025·Biomedicines
DOI 10.3390/biomedicines13112676PMC PMC12649990
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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.

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  • Autonomic impairment might further exacerbate risk for QTc interval prolongation in individuals with hypothalamic/pituitary tumors, along with electrolyte abnormalities and high-risk medications.

    “Along with electrolyte abnormalities related to hormone deficiencies and concurrent use of high-risk medications, autonomic impairment might further exacerbate risk for QTc interval prolongation that has been noted in some individuals with hypothalamic/pituitary tumors (62, 63).”

    From Approach to the patient with acquired hypothalamic syndrome (2026) · cites this paper as [63]

    The Discussion (section 4; page unavailable) links certain hypothalamic–pituitary lesions to QTc prolongation and proposes altered autonomic regulation as a possible mechanism. The Introduction (section 1; page unavailable) also reports electrolyte disturbances and QT-prolonging drugs in some cases. However, the paper does not establish that the electrolyte abnormalities were caused by hormone deficiencies; its Conclusions say the role of pituitary hormone deficiencies remains unclear. (LLM, conf=0.82)

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Authors
Gasco, V., Cuboni, D., Siclari, S., Mocellini, F., Sibilla, M., Grottoli, S., Ghigo, E., & Maccario, M.
Affiliations
University of Turin (IT)
Corresponding author
Gasco, Valentina
ORCID
Venue
Biomedicines
Publisher
MDPI AG
Published
2025-10-31
Volume
13
Issue
11
Pages
2676
ISSN
2227-9059 (ISSN-L)
DOI
10.3390/biomedicines13112676
PMC
PMC12649990
OpenAlex
W4415723870
Cited by
1
References
61
Citations by year
2026: 1
FWCI
0.70
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomedicines (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
QTc prolongation, hypopituitarism, long QT syndrome, acquired long QT syndrome, hypothalamic-pituitary dysfunction, pituitary adenoma, craniopharyngioma, Rathke's cleft cyst, age as predictor, potassium deficiency, albumin-corrected calcium, electrolyte imbalance, hormone replacement therapy, myocardial repolarization

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