Correlation of Serum Follicular Stimulating Hormone ( FSH ) and Luteinizing Hornone ( LH ) as Measured by Radioimmunoassay in Disorders of Sexual Development

Serum FSH and LH levels in 104 patients with disorders of sexual development were determined by radioimmunoassay and compared with serum FSH and LH levels in 164 normal individuals. 32 of 35 gonadal dysgenesis patients (ages 4.8-18.9 yr) had serum FSH levels which were elevated above the range of normal for chronological age, and 19 had serum LH levels similarly elevated. All patients with elevated serum LH levels were 11 yr of age or older. However, 8 of 10 gonadal dysgenesis patients, ages 4.810.9 yr, had serum FSH levels elevated above the normal range. In accord with these observations was the finding that in normal girls, serum FSH levels may increase at an earlier age than do serum LH levels (FSH, 5-8 yr of age; LH, 9-10 yr of age). These data indicate that serum FSH determinations may be helpful in diagnosing gonadal dysgenesis during childhood. Serum gonadotropin levels within the range of normal for chronological age were found in 2 of 18 girls with idiopathic isosexual precocity. The other 16 had serum FSH levels elevated above the range of normal for chronological age, and 8 also had serum LH levels similarly elevated. In all instances serum FSH and LH levels were in the range expected for the stage of sexual development. In 35 boys, ages 13.1-17.8 yr, with delayed adolescence, serum gonadotropin levels correlated with stage of sexual development and, therefore, were often less than those expected for age. 8 patients with premature pubarche, 5 patients with premature thelarche, and 3 patients with adolescent gynecomastia had serum gonadotropin levels within the range of normal for chronological age. Dr. Blizzard is an Eudowood Professor of Pediatrics. Received for publication 15 April 1970 and in revised form 17 June 1970. INTRODUCTION Insight frequently is gained in understanding normal physiologic mechanisms-by studying developmental aberrations occurring in nature. This principle prompted us to correlate serum concentrations of FSH and LH with the clinical state in patients with various disorders of sexual development and to compare these values with those found in normal individuals at various ages and stages of sexual development. MATERIALS AND METHODS Serums from 104 patients with anomalous sexual development were obtained at the time of referral (1964-69) and stored at -20'C. Serums were also obtained from 93 normal females (ages 2-31 yr), 71 normal males (ages 5-18 yr), and 12 hypopituitary patients (ages 13-25 yr). The LH concentrations in some of these individuals were reported previously (1), as were the radioimmunoassay techniques for determining FSH and LH (2-9). Results are reported as milli International Units (mIU) of the second international reference preparation of human menopausal gonadotropin (2nd IRP-HMG). The standard deviation (SD) for FSH in multiple assays is ±1.1 mIU/ml at a level of 7.1 mIU and +3.4 mIU at 83.4 mIU/ml. The SD for LH in multiple assays is ±12 mIU at a level of 8 mIU/ml and 3.2 mIU at 35 mIU/ml. Bone ages were evaluated using the Greulich and Pyle standards (10). Height ages were determined from Wilkins' textbook (11). Staging of sexual development in males was according to the system of Tanner (12). Boys in stage I were completely prepubertal; those in stage II had enlargement of the scrotum and testis; those in stage III had enlargement of the penis; those in stage IV had further enlargement of the penis and scrotum and growth of the prostate; and those in stage V had genitalia adult in size. In females stage I was defined as completely prepubertal, stage II as the presence of glandular breast tissue only, stage III as the presence of both breast tissue and sexual hair, and stage IV as the presence of breast tissue, sexual hair, and menarche. The Journal of Clinical Investigation Volume 49 197