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OBJECTIVE: Congenital adrenal hyperplasia (CAH) requires exogenous steroid replacement. Treatment is commonly monitored by measuring 17-OH progesterone (17OHP) and androstenedione (D4). DESIGN: Retrospective cohort study using real-world data to evaluate 17OHP and D4 in relation to hydrocortisone (HC) dose in CAH patients treated in 14 countries. PATIENTS: Pseudonymized data from children with 21-hydroxylase deficiency (21OHD) recorded in the International CAH Registry. MEASUREMENTS: Assessments between January 2000 and October 2020 in patients prescribed HC were reviewed to summarise biomarkers 17OHP and D4 and HC dose. Longitudinal assessment of measures was carried out using linear mixed-effects models (LMEM). RESULTS: Cohort of 345 patients, 52.2% female, median age 4.3 years (interquartile range: 3.1-9.2) were taking a median 11.3 mg/m2 /day (8.6-14.4) of HC. Median 17OHP was 35.7 nmol/l (3.0-104.0). Median D4 under 12 years was 0 nmol/L (0-2.0) and above 12 years was 10.5 nmol/L (3.9-21.0). There were significant differences in biomarker values between centres (p < 0.05). Correlation between D4 and 17OHP was good in multiple regression with age (p < 0.001, R2 = 0.29). In longitudinal assessment, 17OHP levels did not change with age, whereas D4 levels increased with age (p < 0.001, R2 = 0.08). Neither biomarker varied directly with dose or weight (p > 0.05). Multivariate LMEM showed HC dose decreasing by 1.0 mg/m2 /day for every 1 point increase in weight standard deviation score. DISCUSSION: Registry data show large variability in 17OHP and D4 between centres. 17OHP correlates with D4 well when accounting for age. Prescribed HC dose per body surface area decreased with weight gain.
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Hiperplasia Suprarrenal Congénita , 17-alfa-Hidroxiprogesterona , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Androstenodiona , Niño , Preescolar , Femenino , Humanos , Hidrocortisona/uso terapéutico , Masculino , Progesterona , Sistema de Registros , Estudios RetrospectivosRESUMEN
OBJECTIVES: Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes, diagnosed before age 6 months. We aimed to describe the clinical characteristics, molecular genetics, and long-term follow-up of NDM patients from a single pediatric endocrine center in Israel. METHODS: Retrospective study (1975-2020) of all patients diagnosed with diabetes before 6 months of age, who tested negative for pancreatic autoantibodies. Medical records were reviewed for demographic, familial and medical history, and clinical and biochemical features; a genetic analysis was performed. RESULTS: Of 24 patients, nine had transient neonatal diabetes (TNDM) and 15 permanent neonatal diabetes (PNDM), of whom five had rare syndromic causes. Genetic etiology was revealed in 87.5% of the NDM cohort, and the most common causes were ABCC8 mutations in TNDM and KCNJ11 and insulin gene mutations in PNDM. The switch from insulin to off-label sulfonylurea therapy was successful for 5/9 (56%) of the qualifying candidates. Severe hypoglycemia and diabetic ketoacidosis developed in 2 (8%) patients, and chronic diabetes complications in 5 (21%) patients with more than 10 years NDM. At last follow-up, weight and height of all but two syndromic PNDM patients were normal. The median height-SDS of the TNDM subgroup was significantly taller and the mean weight-SDS significantly heavier than those of the PNDM subgroup (-0.52 (-0.67, -0.09) vs. -0.9 (-1.42, -0.3) (p = 0.035) and 0.22 ± 0.69 vs. -0.89 ± 1.21 (p = 0.02), respectively). PNDM patients showed no incremental change in mean weight SDS over the time. CONCLUSION: The Israeli NDM cohort has clinical and genetic characteristics comparable with other populations. Patients with TNDM were taller and heavier than those diagnosed with PNDM, although both show rapid catch-up growth and reached normal growth parameters. Chronic diabetes complications developed in patients with long-standing NDM.
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Diabetes Mellitus/clasificación , Recién Nacido/crecimiento & desarrollo , Diabetes Mellitus/epidemiología , Femenino , Humanos , Israel/epidemiología , Masculino , Estudios Retrospectivos , Estadísticas no Paramétricas , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To compare clinical outcomes of 3 treatment regimens-glucocorticoids (GCs), oral contraceptives (OCs), or a combination of both-administered to adolescents and young women diagnosed in childhood with nonclassical congenital adrenal hyperplasia (NCCAH), who had been treated with GCs until their adult height was achieved. METHODS: A retrospective study of medical records of 53 female patients with NCCAH followed in 3 tertiary pediatric endocrinology institutes. The 3 treatment groups were compared for the prevalence of hirsutism and acne, standardized body mass index (BMI)-standard deviation score (SDS), and androgen levels at the attainment of adult height (baseline), 1-year later, and at the last documented visit. RESULTS: At baseline, there were no significant differences among groups in BMI-SDS, androgen levels, hirsutism prevalence, acne, or irregular menses. From baseline to the last visit, the rate of hirsutism declined significantly only in the OC group (37.5% vs 6.2%, respectively; P = .03). The rate of acne declined in the combined group (50% vs 9%, respectively; P = .03) with a similar tendency in the OC group (50% vs 12.5%, respectively; P = .05). No significant changes were observed in BMI-SDS for the entire cohort or any subgroup during follow-up. A significant rise in androstenedione (P < .001), testosterone (P < .01), and 17-hydroxyprogesterone (P < .01) levels was observed only in the OC group. CONCLUSION: In girls diagnosed in childhood with NCCAH, who require treatment for hyperandrogenism following completion of linear growth, management should be tailored individually using a patient-centered approach. Treatment with OCs might be better than that with GCs for regression of hirsutism and acne. The long-term effects of elevated levels of androgens associated with this treatment regimen should be further studied.
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Hiperplasia Suprarrenal Congénita , Glucocorticoides , Adolescente , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Hiperplasia Suprarrenal Congénita/epidemiología , Adulto , Androstenodiona , Niño , Anticonceptivos Orales , Femenino , Hirsutismo/tratamiento farmacológico , Hirsutismo/epidemiología , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: Few studies have evaluated the impact of diabetic ketoacidosis (DKA) at diabetes onset on long-term glycemic control in patients with type 1 diabetes (T1D). OBJECTIVE: We aimed to determine any differences in long-term glycemic control between children/adolescents with T1D presenting with DKA at diabetes onset and those without. METHODS: This retrospective study comprised 335 patients diagnosed with T1D from September 2007 to December 2012, among which 132 (39.4%) presented with DKA. Variables compared between patients with DKA at onset and those without: yearly hemoglobin A1c (HbA1c) levels, daily insulin dose, yearly rates of severe hypoglycemia and DKA, percent of patients achieving target HbA1c levels. RESULTS: After the first year of diabetes, the mean daily insulin dose and HbA1c level were significantly higher in the group with DKA at onset (0.74 ± 0.26 vs 0.69 ± 0.27 units/kg/d, P = .049, and 7.85 ± 1.13% vs 7.49 ± 0.94%, P = .01, respectively), despite similarity of therapy (multiple daily injections or continuous subcutaneous insulin infusion), with a similar but not statistically significant trend subsequently. Mean HbA1c since onset was significantly higher in the DKA group (8.08 ± 0.95% vs 7.86 ± 0.95%, P = .025). A significantly higher percentage of patients in the group without DKA at onset achieved a mean level of HbA1c since onset within glycemic targets (32% vs 20.5%, P = .02). In the DKA group, the frequency of subsequent DKA episodes per diabetes years was significantly higher (P = .042). CONCLUSIONS: DKA at diagnosis was associated with less favorable long-term glycemic control as assessed by HbA1c and the rate of DKA episodes. T1D patients presenting with DKA may therefore need stricter treatment and tight follow-up.
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Diabetes Mellitus Tipo 1/diagnóstico , Cetoacidosis Diabética/etiología , Hiperglucemia/prevención & control , Hipoglucemia/prevención & control , Adolescente , Niño , Estudios de Cohortes , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/fisiopatología , Cetoacidosis Diabética/epidemiología , Cetoacidosis Diabética/prevención & control , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Hospitales Pediátricos , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Insulina/efectos adversos , Insulina/uso terapéutico , Resistencia a la Insulina , Israel/epidemiología , Masculino , Estudios Retrospectivos , Factores de Riesgo , Factores SexualesRESUMEN
AIM: This study explored whether using the suggested diagnostic serum basal level of 17-hydroxyprogesterone (6.0 nmol/L) would lead to underdiagnosis of nonclassical congenital adrenal hyperplasia. METHODS: We retrospectively studied 123 patients with nonclassical congenital adrenal hyperplasia, defined as an adrenocorticotropic hormone-stimulated 17-hydroxyprogesterone level of more than 45 nmol/L. Of these 13 had basal 17-hydroxyprogesterone levels of less than 6.0 nmol/L and 110 exceeded that level. The 42 controls had idiopathic premature pubarche. Clinical and laboratory data were reviewed and compared. RESULTS: There were no differences between patients with 17-hydroxyprogesterone levels of <6.0 nmol/L or ≥6.0 nmol/L based on age at presentation, gender, anthropometric measurements, bone age advancement, age at glucocorticoid initiation and hydrocortisone dosage. Patients with basal 17-hydroxyprogesterone <6.0 nmol/L had significantly lower stimulated 17-hydroxyprogesterone levels (p = 0.02) and higher stimulated serum cortisol levels (p < 0.008). Children with nonclassical congenital adrenal hyperplasia and premature pubarche were clinically indistinguishable from controls with idiopathic premature pubarche. Androgen levels were significantly higher in the nonclassical congenital adrenal hyperplasia group. CONCLUSION: A basal 17-hydroxyprogesterone threshold of 6.0 nmol/L was not a sensitive predictive marker for diagnosing nonclassical congenital adrenal hyperplasia. Children whose clinical presentation suggests nonclassical congenital adrenal hyperplasia should undergo diagnostic adrenocorticotropic hormone stimulation testing.
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17-alfa-Hidroxiprogesterona/sangre , Hiperplasia Suprarrenal Congénita/diagnóstico , Adolescente , Hiperplasia Suprarrenal Congénita/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Patients with type 1 diabetes (T1D) are exempt from conscript military service, but some volunteer for national service. OBJECTIVES: To evaluate the effect of national service (military or civil) on metabolic control and incidence of acute diabetes complications in young adults with T1D. METHODS: Clinical and laboratory data of 145 T1D patients were retrieved from medical records. The cohort comprised 76 patients volunteering for national service and 69 non-volunteers. Outcome measures were HbA1c, body mass index-standard deviation scores (BMI-SDS), insulin dosage, and occurrence of severe hypoglycemia or diabetic ketoacidosis (DKA). RESULTS: Metabolic control was similar in volunteers and non-volunteers: mean HbA1c at various time points was: 7.83 ± 1.52% vs. 8.07% ± 1.63 one year before enlistment age, 7.89 ± 1.36% vs. 7.93 ± 1.42% at enlistment age, 7.81 ± 1.28% vs. 8.00 ± 1.22% one year thereafter, 7.68 ± 0.88% vs. 7.82 ± 1.33% two years thereafter, and 7.62 ± 0.80% vs. 7.79 ± 1.19% three years thereafter. There were no significant changes in HbA1c from baseline throughout follow-up. BMI and insulin requirements were similar and remained unchanged in volunteers and controls: mean BMI-SDS one year before enlistment age was 0.23 ± 0.83 vs. 0.29 ± 0.95, at enlistment age 0.19 ± 0.87 vs. 0.25 ± 0.98, one year thereafter 0.25 ± 0.82 vs. 0.20 ± 0.96, two years thereafter 0.10 ± 0.86 vs. 0.15 ± 0.94, and three years thereafter 0.20 ± 0.87 vs. 0.16 ± 0.96. Mean insulin dose in U/kg/day one year before enlistment age was 0.90 ± 0.23 vs. 0.90 ± 0.37, at enlistment age 0.90 ± 0.28 vs. 0.93 ± 0.33, one year thereafter 0.86 ± 0.24 vs. 0.95 ± 0.33, two years thereafter 0.86 ± 0.21 vs. 0.86 ± 0.29, and three years thereafter 0.87 ± 0.23 vs. 0.86 ± 0.28. There were no episodes of severe hypoglycemia or DKA in either group. CONCLUSIONS: Our data indicate that during voluntary national service young adults with T1D maintain metabolic control similar to that of non-volunteers.
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Peso Corporal , Diabetes Mellitus Tipo 1/complicaciones , Cetoacidosis Diabética/epidemiología , Hipoglucemia/epidemiología , Personal Militar , Adolescente , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Hemoglobina Glucada , Humanos , Hipoglucemiantes/administración & dosificación , Incidencia , Insulina/administración & dosificación , Israel , Masculino , Índice de Severidad de la Enfermedad , Voluntarios , Adulto JovenRESUMEN
Athelia is a very rare entity that is defined by the absence of the nipple-areola complex. It can affect either sex and is mostly part of syndromes including other congenital or ectodermal anomalies, such as limb-mammary syndrome, scalp-ear-nipple syndrome, or ectodermal dysplasias. Here, we report on three children from two branches of an extended consanguineous Israeli Arab family, a girl and two boys, who presented with a spectrum of nipple anomalies ranging from unilateral hypothelia to bilateral athelia but no other consistently associated anomalies except a characteristic eyebrow shape. Using homozygosity mapping after single nucleotide polymorphism (SNP) array genotyping and candidate gene sequencing we identified a homozygous frameshift mutation in PTPRF as the likely cause of nipple anomalies in this family. PTPRF encodes a receptor-type protein phosphatase that localizes to adherens junctions and may be involved in the regulation of epithelial cell-cell contacts, peptide growth factor signaling, and the canonical Wnt pathway. Together with previous reports on female mutant Ptprf mice, which have a lactation defect, and disruption of one allele of PTPRF by a balanced translocation in a woman with amastia, our results indicate a key role for PTPRF in the development of the nipple-areola region.
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Mama/anomalías , Anomalías Congénitas/etiología , Mutación del Sistema de Lectura/genética , Perfilación de la Expresión Génica , Homocigoto , Proteínas Tirosina Fosfatasas Clase 2 Similares a Receptores/genética , Adolescente , Adulto , Animales , Mama/patología , Enfermedades de la Mama , Células Cultivadas , Niño , Preescolar , Anomalías Congénitas/patología , Femenino , Fibroblastos/metabolismo , Fibroblastos/patología , Estudio de Asociación del Genoma Completo , Humanos , Lactante , Masculino , Ratones , Pezones/metabolismo , Pezones/patología , Linaje , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
CONTEXT: Central precocious puberty (CPP), treated or untreated, may have implications in adulthood. OBJECTIVE: To assess the reproductive outcome and social adjustment of former CPP women between the 3rd and 5th decades of life. DESIGN: Cross-sectional study of an historical cohort. METHODS: Demographic data and gynaecological history of 214 CPP women aged 25-56 years [135 GnRH analogue (GnRHa)-treated, 18 cyproterone acetate (CyA)-treated, 61 untreated] and of 446 controls with normal puberty, matched for age and year of birth, were recorded in a structured interview. RESULTS: Marital status, education and number of children were similar in CPP women and controls. Clinical hyperandrogenism (acne/hirsutism with oligomenorrhoea) was more frequently reported in CPP women than in controls: GnRHa-treated 29·6% vs 17·4% (P = 0·006), CyA-treated 50% vs 20·4% (P = 0·04), untreated 34·4% vs 17·2% (P = 0·003), with no significant difference between CPP groups. Spontaneous pregnancy was similarly achieved by treated CPP and controls: GnRHa-treated 90·4% vs 93·4%, CyA-treated 86·7% vs 90·2%. Assisted fertilization rate was higher in untreated CPP than treated CPP groups (P = 0·006) and controls (P = 0·03). Untreated CPP was the only parameter associated with clinical hyperandrogenism (OR=2·04, 95% CI, 1·0-4·16, P = 0·07) and fertility problems (OR=3·40, 95% CI, 1·15-10·0, P = 0·047). Course of pregnancy was uneventful in 90·2% of CPP women and 90·9% of controls. CONCLUSIONS: The increased rate of clinical hyperandrogenism among CPP women implies that the underlying neuroendocrine dysfunction persists into adult life. Pubertal suppression treatment may have a protective effect as fertility problems were more prevalent only among untreated CPP women. Educational achievements and marital status were unaffected by CPP.
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Pubertad Precoz/tratamiento farmacológico , Adolescente , Adulto , Niño , Estudios Transversales , Acetato de Ciproterona/uso terapéutico , Femenino , Fertilidad/efectos de los fármacos , Hormona Liberadora de Gonadotropina/agonistas , Hormona Liberadora de Gonadotropina/análogos & derivados , Humanos , Hiperandrogenismo/etiología , Persona de Mediana Edad , Embarazo , Resultado del Embarazo , Pamoato de Triptorelina/uso terapéuticoRESUMEN
CONTEXT: Central congenital hypothyroidism (CCH) is a thyroid hormone deficiency at birth caused by inadequate pituitary stimulation of the thyroid gland. Although primary CH has been studied extensively, studies on CCH are sparse. OBJECTIVES: To assess the prevalence of CCH in Israel and describe its clinical features, neonatal screening results, and outcomes. DESIGN: Multicenter cross-sectional retrospective chart review. SETTING: Nine pediatric endocrine units throughout Israel. PATIENTS: Patients diagnosed with CCH in 1987-2021 were categorized into early (within 14 days of life) and late (after 14 days) diagnosis groups. Newborn screening (NBS) results were retrospectively retrieved from the national NBS program dataset. RESULTS: CCH prevalence in Israel was about 1:42,800 live births. Subjects were 94 patients (54 males), of these, 84% had multiple pituitary hormone deficiencies and 16% had isolated CCH. The median age at diagnosis was 50 days (range, 1-8760), with 66% having moderate to severe hypothyroidism. NBS detected only three infants. Early diagnosis occurred in 34% due to hypopituitarism, while 66% were diagnosed later due to growth and developmental delays. Neurodevelopmental sequelae included mental retardation (12%), learning difficulties (18%), delayed speech (27%), and motor clumsiness (19%), with no significant differences in outcomes between early and late diagnosis. CONCLUSIONS: Despite high rates of neurodevelopmental sequelae, no differences were found between early and late diagnosis groups. Further research is needed to assess the impact of delayed diagnosis on neurological outcomes in newborns with CCH. Improved strategies for detecting CHH in newborns are also necessary.
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BACKGROUND: Poorly controlled adolescents living with type 1 diabetes (T1D) and pump failure of insulin delivery leading to diabetic ketoacidosis (DKA) are still challenging in the western world. AIM: To investigate the effect of a combination modality of long-acting insulin for basal coverage and a pump for boluses, on the incidence of DKA and glycemic parameters in pediatric and young adults with poorly controlled T1D. METHODS: This multicenter, observational retrospective study included 55 patients (age range 3-25 years, 52.7% males) who were treated with the combination modality for a median of 18 months [(IQR)12,47], as part of their clinical care. Data were retrieved at initiation of the combined modality, after 6 months, and at last visit. RESULTS: Cohort's median age at combination modality initiation was 14.5 years [IQR12.4,17.3], and its median HbA1c level was 9.2% [IQR 8.2,10.2]. The main reasons for combination modality initiation were: (a) concern about sustained hyperglycemia on current management in 41.8%, (b) previous DKA episodes in 30.8%, and (c) refusal to wear a pump continuously in 14.6%. The percent of patients experiencing DKA who used the modality till end decreased from 25.4 to 8.8%. The frequency of DKA events per patient month decreased after 6 months from 0.073 (min 0, max 0.5) to 0.020 (min 0, max 0.5), p = 0.01, and at end to 0.016 (min 0, max 0.25), p = 0.007. CONCLUSIONS: The combination modality of once-daily long-acting insulin and pump for boluses is safe, feasible, and effective in preventing DKA among poorly controlled young people living with T1D, unable or un-willing to use advanced closed pumps.
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INTRODUCTION: Data on adult height (AHt) in individuals with non-classical congenital adrenal hyperplasia (NCCAH) are inconsistent. METHODS: We conducted a retrospective study of 109 females diagnosed with NCCAH at age <18 years who reached AHt. We studied AHt compared to target height (THt) and the correlation of AHt with clinical parameters. RESULTS: The mean age at diagnosis was 9.7 ± 4.4 years; the mean follow-up was 10.9 ± 6.3 years. Hydrocortisone treatment (11.0 ± 5.0 mg/m2) was initiated at age 9.7 ± 4.0 years. Bone age was more advanced in girls who presented with central precocious puberty or early puberty (CPP/EP) (n = 43) than with timely puberty. AHt-standard deviation score (SDS) was lower than Ht-SDS at diagnosis (-0.8 ± 1.0 vs. +0.2 ± 1.3; p < 0.001) and -0.3 SDS shorter than THt (p < 0.001). Height, weight, and body mass index-SDS at last visits were similar between patients treated with glucocorticoids (n = 92) and those never treated (n = 17). AHt was comparable between patients with timely puberty and with CPP/EP, with no difference between those treated or not by GnRH analogue. AHt was similar between patients who were fully pubertal (Tanner 5), pre-pubertal (Tanner 1), and pubertal (Tanner 2-4) at diagnosis (158.0 ± 7.6, 158.1 ± 6.1, and 157.5 ± 6.5, respectively; p = 0.9). AHt-SDS was correlated with THt (R = 0.67, p < 0.001) and Ht-SDS at diagnosis (R = 0.7, p < 0.001) but not with age at diagnosis (R = -0.05, p = 0.6), the extent of bone age advancement (R = -0.04, p = 0.72), glucocorticoid treatment duration (R = -0.11, p = 0.34), or dose (R = -0.04, p = 0.70). CONCLUSION: AHt of females diagnosed with NCCAH in childhood was lower than their THt. Glucocorticoid treatment duration and dose, pubertal status at diagnosis, and having CPP or EP were not correlated with AHt.
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Hiperplasia Suprarrenal Congénita , Pubertad Precoz , Humanos , Femenino , Adulto , Preescolar , Niño , Adolescente , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Estudios Retrospectivos , Glucocorticoides/uso terapéutico , Pubertad Precoz/diagnóstico , Pubertad Precoz/tratamiento farmacológico , EstaturaRESUMEN
INTRODUCTION: Diagnosing hypoglycemia in infants and children presents significant challenges. Our objective was to elucidate the diagnoses and clinical features of children with hypoglycemia referred to a pediatric endocrine tertiary clinic. METHODS: Retrospective study of 154 children (0-18 years old) presenting with hypoglycemia, during 1992-2018. RESULTS: The cohort was divided by clinical diagnosis into six groups: ketotic hypoglycemia (n=45, 29.2%), congenital hyperinsulinemic hypoglycemia (n=35, 22.7%), transient hyperinsulinemic hypoglycemia (n=28, 18.2%), metabolic disorder (n=14, 9.1%), systemic disease/syndrome (n=15, 9.7%), and hormone deficiencies (n=8, 5.2%). Two patients had insulinoma and in 7 (4.5%) no diagnosis was elucidated. At diagnosis, 58 (37.7%) were <1 month old, 23 (14.9%) aged 1-12 months, 58 (37.7%) aged 1-6 years, and 15 (9.7%) aged 6-18 years. Hypoglycemia etiology varied among neonates, infants, and children. In eight patients hypoglycemia was asymptomatic. Of 47 patients who completed a diagnostic fast, 31 became hypoglycemic, yet a significant added value for diagnosis was only found in 14 (29.8%) patients. CONCLUSIONS: Hypoglycemia etiology in children is heterogeneous and varies by age. Any hypoglycemia measured in a child should be seriously evaluated as 7% are asymptomatic. Work-up should be tailored based on age, and clinical, biochemical, and imaging findings. Despite extensive work-up, in a significant number of patients the mechanism underlying pediatric hypoglycemia remains an enigma. This emphasizes the unmet needs and challenges in studying pediatric hypoglycemia.
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OBJECTIVES: Case reports show hypertension in children treated with GnRH analogues for central precocious puberty (CPP). However, relevant data on blood pressure are scarce. We aimed to evaluate blood pressure (BP) among girls with idiopathic CPP and early-onset puberty before and during GnRH analogue therapy; and to examine associations of blood pressure with clinical parameters. METHODS: For this retrospective longitudinal cohort study, demographic, anthropometric, clinical, and laboratory data were collected from electronic files. The study group included 112 girls with idiopathic CPP or early-onset puberty followed in a tertiary pediatric endocrinology institute, and a control group of 37 healthy pre-pubertal girls. The main outcome measures were BP percentile, before, and during treatment with GnRH analogue. RESULTS: At baseline, similar proportions of the study and control groups had BP values>90th percentile: 64 (53â¯%) and 17 (46â¯%), respectively (p=0.57). The mean systolic and diastolic BP percentiles measured under treatment remained unchanged. In the study group, baseline BP>90th percentile compared to normal baseline BP was associated with lower birthweight and a higher body mass index-standard deviation score: 2,821 ± 622 vs. 3,108 ± 485â¯g and 1.0 ± 0.7 vs. 0.70 ± 0.8, respectively, p=0.01 for both. CONCLUSIONS: GnRH analogue therapy for precocious or early puberty was not associated with increased blood pressure. The stability of mean blood pressure percentile during treatment is reassuring.
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Pubertad Precoz , Niño , Femenino , Humanos , Hormona Liberadora de Gonadotropina , Estudios Longitudinales , Estudios Retrospectivos , Presión Sanguínea , Factores Inmunológicos/uso terapéuticoRESUMEN
IMPORTANCE: Testicular adrenal rest tumors (TARTs), often found in male patients with congenital adrenal hyperplasia (CAH), are benign lesions causing testicular damage and infertility. We hypothesize that chronically elevated adrenocorticotropic hormone exposure during early life may promote TART development. OBJECTIVE: This study aimed to examine the association between commencing adequate glucocorticoid treatment early after birth and TART development. DESIGN AND PARTICIPANTS: This retrospective multicenter (n = 22) open cohort study collected longitudinal clinical and biochemical data of the first 4 years of life using the I-CAH registry and included 188 male patients (median age 13 years; interquartile range: 10-17) with 21-hydroxylase deficiency (n = 181) or 11-hydroxylase deficiency (n = 7). All patients underwent at least 1 testicular ultrasound. RESULTS: TART was detected in 72 (38%) of the patients. Prevalence varied between centers. When adjusted for CAH phenotype, a delayed CAH diagnosis of >1 year, compared with a diagnosis within 1 month of life, was associated with a 2.6 times higher risk of TART diagnosis. TART onset was not predicted by biochemical disease control or bone age advancement in the first 4 years of life, but increased height standard deviation scores at the end of the 4-year study period were associated with a 27% higher risk of TART diagnosis. CONCLUSIONS AND RELEVANCE: A delayed CAH diagnosis of >1 year vs CAH diagnosis within 1 month after birth was associated with a higher risk of TART development, which may be attributed to poor disease control in early life.
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Hiperplasia Suprarrenal Congénita , Tumor de Resto Suprarrenal , Neoplasias Testiculares , Adolescente , Humanos , Masculino , Hiperplasia Suprarrenal Congénita/genética , Tumor de Resto Suprarrenal/epidemiología , Tumor de Resto Suprarrenal/etiología , Estudios de Cohortes , Neoplasias Testiculares/epidemiología , Neoplasias Testiculares/complicaciones , NiñoRESUMEN
OBJECTIVE: To assess the interrelationship between extent of adrenarche at presentation in girls with precocious adrenarche (PA) born appropriate for gestational age and their growth pattern, pubertal course and adult height. STUDY DESIGN: We reviewed clinical and laboratory data from medical charts of 85 girls with PA aged 5.0 to 8.8 years at referral, stratified in 3 subgroups according to bone age (BA) minus chronological age (CA) ≤0 years; 0
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Glándulas Suprarrenales/crecimiento & desarrollo , Adrenarquia/fisiología , Estatura/fisiología , Edad Gestacional , Menarquia/fisiología , Adulto , Determinación de la Edad por el Esqueleto , Factores de Edad , Desarrollo Óseo/fisiología , Niño , Preescolar , Femenino , Humanos , Registros Médicos , EmbarazoRESUMEN
OBJECTIVE: To evaluate the association between recombinant human growth hormone (rhGH) treatment and intraocular pressure (IOP) in children. STUDY DESIGN: This is an observational cohort study including comparison between children treated with rhGH for at least 12 months (treatment group), matched children prior to treatment (control group), and population age-adjusted normograms of IOP. All children underwent an ocular slit lamp assessment and Goldmann applanation tonometry. Charts were reviewed for cause of therapy, peak stimulated growth hormone level prior to therapy, treatment duration, insulin-like growth factor 1, and rhGH dosage. RESULTS: The treatment group included 55 children and the control group included 24 children. Mean age at examination was comparable at 11.4 ± 3.3 years and 10.3 ± 2.6 years, respectively (P = .13). Mean treatment duration was 37.5 ± 22.8 months and mean rhGH dose was 0.04 ± 0.01 mg/kg/d. Mean IOP was significantly increased in the treatment group compared with the control group and compared with age-matched normograms (16.09 ± 2.2 mm Hg, 13.26 ± 1.83 mm Hg and 14.6 ± 1.97 mm Hg, respectively, P < .001). IOP was positively correlated with treatment duration (r = 0.559, P < .001) and rhGH dosage (r = 0.274, P = .043). CONCLUSION: IOP in children treated with rhGH is increased compared with a similar population without treatment and compared with healthy population normograms. IOP is associated with longer treatment duration and higher dosages.
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Hormona de Crecimiento Humana/efectos adversos , Presión Intraocular/efectos de los fármacos , Hipertensión Ocular/inducido químicamente , Adolescente , Niño , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Hormona de Crecimiento Humana/administración & dosificación , Humanos , Masculino , Hipertensión Ocular/diagnóstico , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Estándares de Referencia , Método Simple Ciego , Factores de Tiempo , Tonometría Ocular/normasRESUMEN
BACKGROUND: The occurrence of celiac disease (CD) in patients with type 1 diabetes (T1D) is increasing. OBJECTIVE: To determine the effect of CD on growth and glycemic control in patients with T1D, and the effects of adherence to gluten-free diet (GFD) on these parameters. PATIENTS AND METHODS: A longitudinal retrospective case-control design was used. The medical files of 68 patients with T1D and duodenal-biopsy-confirmed CD were reviewed for data on weight, height, hemoglobin A1c (HbA1c), frequency of diabetic ketoacidosis (DKA), and severe hypoglycemic events before and after diagnosis and treatment of CD. Findings were compared with 131 patients with T1D only matched for age, gender, and duration of diabetes. RESULTS: CD was diagnosed in 5.5% of all patients with T1D attending our center during the study period; 26% of the patients with CD were symptomatic. There were no significant differences in glycemic control or frequency of severe hypoglycemia or DKA events between the study and control groups. Body mass index-standard deviation score (SDS), height-SDS, and HbA1c values were marginally but not significantly higher in the control than the study group and similar in subjects with CD with good or fair/poor adherence to a GFD throughout follow-up. CONCLUSIONS: Patients with T1D and CD treated with GFD have growth and measures of metabolic control similar to those with T1D without CD. The decision whether asymptomatic celiac patients should be put on a GFD or only symptomatic patients has to be weighed against possible short- and long-term consequences of no intervention, and should be based on more evidence from larger randomized studies.
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Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/fisiopatología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/fisiopatología , Hemoglobina Glucada/análisis , Crecimiento , Adolescente , Adulto , Estatura , Índice de Masa Corporal , Estudios de Casos y Controles , Enfermedad Celíaca/dietoterapia , Niño , Preescolar , Cetoacidosis Diabética/epidemiología , Dieta Sin Gluten , Femenino , Humanos , Hipoglucemia/epidemiología , Estudios Longitudinales , Masculino , Estudios RetrospectivosRESUMEN
CONTEXT: Data is needed regarding the effect of SARS-CoV-19 infection on young people with established type 1 diabetes. Identifying the disease outcomes, short and long-term sequelae may help to establish an evidence-based prevention and education policy for sick days management and DKA prevention. OBJECTIVE: This work aims to describe clinical manifestations of SARS-CoV-2 infection in children, adolescents, and young adults with established type 1 diabetes (T1D) and explore the effects of COVID-19 on glycemic control and disease course. METHODS: An observational study was conducted at 3 pediatric diabetes clinics in Israel between mid-March 2020 and mid-March 2021. Included were young people with established T1D, age younger than 30 years, who tested positive for SARS-CoV-2 (quantitative real-time polymerase chain reaction). Data were collected from medical files, diabetes devices, and COVID-19 questionnaire. Outcome measures were analyzed by the presence/absence of clinical symptoms (symptomatic/asymptomatic) and by age group (pediatric, <â 19 years/young adults, 19-30 years). RESULTS: Of 132 patients, mean age 16.9â ±â 5.3years, with COVID-19-confirmed infection, 103 (78%) had related symptoms; the most common were headaches, fatigue, fever, and loss of sense of smell. All had a mild disease course, but 4 required hospitalization and 2 cases were directly related to COVID-19 infection (pleuropneumonia in a patient with immunodeficiency syndrome, 1 case of diabetic ketoacidosis). Logistic regression analysis showed that age (odds ratio [OR]â =â 1.11; 95% CI, 1.01-1.23; Pâ =â .033), elevated glucose levels (ORâ =â 5.23; 95% CI, 1.12-24.41; Pâ =â .035), and comorbidities (ORâ =â 8.21; 95% CI, 1.00-67.51; Pâ =â .050) were positively associated with symptomatic infection. Persistent symptoms occurred in 16.5% of the cohort over a median of 6.7 months; age (ORâ =â 1.14; 95% CI, 1.01-1.29; Pâ =â .030) and elevated glucose levels (ORâ =â 3.42; 95% CI, 1.12-10.40; Pâ =â .031) were positively associated with persistent symptoms. Usually, no change was reported in glucose levels (64%) except for a temporary deterioration in glycemic control during the short infection period. CONCLUSION: Young people with established T1D experience mild COVID-19 infection. Elevated glucose levels during COVID-19 infection and older age were associated with prolonged disease course.
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COVID-19 , Diabetes Mellitus Tipo 1 , Cetoacidosis Diabética , Adolescente , Adulto , COVID-19/complicaciones , COVID-19/epidemiología , Niño , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/epidemiología , Cetoacidosis Diabética/epidemiología , Cetoacidosis Diabética/etiología , Glucosa , Control Glucémico , Humanos , SARS-CoV-2 , Adulto JovenRESUMEN
Objectives: International guidelines recommend additional salt supplementation during infancy in classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The influence of corticoid medication and growth has not been assessed. Aim: To investigate the current use of salt supplementation, fludrocortisone (FC) and hydrocortisone (HC) dosage as well as weight, height, BMI and blood pressure (BP) in CAH children aged 0-3 years. Methods: Retrospective multicentre analysis using data from the I-CAH registry. Salt-treated (ST) and non-salt-treated (NST) children were compared regarding FC and HC dosage, weight, height and BP at 0, 3, 6, 9, 12, 18, 24, 30, and 36 months. Results: We analysed 2483 visits of 331 patients born after year 2000 in 13 countries (male, n = 145) with 203 ST patients (61%). NST children had significantly higher FC dosages at 1.5-4.5 months and higher HC dosages until 1.5 months of age. No differences in weight, length and BP between subgroups were observed. Children of the whole cohort showed increased BMI-SDS during the study period and about half of the reported BP readings were >P95. Conclusion: In children treated with additional salt supplementation, FC and HC dosages are lower during the first months of life but without differences in weight, length and BP until 3 years of age compared to NST children. All children showed an increase in BMI-SDS and a high rate of BP readings >P95 until 3 years, indicating the start of weight gain and negative effects on blood pressure already in very early life.
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Hiperplasia Suprarrenal Congénita , Glucocorticoides , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Presión Sanguínea , Niño , Preescolar , Suplementos Dietéticos , Fludrocortisona/uso terapéutico , Glucocorticoides/uso terapéutico , Humanos , Hidrocortisona/uso terapéutico , Masculino , Mineralocorticoides/uso terapéutico , Estudios Retrospectivos , Cloruro de Sodio Dietético/uso terapéuticoRESUMEN
OBJECTIVE: As there are no standard criteria for monitoring suppression during treatment of central precocious puberty (CPP) with gonadotrophin-releasing hormone analogues (GnRHa), we assessed the use of pelvic ultrasound examination for this purpose. DESIGN/PATIENTS/MEASUREMENTS: In 31 girls with CPP, transabdominal pelvic ultrasound examination was performed before initiation of therapy with GnRHa, after approximately 3 and 6 months, at last treatment visit and after its discontinuation. RESULTS: Three months after treatment initiation, there was a significant decrease in most uterine and ovarian parameters, with at least three parameters decreased in each patient. Endometrial echo was found in 80% of girls before therapy, in 52% (13/25) after 3 months of therapy, in 24% (6/25) after 6 months and in none on the last treatment visit (P < 0·001). In the course of treatment (mean therapy duration 2·5 ± 0·9 years), uterine parameters showed no significant change; ovarian parameters initially showed a decrease and later a modest increase although they were still smaller than before therapy. Within 3-11 months after therapy discontinuation, endometrial echo was detected in 85%, with a significant increase in uterine and ovarian parameters. CONCLUSIONS: This prospective study indicates that comparison of individual ultrasound measurements throughout the course of treatment in girls with CPP provides a valid assessment of the suppression of the hypothalamo-pituitary-gonadal axis achieved GnRH therapy. Uterine parameters and absence of endometrial echo were found to be better indicators of adequate suppression than ovarian parameters.