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At least 19 recordsLinked to original sources
PubMed1979

Cytotoxic activity of 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane (mitotane) and its analogs on feminizing adrenal neoplastic cells in culture.

Mitotane [1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane], an antineoplastic agent for inoperable adrenal carcinoma, was studied for its cytotoxic activity on a clonal line of feminizing human adrenal neoplastic cells (Fang-8 cells) in culture. At concentrations higher than 1.68 X 10(-4) M, mitotane produced a dose-related toxic effect on the cells. The effect of the drug was specific to Fang-8 cells because the same treatment produced little or no toxicity on lines of rat pituitary GH3 cells and human skin fibrocytes. The effect of mitotane to Fang-8 cells was a reversible one. Electron microscopic pictures revealed that the drug was causing mitochondrial degeneration. In this testing system, several isomers and analogs of mitotane were found equally or more toxic than was mitotane itself. The dichloro- or trichloroethylene structure was essential for the cytotoxic activity while the chloro substituents on phenyl rings appeared to be unimportant. This system appears to be useful in elucidating the biochemical mechanism of mitotane action on adrenal cancer.

Adrenal Gland Neoplasms↗
PubMed1977

[Metabolism of o,p'-DDD (mitotane) in human and animals. Actual notions and practical deductions (author's transl)].

The metabolism of o,p'-DDD (mitotane), a well-known inhibitor of adrenal steroidogenesis in man and animal, is reviewed. Following oral administration, about 65% of the ingested drug were found to pass in the stool. The drug appeared in the urine in metabolized forms: o,p'-DDA and mono-and dihydroxylated derivatives of o.p'-DDA. These latters were found as well in the stools. An unsaturated metabolite, o,p'-DDE was described in plasma and tissues in man. Serum specimens of treated patients were analyzed for o,p'-DDD during various phases of therapy: the levels and the rate of rise during treatment were very variable (5 to 90 microng/ml). Tissue levels were obtained from animals (rats, dogs) or men (biopsy as well as autopsy): o,p'-DDD was primarily found stored in adipose tissue and fat-containing tissues, essentially adrenals. Practical conclusions can be drawn from these results: there is no correlation between the dose of o,p'-DDD administered and its blood level; there is no correlation between blood levels and the patient's responsiveness to the drug; there is a possibility that the molecule transformed in an active metabolite through its metabolism.

Animals↗
PubMed1978

o,p'-DDD (mitotane) therapy of adrenal cortical carcinoma: observations on drug dosage, toxicity, and steroid replacement.

Four patients with adrenal cortical carcinoma were treated with standard doses of o,p'-DDD. Plasma levels of o,p'-DDD and its metabolites o,p'-DDA and o,p'-DDE were measured. o,p'-DDD was measurable for up to 8 months after stopping therapy, and trace levels of metabolites were detectable at 18 months. Although 2 of 3 patients with measurable disease had objective tumor response and one patient achieved a complete response, severe drug toxicity occurred in all patients and signs of adrenal insufficiency occurred in three. Low dose therapy with o,p'-DDD is suggested, together with full gluco and mineralocorticoid replacement. Measurement of o,p'-DDD and its metabolites in plasma may prove clinically useful in developing effective but less toxic dosage schedules.

Adrenal Cortex Neoplasms↗
PubMed1979

The continued importance of adrenalectomy in the treatment of Cushing's disease.

Eighteen patients with pituitary-dependent Cushing's disease have been treated during a ten-year period. Eleven of these received a total of 14 alternative forms of therapy in an attempt to control the clinical manifestations of Cushing's disease prior to adrenalectomy. However, no substantial improvement was noted in these patients, who included four receiving conventional pituitary irradiation, five receiving cyproheptadine, two receiving mitotane, and one each receiving metyrapone and phenytoin. One patient had an attempted transsphenoidal hypophysectomy that could not be accomplished because of hemorrhage. A complete remission of the signs, symptoms, and laboratory abnormalities of Cushing's disease occurred in all 18 patients following bilateral adrenalectomy. There was no operative mortality and morbidity was minimal. This experience confirms that bilateral adrenalectomy is a rapid, safe, and permanent means of reversing hypercortisolism and that it should remain an integral part of the treatment of Cushing's disease.

Adolescent↗
PubMed1978

Adrenal cortical carcinoma.

A review of 28 cases of adrenal cortical carcinoma provides some insights into the natural history of this disease and suggests modifications in current techniques of diagnosis and management. Our patients ranged in age from 1 to 69 years but it is notable that all of our male patients were more than 39 years old. In addition the men tended to have high stage tumors that were nonfunctional. Female patients, on the other hand, were more evenly distributed in terms of stage, function and age at diagnosis. Staging was extremely important and is discussed in some detail. A dismayingly large number of patients were found to have stage 3 or 4 tumor at initial diagnosis, suggesting that aggressive and rapid evaluation and a high index of suspicion are important to optimize survival. Function is helpful but non-function is common and should not dissuade one from the diagnosis. Excretory urography with tomography followed by angiography frequently will provide the diagnosis. Endocrinologic evaluation should be done with alacrity. Survival with high stages of disease is poor and lengthy evaluation should not be allowed to delay prompt and, hopefully, curative surgery. Surgical resection is the key to cure; chemotherapy and radiotherapy provided relatively poor results in our hands although mitotane has shown a 34 to 54 per cent response rate.

Adolescent↗
PubMed1978

Pregnancy in a case of Nelson's syndrome.

A woman suffering from Cushing's disease from the age of 17 who had been treated consecutively with pituitary irradiation, bilateral partial adrenalectomy and o,p'-DDD (Mitotane, USP) presented the clinical picture of Nelson's syndrome (hypoadrenalism with secondary hypersecretion of ACTH and MSH) at the age of 32. Under substitution therapy with corticoids she became pregnant for the first time at the age of 38. The course of the pregnancy was normal and at term she was delivered of a normal child by Cesarean section. The materno-fetal relationship, the increased risk of pituitary infarction during pregnancy and the possible teratogenic effect of chemotherapy in such cases are discussed.

Adrenal Cortex Hormones↗
PubMed1975

Adrenal cortical carcinoma. A study of 32 patients.

Fifteen males and 17 females with adrenal cortical carcinoma were reviewed. Their average age at diagnosis was 50.33 years plus or minus 12.26 SD for males and 39.76 years plus or minus 12.02 SD for females. The 5-year survival rate in this series was 31.25%. Abdominal pain, weakness, and weight loss were the primary presenting symptoms, whereas abdominal mass, distant lymphadenopathy, hepatomegaly, and edema of the lower extremities were the main presenting signs. The major sites of distant metastatic involvement were the lungs, liver, lymph nodes, and bones. The best available mode of therapy was surgery. The use of ortho para 'DDD (o,p'DDD), either in addition to surgery or as the only mode of therapy, was not associated with any significant advantage to the patient. Female patients had a longer survival than males, probably because of their younger age at diagnosis.

Adenoma↗
PubMed1975

Effect of o,p'-dichlorodiphenyldichloroethane on glutathione reductase activity and content of SH groups in the dog adrenals.

The effect of o, p'-dichlorodiphenyldichloroethane (DDD), a compound inducing atrophy of the adrenal cortex and blocking steroid production, on glutathione reductase activity was studied. As a result of feeding dogs with DDD in a dose of 50 mg/kg body weight for 14 days activation of glutathione reducatase took place in the homogenate, cytoplasmic fraction, and disintergrated mitochondria of the adrenals. On the additon of DDD in vitro the activity of the enzyme was unchanged. The content of SH groups expressed per 100 mg tissue was reduced in the homogenate and in all subcellular fractions. If expressed per 100 mg protein in the level of SH groups was lowered only in the microsomes and the disintergrated mitochondria.

Adrenal Glands↗
PubMed1977

Estimation of o,p'-DDD in plasma by gas-liquid chromatography.

A method is described for the estimation of o,p'-DDD in plasma. To 50 microl plasma, 0.2 ml acetone is added. The mixture is extracted with 2 ml n-heptane containing p,p'-DDD as an internal standard. Water is removed by adding desiccated sodium sulfate. The organic phase can be injected into a gas chromatograph equipped with an electron capture detector. The o,p'-DDD content of the sample can be read from a calibration curve. Recovery of o,p'-DDD added to plasma is over 93%. The same procedure can be used for the estimation of o,p'-DDE.

Chromatography, Gas↗
PubMed1977

Experience with adrenal cortical carcinoma.

Eight cases of histologically proved cortical carcinoma are reviewed and compared with several series from the literature. Emphasis is given to defining endocrinologic function in these tumors and to the role of nonoperative treatments. Whereas surgical therapy offered significant demonstrated in any of the patients.

Adrenal Cortex↗