ABSTRACT
Background: Cortisol has been implicated in hypertension and lately reported to be regulated at the pre-receptor level by the 11ßHSD1 enzyme, which converts cortisone (E) to cortisol (F). Over expression ofthis enzyme in adipose tissue could determine an increase in available cortisol that interacts with the mineralocorticoid receptor (MR) in renal, brain and heart tissue, leading to similar hypertensive effects as in 11ßHSD2 impaired patients. Severa! polymorphisms have been reported in HSDl IB 1 gene (CAI5, CAI9 and InsA83557), which could modify HSDl IB 1 gene expression or activity. Aun: To determine the distribution and prevalence of CAI5, CAI9 and InsA83557 in the HSDl IBl gene, and to correlate these results with biochemical parameters in cortisol/ ACTH (HPA) and renin-angiotensin-aldosterone (RAA) axis in patients with essential hypertension (EH). Patients and Methods: We studied 113 EHpatients (76 non-obese and 37 obese, with a body mass índex >30 kg/m²) and 30 normotensive adults (NT). In each patient, we measured serum levéis of E E, serum aldosterone (SA), plasma renin activity (PRA), adrenocorticotrophic hormone (ACTH), the urinary free cortisol/creatinine (UFF/Cr), F/ACTH and SA/PRA ratios. Each polymorphism was studied by PCR and 8 percent polyacrylamide gel electrophoresis. Statistical associations were evaluated by Pearson correlations and the genetic equilibñum by the Hardy-Weinberg (H-W) equation. Results: We found all three polymorphisms in the EH and the NT group, both in genetic equilibñum. In obese essential hypertensives, the CAI5polymorphism showed association with SA/PRA ratio (r =0.189, p =0.012) and F/ACTH (r =0.301, p 0.048); CA19 also showed correlation with F/ACTH in obese EH (r = 0.220, p 0.009). The InsA83557polymorphism correlated with UFF/Cr in both EH (r =0.206; p =0.03), and in obese EH (r =0.354; p =0.05). Conclusions: The CAI5 and CAI9 polymorphism correlated with changes in biochemical parameters...
Subject(s)
Adult , Female , Humans , Male , Young Adult , Hypertension/genetics , Polymorphism, Genetic , /genetics , /metabolism , Adrenocorticotropic Hormone/blood , Aldosterone/blood , Case-Control Studies , Chronic Disease , Cortisone/biosynthesis , Gene Frequency , Hydrocortisone/blood , Hypertension/enzymology , Microsatellite Repeats , Obesity/enzymology , Obesity/genetics , Polymerase Chain Reaction , Renin/blood , Young AdultABSTRACT
We describe a 39-year-old woman with a severe chronic mood disorder, refractory to antidepressive treatment, who showed a marked improvement after a self prescription of very high doses of liothyronine (T3). A modified Refetoff protocol was carried out to study the rol of high doses of thyroid hormones on her clinical and biochemical responses. Depression severity and change was assessed by the HAM-D and MADRS rating scales. Sequencing of thyroid receptors TRalpha1 and TRbeta1 was done and no abnormal findings were obtained. At the final stage of the study plasma T3 and free T3 were >800 ng/dl (80-180) and 1.409 pg/dl (230-420),respectively. No changes in the cardiovascular parameters, alcaline phosphatase isoenzymes or ferritine were observed. An improvement in mood was confirmed by a marhed drop in the rating scales scores (HAM-D 24 to 8; MADRS 40 to 11). These results support the existence in this patient of a peripheral resistance to thyroid hormone (RTH) and the response of depressive symptoms to high dosis of T3 Screening for RTH in refractory chronic depression may pro vide access to alternative and more efficacious treatments for this psychiatric condition.
Describimos el caso de una mujer de 39 años portadora de un trastorno del ánimo crónico y refractario a tratamiento, que experimentó una marcada mejoría de sus síntomas depresivos luego de auto-prescribirse altas dosis de liotiranina (T3). Se le sometió a un protocolo de Refetoff modificado a fin de estudiar los efectos de altas dosis de hormona tiroidea en sus síntomas clínicos y en variables bioquímicas. La severidad y cambio en la intensidad de la depresión se evaluó mediante la aplicación de las escalas HAM-D y MADRS. Se secuenciaron los receptores de hormona tiroidea TRalfa1 y TRbeta1, sin hallazgos anormales. Al final del estudio los niveles plasmáticos de T3 y T31ibre fueron >800 ng/dl (80-180) y 1.409 pg/dl (230-420), respectivamente. No hubo cambios en los parámetros cardiovasculares, fosfatasas alcalinas ni ferritina. Una marcada mejoría del ánimo fue confirmada por la disminución de los puntajes de las escalas aplicadas (HAM-D24 a 8; MADRS 40 a 11). Estos resultados apoyan la existencia de una resistencia periférica a hormona tiroidea (RHT) en esta paciente y la respuesta de los síntomas anímicos a altas dosis de liotironina. La búsqueda de RHT en pacientes con depresión crónica refractaria podría dar acceso a tratamientos alternativos más eficaces para esta condición psiquiátrica.