Adrenocortical adenomas with regression and myelolipomatous changes: urinary steroid profiling supports a distinctive benign neoplasm.

BACKGROUND: Adrenocortical neoplasms are classically divided into adenomas (ACA) and carcinomas (ACC). Heterogeneous appearance and greater size are criteria to suggest malignancy, along with the urinary steroid profile (USP). The presence of regression and myelolipomatous changes in adenomas (ACA-RML) can contribute to confusion with ACC and its USP remains unknown. OBJECTIVE: To evaluate the features of ACA-RML in comparison with other adrenocortical neoplasms. METHODS: We selected consecutive ACA (11), ACA-RML (7) and ACC (13) cases for which USP analysis was performed before surgery and tissue was available for histological evaluation (King's College Hospital, 2005-2012). Cases were classified according to WHO and Armed Forces Institute of Pathology criteria. USPs were obtained by gas chromatography/mass spectrometry. Total excretion of individual steroids and indices (sums and ratios chosen to reflect steroid metabolic activity) were compared between ACA-RML, ACA and ACC. RESULTS: In comparison with ACA, tumours in ACA-RML were significantly larger (8·5 ± 2·4 vs 3·5 ± 1·0, P = 0·002), presented in older patients and showed relatively higher incidence in males. Mitotic figure counts were significantly lower (0·39 ± 0·04 vs 0·93 ± 0·11 in ACA, P = 0·001) and revealed higher frequency of apoptotic cells (100% vs 9% in ACA, P = 0·001). The USP of ACA-RML showed no diagnostic features of ACC. No differences from ACA were significant, but there was a tendency towards lower dehydroepiandrosterone DHA and DHA metabolites. CONCLUSIONS: ACA-RML reveals distinctive histological features and lack of USP markers of malignancy. More cases of this rare tumour may confirm differences from ACA in steroid excretion. It is important to recognize ACA-RML because its size and heterogeneous appearance raise the possibility of ACC.

Effective treatment of pulmonary tuberculosis restores plasma leptin levels.

An impaired immune response in tuberculosis patients seems to be related to weight loss that coexists with an immunoendocrine imbalance. Thus, wasting is well-recognised as a prominent feature of tuberculosis (TB), which may not be reversed even after six months of treatment. Adipokines may play a role in the immune response to M. tuberculosis, and TB may impair the expression of inflammatory adipokines, such as leptin. We aimed to study patients with pulmonary TB before and six months after treatment, by measuring plasma leptin, soluble leptin receptor and adiponectin, weight and body mass index. Nineteen patients with a diagnosis of pulmonary TB were included in the study. Blood samples were obtained before and six months after treatment, to measure plasma adipokine levels. We found an increase in plasma leptin levels after treatment (p<0.05). Even though BMI also increased, the extent was not enough to account for the changes in the leptin levels. On the other hand, plasma soluble leptin receptor and adiponectin levels did not change significantly after treatment. In conclusion, these results suggest that active TB infection may affect the expression of leptin, in addition to the wasting that may occur in these patients, and that effective TB treatment increases circulating leptin levels, probably restoring normal immunological competence.

Liver AMP/ATP ratio and fructokinase expression are related to gender differences in AMPK activity and glucose intolerance in rats ingesting liquid fructose.

Women, but not men, show an association between fructose consumption and an increased risk of Type 2 diabetes mellitus. As rats are considered a model for human fructose metabolism, we sought to determine whether such a gender-related difference is present in Sprague-Dawley rats and to analyze the molecular mechanism behind. Male and female Sprague-Dawley rats had free access to water or to a 10% w/v fructose solution for 14 days. Plasma analytes, liver triglycerides and enzyme activities and the expression of enzymes and transcription factors related to fatty acid metabolism, insulin signaling and glucose tolerance were determined. Fructose-fed rats had hypertriglyceridemia, steatosis and reduced fatty acid oxidation activity, although the metabolic pattern of fructose-fed female rats was different to that observed for male rats. Fructose-fed female, but not male rats, showed no change in plasma leptin; they had hyperinsulinemia, an altered glucose tolerance test and less liver insulin receptor substrate-2. Further, only fructose-fed female rats had increased adenosine 5'-monophosphate (AMP)-activated protein kinase activity, resulting in a decreased expression of hepatic nuclear factor 4 and sterol response element binding protein 1. These differences were related to the fact that liver expression of the enzyme fructokinase, controlling fructose metabolism, was markedly induced by fructose ingestion in female, but not in male rats, resulting in a significant increase in the AMP/adenosine 5'-triphosphate (ATP) ratio and, thus, AMP-activated protein kinase activation, in female rats only. The difference in fructokinase induction could explain the higher metabolic burden produced by fructose ingestion in the livers of female Sprague-Dawley rats.