Warthin-like and classic papillary thyroid cancer have similar clinical presentation and prognosis

ABSTRACT Objective Warthin-like papillary thyroid cancer (WL-PTC) is an uncommon variant of PTC, usually associated with lymphocytic thyroiditis. Scarce evidence suggests that WL-PTC has similar clinical presentation to classic PTC (C-PTC), with no studies comparing risks of recurrence and response to treatment between both variants. Our objective was to describe the clinical presentation and prognosis of WL-PTC and compare it to C-PTC. Subjects and methods Retrospective analysis of a prospective cohort, including 370 (96%) patients with C-PTC and 17 (4%) with WL-PTC, consecutively treated with total thyroidectomy with or without RAI, followed for at least 6 months. We compared clinical presentation, risk of mortality and recurrence, as well as response to treatment between both variants. Results Of the total cohort: 317 (82%) female, 38 ± 13.5 years, median follow-up 4 years (0.5-28.5); most of them stage I and low/intermediate risk of recurrence. We found no differences regarding clinical-pathological data and risk of recurrence. WL-PTC was associated with a higher rate of anti-thyroglobulin antibodies (TgAb) (65% vs. 36%, p = 0.016) and lymphocytic thyroiditis (59% vs. 34%, p = 0.03). The rates of biochemical and structural incomplete responses were similar in both variants. WL-PTC had a lower rate of excellent response (23% vs. 54%, p = 0.01), which became non-significant when performing analysis by TgAb presence (50% vs. 67%, p = NS). Conclusions WL-CPT and C-CPT have similar clinical presentation and rate of recurrence. The lower rate of excellent response to treatment in WL-PTC is due to a higher frequency of TgAb. WL-PCT should not be considered an aggressive variant of PTC.

Cholestasis secondary to hyperthyroidism in Graves disease: report of one case / Colestasia en un paciente con hipertiroidismo por enfermedad de Graves: informe de un caso

ABSTRACT Hyperthyroidism can induce elevation in several liver function tests including aminotransferases, alkaline phosphatases and, less frequently, serum bilirubin. These alterations are usually mild and asymptomatic. We report a 26 year-old male presenting with palpitations, progressive jaundice, choluria and generalized itching. Laboratory tests were compatible with hyperthyroidism and a mild elevation of bilirubin, alkaline phosphatases and gamma glutamyl transpeptidase. A liver biopsy showed portal hepatitis with canalicular cholestasis. The patient was treated temporarily with glucocorticoids, cholestyramine and betablockade. Thereafter, he was treated with radioactive iodine, after which serum bilirubin decreased steadily until normalization in ten weeks.

El hipertiroidismo puede producir elevación de aminotransferasas, fosfatasas alcalinas y, menos frecuentemente, de bilirrubina sérica. Habitualmente, estas alteraciones son leves y asintomáticas. Reportamos un hombre de 26 años con hipertiroidismo secundario a enfermedad de Basedow-Graves, que debutó con un cuadro colestásico, inicialmente estudiado por sospecha de patología hepática autoinmune que incluyó biopsia hepática. Posteriormente, se diagnosticó hipertiroidismo que fue tratado con glucocorticoides, colestiramina y beta bloqueo como puente a terapia definitiva con radioyodo. La evolución mostró disminución progresiva hasta la normalización de bilirrubina sérica.

Manejo de nódulos tiroideos y cáncer de tiroides con lobectomía: experiencia de un equipo multidisciplinario / Management of thyroid nodules and thyroid cancer with lobectomy: experience of a multidisciplinary team

INTRODUCCIÓN: La extensión de la cirugía es motivo de controversia en el manejo de nódulos y cáncer diferenciado de tiroides (CDT). En nódulos benignos e indeterminados que requieran cirugía, la lobectomía es de elección, mientras que en CDT debe considerarse en tumores intratiroideos ≤ 4 cm. NUESTRO OBJETIVO objetivo fue reportar la primera cohorte chilena de nódulos tiroideos y CDT tratados con lobectomía por un equipo multidisciplinario. SUJETOS Y MÉTODOS: Se incluyeron pacientes sometidos a lobectomía por nódulos tiroideos y CDT que cumplieran: 1) tumor intratiroideo ≤4cm si punción aspirativa (PAF) Bethesda I, III, IV, V o VI; sin límite de tamaño si PAF Bethesda II, y 2) sin hallazgos sospechosos en la ecografía preoperatoria. En pacientes con CDT se describió presentación clínica, complicaciones y tipo de respuesta a tratamiento según ATA 2015 y MINSAL 2020. RESULTADOS: Se incluyeron 105 pacientes, edad 38±11 años, 84 (80%) mujeres, diámetro 2,2±1,5cm: 41 (39%) benignos y 64 (61%) CDT. De los CDT, 44 (69%) tenían cáncer papilar, 7 (11%) cáncer folicular y 13 (20%) NIFTP. Todos eran etapa I. Según MINSAL, 55 (85,9%) de riesgo muy bajo/bajo y 9 (14,1%) intermedio. Según ATA, 51 (80%) y 13 (20%) de riesgo bajo e intermedio, respectivamente. Se indicó totalización precoz y ablación con radioyodo en 6 (9,4%) pacientes: 4 por invasión venosa y 2 por CPT variedad sólida. De los 39 no totalizados seguidos ≥6 meses, no hubo casos de respuesta incompleta. Respecto a las complicaciones, ningún paciente tuvo hipocalcemia y 10 (9,5%) tuvieron disfonía transitoria. CONCLUSIONES: En pacientes con nódulos tiroideos o CDT seleccionados, la lobectomía es una alternativa adecuada. En CDT logra buen control de enfermedad sin necesidad de tratamiento adicional en cerca de 90% de los pacientes, con muy baja morbilidad asociada.

INTRODUCTION: The extension of surgery is a matter of debate in the management of thyroid nodules and differentiated thyroid cancer (DTC). While lobectomy is the procedure of choice in benign and indeterminate nodules that require surgery, it is an option in intrathyroidal DTC up to 4 cm. OUR OBJECTIVE was to report the first Chilean cohort of patients with thyroid nodules and DTC treated with lobectomy by a multidisciplinary team. SUBJECTS AND METHODS: We included patients with thyroid nodules treated with lobectomy, who met the following inclusion criteria: 1) intrathyroidal tumor ≤ 4cm if fine-needle aspiration biopsy (FNA) was Bethesda I, III, IV, V o VI; without size limit if FNA was Bethesda II, and 2) non-suspicious findings in preoperative ultrasound. In patients with DTC we described clinical presentation, complications and response to treatment according to ATA 2015 and MINSAL 2020. RESULTS: We included 105 patients, 38±11 years old, 84 (80%) female, diameter 2.2±1.5cm: 41 (39%) benign and 64 (61%) DTC. Among DTC, 44 (69%) had papillary thyroid cancer, 7 (11%) follicular thyroid cancer and 13 (20%) NIFTP. All had stage I DTC. According to MINSAL, 55 (85.9%) were very low/low, and 9 (14.1%) intermediate risk. According to ATA, 51 (80%) and 13 (20%) were low and intermediate risk, respectively. Six (9.4%) patients required early completion thyroidectomy and radioiodine ablation: 4 due to angioinvasion and 2 due to solid variant PTC. None of the 39 non-completed patients followed for at least 6 months had incomplete response. Regarding complications, there were no cases of hypocalcemia and 10 (9.5%) patients had transient dysphonia. CONCLUSIONS: In properly selected patients with thyroid nodules or DTC, lobectomy is an appropriate treatment option. In DTC, lobectomy accomplishes adequate disease control without need of further treatment in nearly 90% of patients, with very low associated morbidity.

In properly selected patients with differentiated thyroid cancer, antithyroglobulin antibodies decline after thyroidectomy and their sole presence should not be an indication for radioiodine ablation

ABSTRACT Objective Our objective was to evaluate the trend of antithyroglobulin antibodies (TgAb) during follow-up of patients with differentiated thyroid cancer (DTC) treated without RAI, as well as their role in the risk of recurrence. Subjects and methods This was a prospective, descriptive study. A total of 152 consecutive patients with DTC treated in a single institution undergoing total thyroidectomy without RAI and followed for a median of 2.3 years (0.5-10.3) were divided in two groups: TgAb(-) (n = 111) and TgAb(+) (n = 41). Patients were classified according to AJCC 7th and 8th editions, as well as to their risk of recurrence and response to treatment categories. Results Both groups, TgAb(-) and TgAb(+), were similar regarding patient and tumor characteristics. At the end of follow-up, 90 (59.2%), 57 (37.5%), 3 (2%) and 2 (1.3%) patients achieved excellent, indeterminate, biochemically incomplete and structurally incomplete response, respectively. The risk of structural recurrence was similar in both groups (TgAb[-] 0.9% vs. TgAb[+] 2.4%, p = 0.46). In the TgAb(+) group, TgAb became negative in 10 (24.4%), decreased ≥ 50% without negativization in 25 (60.9%), decreased < 50% in 4 (9.8%) and remained stable or increased in 2 (4.9%) cases. The only incomplete structural response had increasing TgAb during follow-up. Conclusions In properly selected patients with DTC, TgAb concentration immediately after total thyroidectomy should not mandate RAI ablation, and their trend during follow-up may impact the risk of recurrence.

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.

Riesgo de recurrencia en cáncer diferenciado de tiroides: escala MINSAL / Risk of recurrence in differentiated thyroid cancer

Background: Differentiated thyroid cancer (DTC) is generally associated with a favorable prognosis. Its treatment requires surgery, selective use of radioiodine and levothyroxine, and its intensity must be adjusted to the initial risks of mortality and recurrence. Aim: To validate the risk of recurrence classification developed by the Chilean Ministry of Health in 2013 (MINSAL 2013), and compare it with the American Thyroid Association (ATA) 2009 and 2015 classifications. Material and Methods: Retrospective study of 362 patients with DTC aged 44.3 ± 13.4 years (84% women), treated with total thyroidectomy, selective radioiodine ablation and levothyroxine and followed for a median of 4.2 years (range 2.0-7.8). Risk of recurrence was estimated with MINSAL 2013, ATA 2009 and ATA 2015 classifications, and risk of mortality with 7th and 8th American Joint Committee on Cancer (AJCC)/TNM systems. Clinical data obtained during follow-up were used to detect structural and biochemical persistence/recurrence. Results: A mean dose of 104 ± 48 mCi radioiodine was received by 91% of patients. MINSAL 2013 classified 148 (41%), 144 (40%), 67 (19%) and 3 (1%) patients as very low, low, intermediate and high risk of recurrence, respectively. Forty-five (12.4%) patients had persistence or recurrence during follow-up: 33 structural and 12 biochemical. Rates of persistence/recurrence on each category of MINSAL 2013 were 4.1%, 7.6%, 37.3% and 100%, respectively (p < 0.01). Areas under Receiver Operating Characteristic curves for persistence or recurrence of MINSAL 2013, ATA 2009 and ATA 2015 were 0.77 vs 0.73 vs 0.72, respectively. Conclusions: MINSAL 2013 classifies appropriately DTC patients and estimates correctly their risk of persistence or recurrence.

Estudio y manejo de nódulos tiroideos por médicos no especialistas. Consenso SOCHED / Study and management of thyroid nodes by non specialist physicians: SOCHED consensus

The thyroid nodule is a frequent cause of primary care consultation. The prevalence of a palpable thyroid nodule is approximately 4-7%, increasing up to 67% by the incidental detection of nodules on ultrasound. The vast majority are benign and asymptomatic, staying stable over time. The clinical importance of studying a thyroid nodule is to exclude thyroid cancer, which occurs in 5 to 10% of the nodules. The Board of SOCHED (Chilean Society of Endocrinology and Diabetes) asked the Thyroid Study Group to develop a consensus regarding the diagnostic management of the thyroid nodule in Chile, aimed at non-specialist physicians and adapted to the national reality. To this end, a multidisciplinary group of 31 experts was established among university academics, active researchers with publications on the subject and prominent members of scientific societies of endocrinology, head and neck surgery, pathology and radiology. A total of 14 questions were developed with key aspects for the diagnosis and subsequent referral of patients with thyroid nodules, which were addressed by the participants. In those areas where the evidence was insufficient or the national reality had to be considered, the consensus opinion of the experts was used through the Delphi methodology. The consensus was approved by the SOCHED board for publication.

Criterios de juicio moral de estudiantes de Medicina, según el Modelo Intuitivo Social / Survey on moral judgment criteria among medical students

Background: The evaluation of moral judgment criteria in medical students is important to develop effective educational programs in bioethics. Aim: To compare priority judgment criteria and moral judgment tendeney in medical students of first and fifth grade. Material and Methods: The Moral Foundations Questionnaire (MFQ30), to identify moral criteria was applied to 259 students, 63.7% from first year and 50.2% women. Results: The dominant moral tendeney both in first and fifth year students was liberal. Justice and compassion were the most important criteria in men and in women, respectively. Respect towards authority and sanctity were the least important criteria in women and men, respectively. Conclusions: The implications for moral psychology and medical education of these results are discussed.

Del macro al microcarcinoma tiroideo: cambios en las características de presentación del cáncer de tiroides en un centro universitario chileno en 20 años / From macro to micro thyroid carcinoma: records of a clinical hospital from 1991 to 2010

Background: The prevalence of thyroid cancer has increased, particularly in nodules smaller than 10 mm, probably due to the growing use of routine thyroid ultrasound. There is controversy about the biological behavior of micro carcinomas and the relevance of their early detection. Aim: To characterize the clinical presentation of thyroid cancer over 20 years in an University medical center and to evaluate the differences between macro and micro carcinomas. Patients and Methods: We reviewed 1547 surgical biopsy records of thyroid cancer in our institution obtained between 1991 and 2010. Results: We observed a sustained increase in the rate of thyroidectomies for thyroid cancer (per 1000 surgical procedures) in the study period. Papillary, follicular, mixed, medullary and anaplastic carcinomas were observed in 95, 3, 2, 0.5 and 0.1% of biopsies, respectively. The incidence of tumors of less than 10 mm (micro carcinoma) also increased. Those findings were associated with a significant decrease in tumor aggressiveness, determined by a low frequency of surgical margin involvement of thyroid capsule, perithyroid tissue invasion, vascular permeation and lymph node metastases. Conclusions: The increased prevalence of thyroid cancer, especially of micro carcinomas, may reflect the greater use of diagnostic ultrasound or represent a real change in the biological behavior of this disease and our data suggest that further studies are needed to know the impact of early treatment in the outcome of those patients because of the real less histologic agressiveness of micro carcinomas.

Aproximación al patrón de normalidad de TSH para la población chilena según Encuesta Nacional de Salud 2009-2010 / Thyroid stimulating hormone reference values derived from the 2009-2010 Chilean National Health Survey

Background: The determination ofthyroid stimulating hormone (TSH) reference values is critical for the diagnosis ofthyroid diseases. Aim: To explore and discuss different definitions to establish TSH reference values using a Chilean national survey sample. Material and Methods: The 2009-2010 Chilean National Health Survey recruited 5,416participants between the ages of 15 and 96years, from all geographic regions of Chile, including urban and rural zones. TSH was measured in a random subsample of 2,785 adults. Median value, 2.5 and 97.5 percentiles were described in three different populations: total survey population, "disease-free population" and the "laboratory kit disease free population". Results: TSH values were higher among women, the elderly and the less educated population. The 97.5 percentile value in the disease-free population was 7.46 uUl/ml. Using this value as a cut-off, hypothyroidism prevalence would be 4.8% in Chile and estimated pharmacological treatment coverage would be 58%. When laboratory kit cut-offs are used, prevalence rises to 22% and treatment coverage drops to 12%. The 2.5 percentile value in the disease-free population was 0.83 uUl/ml, which yields an estimated hyperthyroidism prevalence of3.89%. Conclusions: Median TSH concentration values in the Chilean "disease-free population" are higher than those proposed by laboratory kits and those of developed countries. TSH values in the general population of Chile are also higher in women, the elderly and the less educated population.

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.

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.

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 .

Prevalencia de hiperaldosteronismo en hipertensión arterial: lecciones del tiempo / Prevalence of hyperaldosteronism in hypertension: lessons of time

Un 30 por ciento de los hipertensos esenciales cursa con actividad de renina plasmática baja. El hiperaldosteronismo primario es la forma patológica clásica de hipertensión con renina baja, la prevalencia de esta enfermedad, ha sido objeto de diversos estudios y controversias a lo largo del tiempo. Nuestros estudios demostraron inicialmente que en los hipertensos esenciales, los niveles de aldosterona eran más altos, los niveles de actividad de renina plasmática eran más bajos y la relación aldosterona/renina plasmática era más alta que en los normotensos. Posteriormente, detectamos en población hipertensa previamente catalogada como esencial en base a normokalemia, un 9.5 por ciento de los pacientes eran portadores de hiperaldosteronismo primario. Los estudios actuales comprenden más de 2000 hipertensos no seleccionados, con una prevalencia de hiperaldosteronismo cercana al 7 por ciento, con valores que oscilan entre 4.6 y el 9.5 por ciento. El análisis de las características clínicas de los pacientes en los últimos estudios, han demostrado que los portadores de hiperaldosteronismo son más jóvenes, requieren un mayor número de drogas para controlar su presión arterial y que sus cifras tensionales al diagnóstico son más altas que los otros hipertensos. En pacientes con hipertensión resiente el hiperaldosteronismo puede encontrarse hasta en un 20 por ciento de ellos. Frente a las nuevas evidencias, es necesario reformular el concepto de hiperaldosteronismo como un proceso patológico continuo, en el que la mayoría de los pacientes se presentan con una forma atenuada de la enfermedad normokalémica y solamente una minoría se presentan con el cuadro clínico clásico.