17-ketosteroids and trilostane

Here we report a case of a renin-producing adrenocortical carcinoma. A 57-year-old woman was referred to our hospital complaining of thirst and generalized muscle weakness. She was diagnosed as being hypertensive and diabetic with associated hypokalemia and she had a hard elastic mass with a diameter of 10 cm on the left side of her neck. An abdominal computed tomography scan revealed a suprarenal mass on the left side (8.5 x 8 x 6.5 cm). Endocrinological examination demonstrated a marked elevation in the patient's serum glucocorticoid and sex steroid hormones as well as plasma renin activity. Histological examination of a sample taken from the neck mass revealed a metastasis from an adrenal carcinoma, which was stained positively with antibodies against cytochrome P450 and renin, establishing the diagnosis of a renin-producing adrenocortical carcinoma. Trilostane was effective in reducing serum cortisol levels, but mitotane was ineffective.

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; 3-Hydroxysteroid Dehydrogenases; Adrenal Cortex Neoplasms; Biopsy, Needle; Catecholamines; Cytochrome P-450 Enzyme System; Dihydrotestosterone; Enzyme Inhibitors; Female; Glucocorticoids; Gonadal Steroid Hormones; Humans; Hydrocortisone; Hypertension; Hypokalemia; Middle Aged; Mitotane; Muscle Weakness; Neoplasm Metastasis; Renin; Thirst; Tomography, X-Ray Computed

Seven patients with Cushing's syndrome were treated with trilostane (WIN 24,540) 4 alpha,5-epoxy-17 beta-hydroxy-3-oxo-5 alpha-androstane-2 alpha-carbonitrile), an inhibitor of adrenal steroid biosynthesis. Trilostane treatment reduced steroid biosynthesis and it also improved biochemical manifestations of the disease in all of the patients treated. The average cortisol secretory rate decreased significantly with treatment, from 47.1 to 23.4 mg/24 h (P less than 0.005), and urinary 17-hydroxycorticosteroids decreased from 15.7 to 8.7 mg/24 h (P less than 0.01). Urinary free cortisol excretion decreased from 277 to 88 microgram/24 h (P less than 0.01), and 0800 h plasma cortisol levels declined from 25.0 to 12.0 microgram/dl (P less than 0.05). Conversely, dehydroepiandrosterone sulfate excretion in urine increased from 1.3 to 5.8 mg/24 h (P less than 0.0025) and in plasma increased from 162 mg/24 h (P less than 0.025). Plasma and urinary free dehydroepiandrosterone increased 2-fold. Urinary 17-ketosteroid excretion increased from 18 to 43 mg/24 h (P less than 0.001). A significant reduction in urinary excretion of tetrahydroaldosterone, tetrahydrodeoxycorticosterone, and 18-hydroxytetrahydrodeoxycorticosterone was observed with treatment. Inhibition of steroid biosynthesis was accompanied by a 2-fold increase in PRA and no change in serum cholesterol levels. Mean arterial blood pressure decreased with treatment from 109 to 97 mm Hg (P less than 0.005), and fasting blood sugar decreased from 117 to 98 mg/dl (P less than 0.005), accompanied by rise in plasma potassium levels from 3.8 to 4.3 milliequivalents/liter (P less than 0.025). Two patients on long term therapy also showed an improvement in clinical features of their disease. There were no significant treatment-related carcinoma, simultaneously producing both an excessive amount of cortisol and ACTH, is described. It is concluded that trilostane is an effective inhibitor of 3 beta-hydroxysteroid dehydrogenase enzyme system in human adrenal gland; it inhibits biosynthesis of cortisol and it is useful in the treatment of Cushing's syndrome.

Topics: 17-Ketosteroids; Adrenal Cortex Hormones; Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Adult; Blood Pressure; Carcinoma; Cushing Syndrome; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dihydrotestosterone; Female; Humans; Hydrocortisone; Kinetics; Male; Middle Aged; Mineralocorticoids; Potassium; Renin