Early Treatment of Hypothalamic Hypogonadism With LH-RH Analog Improved the Long-Term Prognosis of Hypogonadism of Adult-Onset Craniopharyngioma

Abstract

Object: Craniopharyngiomas frequently grow on the cisternal surface of the hypothalamic region. The survival rate for childhood craniopharyngioma has been improving with more long-term survivors. Long-term survivors of childhood craniopharyngioma suffer a number of impairments, which include visual loss, endocrinopathy, hypothalamic dysfunction, cerebrovascular problems, neurologic and neurocognitive dysfunction. GnRH neurons in hypothalamus that send axons to portal blood system in median eminence fire in coordinated, repetitive, episodic manner, producing distinct pulses of GnRH in the portal blood system. In 2001, we experienced the case of hypothalamic hypogonadism after the radical surgery of craniopharyngioma located in the right basal ganglia and hypothalamus. During the operation, pituitary gland and stalk were preserved. The patient had developed panhypopituitarism and hypothalamic hypogonadism after transcranial surgery. The diagnosis of oligospermia and asthenospermia was made. We hypothesized that the hypogonadism was due to the lack of distinct pulses of GnRH after the surgery. The aim of this program was to demonstrate the efficacy of the pulsatile subcutaneous LH-RH therapy for the recovery of gonadal function from hypothalamic hypogonadism and to observe the long-term prognosis after recovery.Method: After a diagnosis of hypothalamic hypogonadism, low dose LH-RH treatment was given to a 29-year-old male with small portable automatically-timed infusion pump, connected to a subcutaneous (s.c.) catheter. Gonadorelin acetate was prepared to the concentration of 0.8mg/ml. Sixteen micrograms of LH-RH s.c. was given every 120 min. Serum levels of gonadotropin and testosterone were monitored. The treatment was continued until his gonadal function normalized. Long-term follow up was continued after low dose LH-RH treatment.Result: After the six months of pulsatile LH-RH treatment, serum level of testosterone turned normal. Then the treatment was paused in 2003. His wife became pregnant with in-vitro fertilization (IVF) in 2007 and gave birth in 2008. Moreover, his wife became pregnant naturally without IVF in 2009 and gave birth in 2010, suggesting the recovery from oligospermia and asthenospermia of her husband. Early recovery from hypothalamic hypogonadism maintained normal gonadal function in 2020.Clinical Lessons: We demonstrated a case of successful treatment of the hypothalamic hypogonadism after the surgery of craniopharyngioma. The pulsatile subcutaneous LH-RH therapy is efficacious for the case with the lack of the distinct pulses of GnRH after radical surgery of craniopharyngioma. Early treatment of hypothalamic hypogonadism with LH-RH analog improved the long-term prognosis of hypogonadism of adult-onset craniopharyngioma.