Macroorchidism and Panhypopituitarism: Two Different Forms of Presentation of FSH-Secreting Pituitary Adenomas in Adolescence

Abstract

Background: FSH-secreting pituitary adenomas are extremely rare in children and are seldom associated with clinical manifestations of high serum gonadotrophin levels. Thus, most patients have a late presentation, usually as macroadenomas. Case Reports: Two different clinical forms of presentation of FSH-secreting pituitary adenomas are reported: one in a 12-year-old boy with macroorchidism due to a pituitary microadenoma, probably FSH-secreting, and the other in a 15-year-old boy with panhypopituitarism due to an FSH-producing macroadenoma. Both patients presented slightly high or high FSH with low LH and high inhibin B levels. In the first case, the microadenoma was treated medically with cabergoline, which failed to reduce FSH and inhibin B levels. No radiological progression has been observed despite increasing testicular volume. In the second case, surgery was performed on the macroadenoma, leading to a decrease in FSH and inhibin B levels. The patient developed severe hypothalamic obesity and is currently under treatment with somatostatin. Conclusions: FSH-secreting pituitary tumors have an extremely variable clinical expression. The discrepancy between normal or slightly increased FSH and low LH values, together with high inhibin B levels, strongly suggests FSH hypersecretion which should be studied.

The syndrome of central hypothyroidism and macroorchidism: IGSF1 controls TRHR and FSHB expression by differential modulation of pituitary TGFβ and Activin pathways

“…Both processes involve TSH beta ( TSHB ) gene expression and TSH glycosylation respectively, and both are known to be dependent on TRHR activation2021. On the other hand, the patient presented with excessive FSH secretion as a neonate which, interestingly, resulted in macroorchidism, as happens in FSH-secreting pituitary adenomas252627. FSH secretion is critically regulated by testicular inhibin B through inhibition of the stimulatory activin-Smad signaling pathway, and IGSF1 was proposed as a putative inhibin B receptor7.…”

“…5B) based on the pituitary de-repression of FSHB transcription at pituitary gonadotropes and the postnatal over-secretion of FSH at mini-puberty, which may lead to premature proliferation of testicular Sertoli cells49, a known cause for macroorchidism in children and adults with FSH-secreting pituitary adenomas252627. These findings are relevant since all IGSF1-deficient patients so far identified with macroorchidism were adolescents and adults4, which has prevented the elucidation of the precise chronology for testicular growth in this disorder.…”

Paediatric Pituitary Adenomas: A Decade of Change

“…Most are FSH-secreting adenomas [2,57]. The diagnosis is typically delayed until the appearance of symptoms related to tumour mass or pituitary hormone deficiency.…”

“…The diagnosis is typically delayed until the appearance of symptoms related to tumour mass or pituitary hormone deficiency. Patients may present with macro-orchidism, ovarian cysts or precocious puberty due to FSH hyperstimulation [2,57]. Diagnosis is based on increased levels of FSH and inhibin B, with normal or low luteinising hormone and testosterone, an increased FSH response to gonadotropin-releasing hormone stimulation, detection of a pituitary mass on MRI, and immunohistochemical confirmation of the surgical specimen [57].…”

Secondary Polycythemia Attributed To An Incidentally Discovered Luteinizing Hormone–Secreting Pituitary Adenoma: A Case Report

“…Surgical removal of the adenoma remains the optimal approach, and when successful, it leads to restoration of normal gonadotropin secretion. Treatment with dopamine agonists, long-acting somatostatin analogues, and GnRH agonists and antagonists has been used with inconsistent results and is thus not recommended as a primary therapeutic approach (13). Occasional case reports have shown that dopamine agonists may reduce autonomous FSH secretion and help complete a pregnancy or improve ovarian hyperstimulation syndrome (14,15).…”