rifampin and Cushing-Syndrome

Topics: Cushing Syndrome; Female; Humans; Hypothyroidism; Iodine; Pregnancy; Pregnancy Complications; Receptors, Thyrotropin; Rifampin; Thyroid Hormones; Thyroiditis, Autoimmune

Aldosterone-producing adenoma (APA) is a main cause of primary aldosteronism (PA). Given that a large benign-appearing unilateral masse (>1 cm in diameter) may represent an aldosterone and cortisol-co-secreting adenoma, dexamethasone suppression testing is required in such patients to exclude or confirm the diagnosis of hypercortisolism. Tuberculosis is highly prevalent in China, and rifamycins are often used in these patients. Rifapentine belongs to the rifamycin family, and we herein for the first time report a case of misdiagnosis of hypercortisolism due to rifapentine use in a patient with APA. Thus, in patients treated with rifapentine, diagnosis of hypercortisolism based on dexamethasone suppression tests can be very misleading.

Topics: Cushing Syndrome; Diagnostic Errors; Humans; Hyperaldosteronism; Male; Middle Aged; Pituitary-Adrenal Function Tests; Rifampin

Potent and selective CYP11B1 inhibitors could be promising therapeutics for the treatment of Cushing's syndrome. Optimization of Ref 1 (5-((1H-imidazol-1-yl)methyl)-2-phenylpyridine) led to compound 44 (5-((5-methylpyridin-3-yl)methyl)-2-phenylpyridine) with a 50-fold improved IC50 value of 2 nM toward human CYP11B1 and an enhanced inhibition of the rat enzyme (IC50 = 2440 nM) compared to Ref 1 (IC50 > 10000 nM). Furthermore, selectivities over CYP11B2, CYP17, and CYP19 were observed, as well as satisfying metabolic stability not only in human and rat plasma but also in liver S9 fraction. Investigation of cytotoxicity and inhibition of hepatic CYP2A6 and CYP3A4 showed that 44 fulfills first safety criteria and can be considered for further in vivo evaluation in rats.

Topics: Animals; Cell Line; Cricetinae; Cushing Syndrome; Cytochrome P-450 CYP11B2; Humans; Liver; Models, Molecular; Pyridines; Pyrimidines; Quantitative Structure-Activity Relationship; Rats; Steroid 11-beta-Hydroxylase

We hereby describe a patient in whom chronic rifampicin treatment led to a misdiagnosis of Cushing's syndrome. He had long-standing insulin-dependent diabetes mellitus and active tuberculosis resistant to conventional treatment. The course was complicated by muscle weakness, lower limb atrophy, unstable glycemic control and hypokalemia. Ectopic Cushing's syndrome was suspected on the basis of high urinary free cortisol excretion (UFC) with a blunted circadian profile of serum cortisol and measurable plasma ACTH concentrations. Dynamic endocrine tests and imaging studies were compatible with occult ectopic ACTH syndrome. After substitution of rifampicin UFC excretion returned to normal within two weeks, as well as the 24-h cortisol profile and dynamic tests. The present case provides a practical example of the possibility to incorrectly suspecting Cushing's syndrome in patients treated with rifampicin, as previously envisaged by pharmacological studies.

Topics: Adrenocorticotropic Hormone; Adult; Corticotropin-Releasing Hormone; Cushing Syndrome; Diabetes Mellitus, Type 1; Diagnostic Errors; Humans; Hydrocortisone; Male; Metyrapone; Rifampin; Tuberculosis, Pulmonary

We have studied the effects of rifampicin on the overnight 1-mg dexamethasone suppression test usually employed to exclude suspected Cushing's syndrome. Previous observations indicate that in humans, rifampicin profoundly attenuates the biological effects of hydrocortisol and prednisolone, probably by increasing the metabolism of these drugs in the liver. The study was carried out in 16 normal volunteers. All subjects had a normal overnight 1-mg dexamethasone suppression test (468 +/- 86 vs. 32 +/- 21 nmol/L; mean +/- SD). In 8 subjects treated with rifampicin (600 mg) for 10 days, the inhibitory effect of dexamethasone on serum cortisol was completely prevented (575 +/- 114 vs. 434 +/- 82). In the remaining 8 rifampicin-treated subjects, the inhibitory effect of 1, 2, or 3 mg dexamethasone on serum cortisol was not observed. When 4 mg dexamethasone were administered, the serum cortisol level was 193 nmol/L, above the expected normal suppression value. The plasma dexamethasone concentration was very low after rifampicin treatment (range, 1.2-4.8 nmol/L). We conclude that when patients are treated with rifampicin, the standard overnight dexamethasone suppression test not only has no diagnostic value, but can be very misleading.

Topics: Adult; Cushing Syndrome; Dexamethasone; Diagnostic Errors; False Positive Reactions; Humans; Hydrocortisone; Male; Middle Aged; Rifampin

Glucocorticoids are used in physiological and pharmacological amounts in the management of a variety of clinical conditions. Concomitant utilisation of other drugs or the presence of some diseases may affect the physiological action of the steroid in the tissues. Phenytoin, phenobarbitone, ephedrine and rifampicin accelerate the metabolism of glucocorticoids thereby decreasing their biological activity. A similar phenomenon occurs in patients with hyperthyroidism. In contrast, glucocorticoid action is enhanced in hypothyroid patients and in those with hepatic damage as the result of a defect in the clearance of the hormone from blood. In turn, glucocorticoids antagonise the effects of cholinesterase inhibitors and ganglion blocking agents. The above mentioned effects should be kept in mind whenever glucocorticoids are utilised in the diagnosis and management of endocrine or non-endocrine conditions.

Topics: Anticonvulsants; Cholinesterase Inhibitors; Contraceptives, Oral; Cushing Syndrome; Dexamethasone; Diuretics; Drug Interactions; Ephedrine; Ganglionic Blockers; Glucocorticoids; Humans; Hypnotics and Sedatives; Insulin; Kinetics; Liver Diseases; Pancuronium; Rifampin; Salicylates; Thyroid Diseases