Alcohol-induced Cushing syndrome: report of eight cases and review of the literature

IntroductionAlcohol-induced hypercortisolism (AIH) is underrecognized and may masquerade as neoplastic hypercortisolism [Cushing syndrome (CS)] obscuring its diagnosis.Objective and methodsIn order to characterize AIH, we performed a chart review of eight patients (4 males and 4 females; 2014-2022) referred for evaluation and treatment of neoplastic hypercortisolism — six for inferior petrosal sinus sampling, one due to persistent CS after unilateral adrenalectomy, and one for pituitary surgery for Cushing disease (CD). Five underwent dDAVP stimulation testing.ResultsAll eight patients had clinical features of hypercortisolism and plasma ACTH levels within or above the reference interval confirming hypothalamic-pituitary mediation. All had abnormal low-dose dexamethasone suppression test and increased late-night salivary cortisol. Only one had increased urine cortisol excretion. In contrast to CD, the 5 patients tested had blunted or absent ACTH and cortisol responses to desmopressin. Two had adrenal nodules and one had abnormal pituitary imaging. Most patients underreported their alcohol consumption and one denied alcohol use. Elevated blood phosphatidyl ethanol (PEth) was required in one patient to confirm excessive alcohol use. All patients had elevations of liver function tests (LFTs) with AST>ALT.ConclusionAIH is an under-appreciated, reversible cause of non-neoplastic hypercortisolism that is indistinguishable from neoplastic CS. Incidental pituitary and adrenal imaging abnormalities as well as under-reporting of alcohol consumption further confound the diagnosis. Measurement of PEth helps to confirm an alcohol use disorder. Elevations of LFTs (AST>ALT) and subnormal ACTH and cortisol responses to dDAVP help to distinguish AIH from neoplastic hypercortisolism

Is cytochrome aa3 from thermus thermophilus a single subunit oxidase?

A reliable procedure has been developed for the purification of the cytochrome c1aa3 complex from the plasma membrane of T. thermophilus. The ratios heme C:heme A:Fe:C were found to be 1:2:3:2 confirming previous results, however, the molecular weight was found to be ~92,000 rather than the ~200,000 reported earlier [1]. Polyacrylamide gel electrophoresis under strongly denaturing conditions and high performance reverse phase liquid chromatography showed that cytochrome c1aa3 is composed of only two subunits in 1:1 ratio. Both polypeptides have blocked N-termini. The smaller subunit (~33,000) binds heme c and presumably no other metals. The larger subunit (~55,000) is thus thought to contain the elements of cytochrome aa3 and therefore be considered a single subunit cytochrome oxidase.The bacterial cytochrome c1aa3 has been compared with beef heart cytochrome oxidase with a number of techniques including optical, EPR [1], Raman, MCD, and Mossbauer [2] spectroscopies. These experiments establish that the fundamental chemical properties of the redox centers are substantially similar in these two proteins.Cytochrome c552 (from Thermus), horse heart cytochrome c, and tetramethylphenylenediamine greatly stimulate the ascorbate oxidase activity of cytochrome c1aa3. This enhancement is characterized by a `high affinity' component which results in only a small velocity increase and a `low affinity' component which gives a large velocity increase. Very similar behavior has been previously observed with mammalian cytochrome oxidase [3].Preliminary experiments show that vesicularized c1aa3 is capable of proton pumping.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25363/1/0000811.pd

Corticotroph tumor progression after bilateral adrenalectomy (Nelson’s syndrome):systematic review and expert consensus recommendations

Corticotroph tumor progression (CTP) leading to Nelson's syndrome (NS) is a severe and difficult-to-treat complication subsequent to bilateral adrenalectomy (BADX) for Cushing's disease. Its characteristics are not well described, and consensus recommendations for diagnosis and treatment are missing

Diagnosis of endocrine disease: Differentiation of pathologic/neoplastic hypercortisolism (Cushing\u27s syndrome) from physiologic/non-neoplastic hypercortisolism (formerly known as pseudo-Cushing\u27s syndrome)

Endogenous hypercortisolism (Cushing\u27s syndrome) usually implies the presence of a pathologic condition caused by either an ACTH-secreting neoplasm or autonomous cortisol secretion from a benign or malignant adrenal neoplasm. However, sustained or intermittent hypercortisolism may also accompany many medical disorders that stimulate physiologic/non-neoplastic activation of the HPA axis (formerly known as pseudo-Cushing\u27s syndrome); these two entities may share indistinguishable clinical and biochemical features. A thorough history and physical examination is often the best (and sometimes only) way to exclude pathologic/neoplastic hypercortisolism. The presence of alcoholism, renal failure, poorly controlled diabetes and severe neuropsychiatric disorders should always raise suspicion that the presence of hypercortisolism may be related to physiologic/non-neoplastic Cushing\u27s syndrome. As late-night salivary cortisol and low-dose dexamethasone suppression have good sensitivity and negative predictive value, normal studies exclude Cushing\u27s syndrome of any form. However, these tests have imperfect specificity and additional testing over time with clinical follow-up is often needed. When there is persistent diagnostic uncertainty, secondary tests such as the DDAVP stimulation test and the dexamethasone-CRH test may provide evidence for the presence or absence of an ACTH-secreting tumor. This review will define and characterize the numerous causes of physiologic/non-neoplastic hypercortisolism and provide a rational clinical and biochemical approach to distinguish it from pathologic/neoplastic hypercortisolism (true Cushing\u27s syndrome)