Supraclavicular swelling in hypothyroidism.

Hypothyroidism can have a variety of presentations. We report here a case of acquired hypothyroidism in a pediatric patient who first presented with bilateral supraclavicular swelling. Hypothyroidism and its presenting signs and symptoms are discussed with a focus on the less common findings that can be associated with hypothyroidism in children.

Pediatric thyroidectomy: a collaborative surgical approach.

INTRODUCTION: We have developed a collaborative approach to pediatric thyroid surgery, with operations performed at a children's hospital by a pediatric surgeon and an endocrine surgeon. We hypothesize that this strategy minimizes specialist-specific limitations and optimizes care of children with surgical thyroid disease. METHODS: Data from all partial and total thyroidectomies performed by the pediatric-endocrine surgery team at a tertiary children's hospital between 1995 and 2009 were collected and analyzed retrospectively. Statistical analyses were performed with IBM SPSS software (SPSS, Chicago, IL). RESULTS: Thirty-five children met the inclusion criteria (69% female; median age, 13 years; median follow-up, 1119 days). The indications for operation were thyroid nodule (71%), genetic abnormality with predisposition to thyroid malignancy (17%), multinodular goiter (5.7%), Grave disease (2.9%), and Hashimoto thyroiditis (2.9%). Sixteen children (46%) underwent thyroid lobectomy, and 19 children (54%) underwent total thyroidectomy. Median length of stay was 1 day (1 day after lobectomy vs 2 days after total thyroidectomy, P < .0001). There were 4 cases of transient hypocalcemia after total thyroidectomy, but there were no nerve injuries or other in-hospital complications in either group (overall complication rate, 11%). CONCLUSIONS: For pediatric thyroidectomy and thyroid lobectomy, collaboration of high-volume endocrine and pediatric surgeons as well as pediatric endocrinologists at a dedicated pediatric medical center provides optimal surgical outcomes.

Testosterone, obesity and insulin resistance in young males: evidence for an association between gonadal dysfunction and insulin resistance during puberty.

OBJECTIVE: To assess the relationships among obesity, insulin sensitivity, and testosterone in pubertal boys. PARTICIPANTS: This study included 20 lean, obese, and type 2 diabetic (T2DM) males, the majority of whom underwent a hyperinsulinemic-euglycemic clamp (n=16). METHODS: Glucose disposal (M value), serum testosterone, and body mass index (BMI) z-score were measured. Differences in testosterone were evaluated by group (lean vs. obese vs. T2DM), while regression was performed to evaluate the relationships among testosterone, obesity and insulin sensitivity. RESULTS: Controlling for Tanner stage, testosterone concentration was significantly lower in obese (p=0.02) and T2DM males (p=0.001) compared to lean males. Furthermore, M value was significantly associated with serum testosterone, even after controlling for BMI and Tanner stage. CONCLUSIONS: These data suggest that obese adolescent boys have lower serum testosterone than controls of the same Tanner stage, and echo the data in adult males associating obesity and insulin resistance with hypogonadism.

A molecular basis for variation in clinical severity of isolated growth hormone deficiency type II.

CONTEXT: Dominant-negative GH1 mutations cause familial isolated growth hormone deficiency type II (IGHD II), which is characterized by GH deficiency, occasional multiple anterior pituitary hormone deficiencies, and anterior pituitary hypoplasia. The basis of the variable expression and progression of IGHD II among relatives who share the same GH1 mutation is poorly understood. OBJECTIVE: We hypothesized that the cellular ratios of mutant/normal GH1 transcripts would correlate with the severity of the IGHD II phenotype. We determined the relative amounts of mutant and normal GH1 transcripts in cell lines and correlated transcript ratios with severity. DESIGN AND PATIENTS: Members of the same IGHD II kindred were genotyped for the GH1 E3+1 G/A mutation by DNA sequencing. Ratios of their 17.5-kDa (mutant)/22-kDa (normal) GH1 transcripts were determined in cultured lymphocytes (CLs), and these ratios were correlated with height sd scores obtained before GH replacement therapy. RESULTS: Ratios of 17.5-/22-kDa GH1 transcripts in CLs from family members with the same IGHD II mutation correlated with differences in their height SD scores. CONCLUSIONS: Our findings suggest that expression levels of both the mutant and normal GH1 allele are important in the pathogenesis of IGHD II, that the ratio of mutant/normal transcripts may be a predictive marker of the penetrance and severity of IGHD II, and that CLs may be useful as surrogates to study GH1 transcript expression of subjects whose anterior pituitary cells are not available.

Growth hormone treatment of early growth failure in toddlers with Turner syndrome: a randomized, controlled, multicenter trial.

CONTEXT: Typically, growth failure in Turner syndrome (TS) begins prenatally, and height sd score (SDS) declines progressively from birth. OBJECTIVE: This study aimed to determine whether GH treatment initiated before 4 yr of age in girls with TS could prevent subsequent growth failure. Secondary objectives were to identify factors associated with treatment response, to determine whether outcome could be predicted by a regression model using these factors, and to assess the safety of GH treatment in this young cohort. DESIGN: This study was a prospective, randomized, controlled, open-label, multicenter clinical trial (Toddler Turner Study, August 1999 to August 2003). SETTING: The study was conducted at 11 U.S. pediatric endocrine centers. SUBJECTS: Eighty-eight girls with TS, aged 9 months to 4 yr, were enrolled. INTERVENTIONS: Interventions comprised recombinant GH (50 mug/kg.d; n = 45) or no treatment (n = 43) for 2 yr. MAIN OUTCOME MEASURE: The main outcome measure was baseline-to-2-yr change in height SDS. RESULTS: Short stature was evident at baseline (mean length/height SDS = -1.6 +/- 1.0 at mean age 24.0 +/- 12.1 months). Mean height SDS increased in the GH group from -1.4 +/- 1.0 to -0.3 +/- 1.1 (1.1 SDS gain), whereas it decreased in the control group from -1.8 +/- 1.1 to -2.2 +/- 1.2 (0.5 SDS decline), resulting in a 2-yr between-group difference of 1.6 +/- 0.6 SDS (P < 0.0001). The baseline variable that correlated most strongly with 2-yr height gain was the difference between mid-parental height SDS and subjects' height SDS (r = 0.32; P = 0.04). Although attained height SDS at 2 yr could be predicted with good accuracy using baseline variables alone (R(2) = 0.81; P < 0.0001), prediction of 2-yr change in height SDS required inclusion of initial treatment response data (4-month or 1-yr height velocity) in the model (R(2) = 0.54; P < 0.0001). No new or unexpected safety signals associated with GH treatment were detected. CONCLUSION: Early GH treatment can correct growth failure and normalize height in infants and toddlers with TS.

Gonadoblastoma and Turner syndrome.

PURPOSE: The presence of a Y chromosome in the extrascrotal gonad of patients with intersex disorders has been associated with a high risk of GB and, potentially, GCT. Recently, modern sophisticated genotyping has revealed a subgroup of TS cases with a mosaic karyotype expressing a Y chromosome. We sought to evaluate this group of patients and address their risk of gonadoblastoma. MATERIALS AND METHODS: We reviewed the records and genotyping of all females newly diagnosed with TS between 1990 and 2002 at Children's Hospital in Denver. All patients with TS and Y chromosome mosaicism underwent gonadectomy, and the specimens were evaluated for the presence of gonadoblastoma on histological analysis and to identify Y chromosome on genotyping. RESULTS: A total of 192 girls with a clinical diagnosis of TS were identified between January 1990 and December 2002. Seven records were unavailable and 19 patients did not have karyotypic analyses available in the hospital charts. Of the remaining 166 patients 67 exhibited mosaic cell lines, of whom 8 had 45,X0/46,XY mosaic pattern and 59 had mosaic patterns without Y chromosomal elements. All 8 patients with Y mosaicism underwent uneventful laparoscopic gonadectomy on an outpatient basis. One patient observed to have bilateral dysgenetic gonads after gonadectomy was excluded from the study. Gonadoblastoma (bilateral 2 patients, unilateral 1) was detected in 3 of 7 patients (43%) with Y mosaicism. CONCLUSIONS: In our series 4.8% of evaluable patients with TS carried a 45,X0/46,XY karyotype. Gonadoblastoma can be evident even at an early age in streak gonads with Y mosaicism and may be bilateral. We recommend prophylactic laparoscopic gonadectomy of streak gonads in patients with TS who carry a Y mosaic genotype, because fertility is not an issue, surgical morbidity is minor and there may be a high potential for malignant transformation of gonadoblastomas in this population.

Is this patient insulin resistant? How much does it matter?

Alex was an obese 10-year-old girl with a family history of type 2 diabetes, hypertension, and perhaps polycystic ovarian syndrome. Her physical examination was significant for a central accumulation of body fat and acanthosis nigricans. Although the laboratory studies indicated that Alex was not diabetic and probably not glucose intolerant, she could be insulin resistant (IR). Should any further evaluation be done? If Alex is IR, what kind of treatment should be offered? The following discussion addresses these questions by reviewing the pathophysiology, diagnosis, and consequences of isolated IR.

Insulin resistance during puberty and future fat accumulation.

Insulin resistance is a known sequela of obesity; however, the relationship of insulin resistance to future weight gain remains unclear. In several studies, insulin resistance has been associated with weight stabilization. For the most part, this relationship has been found in adults who are overweight. To evaluate the relationship of insulin resistance to future fat accumulation in pubertal children, a 3-yr prospective study was carried out. Insulin sensitivity (Si) was determined by Bergman's minimal model in 111 healthy children, aged 9.7-14.5 yr. All children were Tanner stage II or III pubertal development at baseline. Body composition was assessed by body mass index, skinfold thickness, hydrodensitometry, and bioelectric impedance analysis at baseline and annually thereafter for an additional 3 yr. A repeated-measures analysis showed that the change in percentage body fat estimated from skinfold thickness [%BF(SF)] over time changed with increasing Si (P < 0.0001). Si was divided into tertiles for each gender, with the lowest tertile representing the most insulin-resistant children. For girls, those in the lowest tertile maintained their %BF(SF) over 3 yr, whereas those girls in the middle and upper tertile had an increase in their %BF(SF). For boys, those in the lowest tertile showed a decrease in their %BF(SF), whereas those boys in the middle and upper tertile maintained their %BF(SF). These results suggest that during puberty, children who are more insulin resistant have decreased sc fat gain.