The prevalence and volumetry of pituitary cysts in children with growth hormone deficiency and idiopathic short stature.

Background Pituitary cysts have been speculated to cause endocrinopathies. We sought to describe the prevalence and volumetry of pituitary cysts in patients with growth hormone deficiency (GHD) and idiopathic short stature (ISS). Methods Six hundred and eighteen children evaluated for growth failure at the Division of Pediatric Endocrinology at New York Medical College between the years 2002 and 2012, who underwent GH stimulation testing and had a brain magnetic resonance imaging (MRI) prior to initiating GH treatment were randomly selected to be a part of this study. High resolution MRI was used to evaluate the pituitary gland for size and the presence of a cyst. Cyst prevalence, cyst volume and percentage of the gland occupied by the cyst (POGO) were documented. Results Fifty-six patients had a cyst, giving an overall prevalence of 9.1%. The prevalence of cysts in GHD patients compared to ISS patients was not significant (13.5% vs. 5.7%, p=0.46). Mean cyst volume was greater in GHD patients than ISS patients (62.0 mm3 vs. 29.4 mm3, p=0.01). POGO for GHD patients was significantly greater (p=0.003) than for ISS patients (15.3%±12.8 vs. 7.1%±8.0). Observers were blinded to patient groups. Conclusions GHD patients had a significantly greater volume and POGO compared to ISS patients. This raises the question of whether cysts are implicated in the pathology of growth failure.

Pituitary volume in children with growth hormone deficiency, idiopathic short stature and controls.

BACKGROUND: The objective of the study was to describe the pituitary volume (PV) in pediatric patients with isolated growth hormone deficiency (IGHD), idiopathic short stature (ISS) and normal controls. METHODS: Sixty-nine patients (57 male, 12 female), with a mean age of 11.9 (±2.0), were determined to have IGHD. ISS was identified in 29 patients (20 male, 9 female), with a mean age of 12.7 (±3.7). Sixty-six controls (28 female, 38 male), mean age 9.8 (±4.7) were also included. Three-dimensional (3D) magnetic resonance images with contrast were obtained to accurately measure PV. RESULTS: There was a significant difference in the mean PV among the three groups. The IGHD patients had a mean PV 230.8 (±89.6), for ISS patients it was 286.8 (±108.2) and for controls it was 343.7 (±145.9) (p<0.001). There was a normal increase in PV with age in the ISS patients and controls, but a minimal increase in the IGHD patients. CONCLUSIONS: Those patients with isolated GHD have the greatest reduction in PV compared to controls and the patients with ISS fall in between. We speculate that a possible cause for the slowed growth in some ISS patients might be related to diminished chronic secretion of growth hormone over time, albeit having adequate pituitary reserves to respond acutely to GH stimulation. Thus, what was called neurosecretory GHD in the past, might, in some patients, be relative pituitary hypoplasia and resultant diminished growth hormone secretion. Thus, PV determinations by magnetic resonance imaging (MRI) could assist in the diagnostic evaluation of the slowly growing child.

Growth patterns in pubertal HIV-infected adolescents and their correlation with cytokines, IGF-1, IGFBP-1, and IGFBP-3.

OBJECTIVE: This study aims to describe the final adult height (FAH) and pubertal growth patterns in human immunodeficiency virus (HIV)-infected adolescents and to compare these to an age-matched population of seroreverting HIV-exposed, uninfected (HEU) adolescents. It further aims to evaluate the interplay of proinflammatory cytokines with insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), and IGFBP-1 during the pubertal growth spurt. METHODS: HIV-infected (n=34) and HEU (n=12) adolescents who had achieved FAH were evaluated. Auxologic data, viral load, CD4+ T-lymphocyte (CD4) count, and the use of highly active antiretroviral therapy were obtained via a retrospective chart review. Serum interleukin (IL)-1α, IL-6, tumor necrosis factor (TNF)-α, IGFBP-1, IGFBP-3, and IGF-1 were assessed. RESULTS: The mean FAH standard deviation score for the HIV-infected group was -0.78 (±1.1) compared to 0.05 (±0.78) for the HEU (p=0.034). There was a positive correlation between CD4 count and FAH (p=0.019). The mean age and magnitude of peak growth velocity (GV) was within normal limits. IL-1α, IL-6, TNF-α, IGFBP-3, and IGF-1 were not significantly correlated with HIV RNA or height. IGFBP-1 was detectable in 100% of poorly controlled HIV-infected patients and 25% of the HEU cohort (p=0.0003). CONCLUSIONS: The FAH of HIV-infected patients was significantly shorter than that of HEU patients, and it positively correlated with CD4 count. Our cohort demonstrated normal timing and magnitude of peak GV during puberty.

Improved long-term glucose control in neonatal diabetes mellitus after early sulfonylurea allergy.

BACKGROUND: Activating mutations of the ABCC8 gene can lead to permanent neonatal diabetes mellitus (PNDM). Glucose variability in infants with NDM treated with insulin can be extreme. We report long-term glycemic control in a patient with PNDM on sulfonylurea therapy, despite initial allergic reaction. METHODS: A Chinese girl presented on the first day of life with persistent hyperglycemia. Despite treatment with various insulin regimens, hemoglobin (Hb)A1c (normal 4.8%-6.3%) increased from 5.0% at 14 days of age to a peak of 9.7% at 15 months of age. Her average insulin dose was 0.5 units/kg/day. Genetic analysis revealed two novel ABCC8 gene activating mutations encoding the beta-cell sulfonylurea-1 receptor of the ATP-sensitive potassium channel. At age 3 years 2 months, transition from insulin to the oral sulfonylurea glyburide was initiated. After 8 days, she developed urticaria, palmar erythema, and a diffuse maculopapular rash, which resolved when medication was discontinued. At age 3 years 11 months, glyburide was reintroduced at a very low dose and was increased with concomitant weaning of insulin over the following 6 months. RESULTS: Normoglycemia (HbA1c 5.6%) was achieved on glyburide without any further allergic reaction at the age of 4 years 5 months with improved metabolic control. For the next 3 years, HbA1c measurements, and glucose means and variability were significantly lower compared with values during insulin therapy. CONCLUSIONS: As compared with subcutaneous insulin, oral sulfonylureas improved long-term metabolic control in a patient with NDM caused by novel activating mutations in the ABCC8 gene. Desensitization permitted safe oral sulfonylurea therapy in our patient with NDM despite initial allergic reaction. Fewer episodes of hypoglycemia occurred on sulfonylurea than on insulin therapy, which is an advantage in a very young child.

Outcomes of children and adolescents with well-differentiated thyroid carcinoma and pulmonary metastases following ¹³¹I treatment: a systematic review.

BACKGROUND: The optimal dose and efficacy of ¹³¹I treatment of children and adolescents with well-differentiated thyroid carcinoma (WDTC) and pulmonary metastases are not well established. A therapeutic challenge is to achieve the maximum benefit of ¹³¹I to decrease disease-related morbidity and obtain disease-free survival while avoiding the potential complications of ¹³¹I therapy. SUMMARY: We systematically reviewed the published literature on children and adolescents with WDTC and pulmonary metastases treated with ¹³¹I to examine outcomes after ¹³¹I administration and the risks and benefits of therapy. After reviewing 14 published articles, 9 articles met our inclusion criteria encompassing 112 pediatric and adolescent patients with WDTC and pulmonary metastases 21 years of age or younger at diagnosis spanning a follow-up period of 0.6­45 years. ¹³¹I therapy after surgery and thyrotropin suppression resulted in complete, partial, and no disease response in 47.32%, 38.39%, and 14.29% of patients, respectively. Five studies provided data on disease response in relation to ¹³¹I dose. In general, nonresponders received the highest ¹³¹I doses and complete responders received a higher dose than partial responders. The disease-specific mortality rate was 2.68%. Survival was 97.32%. A second primary malignancy occurred in one patient. One out of 11 patients studied experienced radiation fibrosis. CONCLUSIONS: This review confirms that the majority of pediatric and adolescent patients with WDTC and pulmonary metastases treated with ¹³¹I do not achieve complete response to therapy, yet disease-specific morbidity and mortality appear to remain low. It is therefore prudent to use caution in the repeated administration of ¹³¹I to such patients to ensure that adverse effects of therapy do not cause more harm than good in a disease that has an overall favorable natural course. Long-term prospective studies are needed to analyze disease-specific morbidity and mortality, recurrence rate, dose-specific response, and dose-related adverse effects of ¹³¹I in this patient population.

Thyrotropin-secreting pituitary adenoma in an adolescent boy: challenges in management.

Thyrotropinomas tend to be aggressive, invasive tumors that are difficult to resect because of their marked fibrosis and their proximity to vital structures such as the optic chiasm. The latter characteristic also limits the use of radiation therapy. In the few cases reported of children younger than 18 years whose thyrotropinomas were treated surgically, the results were disappointing. We present here the case of a 16-year-old boy with a thyrotropin-secreting pituitary macroadenoma who underwent partial resection via a transsphenoidal approach and was left with significant residual tumor and continued hyperthyroidism. He subsequently received 4 years of long-acting release somatostatin therapy, during which he has remained euthyroid without requiring antithyroid medication. To our knowledge, this is thus far the longest duration of somatostatin therapy in the pediatric age group. This regimen also achieved a decrease in compression of the optic nerve and prevented further tumor growth. We review here the current literature on somatostatin analog treatment including molecular mechanisms and promising new treatment modalities, such as the heterodimerization of dopamine and somatostatin receptors. We conclude that this has been a useful adjuvant treatment for our adolescent patient.

Endometrial thickness, uterine, and ovarian ultrasonographic features in adolescents with polycystic ovarian syndrome.

OBJECTIVE: Our aim was to evaluate uterine and ovarian ultrasonographic features including endometrial thickness (ET) in adolescent females with PCOS, which is limited in this population. METHODS: We performed a retrospective chart review of young females (n=51) ranging in age from 10 to 18 years with the diagnosis of PCOS. Clinical, biochemical and pelvic sonography data were reviewed. Sonographic data included uterine parameters of ET, length, and volume as well as ovarian volume and follicular morphologic features. RESULTS: Data in 51 girls were analyzed. Menstrual periods were reported as irregular in 26/51 (50.9%), amenorrheic in 19/51 (37.2%), regular in 4/51 (7.8%) and metrorrhagia in 2/51 (3.9%). Uterine features revealed that the endometrial stripe was enlarged (>7mm) in 16/51 (31.4%) of girls, all with homogeneous appearance. The uterine length was lower than normal in 22/51 (43.1%) of girls, normal in 21/51 (41.2%), and higher than normal in 8/51 (15.7%). Uterine volume was normal in 31/51 (60.7%) and higher in 20/51 (39.3%) of girls. Enlarged ovarian volume was found in 22/51 (43%) of patients. Mean ovarian volumes were 16.1cm(3) and 13.1cm(3) in bilateral and unilaterally enlarged ovaries, respectively. The morphology of ovarian follicles was studied in a subset of 40 patients. The location of ovarian follicles was peripheral in 81% and mixed in 19%. The number of follicles was also examined in 43 patients. They were few (<5) in 12%, moderate (5-10) in 5% and multiple (>10) in 84% cases. There was the presence of at least one >10mm cyst in 25% of girls. CONCLUSION: Majority of the adolescents with PCOS demonstrated multiple peripheral ovarian follicles, with large ovarian volumes in some, indicating an important role of ultrasonography in the diagnosis of PCOS, even at a younger age. Endometrial thickness, uterine length, ovarian size, and follicular morphology should be carefully examined in cases of adolescent PCOS.

The prevalence of abnormal liver enzymes and metabolic syndrome in obese adolescent females with polycystic ovary syndrome.

OBJECTIVES: We sought to determine the prevalence of abnormal liver enzymes suggestive of nonalcoholic steatohepatitis and metabolic syndrome in obese adolescent females with polycystic ovary syndrome. DESIGN: A retrospective chart review. PARTICIPANTS: Patients included 39 obese (body mass index Z score >/= 2) adolescent females with a diagnosis of polycystic ovary syndrome. Clinical and biochemical data in these patients were reviewed. MAIN OUTCOME MEASURES: Aspartate and alanine aminotransferase levels, lipid panel, blood pressure, body mass index, and glucose intolerance were the main outcome measures of the study. RESULTS: The study showed that 15.4 % (6 of 39) of patients had elevated aminotransferase levels, suggestive of nonalcoholic steatohepatitis, and 43.6 % (17 of 39) of patients qualified as having metabolic syndrome. Finally, 10.2 % (4 of 39) of patients were found to have both liver dysfunction and metabolic syndrome. CONCLUSION: Liver dysfunction consistent with nonalcoholic steatohepatitis and metabolic syndrome are prevalent in obese adolescent females with polycystic ovary syndrome. Therefore, early screening and further work-up for both disease states are warranted in cases of young adolescent females with polycystic ovary syndrome.

Evaluation of adolescents for polycystic ovary syndrome in an urban population.

OBJECTIVE: To assess the quality of diagnostic work-up received by patients with "possible" polycystic ovary syndrome (PCOS). DESIGN: A retrospective chart review. SETTING: A hospital based Pediatric Clinic in New York City. PATIENTS: Sixty female patients aged 13-19 years, with a primary ICD-9 diagnosis of ovarian dysfunction (256), menstrual irregularity (626), or hirsutism (704.1) were randomly selected for evaluation. In addition, 18 patients who were assigned the same ICD-9 codes at the Pediatric Endocrine Clinic were assessed. MAIN OUTCOME: Rates of assessment for diagnostic criteria of PCOS and selected co-morbidities. RESULTS: Twenty-five percent (15/60) of the patients were evaluated for PCOS according to the Rotterdam Criteria, and only 2 were evaluated for common co-morbidities associated with PCOS. Of the 28 patients who presented with two or more signs of PCOS (menstrual irregularity plus either obesity, hirsutism and/or acne), 15 were evaluated for PCOS (54%), but only 7% were assessed for common co-morbidities. All patients referred to the Pediatric Endocrine Clinic received appropriate evaluation for PCOS. In addition, 89% of the study group underwent further assessment for selected complications of PCOS. CONCLUSIONS: Patients presenting to an inner-city pediatric clinic with "possible" PCOS often do not receive a complete diagnostic evaluation. In addition, those evaluated for PCOS are often not adequately screened for the known health consequences associated with this condition. These findings suggest that PCOS is under evaluated and possibly under diagnosed in this pediatric population, which raises serious concerns regarding the potential for major longterm public health consequences.