Serum cholesterol levels are inversely associated with the risk of malignancy in subjects with Bethesda category IV thyroid nodules.

INTRODUCTION: Some epidemiological data suggest that there may be an inverse relationship between cholesterol levels and the risk of thyroid cancer in the overall population. The present study was aimed to evaluate the lipid profile specifically in subjects with Bethesda category IV thyroid nodules, and compare whether there were any differences between those with benign and malignant nodules. METHODS: Single-centre, retrospective study on 204 subjects treated by partial or total thyroidectomy for excision of a Bethesda category IV thyroid nodule, who had undergone a blood lipid profile test in the 12 months prior to surgery. In addition to lipid measures, other demographic, clinical, biochemical and ultrasound data were collected. RESULTS: Seventy-five subjects (36.8%) were diagnosed with thyroid carcinoma in the definitive histopathological examination. Patients with thyroid cancer had lower levels of total cholesterol, LDL-cholesterol and non-HDL-cholesterol than subjects with benign thyroid diseases. There were no differences in HDL-cholesterol, triglycerides or total cholesterol/HDL-cholesterol ratio. There were no differences either between groups in other clinical, biochemical and ultrasound variables, including the use of lipid-lowering drugs. In multivariate analysis, only LDL-cholesterol was independently associated with malignancy. Subjects with follicular carcinoma showed the lowest cholesterol levels, while those with papillary carcinoma had intermediate values between the group with follicular carcinoma and the group with benign thyroid diseases. CONCLUSIONS: In subjects with cytologically indeterminate Bethesda category IV thyroid nodules, levels of total cholesterol, non-HDL-cholesterol and, particularly, LDL-cholesterol are lower among those with malignant nodules.

Successful outcome of pregnancy in a patient with Cushing's disease under treatment with ketoconazole during the first trimester of gestation.

BACKGROUND: Ketoconazole is the most widely used medical treatment for Cushing's syndrome, but, because of its potential to cause birth defects, it is not recommended during pregnancy. Specifically, due to its antiandrogenic effects, ketoconazole entails theoretical risks of interfering with the development of external genitalia in male fetuses. CASE: A pregnancy was diagnosed at 13 weeks of gestation in a 26-year-old woman with Cushing's disease under treatment with ketoconazole. The drug was withdrawn and the patient underwent transsphenoidal surgery at 16 weeks of pregnancy. She did not develop postsurgical adrenal insufficiency and was treated with metyrapone during the second and third trimesters of gestation. Partum was induced at 34 weeks of pregnancy. The patient delivered a healthy male infant with normal external genitalia. CONCLUSION: Treatment with ketoconazole during the critical period of organogenesis did not cause congenital birth defects to the male fetus of a woman with Cushing's disease. This report should be taken into account for future cases of unplanned pregnancies in women with Cushing's syndrome treated with ketoconazole, as well in those cases in which other therapeutic options are not feasible.

Correlation between TSH levels and quality of life among subjects with well-controlled primary hypothyroidism.

PURPOSE: It has been suggested that increasing levothyroxine dose to lower TSH levels within the normal laboratory range might be a therapeutic option for patients with apparently well-controlled primary hypothyroidism who are dissatisfied with their treatment and complain of physical or psychological symptoms. This study assessed whether there is a relationship between TSH levels and health-related quality of life (HRQoL) among subjects with adequately treated hypothyroidism. METHODS: HRQoL was measured with the specific thyroid disease ThyPRO-39 questionnaire in 218 consecutive patients with primary hypothyroidism of any cause attending an Endocrinology Department in a single center. Patients had TSH values within the normal laboratory range on a blood test performed not before than 6 weeks prior to study participation, but they were not aware of their lab results. The association between TSH values and the different ThyPRO-39 scales was analyzed by means of multiple regression models, both linear and additive, in which, in addition to TSH, a wide set of clinical and sociodemographic variables potentially related to HRQoL were also considered. RESULTS: TSH levels and the use of anxiolytic and antidepressant drugs were the only variables that showed a positive linear correlation with the ThyPRO-39 composite scale in the multivariate regression analysis, indicating greater impairment in HRQoL with increasing TSH values. TSH was also independently correlated to scores of scales dealing on tiredness and emotional susceptibility. CONCLUSIONS: In patients with primary hypothyroidism, higher TSH values, even within the normal reference range, are associated with greater deterioration of HRQoL.

TSH Level and Risk of Malignancy in Patients with Bethesda Category IV Thyroid Nodules.

Fine needle aspiration biopsy does not permit to distinguish between benign and malignant follicular thyroid lesions (category IV in the Bethesda Cytopathology System). Some reports have suggested an association between increased serum TSH levels and thyroid cancer, so the aim of this study was to investigate the association between TSH levels and malignancy in patients with follicular thyroid nodules. Therefore, we conducted a retrospective study of all subjects who underwent surgical treatment for Bethesda IV thyroid nodules in a single center (years 2012-2017). A total of 127 patients were analyzed, and malignancy was present in 38.6% of the patients. Using ROC analysis, the best TSH cut-off point to differentiate benign from malignant disease was 2.1 mU/l and the age cut-off with better sensitivity and specificity was 47 years. The proportion of subjects with TSH ≥ 2.1 mU/l was greater among subjects with cancer than in those with benign diseases (65.3 vs 44.9%, P = 0.029). The concurrence of both cut-off points (TSH ≥ 2.1 mU/l and age ≥ 47 years) showed a higher diagnostic accuracy than either of the two variables separately. Therefore, the present study supports an association between serum concentrations of TSH and risk of malignancy among subjects with Bethesda IV thyroid nodules. TSH levels could modify the diagnostic and therapeutic approach of patients with Bethesda IV nodules.

[Uso de los valores de hormona paratiroidea intranodular obtenidos por punción con aguja fina como factor predictivo de hipoparatiroidismo posoperatorio]. / Use of intranodular parathyroid hormone values obtained by fine needle aspiration as a predictive factor of postoperative hypoparathyroidism.

OBJETIVO: Análisis de los valores de hormona paratiroidea (PTH) intranodular obtenidos por punción con aguja fina como factor predictivo de hipoparatiroidismo posoperatorio. MÉTODO: De los 157 pacientes a los que se realizó la medición de la PTH intranodular, se estudiaron 37 que fueron intervenidos quirúrgicamente, estableciendo 15 variables para analizar: edad, sexo, tiempo de evolución, tamaño, cirugía de tiroides asociada, tratamiento preoperatorio con calcimiméticos, litiasis renal, densitometría ósea, aclaramiento de creatinina, calcio y PTH preoperatorios, PTH determinada tras punción con aguja fina, descenso de la PTH intraoperatoria, calcio posoperatorio y malignidad de la tumoración. Estas se compararon con la prueba de ji al cuadrado o el test exacto de Fisher, siendo significativa una p < 0.05, construyéndose así un análisis de regresión logística. RESULTADOS: El uso de calcimiméticos previo a la cirugía, la PTH preoperatoria > 88 pg/dl, el calcio preoperatorio > 12 mg/dl, los valores de PTH intranodular > 2700 pg/dl, el descenso de la PTH intraoperatoria a < 15 pg/dl y el calcio posoperatorio < 8,5 mg/dl fueron variables independientes significativas en el análisis univariante (p < 0.05) para la predicción del hipoparatiroidismo posoperatorio. CONCLUSIONES: Los valores de PTH intranodular pueden predecir qué pacientes tienen mayor riesgo de sufrir un hipoparatiroidismo posoperatorio. Este factor debe tenerse en cuenta durante el estudio y el seguimiento de los pacientes para identificar precozmente posibles complicaciones. OBJECTIVE: To analize if parathyroid hormone (PTH) washout levels can be considered a predictive factor of postoperative hypoparathyroidism and determine its importance relative to other features already known as intraoperative PTH, Ca and PTH preoperative, and others. METHOD: Of the 157 patients to whom a fine needle aspiration (FNA) biopsy with intranodular parathyroid hormone level measurement was performed (washout PTH) 37 who underwent surgery were studied. 15 variables were taken into account when selecting patients for this study: age, gender, evolution length, size, associated thyroid surgery, preoperative treatment with calcimimetics, presence of renal lithiasis, bone densitometry alterations, creatine clearance, preoperative calcium and PTH levels, PTH scores obtained by fine needle aspiration, intraoperative PTH decrease, postoperative calcium levels and tumour malignancy. We compare the nominal values, using the Chi squared or the exact Fisher test, where p < 0.05 was considered statistically significant and perform a logistic regression analysis. RESULTS: The use of calcimimetics prior to surgery, the preoperative PTH level above 88 pg/dl, the preoperative calcium above 12 mg/dl, washout PTH above 2700 pg/dl, intraoperative PTH level decrease below 15 pg/dl, and postoperative calcium levels under 8.5 mg/dl were all independently significant variables in the univariant analysis (p < 0.05) in order to establish an early postoperative hypoparathyroidism. The rest of the variables were not statistically significative. CONCLUSION: The PTH washout levels can predict the appearance of postoperative hypoparathyroidism. This factor must be taken into account during the study and follow-up to identify possible complications and establish an adequate treatment on time.

Adaptation and cross-cultural validation of the Spanish version of the Thyroid-Related Quality-of-Life Patient-Reported Outcome questionnaire.

INTRODUCTION: The ThyPRO questionnaire is the most widely used tool for measuring quality of life in patients with benign thyroid diseases. The purpose of this study was to adapt and validate a Spanish translation of the ThyPRO and its abbreviated version (ThyPRO-39). MATERIAL AND METHODS: Adaptation to the Spanish language was performed using the forward-backward translation method, followed by a pretesting study on five representative patients. The final questionnaire (ThyPROes) was administered to 155 patients with thyroid disorders recruited in a tertiary Spanish hospital. Psychometric properties were evaluated by multitrait scaling and estimation of internal consistency reliability (Cronbach's alpha coefficient). Data from a previous sample of 902 Danish patients were used to analyze differential item functioning (DIF) between the Spanish and the original Danish versions of the questionnaire using ordinal logistic regression. RESULTS: Three of 85 items in ThyPROes and four of the 39 items in ThyPRO-39es lacked convergent validity, while lack of discriminant validity was found for in nine and 14 items of each version respectively. Cronbach's alpha was >0.7 for 12 of 13 scales in the ThyPRO and 10 of 12 scales in the ThyPRO-39es. Eight items in the ThyPROes were flagged with DIF (one with non-uniform DIF), as were two items in the ThyPRO-39es. DIF magnitude was small (explained variance in the item score <3%) in most cases, with a minor impact on scale scores. CONCLUSIONS: The Spanish versions of the ThyPRO and ThyPRO-39 show acceptable psychometric properties and good cross-lingual validity, and are suitable for use in clinical studies.

Adaptation and cross-cultural validation of the Spanish version of the Thyroid-Related Quality-of-Life Patient-Reported Outcome questionnaire / Adaptación y validación transcultural de la versión española del cuestionario Thyroid-Related Quality-of-Life Patient-Reported Outcome

Introduction: The ThyPRO questionnaire is the most widely used tool for measuring quality of life in patients with benign thyroid diseases. The purpose of this study was to adapt and validate a Spanish translation of the ThyPRO and its abbreviated version (ThyPRO-39). Material and methods: Adaptation to the Spanish language was performed using the forward-backward translation method, followed by a pretesting study on five representative patients. The final questionnaire (ThyPROes) was administered to 155 patients with thyroid disorders recruited in a tertiary Spanish hospital. Psychometric properties were evaluated by multitrait scaling and estimation of internal consistency reliability (Cronbach's alpha coefficient). Data from a previous sample of 902 Danish patients were used to analyze differential item functioning (DIF) between the Spanish and the original Danish versions of the questionnaire using ordinal logistic regression. Results: Three of 85 items in ThyPROes and four of the 39 items in ThyPRO-39es lacked convergent validity, while lack of discriminant validity was found for in nine and 14 items of each version respectively. Cronbach's alpha was >0.7 for 12 of 13 scales in the ThyPRO and 10 of 12 scales in the ThyPRO-39es. Eight items in the ThyPROes were flagged with DIF (one with non-uniform DIF), as were two items in the ThyPRO-39es. DIF magnitude was small (explained variance in the item score <3%) in most cases, with a minor impact on scale scores. Conclusions: The Spanish versions of the ThyPRO and ThyPRO-39 show acceptable psychometric properties and good cross-lingual validity, and are suitable for use in clinical studies

Introducción: El cuestionario Thyroid-Related Quality-of-Life Patient-Reported Outcome (ThyPRO) es el instrumento más utilizado para medir la calidad de vida en pacientes con enfermedades tiroideas benignas. Este estudio tiene como objetivo adaptar y validar una traducción al español del ThyPRO y su versión abreviada (ThyPRO-39). Material y métodos: La adaptación al español se realizó utilizando el método de traducción-retrotraducción, seguido de una prueba preliminar en 5 pacientes representativos. El cuestionario definitivo ThyPROes se administró a 155 pacientes con trastornos tiroideos en un hospital terciario en España. Las propiedades psicométricas se evaluaron mediante la matriz multirrasgo-multimétodo y la estimación de la fiabilidad de la consistencia interna (alfa de Cronbach). Se utilizaron datos previos de 902 pacientes daneses para analizar el funcionamiento diferencial de los ítems (FDI) entre la versión original danesa del cuestionario y la española, mediante regresión logística ordinal. Resultados: Tres de 85 ítems del ThyPROes y 4 de 39 del ThyPRO-39es carecían de validez convergente, mientras que 9 y 14, respectivamente, carecían de validez discriminante. El alfa de Cronbach fue >0,7 para 12 de 13 escalas del ThyPROes y 10 de 12 del ThyPRO-39es. Ocho ítems del ThyPROes mostraron FDI (uno con FDI no uniforme) y 2 lo hicieron en el ThyPro-39es. La magnitud del FDI fue pequeña (varianza explicada en la puntuación del ítem <3%) en la mayoría de casos, con un impacto menor en las puntuaciones de las escalas. Conclusiones: Las versiones españolas del ThyPRO y ThyPRO-39 muestran aceptables propiedades psicométricas y buena validez interlingüística, y son adecuadas para su uso en estudios clínicos

Combined treatment with GH and anastrozole in a pubertal boy with Cushing's disease and postsurgical GH deficiency.

Growth failure is a characteristic manifestation of pediatric Cushing's disease. Catch-up growth is usually incomplete after cure of the disease, and final height is often compromised. Possible mechanisms for this phenomenon include postoperative persistence of GH hyposecretion and absence of retardation of bone maturation in spite of GH deficiency. This report describes the outcome in the case of a boy with Cushing's disease for whom GH replacement therapy was combined with anastrozole, an aromatase inhibitor, in order to delay skeletal maturation and extend the available time for linear growth. The case of a 14 years 4-months-old pubertal male (Tanner stage III) with GH deficiency after successful surgical treatment of Cushing's disease is presented. His height was 147.2 cm (-2.34 SDS), and his midparental target height 171.2 cm (-0.95 SDS). Bone age was 13.5 years and predicted adult height 163.2 cm (-2.2 SDS). Combined treatment was administered for 2.5 years. GH was maintained up to age 18 years. Anastrozole induced a substantial deceleration of bone age. Near-final height at 18 years was 169.5 cm (-1.07 SDS). Puberty progressed normally. Compared with population reference data, bone mineral density before GH plus anastrozole treatment was -4.07 SDS in the lumbar spine and -1.85 SDS in the femoral neck. These measures increased to -1.95 and -0.89 SDSs respectively, at 18 years, when GH was discontinued. Combined treatment with GH and aromatase inhibitors could be a therapeutic alternative to improve the stature of pubertal boys with Cushing's disease and postsurgical GH deficiency.