Adrenal carcinoma

Cushing s disease and adrenal carcinomas cause adrenal androgen hypersecretion in high enough concentrations to result in signs of androgen excess (such as acne, menstrual irregularities, and hirsutism) and cause virilization in women.4... 

If endogenous Cushing s syndrome, determine if patient is an appropriate candidate for surgical resection of the tumor. Does the patient have any conditions that contraindicate surgical resection, such as advanced disease (metastatic adrenal carcinoma) ... 

Adrenal carcinoma Surgery Mitotane See above See above See above... 

After metyrapone administration, a patient with a disease of pituitary origin cannot achieve a compensatory increase in the urinary excretion of 17-hydroxycorti-costeroids or 11-deoxysteroids. Moreover, if pituitary corticotrophin is suppressed by an autonomously secreting adrenal carcinoma, there will be no increase in response to metyrapone. On the other hand, if pituitary corticotrophin secretion is maintained, as occurs in adrenal hyperplasia, the inhibition of corticoid synthesis produced by metyrapone will stimulate corticotrophin secretion and the release of metabohtes of precursor urinary steroids, which can be measured as 17-hydroxycortico-steroids. Metyrapone is now used less frequently in the differential diagnosis of Cushing s syndrome because of the ability to measure plasma corticotrophin directly. 

Metyrapone is commonly used in tests of adrenal function. The blood levels of 11-deoxycortisol and the urinary excretion of 17-hydroxycorticoids are measured before and after administration of the compound. Normally, there is a twofold or greater increase in the urinary 17-hydroxycorticoid excretion. A dose of 300-500 mg every 4 hours for six doses is often used, and urine collections are made on the day before and the day after treatment. In patients with Cushing s syndrome, a normal response to metyrapone indicates that the cortisol excess is not the result of a cortisol-secreting adrenal carcinoma or adenoma, since secretion by such tumors produces suppression of ACTH and atrophy of normal adrenal cortex. 

Mitotane (Figure 39-5), a drug related to the DDT class of insecticides, has a nonselective cytotoxic action on the adrenal cortex in dogs and to a lesser extent in humans. This drug is administered orally in divided doses up to 12 g daily. About one third of patients with adrenal carcinoma show a reduction in tumor mass. In 80% of patients, the toxic effects are sufficiently severe to require dose reduction. These... 

In humans, mifepristone causes generalized glucocorticoid resistance. Given orally to several patients with Cushing s syndrome due to ectopic ACTH production or adrenal carcinoma, it was... 

Substrates and Inhibitors Calcium channel blockers and adrenal carcinomas, rarely in lung and gastric carcinomas Yes Yes... 

Adrenal carcinoma Bronchogenic carcinoma FibrolameUar carcinoma Hepatocellular carcinoma Leiomyosarcoma Leukaemia Renal cell carcinoma Rhabdomyosarcoma... 

Mitotane is an inhibitor of intramitochondrial synthesis of pregnenolone and cortisol, used to produce a chemical adrenalectomy in the treatment of adrenal carcinoma and Cushing s disease and syndrome. Its unwanted effects include increased transaminase and alkaline phosphatase activities, reduced leukocjrte, platelet and erythrocyte counts, and myasthenia (1). 

Suramin has been used in the treatment of AIDS and adrenal carcinoma, in both of which there was a high incidence of keratopathy (SED-13, 836). 

Germline mutation in BRCA1 or Hepatoblastoma Rhabdomyosarcoma Adrenal carcinoma Breast or ovarian cancer... 

Decreased concentrations of 17-KSs usually are found in men with primary hypogonadism (Klinefelter s syndrome and castration), in secondary hypogonadism (panhypopituitarism), and in women with pituitary hypoadrenahsm (Addison s disease). Increased concentrations are found in patients with testicular tumors (interstitial cell tumor and chorioepithelioma), adrenal hyperplasia, and adrenal carcinoma, and in some women with hirsutism. 

Rainey WE, Bird IM, Sawetawan C, Hanley NA, McCarthy JL, McGee EA, Wester R, Mason JI (1993) Regulation of human adrenal carcinoma cell (NCI-H295) production of C19 steroids. J Clin Endocrinol Metab 77(3) 731-737... 

The remaining 18% of Cushing s syndrome cases are ACTH-independent and are almost equally divided between adrenal adenomas and adrenal carcinomas, with rare cases caused by micronodular or macronodular hyperplasia." The majority of adrenal cortex tumors are benign adenomas. Adrenal carcinoma is found more often in children than in adults with Cushing s syndrome. 

Unfike the benign adenoma patient, patients with adrenal carcinoma have an unpredictable and unfavorable outcome with surgical resection. Often the complete tumor cannot be excised, leaving the patients with some degree of symptomatology and extra-adrenal involvement. Irradiation can be used if metastases are discovered. In the patient with adrenal carcinoma who is not a surgical candidate, the focus of treatment is on palliative pharmacologic intervention (e.g., mitotane). 

Mitotane appears to be the drug of choice in inoperable functional and nonfunctional adrenal carcinoma. Tumor regression is seen in approximately 35% to 50% of patients, with most regression occurring between the second and fourth month of therapy. Seventy-five percent of patients will exhibit a 30% fall in urinary steroids, with 50% of patients showing an improved clinical response after 5 months of... 

Hypersecretion of cortisol may be due to ectopic ACTH production by nonendocrine malignant tumors (L13, 06), which may raise serum alkaline phosphatase values by a variety of mechanisms (see Section 10). Hyperphosphatasemia has also been reported in association with adrenal carcinomas which may metastasize to the liver (H27). 

Fig. 4. Part of a 20 X 20 cm thin-layer chromatography plate for the assay in urine of B, THS C, allo-THE E, THE F, allo-THP G, THF. Standard compounds have been run in positions 2, 4, 6, and 8. Cortisol is shown in position D and is measurable only if present in abnormally increased amount. The compounds shown in position A are mainly Cm steroids with an a-ketol group. Duplicate extracts from normal adult urines have been run in positions 1 and 3 from a case of adrenal carcinoma in position S from a normal infant in position 7 and from an infant with adrenogenital syndrome in position 9. The plate was sprayed with blue tetrazolium reagent, then heated. From Shackleton et al. (SIO).

Adrenocortical tumours, particularly adrenal carcinomas, may produce excess androgens (DHA. androstenedione and testosterone) causing hirsutism and/or virilisalion in females (see pp. 92-9.T). 

Mitotane is remarkably simply because it preferentially accumiolates in adrenocortical cells. Although treatment is not curative, mitotane is used to decrease symptoms caused by adrenal carcinoma. 

Gl distress, lethargy, somnolence, dizziness, weakness. PO. Stored in fat, slowly released. Palliative treatment of inoperable adrenal carcinoma. ... 

Mitotane (Lysodren) Destroys adrenocortical cells. Used for palliative treatment of metastatic adrenal carcinoma. 

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