LH, progesterone, and TSH can stimulate aldosterone in vitro: a study on normal adrenal cortex and aldosterone producing adenoma.

Endocrine factors different from ACTH or angiotensin II can stimulate aldosterone secretion and have a role in the pathophysiology of hyperaldosteronism. Aldosterone may increase in luteotropic/progestogenic and in hypothyroid states; LH and, occasionally, TSH receptors have been detected in normal adrenal cortex and aldosterone-producing adenoma. The aim of the study was to compare adrenal contents of LH and TSH receptors between normal cortex and aldosterone-producing adenoma and to evaluate the ability of LH, its product progesterone, and TSH to stimulate aldosterone secretion in vitro from primary adrenocortical cells. Surgical aldosterone-producing adenoma fragments from 19 patients and adrenal cortex fragments from 10 kidney donors were used for Western blotting and cell cultures. LH (n=26), TSH (n=19) and progesterone (n=8) receptor proteins were investigated; LH receptor-mRNA was also tested in 8 samples. Aldosterone responses in vitro to LH, progesterone, and TSH stimulation were assayed. LH and TSH receptors were more expressed in adenoma than normal cortex (p<0.01, p<0.05, respectively); progesterone receptor was observed in 6/8 samples. Aldosterone increased after in vitro stimulation with LH (5/12 adenoma, 1/7 normal cells), progesterone (4/5 adenoma, 5/6 normal cells), and TSH (3/5 adenoma and 3/5 normal cells). LH and TSH receptors were more expressed in aldosterone producing adenoma than normal adrenal cortex. LH, progesterone, and TSH can stimulate aldosterone in vitro. Similar mechanisms could participate in vivo in the aldosterone increase in lutheotropic, progestogenic, or hypothyroid states and may exist in both normal adrenal cortex and adenoma in responsive individuals.

microRNA(interference) networks are embedded in the gene regulatory networks.

microRNAs (miRNAs) are a class of endogenous 22-25 nt single-stranded RNA molecules that regulate gene expression post-transcriptionally. They are highly conserved among species with distinct temporal and spatial patterns of expression, each of them potentially interacting with hundreds of messenger RNAs. Since miRNAs, like transcription factors (TFs), are trans-acting factors that interact with cis-regulatory elements, they potentially generate a complex combinatorial code. Moreover, as TFs and genes containing binding sites for TFs have a high probability of being targeted by miRNAs, the basic interplay miRNA/TF renders miRNAs key components of gene regulatory networks. Several biological processes, including diseases such as cancer, have been causatively associated to disturbances of miRNAs/TF interplay both in vitro and in vivo. These aspects, cumulatively, indicate that miRNAs and transcription factors have a crucial role in determining cellular behaviour, highlighting the role of small RNA molecules in regulatory mechanisms and indicating other routes in the evolutionary path of gene expression.

Is the low tri-iodothyronine state a crucial factor in determining the outcome of coronary artery bypass patients? Evidence from a clinical pilot study.

The cardiovascular system is an important target for thyroid hormones. The present study evaluates the changes affecting thyroid hormone metabolism during and 6 days after coronary artery bypass and their relationship with the post-operative outcome of the patients. Thirty-three patients were enrolled in the study; their thyroid hormone profiles were determined at 13 sampling points during surgery and for 6 days afterwards. Serum total tri-iodothyronine (T3) and free T3 (FT3) concentrations decreased significantly after surgery (P<0.001) and they remained significantly low until the end of the study. Free thyroxine (FT4) and T4 declined significantly immediately after surgery (P<0.05 for FT4, P<0.001 for T4) but they returned to baseline values (24 h and 96 h post-surgery respectively). Serum reverse T3 increased remarkably 36 h after surgery (P<0.001) and remained significantly higher than the baseline value throughout the study. A relevant finding was that the days of post-operative hospitalization (10+/-3 days, means+/-S.D.) was inversely correlated with the slope of the recovery of T3 concentration (P<0.001) or with the area under the plasma curves of T3 (P=0.024, time range 72-144 h) and the FT3/FT4 ratio (P=0.037, time range 72-144 h) during the post-operative period. Our data suggest a prolonged reduction of T4 to T3 conversion in patients undergoing cardiac surgery and indicate that the recovery period is the most critical in the evaluation of a possibly successful approach for T3 substitutive therapy.

Perioperative prognostic value of dipyridamole echocardiography in vascular surgery: A large-scale multicenter study in 509 patients. EPIC (Echo Persantine International Cooperative) Study Group.

BACKGROUND: Patients undergoing major vascular surgery are at a relatively high risk of cardiac events, and pharmacological stress echocardiography is increasingly used for perioperative risk stratification. The aim of the current study was to evaluate the value of dipyridamole echocardiography test (up to 0.84 mg/kg over 10 minutes) in predicting cardiac events in a large-scale, multicenter, prospective, observational study design. METHODS AND RESULTS: Five hundred nine patients (mean age 66+/-10 years) were studied before vascular surgery by dipyridamole stress echocardiography in 11 different centers. All patients underwent preoperative clinical risk assessment according to the American Heart Association guidelines. No major complications occurred during dipyridamole stress echocardiography. Technically adequate images were obtained in all patients; however, in 4 patients only the low dipyridamole dose (0.56 mg/kg over 4 minutes) was given for limiting side effects. Eighty-eight (17.3%) had a positive test. Perioperative events occurred in 31 (6.1%) patients: 6 deaths, 11 myocardial infarctions, and 14 episodes of unstable angina. Sensitivity and specificity of dipyridamole stress echocardiography for predicting spontaneous cardiac events were 81% and 87%, respectively, with a positive predictive value of 28% and negative predictive value of 99%. By multivariate analysis, the difference between wall motion score index at rest and peak stress (Deltawall motion score index), test positivity, and ST-segment depression during dipyridamole infusion were independent predictors of any perioperative cardiac event. CONCLUSIONS: Dipyridamole stress echocardiography is safe and well tolerated in patients undergoing major vascular surgery and provides an effective preoperative screening test for the risk stratification of these patients, mainly because of the extremely high negative predictive value, which is a potent predictor of complication-free procedure.