Brenda Kohn

Thyroid dysfunction as a late effect in survivors of pediatric medulloblastoma/Primitive neuroectodermal tumors†

Primary hypothyroidism is a common sequela of craniospinal radiotherapy in the treatment of pediatric brain tumors.

Increased 5alpha-reductase and normal 11beta-hydroxysteroid dehydrogenase metabolism of C19 and C21 steroids in a young population with polycystic ovarian syndrome.

OBJECTIVE To test the hypothesis that 5alpha-reductase (5alphaR) and 11beta-hydroxysteroid dehydrogenase (11beta-HSD) activity are increased in adolescent and young-adult women with PCOS and that an altered regulation of the hypothalamic-pituitary-adrenal (HPA) axis occurred in these subjects. DESIGN Prospective non-randomized study in an academic research environment. PATIENTS Eleven women, aged 14 to 25 years, were studied who were at least one year post-menarche and who had a diagnosis of PCOS based on a history of oligomenorrhea and elevated total and or free serum testosterone. INTERVENTION 24-Hour urinary metabolites were assessed in nine subjects and five underwent stimulation with ovine corticotropin releasing factor (oCRF). OUTCOME MEASURES C19 and C21 steroid urinary metabolite 5-alpha/5-beta pairs, 11-oxo/11-hydroxy products and the ratio of the total 5-alpha/5-beta reduced and 11-oxo/11-hydroxy products were compared to values in control women. Urinary cortisol (F) (sum of conjugated and free, and free F) and total F metabolites (the sum of THE, THF, 5alpha-THF, cortolones, and cortols) were determined. A 1 microg/kg oCRF stimulation test was performed with timed samples determined for plasma ACTH and serum F levels. RESULT The 24-hour total and free urinary F were not different from control. However, the total F metabolites were markedly elevated (7922+/-2666 vs 5418+/-1549 microg/24 h, p<0.01). A marked increase in the total 5-alpha reduced C19 and C21 metabolites was observed in the PCOS population vs control (5084+/-1977 vs 2681+/-1188 microg/24 h, p<0.01). The total urinary 11-oxo/11-hydroxy metabolite ratio was not different, p=0.23. The basal values and response of both ACTH and F to oCRF stimulation were not different from those of controls. CONCLUSION There is a marked increase in 5alphaR metabolism of both C19 and C21 steroids in younger women with PCOS.

Hormonal Effects in Infants Conceived by Assisted Reproductive Technology

Objective. The purpose of this report is to describe 7 infants conceived by assisted reproductive technology (ART) who presented with breast development and/or pubic hair. The clinical presentation in these infants raises awareness that an altered intrauterine hormonal milieu may impact the fetal and infant stages of children conceived by ART. Methods. Between May 2001 and April 2004, 7 children between the ages of 5 and 21 months conceived by ART were referred by their pediatricians to the Division of Pediatric Endocrinology at the New York University School of Medicine for evaluation of possible precocious puberty. Patients were evaluated for the possibility of centrally mediated precocious puberty and pseudoprecocious puberty, with a possible ovarian or adrenal origin. Results. Endocrine evaluation in all patients indicated sex-steroid and hormone levels in the prepubertal range; pelvic sonography confirmed prepubertal ovaries with unstimulated uteri. Clinical follow-up of our patients thus far has not revealed progression of breast development, pubarche, or elevation in sex steroids. Conclusions. It is well established that the developing endocrine system in the fetus and maturation of endocrine-control systems are influenced by hormone concentrations in the fetus. Whether ART alters the intrauterine hormonal milieu for the growing fetus conceived by ART is as yet unknown and is an area of ongoing investigation. Patients conceived through ART, including our patients who presented with hormonal manifestations, will need to be monitored throughout childhood and into adolescence and adulthood to determine if any perturbation exists on the timing of puberty and later fertility.

Hemorrhagic pituitary apoplexy in an 18 year-old male presenting as non-Ketotic hyperglycemic coma (NKHC)

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 patients vision and pupillary responses deteriorated acutely. Following emergency transphenoidal surgery, the patients 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.

Cushing Syndrome from Topical Foam Steroid Use in an Adolescent Male

Cushing syndrome (CS) is suspect in the presence of the clinical phenotype: centripetal obesity, cervical or posterior fat pad, purple striae, proximal muscle weakness, hypertension, glucose intolerance, acne, fatigue, chronic obstructive pulmonary disease, hirsutism, and menstrual irregularity. Depression, emotional lability, anxiety, sleep disturbance, and cognitive deficits are also frequently obser ved.1 If CS is suspected, there should be comprehensive questioning regarding any prior condition, including dermatologic, that may require use of corticosteroids. Although exogenous steroid use is the most common etiology, the source can be elusive and proper diagnosis can be missed. Excessive use of glucocorticoids, nonsystemic (topical and inhaled) and systemic, can result in suppression of the hypothalamic-pituitary-adrenal (HPA) axis.2 However, we think our patient is the first reported pediatric case of CS secondary to the use of the scalp foam (Olux®, clobetasol propionate foam 0.05%; Connetics Corp., Palo Alto, CA) commonly prescribed for treatment of psoriasis.

Identifying Subpopulations Vulnerable to the Thyroid-Blocking Effects of Perchlorate and Thiocyanate

Context Common environmental contaminants can disrupt normal thyroid function, which plays essential but varying roles at different ages. Objective To evaluate the relationship of perchlorate, thiocyanate, and nitrate, three sodium-iodide symporter (NIS) inhibitors, and thyroid function in different age-sex-stratified populations. Design, Setting, Participants, and Intervention This was a cross-sectional analysis of data from the 2009 to 2012 National Health and Nutrition Examination Survey evaluating the exposure to perchlorate, thiocyanate, and nitrate in 3151 participants aged 12 to 80. Main Outcome Measure Blood serum free thyroxine (FT4) as both a continuous and categorical variable. We also assessed blood serum thyroid stimulating hormone. Results Controlling for serum cotinine, body mass index, total daily energy consumption, race/ethnicity, and poverty-to-income ratio, for each log unit increase in perchlorate, FT4 decreased by 0.03 ng/dL in both the general population (P = 0.004) and in all women (P = 0.005), and by 0.06 ng/dL in adolescent girls (P = 0.029), corresponding to 4% and 8% decreases relative to median FT4, respectively. For each log unit increase thiocyanate, FT4 decreased by 0.07 ng/dL in adolescent boys (P = 0.003), corresponding to a 9% decrease relative to median FT4, respectively. Conclusions Our results indicate that adolescent boys and girls represent vulnerable subpopulations to the thyroid-blocking effects of NIS symporter inhibitors. These results suggest a valuable screening and intervention opportunity.

Skeletal growth and bone mineral acquisition in type 1 diabetic children; abnormalities of the GH/IGF-1 axis

Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases diagnosed in childhood. Childhood and adolescent years are also the most important period for growth in height and acquisition of skeletal bone mineral density (BMD). The growth hormone (GH)/insulin like growth factor -1 (IGF-1) axis which regulates growth, is affected by T1DM, with studies showing increased GH and decreased IGF-1 levels in children with T1DM. There is conflicting data as to whether adolescents with TIDM are able to achieve their genetically-determined adult height. Furthermore, data support that adolescents with T1DM have decreased peak BMD, although the pathophysiology of which has not been completely defined. Various mechanisms have been proposed for the decrease in BMD including low osteocalcin levels, reflecting decreased bone formation; increased sclerostin, an inhibitor of bone anabolic pathways; and increased leptin, an adipocytokine which affects bone metabolism via central and peripheral mechanisms. Other factors implicated in the increased bone resorption in T1DM include upregulation of the osteoprotegerin/ receptor-activator of the nuclear factor-κB ligand pathway, elevated parathyroid hormone levels, and activation of other cytokines involved in chronic systemic inflammation. In this review, we summarize the clinical studies that address the alterations in the GH/IGF-I axis, linear growth velocity, and BMD in children and adolescents with T1DM; and we review the possible molecular mechanisms that may contribute to an attenuation of linear growth and to the reduction in the acquisition of peak bone mass in the child and adolescent with T1DM.