The use of ketoconazole in ectopic adrenocorticotropic hormone syndrome

Article Abstract:

The abnormal events within tumor cells can sometimes result in the inappropriate secretion of hormones. Tumors of the pancreas and thymus may sometimes secrete adrenocorticotropic hormone (ACTH), but the most common ectopic secretion of ACTH (the secretion of ACTH outside the pituitary) results from small cell lung cancer. In only 3 percent of the cases of small cell lung cancer are the levels of ACTH high enough to produce the symptoms of Cushing's syndrome. High levels of corticosteroid hormones produce alkalosis (excess alkalinity of body fluids), polyuria (excessive urination), and myopathy (muscle disease). The condition has been traditionally treated with aminoglutethimide, but even at doses high enough to produce unacceptable side effects, the suppression of the symptoms is incomplete. Ketoconazole is an antifungal drug that inhibits the cytochrome P450 enzyme system. It has been used with success in the treatment of Cushing's syndrome, but there is little experience with the drug in the treatment of ectopic adrenocorticotropic hormone syndrome. The authors report the case of a 60-year-old woman with small cell lung cancer. The patient had the symptoms of ectopic adrenocorticotropic hormone syndrome, although there was little Cushingoid appearance. The symptoms of excess mineralocorticoid hormones seemed predominant; these included hypokalemic alkalosis (potassium depletion with alkalinity of body fluids), renal (kidney) concentrating defect, and myopathy (muscle disease). The administration of ketoconazole resulted in the improvement in the patient's endocrine symptoms, which was confirmed by the improvements in laboratory values of blood and urine testing, and continued for five weeks. However, the patient's cancer continued to develop; her ectopic hormone symptoms reappeared and persisted until her death three months later. (Consumer Summary produced by Reliance Medical Information, Inc.)

Evaluation, Corticotropin releasing hormone, Corticotropin-releasing hormone, Ketoconazole

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The role of 1,25-dihydroxyvitamin D in the maintenance of hypercalcemia in a patient with ovarian carcinoma producing parathyroid hormone-related protein

Article Abstract:

Hypercalcemia, or increased levels of blood calcium, is not an uncommon complication of cancer; this condition is called humoral hypercalcemia of malignancy (HHM). Research studies have found that tumors from patients contain a protein that is similar in structure to parathyroid hormone. Under normal conditions, parathyroid hormone stimulates the return of calcium from storage in the bone into the blood, thereby maintaining the necessary amount of calcium in the blood. The abnormal protein found in the tumors, called parathyroid hormone-related protein, is thought to have a similar effect. However, the effects cannot be identical, since patients with HHM have different characteristics than patients with hypercalcemia resulting from an overproduction of parathyroid hormone. In general, patients with HHM have low levels of 1,25-dihydroxyvitamin D (1,25-DHD), another substance that plays a critical role in the regulation of calcium within the body. However, in a recent case of a woman with ovarian cancer, HHM was associated with an increase in 1,25-DHD, rather than a decrease. This observation illustrates that the physiological mechanisms of all cases of HHM are not the same, and that patients should be grouped according to whether their 1,25-DHD is elevated or reduced before comparisons of physiological measurements are made. In the present case, attempts were made to treat the elevated calcium in the blood by giving drugs to inhibit the resorption of calcium from the bone. Although the resorption of calcium was effectively inhibited, the calcium in the blood did not return to normal. This indicates that the hormone-like effects of the tumor on the bone are not the only effects important in the development of HHM. The absorption of calcium by the intestine may also prove to be important in this regard. (Consumer Summary produced by Reliance Medical Information, Inc.)

Ovarian cancer, Hypercalcemia, Calcitriol

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Soluble interleukin-2 receptors and other markers in primary lung cancer

Article Abstract:

Blood samples from 92 patients with lung cancer and 43 healthy controls were analyzed for the concentration of soluble interleukin-2 receptors, as well as other potential tumor markers, including carcinoembryonic antigen, alpha-fetoprotein, beta-chorionic gonadotropin, pregnancy specific-glycoprotein, and beta-2-microglobulin. Of these various proteins, only two appeared to be preferentially associated with lung cancer. Fifty-one percent of the cancer patients had above normal values for the carcinoembryonic antigen, in contrast with only three of the 43 control patients (7 percent). The average amount of soluble interleukin-2 receptors (sIL-2R) was twice as high among the patients than among the control subjects. However, this elevation of sIL-2R was not evenly distributed across all subtypes of lung cancer. The greatest increase in sIL-2R was found among the patients with small cell lung cancer. The large values of sIL-2R in this subgroup account for much of the increase in the overall average of the lung cancer patients as a whole. The increases in sIL-2R concentration in the blood were more modest among the patients with squamous cell carcinoma of the lung, adenocarcinoma, and undifferentiated large cell carcinoma of the lung. Only the differences among the patients with small cell carcinoma proved to be statistically significant. The authors speculate that these results may prove useful in monitoring the extent of lung disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

Interleukin-2, Tumor markers, Drug receptors, CEA (Oncology), Carcinoembryonic antigen

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