Impact of preconception thyrotrophin on obstetric outcomes in the fertile population.

INTRODUCTION: There is evidence that subclinical hypothyroidism is associated with infertility, miscarriage and obstetric complications. However, there is controversy regarding the optimal TSH value in women seeking pregnancy. Current guidelines recommend that hypothyroid women with levothyroxine replacement who are planning pregnancy should optimise the dose of levothyroxine to achieve thyrotrophin (TSH) levels <2.5 mU/l, since these requirements increase in pregnancy, thus reducing the risk of TSH elevation during the first trimester. In women with infertility, who undergo highly complex treatments and have positive thyroid autoimmunity, values of TSH <2.5 mU/l prior to fertility treatment are suggested. Although this is a different population, these «optimal¼ TSH levels were also extended to euthyroid women without evidence of infertility, who are seeking pregnancy. OBJECTIVES: Determine whether preconception TSH levels between 2.5 and 4.64 mIU/l are associated with adverse obstetric outcomes in euthyroid women. MATERIALS AND METHODS: Retrospective cohort study. We evaluated 3265 medical records of pregnant women aged 18-40 years, euthyroid (TSH 0.5-4.64 mU/ml), with TSH measurement at least one year before gestation. 1779 met inclusion criteria. The population was divided according to categories: TSH 0.5-2.4 mU/l (optimal) and TSH 2.5-4.6 mU/l (suboptimal). Information on maternal and fetal obstetric outcomes was collected from each group. RESULTS: We found no statistical difference in the occurrence of adverse obstetric events between the two groups. There was also no difference when adjusting for thyroid autoimmunity, age, body mass index, previous diabetes and previous arterial hypertension. CONCLUSION: Our results suggest that the reference range of TSH used in the general population could be used in women seeking pregnancy, even in the presence of thyroid autoimmunity. Treatment with levothyroxine should be considered only in patients with special situations.

Assessment of the utility of measuring Thyroglobulin mRNA levels by Quantitative Real-Time PCR in the follow-up of differentiated thyroid cancer patients.

INTRODUCTION: The determination of thyroglobulin levels by immunoassay and imaging studies is subject to interference by antithyroglobulin antibodies in up to 30% of cases, suggesting a need to find alternative methods for the follow-up of a significant number of thyroid cancer patients. OBJECTIVES: Assess the sensitivity, specificity, and predictive values of thyroglobulin messenger RNA levels measured by quantitative Real Time-PCR (qRT-PCR) in the blood of patients followed for differentiated thyroid cancer. METHODS: This is a prospective study of Tg-mRNA levels measured with qRT-PCR. A peripheral blood sample was taken in patients with excellent response (69) and with structural incomplete response to treatment (23). Results were analysed using the Unity Real-Time program and expressed as fg/µg RNA. A Receiver Operating Characteristic curve was constructed to assess Tg-mRNA cut-off values. RESULTS: Tg-mRNA levels were not significantly different between the group with excellent response [0.10 fg/µg RNA (0.08-0.17)] and the group with incomplete structural response [0.133 fg/µg RNA (0.07-0.33)] (P < .06). Test sensitivity was 69.6%, specificity was 59.4%, negative predictive value was 85.4% and positive predictive value 36.4% CONCLUSIONS: Our experience shows that this technique could be useful as a rule-out test in selected cases, but its low sensitivity and specificity preclude its usefulness as a first-line test.

Assessment of the utility of measuring Thyroglobulin mRNA levels by Quantitative Real-Time PCR in the follow-up of differentiated thyroid cancer patients. / Evaluación de la utilidad de medir los niveles de ARN mensajero de tiroglobulina por PCR cuantitativa en tiempo real para el seguimiento de pacientes con cáncer diferenciado de tiroides.

INTRODUCTION: The determination of thyroglobulin (Tg) levels by immunoassay is subject to interference by antithyroglobulin antibodies in up to 30% of cases, suggesting a need to find alternative methods for the follow-up of a significant number of thyroid cancer patients. OBJECTIVES: Assess the sensitivity, specificity, and predictive values of thyroglobulin messenger RNA (Tg-mRNA) levels measured by quantitative Real Time-PCR (qRT-PCR) in the blood of patients followed for differentiated thyroid cancer. METHODS: This is a prospective study of Tg-mRNA levels measured with qRT-PCR. A peripheral blood sample was taken in patients with excellent response (n=69) and with structural incomplete response to treatment (n=23). Results were analysed using the Unity Real-Time program and expressed as fg/µg RNA. A Receiver Operating Characteristic curve was constructed to establish Tg-mRNA cut-off values. RESULTS: Tg-mRNA levels were not significantly different between the group with excellent response [0.10fg/µg RNA (0.08-0.17)] and the group with incomplete structural response [0.133fg/µg RNA (0.07-0.33)] (p<0.06). Test sensitivity was 69.6%, specificity was 59.4%, negative predictive value was 85.4% and positive predictive value was 36.4%. CONCLUSIONS: Our experience shows that this technique could be useful as a rule-out test in selected cases, but its low sensitivity and specificity preclude its usefulness as a first-line test.

Role of the Mechanisms of Detection in the Increased Risk of Thyroid Cancer: A Retrospective Cohort Study in an HMO in Buenos Aires.

BACKGROUND: Two hypotheses attempt to explain the increase of thyroid cancer (TC) incidence: overdetection by excessive diagnostic scrutiny and a true increase in new cases brought about by environmental factors. Changes in the mechanism of detection and the risk of incidentally diagnosed TC could result in an increase of TC incidence. METHODS: Retrospective cohort study. We identified incident cases of TC from the pathological reports of patients in a HMO and review of clinical records. The results were analyzed in two periods: 2003-2007 and 2008-2012. Incidence rates expressed per 100,000 person-years (with 95% CI) and relative risk of incidence rates of incidental and nonincidental TC were estimated. RESULTS: The relative risk of incidentally detecting a thyroid cancer in 2008-2012 compared to 2003-2007 was 6.06 (95%CI 1.84-20.04). Clinical evaluations detected 31 (75.6%) cancers in the period 2003-2007 and 70 (51.8%) cancers in the period 2008-2012 (p<0.007). Although tumor median size was significantly lower in the period 2008-2012 (10 vs. 14 mm, p<0.03), tumors greater than 40 mm (4.3%) were only present in 2008-2012. The female/male ratio decreased between analyzed periods from 8 (3-21) to 4 (3-7). CONCLUSIONS: Our findings partially support the hypothesis of increased incidence due to overdetection but do not explain the changes in the increase of larger tumors and decrease in the female/male ratio, which could be secondary to the influence of unidentified environmental factors.

Thyroid lipomatosis in a 36-year-old patient with rheumatoid arthritis and a kidney transplant.

UNLABELLED: Thyroid lipomatosis is a rare disease, as a total of 20 cases have been described in the literature. It is characterized by diffuse infiltration of the stroma by mature adipose tissue and by progressive growth that produces different degrees of compressive symptoms. Our aim is to present the case of a 36-year-old woman who consulted because of dyspnea caused by a multinodular goiter. She underwent surgery with the presumptive diagnosis of a malignant neoplasia, but the pathological examination of the surgical specimen established the diagnosis of thyroid lipomatosis. LEARNING POINTS: Thyroid lipomatosis is a rare, benign disease characterized by diffuse infiltration of the stroma by mature adipose tissue.The pathophysiology of diffuse proliferation of adipose tissue in the thyroid gland is unclear.Thyroid lipomatosis is clinically manifested by a progressive enlargement of the thyroid that can involve the airway and/or upper gastrointestinal tract, producing dyspnea, dysphagia, and changes in the voice.Given the rapid growth of the lesion, the two main differential diagnoses are anaplastic carcinoma and thyroid lymphoma.Imaging studies may suggest a differential diagnosis, but a definitive diagnosis generally requires histopathological confirmation after a thyroidectomy.

Estesioneurablastoma y panhipopituitarismo: presentación de un caso / Esthesionerublastoma and panhypopituitarysm: case report

Objetivos: presentar un caso de estesioneuroblastoma que desarrolla hipopituitarismo como complicación grave de su tratamiento. Realizar una revisión de la literatura reciente sobre el tratamiento y pronóstico de estos tumores. Presentar una sistemática de pesquisa de hipipituitarismo en estos pacientes. Descripción: paciente masculino de 68 años que se presenta con metástasis submaxilar de estesioneuroblastoma. La RMN mostraba una masa neoplásica de gran tamaño centrada sobre el etmoides, que comprometía base de cráneo y corteza fronto-orbitaria izquierda. Intervención: se realizó tratamiento combinado de radio y quimioterapia preoperatorios, y cirugía por vía craniofacial. A los 20 meses ingresa con un cuadro convulsivo e hiponatremia grave. Se hace diagnóstico de panhipopituitarismo y el cuadro revierte con la administración de hidrocortisona de 10 mg vía oral. Conclusión: el estesioneuroblastoma es un tumor infrecuente cuyo tratamiento incluye cirugía, radioterapia y quimioterapia. Es necesario un alto índice de sospecha y el seguimiento de por vida para pesquisar la instalación del hipopituitarismo como complicación grave de su tratamiento.

Objectives. To report a case of esthesioneuroblastoma associated to hypopituitarism as a late complication of its treatment, to review the literature regarding treatment and prognosis and to resent a guideline for the diagnosis of hypopituitarism in these patients. Description. A 68-year-old male patient presented with a submaxilar metastasis of a very large esthesioneuroblastoma that involved both ethmoidal bones and invaded left cribiform plate and frontal lobe. Intervention. The patient underwent combined modality treatment with preoperative radio and chemotherapy, and craniofacial sugery of the tumor. Twenty months later he was admitted with a seizure and severe hyponatremia. A diagnosis of panhypopituitarism was made, and his sodium reverted to normal with de administration of 10 mg of hydrocortisone p.o. Conclusions Esthesioneuroblastomas are rare tumours that require multimodality treatment with surgery, radiotherapy and chemotherapy. Hypopituitarism is a late and potentially fatal complication that must be suspected and tested during the patients‘ whole lifespan.

Carcinoma medular de tiroides familiar (CMTF): primera familia descripta con CMTF asociado a la mutación Cys611Trp del proto-oncogen RET / Familial medullary thyroid carcinoma (FMTC): first family described with FMTC associated to Cys611Trp mutation of RET proto-oncogene

La neoplasia endócrina múltiple tipo 2 (NEM 2) es un síndrome autosómico dominante identificado en 500-1.000 familias hasta la fecha. Todas las variantes de NEM 2 muestran una penetrancia mayor al 90% para la manifestación del carcinoma medular de tiroides, mientras que la penetrancia es menor y variable para el feocromocitoma (50%) y tumoresparatiroideos (25%). El CMTF es una variante rara dentro del NEM 2 en la que cuatro o más miembros de una familiapresentan evidencia de carcinoma medular de tiroides sin manifestación asociada de feocromocitoma o hiperparatiroidismo primario. En los últimos años, el estudio genético del proto-oncogen RET en los casos índices para carcinoma medular y en sus posibles portadores se ha impuesto debido a que se ha demostrado que la tiroidectomía en los primeros 2 a 5 añosde edad puede prevenir o curar el CMT, inclusive antes de su expresión bioquímica en el NEM 2. La indicación detiroidectomía profiláctica es menos clara en CMTF. Con respecto a las mutaciones halladas en el proto-oncogen RET(10q11.2) el 80-90% afectan el codón 634, y con menor frecuencia los codones 918 (10-20%), 620 (6-8%), 618 (3-5%), 611 (2-3%) y 609 (0-1%). En este trabajo presentamos una familia portadora de una mutación heterocigota infrecuente en el proto-oncogen RET, Cys611Trp, (sólo un caso previo mencionado en la literatura internacional) que no fue detectadaen un estudio genético previo. Se plantean dos posibles conductas en los dos niños asintomáticos, portadores de lamutación. Tiroidectomía preventiva, o la conducta expectante hasta la expresión bioquímica. Basándonos en distintosconsensos internacionales, nos inclinaríamos por la primera conducta.

Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant syndrome identified to date in 500-1.000 kindreds. All variants of MEN 2 show a penetrance higher than 90% for medullary thyroid carcinoma (MTC), whilst the penetrance for pheochromocytoma (50%) and parathyroid tumors (25%) is lower and variable. Familial medullary thyroid carcinoma (FMTC) is a rare variant of MEN 2, in which four or more members of a family have MTC without pheochromocytoma or primary hyperpathyroidism. In recent years genetic testing for the proto-oncogene RET mutations in the index case ofMTC and in possible carriers has been used, because it has been demonstrated that prophylactic thyroidectomy before 2– 5 years of age can prevent or cure MTC in MEN 2, even before its biochemical expression. Prophylactic thyroidectomy is not so clearly beneficial in FMTC. Mutations in the proto-oncogene RET (10q11.2) affect codon 634 in 80 – 90%, and less frequently, codons 918 (10-20%), 620 (6-8%), 618 (3-5%), 611 (2-3%) and 609 (0-1%). In this report we describe a family with an infrequent mutation in the proto-oncogene RET, Cys611Trp, (only one case reported in the bibliography). This mutation had not been detected in a previous genetic study, and we discuss herein the clinical management. Two approaches for the 2 asymptomatic young carriers: 1) prophylactic thyroidectomy as soon as the mutation is detected or 2 ) to wait for a positive stimulated calcitonin test and then perform a thyroidectomy. Studies from an international consortium lead us to believe that an early prophylactic thyroidectomy is the appropiate course of action.