0007—Growth Hormone Deficiency and Mixed Hyperlipidemia in a Patient With Klinefelter Syndrome

Case Presentations 0007—Growth Hormone Deficiency and Mixed Hyperlipidemia in a Patient With Klinefelter Syndrome Kelly Mullholand Behm, Paul M. Desrosiers, Nemours Children’s Clinic, Orlando, FL Patient Demographics: The patient is a male Caucasian child with 47,XXY karyotype. Clinical Presentation/Diagnosis: The patient presented at the age of 12 years 11 months with growth velocity (GV) b4 cm/year, Tanner I pubic hair (PH), and testicular volume (TV) of 3 ml. Past Medical History: GV was normal until it decreased from the 75th to the 50th percentile between the ages of 12 and 13 years. Concurrent medications included Concerta (ALZA Corporation, Mountain View, CA) and Wellbutrin (GlaxoSmithKline, Research Triangle Park, NC). Family history included quadruple bypass of the father at the age of 48 years. Evaluation: Provocative testing revealed a peak growth hormone (GH; Esoterix, Esoterix Laboratory, Austin, TX) of 1.5 ng/ml to glucagon and 9.4 ng/ml to clonidine. Insulin-like growth factor-1 (IGF-1) was 129 ng/ml (normal: 152–540 ng/ml). Height and weight were 156 cm (50th percentile) and 47 kg (50th percentile). The diagnosis was isolated growth hormone deficiency (IGHD). Interventions: Norditropin GH was prescribed (0.3 mg/kg/week) at the age of 13 years 3 months. The first-year GV was 12.4 cm/year. GH was discontinued at the age of 15 years 0 month when the patient’s height reached 174 cm (75th percentile). Bone age at this time was 14–15 years, with a GV of 5.7 cm/year. Three months post GH discontinuation, the IGF-1 was 479 ng/ml (normal: 202–957 ng/ml), with an IGFBP3 of 2.4 mg/L (normal: 2.2–4.2 mg/L). The patient’s most recent height at the age of 15 years 6 months was 177.1 cm, with a GV of 0.4 cm/year. Additional findings included mild gynecomastia, Tanner V PH, TV of 4–5 ml, follicle-stimulating hormone of 33.7 mIU/ml (normal: 2.0–9.2 mIU/ml), luteinizing hormone of 4.8 mIU/ml (normal: 0.4–7.0 mIU/ml), and testosterone of 207 ng/ml (normal: 200–620 ng/ml). Mixed hyperlipidemia was also noted, with laboratory results as follows: total cholesterol, 188 mg% (normal: b170 mg%); high-density lipoprotein cholesterol (HDL-C), 32 mg/dl (normal: 31–65 mg/dl); non-HDL-C, 156 mg%; lowdensity lipoprotein cholesterol, 96 mg/dl (normal: b110 mg/dl); triglycerides, 300 mg/dl (normal: 38–152 mg/dl); cholesterol/HDL risk ratio, 5.9 (normal: b5). Discussion/Recommendations: Although patients with Klinefelter syndrome are usually presumed to be tall (possibly due to an extra dose of the SHOX gene on the additional sex chromosome), this is not always true, as evidenced by the rare coexistence of IGHD in this patient. This patient’s normal brain magnetic resonance imaging and the wide variation in his stimulation test results indicate that he will be unlikely to need GH replacement as an adult. His mixed hyperlipidemia needs to be followed closely. Fibrate therapy will be initiated to address both the family history of cardiovascular disease and the increased risk of atherosclerotic coronary vascular disease with Klinefelter syndrome. Testosterone replacement will be necessary in the near future. Counseling regarding sexuality, fertility, plastic surgery for gynecomastia, and breast self-exams (increased risk of breast cancer in Klinefelter syndrome) is needed. The risks of Hashimoto thyroiditis, tumor potential, osteoporosis, and rheumatoid arthritis with Klinefelter syndrome should also be discussed. Transition planning from pediatric to adult care for current and future comorbidities is critical, and academic assistance/counseling should be recommended if education after high school is desired. 0008—Treatment of Familial Hypercholesterolemia With Ezetimibe/ Simvastatin in a Child Less Than 10 Years of Age Valari Cathey, Joni Beck, Aaron Bond, Piers Placket, Pediatric Diabetes & Endocrinology, Oklahoma University Health Sciences Center College of Medicine, Oklahoma City, OK, Baylor University Medical Center, Dallas, TX Patient Demographics: B.I. is a 4-year-old Caucasian girl with familial hypercholesterolemia (FHC). Clinical Presentation: B.I. presented to the clinic at 3 years 2 months of age. After following a pediatric cholesterol-lowering diet for 6 months, as instructed by a registered dietician, B.I.’s lipid levels were as follows: total cholesterol (TC) = 239 mg/dl (National Cholesterol Education Program [NCEP] goal b200 mg/dl); low-density lipoprotein cholesterol (LDL-C) = 176 mg/dl (NCEP goal b130 mg/dl); high-density lipoprotein cholesterol (HDL-C) = 54 mg/dl (NCEP goal N40 mg/dl); and triglyceride (TG) = 57 mg/dl (NCEP goal b150 mg/dl).

0882-5963/$ – see front matter doi:10.1016/j.pedn.2006.01.010

236

Past Medical History: At 2 years 6 months of age, B.I. was diagnosed with FHC by her primary care provider. Family history is significant for a father and two paternal aunts with FHC. Evaluation: B.I. was evaluated by a registered dietitian regarding adherence to her pediatric cholesterol-lowering diet. She was started on lovastatin, 10 mg daily, after baseline creatinine kinase and serum transaminase results fell within normal limits. DNA sequencing revealed pathological mutation in the LDL receptor gene. Intervention: Six months after therapy, TC = 179 mg/dl, LDL-C = 118 mg/dl, HDLC = 54 mg/dl, and TG = 38 mg/dl. Lovastatin plus diet were continued. Nine months after treatment, TC = 207 mg/dl, LDL-C = 144 mg/dl, HDL-C = 55 mg/dl, and TG = 49 mg/dl. Lovastatin was discontinued, and ezetimibe/simvastatin (10/10 mg) were begun. Three months later, TC = 130 mg/dl, LDL-C = 82 mg/dl, HDL-C = 39 mg/dl, and TG = 56 mg/dl. Six months later, TC = 195 mg/dl, LDL-C = 125 mg/dl, HDL-C = 57 mg/dl, and TG = 82 mg/dl. The patient’s height remained at the 75th percentile, and her weight increased to the 90th percentile. All other laboratory results were within normal limits. Discussion: 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) and cholesterol absorption inhibitors are now commonly prescribed to treat FHC in patients older than 10 years. In adults, clinical studies have shown ezetimibe/ simvastatin combination therapy to be more effective than simvastatin therapy alone at decreasing LDL-C, with a similar safety profile. This case illustrates the successful treatment of FHC in a child under 10 years. Long-term studies in this age group are needed to evaluate the long-term safety and efficacy of these agents. 0009—Ameliorating Metabolic Complications of Abnormal Weight Gain in an Adolescent Female on Psychotropic Medications: What did we do Right? Maureen Dever, Department of Endocrinology and Diabetes, St. Christopher’s Hospital for Children, Philadelphia, PA Patient Demographics: 13 year 7 month old obese female of Hispanic (Dominican Republic) descent. She is a 6th grade special education student who lives with her mom and brother. Clinical Presentation/Diagnosis: Patient was referred for hyperlipidemia and abnormal weight gain. 8/6/04, HT.152.9 cm (10 – 25%), WT. 67.5 kg (90 – 97%), BMI 28.8(N97%), Physical examination significant for acanthosis nigricans. Past History: Patient had gained 55 lbs over the year prior to initial visit. Mom reported bpsychosisQ since age 12 and seizure disorder since age 5, treated with Depakote (Abbott Laboratories, North Chicago, IL), Neurontin (Parke-Davis, NY, NY), and Abilify (Otsuka America Pharmaceuticals Co. Ltd., Tokushima, Japan). Patient had dysfunctional uterine bleeding since menarche, June 2004, now controlled with oral contraceptives and Iron supplementation (for secondary anemia). History of reactive airway disease, treated with Albuterol. Family history revealed maternal grandfather, maternal and paternal aunts and uncles with type 2 diabetes mellitus. Evaluation: Initial oral glucose tolerance test (OGTT) revealed diabetes mellitus and insulin resistance (fasting glucose 87, 2-hour glucose 201 mg/dl, fasting insulin 16.7, peak insulin 283.3 microIU/ml). Triglycerides and total cholesterol were elevated (145 mg/dl and 296 mg/dl, respectively). HDL-cholesterol was borderline low (33 nbsp;mg/dl). Liver function tests were very elevated (ALT, 830 U/L; AST, 327 U/L; GGT 155 U/L). Interventions: Instructions were given at our weight management/metabolic syndrome clinic regarding diet (no concentrated sweet, portion controlled, low fat), exercise (20 minutes daily aerobic), healthy behaviors, and home blood glucose monitoring. Metformin HCL was not prescribed secondary to elevated liver enzymes. Her psychiatrist weaned her off all medications. Follow-up visits occurred on 10/04, 11/04, 6/05 and 9/05. Her last visit showed height 155.3 cm (10 – 25%), weight 54.7 kg (50 – 75%), and BMI 22.6 (75 – 85%). Acanthosis nigricans improved. Repeat OGTT (9/9/05) revealed normal glucose (fasting 84, 2 hour 74 mg/dl) and insulin (fasting 5, peak 61 microIU/ml) levels. Lipid panel improved (triglycerides, 60 mg/dl; total cholesterol, 177 mg/dl; and HDL-cholesterol, 49 mg/dl). Liver functions normalized (AST 15 U/L, ALT 15 U/L). Discussion/Recommendations: Our patient’s metabolic complications resolved when her BMI normalized, after her psychiatric medications were discontinued, and a diet and exercise regimen was instituted. Pediatric patients on psychotropic medications warrant careful screening and early intervention by their healthcare providers to avoid the risks associated with excessive weight gain and the metabolic syndrome. 0010—Is Lipoatrophy Still a Problem? Patty Graves, William Zipf, Central Ohio Pediatric Endocrinology and Diabetes Services, Columbus, OH Patient Demographics: A.R., a 14-year-old female Caucasian adolescent diagnosed with type I diabetes at the age of 7 years, had reasonably well-controlled diabetes,

Journal of Pediatric Nursing, Vol 21, No 3 (June), 2006