Inadequate testosterone suppression after medical and subsequent surgical castration in a patient with prostate cancer

Abstract

Androgen deprivation is a cornerstone in prostate cancer management. We present a 69-year-old man, with a poorly differentiated prostate cancer with skeletal and lymph node metastases. After medical and subsequent surgical castration serum testosterone concentrations remained inappropriately high (4.9 and 4.5 nmol/L; castration range < 0.5). For cancer staging a CT was performed which showed bilateral adrenal enlargement. Endocrine workup revealed elevated levels of adrenal androgens and adrenal precursors. Mutation analysis confirmed a non-classical 21-hydroxylase deficiency, that is, a mild form of congenital adrenal hyperplasia (CAH). To suppress adrenocorticotrophic hormone and the excess adrenal androgen secretion, treatment with hydrocortisone and prednisolone was started with success. Inadequate testosterone suppression after castration due to previously undiagnosed CAH has not previously been reported. Considering the estimated prevalence of 1% in selected populations, non-classical CAH should be considered when testosterone is not adequately suppressed after castration in men with prostate cancer.

Figure 1

(A) CT in transaxial plane and (C) coronal plane showing bilateral homogeneous adrenal enlargement (white arrows) in a 69-year-old man diagnosed with a non-classical congenital adrenal hyperplasia. For comparison, normal adrenal glands are shown in (B) and (D).

Figure 2

Schematic illustration of adrenal steroid synthesis. In patients with partial 21-hydroxylase deficiency there is an accumulation of cortisol precursors. The precursors are diverted to biosynthesis of adrenal androgens, which are partially converted to testosterone in peripheral tissues. The accumulation of the precursors is further augmented by a compensatory increase of pituitary adrenocorticotrophic hormone secretion required for sufficient cortisol production.