Volume 23, Issue 5

ABSTRACT Clinical manifestations and outcomes of pituitary adenomas in children are not clearly defined. We retrospectively reviewed cases of pituitary adenomas in children 0-18 years treated at MassGeneral Hospital for Children over 15 years. Thirty-five patients were identified. Age at presentation was 7-18 years. Seventeen had prolactinomas, 3 had somatotropinomas, and 15 had Cushing disease. Thirteen prolactinoma patients were female and most commonly presented with oligomenorrhea (10/13) and galactorrhea (7/13). Nine were successfully treated medically. Two somatotropinoma patients presented with visual disturbances; the third was an incidental finding. Two were cured by transsphenoidal surgery (TSS). Thirteen Cushing disease patients were initially cured by TSS; six recurred after 3-6 years. Patients with or without recurrence did not differ for age, tumor-size and hormone levels. The high recurrence rate of Cushing disease in our series (46%) compared with adults treated surgically at this institution (7%) emphasizes the need for long-term follow-up.

ABSTRACT Objective : To assess the effect of nutritional supplementation on growth in short children born small for gestational age (SGA). Patients : Fifty four short but otherwise healthy children (26 boys), 6.4±1.8 years of age, were referred for growth retardation. Methods : Following a 6 month observation period the participants were randomly allocated to receive growth hormone therapy (GH) 1.26 IU/kg/day (0.042 mg/kg/day) or nutritional program (NUT) or passive observation (OBS). Patients in the nutritional program received 10 mg/day iron, 11 mg zinc-three times a week and 10000 IU/week of vitamin A. The following parameters were obtained 3 monthly: height, weight, dietary intake and serum IGF-1. Results : Six months of nutritional supplement induced growth acceleration somewhat lower than that seen in the growth hormone treated children, but significantly greater than noted in the observation group (OBS 4.6±1.3, NUT 7.9±1.7, GH 9.1±1.8 cm/yr, P < 0·001). Conclusions : Six months of vitamin A, iron and zinc supplementation induces growth acceleration in short children born SGA with subnormal nutrients intake similar to growth hormone therapy.

ABSTRACT Objective: to examine cognitive functions, emotional state and quality of life of patients with Turner syndrome (TS) after growth hormone therapy discontinuation. Patients and Methods: Anthropometric measurements, cognitive functioning, emotional state and quality of life of eighteen Lithuanian patients with TS were compared to that of age- and sex-matched controls. Height and weight of girls with TS were significantly lower than in the controls, though differences in body mass index were not significant. Results: Tension-anxiety (10.61±7.21 vs. 6.72±3.98, p=0.02) and depression-dejection (14.72±11.87 vs. 8.49±6.29, p=0.02) were significantly higher, vigor-activity (13.05±4.77 vs. 16.13± 4.36, p=0.04) was significantly lower and scores of cognitive functioning (53.18±29.46 vs. 26.79±7.31 and 96.94±44.59 vs. 58.07±15.43, p=0.001) were significantly higher (showing worse psychomotoric speed) in patients with TS than in the controls. Quality of life (9.53±5.19 vs. 6.35±4.19, p=0.03) in girls with TS was significantly worse than in healthy girls of the same age. Conclusion , patients with Turner syndrome are shorter, have lower weight, higher waist-to-hip ratio, impaired cognitive functions (worse psychomotoric speed), altered emotional state (higher tension-anxiety and depression-dejection, lower vigor-activity scores) and lower quality of life than age- and sex-matched controls.

ABSTRACT Objective : Although recombinant human growth hormone (rhGH) can unmask central hypothyroidism, few studies have investigated prevalence, predictors and growth consequences of evolving hypothyroidism in children receiving rhGH based on therapeutic indication. We hypothesized that children with GH deficiency (GHD) and greatest severity of GHD would be most likely to develop central hypothyroidism and decreased growth velocity (GV). Design : Retrospective chart review Patients : Children currently receiving rhGH with data available for at least 24 months after rhGH initiation (n=119). Indications included GHD, Prader-Willi syndrome, Turner syndrome, and idiopathic short stature (ISS) and SGA (n=60, 20, 19 and 20 respectively). Methods : We categorized patients as those hypothyroid at baseline (HYPO-B; n=13), those who developed hypothyroidism over 24-months of rhGH (HYPO-24; n=16), and those never hypothyroid (NO-HYPO; n=90). Groups did not differ for age or gender. Results : Central hypothyroidism developed in 25% of GHD patients. For all patients on rhGH, baseline IGF-1 (p=0.007), IGFBP-3 (p=0.006) and peak GH (p=0.02) differed between groups. HYPO-24 had lower baseline IGF-1, IGFBP-3 and peak GH than NO-HYPO, but did not differ from HYPO-B. Peak GH was <7 ng/ml in 100% of HYPO-24, 77% HYPO-B, and 71% NO-HYPO (p=0.01). GV SDS decreased between the first and second years in HYPO-24 in HYPO-24 compared with NO-HYPO. Conclusion : Evolution of central hypothyroidism is more likely in patients receiving rhGH for GHD than other indications, becomes more likely with greater severity of GHD and is associated with a reduction in GV SDS.

ABSTRACT Children born small for gestational age (SGA) are prone to developing obesity, insulin resistance and type 2 diabetes. Adiponectin and leptin are adipocytokines associated with insulin sensitivity parameters. We aimed to relate serum adiponectin and leptin levels with insulin sensitivity parameters in prepuberal SGA children with and without catch-up growth (SGA+CUG; SGA-CUG, respectively) and to analyze the usefulness of these adipocytokines as early markers of insulin resistance. We analysed adiponectin, proinsulin, leptin, growth factors, insulin, HOMA IR and HOMA βcell in 23 SGA+CUG, 26 SGA-CUG children compared with 48 prepuberal appropiate for gestational age (AGA). SGA children had adiponectin levels comparable to AGA children. Leptin levels were different between sexes, showed to be higher in SGA+CUG group (p=0.040) and these were significantly correlated with insulin sensitivity parameters. These results suggest leptin resistance as an adaptive mechanism to increase energy balance, but an altered functional response of adipocytes cannot be discarded.

ABSTRACT The insulin tolerance test (ITT) has been considered the most reliable test in the diagnosis of growth hormone deficiency (GHD), but it is contraindicated in some patients. Recently, the use of GH-Releasing Peptide-2 (GHRP-2) has been validated and reported as a safe and reliable test for the diagnosis of adult severe GHD. We evaluated the GH response to GHRP-2 in 56 children with growth disorders to assess its efficacy. A dose of 2 μg/kg of GHRP-2 was administered intravenously and serum GH concentrations were determined. The Spearman correlation coefficient for GH peak values indicated a favorable correlation with the ITT (P<0.0001). Peak GH concentrations were significantly (p<0.0001) lower in children with (median:3.39 μg/l (ng/ml)) than without (25.10 μg/l (ng/ml)) GHD. In the analysis of sensitivity-specificity curves, the serum concentration at the point where sensitivity crosses specificity was 15 μg/l (ng/ml). The GHRP-2 test was safe and required only one hour or less, and was capable of diagnosing GHD in children.

ABSTRACT Introduction : Burn injury is an important trauma and can cause many hormonal and metabolic changes in the human body. In contrast to the situation with adults, there are inadequate number of studies on children with this condition. Our aim in this study was to determine the changes in the adrenal, thyroid axes and glucose metabolism in the acute and subacute period and relation to the percent total body surface area (TBSA) burned in children with major burn injury. Patients and Method : A total of 90 hospitalized children aged 0-13 years (mean: 3.44±2.90 years) with major fluid burn injury were included in this study. Serum ACTH, cortisol, fasting glucose and insulin and thyroid hormones (free T3 and T4, TSH) were evaluated in the first 24 hours after the burn injury and on day 3 and month 3 consequently in all of the cases. An ACTH stimulation test was performed when necessary. Continuous variables were compared with analysis of variance and categorical variables were compared with the chi-square test. The Pearson correlation was used to determine the relation between ACTH and cortisol and between blood glucose and insulin (on day 1 and 3 and month 3). Also the correlation with the TBSA burned and the hormonal values were evaluated. A p value <0.05 was considered statistically significant. Findings : ACTH and Cortisol level increased in first 24 hours and decreased significantly by time. The change of ACTH and Cortisol level with time was significantly related to the TBSA burned. ACTH and cortisol levels were found significantly correlated in each time-point, but the correlation was highest in 3rd month. The glucose level in the first 24 hours was significantly higher than day 3 and month 3 levels in all of the children. There was again a significant increase in the serum insulin level in the first 24 hours. However there was no difference between day 1 and 3 serum insulin levels. A correlation was found between serum glucose and insulin on the first day but not on day 3 or month 3. Free T3 and T4 levels increased by time. Pairwise comparisons indicated that 1st day free T3 and T4 level was significantly lower than both 3rd day and 3rd month levels. Conclusion : ACTH, Cortisol and fasting blood glucose level increased significantly however serum insulin level was slightly higher in first 24 hours after burns in children. Thyroid hormones were found to be decreased acute period following burns but staying in normal levels.

ABSTRACT Background/Objective: The relationship between vitamin D receptor gene polymorphisms and bone density, osteocalcin and growth was investigated. Subjects: Eighty eight adolescents aged between 8-15, with no history of illness influencing the level of bone parameters, were examined in our study. Methods: Areal BMD for lumbar spine (L1-4) was assessed by dual energy X-ray absorptiometry (DEXA). Height and weight were measured on the day of the DEXA scans. Serum osteocalcin level was determined by using ELISA method. DNA was extracted from white blood cells, amplified by the polymerase chain reaction (PCR) and the polymorphic sites were analyzed by using ApaI, TaqI and FokI restriction enzymes. Results: The most frequent genotypes were FF (% 54.6), Aa (% 53.4) and Tt (% 48.8). No significant relationship was found between VDR genotypes and areal BMD, osteocalcin level or growth in either sex. But there was a strong tendency for a higher BMD at the lumbar spine of TT and AA genotypes compared to tt and Aa genotypes. The children with TT genotype were taller and heavier than the children with tt genotype. Conclusion: Our results suggest that VDR gene TaqI polymorphism may be associated with body weight and bone mass, but more studies with larger groups should be conducted.

ABSTRACT Background : Apelin is a novel adipocytokine produced by white adipose tissue that binds the APJ receptor with high affinity. Insulin may have a role in regulation of apelin synthesis and secretion from the adipose tissue. Objective : To investigate blood apelin concentrations in children with type 1 diabetes mellitus (T1DM) and display association of apelin with adiponectin, body mass index (BMI), lipids and insulin sensitivity. Methods : Thirty patients with T1DM and 45 healthy controls were enrolled. Apelin levels were measured along with BMI, lipids, fasting plasma glucose, HbA1c and adiponectin levels. Results : Plasma apelin and adiponectin levels were significantly higher in the diabetic group when compared to controls. No correlation was found between the apelin blood concentrations and adiponectin, BMI, lipids and insulin sensitivity. Conclusions : Children with T1DM have significantly increased circulating apelin levels when compared to healthy controls. However, no significant relation was found between the apelin and BMI, glucose, lipids and adiponectin levels, and also insulin sensitivity.

ABSTRACT Isovaleric acidemia is a rare autosomal recessive inborn error of leucine metabolism. Two phenotypes with either an acute neonatal or a chronic intermittent presentation were described. The acute type is observed more frequently and is more fatal. We report the case of a girl in childhood who presented with hyperglycemia and metabolic acidosis with an increased anion gap; and preliminarily diagnosed as diabetic ketoacidosis, but further investigation revealed chronic intermittent isovaleric academia. This case is of interest because of the rarity of this presentation. The importance of thinking for inborn errors of metabolism in children with metabolic acidosis in late childhood is emphasized.

ABSTRACT Type Ia Glycogen storage disease is an autosomal recessive hepatic metabolic disease due to a lack of glucose-6-phosphatase (G-6-Pase) activity presenting with growth retardation, lactic acidosis, fasting hypoglycemia with hypoinsulinemia, hyperuricemia, hepatomegaly, and hepatic adenoma with a risk of malignancy. The gene that encodes G-6-Pase was mapped to 17q21. There are some genotype-phenotype correlations. We report a case with delF327 mutation which is devoid of G-6-Pase activity; however clinical presentation in this case differs somewhat. Although correction of hypoglycemia and lactic acidosis with nocturnal intragastric feeding and uncooked starch therapy improves growth failure, mean height of the patients is often less than the target. Normal height and obesity in this case with hepatic steatosis and low hepatic glycogen storage requires clinical re-evaluation since there are some overlapping phenotypes between type Ia GSD and metabolic syndrome. The phenomenon may be related to insulin resistance as a consequence of early aggressive nutrition therapy with frequent low glycemic index meals.

ABSTRACT We report on a 9 year-old boy with atypical McCune Albright syndrome who presented with polyostotic fibrous dysplasia, unilateral testicular enlargement without signs of sexual precocity, and bilateral testicular microlithiasis on sonography. This is the first report of a patient with an atypical form of MAS presenting with unilateral testicular enlargement not associated with sexual precocity, and with testicular microlithiasis.

ABSTRACT Henoch Schönlein Purpura is an IgA mediated vasculitis that is known to be associated with scrotal pathology. However, an association between Henoch Schönlein purpura and ovarian pathology has not been described. We present the case of a girl who developed cystic changes in her ovaries during her course of Henoch Schönlein purpura.

ABSTRACT A 6-week-old girl, the first child of non-consanguineous parents, was admitted to the hospital for evaluation of vomiting. She was small for gestational age (1500 g). On admission, she weighed 1830 g, and appeared dehydrated. The blood glucose was 880 mg/dL. Insulin and C-peptide levels were <1 μIU/ml and 0.1 pmol/L, respectively. Antibodies of diabetes were negative. The serum triglyceride level was markedly elevated (5322 mg/dL). After a few days of insulin therapy, the triglyceride levels dramatically decreased, but cholestasis persisted. A liver biopsy revealed diffuse iron deposition and the diagnosis of neonatal hemochromatosis was established. In neonatal hemochromatosis, diabetes may occur as a result of iron deposition in the pancreas. The coexistence of neonatal diabetes secondary to neonatal hemochromatosis with a fatal course during the infancy period has not been previously reported. In this report, an infant with neonatal diabetes secondary to neonatal hemochromatosis is presented as the first case in the literature involving the coexistence of these two conditions.

ABSTRACT Rathke cleft cysts (RCC) are benign cysts derived from remnants of Rathke cleft, and are rarely symptomatic in children. Symptoms due to RCC are associated with mass effect and pituitary hormone deficiencies. Slow growth rate of the cyst makes its incidence increase with aging. Here we report on a seven year old girl who presented with central diabetes insipidus (CDI). Her sella MRI revealed a lesion in the sellar region which grew rapidly in follow-up. She underwent microneurosurgical operation and the lesion was totally excised. Pathologic examination revealed RCC with degenerative changes. In her follow-up, growth hormone deficiency developed in addition to arginine vasopressin deficiency. Rapid growth of the cyst is not the usual course of RCC's. Mechanisms regarding the cyst growth are unclear as they are in this case. This is the youngest child to date presenting with central diabetes insipidus due to RCC. Rapid growth of RCC can cause CDI in young children.