Severe QT prolongation and torsades de pointe in panhypopituitarism: A reversible endocrine crisis

Torsades de Pointe (TdP) is a fatal arrhythmia that is a potential sequela of a prolonged QT interval. Most cases of TdP arise from medication-induced or congenital prolonged QT¹. This case highlights an underrecognized association between panhypopituitarism and TdP, demonstrating that severe endocrine dysfunction can masquerade as primary cardiac disease^2,3. Early recognition and hormone replacement can transform a fatal arrhythmia into a fully preventable event.

A 27-year-old female with a history of craniopharyngioma status post resection with panhypopituitarism presented with intractable vomiting despite doubling her home hydrocortisone per sick-day protocol. At an outside hospital, she was given stress- dose hydrocortisone and IV levothyroxine. After receiving ondansetron for nausea, she developed TdP. She converted to sinus bradycardia following intravenous magnesium. A dopamine infusion was initiated for bradycardia and she was transferred to the cardiac critical care unit. Lab findings demonstrated severe central hypothyroidism, TSH 0.103 mlU/L (0.4 - 4.2 mlU/L) and acute adrenal crisis, ACTH 2.1 pg/ml (7.2 - 63.3 pg/ml) causing severe electrolyte derangements, including hypokalemia, 2.4 mEq/L (3.5 - 5.2 mEq/L). With prior laboratory work-up including low FSH, LH, and IGF-1, the cause of TdP was ultimately panhypopituitarism. Following electrolyte repletion and hormone replacement, symptoms resolved and QTc normalized.

Cardiovascular manifestations of panhypopituitarism include TdP and bradycardia due to secondary adrenal insufficiency and central hypothyroidism. Paired with increased occurrence of electrolyte abnormalities such as hypokalemia, hypomagnesemia, and hypocalcemia, as seen in this case, there is increased risk for further prolongation of QT interval and progression into florid TdP⁴. While TdP is a complication in panhypopituitarism, it is not well-quantified in medical literature and may not prompt close QT and electrolyte monitoring until a patient is symptomatic, at which point there is a heightened risk of an unstable arrhythmia. The most common association between endocrine disorders and TdP is hypothyroidism which prolongs the potassium repolarization currents in cardiac myocytes⁵. Glucocorticoid deficiency alters calcium homeostasis within the cardiac myocytes, leading to prolonged repolarization and a higher possibility of developing TdP⁶. As discussed in the endocrine society clinical practice guidelines, prompt glucocorticoid replacement prior to levothyroxine administration is imperative in reducing risk of adrenal crisis and earlier initiation of hormone therapy increases likelihood of reversing cardiac sequelae and preventing further arrhythmias⁷.

There are a multitude of well-studied TdP etiologies, including drug-induced or congenital long QT and electrolyte imbalance, but panhypopituitarism is not listed by the AHA⁸. Case reports of TdP in the context of endocrinopathies without electrolyte abnormalities provide evidence that panhypopituitarism can independently cause QT prolongation and TdP⁹. In patients with panhypopituitarism, sudden cardiac events are often the end result of an unchecked endocrine crisis. Panhypopituitarism causing profound bradycardia, electrolyte disturbances, and altered repolarization sets the stage for QT prolongation long before TdP occurs. Despite the rarity of presentation, it is crucial that patients at risk for panhypopituitarism such as those with neurological tumors, pituitary apoplexy, autoimmune hypophysitis, and traumatic brain injury have regular electrolyte and QT monitoring with prompt steroid and thyroid hormone replacement to prevent life- threatening TdP.