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Stikkelbroeck et al. (2001) investigated the prevalence of testicular tumors in 17 adolescent and adult male patients with CAH aged 16 to 40 years. In 16 of 17 patients, one or more testicular tumors ranging in maximal length from to cm were found on ultrasonography. In 6 patients, the testicular tumors were palpable. Undertreatment, defined as the presence of a salivary androstenedione level above the upper reference morning level, was found in 5 of 17 patients at the time of investigation. The other 12 patients were treated adequately or even overtreated at the time of investigation. Nevertheless, 11 of these 12 patients showed testicular tumors on ultrasonography. Tumor size was significantly larger in patients who were heterozygous or homozygous for deletion or conversion of the CYP21 gene than in patients who did not have this genotype. Impairment of Leydig cell function as manifested by decreased plasma levels of testosterone was found in 6 of 17 patients. Semen analysis in 11 patients revealed azoospermia in 3 patients and poor semen quality in 4 patients. The authors concluded that, when carefully sought for, testicular adrenal rest tumors are frequently present in adolescent and adult males with CAH and are often accompanied by impaired spermatogenesis and Leydig cell failure.

Interleukin-6 also is known to activate the HPA axis by stimulating both the CRH - and the AVP -secreting neurons of the paraventricular nucleus of the hypothalamus, and their terminals at the median eminence, the cotricotrophs of the anterior pituitary, and the cortisol-secreting adrenal cells in rats. In the latter it acts through specific receptors expressed mainly in the zona fasciculata and reticularis, but also with lower density in the zona glomerulosa (46,47). The ability of IL-6 to stimulate glucocorticoids, mineralocorticoids, and androgens suggests that this cytokine might have a role in coordinating the response of all adrenocortical zones. Its secretion is regulated by different substances, such as CRH, ACTH, angiotensin II, or immune products such as IL-1/ indicating that IL-6 may play a major role in the interaction of the adrenal function with the immune system (48).

Note: In some animals with signs of hyperadrenocorticism, post-stimulation cortisol levels are not increased but one or more sex hormones (which can cause similar signs as cortisol when present in excess) may be increased. The hormones most likely to increase are: progesterone and/or 17-hydroxyprogesterone and/or androstenedione. Some are now advocating the measurement of all of these sex steroid hormones levels before and after stimulation with ACTH (if results of standard stimulation of cortisol levels are inconclusive or negative).
(Reference: JAVMA 226 (February 2005 ): pp556)

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