Volume 24, Issue 3-4

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Objectives: To determine gender or race differences in associations between adiposity and leptin, and whether adiponectin moderates these relationships. Methods : Subjects were 441 adolescents, 14–18 years old (44% black, 56% white; 50% female, 50% male). Percent body fat (%BF) was measured with dual-energy X-ray absorptiometry. Leptin and adiponectin were measured using immunoassays. Results : Among the four groups (white boys, white girls, black boys and black girls), white girls had the highest adiponectin (p=0.0017) and black girls had the highest leptin (p=0.0164). Percent BF and leptin were positively correlated (p=0.0164). The %BF-leptin relationship was stronger in boys than girls (p<0.0001). Those with lower adiponectin had a stronger %BF-leptin relationship than those with high adiponectin in the entire sample (p=0.0220). Statistical models were adjusted for age, race, gender and the interaction between race and gender. Conclusion : Our data suggest a protective metabolic interaction for adiponectin and lend additional support for obesity prevention strategies in adolescents.

Objective: The relationships between obesity, pubertal development, and height are controversial. Therefore, we compared the prevalence of pubarche, menarche, and voice break between a large collective of obese and normal-weight children and adolescents aged 10–16 years. Methods: We assessed weight, height, pubarche, menarche, and voice break in 1383 obese German children and in 6615 children of a representative national German cohort aged 10–16 years. In all obese children, gonadotropins were determined and birth weight data were collected. Results : Independently of gender, the height standard deviation score (SDS) was significantly greater (0.3–1.0) in obese children <14 years compared to the reference cohort. Independently of age, the percentage of obese boys with pubarche was significantly lower compared to age-matched normal-weight boys. In girls <13 years, the prevalence of obese girls with pubarche was significantly lower compared to age-matched normal-weight girls. In boys ≥11 years, the percentage of obese boys with change of voice was significantly lower compared to age-matched normal-weight boys. In girls ≥11 years, the prevalence of obese girls with menarche was significantly lower compared to age-matched normal-weight girls. Birth weight had no impact on pubarche in the obese children. Luteinizing hormone was >0.3 IU/L in 86% of the children ≥10 years with pubarche. Conclusions : Obese children are taller than normal-weight children up to the age of 14 years. Since obese children demonstrated pubarche, menarche, and voice break later than their normal-weight peers, the increase in height in obese children does not seem to be attributable to earlier onset of puberty.

Hypothalamic obesity (HO) is a major and unsolved problem in patients with medial hypothalamic lesions and is associated with hyperinsulinemia and hyperleptinemia. The purpose of this study was to create a rodent model that mimics metabolic changes in HO for use in therapeutic testing. Female Sprague-Dawley rats were used to test the individual and combined effects of two types of medial hypothalamic lesions: arcuate nucleus (ARC) lesions by injection of monosodium glutamate at neonatal age, and ventromedial nucleus (VMN) lesions by passing an anodal current through an electrode placed in the VMN at age 80 days. Adiposity in ARC-lesioned animals was associated with decreased food intake and stunted growth, while VMN lesions were associated with hyperphagia but not reduced growth. The greatest weight gain (weight at age 200 days 712±65 vs. 451±19 g in controls), hyperphagia (food intake 10 days following surgery 33±0.8 vs. 18.5±0.7 g/day in sham-treated rats), hyperinsulinemia and hyperleptinemia occurred in rats that received both ARC and VMN lesions. Thus, the combined medial hypothalamic lesions result in an obesity phenotype similar to that of patients that suffer from HO and are consequently more suitable for testing potential therapeutics for this disorder than lesions of single hypothalamic nuclei.

Congenital hypothyroidism (CH) resulting from deficient production of thyroid hormone is one of the most commonly encountered diseases in pediatric endocrinology. Thyroid hormones play a crucial role in normal cerebral and growth maturation. These harmful effects on the cerebral and growth maturation can be prevented by early diagnosis and sufficient treatment in the first weeks of life. Diagnosis must be determined immediately within days after birth and effective treatment must begin. Unfortunately, despite the presence of national neonatal screening programs, CH cases are still rarely seen. In our study, it was aimed to assess the outcome of having determined an early diagnosis of CH and initiating treatment with thyroid stimulating hormone (TSH) screening test on live born babies over a period of 7 years in our hospital. With this aim, 93,897 live births were evaluated in the Doctor Faruk Sükan Obstetrics and Pediatrics Hospital between the years of 1999 and 2007. All neonates were screened with the TSH test. CH was determined in 43 (1/2183) of all cases and treatment was begun. The importance of this test was emphasized in that the test should be performed routinely on all neonates to obtain an early diagnosis and so that treatment for CH can begin.

Background: Congenital hypothyroidism (CH) affects approximately 1:3000–1:4000 infants. Objectives: To determine the prevalence of CH and isolated hyperthyrotropinemia (IHT) in newborns selected in mass screening for CH. Methods: Mass screening of 233,120 neonates born in southeastern Poland was carried out and CH-suspected children were identified. Serum thyroid-stimulating hormone and free thyroxine levels were determined during first confirmation and diagnosis re-evaluation in 118 and 34 children, respectively. Additionally, the patients were subjected to thyroid ultrasonography (n=53) and/or scintiscan (n=28). Results: Out of 118 children, first confirmation indicated CH in 58 neonates and IHT in 4 neonates. Out of these, 34 were re-evaluated with regard to diagnosis. A final diagnosis of permanent CH was reported in 34 children with thyroid dysgenesis (n=27) or dyshormonogenesis (n=7), transient CH affected 15 children, and permanent IHT was diagnosed in 6 children. CH prevalence was 1:4570 (permanent 1:6475, transient 1:38,853) and permanent IHT 1:38,853. Conclusions: The prevalence of CH and IHT corresponds to the prevalence of the condition in iodine-sufficient and borderline iodine-deficient areas.

Aim: The aim of the study was to investigate the influence of dietary intake of commercial hydrolyzed collagen (Gelatine Royal ® ) on bone remodeling in pre-pubertal children. Methods: A randomized double-blind study was carried out in 60 children (9.42±1.31 years) divided into three groups according to the amount of partially hydrolyzed collagen taken daily for 4 months: placebo (G-I, n=18), collagen (G-II, n=20) and collagen+calcium (G-III, n=22) groups. Analyses of the following biochemical markers were carried out: total and bone alkaline phosphatase (tALP and bALP), osteocalcin, tartrate-resistant acid phosphatase (TRAP), type I collagen carboxy-terminal telopeptide, lipids, calcium, 25-hydroxyvitamin D, insulin-like growth factor-1 (IGF-1), thyroid-stimulating hormone, free thyroxin and intact parathormone. Results: There was a significantly greater increase in serum IGF-1 in G-III than in G-II (p<0.01) or G-I (p<0.05) during the study period, and a significantly greater increase in plasma tALP in G-III than in G-I (p<0.05). Serum bALP behavior significantly (p<0.05) differed between G-II (increase) and G-I (decrease). Plasma TRAP behavior significantly differed between G-II and G-I (p<0.01) and between G-III and G-II (p<0.05). Conclusion: Daily dietary intake of hydrolyzed collagen seems to have a potential role in enhancing bone remodeling at key stages of growth and development.

Aim: The aim of the study was to identify patients with transitory elevation (TE) of 17-hydroxyprogesterone (17-OHP) using neonatal screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OHD) and to compare them with patients with 21-OHD. Methods: This was a retrospective study of patients with high 17-OHP levels detected during newborn screening in Madrid, Spain. Results: 17-OHP levels were significantly higher in the 33 21-OHD patients, who tended to present hyponatraemia and hyperkalemia. The TE-17-OHP group was characterized by normal initial physical examination (88.8% vs. 39.4%), lower gestational age and a higher number of stressful perinatal factors. 17-OHP levels decreased spontaneously in this group. Molecular diagnosis allowed us to discard the most frequent mutations associated with 21-OHD. Conclusions: Newborns with slightly increased 17-OHP levels and normal results for physical examination, acid-base equilibrium, glycemia, electrolytes and perinatal stress factors should be carefully evaluated. Decisions on treatment should be postponed until these results are available.

Objectives: The ternary complex is composed of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and acid labile subunit (ALS). Growth hormone (GH) promotes IGFBP-3 proteolysis to release free IGF-I, ALS, and IGFBP-3 fragments. Our aim was to determine whether elevated GH levels during GH stimulation testing would trigger IGFBP-3 proteolysis. Design: This prospective study of 10 short prepubertal children (height standard deviation score –2.37±0.31) used arginine and GH releasing hormone stimulation to study dynamic changes in the ternary complex moieties. IGFBP-3 was measured in two assays: a radioimmunoassay (RIA) that detects both cleaved and intact IGFBP-3; and an immunochemiluminescence assay (ICMA) that detects only intact IGFBP-3. Results: IGFBP-3 measured by RIA increased by 19% (p<0.05), while IGFBP-3 measured by ICMA did not significantly increase (6.1%). Conclusion: The significant increase in IGFBP-3 measured by RIA, but not ICMA, provides evidence of IGFBP-3 proteolysis during acute GH stimulation.

Objective: Low 25-hydroxyvitamin D (25OHD) concentrations have been associated with tumors and osteopenia or fractures in adults with neurofibromatosis type 1 (NF1). We report 25OHD concentrations in 109 children with NF1 and 218 controls matched for age, sex, geographic location, and time of year. Methods: Children with NF1 were recruited (n=109; 2–17 years), and clinical data and dual-energy X-ray absorptiometry measurements were obtained. 25OHD concentrations were measured in subjects and controls. Results: More NF1 individuals (50%) were in the 25OHD insufficient or deficient range (<30 ng/mL) (1 ng/mL=2.496 nmol/L) compared to controls (36%) (p=0.0129). 25OHD concentrations were higher in individuals with neurofibromas after controlling for age (p=0.0393), and were negatively associated with whole-body subtotal bone mineral density (BMD) z-scores (p=0.0385). Conclusions: More children with NF1 had 25OHD concentrations <30 ng/mL, potentially because of increased pigmentation and/or decreased sunlight exposure. In contrast to adults, decreased 25OHD concentrations were not associated with neurofibromas, and there was no positive association between 25OHD and BMD.

Recombinant human growth hormone (rhGH) is used for replacement therapy of pediatric hypopituitary dwarfism. Growth rate in children was observed to be better on the daily injection schedule compared with the currently used therapeutic regimen of thrice a week injection. Thus, a controlled release formulation would overcome the drawback of traditional rhGH therapy such as the need for multiple injections. Poloxamers are a family of triblock copolymers consisting of two hydrophilic blocks of polyoxyethylene separated by a hydrophobic block of polyoxypropylene, which form micelles at low concentrations and form clear thermally reversible gels at high concentrations. We used poloxamer gels to develop a controlled release formulation of hGH. The objective of this study was to develop an in situ gel forming drug delivery system for hGH using the minimum possible ratio of poloxamer 407 (P407). Decreasing the concentration of poloxamer could reduce the risk of hypertriglyceridemia induction. Different additives were added to the poloxamer formulations. It was observed that among different additives polyvinylpyrrolidone k30 (PVP k30) and polyvinyl alcohol (PVA) decrease poloxamer concentration required to form in situ gelation from 18% to 10%. The dynamic viscoelastic properties of the samples were determined. Both the storage modulus and the loss modulus of the samples increased abruptly as the temperature passed a certain point. It can be concluded that combining P407 and PVP and PVA could be a promising strategy for preparation of thermally reversible in situ gel forming delivery systems of hGH with low poloxamer concentration.

Objective: Mutations in the EIF2AK3 gene are known to cause Wolcott-Rallison syndrome (WRS), a rare recessive disorder characterized by early-onset diabetes, skeletal abnormalities, and liver dysfunction. To date, studies on WRS have revealed several mutation types leading to onset of the disease. In the present study, we analyzed the EIF2AK3 gene in a 10-year-old WRS patient and his parents to study the clinical features and the mechanism for genetic onset of WRS. Method: A patient diagnosed with WRS and his parents were chosen as research subjects. PCR techniques were used to amplify the 17 exons of the EIF2AK3 gene and DNA direct assay techniques were used for gene mutation analysis. Result: Gene mutation analysis revealed a 1798 A/T heterozygous mutation in exon 9 of the patient’s EIF2AK3 gene. This nonsense mutation can lead to a C-stop and result in a truncated protein of 532 amino acid residues in length (C532STOP). The patient’s parents are nonconsanguineous and the patient’s father carries the same mutation, while the mother carries no EIF2AK3 mutation. Conclusion: ETF2AK3 gene mutations can lead to the onset of WRS. The study results provide knowledge that furthers our understanding of the genetic mechanism of WRS.

Wilson’s disease rarely presents with isolated neurological complaints without any hepatic involvement. Refractory rickets with Wilson’s disease has been infrequently reported in literature. We are reporting a case of isolated neurological Wilson’s disease associated with refractory rickets which on complete evaluation was diagnosed as familial hypophosphatemic rickets.

Background: HNF1A-MODY (MODY3) is a common subtype of autosomal dominant diabetes. Unlike HNF4-MODY where fetal macrosomia and early postnatal hyperinsulinemic hypoglycemia have been reported, history of transient insulin overproduction has not yet been recognized in individuals with HNF1A-MODY. Case report: Here, we report on a 40-year-old male patient with HNF1A mutation p.Arg272His (c.815G>A) having a history of fetal macrosomia (4750 g, 59 cm), and, at least, one attack of symptomatic hypoglycemia in childhood. Diabetes was subsequently diagnosed at 19 years of age. The proband’s daughter who developed diabetes at 16 years carries the same mutation, but her birth weight and length were in the upper normal range, and she never experienced hypoglycemic symptoms. Conclusion: The observation of fetal macrosomia and hypoglycemia in childhood is indicative of a biphasic impact of the HNF1A mutation on β-cell function over the lifespan, leading from inappropriate insulin oversecretion to final clinical diabetes.

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A Chinese adolescent girl presented with secondary amenorrhea. During follow-up, she gradually developed Cushingoid features and virilization. After a series of endocrine investigations, including urinary steroid profiling, a diagnosis of adrenocortical carcinoma was made. The treatment and prognosis of the disease are discussed.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing syndrome in children, often occurring in association with Carney complex. We report a case of Cushing syndrome due to isolated non-familial PPNAD. The child presented with typical clinical characteristics, growth retardation and obesity. Liddle’s test was positive but micronodular appearance was not evident on CT scan and MRI; selective venous sampling revealed higher cortisol concentrations in the right adrenal vein. The patient underwent a laparoscopic right adrenalectomy. Postoperatively, hypercortisolism signs disappeared but after the second year a slight increase in urinary cortisol was noted and the patient developed osteopenia. Although significant catch-up growth occurred postoperatively, height did not normalize over the next 2 years. When she entered puberty, treatment with a luteinizing-hormone-releasing hormone agonist was initiated and growth hormone was added. Almost 5 years later a left adrenalectomy was also performed. Thereafter, complete disease remission was observed, the patient’s growth accelerated and her osteopenia reversed.

Maternal adrenal cortical carcinoma in pregnancy is rare. We report a case of an infant born to a mother with a history of adrenal cortical carcinoma. The pregnancy was complicated by fetal exposure to mitotane and dexamethasone. Despite the potential teratogenic exposures, there was no evidence of adrenal dysfunction in the infant. Growth and development at 12 months of age are normal and prognosis appears favorable. The long-term impact of fetal exposure to mitotane and glucocorticoid requires further investigation.

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Objective: Descriptive data characterizing the frequency of various chief complaints and presenting symptomatology in children with hyperthyroidism are lacking. Furthermore, difficulties in recognizing atypical presentations may delay diagnosis and increase morbidity. Methods: We performed a retrospective review of the medical records of 76 children with hyperthyroidism to characterize their chief complaints at initial presentation to care and document other presenting symptomatology. Results: Cardiac symptoms were the most frequent chief complaint, accounting for 23% of presenting complaints. Major mood and behavior disturbances were also frequently present (21%), but were infrequently cited as the chief complaint (6%). Conclusions: This study is the first to describe chief complaints separately from the other signs and symptoms of hyperthyroidism noted at the time of presentation to medical attention. Cardiac complaints were the most common; however, complaints associated with behavioral and mood disorders also occurred frequently. Clinicians should be aware of these presentations so that hyperthyroidism is diagnosed promptly to avoid morbidity associated with delayed diagnosis.

Aim: Aplasia cutis congenita (ACC) has been observed after fetal exposure to the antithyroid drug methimazole (MMI), but not reported after propylthiouracil (PTU), the current antithyroid drug of choice during pregnancy. This occurrence has implications for patient information and causal research. Case report: We describe a surviving term co-twin to a mother with hyperthyroidism exposed to PTU from conception to 34 weeks of gestation presenting with ACC at birth. Discussion: The association between PTU exposure and ACC is clinically relevant and allows speculation on the etiology. A similar mechanism to the classical MMI-induced ACC is postulated, unless a vascular etiology suggested by a vanishing twin or maternal hyperthyroidism itself is causal. Coincidence of PTU exposure and ACC seems unlikely. Conclusion: ACC in a newborn after PTU exposure during pregnancy hitherto observed only after MMI strongly encourages further reports of similar cases that may remain clinically underdiagnosed or unreported. Such confirmation could have significant implications for maternal treatment of hyperthyroidism, common in women of childbearing age.

Ectopic adrenocorticotrophic hormone (ACTH) secretion is a rare cause of Cushing syndrome in paediatric age, due to tumours arising from different tissues. To date, only 11 reports of ACTH-secreting pancreatic tumours in children and adolescents exist in the literature. We present a paediatric case of Cushing syndrome caused by ectopic ACTH secretion. This was caused by a large acinar cell carcinoma that developed in the pancreas of a 3-year-old girl.

Aim: The prevalence of Turner syndrome (TS) at birth has been estimated as approximately 1 in 2500 live female births. An increased risk of TS in subsequent pregnancies for couples who already have a daughter with TS has not been reported. Methods: We reviewed the records of 140 patients to evaluate the presence of familial TS occurrence. Results: Recurrence of TS was observed in 1.4% of our case series, which represents a 35-fold increased probability of having a second child with TS compared to no recurrence. Conclusion: This observation suggests that a risk of recurrence is possible, even though it is generally assumed that the likelihood of recurrent pregnancies with TS is similar to that in the general population. A wider study would be useful to confirm these data to improve genetic counseling for families with a daughter with TS.

Virilization in an adolescent patient can occur for multiple reasons (ovarian, suprarenal or exogenous reasons). We des­cribe a 14-year-old patient with 1-year secondary amenorrhea, who had an ovarian mature teratoma as a cause of her clinical history.

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Adrenocortical tumors are rare in childhood and adolescence. Virilization, alone or in combination with signs of overproduction of other adrenal hormones, is the most common clinical presentation. Here we report an unusual case of an African-American female adolescent presenting with idiopathic acquired generalized anhidrosis, dysregulation of body temperature, absence of adult body odor and dry skin in the face of a virilizing para-adrenocortical adenoma. Virilization signs regressed soon after removal of the tumor, but normalization of the 3α-androstenediol glucuronide (3α-AG) took longer compared to other measurable androgens; accompanied by anhidrosis. The association of remitting anhidrosis with normalized levels of 3α-AG suggests it might be a possible mechanism for anhidrosis. High 3α-AG levels might implicate the increased peripheral conversion of weak pro-androgens with different biochemical structure. We recommend obtaining 3α-AG beside other androgens in virilized patients with atypical dermatological symptoms in the face of hyperandrogenism.

Background: Concurrent deficiencies of three hormones in patients with Turner’s syndrome (TS) have rarely been reported. Here, we describe a case of a young girl who had Turner’s syndrome with concomitant chronic lymphocytic thyroiditis, growth hormone deficiency, and hypothyroidism with cardiopericarditis. Case: An 11-year-old girl was referred to the outpatient clinic because of short stature, ochriasis, and cardiopalmus. Her ultrasound revealed absence of ovarian tissue. Karyotype examination suggested Turner’s syndrome with sex hormone deficiency. She was found to have an abnormal thyroid gland and elevated thyroid stimulating hormone (TSH). A positive thyroid autoantibody titer confirmed the diagnosis of chronic lymphocytic thyroiditis with hypothyroidism. Furthermore, her growth hormone levels were well below normal. Diagnosis : A multi-endocrine disorder, i.e., Turner’s syndrome with chronic lymphocytic thyroiditis, growth hormone deficiency, and hypothyroidism with cardiopericarditis was diagnosed. Growth hormone and thyroxin substitution therapy was suggested.

We report an association of sacral agenesis and hypopituitarism in a child born of a diabetic mother. The child presented with short stature and evaluation revealed sacral agenesis, growth hormone deficiency (GHD) and adrenal insufficiency. This association might be important as short stature in children with sacral agenesis is usually attributed to mechanical factors. Early detection of GHD and treatment might help the child in gaining height.

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