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1.
Front Nutr ; 10: 1188612, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37215216

RESUMO

Introduction: Vitamin D insufficiency is a global health problem affecting healthy and diseased individuals, including patients with Hashimoto's thyroiditis (HT). Identifying dietary factors that may affect vitamin D levels and providing dietary guidelines accordingly can alleviate this problem. We therefore aimed to identify still unknown associations of dietary patterns, assessed through the Food Frequency Questionnaire (FFQ) with vitamin D blood levels. Materials and methods: FFQ was collected from 459 patients from Croatian Biobank of Patients with Hashimoto's thyroiditis (CROHT), while total 25(OH)D was measured from their stored serum samples. We performed linear regression analysis between vitamin D levels and weekly intake of 24 food groups in 459 patients with HT (ALL), and in two disease-severity groups (MILD and OVERT). Results: The main results of our study are observations of: (1) an inverse association between vitamin D levels and coffee consumption (ALL: ß = -0.433, p = 0.005; OVERT: ß = -0.62, p = 0.008); (2) an inverse association between vitamin D levels and sweets consumption (ALL: ß = -0.195, p = 0.034; OVERT: ß = -0.431, p = 0.006); (3) positive association between vitamin D levels and vegetable consumption (ALL: ß = 0.182, p = 0.019; OVERT, ß = 0.311, p = 0.009). Importantly, effect sizes of all three associations were more prominent in HT patients with prolonged and more severe disease (OVERT). Conclusion: Further research into the functional and causal relationships of the observed associations is important to provide guidance regarding coffee/sugar intake on vitamin D status. A well-balanced diet can help prevent vitamin D deficiency and improve the quality of life of patients with HT, especially those in later stages of disease characterized by greater metabolic imbalance.

2.
Genes (Basel) ; 13(8)2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-36011254

RESUMO

BACKGROUND: McCune-Albright is a rare syndrome, caused by mutation of the GNAS1 gene, and is characterized by an appearance of multiple endocrinopathies, most commonly premature puberty, polyostotic fibrous dysplasia and skin changes called cafe au lait macules. CASE REPORT: We present the case of a patient who is, to the best of our knowledge and after extensive review of literature, the youngest McCune-Albright syndrome patient with growth hormone excess, diagnosed at 8.9 months of age. An extensive diagnostic procedure was done upon the diagnosis. Hormonal assessment was performed and all hormone levels were within reference range, and an additional oral glucose suppression that noted the presence of growth hormone excess. Magnetic resonance imaging of the pituitary gland did not detect a tumor process. The genetic analysis of the GNAS1 gene from skin punch biopsy came back negative. Octreotide was administered as therapy for growth hormone excess at 9.8 months. After the introduction of therapy, we noted a decrease in growth rate from 29.38 to 16.6 cm/year. CONCLUSION: This case report emphasizes the lack of available data on treatment of growth hormone excess and follow-up in pediatric population and the need for further research.


Assuntos
Acromegalia , Displasia Fibrosa Poliostótica , Acromegalia/diagnóstico , Acromegalia/genética , Manchas Café com Leite/genética , Criança , Displasia Fibrosa Poliostótica/diagnóstico , Displasia Fibrosa Poliostótica/genética , Humanos , Síndrome
3.
Genes (Basel) ; 13(4)2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35456364

RESUMO

BACKGROUND: Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare monogenetic autosomal recessive disorder caused by a mutation in the autoimmune regulator (AIRE) gene characterized by complex phenotypic characteristics discovered over years of follow-up. METHODS: 7 patients were recruited in this case series in a period of the last 37 years from Southern Croatia. All patients were screened for AIRE R257X mutations. RESULTS: This study group had a mean current age of 25.3 years (age range from 5.4 to 40.2 years), while the mean age at the onset of the disease was 6.5 years (age range from 0.7 to 9.2 years) and with a mean follow-up period of 17.8 years. The overall prevalence of APECED syndrome is estimated to be 1 in 75,000. The most common initial manifestation of the disease was onychodystrophy, while the first major component of APECED syndrome was chronic mucocutaneous candidiasis. CONCLUSIONS: APECED is a ''multi-faced'' disease based on the very unpredictable and inconsistent onset of major components. Furthermore, based on our results, we suggest that onychodystrophy could be included as a warning sign of APECED syndrome.


Assuntos
Poliendocrinopatias Autoimunes , Adolescente , Adulto , Criança , Pré-Escolar , Croácia/epidemiologia , Seguimentos , Humanos , Lactente , Mutação , Poliendocrinopatias Autoimunes/epidemiologia , Poliendocrinopatias Autoimunes/genética , Adulto Jovem
4.
Children (Basel) ; 9(2)2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35204924

RESUMO

BACKGROUND: Urotensin-II (U-II) is a short cyclic peptide that is widely recognized as one of the most potent vasoconstrictors. U-II plays a role in the pathophysiology of MS, participating in the development of essential hypertension, insulin resistance, hyperglycemia, and a proinflammatory state. METHODS: This study comprised 52 obese children and adolescents with a body mass index (BMI) z score > 2, aged 10 to 18 years. Serum levels of U-II were assessed using an enzyme-linked immunosorbent assay along with other standard biochemical parameters. RESULTS: Elevated serum levels of U-II were recorded in the group of obese subjects with MS when compared with the group of obese subjects without MS (4.99 (8.97-3.16) vs. 4.17 (5.17-2.03) ng/mL, median and IQR, p = 0.026). Furthermore, a subgroup of study subjects with high blood pressure had significantly higher U-II levels in comparison with the normotensive subgroup (4.98 (7.19-3.22) vs. 3.32 (5.06-1.97) ng/mL, p = 0.027), while the subgroup with a positive family history of high blood pressure had significantly higher U-II levels when compared with subjects who had a negative family history of elevated blood pressure (5.06 (6.83-4.45) vs. 3.32 (6.13-2.21) ng/mL, p = 0.039). CONCLUSIONS: To the best of the author's knowledge, this is the first study on the levels of U-II in obese children and adolescents, including a possible link to MS.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34477110

RESUMO

SUMMARY: This is a case report of a child with chronic hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) as a paraneoplastic manifestation of olfactory neuroblastoma (OFN). We hereby report a clinical presentation as well as a pragmatic approach to one of the most common electrolytic disorders in the pediatric population and have emphasized the necessity of involving the sinonasal area in the diagnostic procedure while evaluating possible causes of SIADH. This report indicates that the chronicity of the process along with the gradual onset of hyponatremia occurrence is responsible for the lack of neurological symptoms at the moment of disease presentation. LEARNING POINTS: Hyponatremia is not infrequently attributed to SIADH. Paraneoplastic syndromes are uncommon but they should be considered in the differential diagnosis of pediatric SIADH. Chronic insidious hyponatremia may not be associated with clear neurological symptoms despite its severity.

6.
Nutrients ; 13(8)2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34444953

RESUMO

The aims of this study were to evaluate: (1) associations of vitamin D with the presence/severity of Hashimoto's thyroiditis (HT) and (2) correlations of vitamin D with thyroid-related phenotypes. Total 25(OH)D (vitamin D in the text) was measured from stored serum samples of 461 HT patients and 176 controls from a Croatian Biobank of HT patients (CROHT). (1) Vitamin D levels, and proportions of vitamin D deficiency, were compared between HT cases and controls. HT patients were additionally divided into two groups (MILD and OVERT) to take into account HT severity. (2) Correlations between vitamin D and 10 clinical phenotypes in all HT patients and two subgroups of HT patients were tested using the Spearman correlation test. Our analyses were adjusted for age, gender, BMI, smoking status and seasonality of blood sampling. (1) No significant differences in vitamin D levels, or proportions of vitamin D deficiency, were detected between HT patients of all disease stages and controls. However, a nominally significant difference in vitamin D levels between MILD and OVERT subgroups (OR = 1.038, p = 0.023) was observed. Proportions of individuals with vitamin D deficiency during winter-spring were high: all HT cases (64.69%), MILD (60.64%), OVERT (68.7%), controls (60.79%). (2) A nominally significant negative correlation between vitamin D and TSH in all HT patients (r = -0.113, p = 0.029) and a positive correlation between vitamin D and systolic blood pressure in OVERT HT patients (r = 0.205, p = 0.025) were identified. Our study indicates that there is no association between vitamin D and HT; however, there may be a subtle decrease in vitamin D levels associated with overt hypothyroidism.


Assuntos
Doença de Hashimoto/sangue , Índice de Gravidade de Doença , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Adulto , Bancos de Espécimes Biológicos , Pressão Sanguínea , Estudos de Casos e Controles , Croácia , Feminino , Doença de Hashimoto/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Estações do Ano , Estatísticas não Paramétricas , Vitamina D/sangue , Deficiência de Vitamina D/complicações
7.
J Med Food ; 24(4): 385-393, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32783677

RESUMO

Vitamin D deficiency is associated with a range of chronic diseases, including childhood obesity. Prevalence of vitamin D deficiency in obese children and adolescents ranges from 6.5% to 57%. This cross-sectional study included 92 obese patients with body mass index z-score >2 and 39 subjects in the control group. Anthropometric and laboratory patient assessment were performed, including the fasting 25-hydroxyvitamin D (25(OH)D). Adherence to the Mediterranean diet was assessed by Mediterranean Diet Quality Index for children and adolescents (KIDMED index), while physical activity was evaluated by Physical Activity Questionnaire (PAQ). Serum levels of 25(OH)D were significantly lower in obese subjects compared to the control group (52.0 ± 17.93 vs. 64.09 ± 25.82 nmol/L, P = .003). The subgroup of obese patients with metabolic syndrome (MS) had significantly lower levels of serum vitamin D when compared to the subgroup of obese patients without MS and the control group (46.99 ± 17.11 vs. 54.58 ± 17.93 vs. 64.09 ± 25.82 nmol/L, P = .003). Obese patients with MS had lower PAQ score when compared to obese without MS and the control group (2.32 ± 0.55 vs. 2.49 ± 0.67 vs. 2.85 ± 0.63 nmol/L, P = .002), while no significant differences were observed in the KIDMED index (4.23 ± 1.81 vs. 4.21 ± 2.13 vs. 4.87 ± 2.29, P = .251), respectively. PAQ score was in positive correlation with serum levels of 25(OH)D (r = 0.305, P < .001). This study demonstrated that obese children and adolescents have significantly lower values of serum 25(OH)D. The positive correlation between vitamin D and PAQ score points to the importance of physical activity in the prevention of further cardiovascular complications and MS.


Assuntos
Dieta Mediterrânea , Deficiência de Vitamina D , Adolescente , Índice de Massa Corporal , Criança , Estudos Transversais , Exercício Físico , Humanos , Obesidade/epidemiologia , Vitamina D , Deficiência de Vitamina D/epidemiologia
8.
Croat Med J ; 61(3): 230-238, 2020 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-32643339

RESUMO

AIM: To analyze the association of thyroid function and hormone levels with metabolic syndrome (MetS) and its components. METHODS: This cross-sectional population-based study involved 2183 Croatian individuals with no history of thyroid disease, hypertension, diabetes, and hyperlipidemia. MetS was diagnosed according to the National Cholesterol Education Program's Adult Treatment Panel III criteria. RESULTS: We found no association between thyroid function groups and the prevalence of MetS and its components. Clinically hypothyroid participants showed significantly higher triceps skinfold measurements than subclinically hypothyroid and euthyroid participants. Furthermore, clinically hypothyroid participants had higher abdominal skinfold thickness than subclinically hypothyroid participants. Otherwise, suprailiac and abdominal skinfold measurements were higher in the subclinically and clinically hyperthyroid group of participants compared with euthyroid and subclinically hypothyroid participants. A strong positive association of thyroid-stimulating hormone (TSH) and strong negative association of free triiodothyronine (fT3) and free thyroxine (fT4) levels with HOMA-IR and cholesterol levels were found. Furthermore, the fT4 level also showed a strong negative association with HDL and triceps skinfold thickness. CONCLUSIONS: This study supports the standing that TSH, fT3, and fT4 levels are important variables to determine the association of thyroid function with MetS.


Assuntos
Síndrome Metabólica/sangue , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Autoantígenos/imunologia , Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Medições Luminescentes , Masculino , Pessoa de Meia-Idade , Tireoglobulina/imunologia , Hormônios Tireóideos/sangue , Adulto Jovem
9.
Sci Rep ; 10(1): 1754, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019955

RESUMO

Thyroid volume of Hashimoto's thyroiditis (HT) patients varies in size over the course of disease and it may reflect changes in biological function of thyroid gland. Patients with subclinical hypothyroidism predominantly have increased thyroid volume whereas patients with more pronounced hypothyroidism have smaller thyroid volumes. Suggested mechanism for thyroid atrophy is thyrocyte death due to apoptosis. We performed the first genome-wide association study (GWAS) of thyroid volume in two groups of HT patients, depending on levothyroxine (LT4) therapy, and then meta-analysed across. Study included 345 HT patients in total and 6 007 322 common autosomal genetic variants. Underlying hypothesis was that genetic components that are involved in regulation of thyroid volume display their effect in specific pathophysiologic conditions of thyroid gland of HT patients. We additionally performed immunohistochemical analysis using thyroid tissues and analysed differences in expression levels of identified proteins and apoptotic marker between HT patients and controls. We found genome-wide significant association of two loci, both involved in apoptosis, with thyroid volume of HT patients: rs7212416 inside apoptosis-antagonizing transcription factor AATF (P = 8.95 × 10-9) and rs10738556 near chromatin-remodeling SMARCA2 (P = 2.83 × 10-8). In immunohistochemical analysis we observed that HT patients with homozygous AATF risk genotypes have decreased AATF expression (0.46-fold, P < 0.0001) and increased apoptosis (3.99-fold, P = 0.0001) in comparison to controls. HT patients with heterozygous SMARCA2 genotypes have decreased SMARCA2 expression, albeit without reaching statistical significance (1.07-fold, P = 0.5876), and significantly increased apoptosis (4.11-fold, P < 0.0001). By two lines of evidence we show that two highly plausible genetic loci, AATF and SMARCA2, may be involved in determining the thyroid volume of HT patients. The results of our study significantly add to the current knowledge of disturbed biological mechanisms in thyroid gland of HT patients.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Doença de Hashimoto/genética , Doença de Hashimoto/patologia , Polimorfismo de Nucleotídeo Único/genética , Proteínas Repressoras/genética , Glândula Tireoide/patologia , Fatores de Transcrição/genética , Adulto , Apoptose/genética , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla/métodos , Genótipo , Heterozigoto , Humanos , Hipotireoidismo/genética , Hipotireoidismo/patologia , Masculino , Pessoa de Meia-Idade , Tiroxina/genética
11.
Sci Rep ; 9(1): 5360, 2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30926877

RESUMO

Thyroid antibodies against thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) are key markers of Hashimoto's thyroiditis (HT), the most common autoimmune thyroid disorder. Genetic determinants of thyroid antibodies are still poorly known, especially as they were not studied in patients with thyroid diseases. We performed the first genome-wide association analysis of thyroid antibodies in 430 HT patients that may be considered as population extremes for thyroid antibodies distribution. We detected two suggestively associated genetic variants with TgAb, rs6972286 close to ANKRD7 and LSM8 (P = 2.34 × 10-7) and rs756763 inside CA10 (P = 6.05 × 10-7), and one with TPOAb, rs12507813 positioned between TRIM61 and TRIM60 (P = 4.95 × 10-7). Bivariate analysis resulted with three suggestively associated genetic variants that predispose to both antibodies: rs13190616 inside RP11-138J23.1 (P = 2.01 × 10-6), rs561030786 close to DUBR (P = 7.33 × 10-6) and rs12713034 inside FSHR (P = 7.66 × 10-6). All identified genomic regions have a substantial literature record of involvement with female-related traits, immune-mediated diseases and personality traits that are all characterized by increased thyroid antibody levels. Our findings demonstrate the existence of genetic overlap between thyroid autoimmunity in HT and different non-thyroid diseases characterized by the presence of thyroid antibodies. We also suggest that genetic variants that regulate antibody levels may differ between HT patients and individuals with normal thyroid function.


Assuntos
Autoanticorpos/genética , Autoanticorpos/imunologia , Loci Gênicos , Estudo de Associação Genômica Ampla , Doença de Hashimoto/etiologia , Glândula Tireoide/imunologia , Glândula Tireoide/metabolismo , Adulto , Biomarcadores , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Variação Genética , Doença de Hashimoto/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade
12.
Pediatr Diabetes ; 20(5): 549-555, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30714297

RESUMO

BACKGROUND: Catestatin is a chromogranin A-derived peptide with a wide spectrum of biological activities, such as inhibiting catecholamine release, decreasing blood pressure, stimulating histamine release, reducing beta-adrenergic stimulation, and regulating oxidative stress. OBJECTIVES: The aims of our study were to determine serum catestatin concentrations in obese children and adolescents in regard to presence or absence of metabolic syndrome (MS) and to evaluate the possible relations between catestatin levels and other cardiovascular risk factors. SUBJECTS: Ninety-two obese subjects with a body mass index z score > 2, aged 10 to 18 years, and 39 healthy, normal weight controls were enrolled in the study. METHODS: Serum catestatin concentrations were measured using an enzyme-linked immunosorbent assay. RESULTS: Significantly lower serum catestatin concentrations were recorded in the group of obese subjects compared with a control group (10.03 ± 5.05 vs 13.13 ± 6.25 ng/mL, P = 0.004). Further analyses revealed significantly lower catestatin concentrations in the subgroup of obese patients with MS (9.02 ± 4.3 vs 10.54 ± 5.36 vs 13.13 ± 6.25, P = 0.008). Serum catestatin concentrations were significantly negatively correlated with diastolic blood pressure (r = -0.253, P = 0.014), homeostatic model assessment of insulin resistance (r = -0.215, P = 0.037) and high sensitivity C-reactive protein (r = -0.208, P = 0.044). CONCLUSIONS: To the best of our knowledge, this study is the first to report catestatin concentrations in obese children and adolescents and their possible relations with MS and cardiovascular risk factors in a pediatric population. Obese subjects with MS have lower serum catestatin concentrations than obese subjects without MS and controls.


Assuntos
Cromogranina A/sangue , Síndrome Metabólica/sangue , Obesidade Infantil/sangue , Fragmentos de Peptídeos/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino
13.
Immunol Invest ; 48(2): 198-209, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30332318

RESUMO

BACKGROUND: Hashimoto's thyroiditis (HT) is the most common form of autoimmune thyroid disorders characterized by lower production of thyroid hormones and positivity to autoantibodies to thyroglobulin (TgAb) and/or thyroid peroxidase (TPOAb). We performed a comprehensive phenotypic characterization of patients with HT, with specific focus on thyroid autoimmunity, to get better understanding of disease manifestation. METHODS: We collected information on thyroid-specific phenotypes (TSH, T3, T4, fT4, TgAb, TPOAb, thyroid volume) and other clinical phenotypes (age, body surface area, number of hypothyroidism symptoms, blood pressure) from 290 patients with HT without levothyroxine (LT4) therapy with the aim to test for correlations between thyroid-specific and clinical phenotypes. RESULTS: Our key and novel finding is the existence of significant positive correlation between TgAb levels and the number of symptoms (r = 0.25, p = 0.0001) in HT patients without LT4 therapy that remained significant after adjustment for TPOAb, T3, TSH levels and thyroid volume (ß = 0.66, SE = 0.3, p = 0.0299). Increased TgAb levels are significantly associated with fragile hair (p = 0.0043), face edema (p = 0.0061), edema of the eyes (p = 0.0293) and harsh voice (p = 0.0349). CONCLUSIONS: Elevated TgAb levels are associated with symptom burden in HT patients, suggesting a role of thyroid autoimmunity in clinical manifestations of HT. Based on these results, we recommend screening for TgAb antibodies in HT patients with symptom burden. We also suggest that further work on understandings of symptoms appearance due to their autoimmune or hypothyroid causation is needed.


Assuntos
Autoanticorpos/imunologia , Doença de Hashimoto/epidemiologia , Doença de Hashimoto/etiologia , Tireoglobulina/imunologia , Biomarcadores , Estudos Transversais , Feminino , Doença de Hashimoto/diagnóstico , Humanos , Masculino , Fenótipo , Prognóstico
15.
Int J Endocrinol ; 2018: 6763586, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29755521

RESUMO

Cataract is a rare manifestation of ocular complication at an early phase of T1DM in the pediatric population. The pathophysiological mechanism of early diabetic cataract has not been fully understood; however, there are many theories about the possible etiology including osmotic damage, polyol pathway, and oxidative stress. The prevalence of early diabetic cataract in the population varies between 0.7 and 3.4% of children and adolescents with T1DM. The occurrence of diabetic cataract in most pediatric patients is the first sign of T1DM or occurs within 6 months of diagnosis of T1DM. Today, there are many experimental therapies for the treatment of diabetic cataract, but cataract surgery continues to be a gold standard in the treatment of diabetic cataract. Since the cataract is the leading cause of visual impairment in patients with T1DM, diabetic cataract requires an initial screening as well as continuous surveillance as a measure of prevention and this should be included in the guidelines of pediatric diabetes societies.

16.
Eur J Pediatr ; 176(10): 1393-1404, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28879515

RESUMO

Testicular adrenal rest tumors (TARTs) are common cause of infertility in males with congenital adrenal hyperplasia (CAH). We studied the role of genotype and disease regulation on TART development, their impact on gonadal function, and frequency in 47 21-hydroxylase deficiency (21-OHD) and four 11-hydroxylase deficiency (11-OHD) male patients. Testicular ultrasound (TU), genotype, hormonal measurement in 51, and spermiogram in five patients were performed. TARTs were detected in 14 SW21-OHD and one 11-OHD patient: 1/8 patients aged <7 years (1.8 years old is the youngest), 1/8 patients aged <12 years, 5/17 patients aged <18 years, and in 8/18 adults. All 21-OHD TART patients had exclusively severe mutations of CYP21A2 gene. Poor hormonal control in 8/15 patients with and 12/36 patients without TART indicates correlation of tumor development with poor disease control. None of the TART patients fathered a child. Low inhibin-B was found in 7/15 TART patients. Azoospermia was found in four and oligoasthenozoospermia in one patient. CONCLUSION: TART was detected exclusively in patients with severe CYP21A2 mutations. Disease regulation plays a role in development of TART that impairs testicular function and increases the risk of infertility. Screening for TART by TU is indicated from early childhood. What is Known: • Due to improved diagnostic and therapeutic possibilities, majority of the male patients with congenital adrenal hyperplasia nowadays reach adulthood and screening for long-term complications is becoming more important. • Testicular adrenal rest tumors (TARTs) are common cause of infertility and impaired gonadal function in males with CAH. What is New: • A 1.8-year-old boy described in this paper is the youngest reported patient with TART. • Screening for TART by testicular ultrasound from early childhood, especially in patients with severe CYP21A mutations, is recommended.


Assuntos
Hiperplasia Suprarrenal Congênita/complicações , Tumor de Resto Suprarrenal/etiologia , Infertilidade Masculina/etiologia , Neoplasias Testiculares/etiologia , Adolescente , Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/fisiopatologia , Tumor de Resto Suprarrenal/diagnóstico , Tumor de Resto Suprarrenal/fisiopatologia , Adulto , Fatores Etários , Criança , Pré-Escolar , Estudos Transversais , Progressão da Doença , Genótipo , Humanos , Lactente , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/fisiopatologia , Masculino , Fatores de Risco , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/fisiopatologia , Adulto Jovem
17.
Exp Clin Endocrinol Diabetes ; 125(8): 563-570, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28750427

RESUMO

Background Although environmental factors induce development of type 1 diabetes mellitus (T1DM) in genetically susceptible individuals, many of those factors have been uncovered. Therefore, the aim of the present study was to analyze associations of T1DM with a wide range of environmental factors. Material and Methods A case-control study was conducted on 249 diabetic and 255 healthy individuals from the Dalmatian region of South Croatia. Data regarding risk factors during pregnancy and early life period of the child were evaluated. Results History of antihypertensive intake (p=0.04) and frequency of stressful life events during pregnancy (p=0.01) were associated with higher risk of T1DM, while hypertension was associated with lower risk of T1DM (p=0.01). Maternal age<25 years at delivery was associated with a higher risk of T1DM (p=0.01).Diabetic patients had a positive family history of T1DM or T2DM (p=0.002) more frequently than controls, while history of infectious diseases was inversely associated with the risk of T1DM (p=0.03). A higher risk of T1DM was significantly associated with earlier introduction of cow's milk (p=0.001), higher number of meals consumed per day (p=0.02), higher frequency of carbohydrate (p=0.001) and meat (p=0.01) consumption and stressful life events during childhood (p=0.02) while earlier introduction of fruit was associated with a lower risk of T1DM (p=0.03) Conclusion This case-control study confirmed associations of a large number of environmental factors with development of T1DM with emphasis on the association of mother's antihypertensive intake during pregnancy, which extends our knowledge about environmental factors related with development of T1DM.


Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Estudos de Casos e Controles , Criança , Pré-Escolar , Croácia/epidemiologia , Diabetes Mellitus Tipo 1/etiologia , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/efeitos adversos , Feminino , Humanos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Fatores de Risco
18.
J Steroid Biochem Mol Biol ; 165(Pt A): 51-56, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27041116

RESUMO

Congenital adrenal hyperplasia owing to 21-hydroxylase deficiency is caused by mutation in the CYP21A2 gene. The frequency and spectrum of CYP21A2 mutations and genotype-phenotype correlations among different populations are variable. Aim of this study was to define mutation frequency and spectrum of CYP21A2 gene mutations in patients with classical 21-hydroxylase deficiency (21OHD) and their family members in Croatia and study genotype-phenotype correlation. Clinical features and mutations of CYP21A2 gene in 93 unrelated 21OHD patients and 193 family members were examined. In this cohort, 66 patients were affected with salt wasting (SW) form, and 27 were affected with simple virilizing (SV) form of the disease. Mutations were identified in both alleles (67% compound heterozygous and 33% homozygous) in 91 of 93 patients. Deletions and conversions were found in 18.8% and point mutations in 79.6% alleles. Mutations in 3 alleles (1.6%) remained unidentified (in one patient we found only one, while in other no mutations were found at all). The most common point mutations were Intron 2 splice mutation IVS2-13 A/C>G (35.5%) and p.R357W (16.7%). Genotypes were categorized into Groups 0, A, B and C according to the extent of enzyme impairment. Genotype-phenotype concordance was 100%, 85% and 75% for Groups 0, A and B, respectively. Since only classical 21OHD patients were studied, Group C comprised solely p.P31L mutation and had 73% patients with SV and 27% with SW phenotype. Intrafamilial phenotypic variability was found in two families. CYP21A2 genetic analysis in 193 family members showed that 126 parents were heterozygous carriers, 3 were newly discovered patients, 2 fathers were not biological parents, and mutations were not detected in 3. Among 59 siblings, 32 were heterozygous carriers, 15 carried normal alleles, and 12 were patients (4 newly diagnosed). Genotype-phenotype divergence observed in this study suggests caution in preconceptional counseling and prenatal diagnosis of CAH. High frequency of p.R357W mutation was found in Croatian patients with classical 21-OHD. Genotyping of family members discovered new patients and thus avoided pitfalls in genetic counseling when the parents were found to be affected.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Esteroide 21-Hidroxilase/genética , Hiperplasia Suprarrenal Congênita/etnologia , Alelos , Criança , Pré-Escolar , Estudos de Coortes , Croácia , Feminino , Estudos de Associação Genética , Genótipo , Antígenos HLA/química , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Linhagem , Fenótipo , Mutação Puntual , Irmãos
19.
Acta Medica (Hradec Kralove) ; 60(3): 120-123, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29439758

RESUMO

INTRODUCTION: Testicular torsion is a urological emergency. If not recognized in time, this condition may result in ischaemic injury and loss of testis. Simultaneous bilateral neonatal testicular torsion is extremely rare and is usually misdiagnosed. CASE REPORT: We report a case of a male newborn, who presented with bilateral scrotal swelling and redness of the scrotum. Doppler ultrasound supported the diagnosis of bilateral testicular torsion, with an absent blood flow signal on the right side and a weak signal on the left side. Testicular exploration through scrotal incision was performed and bilateral testicular torsion was found. Right testis was grossly gangrenous, and right orchiectomy was performed. Left testicle was dark but showed recovery after detorsion with some bleeding from incised tunica albugenia. Fixation of the left testicle was performed. At six month follow-up, the left testis showed signs of atrophy and hormonal assay showed very low testosterone and elevated LH and FSH, suggesting hypogonadism. CONCLUSIONS: Management of neonatal testicular torsion is a matter of controversy. Testicular torsion results into acute ischemia and urgent surgical exploration is the key point of management. Although the possibility of salvaging the involved testicles is usually very low it is hard to justify a passive approach to a bilateral torsion resulting in such a devastating condition as anorchia.


Assuntos
Torção do Cordão Espermático/cirurgia , Testículo/cirurgia , Gangrena/cirurgia , Humanos , Recém-Nascido , Masculino , Orquiectomia , Torção do Cordão Espermático/diagnóstico por imagem , Testículo/patologia , Testosterona/sangue
20.
Int J Endocrinol ; 2016: 1823561, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27752263

RESUMO

Obesity and metabolic syndrome (MS) are one of the biggest public health issues in child and adolescent population. To the best of the authors' knowledge, this hospital based study is the first report on the prevalence of MS in obese children and adolescents in Dalmatia, the Mediterranean part of Croatia. The objectives of this study were to determine the prevalence of individual cardiovascular risk factors and MS. Between January 2009 and June 2014, 201 obese subjects aged 6 to 18 were analyzed retrospectively from our Pediatric Endocrine Unit database. The subjects were then classified in two groups of obesity; subjects with BMI z score 2.0-3.0 were classified as moderately obese and subjects with BMI z score > 3.0 were classified as severely obese. The overall prevalence of MS using the modified IDF criteria was 30.3%. The most common component of MS in both groups was arterial hypertension, while impaired fasting glucose was the least common component of MS. Our finding of high prevalence of MS underlines the importance of early childhood obesity treatment.

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