Faculty Bibliography

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.Conflict of interest:None declared

BACKGROUND/AIMS: Studies in adult population have suggested that leptin might play a role in inducing obesity related hypertension mediated by the sympathetic nervous system. This association has not been established for adolescents. Our study is designed to explore the relationship between leptin and norepinephrine levels in pediatric patients and to identify any contributors to hypertension for this population. METHODS: Thirty-nine obese adolescents, divided into four groups by gender and hypertension status were included in the study. Leptin and norepinephrine levels were measured during oral glucose tolerance tests (OGTT) to optimize hormonal secretion. T tests were used to compare baseline levels of glucose, insulin, leptin and norepinephrine at 0 hour point of OGTT between the hypertensive and normotensive patients for both genders. Analysis of covariance (ANCOVA) was used for comparison of subsequent levels between the hypertensive and normotensive groups for in both genders, with the corresponding baseline level as the covariance. Models with and without BMI adjustment were created and their results were found to be consistent. Correlation between leptin and norepinephrine was examined at each time point and through analysis of area under the curve (AUC). RESULTS: Contrary to the previous findings obtained in adult patients, our results did not show any direct relationships between levels of leptin and norepinephrine. A slight decrease in norepinephrine level at 1 hour in the normotensive male group and a significant increase in leptin level at 1 hour in the hypertensive female group was observed. CONCLUSION: Our preliminary data suggest that norepinephrine and leptin levels at 0 and 1 hour during routine OGTT, for males and females, respectively, may help identify a subgroup of obese adolescents who have higher risk for hypertension and cardiovascular complications.

Various inactivating mutations in guanine nucleotide-binding protein, alpha-stimulating activity polypeptide1 (GNAS1) gene have been described with poor phenotype correlation. Pseudohypoparathyroidism type 1a (PHP1a) results from an inactivating mutation in the GNAS1 gene. Hormone resistance occurs not only to parathyroid hormone (PTH), but typically also to other hormones which signal via G protein coupled receptors including thyroid stimulating hormone (TSH), gonadotropins, and growth hormone releasing hormone. In addition, the phenotype of Albright hereditary osteodystrophy (AHO) is observed, which may include short stature, round facies, brachydactyly, obesity, ectopic soft tissue or dermal ossification (osteoma cutis) and psychomotor retardation with variable expression. We present a 2-year-old boy with PHP 1A who initially presented at age 3 weeks with congenital hypothyroidism. By 17 months of age, he manifested osteoma cutis, psychomotor retardation, obesity, brachydactyly and resistance to PTH with normocalcemia and mild hyperphosphatemia. Genetic analysis revealed a novel mutation in exon 13 of GNAS1 in our patient. This mutation, c.1100_1101insA, resulted in a frameshift and premature truncation of bases downstream. This mutation was also found in the mother of this patient who was also noted to have short stature, obesity, brachydactyly and non progressive osteoma cutis, but no hormone resistance.We report a novel heterozygous mutation causing PHP1A with PTH and TSH resistance and AHO which has not been described previously. PHP1A is also a rare presentation of congenital hypothyroidism.Conflict of interest:None declared

Pituitary apoplexy is an acute clinical event usually caused by hemorrhage or infarction in a pituitary adenoma. We report the unusual case of hemorrhagic pituitary apoplexy in an 18 year-old male with previously undiagnosed type 2 diabetes mellitus who presented with unexplained hyperglycemia (glucose 49.2 mmol/l [887 mg/dl]) and obtundation and in whom an initial diagnosis of non-ketotic hyperglycemic coma (NKHC) was made. MRI revealed a heterogeneous mass arising from an expanded sella turcica into the suprasellar cistern. Despite well-controlled glucose levels on continuous insulin infusion, dexamethasone, and initiation of bromoergocriptine (parlodel) therapy, the patient's vision and pupillary responses deteriorated acutely. Following emergency transphenoidal surgery, the patient's vision and mental status improved. Data confirmed preoperative panhypopituitarism; serum prolactin was 396 ng/ml (microg/l). Immunostudies demonstrated tumoral labeling for prolactin, but not for ACTH, GH, TSH, LH, FSH, or P53

Clinical experience with using an aromatase inhibitor to suppress estrogen production during puberty for improvement of growth potential in adolescents with short stature is limited. This report documents treatment of such a patient with a combination of growth hormone and letrozole, a third-generation aromatase inhibitor. Our case demonstrates a favorable outcome on a short-term basis