Endocrine Abstracts

JOINT924

Introduction: Mutations in the PROP1 gene lead to combined pituitary hormone deficiency. The clinical and therapeutic management of hypopituitarism and particularly of adrenal insufficiency (AI) during pregnancy is influenced by lack of standard protocols, different cortisol and ACTH threshold values, a higher risk of complications (including adrenal crisis), and non-specific symptoms. We present the case of a pregnant patient with hypopituitarism due to a PROP1 mutation.

Case presentation: A young Caucasian woman was on regular follow-up for hypopituitarism (GH deficiency, hypothyroidism, AI, and hypogonadism) due to a PROP1 mutation (homozygous pathogenic variant c.150del(p.Arg53AspfsTer112)), receiving hormonal replacement for all deficiencies since childhood. At 28 years old, she achieved pregnancy after ovarian stimulation treatment and in vitro fertilization. Before pregnancy, she was treated with levothyroxine (LT4), modified-release hydrocortisone, and GH replacement therapy (GHRT). The corticotropic and somatotropic axes were adequately replaced, while LT4 dosage had been increased in preparation for assisted reproduction. Once pregnancy was confirmed, GHRT was discontinued and modified-release hydrocortisone was replaced with the standard formulation. Throughout the pregnancy, biochemical monitoring included thyroid function (fT3, fT4) blood glucose and electrolytes, while clinical monitoring focused on symptoms, blood pressure, and weight measurements every 2-3 weeks. As suggested in the literature, during the late second and third trimesters, both hydrocortisone (up to 30 mg/day) and LT4 (up to 3 μg/kg/day) dosages were increased. The patient remained clinically stable and fetal growth was normal for gestational age. At 26 weeks, a glucose tolerance test was performed with normal results. Delivery was planned at a third-level Neonatal Intensive Care and Gynecology center to enable a multidisciplinary approach. The patient delivered a healthy male newborn by C-section at 39 weeks. For adrenal crisis prevention, intravenous hydrocortisone was given at the onset of active labor, followed by a continuous infusion for 24 hours, and additional boluses in the 2 days after delivery due to moderate hyponatremia. After that, oral hydrocortisone was restarted at twice the dose used during pregnancy due to general malaise. LT4 dosage remained also increased in the postpartum period.

Conclusions: The management of AI during pregnancy is hindered by the lack of dedicated guidelines. Hydrocortisone is the glucocorticoid of choice, and a 20-40% dose increase is often needed during the last trimester. Clinical monitoring for signs and symptoms of under- or over-replacement is recommended. Gestation in patients with congenital hypopituitarism is a clinical challenge, but it can be safely managed in specialized centers.