SUN-437 Central Adrenal Insufficiency Unmasked by Pregnancy

Abstract

Recognition and prompt treatment of adrenal insufficiency (AI) during pregnancy are important to prevent maternal adrenal crisis and/or fetal intrauterine growth retardation, death, and low birth weight. The diagnosis may be difficult to establish in pregnancy because of estrogen-induced increases in cortisol-binding globulin (CBG) production, which lead to increased serum cortisol (sF) levels. Placental-derived ACTH levels also increase, confounding the diagnosis of secondary AI [1]. We report a case of a 36-year-old woman who was followed at the NIH for 10 years for partial hypopituitarism secondary to presumed lymphocytic hypophysitis. She initially presented with central diabetes insipidus followed by central hypogonadotropic hypogonadism, growth hormone deficiency and central hypothyroidism; she received physiologic doses of replacement hormones. Prolactin, albumin, CBG, ACTH (9.1-18 pg/ml; nl: 0-46), and the response to annual 250 mcg Cosyntropin stimulation tests were normal, with stimulated sF levels of 18-24 mcg/dl (nl: >18 mcg/dl). In 2017, in anticipation of a planned pregnancy, a Cosyntropin stimulation test was performed off estrogen supplementation; baseline ACTH (26 pg/ml) and CBG were normal, and sF was 9.3, 18.2 and 20 mcg/dl at baseline, 30, and 60 min of the test, respectively. Pregnancy was successfully induced with gonadotropins, progesterone and timed intercourse. Patient had nausea beginning in the first trimester. This worsened at week 36, when she also complained of increased fatigue and vomiting. At that time, morning sF was 12-14 mcg/dl, with corresponding ACTH of 25-33 pg/ml. These values were subnormal for the third trimester of pregnancy, confirming secondary AI [1]. Hydrocortisone replacement was started at a dose of 12mg x 1.6 body surface area (BSA), with improvement in symptoms. At 40 weeks she received stress doses of hydrocortisone during an elective C-section, and delivered a 7-lbs healthy boy without complications. At 40 days postpartum a Cosyntropin stimulation test showed continued evidence of central AI: sF by immunoassay was 6.5 mcg/dl, 13.6 and 16.7 at baseline, 30 and 60 min after Cosyntropin; at the same times, aldosterone was 16.3, 31, and 23 ng/dl (nl:>6). Baseline ACTH was 11.9 pg/ml, DHEAs was 30 (n:45-295 mcg/dl) and CBG was 2.9 mg/dl (nl: 1.7-3.1). She continues to receive physiological hydrocortisone replacement, currently at 10 mg x BSA, without symptoms of AI. This case illustrates that pregnancy may unmask central adrenal insufficiency, in this case, presumably because the adrenal glands could not produce sufficient cortisol to saturate the increased levels of CBG. The persistent post-partum abnormality in our patient suggests also that pituitary function may continue to decline over time, and that women with partial hypopituitarism should be monitored closely during pregnancy for further deficits.