Low-Dose ACTH Stimulation Test in Obesity: A Randomized Dose Assessment.

Background: The short cosyntropin test is widely used for adrenal insufficiency screening and diagnosis. Lower cosyntropin doses may have greater sensitivity vs. the standard dose in detecting adrenal dysfunction. Obesity and overweight are increasing, impacting the clinical presentation of some diseases. Currently more than 50% of the subjects diagnosed with autoimmune adrenal insufficiency have a BMI greater than 25, and hence individuals living with overweight and obesity are more frequently requiring evaluation of the adrenal cortical function. Fixed-dose cosyntropin stimulation may not be appropriate for individuals with obesity. Objective: The primary objective was to compare cortisol response to a weight-adapted cosyntropin dose vs. a fixed low dose (1 µg) and a more physiologically fixed dose (10 µg). Methods: Twenty individuals with obesity and 20 age-matched healthy controls underwent in a randomized sequence at least one-week apart, to the The short cosyntropin test with three different doses, 0.2 µg/kg of body weight, 1 or 10 µg fixed dose stimuli. The assessment and data analysis were blinded to the individual and the investigator. Results: Cortisol response was reduced in the group with obesity with the 1 µg fixed dose stimuli at 30 minutes (median, IQR) 649.6 µg, 567.3-738.4 µg for the control group vs. 568.6 µg, 528.4-623.13 µg, p=0.04; there was a lower cortisol peak at 60' in all the three evaluated doses, with a dose-dependent trend. A weight-adapted cosyntropin dose of 0.2 µg in obesity produces a similar response to the one observed in individuals without obesity. The 1 µg ACTH test falls short on stimulating the cortisol adrenal response in individuals with obesity.

Association study in Mexican patients with thyrotoxic hypokalemic periodic paralysis.

Hypokalemic periodic paralysis type 1 (OMIM; HOKPP1) and type 2 (OMIM; HOKPP2) are diseases of the muscle characterized by episodes of painless muscle weakness, and is associated with low potassium blood levels. Hyperthyroidism has been associated with thyrotoxic periodic paralysis (TTPP) (OMIM; TTPP1 and TTPP2), and genetic susceptibility has been implicated. In the present study, the clinical and epidemiological characteristics of patients with TTPP are described, together with their association with genetic variants reported previously in other populations. A prospective and a retrospective search of the medical records of patients who attended the emergency department at the Hospital Universitario 'Dr. Jose E. Gonzalez' in Monterrey, Nuevo León, Mexico, and were diagnosed with TTPP was performed. A total of 16 gene variants in the genes MUC1, CACNA1S, KCNE3 and SCN4A, and nine ancestry informative markers (AIMs), were analysed by Multiplex TaqMan™ Open Array assay, and a genetic association study was performed. A total of 11 patients were recruited, comprising nine males and two females (age range, 19-52 years) and 64 control subjects. Only two cases (18%) had a previous diagnosis of hyperthyroidism; the rest were diagnosed subsequently with Graves' disease. Based on the analysis, two DNA variants were found to potentially confer an increased risk for TTPP: S1PR1 rs3737576 [odds ratio (OR), 4.38; 95% confidence interval (CI), 1.08-17.76] and AIM rs2330442 (OR, 4.50; 95% CI, 1.21-16.69), and one variant was suggested to be possibly associated with TTPP, namely MUC1 rs4072037 (OR, 3.08; 95% CI, 0.841-1.38). However, there were no statistically significant associations between any of the 24 DNA variants and TTPP in a population from northeast Mexico.

Prevalence of liver fibrosis in an unselected general population with high prevalence of obesity and diabetes mellitus. Time for screening?

INTRODUCTION: Cirrhosis and liver cancer are currently common causes of death worldwide. The global epidemic of obesity has increased the incidence of nonalcoholic fatty liver disease (NAFLD) and cirrhosis in recent years. Advanced fibrosis increases the morbimortality rate in NAFLD. The Mexican population has one of the highest prevalence of obesity and diabetes mellitus (DM) worldwide. AIM: To determine the prevalence of advanced liver fibrosis in Mexican general population. METHODS: Adult individuals, without a history of liver disease nor heavy alcohol consumption were randomly sampled from 20,919 participants of a health and nutrition survey applied to the general population. Clinical and laboratory evaluations were performed to calculate the NAFLD fibrosis score (NFS) (an extensively validated non-invasive method). Two cut-off points were used. Advanced fibrosis was defined as a result >0.676. RESULTS: In total 695 individuals were included. The mean age was 47.8±16.4. The majority were between 20 and 50 years (59%), 70.2% were female, 35.5% showed obesity and 15.8% DM. The 93% had normal serum ALT. Based on the NFS results, 56 individuals (8.1%) had a high probability of fibrosis. Most patients from this subgroup showed normal serum ALT (92.9%), 89.3% were >45yr. old, 52% were obese and 27% suffered from DM. CONCLUSIONS: Based on these results, 8.1% of Mexican general population without a history of liver disease is at high risk of having advanced liver fibrosis and complications and death derived from cardiovascular disease and cirrhosis. Most of them showed normal ALT serum levels.

Are cord blood visfatin concentrations different depending on birth weight category?

BACKGROUND AND OBJECTIVE: Increased visceral adipose tissue mass is strongly associated to metabolic disorders. Visfatin is a visceral fat adipocytokine. There is epidemiological evidence of a link between a suboptimal gestational environment and a greater propensity to develop metabolic disease in adult life. The objective of this study was to establish whether visfatin concentrations in umbilical cord blood are different in newborns small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). SUBJECTS AND METHODS: Term newborns from an university medical center were included in the study. A blood sample was taken from the umbilical cord vein of each baby immediately after birth. Visfatin was measured using an enzyme immunoassay in the study population, consisting of 35 subjects in the SGA group, 58 in the AGA group, and 35 in the LGA group. RESULTS: Cord blood visfatin concentrations were not different in the three groups, with respective values of 2.78 (1.86-4.49) ng/mL, 3.28 (1.98-4.97) ng/mL, and 3.46 (2.48-5.38) ng/mL in the SGA, AGA and LGA groups (p=0.141). Gestational weight gain (GWG) (14.09±6.37kg) was negatively associated to visfatin levels (r=-0.218, p=0.036). GWG is an independent predictor of visfatin concentrations (r2=-0.067, p=0.027). CONCLUSIONS: There were no differences in cord blood visfatin concentrations depending on birth weight. GWG is an independent predictor of visfatin levels in the cord blood of term newborns.

Genetic variants in KCNJ11, TCF7L2 and HNF4A are associated with type 2 diabetes, BMI and dyslipidemia in families of Northeastern Mexico: A pilot study.

The aim of the present study was to investigate whether genetic markers considered risk factors for metabolic syndromes, including dyslipidemia, obesity and type 2 diabetes mellitus (T2DM), can be applied to a Northeastern Mexican population. A total of 37 families were analyzed for 63 single nucleotide polymorphisms (SNPs), and the age, body mass index (BMI), glucose tolerance values and blood lipid levels, including those of cholesterol, low-density lipoprotein (LDL), very LDL (VLDL), high-density lipoprotein (HDL) and triglycerides were evaluated. Three genetic markers previously associated with metabolic syndromes were identified in the sample population, including KCNJ11, TCF7L2 and HNF4A. The KCNJ11 SNP rs5210 was associated with T2DM, the TCF7L2 SNP rs11196175 was associated with BMI and cholesterol and LDL levels, the TCF7L2 SNP rs12255372 was associated with BMI and HDL, VLDL and triglyceride levels, and the HNF4A SNP rs1885088 was associated with LDL levels (P<0.05).

Tumour-induced Osteomalacia Secondary to a Sarcoma.

Tumour-induced osteomalacia (TIO), is a rare paraneoplasatic syndrome found in >95% of benign tumours that secrete fibroblast growth factor 23 - a phosphaturic circulating hormone. A rare case of a TIO secondary to a sarcoma, in a 21-year old man with history of bone fractures and distinctive physical and biochemical characteristics is presented and discussed.

Ovarian and adrenal androgens and their link to high human chorionic gonadotropin levels: a prospective controlled study.

Background. Although the association between human chorionic gonadotropin (hCG) and hyperandrogenism was identified more than 40 years ago, relevant questions remain unanswered. Design and Methods. We conducted a prospective, longitudinal, and controlled study in 23 women with a diagnosis of a complete hydatidiform mole (HM). Results. All participants completed the study. Before HM evacuation mean hCG was markedly higher in the cases than in the control group (P ≤ 0.001). Free testosterone (T) and dehydroepiandrosterone sulfate (DHEA-S) were found to be higher in the cases (2.78 ± 1.24 pg/mL and 231.50 ± 127.20 µ/dL) when compared to the control group (1.50 ± 0.75 pg/mL and 133.59 ± 60.69 µ/dL) (P = 0.0001 and 0.001), respectively. There was a strong correlation between hCG and free T/total T/DHEA-S concentrations (r = 0.78; P ≤ 0.001, r = 0.74; P ≤ 0.001, and r = 0.71; P ≤ 0.001), respectively. In the cases group 48 hours after HM evacuation, hCG levels were found to be significantly lower when compared to initial levels (P = 0.001) and free T and DHEA-S declined significantly (P = 0.0002 and 0.009). Conclusion. Before uterus evacuation, hCG, free T, and DHEA-S levels were significantly higher when compared with controls finding a strong correlation between hCG and free T/DHEA-S levels. Forty-eight hours after HM treatment hCG levels declined and the difference was lost. A novel finding of our study is that in cases, besides free T, DHEA-S was also found to be significantly higher and both the ovaries and adrenal glands appear to be the sites of this androgen overproduction.

1,25-dihydroxyvitamin D and PTHrP mediated malignant hypercalcemia in a seminoma.

BACKGROUND: Seminomas have been rarely associated with malignant hypercalcemia. The responsible mechanism of hypercalcemia in this setting has been described to be secondary to 1,25-dihydroxyvitamin D secretion. The relationship with PTHrP has not been determined or studied.The aim of this study is to describe and discuss the case and the pathophysiological mechanisms involved in a malignant hypercalcemia mediated by 1,25-dihydroxyvitamin D and PTHrP cosecretion in a patient with seminoma. CASE PRESENTATION: A 35-year-old man was consulted for assessment and management of severe hypercalcemia related to an abdominal mass. Nausea, polyuria, polydipsia, lethargy and confusion led him to the emergency department. An abdominal and pelvic enhanced CT confirmed a calcified pelvic mass, along with multiple retroperitoneal lymphadenopathy. Chest x-ray revealed "cannon ball" pulmonary metastases. The histopathology result was consistent with a seminoma. Serum calcium was 14.7 mg/dl, PTH was undetectable, 25-dihydroxyvitamin D was within normal values and PTHrP and 1,25-dihydroxyvitamin were elevated (35.0 pg/ml, and 212 pg/ml, respectively). After the first cycle of chemotherapy with bleomycin, etoposide and cisplatin, normocalcemia was restored. Both PTHrP and 1,25-dihydroxyvitamin D, dropped dramatically to 9.0 pg/ml and 8.0 pg/ml, respectively. CONCLUSION: The association of seminoma and malignant hypercalcemia is extremely rare. We describe a case of a patient with a seminoma and malignant hypercalcemia related to paraneoplastic cosecretion of 1,25-dihydroxyvitamin D and PTHrP. After successful chemotherapy, calcium, PTHrP and 1,25-Dihydroxyvitamin D returned to normal values.

Continuous glucose monitoring in acute coronary syndrome / Monitoreo continuo de glucosa en pacientes con síndrome coronario agudo

Background: Diabetes mellitus is an independent risk factor for cardiovascular disease. Objective: To compare the efficacy of devices for continuous glucose monitoring and capillary glucose monitoring in hospitalized patients with acute coronary syndrome using the following parameters: time to achieve normoglycemia, period of time in normoglycemia, and episodes of hypoglycemia. Methods: We performed a pilot, non-randomized, unblinded clinical trial that included 16 patients with acute coronary artery syndrome, a capillary or venous blood glucose ≥ 140 mg/dl, and treatment with a continuous infusion of fast acting human insulin. These patients were randomized into 2 groups: a conventional group, in which capillary measurement and recording as well as insulin adjustment were made every 4h, and an intervention group, in which measurement and recording as well as insulin adjustment were made every hour with a subcutaneous continuous monitoring system. Student's t-test was applied for mean differences and the X² test for qualitative variables. Results: We observed a statistically significant difference in the mean time for achieving normoglycemia, favoring the conventional group with a P = 0.02. Conclusion: Continuous monitoring systems are as useful as capillary monitoring for achieving normoglycemia.

Antecedentes: La diabetes mellitus es un factor de riesgo independiente de enfermedad cardiovascular. Objetivo: Comparar la eficacia de los dispositivos de monitorización continua de glucosa y monitorización de glucosa capilar en pacientes hospitalizados con síndrome coronario agudo, mediante los siguientes parámetros: tiempo en lograr normoglucemia, periodo en normoglucemia y número de hipoglucemias. Métodos: Ensayo clínico no aleatorizado, no ciego, que incluyó a 16 pacientes con síndrome coronario agudo, glucosa capilar o venosa ≥ 140mg/dl, en tratamiento con infusión de insulina humana de acción rápida durante 48 h. Se distribuyeron en 2 grupos: convencional, con medición y registro de glucosa capilar, y ajuste de insulina cada 4h, y de intervención, con medición y registro de glucosa intersticial y ajuste de insulina cada hora a través de un dispositivo de monitorización continua colocado vía subcutánea. Se aplicaron pruebas t para diferencia de medias y prueba de X² para las variables cualitativas. Resultados: Se observó diferencia significativa en la media del tiempo para lograr normoglucemia a favor del grupo convencional, con un valor de p = 0.02. Conclusión: Los dispositivos de monitorización continua de glucosa son tan útiles como la monitorización de glucosa capilar para lograr normoglucemia.

Continuous glucose monitoring in acute coronary syndrome.

BACKGROUND: Diabetes mellitus is an independent risk factor for cardiovascular disease. OBJECTIVE: To compare the efficacy of devices for continuous glucose monitoring and capillary glucose monitoring in hospitalized patients with acute coronary syndrome using the following parameters: time to achieve normoglycemia, period of time in normoglycemia, and episodes of hypoglycemia. METHODS: We performed a pilot, non-randomized, unblinded clinical trial that included 16 patients with acute coronary artery syndrome, a capillary or venous blood glucose ≥ 140 mg/dl, and treatment with a continuous infusion of fast acting human insulin. These patients were randomized into 2 groups: a conventional group, in which capillary measurement and recording as well as insulin adjustment were made every 4h, and an intervention group, in which measurement and recording as well as insulin adjustment were made every hour with a subcutaneous continuous monitoring system. Student's t-test was applied for mean differences and the X(2) test for qualitative variables. RESULTS: We observed a statistically significant difference in the mean time for achieving normoglycemia, favoring the conventional group with a P = 0.02. CONCLUSION: Continuous monitoring systems are as useful as capillary monitoring for achieving normoglycemia.

Hemoglobin A1c: a reliable and accurate test for diabetes care? A prospective study in Mexico / Hemoglobina A1c: ¿una prueba precisa y confiable para el cuidado de la diabetes ? Estudio prospectivo en México

Objective. To compare the concordance correlation coefficient for HbA1c results in an in-field experience. Materials and methods. A prospective study in Monterrey, Mexico from April to August 2012 was conducted to evaluate the day-to-day clinical situation when measuring HbA1c. Blood samples from 38 consecutive patients were sent to seven local laboratories and one international reference laboratory. Results. Poor concordance was found in 4 out of 7 laboratories, moderate in 2 out of 7, and significant in just one. HbA1c values from three laboratories fluctuated more than 1% above or below the reference laboratory in more than 30% of cases, and more than 2% in 10%-20% of subjects. Conclusions. Standardized HbA1c measurement has not occurred worldwide. Physicians should be aware of this issue and be cautious of HbA1c guidelines on diabetes diagnosis or management until proper standardization programs are implemented.

Objetivo. Comparar el coeficiente de correlación de concordancia de HbA1c. Material y métodos. Estudio prospectivo en Monterrey, México, de abril a agosto de 2012 para evaluar la medición de la HbA1c. Participaron 38 individuos y se envió la muestra a 7 laboratorios locales y a uno internacional de referencia. Resultados. Se encontró pobre concordancia en 4 de 7 laboratorios, moderada en 2 y una concordancia significativa en uno. Los valores de HbA1c de tres laboratorios fluctuaron más de 1% del laboratorio de referencia en más de 30% de los casos y más de 2% en 10 a 20%. Conclusiones. La estandarización de la HbA1c no está concluida. Los médicos deberían tomar con cautela las recomendaciones de las guías para HbA1c en el diagnóstico o manejo de la diabetes hasta que se implementen los programas de estandarización.

Hyperglycemia related to high-dose glucocorticoid use in noncritically ill patients.

BACKGROUND: Glucocorticoids commonly cause drug-induced diabetes. This association is well recognized but available evidence does not answer clinically relevant issues in subjects without diabetes. METHODS: Thirty-five individuals without diabetes with a recent diagnosis of acute lymphoblastic leukemia or non-Hodgkin's lymphoma on high-dose glucocorticoid therapy were studied. Close systematic monitoring of fasting and postprandial glycemia and fasting insulin determinations, HOMA-insulin resistance and HOMA ß-cell function were performed. The primary objective was to define the incidence of secondary diabetes in patients treated with high-dose glucocorticoids. Secondary objectives were to specify the intensity, the moment it appears and the evolution of hyperglycemia, in addition to the risk factors, mechanisms and impact of continuous and cyclical glucocorticoids on the development of hyperglycemia. RESULTS: Mean age of patients was 38.4 ± 18.7 years. The incidence of diabetes was 40.6% and was found after the first week; half the time it occurred between the second and fourth. Two-thirds spontaneously normalized by eight weeks. Continuous glucocorticoid administration had a higher incidence of fasting hyperglycemia (P = 0.003). Mean peak insulin levels were significantly higher in cases of diabetes. CONCLUSIONS: High-dose prednisone for 2 to 3 months produced an elevated incidence of diabetes, usually with mild hyperglycemia occurring between the second and fourth week, normalizing spontaneously in all cases. Hyperglycemia was more frequent with continuous doses and occurred in cases with increased insulin resistance. The clinical and therapeutic characteristics of our participants, who were otherwise healthy, could represent the clinical setting of many patients with illness from other medical areas that might require high doses of GC for six to twelve weeks.

Hemoglobin A1c: a reliable and accurate test for diabetes care? A prospective study in Mexico.

OBJECTIVE: To compare the concordance correlation coefficient for HbA1c results in an in-field experience. MATERIALS AND METHODS: A prospective study in Monterrey, Mexico from April to August 2012 was conducted to evaluate the day-to-day clinical situation when measuring HbA1c. Blood samples from 38 consecutive patients were sent to seven local laboratories and one international reference laboratory. RESULTS: Poor concordance was found in 4 out of 7 laboratories, moderate in 2 out of 7, and significant in just one. HbA1c values from three laboratories fluctuated more than 1% above or below the reference laboratory in more than 30% of cases, and more than 2% in 10%-20% of subjects. CONCLUSIONS: Standardized HbA1c measurement has not occurred worldwide. Physicians should be aware of this issue and be cautious of HbA1c guidelines on diabetes diagnosis or management until proper standardization programs are implemented.

The prevalence and clinical characteristics of glucose metabolism disorders in patients with liver cirrhosis. A prospective study.

AIMS: To define the prevalence and clinical characteristics of glucose metabolism disorders (GMD) in patients with compensated liver cirrhosis (LC). MATERIAL AND METHODS: Fasting plasma glucose (FPG) levels were measured to 130 patients with clinically stable LC. Oral glucose tolerance tests (OGTT) and fasting plasma insulin determinations were performed to patients with normal FPG. Insulin resistance (IR) was calculated with HOMA2-IR index. GMD were classified according to FPG and OGTT tests results and to the chronologic relation between diagnosis of diabetes mellitus (DM) and LC as follows: type-2 DM (T2DM), hepatogenous diabetes (HD) and impaired glucose tolerance. Patients from all groups were compared. RESULTS: The prevalence of GMD were as follows: T2DM in 25 patients (19.2%, 95% CI 12.5-25.9), HD in 28 (21.5%, 95% CI 14.5-28.5) and IGT in 36 (38.5%, 95% CI 30.1-46.7). The total of patients with GMD was 79.2% (95% CI 72.3-86.1). In 41% of cases GMD were subclinical and 48.7% of patients had IR. Patients with T2DM had a higher number of variables with significant differences compared with the other groups (more marked compared to the patients without GMD). The only differences between the patients with T2DM and HD were hypercreatininemia: 1.14 ± 0.53 vs. 0.84 ± 0.22 mg/dL (p = 0.005) and family history of DM: 8 (32%) vs. 2 (7%) (p = 0.02). CONCLUSION: Almost 80% of patients with compensated LC had GMD. Half of them were subclinical. The patients with T2DM had marked clinical differences compared to patients from the other groups, particularly renal impairment.

Androgenetic alopecia and insulin resistance in young men.

BACKGROUND: Epidemiological studies have associated androgenetic alopecia (AGA) with severe young-age coronary artery disease and hypertension, and linked it to insulin resistance. We carried out a case-control study in age- and weight-matched young males to study the link between AGA and insulin resistance using the homeostasis model assessment of insulin resistance (HOMA-IR) index or metabolic syndrome clinical manifestations. METHODS: Eighty young males, 18-35 years old, with AGA > or = stage III in the Hamilton-Norwood classification, and 80 weight- and age-matched controls were included. Alopecia, glucose, serum insulin, HOMA-IR index, lipid profile and androgen levels, as well as metabolic syndrome criteria, were evaluated. RESULTS: The HOMA-IR index was significantly higher in cases than controls. Nonobese cases had a higher mean diastolic blood pressure and a more frequent family history of AGA than nonobese controls. A borderline difference in the HOMA-IR index was found in obese AGA cases vs. obese controls [P = 0.055, 95% confidence interval (CI) 2.36-4.20 vs. 1.75-2.73]. Free testosterone values were significantly higher in controls than cases, regardless of body mass index (BMI). A statistically significant additive effect for obesity plus alopecia was found, with significant trends for insulin, the HOMA-IR index, lipids and free testosterone when BMI and alopecia status were used to classify the participants. CONCLUSIONS: Our results support the recommendation for assessing insulin resistance and cardiovascular-related features and disorders in all young males with stage III or higher AGA, according to the Hamilton-Norwood classification.