Chirag Kapadia

Endocrine phenotype of 6q16.1–q21 deletion involving SIM1 and Prader–Willi syndrome-like features

Proximal interstitial 6q deletion involving Single‐minded 1 (SIM1) gene causes a syndromic form of obesity mimicking Prader–Willi syndrome. In addition to obesity, Prader–Willi syndrome includes several other endocrinopathies, such as hypothyroidism, growth hormone deficiency, and hypogonadotropic hypogonadism. The endocrine phenotype of interstitial 6q deletion remains largely unknown, although clinical similarities between Prader–Willi syndrome and interstitial 6q deletion suggest endocrine abnormalities also may contribute to the interstitial 6q deletion phenotype. This report describes the endocrine phenotype in a propositus with the Prader–Willi‐like syndrome associated with an interstitial 6q deletion including the SIM1 gene. Detailed endocrine evaluation of the propositus during childhood and adolescence revealed hypopituitarism, though initial endocrine evaluations during infancy were unremarkable. Our patient raises the possibility that hypopituitarism may be part of the phenotype, especially short stature, caused by interstitial 6q deletion. SIM1 plays an important role in the development of neuroendocrine lineage cells, implicating SIM1 haploinsufficiency in the pathophysiology of hypopituitarism seen in our propositus. Early identification of endocrine abnormalities can improve clinical outcome by allowing timely introduction of hormone replacement therapy. Hence, we suggest that detailed endocrine evaluation and longitudinal endocrine follow up be performed in individuals with proximal interstitial 6q deletion involving SIM1.

Parathyroid hormone reserve in 22q11.2 deletion syndrome

Objective: We hypothesized that most patients with 22q11.2 deletion and a history of hypocalcemia have inadequate parathyroid function, manifested by intact parathyroid hormone levels below normal. We aimed to evaluate intact parathyroid hormone levels both during normocalcemia and at hypocalcemia, in this population.Study Design: Retrospective chart review of 103 patients with 22q11.2 deletion born since 1997 and cared for at the Childrens Hospital of Philadelphia. Calcium and intact parathyroid hormone drawn simultaneously were recorded, along with clinical presentation at hypocalcemia.Results: Forty-seven simultaneous Ca/intact parathyroid hormone values were available. Seventy-nine percent of calcium levels and 81% of parathyroid hormone levels were within normal range. There were 19 patients with a history of symptomatic hypocalcemia, for whom any available simultaneous Ca/parathyroid hormone levels, before, during, or after hypocalcemia were analyzed. In this subgroup, 59% of calcium and 76% of parathyroid hormone levels were normal. None had an intact parathyroid hormone of >39.2 pg/mL at hypocalcemia. Seventy-three percent of hypocalcemic events had a precipitating stressor.Conclusions: Hypoparathyroidism in 22q11.2 deletion is mild, manifesting as a phenomenon of decreased parathyroid hormone reserve. Subjects are normocalcemic most of the time, but are unable to mount elevated intact parathyroid hormone levels, and therefore unable to correct hypocalcemia, in response to stressors.

Hemoglobin A1c measurement for the diagnosis of Type 2 diabetes in children

Laboratory measurements of hemoglobin A1c above 6.5% were approved as an additional diagnostic criteria for diabetes mellitus by the American Diabetes Association in 2010. Several recent pediatric studies have cast HbA1c measurement in children in an unfavorable light in the pediatric population, by comparing HbA1c measurements to results on oral glucose tolerance test (OGTT) or fasting plasma glucose (FPG). However, many of these studies do not recognize that diabetes diagnostic criteria are based upon long-term health outcomes. In this sense, OGTT and FPG have themselves never been validated in the pediatric population. Studies to validate diagnostic tests for diabetes in pediatric populations may take a substantial period of time, and may prove unfeasible. However, studies that tie diagnostic results as a child to diagnostic results as an adult may be more feasible and may provide the data needed to determine which pediatric diagnostic criteria to use. Thus, for the time being, except for cases of hemoglobinopathy, cystic fibrosis, and a few other exceptions, describing HbA1c as ‘lacking in sensitivity or specificity’ in the pediatric population because of lack of correlation with OGTT is not scientifically sound.

ADRENAL SUPPRESSION SECONDARY TO INTERACTION OF COMBINED INHALED CORTICOSTEROID AND ANTIFUNGAL AGENT.

Objective: Inhaled corticosteroids (ICS) are exogenous glucocorticoids that typically have minimal systemic effects at standard doses. They are metabolized by the cytochrome P450 (CYP450) enzyme pathway in the liver, thus they can cause unwanted side effects when used in conjunction with medications affecting this system. Here we present a case of adrenal suppression (AS) secondary to combined usage of ICS and posaconazole, a known CYP450 inhibitor. Methods: Clinical and laboratory data were isolated and are presented. Results: A 9 year old Caucasian female with history of hyper IgE syndrome. On chronic fluticasone and posaconazole for Aspergillus infection, presented with fatigue & “facial puffiness” (Cushingoid features). Low morning cortisol [0.3mcg/dL] prompted further evaluation. Low-dose [1 mcg] ACTH-stimulation test with peak cortisol level <1mcg/dL. Other causes of hypocortisolism were ruled out. Started on physiologic hydrocortisone [10mg/m2/day] and fluticasone discontinued. After weaning hydroc...

Growth Tracking in Severely Obese or Underweight Children

This study examines the utility of various growth charts, including a new modified CDC BMI z score chart, in tracking children with normal and problematic growth. OBJECTIVES: To illustrate the difficulties in optimal growth monitoring of children with severe obesity or underweight by using the Centers for Disease Control and Prevention (CDC) 2000 age- and sex-specific BMI percentile growth charts. We also aimed to examine the utility of a new modified CDC BMI z score chart to monitor growth in children with normal and extreme BMI percentiles by using real-life clinical scenarios. METHODS: Modified BMI z score charts were created by using the 2000 CDC algorithm. Three cases of children with extreme BMI values and abnormal growth patterns were plotted by using the standard CDC 2000 clinical growth chart, the modified BMI z score chart, and the CDC BMI percentile chart, modified to include the percentage of the 95th percentile (%BMIp95) curves. RESULTS: Children with severe obesity could not be plotted on the standard CDC BMI percentile chart because their BMI points lay above the chart cutoff. Children with a low BMI (<3%) were also difficult to track on the standard BMI percentile chart. The addition of the %BMIp95 scale to the standard BMI percentile chart allowed tracking of severely obese children; however, it did not address severely underweight children and required a change of units within the chart when transitioning from normal to obese BMIs. The modified BMI z score chart allowed uniform tracking. CONCLUSIONS: The modified CDC z score chart is suitable for growth tracking of children with normal and extreme growth patterns; the measures correlate well with the %BMIp95, and the chart can be incorporated easily into existing electronic health record systems for clinical use.

Case 1: Absent Pubertal Development in a 17.5-year-old Girl.

1. Madhia Shahid, MD* 2. Don McClellan, MD* 3. Chirag Kapadia, MD* 1. *Department of Endocrinology, Phoenix Children’s Hospital, Phoenix, AZ. A 17.5-year-old previously healthy girl presents with lack of breast development and menarche. She denies any abdominal pain, fatigue, headache, or vision changes. She also denies excessive exercise or dieting. She is not taking any medications. She has never been sexually active and denies any drug abuse. Her mother and older sister achieved menarche at age 12 years. The remainder of her medical history is unremarkable. On physical examination, the girl’s weight is 45 kg (5th percentile), height is 153.5 cm (7th percentile), and body mass index is 19 (20th percentile). Vital signs are normal, and she has no dysmorphic features. She is attentive, interactive, and cooperative during her examination. The thyroid gland is of normal size. Her skin evaluation yields normal results, with no abnormal hair distribution. She does not have any breast development (Sexual Maturity Rating 1). She does have dark, coarse pubic hair spreading sparsely over the junction of the pubes (Sexual Maturity Rating 3). She has no clitoromegaly or vaginal discharge. Her abdomen is soft, nontender, and nondistended without hepatosplenomegaly or palpable masses. There are no other findings of note on her physical examination. Results of her comprehensive metabolic panel, thyroid function tests, and …

Comorbidities of Thyroid Disease in Children

Thyroid disease even when treated results in mild persistent issues in cognition, weight, and mood in a subset of the population. Outcomes in congenital hypothyroidism are good but mild brain development issues are present in a subset of patients; growth is fine in nearly all treated patients. Prolonged hypothyroidism or hyperthyroidism impairs and alters growth outcomes even after the disease is identified and treated.

Is A1C Less Concordant with OGTT in Children as Compared in Adults? Data from a Hispanic Community in Arizona

Early efforts to identify hyperglycemia and those at risk for developing type 2 diabetes (T2DM) are warranted. For decades, the diagnosis of T2DM has been based on plasma glucose (PG) criteria but recent recommendations include the use of A1C for identifying hyperglycemia. These recommendations are based upon adult studies and data suggests that A1C may be less concordant in children, as compared to adults. The purpose of our study was to compare A1C, fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT) between adolescents and adults in Hispanic population at disproportionate risk for developing T2DM. Methods: Data from self-identified as Latino, 91 overweight adolescents, and 406 overweight adults were assessed after an overnight fast for A1C, FPG and OGTT results. Receiver Operator Characteristics Curves for A1C vs. any hyperglycemia (prediabetes or diabetes) were then developed. Result: 26 (28.6%) of the adolescents and 209 (51.5%) of adults exhibited hyperglycemia according to FPG and/OGTT. The prevalence of hyperglycemia as defined by an A1C>5.7% was 30.8% in adolescents and 55.6% in adults. Of the 26 adolescents, hyperglycemic on FPG and /or OGTT only 9 had A1C>5.7% for a sensitivity of 34.6%. This in contrast to adults, where the sensitivity of A1C>5.7% was 74.2%. Positive predictive value (PPV) for the A1C threshold of 5.7% was 32.1% in adolescents vs. 73.7% in adults. Conclusion: Concordance of A1C with other measures of hyperglycemia is lower in overweight Hispanic adolescents, as compared to overweight Hispanic adults.