Definición de los rangos de referencia de T4 libre, TSH y tiroglobulina en sujetos sanos del Distrito Sanitario de Jaén / Definition of reference ranges for free T4, TSH, and thyroglobulin levels in healthy subjects of the Jaén Health District

Antecedentes y objetivos: Las guías de tratamiento de disfunción tiroidea recomiendan definir los intervalos de referencia de las hormonas tiroideas de cada área mediante la evaluación de datos de población local considerando el grado de nutrición yódica de la misma. El objetivo de este estudio fue definir los rangos de referencia de la tiroxina libre (T4L), TSH y tiroglobulina en población general de Jaén, área con un nivel de nutrición yódica adecuado, y si estos estaban afectados por la yoduria. Material y métodos: Estudio descriptivo transversal realizado en 1.003 sujetos de población general en el Distrito Sanitario de Jaén. El yodo urinario, T4L, TSH, tiroglobulina y los anticuerpos antitiroperoxidasa (anti-TPO) fueron analizados en función de la edad y el sexo. Resultados: La mediana de yoduria fue 110,59μg/l y la media 130,11μg/l. La mediana de TSH fue 1,83μUI/ml (p2,5=0,56μUI/ml, p97,5=4,66μUI/ml). La mediana de T4L fue 0,84ng/dl (p2,5=0,62ng/dl, p97,5=1,18ng/dl). El 5,7% de los sujetos tenían anticuerpos anti-TPO positivos. No existía correlación entre los valores de T4L, TSH ni los anticuerpos anti-TPO con los niveles de yoduria. Los sujetos con anticuerpos anti-TPO positivos tenían una TSH más elevada (3,34μUI/ml frente 2,14μUI/ml; p=0,001; odds ratio=2,42). Conclusiones: El yodo urinario en Jaén está dentro de los valores recomendados por la Organización Mundial de la Salud. Los rangos de referencia de T4L, TSH y tiroglobulina no son diferentes a lo descrito en la literatura y no difieren según la yoduria. La prevalencia de anticuerpos anti-TPO positivos es semejante a la descrita en otras poblaciones de España (AU)

Background and objectives: The treatment guidelines for thyroid dysfunction recommend defining reference ranges for thyroid hormones in each area through assessment of local population data considering the iodine nutritional status. The aim of this study was to define the reference ranges of free thyroxine (FT4), TSH, and thyroglobulin levels in a general population from Jaen, an area of southern Spain with an adequate iodine nutritional status, and whether they were associated with urinary iodine levels. Patients and methods: A cross-sectional study was conducted in 1,003 subjects of the general population of the Jaen Health District. Levels of urinary iodine, FT4, TSH, thyroglobulin, and thyroid peroxidase (TPO) antibodies were measured according to age and sex. Results: Median and mean urinary iodine levels were 110.59μg/L and 130.11μg/L respectively. Median TSH level was 1.83μIU/mL (p2.5=0.56μIU/mL, p97.5=4.66μIU/mL). Median FT4 level was 0.84ng/dL (p2.5=0.62ng/dL, p97.5=1.18ng/dL). TPO antibodies were detected in 5.7% of subjects. There was no correlation between urinary iodine levels and FT4, TSH or TPO antibodies. Subjects with positive TPO antibodies had higher TSH levels (3.34μIU/L versus 2.14μIU/mL, P=.001; odds ratio=2.42). Conclusions: Urinary iodine levels in Jaen are optimal according to World Health Organization standards. Reference ranges of FT4, TSH, and thyroglobulin do not differ from those reported in the literature and are no associated to urinary iodine levels. The prevalence of positive TPO antibodies was similar to that reported in other Spanish areas (AU)

Definition of reference ranges for free T4, TSH, and thyroglobulin levels in healthy subjects of the Jaén Health District. / Definición de los rangos de referencia de T4 libre, TSH y tiroglobulina en sujetos sanos del Distrito Sanitario de Jaén.

BACKGROUND AND OBJECTIVES: The treatment guidelines for thyroid dysfunction recommend defining reference ranges for thyroid hormones in each area through assessment of local population data considering the iodine nutritional status. The aim of this study was to define the reference ranges of free thyroxine (FT4), TSH, and thyroglobulin levels in a general population from Jaen, an area of southern Spain with an adequate iodine nutritional status, and whether they were associated with urinary iodine levels. PATIENTS AND METHODS: A cross-sectional study was conducted in 1,003 subjects of the general population of the Jaen Health District. Levels of urinary iodine, FT4, TSH, thyroglobulin, and thyroid peroxidase (TPO) antibodies were measured according to age and sex. RESULTS: Median and mean urinary iodine levels were 110.59µg/L and 130.11µg/L respectively. Median TSH level was 1.83µIU/mL (p2.5=0.56µIU/mL, p97.5=4.66µIU/mL). Median FT4 level was 0.84ng/dL (p2.5=0.62ng/dL, p97.5=1.18ng/dL). TPO antibodies were detected in 5.7% of subjects. There was no correlation between urinary iodine levels and FT4, TSH or TPO antibodies. Subjects with positive TPO antibodies had higher TSH levels (3.34µIU/L versus 2.14µIU/mL, P=.001; odds ratio=2.42). CONCLUSIONS: Urinary iodine levels in Jaen are optimal according to World Health Organization standards. Reference ranges of FT4, TSH, and thyroglobulin do not differ from those reported in the literature and are no associated to urinary iodine levels. The prevalence of positive TPO antibodies was similar to that reported in other Spanish areas.

Diabetes, tumor ovárico, hiperparatiroidismo y cáncer papilar: ¿una asociación casual? / Diabetes, ovarian tumor, hyperparathyroidism, and papillary cancer: association by chance?

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Genetic diagnosis of idiopathic hypogonadotrophic hypogonadism: a new point mutation in the KAL2 gene.

Kallmann Syndrome (KS) is a genetic disease of embryonic development which is characterized by the association of hypogonadotropic hypogonadism (HH) due to a deficit of the gonadotropin-releasing hormone (GnRH) and a hypo/anosmia (including a hypoplasia of the nasal sulcus and agenesis of the olfactory bulbs). Even though it is a genotypically and phenotypically heterogeneous clinical disease, there are some key genes related to KS (KAL1, FGFR1 (KAL2), GNRHR, KISSR1 (GPR54), GNRH1, NELF and PROK2). The aim of this study was to present a case report of a genetic diagnosis of KS linked to the presence of mutations in the FGFR1 (fibroblast growth factor receptor 1, also known as KAL2) gene. This diagnosis was made in a 44-year old female affected by a hypogonadism for which she had received intermittent treatment until she was 30 years old based on the patient's own decision. The molecular analysis of FGFR1 identified the mutation c. 246_247delAG (p.T82Xfs110) in heterozygosis on exon 3 of the KAL2 gene. This is the first report of this mutation related to idiopathic hypogonadotrophic hypogonadism (IHH).

Tumoral EPAS1 (HIF2A) mutations explain sporadic pheochromocytoma and paraganglioma in the absence of erythrocytosis.

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are chromaffin-cell tumors that arise from the adrenal medulla and extra-adrenal paraganglia, respectively. The dysfunction of genes involved in the cellular response to hypoxia, such as VHL, EGL nine homolog 1, and the succinate dehydrogenase (SDH) genes, leads to a direct abrogation of hypoxia inducible factor (HIF) degradation, resulting in a pseudo-hypoxic state implicated in PCC/PGL development. Recently, somatic post-zygotic mutations in EPAS1 (HIF2A) have been found in patients with multiple PGLs and congenital erythrocytosis. We assessed 41 PCCs/PGLs for mutations in EPAS1 and herein describe the clinical, molecular and genetic characteristics of the 7 patients found to carry somatic EPAS1 mutations; 4 presented with multiple PGLs (3 of them also had congenital erythrocytosis), whereas 3 were single sporadic PCC/PGL cases. Gene expression analysis of EPAS1-mutated tumors revealed similar mRNA EPAS1 levels to those found in SDH-gene- and VHL-mutated cases and a significant up-regulation of two hypoxia-induced genes (PCSK6 and GNA14). Interestingly, single nucleotide polymorphism array analysis revealed an exclusive gain of chromosome 2p in three EPAS1-mutated tumors. Furthermore, multiplex-PCR screening for small rearrangements detected a specific EPAS1 gain in another EPAS1-mutated tumor and in three non-EPAS1-mutated cases. The finding that EPAS1 is involved in the sporadic presentation of the disease not only increases the percentage of PCCs/PGLs with known driver mutations, but also highlights the relevance of studying other hypoxia-related genes in apparently sporadic tumors. Finally, the detection of a specific copy number alteration affecting chromosome 2p in EPAS1-mutated tumors may guide the genetic diagnosis of patients with this disease.

Is increasing urinary albumin a better marker for microvascular than for macrovascular complication of type 2 diabetes mellitus?

AIMS: The aims of the study were to evaluate the prevalence of increased urinary albumin excretion (UAE) and associated cardiovascular risk factors and vascular diabetes complications in patients with type 2 diabetes mellitus (DM). METHODS: We studied 975 patients in a cross-sectional design from 1998 to 2000. Frequency of micro- and macroalbuminuria, and their associations with cardiovascular risk factors and vascular DM complications, were examined. RESULTS: Prevalence of increased UAE was 28.5% (18.3% micro- and 10.2% macroalbuminuria). Body mass index (BMI) (only females) and hemoglobin (Hb)A1c significantly correlated with macroalbuminuria (p = 0.034, p = 0.027, respectively), while high blood pressure (diastolic) was associated with microalbuminuria (p = 0.008). Diabetes duration, high systolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides were significantly correlated with both micro- and macroalbuminuria. Increased UAE was associated with neuropathy (relative risk (RR) 2.12, confidence interval (CI) 1.07-4.19), retinopathy (RR 2.19, CI 1.76-2.74) and hypertension (RR 2.91, CI 1.77-4.78), but not with cardiovascular disease, high cholesterol and peripheral vascular disease. In the multiple logistic regression analysis, a significant association of albuminuria was found with diabetes duration (odds ratio (OR) 1.59, CI 0.98-2.58; p < 0062), hypertension (OR 3.42, CI 2.22-5.27; p < 0.0001), low HDL cholesterol (OR 1.78, CI 1.31-2.43; p < 0.0003), current smoking status (OR 2.19, CI 1.32-3.64; p < 0.0024), and increased serum creatinine (OR 11.16, CI 5.7-21.7; p < 0.0001). CONCLUSION: Prevalence of increased UAE was similar to that described in other geographically close populations. The stronger association found with microvascular diabetes complications suggests that increased UAE is a better predictor for renal damage than for cardiovascular disease in this type 2 DM population.