Case report: Androgen-secreting adrenocortical tumors in eight cats

Abstract

Urine marking, aggression, and other behavioral concerns are common reasons for cat owners to seek veterinary care. Empiric treatment for lower urinary tract disease or primary behavior disorders are commonly pursued, especially in those cases with normal routine laboratory evaluations. Herein, we report the clinicopathologic findings in eight sexually altered cats that were diagnosed with androgen-secreting adrenocortical tumors. Nearly all cats (n = 7) initially were evaluated for inappropriate urination and pungent urine, with additional behavioral concerns including aggression (n = 3) and excess vocalization (n = 4) commonly reported. Penile barbs (n = 5) were identified in all five male cats, and an enlarged clitoris was observed in one female cat. Testing of serum androgen concentrations revealed abnormally high androstenedione (n = 1) or testosterone (n = 7) concentrations. In the five cases with available adrenal tissue, histopathologic evaluation identified either an adrenocortical adenoma (n = 3) or adrenocortical carcinoma (n = 2). Hormonal abnormalities resolved and clinical signs improved in the four cats that underwent surgical adrenalectomy, with each of these cats surviving >1 year. However, clinical signs were minimally impacted with medical treatments, including one cat in which trilostane treatment failed to improve clinical signs or testosterone concentrations. This collection of cases underscores the importance of a detailed physical examination as well as the consideration of endocrine disturbances in cats undergoing evaluation for inappropriate urination or aggression. Furthermore, this report adds to the growing body of evidence that sex-hormone secreting adrenal tumors in cats may be an under-recognized syndrome.

Keywords: adrenal; aggression; androstenedione; behavior; periuria; testosterone.

Figure 1

Images of the penis in a 7-year-old neutered male domestic shorthair cat (case 1) that underwent surgical adrenalectomy for a androstenedione-secreting adrenal tumor. Serum androstenedione concentration prior to surgery was 3.2 nmol/L (RI 0.35–2.1 nmol/L), which decreased to 0.35 nmol/L 3 weeks after surgery. (A) Penile barbs are apparent immediately prior to surgery. (B) The penile barbs had substantially regressed 2 weeks post-adrenalectomy.

Figure 2

Immunohistochemical labeling showing expression (red chromagen deposit) of steroidogenic enzymes in an androgen-secreting adrenal mass (A, C, E) of a cat, and in normal feline adrenal cortex (B, D, F). The expression of 17α-hydroxylase cytochrome P450 [P450c17; (A, B)], cytochrome b5 [b5; (C, D)] and cytochrome P450 21-hydroxylase [P450c21; (E, F)] are shown. (A) The inset shows the entire mass, surrounded by a compressed band of normal cortex (small arrows). Note P450c17 is strongly expressed in the developing tumor (block arrows) but is undetectable in the cortex around it (small arrows). (B) P450c17 expression is localized in the zona fasciculata (ZF) but not the glomerulosa (ZG) of a normal feline adrenal cortex. (C) Note b5 expression in lipid-laden tumor cells at the periphery of the mass. (D) Expression of b5 is detected in the ZG of normal feline adrenal cortex. (E) Expression of P450c21 is strong throughout the compressed cortex (small arrows) surrounding the tumor, which lacks detectable P450c21 expression by comparison (block arrow). (F) Note, the expression of P450c21 also extends throughout all cortical zones to the medulla (M) of the normal feline adrenal cortex.

Figure 3

Hematoxylin and eosin staining and immunohistochemical labeling for met-enkephalin and GATA-4 from an androgen-secreting adrenal mass in a cat. (A) [4×] Hematoxylin and eosin stain of adrenocortical carcinoma (asterisk) compressing the adrenal medulla (arrowhead), and non-neoplastic adrenal cortex (×) (B) 100× magnification of the same region. (C) [10×] Medullary chromaffin cells expressing met-enkephalin. The neoplastic cells and non-neoplastic adrenal cortex are negative. (D) [20×] Approximately 60% of the neoplastic cells exhibit nuclear labeling for GATA-4 (arrows). The medullary chromaffin cells and non-neoplastic adrenal cortical cells are negative.