Keywords

1 Epidemiology and Clinical Presentation

  • Pituitary adenomas that hypersecrete functional follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH) are extremely rare.

  • Although many nonfunctioning pituitary adenomas demonstrate positive immunoreactivity for FSH and LH, the overwhelming majority of these tumors are clinically silent [1], as discussed previously in chapter 10.

  • In women, functional gonadotroph adenomas may cause ovarian stimulation syndrome with enlarged ovaries, pelvic pain, galactorrhea, and/or menstrual abnormalities [2, 3]. Levels of circulating estradiol are typically elevated.

  • In men, excess levels of serum testosterone with testicular enlargement have been reported.

  • In boys, precocious puberty has been reported.

  • Functioning gonadotroph adenomas are often plurihormonal tumors, which may co-secrete TSH, prolactin, and/or GH.

  • Exacerbation of disease has been reported with administration of gonadotropin-releasing hormone agonists such as leuprolide [4].

2 Diagnosis

2.1 Imaging

  • Imaging characteristics of gonadotroph adenomas are similar to those described for other functioning adenomas.

2.2 Histopathology

  • Adenomas may demonstrate immunoreactivity for FSH, LH, or both, and invariably for the gonadotrophic transcription factor SF-1.

  • Many of these adenomas will also demonstrate immunoreactivity for the alpha-subunit (Fig. 16.1) [5].

    Fig. 16.1
    figure 1figure 1

    Gonadotropin-secreting adenoma. Gonadotropin-secreting adenomas or gonadotroph cell adenomas are characteristically chromophobic tumors (a) with diverse histopathological arrangements. Tumors may have papillary arrangements (b), nested arrangements (c), and focal oncocytic appearance (d). Gonadotroph adenomas show variable immunoreactivity for follicle-stimulating hormone (FSH) (e), luteinizing hormone (LH) (f), and the alpha-subunit of glycoproteins (g). Gonadotroph cell adenomas are mostly composed of well-differentiated, elongated cells with a degree of cellular polarity at the ultrastructure level. Secretory granules are small and tend to be located at the periphery of the cytoplasm (h)

    Full size image

  • Electron microscopy may demonstrate different structural features in the adenomas of men versus those of women. Gonadotroph adenomas in men resemble null-cell adenomas, with poorly or moderately developed cytoplasmic organelles. In women, tumors tend to be well differentiated, with distinctive vesicular dilatation of the Golgi complex (“honeycomb Golgi”) [6].

3 Clinical Management

  • As with most functional pituitary adenomas, transsphenoidal surgical resection remains the mainstay of treatment.

  • Dopamine agonist therapy (cabergoline or bromocriptine) has been reported to be an effective medical treatment for a subset of these tumors [7].

  • Successful treatment with a gonadotropin-releasing hormone antagonist also has been reported [8].

  • Resolution of ovarian hyperstimulation, reduction of ovary size, and successful pregnancy have been reported following effective treatment.

  • Gonadotropin-releasing hormone agonists should be avoided in these patients, as they may promote tumor growth [9, 10].