The patient was the firstborn child to her 25-year-old mother and 32-year-old father, who were non-consanguineous. She was born by a normal vaginal delivery at term following a normal pregnancy. Her birth weight was 1700 g and she was 38 cm long. Interventricular communication of the membranous septum was diagnosed at birth, but surgery was not indicated. The patient presented with a delay in speech and walking, as well as poor school performance. She required a blood transfusion at age 4 because of severe anemia and thrombocytopenia, and she had undergone four orthopedic surgeries since the age of 14 to correct severe scoliosis.
At age 5, the patient underwent a genetic evaluation due to short stature and facial dysmorphism (a high prominent forehead, facial asymmetry, trigonocephaly, asymmetrically set ears, and retrognathia), which demonstrated RC11. Twenty-five metaphases were analyzed by GTG banding, which revealed the presence of RC11 in all segments and a loss of p15 and q25 in two segments (46,XX,r(11)(p15q25)). At that time, the results of a hormonal evaluation (somatotrophic and thyroid axes) were normal. At age 7, she presented with precocious puberty. At this time, hormonal blocking with a gonadotropin-releasing hormone analogue was initiated and continued from 8 to 11 years of age. She experienced menarche at age 12. These evaluations and treatments were performed at another institution.
At age 13, the patient underwent an investigation for hirsutism, which revealed normal levels of DHEA-S, androstenedione, testosterone, estradiol (E2), and thyroid-stimulating hormone (TSH). She had high levels of fasting plasma glucose ((FPG): 138 mg/dl; normal range (NR): 70-99)) and insulin (24.8 U/ml). A pelvic ultrasound examination was unremarkable, except for a borderline ovarian volume of 10 ml. The patient experienced significant weight gain after the age of 15.
At age 20, a laboratory evaluation in our unit showed normal levels of androstenedione (1.11 mmol/l; NR: 0.3-3.3), total testosterone (41 ng/dl; NR: 10-75), and DHEA-S (237.5 ng/ml; NR: 148-407) but dihydrotestosterone levels were elevated (437.5 pg/ml; NR: 23-368). TSH (1.34 muUI/ml; NR: 0.3-5.0) and prolactin (21.1 ng/ml; NR: <23) levels were normal. Cushing's syndrome and congenital adrenal hyperplasia were excluded by a normal overnight suppression 1 mg dexamethasone test (cortisol: 0.4 mug/dl; normal suppression <1.8) and normal levels of 17-hydroxyprogesterone (94 ng/dl; NR: <200) respectively. No signs or symptoms of acromegaly were present. She presented with high levels of FPG (138 mg/dl), HbA1c (7.3%; NR: <5.8%), insulin (26 U/ml), and she had insulin resistance, as assessed by the homeostatic assay (HOMA-IR; 9.82). There was mild thrombocytopenia with normal remaining hematological series. The lipid profile was normal.
Treatment was started with 1500 mg/day of metformin, 0.035 mg of ethinyl estradiol combined with cyproterone acetate (1 mg), 5 mg/day finasteride, and a hair lotion containing 17alpha-E2. Spironolactone was administered at an initial dose of 25 mg in the first month and was progressively increased up to 100 mg/day according to the tolerance of the patient.
After 6 months, the patient presented with adequate glycemic control (HbA1c: 5.3%), a weight reduction of 4.3 kg in 4 months, substantial improvement of alopecia, and a slow hair growth rate.