Hypopituitarism induced by continuous infusion of PGI2 analogues

Background Continuous infusion of PGI₂ analogues, such as epoprostenol and treprostinil, has improved the prognosis of patients with severe pulmonary hypertension (PH) (Ref. 1). However, these therapies can cause complications, including catheter-related infections, thrombocytopenia, and ascites (Ref. 2). Hypopituitarism has also been reported as a potential complication, but its clinical features, management, and outcomes remain unclear. Further investigation is needed to improve diagnosis and treatment strategies. Methods This retrospective cohort study included patients with PH treated with epoprostenol or treprostinil at 15 PH centers between 1999 and 2024. Diagnoses of hypopituitarism were based on decreased adrenocorticotropic hormone (ACTH) levels. Data on patient demographics, clinical presentations, endocrine abnormalities, hemodynamic parameters, treatment strategies, and outcomes were collected and analysed. Results A total of 22 female patients were included, with idiopathic pulmonary arterial hypertension being the most common underlying condition (n = 14, 63.6%). The mean age was 38.8 ± 7.9 years. Hypopituitarism classification revealed isolated pituitary dysfunction in 54.5% (n = 12), partial dysfunction in 18.1% (n = 4), and complete dysfunction in 27.2% (n = 6). Epoprostenol was the predominant PGI₂ analogue (n = 20, 90.9%), compared with treprostinil (n = 2, 9.1%). At hypopituitarism onset, the median PGI₂ dose was 67.2 ng/kg/min (31.8–88.7 ng/kg/min), with a median treatment duration of 889.0 days (450.5–1941.5 days), indicating no clear relationship with dose or duration. Fatigue (n = 21, 95.4%) and loss of appetite (n = 20, 90.9%) were the most common symptoms. Approximately half of the patients experienced non-specific symptoms such as fever (n = 9, 40.9%) or vomiting (n = 11, 50.0%). Endocrine abnormalities included hyponatremia (n = 10, 45.4%) and hypoglycemia (n = 4, 18.1%), which resolved without prolonged treatment. One patient (4.5%) presented with shock but recovered without extended intravenous therapy. Right heart catheterization data at hypopituitarism onset, available for 16 patients (72.7%), showed no significant changes in mean pulmonary arterial pressure (37.7 ± 12.8 vs. 33.3 ± 12.6 mmHg, p = 0.199) or cardiac index (4.0 ± 1.3 vs. 4.0 ± 1.2 L/min/m², p = 0.090) compared to data from 1–2 years earlier. Most patients continued PGI₂ therapy after hypopituitarism onset (63.6%), with 50.0% at the same dose and 13.6% at a reduced dose. Hydrocortisone was administered to 81.8% of patients, resulting in clinical stabilization. No deaths were reported. Conclusions Hypopituitarism can develop during continuous PGI₂ analogue infusion for PH, independent of dose or treatment duration. This study, the largest case series, emphasizes the need for ACTH screening and supports hydrocortisone therapy as an effective management strategy.