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SUMMARY Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases.
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Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases.
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Enfermedades de la Corteza Suprarrenal , Síndrome de Cushing , Humanos , Niño , Femenino , Enfermedades de la Corteza Suprarrenal/genética , Enfermedades de la Corteza Suprarrenal/diagnóstico , Enfermedades de la Corteza Suprarrenal/patología , Síndrome de Cushing/genética , Adrenalectomía/efectos adversos , Hidrocortisona , Hormona Adrenocorticotrópica , Subunidades Catalíticas de Proteína Quinasa Dependientes de AMP CíclicoRESUMEN
INTRODUCTION: Acute thyrotoxic myopathy (ATM) is a rare and potentially lethal complication of thyrotoxicosis. The typical clinical symptoms of ATM are characterized by bulbar paralysis. Reports of the successful treatment of ATM are sporadic due to its low incidence. However, no English literature has reported Chinese patients with ATM and neck pain. Here, we report for the first time a Chinese patient with ATM and neck pain who recovered through large doses of systemic glucocorticoids and one intrathyroidal steroid injection. CASE REPORT: A 23-year-old woman visited our hospital with a two-year history of progressive weakness of her bulbar muscles, hoarseness, cough when swallowing, dysphagia, and a one-month history of recurrent painful swelling of the thyroid gland. She was diagnosed with ATM, chronic thyrotoxic myopathy (CTM), and Graves' ophthalmopathy (GO) due to Graves' disease (GD). After she was treated with a combination of low-dose glucocorticoids, antithyroid drugs (ATDs), propranolol, and ultrasound-guided percutaneous intrathyroidal injection of glucocorticoids, her bulbar paralysis, proximal myopathy, and neck pain simultaneously improved without recurrence during follow-up. To our knowledge, this is the first case report of a patient with ATM, CTM, GD, GO and neck pain treated by administering a combination of low-dose glucocorticoids, one intrathyroidal steroid injection and antithyroid agents. CONCLUSIONS: Clinicians should consider ATM and intervene with aggressive glucocorticoid therapy, and this is the key to reversing the progression of ATM when a patient has bulbar paralysis and thyrotoxic symptoms. Our case report references the clinical diagnosis and treatment of such cases.
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Parálisis Bulbar Progresiva , Enfermedad de Graves , Oftalmopatía de Graves , Enfermedades Musculares , Tirotoxicosis , Humanos , Femenino , Adulto Joven , Adulto , Parálisis Bulbar Progresiva/complicaciones , Parálisis Bulbar Progresiva/tratamiento farmacológico , Dolor de Cuello/etiología , Dolor de Cuello/complicaciones , Tirotoxicosis/complicaciones , Tirotoxicosis/tratamiento farmacológico , Tirotoxicosis/diagnóstico , Enfermedad de Graves/complicaciones , Enfermedad de Graves/tratamiento farmacológico , Antitiroideos/uso terapéutico , Glucocorticoides/uso terapéutico , Enfermedades Musculares/complicaciones , Enfermedades Musculares/tratamiento farmacológico , Esteroides/uso terapéuticoRESUMEN
Introduction: Chronic thyrotoxic myopathy (CTM) is a common, easily neglected complication of hyperthyroidism. There are currently no standard diagnostic criteria for CTM, and the ultrasonic characteristics of CTM-affected skeletal muscle remain unclear. Herein, we aimed to evaluate hyperthyroid patients for CTM by ultrasound and identify ultrasonic muscle parameter cutoffs for CTM diagnosis. Materials and methods: Each participant underwent ultrasonography. The original (muscle thickness (MT), pennation angle (PA), and cross-sectional area (CSA)) and corrected (MT/height (HT), MT/body mass index (BMI), CSA/HT, and CSA/BMI) parameters of the vastus lateralis and vastus medialis (VM) were evaluated. The diagnostic effectiveness of ultrasound for predicting CTM was determined using receiver operating characteristic (ROC) curve analysis. Our study included 203 participants: 67 CTM patients (18 males, 49 females), 67 non-CTM patients (28 males, 39 females) and 69 healthy controls (20 males, 49 females). Results: The CTM group had lower muscular ultrasonic and anthropometric parameters, higher thyroid hormone and thyroid-stimulating hormone receptor antibody (TRAb) levels, and a longer duration of hyperthyroidism than the non-CTM group (P < 0.05). The VM-PA, VM-CSA, VM-CSA/HT, and VM-CSA/BMI were lower in females than in males (P < 0.05). Free thyroxine (FT4) and TRAb both showed significant negative correlations with VM-MT, VM-MT/HT, VM-CSA, and VM-CSA/HT (P < 0.05). VM-MT/BMI and VM-CSA/HT, respectively, best predicted male and female CTM (AUC = 0.84, 0.85; cutoff ≤ 0.07, < 4.01). Conclusion: Ultrasound measurement of muscular parameters, especially in the VM, is a valid and feasible way of diagnosing and characterizing possible CTM in hyperthyroidism.
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OBJECTIVE: Intrauterine growth restriction followed by postnatal catch-up growth (CG-IUGR) increases the risk of insulin resistance-related diseases. Low-density lipoprotein receptor-related protein 6 (LRP6) plays a substantial role in glucose metabolism. However, whether LRP6 is involved in the insulin resistance of CG-IUGR is unclear. This study aimed to explore the role of LRP6 in insulin signaling in response to CG-IUGR. METHODS: The CG-IUGR rat model was established via a maternal gestational nutritional restriction followed by postnatal litter size reduction. The mRNA and protein expression of the components in the insulin pathway, LRP6/ß-catenin and mammalian target of rapamycin (mTOR)/S6 kinase (S6K) signaling, was determined. Liver tissues were immunostained for the expression of LRP6 and ß-catenin. LRP6 was overexpressed or silenced in primary hepatocytes to explore its role in insulin signaling. RESULTS: Compared with the control rats, CG-IUGR rats showed higher homeostasis model assessment for insulin resistance (HOMA-IR) index and fasting insulin level, decreased insulin signaling, reduced mTOR/S6K/ insulin receptor substrate-1 (IRS-1) serine307 activity, and decreased LRP6/ß-catenin in the liver tissue. The knockdown of LRP6 in hepatocytes from appropriate-for-gestational-age (AGA) rats led to reductions in insulin receptor (IR) signaling and mTOR/S6K/IRS-1 serine307 activity. In contrast, LRP6 overexpression in hepatocytes of CG-IUGR rats resulted in elevated IR signaling and mTOR/S6K/IRS-1 serine307 activity. CONCLUSION: LRP6 regulated the insulin signaling in the CG-IUGR rats via two distinct pathways, IR and mTOR-S6K signaling. LRP6 may be a potential therapeutic target for insulin resistance in CG-IUGR individuals.
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Retardo del Crecimiento Fetal , Resistencia a la Insulina , Insulina , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad , Proteínas Quinasas S6 Ribosómicas , Animales , Femenino , Humanos , Ratas , beta Catenina/genética , Retardo del Crecimiento Fetal/genética , Retardo del Crecimiento Fetal/metabolismo , Insulina/metabolismo , Resistencia a la Insulina/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/genética , Receptor de Insulina/genética , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
RATIONALE AND OBJECTIVES: Neurodegeneration is an early event in the pathogenesis of diabetic retinopathy (DR). We assessed the white matter microstructural integrity of the visual pathway in diabetes patients vs. healthy subjects, and investigated the advantages of generalized Q-sampling imaging (GQI) in the assessment of the visual pathway. MATERIALS AND METHODS: T1-weighted, T2-weighted fluid-attenuated inversion recovery, and simultaneous multislice- diffusion sequences were acquired from 21 DR patients, 29 diabetes patients without DR (NDR group), and 28 age- and gender-matched healthy controls. Diffusion source images were reconstructed to GQI. Region of interest (ROI)-based analysis was utilized to evaluate microstructural alterations in the visual pathway. Multivariate linear regression analysis (forward stepwise method) was performed to investigate associations between clinical data and mean GQI parameters. RESULTS: ROI-based analyses indicated that the GQI parameters generalized fractional anisotropy, quantitative anisotropy (QA), and normalized QA (NQA) were significantly lower in the NDR group than in the healthy controls, and even lower in the DR group than in the NDR group. Disease duration was significantly and negatively correlated with mean generalized fractional anisotropy and mean NQA. CONCLUSION: GQI could sensitively and non-invasively evaluate the visual pathway in diabetes patients. The nerve fibers of the visual pathway were damaged before the onset of retinopathy, and this damage was aggravated after retinopathy onset, as a consequence of long exposure to hyperglycemia.
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Diabetes Mellitus Tipo 2 , Enfermedades de la Retina , Sustancia Blanca , Anisotropía , Encéfalo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Humanos , Vías Visuales/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagenRESUMEN
OBJECTIVE: To survey the status of iodine nutrition and the prevalence of thyroid diseases in Guangxi, China, and to explore the risk factors for positive thyroid antibody. METHODS: We used the multistage stratified cluster random sampling method to select a total of 2488 subjects from an urban and a rural location. All the subjects completed a questionnaire survey, blood and urine samples were also collected, and B-mode thyroid ultrasound was used to determine thyroid function and detect thyroid antibodies. RESULTS: 1) The median level of urinary iodine was 148.53 µg/L in school-age children in Guangxi, China. 2) The prevalence rates for thyroid diseases were as follows: hyperthyroidism, 0.89 %; subclinical hyperthyroidism, 1.05 %; hypothyroidism, 0.69 %; and subclinical hypothyroidism, 8.87 %. The rates of thyroid antibody positivity were as follows: thyroid peroxidase antibody (TPOAb), 13.60 %; thyroglobulin antibody (TGAb), 13.60 %; thyroid antibodies, 18.2 %; and thyroid nodules, 16.94 %. 3) The rate of TPOAb positivity was significantly higher in women aged 18-29, 30-39, 40-49, or 60-69 years than in men in the same age groups (P < 0.05), and the TGAb positivity rate was significantly higher in women than in men of the same age group (P < 0.05). 4) The rate of thyroid antibody positivity was significantly higher in individuals with iodine deficiency than in individuals with adequate iodine (21.6 % vs 18.4 %) or excess iodine (21.6 % vs 15.5 %) (both P < 0.05). 5) The female sex and a family history of thyroid diseases were the major risk factors for thyroid antibody positivity (odds ratio [OR] 3.010, P <0.05; OR 2.486, P <0.05). CONCLUSION: The overall level of iodine is adequate in Guangxi, China; this level should be maintained to prevent the thyroid diseases related with iodine deficiency or excess of iodine. Female sex and a family history of thyroid diseases are independent risk factors for thyroid antibody positivity.
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Hipotiroidismo , Yodo , Enfermedades de la Tiroides , Adolescente , Adulto , Anciano , Niño , China/epidemiología , Femenino , Humanos , Hipotiroidismo/inducido químicamente , Hipotiroidismo/epidemiología , Yoduro Peroxidasa , Yodo/orina , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Enfermedades de la Tiroides/epidemiología , Tirotropina , Adulto JovenRESUMEN
OBJECTIVE: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. METHODS: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. RESULTS: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). CONCLUSION: An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
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Índice Glucémico , Ácido Úrico/sangre , Anciano , Pueblo Asiatico , Glucemia/análisis , China/epidemiología , Estudios de Cohortes , Diabetes Mellitus/sangre , Femenino , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: A relationship between hyperthyroidism and insulin secretion in type 2 diabetes mellitus (T2DM) has been reported. Therefore, this study explored the use of first-phase insulin secretion in the differential diagnosis of thyroid diabetes (TDM) and T2DM. METHODS: In total, 101 patients with hyperthyroidism were divided into hyperthyroidism with normal glucose tolerance (TNGT), hyperthyroidism with impaired glucose regulation (TIGR), and diabetes (TDM) groups. Furthermore, 96 patients without hyperthyroidism were recruited as control groups (normal glucose tolerance [NGT], impaired glucose regulation [IGR], and T2DM). The following parameters were evaluated: homeostasis model assessment (HOMA)-IR, HOMA-ß, modified ß-cell function index (MBCI), peak insulin/fasting insulin (IP/I0), AUCins-OGTT, and AUCins-OGTT/AUCglu-OGTTfrom the oral glucose tolerance test (OGTT) insulin release test were utilized to assess the second-phase insulin secretion, while the IP/I0, AIR0'~10', and AUCins-IVGTTfrom the intravenous glucose tolerance test (IVGTT) insulin release test were used to assess the first-phase insulin secretion. RESULTS: In the OGTT, the HOMA-ß values of the TNGT and TDM groups were higher than those of the NGT and T2DM groups (all P< 0.05). In the hyperthyroidism groups, the MBCI of the TDM group was lower than that of the TNGT and TIGR groups (all P< 0.05). Among the control groups, the MBCI values of the IGR and T2DM groups were lower than that of the normal glucose tolerance (NGT) group (all P< 0.05). In the IVGTT, insulin secretion peaked for all groups at 2-4 min, except for the T2DM group, which showed a low plateau and no secretion peak. The IP values of the TNGT, TIGR, and TDM groups were higher than those of the NGT, IGR, and T2DM groups (all P< 0.05). The Ip/I0, AIR0'~10', and AUCins-IVGTTvalues of the TDM group were higher than those of the T2DM group but were lower than those of the TNGT, TIGR, NGR, and IGR groups (all P< 0.05). Compared with the other five groups, the Ip/I0, AIR0'~10', and AUCins-IVGTTvalues of the T2DM group were significantly decreased (all P< 0.05). The Ip/I0and AUCins-IVGTTvalues of the TNGT group were higher than those of the NGT group (all P< 0.05). CONCLUSIONS: ß-cell function in TDM patients is superior to that in T2DM patients. First-phase insulin secretion could be used as an early diagnostic marker to differentiate TDM and T2DM.
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Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Insulina/metabolismo , Enfermedades de la Tiroides/sangre , Enfermedades de la Tiroides/diagnóstico , Glándula Tiroides/patología , Adulto , Glucemia/metabolismo , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/patología , Diagnóstico Precoz , Ayuno/sangre , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Hipertiroidismo/sangre , Hipertiroidismo/diagnóstico , Hipertiroidismo/patología , Insulina/sangre , Resistencia a la Insulina/fisiología , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/patología , Masculino , Persona de Mediana Edad , Enfermedades de la Tiroides/patología , Tirotropina/sangreRESUMEN
OBJECTIVES: Aberrant circulating adipokines are considered to be related to the pathological mechanism of polycystic ovary syndrome (PCOS). This study aims to evaluate the relationship between plasma omentin-1 levels, metabolic and hormonal parameters in the setting of non-obese Chinese women with PCOS. MATERIAL AND METHODS: This was a case-controlled, cross-sectional study of 153 non-obese (BMI<25kg/m(2)) PCOS and 114 age-matched healthy non-obese control individuals. Levels of plasma omentin-1, fasting blood glucose, insulin and sexual hormones and ovary volume were analyzed in all subjects. RESULTS: Plasma omentin-1 levels of non-obese PCOS individuals were significantly lower than in healthy non-obese controls. Body Mass Index (BMI), homeostasis model of assessment for insulin resistance index (HOMA-IR), levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), LH/FSH ratio and ovary volume (OV) were significantly higher in subjects with PCOS than controls. In the HOMA-IR stratified subgroups, PCOS individuals with insulin resistance had lower omentin-1 than those without insulin resistance after BMI adjustment. Omentin-1 was negatively correlated with BMI, HOMA-IR and fasting insulin. Multiple linear regressions revealed that BMI contributed to omentin-1 levels. Ovary volume was negatively correlated to HOMA-IR but had no correlation with omentin-1. CONCLUSIONS: Plasma omentin-1 concentrations were decreased in the non-obese PCOS group. Insulin resistance could further decrease plasma omentin-1 in non-obese individuals with PCOS independent of BMI status.
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Citocinas/sangre , Resistencia a la Insulina/fisiología , Lectinas/sangre , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/fisiopatología , Adolescente , Adulto , Glucemia/análisis , Índice de Masa Corporal , Peso Corporal , Estudios de Casos y Controles , China , Estudios Transversales , Ayuno , Femenino , Hormona Folículo Estimulante/sangre , Proteínas Ligadas a GPI/sangre , Humanos , Insulina/sangre , Hormona Luteinizante/sangre , Obesidad , Ovario/patología , Síndrome del Ovario Poliquístico/patología , Testosterona/sangre , Adulto JovenRESUMEN
OBJECTIVE: To investigate the association between obesity and prevalence of metabolic syndrome (MS) with its associated risk factors, in children and adolescents. METHODS: A stratified random sampling method was used to select 7893 students from 6 to 18 years of age from 14 out of 396 primary and secondary schools in Nanning city. All the students had undergone physical examination and blood tests including the following risk factors related to metabolic syndrome: fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), alanine amino shift enzyme (ALT), aspartic acid amine shift enzyme (AST) and fasting insulin (FINS). The homeostasis model assessment insulin resistance index (HOMA-IR) was also measured. RESULTS: (1) The prevalence rate of MS in normal group was 0.57%. In both the overweight and obesity groups, the prevalence rates of MS were 4.53% and 26.80%, respectively. (2) These indices in obesity group were higher than other two groups (P < 0.05). The result of overweight group was higher than normal group (P < 0.05). (3) Waist circumference (OR = 1.087, 95%CI: 1.033 - 1.143), SBP (OR = 1.073, 95%CI: 1.032 - 1.116), FBG (OR = 1.394, 95%CI: 1.568 - 3.423), TG (OR = 3.213, 95%CI: 1.410 - 7.319) and HDL-C (OR = 0.001, 95%CI: 0.000 - 0.012) were detecting indices which had statistically significant with MS in binary logistic regression analysis. CONCLUSION: Metabolic syndrome and obesity were closely related in children and adolescents while its prevalence and risk factors increased with the severity of obesity.
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Síndrome Metabólico/complicaciones , Obesidad/complicaciones , Adolescente , Niño , China/epidemiología , Femenino , Humanos , Masculino , Síndrome Metabólico/epidemiología , Obesidad/epidemiología , Factores de Riesgo , MuestreoRESUMEN
OBJECTIVE: To investigate the relationship between the polymorphic (AT)n repeats in 3ountranslated region of exon 4 of CTLA4 gene [CTLA4(AT)n] and Graveso disease (GD) in Zhuang nationality population of Guangxi province. METHODS: The studied groups comprised 48 patients with GD and 44 normal controls. Amplification of target DNA was carried out by polymerase chain reaction (PCR). The amplified products were run by 8% polyacrylamide gel electrophoresis, and then followed by 0.1% silver staining. Some of amplified products were sequenced directly. RESULTS: Nineteen alleles of CTLA4 gene microsatellite polymorphism were found in Guangxi Zhuang nationality individuals. The 106 bp long allele was apparently increased in patients with GD of Zhuang nationality but not in healthy controls (P< 0.05). CONCLUSION: CTLA4 gene microsatellite polymorphism is strongly associated with Graveso disease in Zhuang nationality population of Guangxi province. CTLA4(AT)n 106 bp may be the susceptible gene in GD patients of Zhuang nationality in Guangxi; 19 alleles of CTLA4 gene microsatellite polymorphism were found in Guangxi Zhuang nationality individuals.