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Top 5 Endocrinology Concerns for the Office Pediatrician

Top 5 Endocrinology Concerns for the Office Pediatrician. Bassem Dekelbab, MD Assistant Professor of Pediatrics Pediatric Endocrinologist St. John Providence Children’s Hospital/ Beaumont Children’s Hospital. St. John Hospital & Medical Center Pediatric Specialty Care: The Most

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Top 5 Endocrinology Concerns for the Office Pediatrician

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  1. Top 5 Endocrinology Concerns for theOffice Pediatrician Bassem Dekelbab, MD Assistant Professor of Pediatrics Pediatric Endocrinologist St. John Providence Children’s Hospital/ Beaumont Children’s Hospital St. John Hospital & Medical Center Pediatric Specialty Care: The Most Frequent Reasons for Calling an Expert Thursday, May 8, 2014

  2. Nothing to disclose

  3. Topics to cover Labs abnormalities that trigger referral in the following areas: • Thyroid functions • Obesity and excessive weight gain • Early puberty • Short stature • Glucose issues

  4. Thyroid Case # 1 • 15 yr girl with nervousness, palpitations, difficulty concentrating at school. No goiter on exam. Her TSH was normal 1.4, but her total T4 was increased 16.4 (Nl 4.7-12.4) • Additional tests? • Diagnosis? • Treatment?

  5. Thyroid Hormone Transport • More than 99% of circulating T4 and T3 is bound (FT4 0.03%, FT3 0.3%) • Thyroxine-binding globulin (TBG): 75% • Transthyretin (TTR), also called thyroxine-binding prealbumin (TBPA):10%-15% • Albumin:7% • HDL: 3%

  6. Increased Total T4 and T3by Increasing TBG • Drugs • Oral contraceptives and other sources of estrogen • Methadone • Clofibrate • 5-Fluorouracil • Heroin • Tamoxifen • Conditions • Pregnancy • Infectious/chronic active hepatitis • HIV infection • Biliary cirrhosis • Acute intermittent porphyria • Genetic factors

  7. Decreased Total T4 and T3 by Decreasing TBG Levels or Binding of Hormone to TBG • Drugs • Glucocorticoids • Androgens • L-Asparaginase • Salicylates • Antiseizure medications, phenytoin, carbama-zepine • Furosemide • Conditions • Genetic factors • Acute and chronic illness

  8. Thyroid Case # 2 • 13 yr girl with nervousness, palpitations, difficulty concentrating at school. No goiter on exam. Her TSH was normal 0.8 , but her free T3 was increased 5.8 pg/ml (Nl 2.3-5 pg/ml SJH , 2.3-4.2 pg/ml WBH) • Additional tests? • Diagnosis? • Treatment?

  9. Production of T4 and T3 • T4 : primary secretory product of the thyroid • T3 is derived from 2 processes • About 80% of circulating T3 comesfrom deiodination of T4 in peripheral tissues • About 20% comes from direct thyroid secretion • T4 is biologically inactive in target tissues until converted to T3 • T3 :the biologically active hormone responsible for the majority of thyroid hormone effects

  10. Thyroid Function Tests: Normal Range Ped Endo Rev Oct 2007

  11. Thyroid Case # 3 • A 13 year old girl is experiencing fatigue. She is recovering from Sinusitis. Her thyroid is easy to feel on exam. Free T4 is 1.1 and TSH is 4.6 Thyroglobulin antibodies are positive • Does she have primary hypothyroidism? • Are these results likely the cause of her symptoms? • What additional tests if any are indicated?

  12. Thyroid Autoantibodies Thyroid Peroixdase (TPO) and Thyroglobulin (TG) Ab • Appear secondary to thyroid injury • TPO Ab more specific • Present in about 5% of children: non-specific • When to order: TSH, Goiter • mildly TSH (risk of hypothyroidism in future) • No need to repeat for monitoring • No treatment for positive Ab with normal thyroid function

  13. Thyroid Case # 4 • 8 mo female infant is being evaluated for FTT. Thyroid studies showed TSH 6.7 mIU/ml with normal FT4 1.1 ng/dl • Additional tests? • Imaging studies? • Diagnosis? • Treatment?

  14. Thyroid Function Tests: Normal Range Ped Endo Rev Oct 2007

  15. Obesity Case # 1 • As part of an obesity work-up in a 12 year old girl whose height is increasing along the 90th %ile, you find free T4 of 1.10 and TSH of 6.5 (normal 0.5-4.5). There is no goiter and the exam is normal except for the obesity. • Does she have hypothyroidism? • Is this “subclinical hypothyroidism”? • Should you refer right away for evaluation and treatment or follow in your office?

  16. Thyroid function in the nutritionally obese child and adolescent Current Opinion in Pediatrics 23(4), August 2011

  17. Obesity Case # 2 • 14-year 3-months African American female • Ht 160.4 cm, wt 78.1 kg, BMI 30.4 • Mild facial acne. No abnormal hair distribution. No acanthosis. Lost 15 lb over last year • FBS 88, Hgb A1c 5.8%, normal thyroid studies • Fasting insulin 20.7 mcunit/ ml [normal 4-17] • Total cholesterol 159 • HDL chol 62 • LDL chol 87 • TG 48

  18. Insulin Resistance in Children • The use of any index of Insulin Resistance is complicated by • Lack of standardized measures for the quantification of insulin • Need to be assured that the blood sample is obtained in a truly fasting state • Increase in IR from stage 1 to stage 3 of puberty • Endocrine Society Clinical Practice Guideline 2008

  19. Insulin Resistance in Children • In the clinical setting, fasting insulin is an unreliable measure of insulin sensitivity, and testing of aliquots of a common sample assayed in different laboratories has shown disparate results. • Even if a uniformly reliable insulin assay became available, separate standards would need to be developed by genders, ethnic groups, and pubertal stages On behalf of ESPE-LWPES-ISPAD-APPES-APEG-SLEP-JSPE, and the Insulin Resistance in Children Consensus Conference Group Clin Endocrinol Metab. Dec 2010; 95(12): 5189–5198

  20. Laboratory Assessments to be Considered in Primary Care Settings

  21. Early puberty case • 7 yr 10 mo WF with pubic hair for few months • Some body odor. No oily skin, acne, axillary hair, breast or vaginal bleeding / discharge. • Rapid wt gain • PE: few pubic hairs of labia majora • 17 hydroxyprogesterone 11 ng/dL [3-82] • DHEA-S of 176.4 mcg/dL [19-144] • FSH 0.6 mU/mL, LH less than 0.1 mU/mL • Total testosterone of 11 ng/dL [3-10] • Thyroid studies were normal • Bone age 8 yr 9 mo

  22. Premature Adrenarche • Pubarche before 8yr in girl and 9 yr in boys • More common in girls, 3-8 yr • Obesity, low birth wt, family Hx of PCOS • Racial/ ethnic • CNS abnormalities • Growth velocity may be increased, Taller than avg • Bone age advanced by 1-2 yr • DHEAS, DHEA, 17OHP, Androstenedione, and Testosterone may be elevated for chronologic age but normal for Tanner stage • Normal puberty progress/ final height • Insulin resistance, PCOS

  23. Short Stature Case 14 yr WM with short stature • GV 2 inch over last yr • PMH: neg, no Med • F 5f 8in, M 5f 5in • Bone age 12 yr 6 mo • Normal TSH/ FT4 • Low IGF-1 206 ng/ml

  24. Insulin like Growth Factor [IGF-1] Age: less accurate < 5 yr Nutrition, Liver/ renal disease, Pubertal status, hypothyroidism Lab Assay !!! Brain Tumor/ Cranial radiation IGF-II Less GH-dependent, but less age dependent IGF-Binding Protein [IGF-BP3] Age Less nutrition-dependent

  25. Glucose Issue Case-1 9 yr WF with + urine dipstick during routine PE • UA: negative, FBS 124, Hgb A1c 5.9% • Asymptomatic, normal BMI / exam • FMH: • Father FBS 110, OSA [uses CPAP] • Paternal GF 61 yr [type 2 DM for 30 yr] • Studies: • Fasting BS 110, 2hr postmeal BS 142 • Home MBG: 80-90s AM, 100-120 bedtime [160,180] • Human Insulin Ab 3.6 [ 0 - 5 ] • Anti GAD 65 Ab 34 [< 0.5 ] • ICA 512 Ab 6.8 u/ml [ < 1.0 ] • She developed frank diabetes in 1 yr

  26. Diagnostic sensitivity and specificity of islet antigen autoantibodies

  27. Effect of multiple autoantibodies on the risk of developing type 1 diabetes mellitus

  28. 10 yr WF seen for routine exam Positive glucose on urine dipstick Negative repeat urine dipstick 2 hr later, but random meter glucose 153 No symptoms Past Med History: unremarkable Meds: Singulair, Nasonex, Claritin Family Med History: Paternal uncle and grandmother have diabetes. Dad has hypothyroidism Normal exam and BMI Glucose Issue Case-2

  29. Oral Glucose Tolerance TEST OGTT (75 gm) 0 min: 102 30 min: 174 60 min: 216 90 min: 233 120min: 195 Hgb A1c: 6.3 % (lab) Started on 5 units of Lantus insulin daily Hgb A1C 5.8% (office) Diabetes Autoimmune Panel: negative [Insulin, Islet cell, Glutamic Acid Decarboxlyase GAD antibodies]

  30. On Insulin Off Insulin DAD

  31. Beta Cell and Insulin Secretion

  32. Glucokinase inactivating mutations Homozygous mutation: Neonatal Diabetes Heterozygous mutation: MODY 2 Persistent mild hyperglycemia: Routine screening, pregnancy Hemoglobin A1c around the upper limit of normal OGTT: small increment increase Parents may have “T2DM”, autosomal Dominant: one parent will have mildly increased FBS No significant deterioration, no complications No treatment is needed

  33. Thank You Any Easy Question ?

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