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Context Variants in melanocortin 4 receptor (MC4R) pathway-related genes have been associated with obesity. The association of these variants with cardiometabolic parameters are not fully known. Objective We compared the severity of obesity and cardiometabolic risk markers in children with MC4R pathway-related clinically reported genetic variants relative to children without these variants. Methods A retrospective chart review was performed in children with obesity who underwent multigene panel testing for monogenic obesity. Results Data on a total of 104 children were examined, with 93 (89%) identified as White. Thirty-nine (37.5%) patients had clinically reported variants in the MC4R pathway, and the remaining 65 patients did not have reported MC4R pathway-related variants. Among the MC4R -related variants, PCSK1 risk alleles were most common, reported in 15 children (14%). The maximum body mass index percent of the 95th percentile was not different between groups (P =.116). Low-density lipoprotein cholesterol (LDL-C) was not different between groups (P =.132). However, subgroup analysis demonstrated higher LDL cholesterol in children with the PCSK1 c.661A>G risk allele relative to those with MC4R- related variant of uncertain significance (P =.047), negative genetic testing (P =.012), and those with non-M C4R related variants (P =.048). The blood pressure, fasting glucose, hemoglobin A1C, total cholesterol, alanine transaminase, and high-density lipoprotein cholesterol were not different between groups. Conclusion Variants in the MC4R pathway-related genes were not associated with severity of obesity and cardiometabolic risk markers except for the c.661A>G PCSK1 risk allele, which was associated with higher LDL-C levels. [ABSTRACT FROM AUTHOR]

OBJECTIVE. The aim of this study was to review our institutional experience managing pheochromocytomas and paragangliomas in children. METHODS. A retrospective chart review of the Mayo Clinic database from 1975 to 2005 identified 30 patients < 18 years of age with histologically confirmed pheochromocytoma or paraganglioma. RESULTS. There were 12 patients with pheochromocytomas and 18 with paragangliomas. The most common presenting symptoms were hypertension (64%), palpitation (53%), headache (47%), and mass-related effects (30%). Nine patients (30%) had a genetic mutation or documented family history of pheochromocytoma or paraganglioma. Fourteen patients (47%) had malignant disease, whereas 16 (53%) had benign disease. Logistic analysis showed that statistically significant risk factors for malignancy were (1) paraganglioma, (2) apparently sporadic, as opposed to familial, pheochromocytoma or paraganglioma, and (3) tumor size of >6 cm. Surgical resection was performed for 28 patients (93%), with perioperative mortality and major morbidity rates of 0% and 10%, respectively. Resection achieved symptomatic relief for 25 patients (83%). All patients with benign disease appeared cured after resection. For patients with malignant disease, the 5- and 10-year disease-specific survival rates were 78% and 31%, respectively, and the mean survival time was 157 [+ or -] 32 months. CONCLUSIONS. The incidence of malignant pheochromocytoma/paraganglioma was high in children (47%), particularly those with apparently sporadic disease, paraganglioma, and tumor diameters of >6 cm. Patients with a known genetic mutation or familial pheochromocytoma/paraganglioma were more likely to achieve resection with negative microscopic margins and had improved disease-specific mortality rates. Surgical resection remains the treatment of choice for pheochromocytoma and paraganglioma. Key Words pheochromocytoma, paraganglioma, children, surgery Abbreviations VMA--vanillylmandelic acid HVA--homovanillic acid MIBG--meta-iodobenzylguanidine, PHEOCHROMOCYTOMA AND PARAGANGLIOMA are exceptionally rare neoplasms in children. Both tumors develop from neural crest cell lineage, stain positive for chromaffin, and produce catecholamines, including dopamine, norepinephrine, and epinephrine. Tumors [...]

Objective. Primary hyperparathyroidism (HPT) is unusual in children. We reviewed our experience with HPT to better characterize these children. Methods. The retrospective review of patients Results. Fifty-two patients were identified. Median age was 16.8 years (range: 4-18.9) with a female-to-male ratio of 3:2. Eighty-five percent had an elevated parathyroid hormone (PTH) level, and 15% had an inappropriately normal PTH level during hypercalcemia. Serum calcium was elevated in all patients except for 2 with multiple endocrine neoplasma (MEN)-IIA and 1 with familial non-MEN HPT, but both had elevated PTH levels. Alkaline phosphatase levels were significantly higher in children with documented bone involvement. At presentation 41 patients (79%) were symptomatic and end-organ damage (nephrocalcinosis, nephrolithiasis, acute pancreatitis, or bone involvement) occurred in 23 patients (44%). Thirty-four patients (65%) had a single adenoma; hyperplasia was identified in 16 patients (27%), and of these cases, 57% occurred in patients diagnosed with MEN-I. Short-term complications included transient hypocalcemia in 29 patients (56%) and transient vocal cord paralysis in 2 patients (4%). Long-term complications were significant for permanent hypocalcemia in 2 patients (4%) and no recurrent laryngeal nerve injuries. No parathyroid abnormalities were identified during exploration in 4 (8%) children. Long-term follow-up was achieved in 98% of patients for a mean and median of 13 years. Resolution of hypercalcemia was achieved in 94% of cases. Conclusion. The diagnosis of primary HPT in pediatric patients is frequently delayed, is commonly symptomatic, and has significant morbidity. For children in whom HPT is suspected, evaluation of serum calcium and PTH levels is diagnostic in 100% of children. Parathyroid resection is effective at restoring normal serum calcium, has few complications, and is the treatment of choice for children with primary hyperparathyroidism. Pediatrics 2005;115:974-980; children, MEN, hypercalcemia, parathyroid adenoma., ABBREVIATIONS. HPT, hyperparathyroidism; PTH, parathyroid hormone; MEN, multiple endocrine neoplasia. Hyperparathyroidism (HPT) predominantly affects adults (incidence of 1 in 1000) and is very rare in children (incidence of 2-5 in [...]

Background. Intra-articular and intradermal steroids are often used for their antiinflammatory effect. There is limited experience with intra-articular and intralesional administration of corticosteroids in the pediatric age group. Design/Methods. We performed a retrospective chart review of 3 pediatric patients who developed Cushing&apos;s syndrome after local administration of triamcinolone acetonide (TCA). Results. Two females 9 and 17 years old, received intra-articular injections of TCA. One patient received multiple injections of TCA into the interphalangeal joints (cumulative dose: 120 mg), whereas the other received a single injection of 40 mg, a dose that is considered to be in the therapeutic range, into the hip joint. The third patient, a 7-year-old female, received multiple intralesional injections of TCA. These patients developed signs and symptoms of hypercortisolism that appeared 4 to 6 weeks after local administration of TCA and lasted for 4 to 6 months after the last dose of TCA. TCA was detectable in the plasma and urine by the liquid chromatography/tandem mass spectrometry method 4 to 5 months after the last dose of the steroid. Conclusions. We noted evidence for Cushing&apos;s syndrome in 3 pediatric patients after intra-articular or intradermal administration of TCA. One of them had received a therapeutic dose of TCA. The possibility of hypothalamic-pituitary-adrenal axis suppression should be considered in patients who have received intra-articular or intradermal steroid injections, particularly in those who have had multiple or relatively high doses. Pediatrics 2004;113:1820-1824; Cushing&apos;s syndrome, triamcinolone acetonide, intra-articular, intradermal., ABBREVIATIONS. TCA, triamcinolone acetonide; LC-MS/MS, liquid chromatography/tandem mass spectrophotometry; ACTH, adrenocor ticotropic hormone. Glucocorticoids are potent antiinflammatory agents used for the treatment of a variety of disorders. When given systemically, [...]

Introduction: Transgender and gender diverse individuals may choose to provide their infants with human milk. Lactating transgender men may experience gender dysphoria and desire to initiate or reinitiate gender-affirming testosterone therapy. However, there is limited safety data regarding use of testosterone during lactation. Main Issue: A 30-year-old G2P2 transgender man with gender dysphoria sought to initiate gender-affirming testosterone therapy while lactating. Management: Subcutaneous testosterone was self-administered beginning at 13 months post-partum. We prospectively collected data on circulating testosterone concentrations in parent serum, milk, and infant serum over 5 months until the infant self-weaned. The infant was monitored for growth and development at routine pediatric outpatient appointments. Parent serum testosterone concentrations rose with the initiation of testosterone therapy, reaching therapeutic concentrations by Day 14. Milk testosterone concentrations also increased with a maximum concentration of 35.9 ng/dl when the lactating parent was on a dose of 80 mg subcutaneous testosterone cypionate weekly. The calculated milk/plasma ratio remained under 1.0 and the calculated relative infant dose remained under 1%. The infant had no observable side effects, and his serum testosterone concentrations remained undetectable throughout the study period. Conclusion: This is the first study with data regarding human milk and infant serum testosterone concentrations during the initiation of gender-affirming testosterone therapy in a lactating individual. This evidence can help families and clinicians with decisions regarding lactation and testosterone use. [ABSTRACT FROM AUTHOR]

Drugs called bisphosphonates may be beneficial in children with hypercalcemia. Hypercalcemia occurs when blood calcium levels become excessive. Researchers used bisphosphonates to treat hypercalcemia in a five-year old child with leukemia, a 16-year-old who was immobilized after surgery and a 14-year-old with chronic hypercalcemia. Calcium levels returned to normal in all three and few side effects occurred. Bisphosphonates are routinely used in adults but their long-term effects on children are not known., Most clinicians only have a limited experience in treating childhood hypercalcemia with bisphosphonates. We report our experience in the use of intravenous and oral bisphosphonates in a 5-year-old with hypercalcemia secondary to acute lymphocytic leukemia, a 16-year-old with immobilization hypercalcemia, and a 14-year-old with chronic hypercalcemia of unknown cause. Single infusions of 0.5 mg/kg and 1 mg/kg of intravenous pamidronate were administered over 4 hours. No adverse reactions were observed except for hypocalcemia. A dose between 10 and 20 mg of oral alendronate was successfully used to maintain normocalcemia in the patient with chronic hypercalcemia. In our experience, the administration of bisphosphonates has enabled us to achieve normocalcemia in all cases, and in all cases there were no significant side effects. Long-term potential side effects from their use in children during the active phase of growth remain unknown. Pediatrics 1998;102:990-993; hypercalcemia, pamidronate, alendronate, side effects., ABBREVIATION. IV, intravenous. The experience that clinicians have acquired from treating childhood hypercalcemia with bisphosphonates remains limited. In adult patients these agents have been commonly and effectively used for years. [...]