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Background MEN-2B syndrome is comprised of the association of MTC, PHEOs and multiple mucosal neuromas. The latter is a phenotype pathognomonic of this syndrome, but expressivity of the mucosal neuroma phenotype is less than 100%. The RET genotype-phenotype correlations are well recognized. MEN-2B is transmitted as an autosomal dominant trait. The germline point mutations are gain-of-function, causing RET activation. Most cases of MEN-2B have a codon 918 mutation (exon 16) of the intracellular tyrosine kinase domain of RET proto-oncogene. Recently, classification based on the pathogenesis and molecular correlation of the mutations involved in MEN-2A and MEN-2B places these mutations into a cluster 2 (kinase receptor signaling) and its downstream pathway: the mutated protein RET interacts with and alters the activity of several effector proteins of the receptor kinase intracellular signaling pathway. Case presentation 9 year old female presenting with 2 weeks of neck pain and left anterior neck mass. No history of radiation exposure to the head or neck; no family history of thyroid cancer or pheochromocytoma. VS: BP 90/60 mm Hg, HR 85 bpm, height 130 cm (-1.1 SD). Phenotype: long faces, lingual mucosal neuromas with involvement of the lips, pectus excavatum, and arachnodactyly. Thyroid exam: left, firm ~ 2cm x 2cm-sized thyroid nodule, not fixed. Laboratory studies: Calcitonin: 226 pg/mL (0-5)- high; Chromogranin A: 8 nmol/L (0 - 5) elevated; CEA: 4.4 ng/ml (0 - 4.7) borderline high. Thyroid US: left thyroid lobe hypoechoic complex nodule 1.5 x 1.8 x 2.8 cm with coarse calcifications. US-guided FNAB, cytology: atypical cells, salt/pepper chromatin, amyloid (+). Immunohistochemical staining (+) for calcitonin. Diagnosis: MTC (Medullary Thyroid Carcinoma). Pheochromocytoma screen: plasma free metanephrine: 33 pg/mL (0-62), pelvic MRI with/without contrast and I-123 MIBG were normal. Genetic study: germline mutation, RET M918T (highest aggressiveness). Total thyroidectomy with central compartment lymph node dissection was performed. Pathology: pT1b (> 1 cm, < 2 cm), no nodal extension. Postoperative Calcitonin: < 2.0 pg/mL. Conclusions Identification of the mucosal neuroma phenotype in a child should alert the clinician to the diagnosis of MTC, a rare aggressive cancer syndrome. The diagnosis of MTC is made from calcitonin measurements and FNAB. Confirmation by positive immunostaining of tumor tissue for calcitonin is necessary with exclusion of pheochromocytoma. The finding of a germline mutation (sporadic/hereditary) in the RET gene in proband necessitates genetic testing in all first-degree relatives. After surgical intervention (in accordance to genotype-phenotype stratification), surveillance with calcitonin levels (as a marker of persistent/recurrent disease), CEA, Chromogranin A, and thyroid US along with plasma free metanephrines is recommended

Background: ACTH-secreting macroadenomas account for 4-10% of Cushing's disease[1]; remission rates in patients with ACTH macroadenoma undergoing surgery are low(<65% in most series)[2]Case Report: A 16 year old female was evaluated for obesity(BMI > 97th percentile), hypertension, and oligomenorrhea. Cushing's syndrome was confirmed with elevated urinary cortisol level at 628.7mug/24 hr(42-218), elevated midnight serum cortisol (22mug/dl)[3], and no suppression of cortisol(21.8mug/dl) after 1-mg overnight dexamethasone suppression test. MRI brain showed an intra- and suprasellar mass consistent with a pituitary macroadenoma(1.3x1.6x1cm); MRI of the abdomen revealed no adrenal mass. Transphenoidal surgery(TSS) was performed. Histopathology confirmed tissue diffusely positive for ACTH immunostaining, consistent with an ACTH-secreting adenoma. MRI brain post-op showed no evidence of residual pituitary tumor. Prednisone was administered for 5 days post-op due to hypotension presumed resulting from cortisol withdrawal. Cortisol level on post-op day 5 was 2.2mug/dl. Morning cortisol levels ranged between 8.3-15.2 mug/dl(6-21), and 24-hr urinary free cortisol levels(UFC) ranged between 3.8-4.8 mug/24hr(3-55). Despite gradually increasing 24-hr UFC, sequential MRI brain revealed no evidence of tumor. Twelve months after surgery, relapsed CD was confirmed with elevated UFC 65 mug/24hr. Fifteen months after surgery, UFC was elevated at 239 mug/24hr. MRI revealed tumor in the pituitary floor with involvement of both lobes. Patient underwent a second TSS, however tumor was incompletely resected due to bilateral cavernous sinus invasion. Cortisol level at 8 PM on post-op day 4 was 25.6mug/dl. MRI brain confirmed residual tumor and stereotactic gamma knife radiosurgery was planned.Discussion: Current literature in CD suggests that serum cortisol levels below 2mug/dl on day 3-5 post TSS predict long term remission, while levels of 2-4.9mug/dl warrant follow-up but no immediate intervention.[4] Since our patient was on prednisone post TSS, the cortisol level of 2.2mug/dl on post-op day 5 cannot be definitively relied upon for its predictive value. In children with CD, low UFCs after TSS are not good predictors of sustained remission.[5] Since surgery is less often curative in CD patients with ACTH-secreting macroadenoma and since no single cortisol cut-off value excludes all patients with recurrence, close monitoring is warranted in all patients with pituitary ACTH macroadenoma

Introduction: Vitamin D intoxication is a rare cause of hypercalcemia. There is a recent increase in reports of pediatric cases of hypercalcemia, secondary to vitamin D intoxication. This trend is attributable to the growing popularity of vitamin D supplements, especially as Vitamin D is being marketed as a "panacea" for a number of medical problems.Immigrant families often travel to their countries of origin, where vitamin supplements are available in formulations different from the US. Parents may not report using supplements to their child's pediatrician, as these supplements are perceived "safe" with no dangerous side effects.Case Presentation: A three year old toddler presented to the emergency room with emesis, polyuria, and lethargy. On inquiry, the family reported use of a multivitamin gel (made in Ecuador) dispensed at 1 tsp bid. Per the manufacturer's label, 5 grams (aD;one teaspoon) contains 0.096 mg (aD;100 IU) of cholecalciferol. A standard conversion of 1mug of cholecalciferol equals 40 IU1, secondary to conversion error this patient received 7,680 IU per day and 108,000 IU total vitamin D3 over 14 days, which is toxic. "Teaspoon" dosage inaccuracies and potentially excessive administration by caretakers compounded vitamin D toxicity.Initial lab values revealed Ca 16 mg/dl, iPTH 2.25 pg/mL (15-65), 25 OH vit D3: >512ng/mL(30-100), and UCa/UCreatinine 1.14mg/mg(<0.2). Hydration, lasix, calcitonin (6 days), and prednisolone (7 days) were used to manage the hypercalcemia. After 15 days of treatment, the 25 OH vitamin D3 was 324 ng/ml and the calcium decreased to 11.2 mg/dL. Conclusion s: In our case, dispensing and labeling errors led the parents to administer high doses of vitamin D to their toddler, leading to hypercalcemia. This highlights several issues regarding vitamin supplement usage.First, physicians should be aware of the dosage conversion of vitamin D in terms of IU, mg and mcg to calculate if the prescribed dose is appropriate for their patients. In addition, as there are no established manufacturing standards for certain vitamin supplement formulations-such as gels-caution should be exercised as more reports are emerging of toxic ingestion from overzealous supplementation. Verification of supplement source and composition is essential. Lastly, educating parents about the safe use of vitamin D supplements-emphasizing the need to report imported supplements to the patient's pediatrician-is important to avoiding erroneous toxic ingestion

We report a case of a 5-year-old female who presented with vaginal bleeding of unexplained etiology. There was no evidence of precocious puberty by history and physical examination. Endocrine laboratory studies were in the normal range for a prepubertal female. On vaginoscopy, a friable, granulomatous mass that bled easily was discovered within the vaginal vault. Pelvic sonography and magnetic resonance imaging of the pelvis was significant for a left adnexal mass. Surgical exploration and histological analysis revealed an unusual fibrohistiocytic proliferation. This unusual case broadens the differential diagnosis for vaginal bleeding in the prepubertal child (Table1)

BACKGROUND: Activating mutations of the thyroid stimulating hormone receptor gene (TSHR) are rare in the neonate and in the pediatric population. They are usually present in the germline, and are either inherited or occur de novo. Somatic mutations in TSHR are unusual in the pediatric population. METHODS: We describe a nine-month-old infant with thyrotoxicosis who harbored an activating somatic mutation in TSHR that was not present in the germline. RESULTS: As genomic DNA analysis failed to show a TSHR gene mutation, a radioiodide scan was performed to reveal a unilateral localization of uptake suppressing the remaining thyroid tissue. Genomic and complementary DNA analyses of the active thyroid tissue, removed surgically, identified a missense mutation (D633Y) located in the sixth transmembrane domain of the TSHR. The absence of this TSHR mutation in circulating mononuclear cells and in unaffected thyroid tissue confirmed the somatic nature of this genetic alteration. CONCLUSIONS: To the authors' knowledge, this is the youngest patient to receive definitive treatment for hyperthyroidism due to an activating mutation of TSHR

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

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

OBJECTIVE: To assess experience with growth hormone (GH) therapy in patients with familial dysautonomia (FD).Study design Of 580 patients with FD registered at the Dysautonomia Center at New York University Medical Center, 13 patients (8 males, 5 females) aged 1.10 to 15.10 years received GH treatment. GH doses ranged from 0.2 to 0.3 mg/kg/wk; one patient received 0.14 mg/kg/wk. Information regarding auxologic data, skeletal age, pubertal status, and spinal deformity before and after GH therapy was obtained from center records and treating endocrinologists. Growth velocity was analyzed before and during GH treatment at 0 to 6 months, 6 to 12 months, 1 to 2 years, and >2 years. RESULTS: Before GH therapy, growth velocity was <5 cm/y in 10 patients and 5 to 6 cm/y in three patients. In the first six months of GH therapy, growth velocity exceeded pretreatment rates in all but one patient; 10 patients achieved an annualized growth rate >7 cm/y. Six of nine patients treated for more than one year grew >5 cm/y. Less than optimal treatment responses were attributed to poor compliance, intercurrent illness, scoliosis, or advanced puberty. CONCLUSION: The data demonstrate that GH treatment in patients with FD may increase growth velocity, at least in the short term. This experiential data supports a future prospective study