Rare Presentation of Adrenocortical Carcinoma in a 4-Month-Old Boy.

Adrenocortical carcinoma (ACC) is a rare malignancy and even rarer in infancy. Most of these tumors in pediatric age group are hormonally active and predominantly present with virilization. Cortisol hypersecretion presenting as Cushing syndrome is extremely rare and seen in older age groups. We report a 4-month-old infant who presented with linear growth arrest and excessive weight gain in early infancy, consequently diagnosed with ACC. On long-term follow-up for 7 years, he remained metastasis free following surgical resection and was not treated with chemotherapy.

Should children with isolated premature adrenarche be routinely evaluated for non-classical congenital adrenal hyperplasia?

BACKGROUND: Current clinical practice is to evaluate children presenting with premature adrenarche (PA) for non-classical congenital adrenal hyperplasia (NC-CAH). Our main objective was to assess the prevalence of NC-CAH among children presented with PA. Additional objectives were to ascertain whether subpopulations were prone to NC-CAH, and therefore justified to be tested, and if obesity is a factor that can exclude the need for CAH testing. METHODS: A retrospective chart review of all children ≤11 years, who presented to our clinic with PA between January 2012 and May 2015 (n=103) was conducted. PA was defined based on commonly accepted clinical criteria. RESULTS: We did not identify any subjects with NC-CAH but one was affected with previously undiagnosed classical simple virilizing CAH (SV-CAH). The subject was born prior to the implementation of CAH newborn screening in the state of birth. The affected subject was of Middle Eastern origin and also obese (BMI >95 percentile for age and sex). CONCLUSIONS: Undiagnosed CAH is an uncommon cause of PA, and therefore routine screening for NC-CAH in every case of PA may not be justified, although, perhaps, should still be considered in high risk ethnicities. Obesity does not appear to exclude the possibility of being affected with mild or NC-CAH.

A teenage boy with hypocalcemia after radioablation for Graves' disease.

Excessive thyroid hormone production, as seen in Graves' disease, stimulates osteoblast-mediated bone turnover in favor of bone resorption. Acute reversal of bone resorption can lead to hungry bone syndrome (HBS), a state of rapid calcium deposition into newly synthesized osteoid resulting in hypocalcemia. Hypocalcemia due to subsequent functional or relative hypoparathyroidism is a recognized complication of therapy for Graves' disease. HBS is most recognized as an outcome of rapid correction of vitamin D deficiency or of acute hypoparathyroidism in cases of parathyroid gland function disruption after surgical removal of the thyroid. We report the case of an adolescent boy with Graves' disease who presented with hypocalcemia after radioactive iodine (131I) therapy due to HBS. Our report highlights the risk of HBS and severe hypocalcemia following treatment for Graves' disease in pediatric patients and also underscores the importance of pretreatment assessment and intervention for coexistent vitamin D deficiency.

Severe mandibuloacral dysplasia-associated lipodystrophy and progeria in a young girl with a novel homozygous Arg527Cys LMNA mutation.

CONTEXT: Mandibuloacral dysplasia (MAD) is a rare autosomal recessive progeroid syndrome due to mutations in genes encoding nuclear lamina proteins, lamins A/C (LMNA) or prelamin A processing enzyme, and zinc metalloproteinase (ZMPSTE24). OBJECTIVE: The aim of the study was to investigate the underlying genetic and molecular basis of the phenotype of a 7-yr-old girl with MAD belonging to a consanguineous pedigree and with severe progeroid features and lipodystrophy. DESIGN AND PATIENT: The patient developed mandibular hypoplasia during infancy and joint stiffness, skin thinning, and mottled hyperpigmentation at 15 months. Progressive clavicular hypoplasia, acroosteolysis, and severe loss of hair from the temporal and occipital areas were noticed at 3 yr. At 5 yr, cranial sutures were still open and lipodystrophy of the limbs was prominent. GH therapy from the ages of 3-7 yr did not improve the short stature. Severe joint contractures resulted in abnormal posture and decreased mobility. We studied her skin fibroblasts for nuclear morphology and immunoblotting and determined the in vitro effects of various pharmacological interventions on fibroblasts. RESULTS: LMNA gene sequencing revealed a homozygous missense mutation, c.1579C>T, p.Arg527Cys. Immunoblotting of skin fibroblast lysate with lamin A/C antibody revealed no prelamin A accumulation. Immunofluorescence staining of the nuclei for lamin A/C in fibroblasts revealed marked nuclear morphological abnormalities. This abnormal phenotype could not be rescued with inhibitors of farnesyl transferase, geranylgeranyl transferase, or histone deacetylase. CONCLUSION: Severe progeroid features in MAD could result from LMNA mutation, which does not lead to accumulation of prenylated lamin A or prelamin A.

Prevalence and clinical features of type 1.5 diabetes mellitus in children.

AIM: To classify children with diabetes mellitus as type 1, 1.5 or 2, based on strict criteria, and then compare their features and treatment. METHODS: In this retrospective study, all children with diabetes mellitus in our clinic with antibody status available (n = 120) were reclassified as type 1, 1.5 or type 2 based on status of antibodies to the pancreas and presence of obesity and/or acanthosis nigricans, and their features compared. RESULTS: Sixty-four percent of type 2 patients were reclassified as type 1.5. Type 1.5 patients had significantly lower BMI SDS, blood pressure and acanthosis nigricans than type 2 patients. They had a higher insulin requirement (0.82 +/- 0.44 U/kg/day) than type 1 (0.72 +/- 0.35 U/kg/day) or type 2 (0.28 +/- 0.3 U/kg/day) patients. Total cholesterol, HDL-cholesterol, ALT and AST significantly worsened from type 1 to 1.5 to type 2 patients. CONCLUSIONS: Type 1.5 diabetes mellitus should be considered among obese adolescents presenting as type 2, as their clinical course is more aggressive and insulin requirement higher.

Chemokines and inflammation in the nasal passages of infants with respiratory syncytial virus bronchiolitis.

This study measured chemokines in nasal lavage fluids (NLF) from infants with respiratory syncytial virus (RSV) bronchiolitis, defined by lung hyperinflation and wheezing. Comparison was made to RSV-positive infants without bronchiolitis and RSV-negative infants with acute respiratory illnesses. RSV-positive illnesses were associated with increased epithelial shedding, increased RANTES/protein ratios, and increased IL-8/protein ratios in NLF compared to RSV-negative illnesses. Among RSV-positive infants, bronchiolitics had greater total cell counts and percentage epithelial cells in NLF than nonbronchiolitics. Bronchiolitics also had roughly twice the NLF RANTES/IL-8 ratio than nonbronchiolitics (P =.043). Semiquantitative reverse transcriptase-polymerase chain reaction of nasal epithelium suggested similar RANTES/IL-8 ratio increases among bronchiolitics. A more mildly affected, RSV-positive outpatient population showed none of these differences. We conclude that RSV bronchiolitis is associated with a shift toward relatively more RANTES in nasal secretions of infants sick enough to require hospitalization, and mucosal epithelium may contribute to this process. Similar processes in the lower airways may enhance inflammation due to RANTES-responsive cell types and affect clinical manifestations.