Atypical Cushing's syndrome associated with bronchial carcinoid.

Preliminary Communications MEDICBJOURNAL 291 Phree radioactive compounds could be detected in chromato-grams of the urine after administration of 35S methimazole, of which two were probably 35S methimazole and VISO4. The third compound could be detected at the origin after the urinary sulphate had been removed by precipitation with barium chloride. After administration of propylthiouracil chrormato-graphs of the urine showed that the 35S label remained at the origin with the chromatographic system used, and few or no counts running as propylthiouracil could be detected. COMMENT Propylthiouracil and methimazole are generally thought to be equivalent drugs for the treatment of thyrotoxicosis. Our results reflect differences in metabolism of the drugs, including distribution space, plasma half-life, absorption, and excretion. Intrathyroid metabolism may also differ. Thus we have found (Gallagher, Londono, and Alexander, to be published) that the T/S (thyroid/serum radioactivity) ratio in rats reaches 3 after administration of 35S methimazole, and 40 for 35S propylthiouracil. The differences in drug metabolism may influence their therapeutic efficacy. The latter may also be influenced by host factors such as renal failure. These preliminary results provide measurements of plasma radioactivity only. Studies to determine the chemical form. of the antithyroid drug in the plasma are in progress. Nevertheless , if the 35S is split off it is unlikely that the residue of the molecule would have antithyroid activity, and the label would probably be rapidly excreted, mainly as 35SO. In the rat thyroid the 35S label is present mainly as '5SO4 after adnmin-We wish to thank Dr. E. B. Astwood for advice and help throughout this study. The Medical Departnent of British Schering provided the "S-labelled methimazole and carbimazole. Adrenocortical hyperactivity associated with neoplasms arising outside the pituitary-adrenal system has been increasingly recognized in recent years. Allott and Skelton (1960) reviewed 38 reports of this association and suggested a causal relationship. The mechanism of this relationship was elucidated by Liddle et at. (1963) when they demonstrated the presence of a corticotrophin-like substance in the associated neoplasm. Similar evidence has been provided by many others. Further reports have been reviewed by O'Riordan et al. (1966) and Friedman et al. (1966), and the neoplasm most commonly concerned is an oat-cell bronchial carcinoma. Nevertheless, the condition has occurred with other neoplasms, particularly of the thymus, pancreas, and, more rarely, with bronchial adenomas or carcinoids. Some of the carcinoids have been of an unusual type (Cohen et al., 1960). We wish …