Gonadotropin Suppression for 7 Years After a Single Histrelin Implant for Precocious Puberty

Douglas Villalta; Jose B. Quintos


J Endo Soc. 2022;6(2) 

In This Article

Case Report

A boy aged 10 years and 3 months presented to the endocrine clinic with precocious puberty and advanced bone age. The family reported he had pubic hair development at 10 years. However, his pediatrician was concerned about an adult serum testosterone level. He denied vomiting, headaches, fatigue, blurry vision, polydipsia, polyuria, cold intolerance, heat intolerance, constipation, abdominal pain, diarrhea. His blood pressure was 115/65 mmHg, heart rate was 80 bpm, weight was 35.2 kg (66th percentile). His height was 141.5 cm (62nd percentile) and his height velocity was 10.7 cm/year. His mid-parental height was 175.3 cm. Body mass index (BMI) was 17.58 kg/m[2] (65th percentile). Bone age was read as 11 years 6 months at a chronological age of 9 years and 11 months. Physical exam showed Tanner 3 pubic hair, Tanner 4 genitalia, and testicular volume of 15 mL. Screening laboratory investigation revealed a random luteinizing hormone (LH) level of 9.4 mIU/mL, random follicle-stimulating hormone (FSH) of 16.3 mIU/mL, prolactin 10 ng/mL, dehydroepiandrosterone sulfate (DHEAS) 127 mcg/dL, 17-OHP 217 ng/dL, and testosterone 628 ng/dL. Brain magnetic resonance imaging was unremarkable and did not show any pituitary lesions. He was initially started on a once-monthly 11.25 mg Lupron-Depot injection for 4 months before receiving a single 50 mg histrelin implant. Laboratory results 5 months after gonadotropin-releasing hormone (GnRH) suppression showed a random LH level of 0.2 mIU/mL, random FSH 0.1 mIU/mL, and testosterone 5 ng/dL. Physical exam showed Tanner 3 pubic hair, Tanner 4 genitalia, and testicular volumes of 12 mL. Growth velocity at that time was 11.3 cm/year. Six months postimplant he had a growth velocity of 2.2 cm/year. At the age of 11 years, he was started on medical marijuana for treatment of refractory seizures. At 11 years and 10 months, his bone age was 13 years. The testicular volume at this time was 12 mL bilaterally. Laboratory results showed continued pubertal suppression with random LH of 0.16 mIU/mL, random FSH 0.16 mIU/mL, and testosterone 5 ng/dL.

The patient and family were lost to follow-up for 5 years, returning at the age 17 years and 6 months because the mother was concerned the patient had not yet developed facial or chest hair and noticed breast tissue. Height at this time was 167.8 cm (13th percentile), weight was 63.6 kg (40th percentile), BMI was 22.59 kg/m2 (63rd percentile), and growth velocity was 2.5 cm/year. Physical examination showed Tanner 3 to 4 glandular breasts, Tanner 3 pubic hair, 8 mL right testicle and 10 mL left testicle, Tanner 4 genitalia, and moderate axillary hair. Laboratory results at this time showed random LH 0.10 IU/mL, random FSH 0.34 IU/mL, testosterone 8 ng/dL. He has normal 46 XY karyotype. A bone age x-ray was done after the visit, which showed a bone age of 14 years at a chronological age 17 years and 7 months. The histrelin implant was removed during a same day procedure under general anesthesia. The implant was removed in portions and complete removal was confirmed with ultrasound. Laboratory results obtained 4 months after removal of the implant showed a random LH of 5.6 IU/mL, random FSH 4.3 IU/mL, and testosterone 506 ng/dL. At 4 months after removal of histrelin implant, the mother noted facial hair development. Physical exam showed Tanner 3 glandular breasts, Tanner 4 pubic hair, Tanner 4 genitalia, 10 mL right testicle and 12 mL left testicle. Height was 170.4 cm (21st percentile), weight 64.6 kg (39th percentile), BMI 22.25 (53rd percentile), and growth velocity was 5.5 cm/year. Gynecomastia remained significant 4 months after removal of implant and despite pubertal hormone levels.