Empty Sella (ES) is a radiological diagnosis characterized by the expansile dilation of the sella turcica, resulting in pituitary compression and partial or complete filling with cerebrospinal fluid (CSF). ES has a prevalence rate of 8% to 35% in the general population, predominantly observed in women aged 30 to 40 years [1]. ES is classified as primary empty sella (PES) and secondary empty sella (SES). The prevalence of hypopituitarism due to ES is estimated to range between 19 and 68% [2]. The growth hormone axis is most commonly affected, closely followed by the gonadotropic axis. Additionally, sporadic cases of hyperprolactinemia have also been documented [3, 4].

Hypogonadotropic hypogonadism (HH) is a disorder characterized by impaired testicular function caused by lesions in the hypothalamus or pituitary gland [5]. The presence of HH not only causes significant mental and psychological distress to patient and their families but also imposes a substantial burden on society. Androgen replacement therapy is an effective approach to maintaining male sexual function and secondary sexual characteristics [6]. Moreover, for individuals with reproductive aspirations, gonadotropin replacement has the potential to promote testicular growth, stimulate spermatogenesis, improve sperm motility, and facilitate fertility in selected male patient, offering hope for the realization of parenthood [5].

This study presents a case report of a male patient diagnosed with secondary HH and ES who underwent treatment with micropump pulse gonadotropin-releasing hormone (GnRH), resulting in a favorable therapeutic outcome. Additionally, a comprehensive review of the relevant literature was undertaken, comparing the findings with conventional approaches to HH management, providing valuable insights into the diagnosis and treatment of this condition.

A 45-year-old male was referred to our department in June 2021 due to a 3-month history of fatigue and decreased libido. The patient has a history of successful tuberculosis treatment and no other medical conditions. He has a smoking history of over 20 years, with a daily consumption of 15–20 cigarettes, and has never tried to quit. The patient has been married for over 20 years, but tragically lost his only son. He does not have any other children, and there is no significant family medical history.

Three months prior to admission, the patient experienced unexplained fatigue and hyposexuality, but unfortunately, his symptoms were not appropriately addressed, and no further treatment was provided. One month prior to admission, the patient developed tender bilateral breast enlargement without lactation. An MRI conducted at a local hospital revealed an ES, bilateral ethmoid sinusitis, and a cyst in the left maxillary sinus. Additionally, the ultrasound of the male reproductive system detected no abnormalities in the bilateral testicles, while a breast ultrasound confirmed gynecomastia. The results of visual acuity and visual field tests were within normal range. Sex hormone analysis showed elevated levels of prolactin (PRL) at 452.6 pmol/L (55.97–278.35 pmol/L), estradiol (E2) at 55.10 pg/mL (< 20–47 pg/mL), but T levels dropped to 0.58 noml/L (6.07–27.10 noml/L). The local hospital diagnosed the patient with "Empty Sella, Hyperprolactinemia" and prescribed Bromocriptine Mesylate tablets 2.5 mg once daily and Rubi tablets (a traditional Chinese medicine for promoting blood circulation and dispersing knot) 5 tablets thrice daily for a month, but no significant improvement in the mentioned symptoms were observed. Subsequently, the patient sought additional treatment at our hospital and was admitted with a diagnosis of "Empty Sella, Hypogonadism".

On admission, the patient underwent a physical examination that yielded the following measurements: height of 176 cm, weight of 69 kg, body temperature of 36.3 °C, pulse rate of 84 bpm, respiratory rate of 19 breaths per minute, and blood pressure of 113/81 mmHg. The patient had a beard and normal distribution of body hair, including abundant and dark underarm hair. Adam's apple was visible, and there was no sign of thyroid enlargement.

Reexamination of the sellar area by MRI in our hospital after admission revealed ES, the sella was not enlarged and the bottom of the sella was not sunken. The pituitary gland in the sellar region was thin, with a height of about 1.45 mm. The pituitary gland showed obvious uniform enhancement on enhanced scan. The rest of the sellar region was filled with CSF signal shadow (Fig. 1). Bilateral color Doppler ultrasound revealed bilateral development of the mammary glands. Additionally, the color Doppler scan of the male reproductive system revealed that the right testicle measured 3.9 cm in length and 1.8 cm in thickness. The right epididymal head had a thickness of 0.66 cm. Similarly, the left testicle measured 4.0 cm in length and 1.83 cm in thickness, with the left epididymal head having a thickness of 0.67 cm. Ultrasonography revealed no obvious abnormalities in the bilateral adrenal glands.

Magnetic resonance imaging (MRI) revealed a partially empty sella (arrow). A. Sagittal T1W. B. Coronal T1W

Endocrine function tests revealed decreased FSH levels of 0.03 mIU/mL (1.27–19.26 mIU/mL), LH 0.02 mIU/mL (1.24–8.62 mIU/mL), and T 0.72 nmol/L (Table 1). Other endocrine hormone levels were within the normal range: PRL 4.69 ng/mL (2.64–13.13 ng/mL), E2 11.00 pg/mL (<20–47 pg/mL), progesterone (P) 0.81 pg/ml (0.14–2.06), sex hormone-binding globulin (SBHG) 133.0 nmol/L (34.3–147 nmol/L), dehydroepiandrosterone (DHEA) 208.7ug/dL (139.7–484.4 ug/dL); thyroid-stimulating hormone (TSH) 1.23 mU/L (0.27–4.2 mIU/L), free triiodothyronine (FT3) 4.59 pmol/L (3.1–6.89 pmol/L), and free thyroxine (FT4) 13.49 pmol/L (11–22 pmol/L); adrenocorticotropic hormone (ACTH) 68.47 ng/mL (7.2–63.3 ng/L), cortisol 606.3 nmol/L (66–579.4 nmol/L); growth hormone (GH) 1.35ug/L (0–8 ug/L) and insulin-like growth factor-1 (IGF-1) 116 ng/mL (115–307 ng/mL). Blood count, blood glucose, glycosylated hemoglobin, liver function, and renal function were all normal. The GnRH stimulation test (gonarelin 100 mg i.v.) was successfully performed: The peak LH value was more than three times the baseline value (0.11 IU/L to 0.46 IU/L), with a peak at 60 min. Similarly, peak FSH was more than double baseline (0.05 to 0.12 IU/L), peaking at 120 min. Human chorionic gonadotropin (HCG) stimulation test (HCG 2000U i.m.) was performed: The peak level of T increased to more than twice the value at baseline (0.5 ng/mL to 8.4 ng/mL) and peaked at 72 h. Semen analysis was performed: The sperm concentration (million/mL) was measured as 232.3 (normal: ≥ 15), the forward motile sperm rate (%) was recorded as 0 (normal: ≥ 32%), the immobile sperm rate (%) was 99.9, and the sperm activity rate (%) was found to be 0.1 (normal: ≥ 40%, Fig. 2). And the majority of sperm are in a dormant state (Fig. 3A).

Sperm motility rate and semen concentration results. A. sperm concentration, B. the forward motile sperm rate (%), C. the immobile sperm rate (%), D. the sperm activity rate (%)

The status of progressive spermatozoa (purple), nonprogressive spermatozoa (red) and immobile sperm (yellow). A. pre-treatment, B. 3 months post-treatment, C. 6 months post-treatment

Diagnostic considerations were made based on these findings. The patient was ultimately diagnosed with ES and hypogonadotropic hypogonadism. The patient's desire for a possible second birth prompted a consultation with a neurosurgeon to assess the feasibility of the surgical intervention, despite its limited potential benefit. Consequently, the patient was prescribed oral tamoxifen at a daily dosage of 20 mg to reduce breast development, and received pulsed gonadotropin (Maanshan FengYuan Pharmaceutical Co., LTD., Anhui, China) infusion using a micropump (Shanghai Minimally Invasive Life Technology Co., LTD., Shanghai, China). The micropump was administered a 10 μg dose within 1 min every 90 min.

After 1 month of treatment initiation, LH, FSH, and T levels returned to normal (Table 1), accompanied by a gradual improvement in fatigue and hyposexuality symptoms. Following 3 months of treatment, tamoxifen was discontinued, and the semen analysis displayed a sperm concentration of 191.1 million/ml, along with a forward motile sperm rate of 12.9%, an immobile sperm rate of 71%, and a motile sperm rate of 29% (Fig. 2). And Partial immobile sperm transition to progressive sperm (Fig. 3B). The treatment with a GnRH pulse (10 ug/90 min) was continued. During the six-month follow-up, semen analysis demonstrated additional improvements, including a sperm concentration of 233.8 million/ml; a forward motility rate of 43.7%, an immobile sperm rate of 20.1%, and a motility rate of 79.9% (Fig. 2). There is a significant decrease in the proportion of immobile sperm and a significant increase in the proportion of progressive sperm (Fig. 3C). Notably, normal sperm count did not change significantly. The GnRH pulse treatment (10 μg/90 min) was continued. The patient's wife successfully conceived naturally after 9 months of treatment. Subsequently, after 10 months of treatment, the GnRH pump was discontinued, and maintenance androgen replacement therapy was initiated.