Testosterona inhibe la actividad de la aldosterona sintasa silvestre y quimérica in vitro

Background: Familial hyperaldosteronism type I is caused by the generation of a chimeric aldosterone synthase enzyme (ASCE) which is regulated by ACTH instead of angiotensin II. We have reported that in vitro, the wild-type (ASWT) and chimeric aldosterone synthase (ASCE) enzymes are inhibited by progesterone and estradiol does not affect their activity. Aim: To explore the direct action of testosterone on ASWT and ASCE enzymes. Material and Methods: HEK-293 cells were transiently transfected with vectors containing the full ASWT or ASCE cDNAs. The effect of testosterone on AS enzyme activities was evaluated incubating HEK-cells transfected with enzyme vectors and adding deoxycorticosterone (DOC) alone or DOC plus increasing doses of testosterone. Aldosterone production was measured by HPLC-MS/MS. Docking of testosterone within the active sites of both enzymes was performed by modelling in silico. Results: In this system, testosterone inhibited ASWT (90% inhibition at five pM, 50% inhibitory concentration (IC50) =1.690 pM) with higher efficacy andpotency than ASCE (80% inhibition at five pM, IC50=3.176 pM). Molecular modelling studies showed different orientation of testosterone in ASWT and ASCE crystal structures. Conclusions: The inhibitory effect of testosterone on ASWT or ASCE enzymes is a novel non-genomic testosterone action, suggesting that further clinical studies are needed to assess the role of testosterone in the screening and diagnosis of primary aldosteronism.

Metástasis pancreática como debut de carcinoma papilar de tiroides: caso clínico y revisión del perfil clínico patológico y molecular / Papillary thyroid carcinoma presenting with pancreatic metastases: report of one case

Pancreatic metastases of papillary thyroid carcinoma (PTC) are exceptional. We report a 80-year-old man consulting for obstructive jaundice and dysphonia. Abdominal ultrasonography showed biliary dilation and abdominal magnetic resonance imaging (MRI) showed a pancreatic head mass of 36 mm. A left vocal cord paralysis was confirmed and cervical computed tomography (CT) showed multiple thyroid nodules of up to 35 mm associated with bilateral cervical lymph nodes (LN). Positron emission tomography ( 18 F-FDG PET/CT) evidenced hyper-metabolic activity in bilateral cervical LN, lungs, pancreas and left intercostal soft tissue, as well as left gluteus. Thyroid biopsy reported a tall-cell variant of PTC, and endoscopic ultrasound guided fine needle aspiration (EUS-FNA) of pancreatic mass confirmed PTC metastasis. The molecular study was positive for BRAFV600E. Pancreatic metastasis from PTC can be accurately diagnosed with 18 F-FDG PET/CT and EUS-FNA, which is consistent with a predominant expression of BRAFV600E mutation and, thus, an aggressive presentation with poor short-term survival.

Disfunción tiroidea y trastornos del ánimo: revisión del estado del arte / Thyroid dysfunction and mood disorders: review of the state of the art

La relación entre función tiroidea y trastornos del ánimo se ha observado desde hace más de 50 años. Las hormonas tiroideas, actúan en el cerebro modulando génicamente proteínas asociadas a la fisiopatología de los trastornos del ánimo y potenciando los sistemas de neurotransmisión serotoninérgica y noradrenérgica. En el tratamiento de un episodio depresivo, la normalización de hormonas tiroideas es fundamental, y debe realizarse en todo paciente con sintomatología anímica, especialmente en aquellos con respuestas insuficientes a tratamiento, que requieren niveles de hormonas más estrictos que lo recomendado para población general. En pacientes eutiroideos, la potenciación con triyodotironina ha sido probada, pero también se ha utilizado T4 en altas dosis en casos resistentes, en que se postula que pudiese existir un estado de resistencia a hormonas tiroideas, no reflejado en los niveles hormonales periféricos evaluados rutinariamente. Las enzimas deiodasas, el receptor de hormona tiroidea, y el transportador de hormona tiroidea en la barrera hematoencefálica son blancos a investigar. Los objetivos de la presente revisión son ofrecer orientaciones respecto del uso de hormonas tiroideas en pacientes con trastornos del ánimo, una puesta al día sobre la relación entre hormonas tiroídeas y sistema nervioso central, y las interacciones entre psicofármacos y función tiroidea.

The relationship between thyroid function and mood disorders has been observed for more than 50 years. Thyroid hormones act in the brain genetically modulating proteins associated with the pathophysiology of mood disorders and potentiating the serotonergic and noradrenergic neurotransmission systems. In the treatment of a depressive episode, the normalization of thyroid hormones is essential, and should be performed in all patients with mood symptoms, especially in those with insufficient responses to treatment, which require more stringent hormone levels than recommended for the general population. In euthyroid patients, potentiation with triiodothyronine has been proven, but T4 has also been used in high doses in resistant cases, in which it is postulated that there might be a state of resistance to thyroid hormones, not reflected in the peripheral hormonal levels evaluated routinely. The enzymes deiodasas, the thyroid hormone receptor, and the thyroid hormone transporter in the blood brain barrier are white to investigate. The objectives of this review are to provide guidance regarding the use of thyroid hormones in patients with mood disorders, an update on the relationship between thyroid hormones and central nervous system, and the interactions between psychoactive drugs and thyroid function.

Actualización en el manejo clínico de la hipertensión hiporreninémica / Update in the clinical management of low renin hypertension

The renin-angiotensin-aldosterone system modulates volume, sodium and potassium homeostasis. In the setting of a high sodium diet, up to 30% of patients with hypertension have a low or suppressed renin and increased volume. This phenotype of low renin hypertension (LRH) is multifactorial and includes infrequent inherited genetic syndromes, milder phenotypes of classic diseases and environmental exposures. All these conditions have in common a higher cardiovascular risk mediated by the over activation of the mineralocorticoid receptor (MR), present not only in the kidney, but also in vasculature, myocardium and adipocytes. Consequently, the aim of LRH treatment goes beyond the control of blood pressure and requires antagonizing MR with specific pharmacologic agents, pursuing normalization of renin as a clinical objective. Due to the unusual evaluation of renin status by non-endocrinologists and lack of disease awareness, only a minority of hypertensive patients receive this pathophysiologically-driven treatment that should reduce cardiovascular outcomes.

Discrepancia en concentraciones de hormonas tiroideas libres medidas por distintos inmunoensayos / Discrepancy in concentrations of free thyroid hormones measured by different immunoassays

Abstract: Thyroid function is assessed by measuring thyrotropin and free and total thyroid hormone concentrations. There are interferences with the results of immunoassays that can lead to an incorrect diagnosis, of which the most frequent are the binding of thyroid hormones to heterophile antibodies, rheumatoid factor, anti-Ruthenium antibodies, the intake of biotin and anti-streptavidin antibodies. We present three cases of clinically euthyroid patients, with normal TSH, high free T4 and T3, and normal total T4 and T3 performed in a Roche Diagnostics ® COBAS 8000 device. When the test was repeated on a Siemens® Immulite device, the free and total hormones were within normal ranges. In the Roche Diagnostics ® assay, the presence of biotin or anti-Ruthenium or anti-streptavidin antibodies interferes with the formation of the complex responsible for the emission of light that allows inferring concentrations of thyroid hormones. The Siemens test works differently since the emission of light depends on the binding of T4 to an antibody conjugated with alkaline phosphatase not participating in the process biotin, streptavidin or ruthenium so this interference is avoided. This possible interference in immunoassays should be taken into account in case clinical manifestations differ from these laboratory determinations, to avoid a diagnosis and potential inappropriate treatment.

Resumen: La función tiroidea se evalúa midiendo tirotropina y concentraciones de hormonas tiroideas libres y totales. Existen interferencias con los resultados de inmunoensayos que pueden llevar a un diagnóstico incorrecto, de ellas, las más frecuentes son la unión de hormonas tiroideas a anticuerpos heterófilos, el factor reumatoide, anticuerpos anti Rutenio, la ingesta de biotina y anticuerpos anti estreptavidina. Se presentan tres casos de pacientes clínicamente eutiroideos, con TSH normal, T4 y T3 libres elevadas, y T4 y T3 totales normales realizadas en un equipo COBAS 8000 de Roche Diagnostics®. Cuando se repitió el ensayo en un equipo Immulite de Siemens®, las hormonas libres y totales estaban dentro de rangos normales. En el ensayo de Roche Diagnostics ®, la presencia de biotina o anticuerpos anti Rutenio o anti estreptavidina, interfiere con la formación del complejo responsable de la emisión de luz que permite inferir las concentraciones de las hormonas tiroideas. El ensayo de Siemens funciona de manera diferente ya que la emisión de luz depende de la unión de la T4 a un anticuerpo conjugado con fosfatasa alcalina no participando en el proceso biotina, estreptavidina o Rutenio por lo que se evita esta interferencia. Esta posible interferencia en inmunoensayos debe ser tenida en cuenta en caso de que las manifestaciones clínicas difieran de estas determinaciones de laboratorio, para evitar un diagnóstico y potencial tratamiento inadecuado.

Estudio e identificación de microRNA en exosomas urinarios en hipertensión arterial mineralocorticoide / Study and identification of microRNA in urinary exosomes in mineralocorticoid arterial hypertension

About 15% of the essential hypertensive patients would have a low activity of the 11ßHSD2 enzyme, which inactivates cortisol (F) to cortisone (E). Gene expression can be negatively regulated by miRNA. Urinary exosomes and their specific content (miRNA/proteins) represent a valuable tool as a biomarker for the diagnosis and prognosis of the disease. Aim: To evaluate the expression of miRNA specific for 11ßHSD2 in samples of urinary exosomes and to determine its association with biochemical variables associated with mineralocorticoid metabolism. Subjects and Methods: Cross-sectional study in subjects between 10-60 years. They were classified into subjects with high F/E (> p75) and low cortisone (< p25) and control subjects. The urinary exosomes were isolated with the Invitrogen kit. Bioinformatic analysis was performed with Mir Walk to identify specific miRNAs of HSD11B2. The expression of miRNA was evaluated by qRT PCR. The comparisons were made with the Mann-Whitney test. Results: 7.1% of the subjects are suggestive of a partial deficiency of 11ßHSD2 (NC-AME). The expression of miR-488 was higher in NC-AME than in controls (5839 ± 1719 vs 3,437 ± 2,581; p = 0.01). We found positive associations between mir-615 and ARP; miR-488 and the sodium/potassium ratio; miR-1205 with age and urinary sodium excretion; miR-494 with age, activity MMP9 and NGAL. Conclusion: We identified high expression of miR488 in NC-AME subjects and associations of miRNAs with biochemical variables associated with mineralocorticoid metabolism. Thus, exosomes and their miRNA content could be potential regulators and biomarkers of 11ßHSD2 activity.

Hiperaldosteronismo primario y otras formas de hipertensión arterial endocrina / Primary hyperaldosteronism and other forms of endocrine arterial hypertension

La hipertensión arterial (HTA) dependiente de mineralocorticoides representa actualmente una de las formas secundarias de hipertensión de mayor prevalencia. Entre las causas más prevalentes está el hiperaldosteronismo primario (HAP) cuya prevalencia es cercana al 10 por ciento de la población de hipertensos. El HAP se detecta principalmente por una elevación de la razón aldosterona a actividad renina plasmática (ARR), ya que la hipokalemia es infrecuente de encontrar. La fisiopatología del HAP se presenta como un desequilibrio en el control electrolítico a nivel renal, por mayor actividad del receptor mineralocorticoides (MR), lo cual aumenta el volumen intravascular y la presión arterial. Recientemente se ha demostrado también que el exceso de aldosterona afecta también el endotelio vascular, el tejido cardiaco entre otros. Este exceso puede ser por una alteración a nivel de la glándula suprarrenal (generalmente hiperplasia o adenoma) o formas genéticas (familiares). Por otra parte, alteraciones parciales o totales de la enzima 11ß-Hidroxiesteroide deshidrogenasa tipo 2 (11ß-HSD2) resulta en una metabolización total o parcial de cortisol, imitando los efectos de aldosterona sobre MR. La actividad de esta enzima se evalúa midiendo la razón cortisol a cortisona en suero por HPLC-MS/MS. La prevalencia de alteraciones parciales de la actividad de la enzima 11ß-HSD2 en estudios de cohorte alcanza en alrededor del 15 por ciento en población hipertensa. El diagnóstico del HAP o deficiencias de 11BHSD2, permitiría un tratamiento específico del cuadro hipertensivo mediantes el uso de bloqueadores del receptor mineralocorticoideo y/o uso de corticoides de acción prolongada sin actividad mineralocorticoidea como dexametasona o betametasona.(AU)

Mineralocorticoid arterial Hypertension represents currently one of the secondary forms of hypertension most prevalent. Among the most prevalent causes is the primary aldosteronism (PA) whose prevalence is close to 10 percect of the hypertensive population. PA is detected by elevated aldosterone to plasma renin activity ratio (ARR) and the hypokalemia is rare to find. The pathophysiology of PA is presented as a renal electrolyte imbalance, increasing mineralocorticoid receptor (MR) activity, intravascular volume and blood pressure. Recently it has also shown that excessive aldosterone also affects vascular endothelium, heart tissue among others. This excess can be associated to an adrenal gland (usually hyperplasia or adenoma) or genetic (familiar) alteration. Similarly, partial or total impairment in 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) enzyme affects the cortisol metabolism, mimicking the effects of aldosterone on MR. The activity of this enzyme is evaluated by measuring the serum cortisol to cortisone ratio by HPLC-MS/MS. The prevalence of partial alterations of the activity of 11ß-HSD2 enzyme in cohort studies reached at around 15 percent in hypertensive population. The diagnosis of PA or an impairment in 11ß-HSD2 activity allows specific treatments of hypertensive patients using mineralocorticoid receptor blockers and/or use of long-acting corticosteroids without mineralocorticoid activity as dexamethasone or betamethasone.(AU)

Consideraciones para el diagnóstico de linfoma primario de tiroides: esperiencia en 6 casos / Primary thyroid lymphoma: report of six cases

Background: Primary thyroid lymphoma is uncommon but must be suspected in certain clinical situations. Aim: To report a series of six patients with primary thyroid lymphoma. Patients and Methods: Six patients aged 50 to 84 years (five women), treated between 2004 and 2010. All patients had rapidly growing cervical mass; four had compressive signs and symptoms. In three cases the lymphoma was associated to Hashimoto's thyroiditis. Needle biopsy was performed in three patients. In one case was diagnostic for lymphoma and in the other two was suspicious. Five patients had a diffuse large B cell lymphoma, one of them associated to an extranodal marginal zone B cell lymphoma. One patient had a follicular lymphoma. Conclusions: Thyroid lymphoma must be suspected in female patients with rapidly growing cervical mass, older than fifty years, with a nodular goiter suspicious of malignancy (firm, non-tender, fixed and associated to compression signs). The diagnostic must be confirmed with a needle biopsy (fine needle or TrueCut®) and, if it's necessary open biopsy.

Utilidad de la PTH intraoperatoria como predictor de curación quirúrgica en hiperparatiroidismo primario / Usefulness of intraoperative parathormone measurement to predict surgical cure in primary hyperparathyroidism

Background: The aim of the surgical treatment of primary hyperparathyroidism (PHPT) is to achieve its complete cure, evidenced by normal serum calcium in the postoperative period. Measurement of intraoperative serum parathormone (PTH) can be useful to predict complete cure of the disease. Aim: To assess the usefulness of intraoperative PTH measurement to predict complete cure of PHPT Material and methods: Serum PTH was measured to all patients operated for PHPT between 2003 and 2008, before and five and ten minutes after the excision of the parathyroid gland causing the disease. The criteria for complete cure were normal serum calcium at 24 hours and 6 months after surgery and the pathological confirmation of parathyroid gland excision. Results: Eighty-eight operated patients, aged 58±15 years (72 females) were studied. Sixty four percent were asymptomatic and their preoperative serum calcium was 11.6± 1.2 mg/dl. A normal serum calcium was achieved in 86 patients (98 percent) at 24 hours and 50 of 52 patients followed for six months (96 percent). The pathological study disclosed an adenoma in 69 (78 percent), and multiglandular disease in 16 (18 percent), a parathyroid cancer in one and a normal gland in one patient. Intraoperative PTH predicted early and definitive cure in 97 percent and 100 percent of patients with a single adenoma, respectively. Among patients with multiglandular disease, the predictive figures were 94 percent and 100 percent, respectively. Conclusions: Intraoperative PTH measurement efficiently predicts early and definitive surgical cure of PHPT.

Diseño de una escala ecográfica predictora de malignidad en nódulos tiroideos: Comunicación preliminar / An ultrasound score to predict the presence of papillary thyroid carcinoma: Preliminary report

Background: Thyroid nodules are common and associated to a low risk of malignancy. Their clinical assessment usually includes a fine neddle aspiration biopsy (FNAB). Aim To identify ultrasonographic characteristics associated to papillary thyroid carcinoma (PTC) and generate a score that predicts the risk of PTC. Material and methods: Retrospective review of all fine needle aspiration biopsies of the thyroid performed in a lapse of two years. Biopsies that were conclusive for PTC were selected and compared with an equal amount of randomly selected biopsies that disclosed a benign diagnosis. Results: One hundred twenty two biopsies of a total of 1,498 were conclusive for PTC. Univariate analysis showed associations with PTC for the presence of micro-calcifications (Odds ratio (OR) 49.2: 95 percent confidence intervals (CI) 18.7-140.9), solid predominance (OR 25.1; 95 percent CI 6-220), hypoechogenicity (OR 23.5, 95 percent CI 6.5-122.6), irregular borders (OR 17, 95 percent CI 7.2-42.9), lymph node involvement (OR 12.3, 95 percent CI2.7-112), central vascularization (OR 12.2, 95 percent CI 4.8-33.3), local invasion and hyperechogenicity (OR 0.2; CI95 percent CI 0.03-0.6). Multivariate analysis disclosed microcalcifications (OR 28.1; CI 95 percent 8.9-89), hypoechogenicity (OR 9.4; 95 percent CI 1.5-59.5) and irregular borders (OR 4.7; CI 95 percent 1.5-15) as the variables independently associated with the presence of PTC. The prevalence of PTC in the presence of the three variables was 97.6 percent (Likelihood ratio (LR) 45) and 5.4 percent in their absence (LR 0.06). Conclusions: This scale predicts the presence or absence of PTC using simple ultrasound characteristics.

Marcadores de inflamación endotelial subclínica en una familia con hiperaldosteronismo familiar tipo I por mutación de novo / Subclinical endothelial inflammation markers in a family with type I familial hyperaldosteronism caused by a de novo mutation

Background: Type I familial hyperaldosteronism is caused by the presence of a chimaetic gene CYPl 1B1/CYP11BZ which encodes an enzyme with aldosterone synthetase activityregulated by adrenocorticotrophic hormone (ACTH). Therefore, in patients with FH I is possible to normalize the aldosterone levels with glucocorticoid treatment. Recently it has been shown that aldosterone plays a role in the production of endothelial oxidative stress and subclinical inflammation. Aim: To evaluate subclinical endothelial inflammation markers, Me Metalloproteinase 9 (MMP-9) and ultrasensitive C reactive protein (usPCR), before and after glucocorticoid treatment in family members with FH-I caused by a de novo mutation. Patients and methods: We report three subjects with FH-I in a single family (proband, father and sister). We confirmed the presence of a chimaeric CYPl 1B1/CYP11B2 gene by ¡ong-PCR in all of them. Paternal grandparents were unaffected by the mutation. The proband was a 13year-old boy with hypertension stage 2 (in agree to The JointNational Committee VII, JNC-vIl), with an aldosterone/plasma rennin activity ratio equal to 161. A DNA paternity test confirmed the parental relationship between the grandparents and father with the index case. MMP-9 and usPCR levels were determined by gelatin zymography and nephelometry, respectively. Results: All affected subjects had approximately a 50 percent increase in MMP-9 levels. Only the father had an elevated usPCR. The endothelial inflammation markers returned to normal range after glucocorticoid treatment. Conclusions: We report a family canying a FH-I caused by a de novo mutation. The elevation of endothelial inflammation markers in these patients and its normalization after glucocorticoid treatment provides new insight about the possible deleterious effect of aldosterone on the endothelium.

Hiperaldosteronismo primario / Primary aldosteronism

Primary aldosteronism (PA) is a known cause of hypertension. In the kidney, aldosterone promotes sodium and water reabsorption, increasing the intravascular volume and blood pressure (BP). In the cardiovascular system, aldosterone modifies endothelial and smooth muscle cell response, increasing cardiovascular risk in a blood pressure-independent way. Recently a high prevalence of PA (near to 10 percent) in hypertensive population, has been detected measuring plasma aldosterone/renin activity ratio (ARR) as screening test. This ratio increases along with the severity of the hypertensive disease. The diagnostic work up of PA should confirm the autonomy of aldosterone secretion from the renin-angiotensin system and should differentiate the clinical subtypes of the disease. These are idiopathic aldosteronism (IA) and aldosterone-producing adenoma (APA). Other causes are familial hyperaldosteronism (FH) type I (glucocorticoid-remediable aldosteronism), FH-II (non glucocorticoid-remediable aldosteronism), primary adrenal hyperplasia and adrenal carcinoma. This article reviews the prevalence, diagnosis and treatment of PA and also the clinical, biochemical and genetic characteristics ofits different subtypes.

Regiones polimórficas del gen 11ß-hidroxiesteroide deshidrogenasa tipo 1 (11ßHSD1) en hipertensión arterial esencial: Posible rol etiopatogénico / Possible pathogenetic role of 11ß-hydroxysteroid dehydrogenase type 1 (11ßHSD1) gene polymorphisms in arterial hypertension

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...

Variabilidad fenotípica y estrés oxidativo endotelial en una familia con hiperaldosteronismo familiar tipo I / Phenotypical variability and endothelial oxidative stress in a family with type I familial hyperaldosteronism

Type I familial hyperaldosteronism (HAF-I) is caused by the presence of a chimeric gene CYP11B1/CYP11B2 which encodes an enzyme with aldosterone synthetase activity regulated by ACTH. HAF-I patients present with severe hypertension at young ages and a greater risk of stroke. AIM: To characterize clinical and biochemical presentation of family members with HAF-I. To evaluate endothelial oxidative stress markers before and after glucocorticoid treatment. PATIENTS AND METHODS: We evaluated three family members with HAF-I confirmed with a genetic test (XL-PCR) for chimeric gene CYP11B1/CYP11B2. The index case was a 13 years old boy with stage 2 hypertension (Joint National Committee VIIth report), plasma aldosterone/ plasma renin activity (AP/ARP) ratio of161 and normal plasma potassium. His father had primary hyperaldosteronism diagnosed at 25 years of age with hypertension and hypokalemia. His sister was 15 years old, with a normal blood pressure and an AP/ARP ratio of 37.6. RESULTS: All subjects had plasma xanthine-oxidase levels in the upperlimit of normal. Malondialdehyde was above normal in the index case and his father. These markers returned to normal with glucocorticoid treatment. CONCLUSIONS: We report a HAF-I carrying family with a wide phenotypical variability between affected members. Elevation of endothelial oxidativestress markers and its normalization after glucocorticoid treatment, may indicate that aldosterone produces endothelial damage and increases cardiovascular risk.

Depresión refractaria y resistencia periférica a hormona tiroidea: el efecto de altas dosis de triyodotironina / Refractory depression and peripheral resistance to thyroid hormone: the effect of high doses of triodothyronine

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.

Carcinoma familiar del tiroides no medular (CFTNM): características de presentación en 17 casos / Clinical features of 17 patients with familial non medullary thyroid carcinoma

Background: Papillary thyroid carcinoma can have familial aggregation. Aim: To compare retrospectively familial non medullary thyroid carcinoma (FNMTC) with sporadic papillary thyroid carcinoma (PTC). Material and methods: Retrospective analysis of medical records of patients with thyroid carcinoma. An index case was defined as a subject with the diagnosis of differentiated thyroid carcinoma with one or more first degree relatives with the same type of cancer. Seventeen such patients were identified and were compared with 352 subjects with PTC. Results: The most common affected relatives were sisters. Patients with FNMTC were younger than those with PTC. No differences were observed in gender, single or multiple foci, thyroid capsule involvement, surgical border involvement, number of affected lymph nodes and coexistence of follicular hyperplasia. Patients with FNMTC had smaller tumors and had a nine times more common association with lymphocytic thyroiditis. Five patients with FNMTC had local recurrence during 4.8 years of follow up. Conclusions: Patients with FNMTC commonly have an associated chronic thyroiditis, are younger and have smaller tumors than patients with PTC.

Tiroglobulina y sus limitaciones en el seguimiento del carcinoma diferenciado del tiroides: Report of two cases / Recurrence of differentiated thyroid carcinoma without concomitant elevation of serum thyroglobulin

Thyroid carcinoma is the most prevalent endocrine tumor, and the papillary carcinoma (PC) is the most common histological type. In the follow-up, after thyroidectomy serum thyroglobulin (s-Tg) is used as a marker to evaluate recurrence of thyroid carcinoma. In most cases, this parameter allows an adequate diagnosis, but occasionally s-Tg may miss the detection of a recurrence. We report a 57 year-old female and a 36 year-old male sujected to a total thyroidectomy for a papillary thyroid carcinoma with intermediate and high-risk of recurrence. Both had a cervical recurrence without a concomitant increase in s-Tg levels. In both, Tg staining was positive in the tumor cells. These cases confirm that in these patients, the follow-up must be done with measurement of s-Tg and complementary diagnostic tests.

Alta prevalencia de disfunción tiroidea en pacientes psiquiátricos hospitalizados / High prevalence of thyroid dysfunction among psychiatric inpatients

Background: Thyroid dysfunction is frecuent in psychiatric outpatients and in the general Chilean population but there is no information about the prevalence of thyroid diseases in Chilean psychiatric inpatients. Aim: To retrospectively assess the frequency of thyroidal diseases in psychiatric inpatients. Material and Methods: Clinical charts and thyroid assessment of 241 psychiatric inpatients (147 women, mean age 33±16 years) attended in a University Psychiatric Clinic, were reviewed. Psychiatric diagnosis at discharge was made according to DSM IV criteria and endocrine diagnosis was made based on international criteria. Results: Forty nine patients (20.7%) had thyroid abnormalities. Forty four patients had hypothyroidism (18.3%) and five had hyperthyroidism (2.35%). No specific associations were found between gender or psychiatric diagnosis and endocrine abnormalities. Conclusions: In this sample, the prevalence of thyroid abnormalities was similar to other reports in psychiatric inpatiens and higher than in the general population in Chile.

Asociación de la región microsatélite AGAT del gen receptor de mineralocorticoides con los niveles de actividad renina en hipertensos esenciales / Microsatellite marker AGAT of the mineralocorticoid receptor gene is associated with plasma renin activity in patients with essential hypertension

Background: Hypertensive states could result from constitutive activation of mineralorticoid receptor (MR) that generates salt retention and blood pressure elevation. Moreover, microsatellite regions can be associated to the regulation of the gene expression, producing subtle pathologies. Aim: To determine the influence of microsatellite marker AGAT of the mineralocorticoid receptor gene in the plasma renin activity (PRA) and serum aldosterone (SA) levels of essential hypertensives (HT). Patients and Methods: We studied 292 HT patients and 57 normotensive (NT) controls. Blood samples were collected for PRA, SA and DNA isolation. Subjects were genotyped according to the length of the tetranucleotide AGAT repeat using polymerase chain reaction and polyacrylamide gel electrophoresis. Based on the normal distribution, we considered 13 to 15 repeats as a habitual (H) length and less than 13 or more than 15 repeats, as non-habitual (non-H). Results: We detected 8 different lengths in the AGAT repeat (allele) in both groups, ranging from 9-17 repeats, where the allele 11 was not detected in either hypertensive or normotensive groups. The allelic distribution was different in both groups (c2=37.57, 4GL, p <0.001). In hypertensive patients, the H group showed higher PRA levels (median (Q1-Q3)) than the non-H group: 1.3 (0-7-3.5) vs 1.0 (0.5-2.3) ng/mL*h, p <0.05. The SA levels did not show differences between both groups, but the SA*PRA product was higher in the H group than the no-H group: 9.3 (3.0-24.6) vs 6.5 (2.5-14.6) p <0.05. In normotensive patients, no differences were observed in PRA, SA and SA*PRA between both groups. Conclusion: These results show association between the length of the AGAT repeat with the PRA in HT, suggesting a plausible role in the control of the MR gene expression, and secondarily in the regulation of blood pressure .