Evaluation of the Efficacy and Safety of Switching to Pasireotide in Patients With Acromegaly Inadequately Controlled With First-Generation Somatostatin Analogs.

Introduction: Acromegaly is a rare, serious endocrine disorder characterized by excess growth hormone (GH) secretion by a pituitary adenoma and overproduction of insulin-like growth factor I (IGF-I). Transsphenoidal surgery is the treatment of choice, although many patients require additional interventions. First-generation somatostatin analogs (SSAs) are the current standard of medical therapy; however, not all patients achieve control of GH and IGF-I. Outcomes from a Phase IIIb open-label study of patients with uncontrolled acromegaly on first-generation SSAs switching to pasireotide are reported. Methods: Adults with uncontrolled acromegaly (mean GH [mGH] ≥1 µg/L from a five-point profile over 2 h, and IGF-I >1.3× upper limit of normal [ULN]) despite ≥3 months' treatment with maximal approved doses of long-acting octreotide/lanreotide received open-label long-acting pasireotide 40 mg/28 days. Pasireotide dose could be increased (maximum: 60 mg/28 days) after week 12 if biochemical control was not achieved, or decreased (minimum: 10 mg/28 days) for tolerability. Patients who completed 36 weeks' treatment could continue receiving pasireotide during an extension (weeks 36-72) when concomitant medication for acromegaly was permitted. Primary endpoint was proportion of patients with mGH <1 µg/L and IGF-I 2.5 µg/L. For patients who entered the extension, 14.8% (95% CI: 8.1-23.9), 12.5% (95% CI: 6.4-21.3), 14.8% (95% CI: 8.1-23.9) and 11.4% (95% CI: 5.6-19.9) had mGH <1 µg/L and IGF-I

High prevalence of humoral autoimmunity in first-degree relatives of Mexican type 1 diabetes patients.

AIMS: To assess the prevalence of autoantibodies (Aab) to insulin (IAA), glutamic acid decarboxylase 65 (GADA) and insulinoma antigen 2 (IA-2A), as well as human leukocyte antigen (HLA) class II alleles, in first degree relatives (FDR) of Mexican patients with type 1 diabetes (T1D), and to explore whether these parameters mirror the low incidence of T1D in the Mexican population. METHODS: Aab titers were determined by ELISA in 425 FDR, 234 siblings, 40 offspring and 151 parents of 197 patients with T1D. Typing of HLA-DR and -DQ alleles was performed in 41 Aab-positive FDR using polymerase chain reaction with allele-specific oligotyping. RESULTS: Seventy FDR (16.47%) tested positive for Aab. The siblings (19.2%) and the offspring (25%) had significantly higher prevalence of Aab than the parents (9.9%). GADA was the most frequent Aab. Almost half of the Aab-positive FDR had two different Aab (45.7%), and none tested positive for three Aab. The highest prevalence of Aab was found among women in the 15-29 years age group. Moreover, the positivity for two Aab was significantly more frequent among females. A considerable number of FDR (48.8%) carried the susceptible HLA-DR3, -DR4, -DQB1*0201 or -DQB1*0302 alleles, but almost none had the high risk genotype HLA-DR3/DR4. CONCLUSIONS: FDR of Mexican T1D patients have high prevalence of islet Aab, comparable to countries with the highest incidence of T1D. However, Aab positivity does not seem to be associated with HLA risk genotypes, which may have an impact on the low incidence of T1D in Mexico.

[Alterations of the thyroid function in patients with morbid obesity]. / Alteraciones de la función tiroidea en pacientes con obesidad mórbida.

INTRODUCTION: The morbid obesity (BMI greater than or equal to 40 kg/m2) is associated with dysfunction of the hypothalamus-pituitary-thyroid axis, showing high levels of thyrotropin (TSH), triiodothyronine (T3) total and free, suspecting a real thyroid condition. Our objetive was to describe the alterations in thyroid function in patients with morbid obesity, determining serum levels of TSH, total T3, free T4 and thyroid peroxidase antibodies (TPO). METHODS: Prospective, descriptive, observational, cross-sectional study, we enrolled 52 patients with morbid obesity, at the obesity clinic, from department of Endocrinology, since January 2009 to July 2011. All patients signed a letter of informed consent. Patients with known thyroid disorders and/or under the use of levothyroxine or other medication that causes alteration in thyroid function were excluded. Statistical analysis was performed using measures of central tendency, simple frequencies, percentages and Spearman's correlation. RESULTS: The prevalence of primary hypothyroidism was 8%, 6% subclinical hypothyroidism and thyroid function alterations secondary to obesity of 23% (elevated TSH and/or free T4 Total T3 with normal and TPO antibody negative). CONCLUSIONS: Most morbidly obese patients haven't autoimmune thyroid dysfunction; the alterations in thyroid function are caused by an effect of homeostasis against obesity and can be corrected by reducing weight.

Introducción: La obesidad mórbida (IMC greater than or equal to 40 kg/m2) se asocia con disfunción del eje hipotálamo-hipófisis- tiroides, presentando elevación de tirotropina (TSH), de la triyodotironina (T3) total y libre, sospechando de una auténtica afección tiroidea. El objetivo fue describir las alteraciones en la función tiroidea en pacientes con obesidad mórbida, determinando niveles séricos de TSH, T3 total, T4 libre y anticuerpos antiperoxidasa (TPO).Métodos: estudio prospectivo, descriptivo, observacional y transversal, incluyó 52 pacientes con obesidad mórbida de la clínica de obesidad del departamento de Endocrinología, de enero del 2009 a julio del 2011. Se excluyeron pacientes con alteraciones tiroideas conocidas y/o bajo el uso de levotiroxina u otro medicamento que cause alteración en el perfil tiroideo. El análisis estadístico se realizó con medidas de tendencia central, frecuencias simples, porcentajes y se realizó correlación de Spearman.Resultados: la prevalencia de hipotiroidismo primario fue de 8 %, hipotiroidismo subclínico en 6 % y las alteraciones en el perfil tiroideo secundarias a obesidad del 23 % (elevación de TSH y/o T3 total con T4 libre normal y anticuerpos TPO negativos).Conclusiones: la mayoría de los pacientes con obesidad mórbida no presentan disfunción tiroidea autoinmune, las alteraciones en el perfil tiroideo son causadas por un efecto de homeostasis frente a la obesidad y pueden ser corregidas al disminuir de peso.