ACTH deficiency and PGI2 therapy in chronic thromboembolic pulmonary hypertension

Abstract

Case 1 was a 26-year-old female. She developed chronic thromboembolic pulmonary hypertension (CTEPH) at 16 years of age, after the surgical removal of an ovarian tumour. She was given sildenafil at the age of 22, followed by prostaglandin I2 (PGI2) therapy for severe pulmonary hypertension (mean pulmonary arterial pressure [mPAP] 58 mm Hg, and pulmonary vascular resistance [PVR] 1121.2 dyn s/cm). She had never received steroid therapy. She developed appetite loss, diarrhea and systemic edema 4 years after the initiation of PGI2 therapy. Her systemic edemawas improved with diuretic administration plus a slight increase in the dose of PGI2 (from 10 to 10.5 ng/kg/min); however, anorexia, diarrhea, and general fatigue persisted. In addition, her serum Na level dropped to less than 130 mmol/L (normal range: 135–145). Both her cortisol and adrenocorticotropic hormone (ACTH) levels were low, at 3.4 μg/dL (normal range: 5.0–25.0) and 5 pg/mL (normal range: 5–46), respectively. An intravenous injection of ACTH (50 μg) yielded a lower (15.1 pg/mL) than normal peak serum cortisol (normal response: N20) at 60 min, which indicated adrenal insufficiency. In addition, her plasma ACTH response decreased after a challenge with 100 μg of corticotrophin-releasing hormone (CRH; Table 1). Intravenous injections of thyrotropin-releasing hormone (TRH, 500 μg), growth hormone-releasing hormone (GRH, 100 μg), and luteinising hormone-releasing hormone (LH-RH, 100 μg) showed normal responses for thyroid-stimulating hormone (TSH), growth hormone (GH), luteinising hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) secretion. Magnetic resonance imaging (MRI) did not reveal any pituitary or adjacent lesions. No autoantibodies were detected, including antipituitary antibody, antiphospholipid antibody (APA), lupus anticoagulant (LA), thyroid stimulating antibody (TsAb), thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb). These results indicated isolated ACTH deficiency (IAD). The patient's anorexia, diarrhea, and hyponatremia rapidly improved