Genital abnormalities in infants associated with administration of progesteroids to their mothers.

DR. SHELDON G. LEIBOw: Case 1. The first patient is an infant girl who was first seen here on October 6, 1958 at the age of 2 months by Dr. Gardner. She was referred for evalua tion because of an enlarged clitoris present since birth. The child was born on August 5, 1958, the ninth pregnancy of a 39-year-old mother. Her mother had a history of three spontaneous abortions, two of which had preceded the birth of the patient. In view of this obstetric history, her mother was given hormone therapy in her second month of pregnancy (December 9, 1957). Treatment consisted of: U.S.P. desic. cated thyroid, 65 mg/day; 17-alpha-ethinyl-19nortestosterone (Fig. 1), 5 mg twice daily; and diethylstilbestrol 5 mg twice daily. On December 30, diethylstilbestrol was increased by 5 mg/day, once weekly, until a daily dose of 75 mg was achieved. The other hormones were continued at the original dosage. All therapy was discontinued in the thirty-fifth week of gestation. Two other developments of interest occurred during this pregnancy. Glycosuria was noted for the first time during the second month and was treated with a 1,500 calorie diet and 27 units of isophane (NPH) insulin daily. There was no antecedent history of maternal diabetes, and insulin was not required after termination of the pregnancy. The child's mother fell dun ing her fifth month of pregnancy, developing some spotty vaginal bleeding which ceased promptly after several days of bed rest. A full-term infant weighing 3,430 gm was delivered on August 4, 1958. The neonatal course was uneventful. There were no episodes of diarrhea, vomiting, fever or dehydration. The mother was apparently well and had no evidences of masculinization. Five siblings of the patient were well and apparently nor mal. Their ages ranged from 19 to 6 years (3 girls and 2 boys). There was no family history of endocrine disease and, specifically, none of abnormal genitalia. The patient was first seen as an outpatient at 2 months of age. Her development had been normal. There had been no progression in the size of her clitoris nor had she developed any other evidences of virilization. Her height was 61 cm (97th percentile). Her clitoris was 2.5 cm long and 1 cm in diameter (Fig. 2). There was no visible urethral orifice in the phallus. The labia majora were somewhat enlarged with some rugae. Gonadal masses were not palpated in the labia nor in the inguinal canals. The introitus appeared normal except for minimal posterior labioscrotal fusion. Abdominal masses were not felt. There was no pubic hair nor other evidence of virilization, except as noted. The remainder of the examination was normal. A smear of the buccal mucosa by the Barr tech nique revealed the nuclei of cells to be chro matin-positive, as is seen in females. She was admitted to Syracuse Memorial Hospital on November 17, 1958, at the age of @ months, for further studies. She had done well without any evidence of progression of viriization. The systolic blood pressure by palpation was 80 mm Hg. The weight of 7.03 kg was at the 75th percentile level, and the