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1.
Hormones (Athens) ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38311659

RESUMO

Premature ovarian failure (POF) defines the occurrence of ovarian failure prior to the age of 40. It occurs in one out of 100 women but is very rare before age 20 (1:10,000). Maturity-onset diabetes of the young (MODY), caused by mutations in the HNF1A gene, is also a rare disorder; all types of MODY account for 1-2% of adult diabetic cases. These two rare nosologic entities coexisted in an adolescent girl evaluated for delayed puberty. Although this combination could represent a chance association, an interrelation might exist. We examined HNF1A expression in human fetal and adult ovaries by immunohistochemistry using a polyclonal HNF1A antibody. HNF1A protein was expressed in both the fetal and adult human ovaries. Based on these findings, we hypothesize that HNF1A participates in ovarian organogenesis and/or function and that mutations in the HNF1A gene might represent another molecular defect causing POF, possibly in combination with other genetic factors. The study underlines the importance of rare clinical paradigms in leading the way to elucidation of the pathogenetic mechanisms of rare diseases.

2.
Clin Endocrinol (Oxf) ; 82(4): 543-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25041270

RESUMO

BACKGROUND: Nonclassical congenital adrenal hyperplasia (NC-CAH) is caused by mutations of the CYP21A2 gene. The clinical manifestations and hormonal derangements of NC-CAH are quite variable. OBJECTIVES: (i) To define the phenotype and its relation to genotype according to gender and age and (ii) to evaluate the validity of currently applied hormonal criteria for establishing the diagnosis of NC-CAH. PATIENTS AND METHODS: The clinical, hormonal and molecular data of 280 subjects (235 female) with NC-CAH and a median age of 17·6 years were analysed. CYP21A2 genotyping was performed in all subjects. RESULTS: The majority of females aged less than 8 years presented with premature pubarche (88·3%), while those older than 8 presented with a polycystic ovary-like phenotype (63·2%). A total of 7·7% of the females and 51·1% of the males were asymptomatic at the time of diagnosis. In the total group, 50·4% of the subjects were compound heterozygotes for one classical (C) and one nonclassical (NC) mutation, while 46% of the alleles studied carried the p.V281L mutation. Basal 17OHP values were below 6 nm (2 ng/ml) in 2·1% of the subjects with NC-CAH, but none had peak 17OHP values post-ACTH lower than 30 nm (10 ng/ml). CONCLUSIONS: NC-CAH has a variable phenotype depending on the age, gender and the presence of a classical mutation. A peak cut-off value of 17OHP post-ACTH lower than 30 nm excludes the diagnosis of NC-CAH, whereas basal 17OHP <6 nm may represent a false-negative result. A significant number of patients harboured a classical mutation, a finding which requires genotyping of the partner for genetic counselling.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Mutação , Esteroide 21-Hidroxilase/genética , Adolescente , Adulto , Idoso , Alelos , Criança , Pré-Escolar , Feminino , Genótipo , Heterozigoto , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fenótipo , Síndrome do Ovário Policístico/fisiopatologia , Adulto Jovem
3.
Horm Metab Res ; 45(5): 383-6, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23386413

RESUMO

The question of the contribution of CYP21A2 heterozygosity to the development of polycystic ovary syndrome (PCOS) has repeatedly been raised in the literature. The available data, however, do not offer a satisfactory answer. The discrepancy must be attributed, primarily, to the small number of subjects in the various studies, the type of selected phenotype, and the number of searched mutations. The aim of the study was to define the contribution of CYP21A2 heterozygous mutations to the pathogenesis of PCOS. We searched for 14 molecular defects of the CYP21A2 gene in 197 PCOS women, employing allele specific PCR. Androgen levels were determined at baseline by appropriate methodology in the follicular phase. PCOS women with 17-hydroxyprogesterone (17OHP) basal values >2 ng/ml and/or post-ACTH >10 ng/ml were excluded. Appropriate controls were included. The frequency of the CYP21A2 heterozygous mutations in PCOS women and in controls was 7.6% and 5.9%, respectively [p-value (PCOS vs. controls): 0.663]. Homozygosity for CYP21A2 gene defects was not detected. In conclusion, the contribution of CYP21A2 heterozygous mutations to the pathogenesis of PCOS is not substantiated by our data. Moreover, 17-hydroxyprogesterone values of < 10 ng/ml post-ACTH exclude homozygosity of CYP21A2 mutations.


Assuntos
Predisposição Genética para Doença , Mutação/genética , Síndrome do Ovário Policístico/enzimologia , Síndrome do Ovário Policístico/genética , Esteroide 21-Hidroxilase/genética , Adulto , Androgênios/sangue , Estudos de Casos e Controles , Feminino , Heterozigoto , Homozigoto , Humanos , Síndrome do Ovário Policístico/sangue , Adulto Jovem
4.
Horm Metab Res ; 42(4): 285-9, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20119886

RESUMO

The aim of the work was to assess thyroid function in children and adolescents in an iodine replete area and to explore possible effects of age, gender, puberty, and adiposity. Thyrotropin (TSH), total triiodothyronine (T (3)), total thyroxine (T (4)), free thyroxine (FT (4)), and the T (4)/T (3) ratio were determined for 440 schoolchildren (200 boys and 240 girls), aged 5-18 years, living in an iodine replete region. Body Mass Index (BMI), BMI standard deviation score (BMI-SDS), and Body Surface Area (BSA) were calculated. In girls there was a negative correlation of TSH, T (3), and FT (4) values with age. In boys there was a negative correlation only of T (3) values with age. Girls had lower TSH, T (4), and T (3) values, whereas boys had only lower T (3) values at puberty compared to the prepubertal stage. Girls had lower TSH values than boys (p<0.03) only at puberty. BMI-SDS in boys and girls were 0.21 and 0.03, respectively. BMI-SDS was not related to TSH, T (4), or T (3) in either gender, whereas it was negatively related to T (4)/T (3) ratio in boys and to FT (4) in girls. We conclude that estrogens may exert a suppressive effect on the pituitary-thyroid axis after puberty. TSH values are not correlated with BMI-SDS, whereas T (4)/T (3) ratio in boys and FT (4) in girls are negatively correlated with BMI-SDS.


Assuntos
Envelhecimento/sangue , Índice de Massa Corporal , Iodo/deficiência , Puberdade/sangue , Caracteres Sexuais , Hormônios Tireóideos/sangue , Tireotropina/sangue , Adolescente , Antropometria , Criança , Feminino , Grécia , Humanos , Masculino , Instituições Acadêmicas , Tri-Iodotironina/sangue
5.
J Endocrinol Invest ; 31(5): 406-15, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18560258

RESUMO

UNLABELLED: Diabetes mellitus Type 1 (T1D) is an autoimmune disorder attributed to both genetic and environmental factors. The aim of this study was to identify certain stressful conditions potentially associated with the pathogenesis and/or expression of T1D. The study group included 107 children with diabetes (CD) and 153 controls of comparable age and gender distribution at diagnosis of T1D (10.73+/-3.62 yr vs 9.59 +/-3.42 yr, respectively). The parents of both groups completed a questionnaire on socioeconomic status and stressful life events or adverse situations at home and school. RESULTS: Lower social class was more prevalent among the mothers of CD (p=0.002) in comparison with the controls. Stressful life events (parental death, divorce, parental job loss), problems at home (parental abuse, parental dispute) and at school (poor performance) were more frequently observed in the CD group than in the controls (parental death: p=0.05, job loss: p=0.05, parental abuse: p=0.002, quarrels between parents: p=0.05, and among siblings p=0.002, poor school performance: p=0.037). A stepwise logistic regression analysis indicated that lower maternal social class [odds ratio (OR): 3.86, 95% confidence interval (CI): 1.37,10.9], parental dispute or divorce (OR: 2.78, 95%CI: 0.97,7.95), body mass index (OR: 0.87, 95%CI: 0.78,0.97), increasing age (OR: 1.14, 95%CI: 1.02,1.27) were the factors potentially influencing the occurrence of T1D, while the 2-yr period prior to diabetes occurrence emerged as the most important one (OR: 2.49, 95%CI: 1.14,5.42). CONCLUSION: Children with diabetes seem to experience certain stressful conditions with significantly increased frequency compared to controls, especially during the 2 yr preceding the diagnosis of T1D, with a higher clustering in those of lower social class. The resultant stress possibly contributes to the development of T1D in genetically susceptible individuals.


Assuntos
Diabetes Mellitus Tipo 1/etiologia , Estresse Psicológico/complicações , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Acontecimentos que Mudam a Vida , Masculino , Classe Social
6.
Horm Metab Res ; 39(7): 524-8, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17611907

RESUMO

An earlier adiposity rebound, suggestive of adult obesity, has been reported in children with congenital hypothyroidism. We undertook this study to evaluate the effect of congenital hypothyroidism on: 1) the timing of adiposity rebound, 2) the long-term prognosis of BMI status, and 3) the factors potentially affecting adiposity in subjects with congenital hypothyroidism. We found that in children with congenital hypothyroidism the BMI values were higher during the first years of life compared to normal population, but subsequently normalized. After the initial rise of BMI, the decline (nadir) and subsequent rise (adiposity rebound), usually occurring in normal children at an age greater than 30 months, was less evident in our group of children with congenital hypothyroidism. The severity of hypothyroidism affected BMI values at 6 and 12, but not at 36 months of age. In conclusion, in children with congenital hypothyroidism, 1) the high BMI values in early childhood normalize in adolescence, and 2) the normally expected BMI fluctuations during the first years of life are attenuated. These findings constitute indirect evidence that thyroid function during fetal and neonatal life affects BMI status during the first years of life.


Assuntos
Adiposidade/fisiologia , Índice de Massa Corporal , Hipotireoidismo Congênito/complicações , Hipotireoidismo Congênito/fisiopatologia , Obesidade/complicações , Obesidade/fisiopatologia , Adolescente , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
7.
J Endocrinol Invest ; 29(5): 462-6, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16794371

RESUMO

Inactivating PROP1 gene alterations are responsible for over 50% of familial combined pituitary hormone deficiency cases. Pituitary enlargement followed by regression and subnormal pituitary size has been documented in a number of PROP1 deficient patients. Data derived from PROP1 deficient mice (Ames dwarfs) have revealed some of the underlying cellular mechanisms. Nevertheless, long-term magnetic resonance imaging (MRI) findings in two PROP1 deficient patients suggest the evolution of pituitary pathology as more complex and persistent than previously described. Patient A had enlarged pituitary gland (pituitary height: 9-10 mm), demonstrated by serial MRI carried out from age 5 to 8.5 yr, small pituitary gland (4 mm) at age 10 yr and pituitary enlargement (11 mm) at age 19 yr. Patient B had a pituitary gland of normal size at age 7 yr (5 mm), whereas at age 14.3 and 16.3 yr, an enlarged pituitary gland was disclosed (10 and 11 mm, respectively). Both series of events are suggestive of a persistent pathophysiological mechanism in the pituitary gland of patients with PROP1 gene defects. Therefore, long-term pituitary follow-up by MRI in such patients may be necessary even in the case of a small or normal pituitary gland. It must be noted that current data from the Ames dwarf mouse cannot fully explain the observed pituitary size fluctuation.


Assuntos
Proteínas de Homeodomínio/genética , Doenças da Hipófise/fisiopatologia , Hipófise/patologia , Hormônios Hipofisários/deficiência , Adolescente , Criança , Pré-Escolar , Humanos , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Doenças da Hipófise/genética , Doenças da Hipófise/patologia
8.
Thyroid ; 15(9): 1061-6, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16187915

RESUMO

Thyroid dysfunction, especially hypothyroidism caused by Hashimoto's thyroiditis is more frequently observed in girls with Turner's syndrome (TS). The aim of the present study was to evaluate prevalence, etiology, karyotype distribution and age at onset of thyroid pathology in girls with TS. Data recorded in 84 girls with TS attending our clinic were analyzed. The mean age +/- standard deviation [SD] at their initial evaluation was 10.3 +/- 3.7 years (range, 0.5 to 19 years) and the mean period of observation was 8.4 +/- 4.4 years. The thyroid function had been evaluated at least once per year in all patients and thyroid autoantibodies (ATA) were available in 51 (60.7%). Hypothyroidism was detected in 24% of the studied subjects and hyperthyroidism in 2.5%. Elevated values of thyroid autoantibodies were detected in 42% of girls with TS, whose ATA had been determined, and 65% had hypothyroidism. Thyroid dysfunction was first noted after the age of 8 years with no difference in the distribution of new cases at the different ages or pubertal stages. There was no difference in the incidence of thyroid dysfunction related to the type of karyotype abnormality. Thyroid dysfunction is more frequently encountered in girls with TS (hypothyroidism: 24% in the total group and 65% in those with positive ATA, hyperthyroidism: 2.5%). Thyroid dysfunction was observed after the age of 8 years with no difference in the occurrence of new cases in the various age groups thereafter. Hence, thyroid function should be evaluated yearly in girls with TS past the age of 8 years and more frequently in those with positive thyroid autoantibodies.


Assuntos
Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/etiologia , Síndrome de Turner/complicações , Síndrome de Turner/epidemiologia , Adolescente , Adulto , Fatores Etários , Idade de Início , Autoanticorpos/análise , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Hipertireoidismo/complicações , Lactente , Iodeto Peroxidase/sangue , Cariotipagem , Doenças da Glândula Tireoide/genética , Testes de Função Tireóidea , Tireoidite Autoimune/complicações , Tireoidite Autoimune/epidemiologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Síndrome de Turner/genética
9.
J Eur Acad Dermatol Venereol ; 19(1): 30-4, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15649188

RESUMO

BACKGROUND: The relationship between granuloma annularae (GA) and diabetes mellitus (DM) is controversial. OBJECTIVE: To investigate the relationship between multiple lesions of GA and carbohydrate metabolism in children. SUBJECTS AND METHODS: Fifteen children (seven boys, eight girls, mean age 4.8 years) with five or more lesions of GA were evaluated. A personal and family history of DM or other autoimmune diseases was obtained and the glycaemic and insulin response during an oral glucose tolerance test (OGTT) was determined. Thirteen children with a negative personal and family history of DM served as controls for the OGTT and 100 other children as 'clinical controls'. RESULTS: At the 30-min sampling of the OGTT the mean insulin values were comparable in GA children and controls (P=0.1), while the mean glucose values were significantly higher in GA children than in controls (P=0.005). All other insulin values during the OGTT were significantly lower in GA children than in controls, while all other glucose values were comparable in GA children and controls with all indices applied. Eleven out of 15 GA children had a positive family history of DM (73.3% vs. 16% of the clinical controls; P<0.0001). CONCLUSION: Multiple lesions of GA in children are associated with significantly lower serum insulin values than in controls and mildly impaired glucose tolerance.


Assuntos
Granuloma Anular/sangue , Insulina/sangue , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Feminino , Teste de Tolerância a Glucose , Humanos , Lactente , Masculino , Estudos Prospectivos
11.
Clin Pediatr (Phila) ; 42(1): 59-65, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12635983

RESUMO

The "short normal" child constitutes a real challenge for the pediatric endocrinologist. In a subgroup of short normal children, puberty starts at a normal age but with low height, and hence, the final height is expected to be quite compromised. Efforts to improve the outcome in this group have been made in the past with equivocal results. We present the growth data of 8 short girls with normal growth hormone values on provocative testing and low height at puberty initiation. At intervention the height and the stage of puberty were 129.3 +/- 5 cm and II to III, respectively, and the predicted height was 148.8 +/- 2.6 cm. Gonadotropin releasing hormone analog, triptorelin (3.6 +/- 0.5 microg/kg/day) and growth hormone (0.5 IU/kg/week) were used in different sequential order and simultaneously in each child. The mean total treatment period was 47.6 +/- 11.2 months. The mean predicted and the mean final height in the total group were 148.8 +/- 2.6 and 154.5 +/- 3.6 cm, respectively (p:0.028). The final height did not differ from the target height (154.8 +/- 8 cm versus 154.5 +/- 3.6 cm), while in 4 children, the final height was greater than the target height. The height gain (delta Final height - Predicted height) was 5.7 +/- 1.3 cm. If we analyze separately the girls in whom growth hormone was started first and gonadotropin releasing hormone analog followed versus those who started the analog first, the delta Final height - Predicted height was 8 +/- 3 cm in the former and 4.8 +/- 3.1 cm in the latter (p:0.03). It seemed that the difference was accounted for by duration of growth hormone therapy (51.3 +/- 10.6 months versus 28.6 +/- 10.6 months) (p:0.026), rather than by other factors. In conclusion, under the conditions of the present study, the combination of puberty arrest and growth hormone therapy significantly improved predicted height. The most significant determinant of the height gain was the duration of growth hormone therapy.


Assuntos
Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/administração & dosagem , Pamoato de Triptorrelina/administração & dosagem , Determinação da Idade pelo Esqueleto , Estatura/efeitos dos fármacos , Criança , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Transtornos do Crescimento/diagnóstico , Humanos , Injeções Subcutâneas , Valor Preditivo dos Testes , Estudos Prospectivos , Resultado do Tratamento
12.
Clin Endocrinol (Oxf) ; 57(5): 669-76, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12390343

RESUMO

OBJECTIVE: The management of children with congenital adrenal hyperplasia (CAH) remains a challenge, especially with regard to growth potentials. The objective of our analysis was to uncover the factors that influence the growth and final height of patients with CAH. DESIGN: The linear growth pattern and body mass index (BMI) at different developmental stages (birth to 2 years, 2 years to puberty initiation and puberty initiation to final height) and the final height achieved were analysed retrospectively in 48 patients with 21-hydroxylase deficiency; 17 with the salt-wasting (SW) form, 25 with the simple virilizing (SV) and six with the nonclassical (NC) form. RESULTS: Mean final height (FH) and FH-SDS were, respectively, 170.8 +/- 5.6 m and -0.57 +/- 0.8 in males and 156.7 +/- 6 cm and -0.61 +/- 1 in females with the SW form, 166.1 +/- 6.1 cm and -1.05 +/- 1 in males and 151.6 +/- 5.4 cm and -1.4 +/- 1 in females with the SV form and 159.7 +/- 6.9 cm and 0.3 +/- 1.4 in females with the NC form. In subjects with the SW form, height SDS at 2 years, at puberty initiation and at FH were -0.18 +/- 0.9, 0.11 +/- 1.28 and -0.6 +/- 1.0, respectively. FH achieved was not different from target height (TH) in the SW group, but it was significantly lower than TH in the SV group (P = 0.003). FH in the SW group showed a positive correlation to the height achieved at 2 years of age (r = 0.68, P = 0.019), and height at 2 years was negatively related to the hydrocortisone dose in the birth to 2-year period (r = -0.79, P = 0.011). FH showed no correlation to hydrocortisone dose at any of the three developmental periods studied. BMI-SDS were not different in the various forms of CAH and showed no correlation to FH or hydrocortisone dose. Age at menarche was comparable to that in our general population. CONCLUSIONS: Under our conditions of management, the final height of patients with the salt-wasting form was comparable to the target height and to the most favourable literature data. The patients with the simple virilizing form fare less well, mainly due to delayed diagnosis and consequent advancement of bone age and early puberty. In salt-wasting patients, height at 2 years is comparable to normals, it is influenced by the hydrocortisone dose and is related to the final height. Some height is lost during puberty. Hence, monitoring treatment over the first 2 years and during puberty is critical for the outcome in these patients.


Assuntos
Hiperplasia Suprarrenal Congênita/fisiopatologia , Estatura , Crescimento , Puberdade , Adolescente , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hormônio Adrenocorticotrópico/uso terapêutico , Adulto , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Resultado do Tratamento
13.
J Pediatr Endocrinol Metab ; 14(8): 1107-11, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11592567

RESUMO

Adrenarche was evaluated in five patients, aged 17.4 +/- 3 years, with combined pituitary hormone deficiency (CPHD), caused by a PROP-1 gene defect. Adrenocorticotrophic hormone (ACTH), cortisol and dehydroepiandrosterone sulfate (DHEAS) were determined prior to and following the administration of corticotropin-releasing hormone (CRH) in four of the five patients, while only basal values of ACTH, cortisol and DHEAS were determined in the fifth. In the four patients in whom a CRH test was carried out, the mean basal values of cortisol, ACTH and DHEAS were 289 +/- 140 nmol/l, 4.5 +/- 1.7 pmol/l and 0.26 +/- 0.36 micromol/l, respectively. The corresponding post-CRH peak values were 584 +/- 204 nmol/l, 12.7 +/- 3.9 pmol/l and 0.43 +/- 0.41 micromol/l. In the fifth patient, basal ACTH, cortisol and DHEAS values were 4 pmol/l, 411 nmol/l, and 2.33 micromol/l, respectively. Thus the basal and post CRH values of DHEAS (a marker of adrenarche) were low for age, while basal and post-CRH cortisol and ACTH values were within normal limits. For the interpretation of these findings two hypotheses can be proposed: 1) The PROP-1 gene is only expressed in the pituitary, and the role of PROP-1 is related to the maturation of the cells which synthesize the presumed adrenal androgen stimulating hormone (AASH). 2) The PROP-1 gene is also expressed in the adrenal cortex and, when defective, the zona reticularis does not function appropriately. Regardless of the interpretation


Assuntos
Proteínas de Homeodomínio/genética , Mutação , Hormônios Hipofisários/deficiência , Puberdade , Zona Reticular/fisiopatologia , Adolescente , Córtex Suprarrenal/metabolismo , Hormônio Adrenocorticotrópico/sangue , Adulto , Hormônio Liberador da Corticotropina , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona/sangue , Feminino , Expressão Gênica , Proteínas de Homeodomínio/fisiologia , Humanos , Hidrocortisona/sangue , Masculino , Hipófise/metabolismo
14.
J Clin Endocrinol Metab ; 86(6): 2845-8, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11397897

RESUMO

Defective steroid synthesis due to 21-hydroxylase deficiency is the most common form of congenital adrenal hyperplasia. Knowledge of the molecular defects causing 21-hydroxylase deficiency in different populations is of both theoretical and practical interest. The types and the relative frequencies of molecular defects and the correlation between the genotype and the phenotype were examined in the Hellenic population. We searched for deletions, conversions, and 11 of the most frequent mutations of the CYP21 gene by Southern blot and allele-specific PCR in 222 chromosomes from 111 unrelated subjects and their parents. The most frequent molecular defects were 1) in the salt wasting form, I(2) splice (42.9%), deletions and conversions (24.5%), and Q318stop (14.3%); 2) in the simple virilizing form, I172N (35.3%), I(2) splice (29.4%), and P30L (19.1%); and 3) in the nonclassical form, V281L (41.1%), P30L (21.4%), and P453S (14.3%). Compared with other populations, Greek patients had a higher frequency of Q318stop in the salt-wasting form, of P30L in both simple virilizing and nonclassical forms and of P453S in the nonclassical form. The concordance of genotype to phenotype in the total sample was 87%. However, the concordance rate was different in the three forms of the disease. Thus, complete concordance was detected in the genotypes predicting the salt-wasting phenotype, a slightly lower concordance (95.2%) was detected in the genotypes predicting the simple virilizing phenotype, and the lowest concordance (67.6%) was observed in genotypes predicting the nonclassical phenotype. In conclusion, the concordance between genotype and phenotype decreases as the severity of the disease diminishes. This should be taken into consideration in genetic counseling and antenatal intervention.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Mutação/genética , Esteroide 21-Hidroxilase/genética , Hiperplasia Suprarrenal Congênita/classificação , Conversão Gênica , Deleção de Genes , Frequência do Gene , Genótipo , Grécia , Humanos , Fenótipo
15.
J Pediatr Endocrinol Metab ; 14(4): 397-405, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11327373

RESUMO

The growth data of 156 children (100 boys, 56 girls) with growth hormone deficiency (GHD), treated with human growth hormone (GH) for 5.7+/-3.7 years, from 1970-1997, were retrospectively analyzed to assess the efficacy of GH treatment and the factors involved. 62.2% of the studied population had idiopathic GHD (IGHD) and 35.2% had organic GHD (OGHD). At initiation of treatment, chronological age (CA) was 10.1+/-4.0 years in children with IGHD and 9.7+/-4.0 years in those with OGHD, while bone age (BA) was 7.0+/-3.7 and 7.7+/-3.2 years, respectively. The SDS of the growth velocity during the first year of therapy (GV1) was negatively related to CA at start of therapy (r = -0.53, p = 0.01). 109 children have reached final height (FH): 67 boys (FH = 165.3+/-6.3 cm) and 42 girls (FH = 153.9+/-5.4 cm). FH SDS was not significantly different from target height (TH) SDS. In the total group, FH SDS was positively related to height SDS for CA and BA at start of therapy (p = 0.01, p = 0.001, respectively), to TH SDS (r = 0.40, p = 0.001), and to GV1 (r = 0.33, p = 0.001). TH SDS was not different between the IGHD and OGHD groups (-1.02+/-0.8 vs. -0.94+/-6.9). The height gain at puberty did not differ between the groups with induced or spontaneous puberty in boys (23.7+/-8.6 vs. 25.4+/-6.9, not significant), while in girls it was higher in the group with spontaneous puberty (12.7+/-7.3 vs. 20.0+/-9.0, p = 0.008). The age and height at start of puberty was higher in girls and boys with induced puberty. In the total group, the FH SDS of children with induced puberty was higher in comparison with those with spontaneous puberty (-1.0+/-0.8 vs. -1.7+/-0.9, p = 0.001) and it was positively related to the height at start of puberty. When the two sexes were analyzed separately, the difference reached significance only in boys. In conclusion, children with GHD on GH treatment achieved a final height which was comparable to their genetic potential. The FH of children with OGHD was not different from those with IGHD. The age and height at start of puberty were the most significant determining factors for FH. Hence, a better FH might be expected by delaying or arresting puberty.


Assuntos
Estatura , Crescimento , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Puberdade/fisiologia , Adolescente , Fatores Etários , Estatura/genética , Criança , Feminino , Grécia , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Masculino , Resultado do Tratamento
16.
Psychother Psychosom ; 70(2): 78-85, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11244388

RESUMO

BACKGROUND: The objectives of this study of children and adolescents with diabetes were to: (1) examine whether maternal expressed emotion (EE), in the form of critical comments (CC), hostility and emotional overinvolvement (EOI), is related to metabolic control; (2) determine if CC and EOI are separately related to poor metabolic control, and (3) ascertain whether high EE is related to psychopathology in these children. METHODS: The Present Episode version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children (Kiddie-SADS-P/K-SADS-P) interview was administered to 55 children and adolescents with diabetes and the parental EE instrument, the 5-min speech sample, to 55 mothers. The same instruments were utilized with the 54 controls and their mothers. Glycosylated hemoglobin A1 values were used as a measure of metabolic control. RESULTS: More than half of the children with diabetes (58.2%) had mild to moderate symptoms of anxiety or depression as compared to 9.3% of the controls. High EE was exhibited by 70.9% of the index group mothers in contrast to only 29.6% of the control group mothers. High maternal EE was not related to the psychopathology of children with diabetes. High maternal EE and in particular its EOI component and excessive detail (a subcategory of EOI) were related to poor metabolic control of the index children. CONCLUSIONS: Maternal EE is related to metabolic control in childhood diabetes; maternal EOI in particular is related to poor metabolic control. Mental health professionals should work with mothers of children with diabetes in an effort to modify such attitudes and emotions.


Assuntos
Afeto , Diabetes Mellitus Tipo 1/metabolismo , Hemoglobinas Glicadas/metabolismo , Comportamento Materno/psicologia , Mães/psicologia , Adulto , Criança , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Transtornos do Humor/diagnóstico , Transtornos do Humor/epidemiologia , Relações Mãe-Filho , Índice de Gravidade de Doença
17.
J Pediatr Endocrinol Metab ; 14 Suppl 5: 1303-8; discussion 1317, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11964027

RESUMO

Data related to genetics of congenital adrenal hyperplasia with emphasis on CYP21 gene defects are briefly outlined. Mutations of the StAR gene lead to impaired translocation of cholesterol from the outer mitochondrial membrane to the inner mitochondria, a rate limiting step in steroidogenesis in the adrenals and the gonads. The clinical picture is characterized by adrenal and gonadal insufficiency and sex reversal in XY individuals. Molecular defects of the CYP17 gene encoding 17alpha-hydroxylase can cause hypertension, impaired sexual maturation and impaired sexual differentiation in XY individuals. Molecular defects of the CYP11B1 gene lead to 11-hydroxylase deficiency, which is clinically expressed with virilization of the external genitalia of the female and precocious puberty in the male, as well as hypertension in both sexes. The HSD3beta1 and HSD3beta2 genes encode two isoenzymes (3betaHSDI and 3betaHSDII). The clinical picture results from either absence or diminished activity of type II 3betaHSD, resulting from mutations of the HSD3beta2 gene. The most frequent form of CAH (90% of all patients) is due to deletions, conversions or point mutations of the CYP21 gene, which encodes the enzyme 21-hydroxylase. There is a wide range of clinical expression primarily explained by the type of the molecular defect. The ratio of genotype to phenotype concordance varies in the different forms of the disease, the highest one being encountered in the non-classical form. Heterozygosity of CYP21 mutations may be expressed as premature pubarche.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/epidemiologia , Frequência do Gene , Grécia/epidemiologia , Humanos , Fosfoproteínas/deficiência , Fosfoproteínas/genética , Esteroide Hidroxilases/deficiência , Esteroide Hidroxilases/genética
18.
J Pediatr ; 136(3): 359-64, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10700693

RESUMO

OBJECTIVE: To investigate whether "white coat hypertension" (WCH) in adolescents is an innocent phenomenon or is associated with early changes of the vascular system and/or increased stress response, reflected in the urinary endothelin and cortisol values, respectively. STUDY DESIGN: The study group included 36 subjects, 14 with WCH (8 males and 6 females) aged 12.9 +/- 3 years and 22 normotensive control subjects (12 males and 10 females) aged 13 +/- 3.5 years. WCH was defined as systolic and/or diastolic blood pressure (BP) > or =95th percentile for age, sex, and height and with reported normal BP measurements at home. Urinary endothelin (UET1), urinary free cortisol (UFC), and plasma renin levels were determined by radioimmunoassay; and urinary albumin levels were determined by nephelometry. For statistical analysis, the Mann Whitney U test, Spearman correlation coefficient, and multivariate analysis of variance/multivariate analysis of covariance were used, as applicable. RESULTS: The 24-hour values of UET1 and UFC were greater in male subjects with WCH than in male control subjects (P =.02), whereas no such difference was found in female subjects. The difference in UFC values in male subjects was accounted for by the day values. In subjects with WCH, and not in control subjects, a positive correlation of UET1 to UFC (r = 0.59, P =.027), diastolic BP (r = 0.55, P =.04), and mean BP (r = 0.65, P =.012) was detected. CONCLUSIONS: Our data indicate that WCH in adolescence may not be an innocent phenomenon and may represent a prelude to permanent idiopathic hypertension of adulthood.


Assuntos
Endotelinas/urina , Hidrocortisona/urina , Hipertensão/psicologia , Hipertensão/urina , Adolescente , Índice de Massa Corporal , Criança , Feminino , Humanos , Masculino
19.
Genet Couns ; 10(3): 245-50, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10546095

RESUMO

A caucasian boy with distinct oriental-like facies, short stature, brachydactyly, congenital ventricular septal defect, glaucoma, and speech disorder is reported. Routine laboratory tests, karyotype, and hormonal profile (IGF 1, growth hormone during provocative testing, thyroid hormones, prolactin, gonadotrophins) were normal. Radiologic skeletal survey did not disclose any abnormality. Both parents were apparently normal, but short in stature.


Assuntos
Anormalidades Múltiplas/genética , Face/anormalidades , Dedos/anormalidades , Glaucoma/genética , Transtornos do Crescimento/genética , Comunicação Interventricular/genética , Distúrbios da Fala/genética , Anormalidades Dentárias/genética , População Branca/genética , Estatura , Criança , Humanos , Masculino , Síndrome
20.
J Clin Endocrinol Metab ; 84(5): 1570-4, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10323382

RESUMO

On the basis of hormonal studies, the incidence of defective steroidogenesis in children with premature adrenarche (PA) in the various reports ranges from 0-54%. Molecular studies have not been reported to date. The aim of the present study was to search for defects in the CYP21 gene in children with PA and to detect possible correlations of the molecular defect to pertinent hormonal and clinical data. In 48 children with PA (40 females and 8 males) and without signs of virilization, a Synachten test and molecular studies were carried out. DNA analysis was performed using the Southern blot technique and allele-specific PCR. Synachten (0.25 mg) was given i.v., and 17-hydroxyprogesterone and cortisol were determined at 0 and 60 min. At baseline, delta4-androstenedione, dehydroepiandrosterone sulfate, and 11-deoxycortisol were also determined. Bone age was evaluated using the Greulich and Pyle atlas. Abnormal genotype was detected in 45.8% of the studied subjects; 8.3% were homozygotes, with genotypes concordant with the nonclassical phenotype of 21 hydroxylase deficiency, and 37.5% were heterozygotes for 9 different molecular defects of the CYP21 gene. The children with no detectable molecular defect were designated normal. The 60 min post-Synachten values in homozygotes (17.9 +/- 7.1 ng/mL) and heterozygotes (7.1 +/- 3.6 ng/mL) were significantly higher than that in normal subjects (3.3 +/- 1.5 ng/mL), but with significant overlapping of values. The mean difference between bone age and chronological age differed in the three groups with overlapping values. The basal delta4-androstenedione level was lower in the normal subjects (0.65 +/- 0.3 ng/mL) than in those with abnormal genotype (1.1 +/- 0.8 ng/mL). The data indicate that the incidence of molecular defects in PA is quite high. The CYP21 heterozygocity is clinically expressed in some subjects prepubertally. In a significant number of cases the genotype cannot be predicted by the age of onset of PA, the mean difference between bone age and chronological age, or the results of a Synachten test. Follow-up of these children through puberty is imperative and may reveal the clinical significance of the molecular defect, namely more hypertrichosis, intense acne, early puberty, possible abnormal menses, and/or fertility problems in the affected.


Assuntos
Sistema Enzimático do Citocromo P-450/genética , Puberdade Precoce/genética , Hormônio Adrenocorticotrópico , Idade de Início , Alelos , Criança , Pré-Escolar , DNA/análise , DNA/genética , Feminino , Cabelo/crescimento & desenvolvimento , Heterozigoto , Homozigoto , Hormônios/sangue , Humanos , Masculino , Mutação Puntual , Reação em Cadeia da Polimerase , Puberdade Precoce/enzimologia , Esteroide 21-Hidroxilase
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