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Efectos endocrinológicos del litio: Mecanismos fisiopatológicos e implicancias clínicas
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Manríquez, Fernando

; Mosso, Lorena

; Fardella, Carlos

Revista médica de Chile

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Abr 2024, Volume 152 Nº 4 Páginas 498 - 507

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

ABSTRACT Lithium carbonate has a narrow therapeutic range capable of producing various adverse effects; despite this fact, it is used as first-line therapy in patients with bipolar disorder (BD) thanks to its high effectiveness. Among its adverse events are several conditions at the endocrine level, such as hypothyroidism, hyperthyroidism, hypercalcemia, hyperparathyroidism, and nephrogenic diabetes insipidus. The adherence to current guidelines for monitoring those events is low. The objective of this review is to provide insight into the pathophysiological mechanisms of the endocrine effects of lithium and give recommendations based on the current literature for the monitoring and treatment of these conditions.

RESUMEN El carbonato de litio es un fármaco con estrecho margen terapéutico capaz de producir diversos efectos adversos, a pesar de lo cual se utiliza como tratamiento de primera línea en pacientes con trastorno afectivo bipolar (TAB) gracias a su alta efectividad. Entre sus efectos adversos se encuentran varias afecciones a nivel endocrino, como hipotiroidismo, hipertiroidismo, hipercalcemia, hiperparatiroidismo y diabetes insípida nefrogénica. La adherencia a las recomendaciones de monitoreo de estas reacciones es baja. El objetivo de esta revisión es proporcionar información sobre los mecanismos fisiopatológicos de los efectos endocrinos del litio y dar recomendaciones basadas en la literatura para el seguimiento y tratamiento de estas condiciones.

https://doi.org/10.4067/s0034-98872024000400498

Active surveillance is a feasible and safe strategy in selected patients with papillary thyroid cancer and suspicious cervical lymph nodes detected after thyroidectomy
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Solórzano, Marlín

; Lustig, Nicole

; Mosso, Lorena

; Espinoza, Martín

; Santana, Roberto

; Gonzalez, Hernan

; Montero, Pablo H.

; Cruz, Francisco

; Solar, Antonieta

; Domínguez, José Miguel

Archives of Endocrinology and Metabolism

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2024, Volume 68 elocation e230146

Resumo: En | Texto: En | PDF: En

ABSTRACT Objective: After initial treatment, up to 30% of patients with papillary thyroid cancer (PTC) have incomplete response, mainly cervical lymph node (LN) disease. Previous studies have suggested that active surveillance (AS) is a possible option for these patients. Our aim was to report the results of AS in patients with PTC and cervical LN disease. Materials and methods: In this retrospective observational study, we included adult patients treated and followed for PTC, who presented with cervical LN disease and were managed with AS. Growth was defined as an increase ≥ 3mm in either diameter. Results: We included 32 patients: 27 (84.4%) women, age of 39 ± 14 years, all initially treated with total thyroidectomy, and 22 (69%) with therapeutic neck dissection. Cervical LN disease was diagnosed 1 year (0.3-12.6) after initial management, with a diameter of 9.0 mm (6.0-19.0). After a median AS of 4.3 years (0.6-14.1), 4 (12.5%) patients had LN growth: 2 (50%) of whom were surgically removed, 1 (25%) was effectively treated with radiotherapy, and 1 (25%) had a scheduled surgery. Tg increase was the only predictive factor of LN growth evaluated as both the delta Tg (p < 0.0366) and percentage of Tg change (p < 0.0140). None of the included patients died, had local complications due to LN growth or salvage therapy, or developed distant metastases during follow-up. Conclusions: In selected patients with PTC and suspicious cervical LNs diagnosed after initial treatment, AS is a feasible and safe strategy as it allows effective identification and treatment of the minority of patients who progress. Objective 30 (PTC response (LN (AS methods study Results 3 84.4% 844 84 (84.4% women thyroidectomy 69% 69 (69% dissection 0.312.6 03126 0.3 12.6 0 12 6 (0.3-12.6 management 90 9 9. 6.019.0. 60190 6.0 19.0 . 19 (6.0-19.0) 43 4. 0.614.1, 06141 0.6 14.1 , (0.6-14.1) 12.5% 125 5 (12.5% 50% 50 (50% removed 25% 25 (25% radiotherapy surgery p 0.0366 00366 0366 0.0140. 00140 0.0140 0140 0.0140) died therapy followup. followup follow up. follow-up Conclusions progress 84.4 8 (84.4 (69 312 0.312. 0312 03 0. 126 12. (0.3-12. 019 6.019.0 6019 60 6. 190 19. (6.0-19.0 614 0.614.1 0614 06 141 14. (0.6-14.1 12.5 (12.5 (50 (25 0.036 0036 036 0014 0.014 014 84. (84. (6 31 0.312 031 (0.3-12 01 6.019. 601 (6.0-19. 61 0.614. 061 (0.6-14. (12. (5 (2 0.03 003 001 0.01 (84 ( 0.31 (0.3-1 6.019 (6.0-19 0.614 (0.6-14 (12 0.0 00 (8 (0.3- 6.01 (6.0-1 0.61 (0.6-1 (1 (0.3 (6.0- (0.6- (0. (6.0 (0.6 (0 (6.

https://doi.org/10.20945/2359-4292-2023-0146

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

; Muñoz, Francisco

; Donoso, Francisca

; López, Jorge

; Bruera, María José

; Ruiz-Esquide, Magdalena

; Mosso, Lorena

; Lustig, Nicole

; Solar, Antonieta

; Droppelmann, Nicolás

; Montero, Pablo H.

; González, Hernán E.

; Domínguez, José Miguel

Archives of Endocrinology and Metabolism

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Out 2020, Volume 64 Nº 5 Páginas 542 - 547

Resumo: En | Texto: En | PDF: En

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.

https://doi.org/10.20945/2359-3997000000270 436 downloads

Cholestasis secondary to hyperthyroidism in Graves’ disease. Report of one case
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Barra, María I.

; Olmos, Roberto

; Barrera, Francisco

; Mosso, Lorena

; Domínguez, José M.

Revista médica de Chile

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Mai 2020, Volume 148 Nº 5 Páginas 697 - 701

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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.

771 downloads

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
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Zavala, Luis Felipe

; Barra, María Inés

; Olmos, Roberto

; Tuttle, Michael

; González, Hernán

; Droppelmann, Nicolás

; Mosso, Lorena

; Domínguez, José M.

Archives of Endocrinology and Metabolism

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Jun 2019, Volume 63 Nº 3 Páginas 293 - 299

Resumo: En | Texto: En | PDF: En

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.

https://doi.org/10.20945/2359-3997000000123 865 downloads

Riesgo de recurrencia en cáncer diferenciado de tiroides: escala MINSAL
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Domínguez, José Miguel

; Martínez, María Teresa

; Massardo, José Miguel

; Muñoz, Suelí

; Droppelmann, Nicolás

; González, Hernán E.

; Mosso, Lorena

Revista médica de Chile

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Mar 2018, Volume 146 Nº 3 Páginas 282 - 289

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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.

https://doi.org/10.4067/s0034-98872018000300282 3702 downloads

Estudio y manejo de nódulos tiroideos por médicos no especialistas. Consenso SOCHED
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Tala, Hernán

; Díaz, René E.

; Domínguez Ruiz-Tagle, José Miguel

; Sapunar Zenteno, Jorge

; Pineda, Pedro

; Arroyo Albala, Patricia

; Barberán, Marcela

; Cabané, Patricio

; Cruz Olivos, Francisco

; Gac, Patricio E.

; Glasinovic Pizarro, Andrea

; González, Hernán E.

; Grob, Francisca

; Hidalgo Valle, Maria Soledad

; Jaimovich, Rodrigo

; Lanas, Alejandra

; Liberman, Claudio

; Lobo Guiñez, Maite

; Madrid, Arturo

; Moreno Seguel, Marcela

; Mosso, Lorena

; Munizaga, Fernando C.

; Ortiz Parada, Eugenia

; Osorio Gonnet, Fernando

; Slater Morales, Jeannie

; Solar, Antonieta

; Stehr, Carlos

; Vásquez Rodríguez, Félix

; Véliz, Jesús

; Villaseca Najarian, Roberto

; Wohllk, Nelson

Revista médica de Chile

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Ago 2017, Volume 145 Nº 8 Páginas 1028 - 1037

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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.

https://doi.org/10.4067/s0034-98872017000801028 28478 downloads

Criterios de juicio moral de estudiantes de Medicina, según el Modelo Intuitivo Social
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Bedregal, Paula

; León, Tomás

; Shand, Beatriz

; Mosso, Lorena

Revista médica de Chile

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Jun 2013, Volume 141 Nº 6 Páginas 704 - 709

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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 tendency 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.

8060 downloads Citado 1 vez em SciELO

Del macro al microcarcinoma tiroideo: cambios en las características de presentación del cáncer de tiroides en un centro universitario chileno en 20 años
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Mosso, Lorena

; Campusano, Claudia

; González, Hernán

; Domínguez, José Miguel

; Salman, Patricio

; Suazo, Valeria

; Solar, Antonieta

; Cerda, Jaime

Revista médica de Chile

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Abr 2013, Volume 141 Nº 4 Páginas 442 - 448

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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.

4518 downloads Citado 2 vezes em SciELO

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Aproximación al patrón de normalidad de TSH para la población chilena según Encuesta Nacional de Salud 2009-2010
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Mosso, Lorena

; Margozzini, Paula

; Trejo, Pamela

; Domínguez, Angélica

; Solari, Sandra

; Valdivia, Gonzalo

; Arteaga, Eugenio

Revista médica de Chile

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Jan 2013, Volume 141 Nº 1 Páginas 95 - 103

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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.

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11.

Utilidad de la PTH intraoperatoria como predictor de curación quirúrgica en hiperparatiroidismo primario
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Domínguez, José Miguel

; Velasco, Soledad

; Goñi, Ignacio

; León, Augusto

; González, Hernán

; Claure, Raúl

; Arteaga, Eugenio

; Campusano, Claudia

; Fardella, Carlos

; López, José Manuel

; Mosso, Lorena

; Rodríguez, José Adolfo

; González, Gilberto

Revista médica de Chile

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Dez 2009, Volume 137 Nº 12 Páginas 1591 - 1596

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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%) at 24 hours and 50 of 52 patients followed for six months (96%). The pathological study disclosed an adenoma in 69 (78%), and multiglandular disease in 16 (18%), a parathyroid cancer in one and a normal gland in one patient. Intraoperative PTH predicted early and definitive cure in 97% and 100% of patients with a single adenoma, respectively. Among patients with multiglandular disease, the predictive figures were 94% and 100%, respectively. Conclusions: Intraoperative PTH measurement efficiently predicts early and definitive surgical cure of PHPT.

5737 downloads Citado 2 vezes em SciELO

12.

Diseño de una escala ecográfica predictora de malignidad en nódulos tiroideos: Comunicación preliminar
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Domínguez, José Miguel

; Baudrand, René

; Arteaga, Eugenio

; Campusano, Claudia

; González, Gilberto

; Mosso, Lorena

; Cavada, Gabriel

; Cruz, Francisco

; Torres, Javiera

; Solar, Antonieta

; Arias, Tatiana

; Pizarro, Alejandra

; Gómez, Marcelo

; Fardella, Carlos

Revista médica de Chile

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Ago 2009, Volume 137 Nº 8 Páginas 1031 - 1036

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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% confidence intervals (CI) 18.7-140.9), solid predominance (OR 25.1; 95% CI 6-220), hypoechogenicity (OR 23.5, 95% CI 6.5-122.6), irregular borders (OR 17, 95% CI 7.2-42.9), lymph node involvement (OR 12.3, 95% CI2.7-112), central vascularization (OR 12.2, 95% CI 4.8-33.3), local invasion and hyperechogenicity (OR 0.2; CI95% CI 0.03-0.6). Multivariate analysis disclosed microcalcifications (OR 28.1; CI 95% 8.9-89), hypoechogenicity (OR 9.4; 95% CI 1.5-59.5) and irregular borders (OR 4.7; CI 95% 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% (Likelihood ratio (LR) 45) and 5.4% in their absence (LR 0.06). Conclusions: This scale predicts the presence or absence of PTC using simple ultrasound characteristics.

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13.

Marcadores de inflamación endotelial subclínica en una familia con hiperaldosteronismo familiar tipo I por mutación de novo
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Stehr, Carlos B

; Carvajal, Cristian A

; Lacourt, Patricia

; Alcaíno, Hernán

; Mellado, Rosemarie

; Cattani, Andreína

; Mosso, Lorena M

; Lavandera, Sergio

; Fardella, Carlos E

Revista médica de Chile

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Set 2008, Volume 136 Nº 9 Páginas 1134 - 1140

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

Background: Type I familial hyperaldosteronism is caused by the presence of a chimaeñc 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. Residís: All affected subjects had approximately a 50% 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 deleteríous effect of aldosterone on the endothelium.

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14.

Hiperaldosteronismo primario
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Fardella, Carlos E

; Mosso, Lorena M

; Carvajal, Cristian A

Revista médica de Chile

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Jul 2008, Volume 136 Nº 7 Páginas 905 - 914

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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%) in hypertensive population, has been detected measuring plasma aldosterone/renin activity ratio (ARR) as screening test. This ratio increases along with the severity ofthe 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

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15.

Regiones polimórficas del gen 11ß-hidroxiesteroide deshidrogenasa tipo 1 (11ßHSD1) en hipertensión arterial esencial: Posible rol etiopatogénico
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Morales, Mauricio A

; Carvajal, Cristian A

; Ortiz, Eugenia

; Mosso, Lorena M

; Artigas, Rocío A

; Owen, Gareth I

; Fardella, Carlos E

Revista médica de Chile

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Jun 2008, Volume 136 Nº 6 Páginas 701 - 710

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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% 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 in HPA and RAA axis of obese essential hypertensives. These changes mayresult of modifications in the expression of 11ßHSD1, leading to increased cortisol and aldosterone levéis independent of ACTH and renin control, respectively

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