Prenatal manifestation of isolated ACTH-deficiency

Abstract

In a 34 yr old pregnant woman, serum(S)-HPL (3.3 ug/ml, 34 weeks)and urinary (U)-HCG (19000 IU/24 h, 28 weeks) were normal, but U-estriol (5.4, 4.5, 3.5mg/24h at 32, 33 and 34 weeks) was low without any complications. A boy (48.5 cm, 2980 g) was delivered after 38 weeks with Apgar score 9/10/10. He had neonatal hypoglycemia (31 mg/dl), muscular hypotonia, transient hyperbilirubinemia, and unilateral cryptorchidism. U-16-hydroxylated steroids and THE-response to ACTH were normal excluding placental sulfatase deficiency and congenital adrenal hypoplasia, but U-THS after a single dose of metyrapone(M, 500mg/m2) was <60μg/12h. At age 4 yrs, extreme fatigue, spells of daytime sleep, and aggressive behavior occurred 3 - 4 times a week. Plasma cortisol (F) responded to ACTH (4.0 - 20.3 μg/dl), but U-THS after M was extremely low (<10 μg/m2/12h). With severe insulin induced hypoglycemia (14 mg/dl), S-ACTH increased insufficiently (87 to 102 pg/ml, normal maximum 216-522pg/ml). GH-response to insulin and arginine and TSH response to TRH were normal, while the LH and FSH response to LHRH was low. Treatment with F (10 mg daily) resulted in disappearance of the symptoms. It is concluded that fetal ACTH-deficiency may be a cause of low maternal U-estriol.