Pediatric Endocrinology Outpatient Clinic Research Articles

Clinical observations and treatment of pediatric homozygous familial hypercholesterolemia due to a low-density lipoprotein receptor defect

Clinical observation and treatment of children with homozygous familial hypercholesterolemia (HoFH) has rarely been reported. We report clinical observations and treatment of 10 ethnic Chinese children with HoFH due to low-density lipoprotein receptor (LDLR) defect. In children with HoFH, we evaluated the response to conventional cholesterol-lowering drug therapy and performed LDLR gene analysis. A retrospective review of lipid profile changes in pediatric patients diagnosed with HoFH seen in our pediatric endocrinology outpatient clinic was performed. HoFH was diagnosed by molecular study of these patients and their parents. One novel (c.64del G) and 12 known mutations were found in the LDLR gene. Mutation of p.C308Y was the most common and was found in 26% of the studied alleles.Seven patients had fair responses to conventional drug therapy (high-dose statin with ezetimibe) with a reduction of 50% or more of the total cholesterol levels. The low-density lipoprotein-cholesterol levels of three patients decreased to lower than 160mg/dL. One who had a good response to conventional drug therapy developed significant atheromatous plaques (largest plaque: 7.4×2.7cm) in the extracranial carotid arteries and myocardial ischemia changes at 11years old. The results suggest that despite aggressive therapy, many patients are not well controlled; atherosclerosis may progress, and novel therapies are required.

Isolated hyperthyrotropinemia in childhood obesity and its relation with metabolic parameters.

The aim of the presented study was to evaluate the prevalence of isolated hyperthyrotropinemia (IH) in obese children and the relation between anthropometric and metabolic parameters. Hospital records of the children, who presented to the Pediatric Endocrinology outpatient clinic of our institution with obesity, and age and gender-matched healthy children, who had undergone thyroid function test for any reason were retrospectively reviewed. The prevalence of IH was significantly higher in the obese group than in the controls (9.2 and 3.8 %, respectively). Body mass index-standard deviation score (BMI-SDS), thyroid-stimulating hormone (TSH), lipid parameters were significantly different in the obese group than in the control group. A positive correlation between TSH and BMI-SDS and negative correlation between TSH and free T4 (fT4) levels were found in obese subjects. Stepwise multiple linear regression analysis confirmed that BMI-SDS, fT4 and triglyceride levels were the strongest independent variables correlated with TSH level in obese subjects (r (2) = 0.046, p = 0.001). IH prevalence is higher in obese children as compared to healthy children and the increase in TSH level correlates negatively with serum fT4 and positively with BMI-SDS and triglyceride levels in obese children.

Waist-to-height ratio distinguish obstructive sleep apnea from primary snoring in obese children.

Sleep-disordered breathing is caused by the interaction of multiple factors, including tonsillar hypertrophy, retrognathia, maxillary atresia, neuromuscular abnormalities, activation of inflammatory mediator cascades, and obesity. The prevalence and severity of obesity among children and adolescents increased worldwide during recent decades and has thus become a public health concern. The aim of this study is to assess the metabolic and anthropometric changes associated with sleep-disordered breathing in obese children. Prospective assessment of prepubertal obese children followed at a pediatric endocrinology outpatient clinic that had history of frequent snoring. Children were submitted to polysomnography, measurements of body weight, height, blood pressure, neck circumference, and waist circumference. BMI, neck-to-height, and waist-to-height ratios were calculated. Laboratory tests included a complete blood count, liver function tests, lipid profile, and glucose metabolism assessment. Additionally, the presence of metabolic syndrome was assessed. Differences between obstructive sleep apnea and primary snoring groups were calculated using unpaired t-test, Fisher's exact test or Mann-Whitney test (p < 0.05). The sample included 20 children with primary snoring and nine with obstructive sleep apnea. The two groups did not differ with regard to age, gender, BMI, or BMI z-score, serum lipids, glucose metabolism, cell count, liver function, or arterial blood pressure. Anthropometric data did not differ between groups. The waist-to-height ratio was greater among children with obstructive sleep apnea, compared to those with primary snoring. In the present study, the waist-to-height ratio was greater in children with obstructive sleep apnea and, thus, could distinguish these children from those with primary snoring.

Relapse in pituitary adenoma after resection

Pituitary adenoma in children is rarely reported. Acromegaly is one of clinical manifestation in GH releasing-pituitary adenoma. Recurrence of clinical manifestation after resection must be evaluated for possibility of pituitary adenoma relapse. N,male,15-yo, came to pediatric endocrinology outpatient clinic with the main complain of acromegaly and decreased of visual field which was getting worse since two weeks before(April11, 2011). He was consulted to ophthalmology and neurosurgery outpatient clinic. MRI with contrast revealed pituitary adenoma. Laboratories results showed TSHS:0.9773(0.35-4.94)uIU/ml, prolactin:0.51(4.04-15.2)ng/ml, testosterone less than 2.50(boys:13-17:28-1110)ng/ml, growth hormone was more than 40,00(>10.0)ng/ml. He was performed transsphenoidal removal cystic tumor. Pathological result showed macroscopic: yellowish cystous mass;0.6x0.4x0.2cm whether microscopic: appropiate to pituitary adenoma, non chromophobe. After surgery, patient was given DDAVP nasal spray 10 microgram/day, L-thyroxin 100 microgram once daily. One year after surgery, patient complaint of acromegaly, decreased visual field, especially in right and left temporal side, cephalgia. On physical examination, body weight was 91.5kg, height was184.5 cm. There was hemianopsia bitemporal. Tanner stage was A2P4G4. MRI with contrast showed pituritary adenoma relapse. Bone age was normal with height percentage based on it is about 96.8%. Tanner Whitehouse showed adult height 186.4cm. Thorax X ray showed heart and lungs were normal. Laboratories results revealed IGF1:1359(237-996)microgram/L, FT4:1(0.89-1.76)ng/dl; TSHS:0.3(0.5-4.94)microIU/ml(12-18yo), testosterone:435.1(28-1110) ng/dl. Working diagnosis was pituitary adenoma relapse post tumor resection, panhypopituitarism, diabetes insipidus. Testosterone 150mg once per month was added. Relapse of pituitary adenoma in children must be considered in the recurrence of clinical manifestations.

Crescimento e puberdade na diabetes mellitus tipo 1 – experiência de uma unidade de endocrinologia pediátrica

Type 1 Diabetes Mellitus (T1DM) is the most common endocrine-metabolic disease in children. It is associated with vascular and neuropathic complications, and may also affect growth and development. To correlate the metabolic control and disease duration with growth and puberty in patients with T1DM followed in a Pediatric Endocrinology Outpatient Clinic. Retrospective analysis. Sample obtained from patients with T1DM followed in Hospital Santa Maria Pediatric Endocrinology Outpatient Clinic (Lisbon - Portugal) since 1994 until March 2011. patients diagnosed before the onset of puberty and who had attained their final height during the follow-up. sex, age, weight and height at diagnosis and final, parents' height, growth velocity, pubertal height gain, age at menarche and metabolic control during puberty. 39 patients, 51% female, 82% diagnosed less than five years before puberty. Fifty-four percent presented an average HbA1c between 8-10%, what we considered reasonable. There seems to be a trend towards an inverse association between HbA1c and the maximum speed of growth and pubertal height gain, although not statistically significant. These patients were taller than average at diagnosis (z-score: male 0.9; female: 0.5) and lost height during puberty, yet attained final heights within normal range and matching their target heights. Although HbA1c seems to negatively influence maximum growth rate and pubertal height gain, there was no compromise in final height in this group of patients.

Etiology of Failure to Thrive in Infants and Toddlers Referred to a Pediatric Endocrinology Outpatient Clinic

Etiology of Failure to Thrive in Infants and Toddlers Referred to a Pediatric Endocrinology Outpatient Clinic

Impact of Lifestyle and Dietary Habits on Hypovitaminosis D in Type 1 Diabetes Mellitus and Healthy Children from Qatar, a Sun-Rich Country

There are no population-based studies that have examined the association between vitamin D and type 1 diabetes mellitus (T1DM) and the role of lifestyle habits and dietary factors in young children in the Arabian Gulf and Middle East region. Little data on the intake of these nutrients in Mediterranean countries exist, and predictors of their suboptimal intake are not well defined.The objective of this study was to determine the association between vitamin D status and T1DM and assess the impact of lifestyle and dietary habits on hypovitaminosis D in the young population of the State of Qatar. A matched case-control study was carried out among T1DM children and healthy subjects <16 years of age at the pediatric endocrinology outpatient clinics of the Hamad General Hospital and the primary health care clinics center. The survey was conducted over a period from 6 August to 25 December 2007. The sample included 170 cases and 170 controls matched by age, gender and ethnicity.Face to face interviews were based on a questionnaire that included variables such as sociodemographic information, assessment of non-dietary covariates, assessment of dietary intake including vitamin D, type of feeding, clinical manifestations and laboratory investigations. Their health status was assessed by medical conditions, family history, body mass index, past or present clinical manifestations, serum 25(OH) vitamin D, calcium, alkaline phosphates, phosphorus, hemoglobin A1C, parathyroid hormone, magnesium and creatinine analysis.The study revealed that the incidence of severe vitamin D deficiency was considerably higher in T1DM (28.8%) compared with healthy children (17.1%). Although the mean serum level of vitamin D was significantly lower in T1DM children (15.80+/-9.23 ng/ml), compared with nondiabetic children (18.45+/-9.56 ng/ml), both groups belonged to the mild-moderate vitamin D deficiency category. A family history of vitamin D deficiency (35.3%; p=0.012) and diabetes mellitus (56.5%; p<0.001) was significantly higher in diabetic children. More than half of the diabetic (67.1%) and healthy children (51.2%) had no physical activity in their daily life. Both groups (65.9 vs. 62.9%) had very limited exposure to sunlight. Vitamin D supplement intake was very poor in diabetic children compared with healthy children; 60% of diabetic and 40.6% of healthy children never had any vitamin D supplement. The study revealed that vitamin D serum concentration, phosphorus, hemoglobin A1C, magnesium and creatinine show statistically significant differences between T1DM and healthy control subjects. A significant difference was noted between diabetic and healthy children for fractures (p=0.005), weakness (p=0.001) and gastroenteritis (p=0.025).The present study revealed that vitamin D deficiency is a common problem in Qatari children, but the incidence of vitamin D deficiency becomes very severe in T1DM children, compared with healthy children. This suggests that there is an association between vitamin D deficiency and T1DM. The data show that vitamin D status is dependent on sunshine exposure and dietary vitamin D intake. The results suggest the necessity of nutrition education to promote healthy eating habits among adolescents and their parents.

High prevalence of vitamin D deficiency in type 1 diabetes mellitus and healthy children

Epidemiological studies suggest a link between vitamin D deficiency in early life and the later onset of type 1 diabetes. The aim of this matched case-control study was to find the association between vitamin D and T1DM then to study the difference in the level of vitamin D in T1DM and healthy subjects, and to determine the associated environmental risk factors in young Qatari population. The study was carried out among T1DM children and healthy subjects below 16 years at the pediatric endocrinology outpatient clinics of the Hamad General Hospital and the Primary Health care Clinics (PHCs). The survey was conducted over a period from 6 August to 25 December 2007. The subjects were Qatari nationals male and female aged below 16 years. The study is based on matching by age, gender and ethnicity of 170 cases with those of 170 controls. Face-to-face interviews were based on a questionnaire that included variables such as socio-demographic information, assessment of non-dietary covariates, assessment of dietary intake, vitamin D intake, type of feeding, clinical manifestations and laboratory investigations. Their health status was assessed by medical conditions, family history, BMI, past or present clinical manifestations, 25 (OH)D, Calcium, alkaline phosphatase, phosphorus, HbA1C, PTH, Mg and creatinine analysis. The study revealed that vitamin D deficiency was considerably higher in T1DM children (90.6%) compared to non-diabetic children (85.3%). There was a significant difference found in the mean value of vitamin D between T1DM and non-diabetic children (P = 0.009). There were statistically significant differences between type 1 diabetic and healthy subjects with respect to the occupation of parents (P < 0.001) and consanguinity rate (P < 0.047). Family history of vitamin D deficiency was considerably higher among T1DM children (35.3%) with a significant difference between diabetic and non-diabetic children (22.9) (P < 0.012). Vitamin D supplement with breast milk was very poor in diabetic children (37.4%) compared to non-diabetic children (47.7%). Majority of the studied subjects were breast-fed children (95.1% of diabetic children and 97.2% of healthy children). Multivariate logistic regression analysis revealed that fathers and mothers occupation, family history of DM, physical activity, low duration of time under sun light, breast feeding less than 6 months and low vitamin D level were considered as the main factors associated with the T1DM. In conclusion, the present study revealed that vitamin D deficiency was higher in T1DM children compared to non-diabetic. Moreover, vitamin D deficiency was common in Qatari young population. Vitamin D intake was very poor in children and it shows that supplementing infants with vitamin D might be a safe and effective strategy for reducing the risk of T1DM.

Etiology of Failure to Thrive in Infants and Toddlers Referred to a Pediatric Endocrinology Outpatient Clinic

The aim of this study is to determine the underlying etiology of failure to thrive (FTT) in infants and toddlers referred to an outpatient pediatric endocrinology clinic. A chart review was done on FTT referrals to a pediatric endocrinology outpatient clinic between 2002 and 2005. Majority of patients (51.5%) had a purely nutritional deficiency. The endocrine etiologies included short stature due to being small for gestational age, constitutional or familial short stature (28.9%). The third most common etiology was gastrointestinal disease. Endocrine causes of FTT seem to be rare even in the selected population of patients referred to pediatric endocrine outpatient clinics. In the primary care setting, nutritional assessment and consultation seem to be adequate in the majority of cases. Only a small percentage of the patients with FTT will require a multidisciplinary approach and more extensive work-up.

Treatment of gonadotropin-deficient boys with recombinant human FSH: long-term observation and outcome

Boys with prepubertal onset of hypogonadotropic hypogonadism (HH) are at a risk of poor testis growth and impaired spermatogenesis. One potential cause for this is deficient proliferation of immature Sertoli cells before and during puberty due to the absence of FSH. To evaluate the effects of recombinant human FSH (r-hFSH) and human chorionicgonadotropin (hCG) on testicular function and pubertal development in boys with prepubertal onset of HH. Retrospective clinical study. Two university central hospitals, pediatric referral endocrinology outpatient clinics. Fourteen boys (aged, 9.9-17.7 years) with prepubertal (testicular volume (TV) <3 ml) onset of HH (idiopathic HH, n=2; Kallman syndrome, n=2; idiopathic panhypopituitarism, n=4; organic panhypopituitarism, n=6). Treatment with r-hFSH alone (2 mo-2.8 years) prior to induction of puberty with the combination of FSH and hCG. Progression of puberty, change in serum inhibin B, spermatogenesis. r-hFSH alone increased testicular volume twofold, from 0.9+/-0.6 ml (mean+/-s.d.) to 1.8 +/- 1.1 ml (P<0.005), and serum inhibin B threefold, from 27+/-14 to 80+/-57 pg/ml (P<0.01). Three boys with an apparent absence of postnatal hypothalamic-pituitary-testicular axis activation displayed attenuated inhibin B responses to long-term (>or=1 year) r-hFSH (P<0.01). Further significant increase in both TVand inhibin B occurred with induction of puberty with FSH and hCG (P<0.001). Seven boys provided semen samples: one had azoospermia, and others displayed a maximal sperm count range from 2.9 to 92 million/ml (median 8.5 million/ml). (i) r-hFSH induces prepubertal testis growth and increases circulating inhibin B levels, findings suggesting proliferation of immature Sertoli cells. (ii) Puberty was successfully induced with hCG and r-hFSH following r-hFSH priming. (iii) Inhibin B appears useful for monitoring spermatogenetic activity in boys treated with hCG. (iv) Despite the extremely small initial testis volume, six out of seven patients (86%) primed with r-hFSH displayed sperm in the ejaculate suggesting beneficial effect of r-hFSH priming on testicular function later in life.

Serum Insulin-Like Factor 3 Levels during Puberty in Healthy Boys and Boys with Klinefelter Syndrome

Levels of the Leydig cell-specific hormone insulin-like factor 3 (INSL3) are incompletely characterized in boys during pubertal development. The objective of the study was to characterize changes in INSL3 levels during spontaneous puberty in healthy boys, boys with aromatase inhibitor-induced hypergonadotropic hyperandrogenism, and boys with Leydig cell dysfunction. This was a prospective clinical study. The study was conducted at a university hospital pediatric endocrinology outpatient clinic. Patients included 30 healthy boys with idiopathic short stature (ISS) aged 9.0-14.5 yr and 14 boys with Klinefelter syndrome (KS) aged 10-13.9 yr. In ISS boys, intervention included aromatase inhibitor letrozole or placebo for 24 months. Serum INSL3 levels in relation to bone age, Tanner pubertal stages, and LH and testosterone levels were measured. Onset of puberty was associated with a significant increase in INSL3 levels from 0.06 +/- 0.01 ng/ml at Tanner G1 to 0.32 +/- 0.16 ng/ml at G2 (P < 0.0001). Adult INSL3 levels (> or = 0.55 ng/ml) were attained at bone age 13-14 yr. ISS boys with letrozole-induced hypergonadotropic hyperandrogenism had, after 12 months of therapy, higher INSL3 levels than did placebo treated (0.85 +/- 0.54 vs. 0.26 +/- 0.17 ng/ml, P < 0.01). In KS boys during spontaneous puberty, after an initial increase similar to that in healthy boys, INSL3 concentrations leveled off despite hyperstimulation by LH. Positive correlations occurred between serum INSL3 and LH and between INSL3 and testosterone levels in all three groups (P < 0.0001). In boys, the Leydig cell-specific hormone INSL3 may serve as a new marker for onset and progression of puberty. Pubertal increase in INSL3 levels seems to depend on LH. In KS subjects, INSL3 concentrations indicate Leydig cell dysfunction from midpuberty onward.

Prevalência da retinopatia diabética no Ambulatório de Endocrinologia Pediátrica da Santa Casa de Misericórdia de São Paulo

OBJETIVO: Verificar a prevalência de retinopatia diabética encontrada na população de diabéticos tipo 1, acompanhada no Ambulatório de Endocrinologia Pediátrica da Santa Casa de Misericórdia de São Paulo, entre 29 de agosto de 2000 e 17de agosto de 2001, e sua relação com o sexo, a idade do paciente na ocasião do diagnóstico do diabete e a duração do diabete. MÉTODO: Foi realizado mapeamento de retina, biomicroscopia de fundo e retinografia em 81 pacientes, 41 do sexo feminino e 40 do masculino, a fim de detectar e classificar a retinopatia diabética nessa população. RESULTADOS: A idade dos pacientes variou entre 4 e 23 anos (média = 12,0 ± 12,0), a idade do paciente na ocasião do diagnóstico, entre 6 meses e 15 anos (média = 3,4 ± 5,8) e a duração do diabete, entre 7 meses e 20 anos (média = 5,8 ± 4,4). A retinopatia diabética foi observada em 14 pacientes (17,3%), 7 (8,6%) com a forma não proliferativa muito leve, 5 (6,2%) com forma não proliferativa leve, 1 (1,2%) com forma proliferativa de alto risco e 1 (1,2%) com forma proliferativa avançada. CONCLUSÕES: A prevalência da retinopatia diabética na nossa amostra é 17,3%. Não há diferença entre os portadores e não portadores de retinopatia diabética quanto a sexo e idade do paciente na ocasião do diagnóstico. Quanto maior a duração da diabete, maior a prevalência da retinopatia diabética.