Testosterone-Related Exacerbation of a Prolactin-Producing Macroadenoma: Possible Role for Estrogen

Abstract

Men with PRL-producing macroadenomas often present with hypogonadism and impotence. This report documents exacerbation of a PRL-secreting tumor after two separate 200-mg testosterone enanthate (T) injections despite continued bromocriptine (BRC) therapy. A 37-yr-old man with a 60-mm invasive tumor and a serum PRL level of 13,969 +/- 332 ng/ml (mean +/- SD) responded to BRC therapy with rapid disappearance of visual field defect, headache, and facial pain as well as decrease in serum PRL to 5,103 +/- 1,446 ng/ml. T injection was followed by severe headache, facial pain, and increase in PRL to 13,471 ng/ml. Visual field deterioration and increased tumor size (height, 40-43 mm) by computed tomography were documented. A relationship between T injection and exacerbation of the prolactinoma was not recognized until after a second T injection 3 months later. After that therapy, baseline PRL increased from 6,900 to 12,995 ng/ml. The hypothesis that T was aromatized to estradiol, directly stimulating lactotrophs, was supported by an increase in serum estradiol from 24 to 51 pg/ml after the second T injection. Although T treatment is accepted as appropriate therapy for hypogonadism in men with prolactinomas, it may not only interfere with the response of the tumor to BRC therapy, but even stimulate tumor growth and secretion.

Effects of Gonadal Steroids on the Growth of Human Pituitary Adenomas in vitro

“…This strongly indicates that T was not metabolized to E2 by cultured pituitary tumor cells. This also supports the hypothesis that the growth-stimulating effect observed in a macroprolactinoma following T therapy [19] was due to aromatization of T into E2 in 362 Caronti et al Gonadal Steroids and Pituitary Adenomas peripheral tissues, rather than to aromatization in situ or to a direct stimulating effect of T on the pituitary tumor cell growth. We conclude that androgens, as previously described for estrogens and Pg [10], can sig nificantly modulate the growth of human pi tuitary tumors in vitro and that this effect is receptor-mediated and common to various pi tuitary tumor cell types.…”

“…These findings raise interesting hypotheses on the possible in fluence of sex steroids on the evolution of pituitary tumors: in fact, the alterations of gonadal function which are commonly related to the presence of the pituitary tumor itself might in turn influence tumor evolution. Be cause androgens and estrogens have opposite effects on pituitary adenoma cell prolifera tion, the possible in vivo aromatization of T into E2 by peripheral tissues should also be kept in mind when substitutive androgen therapy is thought necessary for patients pre senting with pituitary tumors, especially pro lactinomas [19],…”

“…Although direct pituitary effects of androgens are supported by the presence of androgen receptor (AR) in the normal pitu itary gland, particularly in the gonadotroph cells [ 17] and in human pituitary tumors [ 18], little is known as to whether androgens can regulate the growth of pituitary tumors. An drogen therapy has been reported to stimulate the growth and hormonal secretion in one case of macroprolactinoma, inducing a signif icant worsening of clinical symptoms [19]. Whether those stimulating effects were relat ed to androgen therapy itself or to indirect estrogenic effects resulting from either periph eral or in situ aromatization of T into E2 is still unclear.…”

Pituitary tumors: pathophysiology, clinical manifestations and management.

“…In addition, symptoms of hypogonadism are expected to improve in the majority of men with prolactinomas, with therapy. It is therefore recommended to withhold testosterone replacement in men with prolactinomas and hypogonadism until prolactin levels are normalized (Prior et al 1987).…”

Correlations between Expression of Estrogen and Androgen Receptors and the Clinical Characteristics of Prolactinoma

“…The serum estradiol also climbed up from 24 to 51 pg/mL soon. They explained that this phenomenon was a result of testosterone having been aromatized to estradiol which in turn directly stimulated the lactrophs, which leading to reappearance of hyperprolactineamia and expansion of the tumor size and its mass effect symptoms [5] .…”