Effects of different regimes of metyrapone on steroid production by a patient with a corticotrophin secreting bronchogenic carcinoma

THE SECRETION of hormones or closely related substances by tumours arising from tissues other than the endocrine glands has been widely reported and was reviewed recently by Bower & Gordan (1965) and Anderson (1966). The commonest example is the production of adrenocorticotrophic hormone (ACTH) by some oatcell carcinomas of the bronchus (Brown, 1928; Christy, 1961; O'Riordan et al., 1966; and others). The prognosis in this condition is even worse than with non-hormone producing oat-cell carcinomas, as high plasma levels of corticosteroids have been claimed to increase tumour growth and spread (Green & Whiteley, 1952; Wolf et al., 1960; Sherlock & Hartmann, 1962). Many attempts have been made to treat the associated adrenocortical hyperfunction but with little successs. Metyrapone (SU-4885, 1,2-bis (3 pyridyl)-2 methyl-i propanone, 'metopirone'. Ciba) inhibits the enzyme 1l-3,-hydroxylase, which is essential for the final step in the synthesis of 11 -hydroxycorticosteroids (11-OHCS), of which the most important in man is cortisol (Friedman, Marshall-Jones & Ross, 1966; Meador et al., 1962; Mattingly et al., 1964). There have been few studies of the value of this drug in treating patients with corticotrophin-secreting tumours (Mattingly et al., 1964; Hugh-Jones, 1964; O'Riordan et al., 1966). O'Riordan et al. (1966) treated two patients with ACTH-secreting tumours, one with a bronchogenic carcinoma who showed very little improvement and one with an anaplastic carcinoma of the thyroid gland who responded well for several months. The dose of metyrapone used was 0-75 g at intervals of 6hr. Treatment with metyrapone in doses at intervals of 6hr has usually proved unsatisfactory. There is evidence, however, that more adequate A. A. H. LAWSON M.B., Ch.B., M.R.C.P.E. University Lecturer in Medicine, Western General Hospital, Edinburgh