Characteristics, clinical laboratory, histopathology, and outcomes of glycogenic hepatopathy in children.

Introduction: Glycogenic hepatopathy (GH) is a rare complication of type I diabetes mellitus (DM1), resulting in abnormal deposition of glycogen in the liver due to poor glycemic control. Clinical characteristics and natural history of GH are not completely understood in children. In this study, we investigated clinical, biochemical, histologic parameters and outcomes in children with GH. Method: This was a retrospective review of patients less than 18 years old diagnosed with GH and DM. GH was confirmed on liver biopsy. Medical records were reviewed for clinical presentation, laboratory tests, and clinical outcomes. Liver biopsy findings were reviewed by a pediatric pathologist (I. A. G.). Results: Nine children were diagnosed with GH and type 1 DM. The median age at diagnosis of GH was 16 (IQR 14.5-17) years. Duration of diagnosis of DM until GH diagnosis was 7 (IQR 5-11) years. The median frequency of diabetic ketoacidosis before GH diagnosis was three times (IQR 2-5.25). Peak Aspartate transaminase (AST) and Alanine transaminase (ALT) ranged from 115 to 797, and 83-389 units/L, respectively. Only two children had mild fibrosis. Seven of nine had steatosis without steatohepatitis. There was no correlation between glycosylated hemoglobin (HbA1c), or other laboratory tests and liver fibrosis on biopsy. HbA1c was 11.2 (IQR 10.2-12.8) at GH diagnosis and 9.8 (IQR 9.5-10.8) with normalization of liver enzymes. Conclusion: GH appears to be related to poor glycemic control in teenagers with long-term diabetes. GH presents with high to very high aminotransferase especially AST > ALT and resolves with modestly improved glycemic control. Diffuse hepatocyte swelling, steatosis, minimal fibrosis without hepatocyte ballooning or lobular inflammation are most common histological features.

Peripheral precocious puberty including congenital adrenal hyperplasia: causes, consequences, management and outcomes.

Peripheral precocious puberty results from peripheral production of sex steroids independent of activation of the hypothalamic-pituitary gonadal axis. It is much less common than central precocious puberty. Causes are variable and can be congenital or acquired. In this review, we will discuss the diagnosis and management of the most common etiologies including congenital adrenal hyperplasia, McCune Albright syndrome, familial male-limited precocious puberty, and adrenal and gonadal tumors.

INCIDENCE OF CENTRAL DIABETES INSIPIDUS IN CHILDREN PRESENTING WITH POLYDIPSIA AND POLYURIA.

OBJECTIVE: Polydipsia and polyuria are common reasons for referral to the Pediatric Endocrine clinic. In the absence of hyperglycemia, diabetes insipidus (DI) should be considered. The objectives of the study were to determine the prevalence of central DI (CDI) in a group of children presenting for evaluation of polydipsia and polyuria, and to determine if predictive features were present in patients in whom the diagnosis of DI was made. METHODS: The study was a retrospective chart review of children presenting to the endocrine clinic with complaints of polydipsia and polyuria over a 5-year period. RESULTS: The charts of 41 patients (mean age 4.9 ± 3.7 years, 28 males) were reviewed. CDI was diagnosed in 8 (20%) children based on abnormal water deprivation test (WDT) results. All but one patient had abnormal magnetic resonance imaging (MRI) findings, the most common being pituitary stalk thickening. Children with DI were older (7.86 ± 4.40 vs. 4.18 ± 3.20 years, P = .01) and had a higher propensity for cold beverages intake and unusual water-seeking behaviors compared to those without DI. Baseline WDT also revealed higher serum sodium (Na) and osmolality. CONCLUSION: The incidence of CDI in children presenting with polydipsia and polyuria is low. Factors associated with higher likelihood of pathology include older age, propensity for cold beverage intake, and higher baseline serum Na and osmolality on a WDT. ABBREVIATIONS: BMI = body mass index CDI = central diabetes insipidus DI = diabetes insipidus Na = sodium WDT = water deprivation test.

Varicocele: a dilemma in adolescent males.

Varicoceles are the most common cause of infertility in men. Despite the high prevalence of varicoceles, only a small percentage of men with varicoceles have subfertility or infertility. In adolescents, the prevalence of varicoceles increases dramatically during puberty to reach adult prevalence rates. The development of varicoceles during puberty can impair testicular growth and function. Data on hormonal and semen parameters in adolescents with varicoceles are limited, making it harder to determine which varicoceles are associated with infertility and which may benefit from surgery. The main indications for varicocelectomy in adolescents with varicoceles include a volume differential between unaffected and affected testes or abnormality in semen analysis.

Hypothalamic obesity syndrome: rare presentation of CNS+ B-cell lymphoblastic lymphoma.

Hypothalamic obesity syndrome can affect brain tumor patients following surgical intervention and irradiation. This syndrome is rare at diagnosis in childhood cancer, but has been reported with relapse of acute lymphoblastic leukemia. Here we present a case of hypothalamic obesity syndrome as the primary presentation of a toddler found to have CNS+ B-cell lymphoblastic lymphoma. Cytogenetic studies on diagnostic cerebrospinal fluid revealed MLL gene rearrangement (11q23). Hyperphagia and obesity dramatically improved following induction and consolidation chemotherapy. We describe a novel presentation of hypothalamic obesity syndrome in CNS B-cell lymphoblastic lymphoma, responsive to chemotherapy.

Three novel missense mutations within the LHX4 gene are associated with variable pituitary hormone deficiencies.

CONTEXT: The LHX4 LIM-homeodomain transcription factor has essential roles in pituitary gland and nervous system development. Heterozygous mutations in LHX4 are associated with combined pituitary hormone deficiency. OBJECTIVES: Our objectives were to determine the nature and frequency of LHX4 mutations in patients with pituitary hormone deficiency and to examine the functional outcomes of observed mutations. DESIGN: The LHX4 gene sequence was determined from patient DNA. The biochemical and gene regulatory properties of aberrant LHX4 proteins were characterized using structural predictions, pituitary gene transcription assays, and DNA binding experiments. PATIENTS: A total of 253 patients from 245 pedigrees with GH deficiency and deficiency of at least one additional pituitary hormone was included in the study. RESULTS: In five patients, three types of heterozygous missense mutations in LHX4 that result in substitution of conserved amino acids were identified. One substitution is between the LIM domains (R84C); the others are in the homeodomain (L190R; A210P). The patients have GH deficiency; some also display reductions in TSH, LH, FSH, or ACTH, and aberrant pituitary morphology. Structural models predict that the aberrant L190R and A210P LHX4 proteins would have impaired DNA binding and gene activation properties. Consistent with these models, EMSAs and transfection experiments using pituitary gene promoters demonstrate that whereas the R84C form has reduced activity, the L190R and A210P proteins are inactive. CONCLUSIONS: LHX4 mutations are a relatively rare cause of combined pituitary hormone deficiency. This report extends the range of phenotypes associated with LHX4 gene mutations and describes three novel exonic mutations in the gene.

Hypopituitarism and neurodevelopmental abnormalities in relation to central nervous system structural defects in children with optic nerve hypoplasia.

OBJECTIVE: Optic nerve hypoplasia (ONH) is a heterogeneous disease with variable findings of pituitary insufficiency, CNS and neurodevelopmental abnormalities. We characterized the spectrum of endocrinopathy in a cohort of children with ONH and attempted to correlate the presence of different midline CNS findings with the degree of hypopituitarism. The correlation of variable CNS abnormalities with the presence of a seizure disorder and neurodevelopmental delay was also examined. METHODS: Charts of 56 patients with ONH referred to our endocrine clinics between 1990 and 2000 were reviewed. Neurodevelopmental assessment was based on questionnaires sent to families during the study period. RESULTS: Forty-six patients (82%) had hypopituitarism, with growth hormone deficiency being the most common endocrinopathy. All patients with diabetes insipidus, hypocortisolism, and hypogonadotropin hypogonadism also had combined pituitary hormone deficiency. Evolving pituitary hormone deficiency was observed in two of 37 patients diagnosed with hypopituitarism in the first 3 years of life. No single midline CNS finding correlated with the presence of hypopituitarism or a seizure disorder. However, hydrocephalus or a seizure disorder was more commonly seen in patients with developmental delay. CONCLUSION: ONH is a heterogeneous disorder with possible multifactorial etiologies. All patients with this diagnosis deserve a comprehensive endocrine and neurodevelopmental evaluation.

Pancreatic enzyme elevations in children with diabetic ketoacidosis.

The incidence of pancreatic enzyme elevations in children with diabetic ketoacidosis (DKA) compared with children with newly diagnosed diabetes without DKA was assessed in a prospective study. Pancreatic enzyme elevations, particularly hyperlipasemia, are common but not associated with significant symptomatology. Acute pancreatitis was diagnosed in 2% of children with DKA.