Ketoconazole is an effective drug with acceptable side effects. It should be used under close liver enzyme monitoring. Hepatotoxicity is usually mild and resolves after drug withdrawal.

This genome-wide methylation analysis reveals the existence of hypermethylated adrenocortical carcinomas, with a poorer prognosis. Hypermethylation in these tumors is important for silencing specific tumor suppressor genes.

Context: Alternatives to transsphenoidal pituitary surgery may be required in Cushing's disease (CD) as a first-or second-line treatment. Mitotane is a potent anti-cortisolic drug but has been rarely investigated in the treatment of CD. Objective: Evaluation of the efficacy and tolerance of mitotane in CD patients. Design and setting: Retrospective analysis of 76 patients treated with mitotane from 219 patients diagnosed with CD between 1993 and 2009 in a single center. Main outcome measure: Remission was defined as normalization of 24-h urinary free cortisol (24-h-UFC). Results: Remission was achieved in 48 (72%) of the 67 long-term treated patients, after a median time of 6.7 (5.2-8.2) months. Mean plasma mitotane concentration at the time of remission was 10.5G8.9 mg/l, with a mean daily dose of 2.6G1.1 g. A negative linear relationship was observed between plasma mitotane concentration and 24-h-UFC (P!0.0001). Seventeen of 24 (71%) patients with durable remission subsequently experienced recurrence, after a median time of 13.2 (5.0-67.9) months. At the time of treatment discontinuation, ACTH concentration was statistically associated with a lower recurrence probability (hazard ratios 0.57 (0.32-1.00), PZ0.05). Intolerance leading to treatment discontinuation occurred in 19 patients (29%). A pituitary adenoma became identifiable during mitotane treatment in 12 (25%) of the 48 patients with initial negative pituitary imaging allowing subsequent transsphenoidal surgery. Conclusion: Mitotane is useful at different stages of CD. Mitotane dose adjustment based on plasma concentration monitoring and side effects could control hypercortisolism in the majority of CD patients.

Previous studies have found a correlation between malnutrition and prognosis in respiratory infections. Our objectives were to determine (i) the percentage of malnutrition, and (ii) its prognosis in patients admitted for coronavirus disease 2019 (COVID-19). In this monocentric retrospective study, we consecutively included all adult patients presenting with acute COVID-19 between 9 April and 29 May 2020. Malnutrition was diagnosed on low body mass index (BMI) and weight loss ≥ 5% in the previous month and/or ≥ 10% in the previous six months. The Nutritional Risk Index (NRI) defined nutritional risk. Severe COVID-19 was defined as a need for nasal oxygen ≥ 6 L/min. We enrolled 108 patients (64 men, 62 ± 16 years, BMI 28.8 ± 6.2 kg/m2), including 34 (31.5%) with severe COVID-19. Malnutrition was found in 42 (38.9%) patients, and moderate or severe nutritional risk in 83 (84.7%) patients. Malnutrition was not associated with COVID-19 severity. Nutritional risk was associated with severe COVID-19 (p < 0.01; p < 0.01 after adjustment for C reactive protein), as were lower plasma proteins, albumin, prealbumin, and zinc levels (p < 0.01). The main cause of malnutrition was inflammation. The high percentage of malnutrition and the association between nutritional risk and COVID-19 prognosis supports international guidelines advising regular screening and nutritional support when necessary.

Numerous clinical studies and experimental investigations using cell culture and animal models suggest that angiotensin II (AngII) via AT(1) receptor activation might induce cardiovascular hypertrophy, fibrosis and atherosclerosis resulting in vascular events such as myocardial infarction, heart failure or stroke and in end-organ damages. However, a question still remains: which part of these damages is due to a direct effect of AngII on its target tissues and which is due to AngII-induced hypertension? In an attempt to answer this question, a new model of transgenic mice, expressing a constitutively activated AT(1A) receptor instead of the wild type receptor has been obtained by homologous recombination. These mice present with a moderate increase of blood pressure (20 mm Hg), hypertrophy of the small kidney arteries but not cardiac hypertrophy. The major phenotypic trait of these mice is the early and progressive development of a cardiovascular fibrosis. In light of these results and those from the literature, there is more and more evidence that in human hypertension, activation of the renin angiotensin system plays a minor role in the development of cardiovascular hypertrophy, but clearly participates to the development of cardiovascular fibrosis.

Abnormal cytoplasmic and/or nuclear β-catenin immunohistochemical staining occurs in about half of ACAs. This suggests the activation of the Wnt/β-catenin pathway, which could be explained by activating mutations of CTNNB1 in 70% of the cases. CTNNB1 mutations are mainly observed in larger and nonsecreting ACAs, suggesting that the Wnt/β-catenin pathway activation is associated with the development of less differentiated ACAs.

We conclude that PDE11A genetic variants may increase predisposition to AIMAH.

Objective: To describe the sequence of hormonal changes during recurrence of Cushing's disease (CD) after successful transsphenoidal surgery (TSS). Design: Retrospective study in a single center. Patients and methods: We studied 101 of the 127 patients treated by TSS for CD between 1996 and 2009, who had hypocortisolism or eucortisolism for at least 3 months post-TSS. We arbitrarily defined 'overt recurrence', as presence of two classical parameters of excess cortisol (increased midnight -either serum or salivary -and 24 h urinary cortisol (UC)), leading to further specific therapeutic action, and 'mild recurrence', as presence of a single classical parameter, leading to simple surveillance. Results: Of the 101 patients, 21 (20.8%) presented with recurrence, 'mild' or 'overt', during long-term follow-up (median 50.4 months, range 7-99). Recurrence occurred less frequently (16.8 vs 50%, PZ0.02), and later (mean 44.7 months, median 43, range 7-94 vs mean 21.5 months, median 17, range 3-61, PZ0.05), in patients with early post-TSS hypocortisolism compared with those with eucortisolism. Increase in midnight cortisol occurred in a mean time of 38.2 months, while UC elevation was observed at 50.6 months. Vasopressin analogs and CRH tests were eventually positive in 85 and 93% of all patients respectively; a positive response to one of the two dynamic tests preceded the increase in midnight cortisol or UC in 71 and 64% of the patients respectively. Conclusion: A positive response to vasopressin analogs and/or CRH tests occurs early in recurrence, followed by an increase in midnight cortisol, while UC elevation is at a later stage.