ESPE Abstracts

Objective: to evaluate combination replacement therapy (CRT) with rFSH and hCG of hypogonadotropic hypogonadism (HH) in boys appropriateness and effectiveness.

Materials: 1 boy with isolated HH (№1) and 2 boys (№2,3) with HH caused by hypopituitarism (HP) included. Antropometric data, Тanner; testosterone (T), LH, FSH, inhibin B, anti-Mullerian hormone (AMH), testicular volumes (TV), bone age (BA) evaluated in all patients. GnRH agonist (0.1 mg), hCG test (2000/m²), brain MRI with contrast, molecular genetics provided. Regimens were the following: №1,2 received 3 testosterone injections 100 mg/month before CRT. №3 received 12 hCG injections 1500 IU/week. Then all patients received rFSH (75 IU/week) and hCG 1000/1500/3000 IU/week. Follow-up was 14.3±6.4 months.

Results: Before puberty HH was diagnosed in noone. №1 diagnosed with HH in 16 years due to complaints. №2 diagnosed with central hypothyroidism (CHT) in 11.9, growth hormone deficiency (GHD) and central hypocorticism (CHC) in 12.3. №3 diagnosed with CHT in 2.9 years, GHD in 3.4, CHC in 8. №3 had PROP-1 mutation diagnosed in 13.3. Before CRT №1 was 16-year-old boy, 174 cm (0.25SD, TH correction 1.01 SD), Tanner 1, TV 1.07 cm³ (<2nd perc), T 1.05nmol/l, inhibin B 50.2 pg/ml, AMH 56.04 ng/ml, BA 14 years (-2.1SD). After 24 months of CRT boy was 18-year-old, 188 cm (2 SD,TH correction 1.43 SD), Tanner 5, TV 9.14 (15th perc), Т 16.05nmol/l, inhibin B153.1 pg/ml, AMH 10.56 ng/ml, BA 15.5 years (>-2 SD). Before CRT №2 was 16.3-year-old, 172.5 cm (-0.24 SD, TH correction 0.9 SD, Tanner 1, TV 3,6 (<2nd perc), Т 0.94 nmol/l, inhibin В 114.5 pg/ml, AMH 30.54 ng/ml, BA 13.5 years (-2.6 SD). After 21 months of CRT boy was 17.9-year-old, 184.5 cm tall (1.48,TH correction 0.83 SD), Tanner 4-5, TV 7 cm³ (3rd perc), Т 20.3 nmol/ml, inhibin B 131.8 pg/ml, AMH 6.01 ng/ml, BA no change. Before CRT №3 was 15.3 years, 165 cm (-0.68SD, TH correction -1.03 SD), Тanner 1, TV 1.5 cm³ (<2nd perc), Т <0.087 nmol/l, inhibin В 22.3 pg/ml, AMH 22.17 ng/ml, BA 14 years (-0.94 SD). After 13 months of CRT boy was 16.3-year-old, 174.5cm tall (0.15 SD, TH correction 0.27 SD), Tanner 4, TV 4.5 cm³ (<2nd perc), Т 18nmol/l, inhibin B 152 pg/ml, AMH 17.58 ng/ml, BA 14.5 years (-1.84 SD).

Conclusion: Late CRT initiation observed in case of isolated HH and in hypopituitarism which is due to the absence of micropenis, cryptorchidism in all the patients. hCG was effective due to secondary sex characteristics development and pubertal testosterone and decreased AMH. rFSH was effective due to pubertal TV, increased inhibin B. HH caused by HP must be diagnosed by inhibin B and AMH. CRT must be initiated promptly.