1. Pediatric Endocrinology Sarah Lawrence Division of Endocrinology CHEO

2. Type 1 Diabetes

3. Epidemiology of Type 1 Prevalence 0.4% of individuals < 18 years Increased risk to family members Sibling5% Father with diabetes6-8% Mother with diabetes2-3% Identical twin30-50%

4. Type 1 Diabetes % Beta Cells Time Genetic predisposition Environmental insult Antibody positive Diabetes

5. Diagnostic Criteria FBG > 7.0 mmol/L OR Casual BG > 11.1 with symptoms OR 2 hour BG in OGTT of > 11.1

6. INITIAL MANAGEMENT

7. New Onset DM: Baseline labs Glucose, urea, creat, lytes, gas Urine for glucose and ketones TSH, thyroid antibodies

8. New Onset DM: Diet 1000 kcal + 100 kcal/year of age i.e. 8 yo child = 1000 + 800 = 1800 kcal 3 meals and 3 snacks Currently use exchange system, but changing to carbohydrate counting Starch15 g Fruit/Sugar10 g Dairy 6 g

9. BG Targets Age (years)Premeal target (mmol/L) HbA1c Target (%) < 56-12< 9.0% 6-124-10< 8.0% >124-8< 7.0%

10. HbA1c & BG levels

11. New Onset - Insulin Dose By weight: 0.5 – 0.75 unit/kg/day 2/3 am, 1/3 pm 2/3 N, 1/3 H i.e. 8 yo, 25 kg By age Am N = 1 unit/year of age AM H is 50% of this PM dose is 50% of the am dose 8 yo am 8N4H pm 4N2H 25 x( 0.5) = 15 Am 10 U 7 N3 H Pm 5 U 3.5 N1.5 H

12. amnoonpm hs am Twice Daily Insulin: NPH + R/analogue

13. amnoonpm hs am Three Times Daily Insulin: NPH + R/analogue

14. Basal-Bolus Insulin Therapy: Insulin Glargine at HS and Mealtime Lispro or Aspart BDLHS Insulin Glargine or Levemir Insulin Lispro or Aspart Time of administration B, breakfast; L, lunch; D, dinner; HS, bedtime. Adapted from: 1.Leahy JL. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc.; 2002. 2.Bolli GB, et al. Diabetologia. 1999;42:1151–1167. Type 1 DM

15. Basal

16. Insulin Injection Sites Picture of lipohypertrophy

17. Insulin adjustment: basic principles New onset, making daily changes until stabilized Established diabetes Highs: High BG same time of day x 3 consecutive days Increase 10% at a time Lows: Unexplained lows 2x/week same time of day 10-20% at a time

18. Insulin adjustment: basic principles Time of DayInsulin to adjust Morningpm N Noonam R Supperam N Bedpm R amnoonhspmam R R N N

19. Hypoglycemia Causes: Too much exercise/activity for which you did not plan Not enough food and/or delay in getting the meal/snack Too much insulin Treatment: <20 kg10 g CHO >20 kg15 g CHO

20. Hypoglycemia Severe hypoglycemia Glucagon <5 years0.5 mg > 5 years1 mg Minidose glucagon protocol Persistently low but alert and unable to manage orally (e.g. during illness or inadvertent insulin error)

21. DKA: How common is it? At diagnosis of diabetes 15-67% present with DKA Established diabetes 1-10% of patients/year Cerebral edema 0.4-1% of episodes of DKA 25% mortality, up to 35% with severe neurologic deficits

22. Cerebral Edema in DKA Who is at risk? Increased risk in new onset DM, more dehydrated and acidotic patients ?treatment factors – rapid infusion of hypo-osmolar fluids, use of bicarbonate Treatment – early intervention is key Raise HOB, + intubate, reduce fluids Mannitol, hypertonic saline

23. Insulin Dose Adjustment Guidelines for Intercurrent Illness TDD = Total Daily Dose

24. Type 2 Diabetes in Children and Youth

26. Example: 95th Percentile Tracking Age BMI 2 yrs 19.3 4 yrs 17.8 9 yrs 21.0 13 yrs 25.1 For Children, BMI Changes with Age Boys: 2 to 20 years BMI

27. Genetic and Environmental Risk factors for T2DM Ethnicity Female gender Family history T2DM Intrauterine factors Maternal history of gestational diabetes Large for gestational age (>4 kg) Small for gestational age (<2.5 kg) Obesity Sedentary behaviour

28. Development of Type 2 Diabetes Normal Insulin resistance Impaired Glucose Tolerance Type 2 Diabetes

29. Acanthosis Nigricans

30. Metabolic Syndrome in Youth by BMI % with Metabolic Syndrome BMI Percentile

31. Treatment of T2DM in Youth Diabetes education for the family Setting glycemic targets HbA1c < 7.0% Lifestyle modification <10% achieve glycemic targets Pharmacotherapy Metformin has been shown to have short term efficacy and safety in adolescents Insulin rescue is required in those with severe metabolic decompensation at diagnosis e.g. DKA, A1C ≥9.0%, symptoms of severe hyperglycemia, ketonuria

32. Presentation of T1DM vs T2DM Type 1Type 2 Up to ¼ overweight Short Course 25-40% DKA FHx T1DM in 5-10% Predominantly white 85% overweight Indolent course 33% ketonuria 5-25% DKA FHx T2DM 74-100% Minority youth

33. Thyroid Disorders

34. Approach to Goitre +ve Chronic lymphocytic thyroiditis -ve Goitrogen, Dyshormonogenesis Thyroid Antibodies Elevated Hypothyroid TSH Goitre Suppressed Hyperthyroid Normal Euthyroid

35. Hypothyroidism

36. Hypothyroidism - Treatment Medication: Thyroxine 75-100 mcg/m2/day Monitor every 6 months until growth complete, then annually: SSx hypo/hyperthyroidism Growth Sexual maturation TSH (aim for 0.25-5 mU/L) + FT4 Recheck TSH 4-6 weeks after dose adjustment

37. Approach to Goitre +ve Chronic lymphocytic thyroiditis -ve Goitrogen, Dyshormonogenesis Thyroid Antibodies Elevated Hypothyroid +ve/-ve: Graves Hashitoxicosis Subacute thyroiditis Thyroid Antibodies Suppressed Hyperthyroid TSH Goitre Normal Euthyroid

38. Graves Disease

39. Hashitoxicosis / Subacute thyroiditis TSH Time FT4 Hyperthyroid phaseHypothyroid phase

40. Hyperthyroidism - Management Medical Management Antithyroid medications Methimazole (MMI, Tapazole TM ) Initial dose:0.4-0.6 mg/kg/day q8-12h Maintenance:0.2-0.3 mg/kg/day q12-24h Propylthiouracil (PTU) Initial Dose:4-6 mg/kg/day q6-8h Maintenance2-3 mg/kg/day q 12h (-24h) Propranolol Iodide Radioactive Iodine Surgery

41. Hyperthyroidism - Management Side Effects of Antithyroid medications: Mild - pruritis, rash, abdominal pain, neutropenia, Serious - agranulocytosis, arthropathy, lupus-like syndrome, hepatitis

42. Hyperthyroidism - Management Medical Management - Monitoring Initially monitor q 4-6 weeks until T4 stabilized on maintenance doses of MMI/PTU, then q 3-4 months. Clinical status T4, TSH Generally continue treatment for 2 years then try off tx and monitor closely for relapse

43. Approach to Goitre +ve Chronic lymphocytic thyroiditis -ve Goitrogen, Dyshormonogenesis Thyroid Antibodies Elevated Hypothyroid +ve Chronic lymphocytic thyroiditis -ve Colloid goitre Thyroid Antibodies Normal Euthyroid +ve/-ve Grave's disease, Subacute thyroiditis Thyroid Antibodies Suppressed Hyperthyroid TSH Goitre

44. Subclinical Hypothyroidism NormalSubclinicalOvert Hypothyroidism Hypothyroidism TSHN FT4N N

45. Summary Thyroid disorders are common in children and adolescents Most commonly present with goitre secondary to autoimmune thyroiditis or a simple colloid goitre TSH and thyroid antibodies is usually all that is required to establish the diagnosis Ultrasound should be limited to those with a palpable nodule

46. Summary The normal range of TSH may be higher in the pediatric population leading to over- investigation /diagnosis and treatment of thyroid disorders Mild elevations of TSH should be verified on repeat testing TSH <10mU/L often normal on repeat

47. Summary Natural history studies suggest a high rate of spontaneous resolution with autoimmune thyroid disease and thus, repeat testing should be done before committing to lifelong thyroid hormone replacement

48. Precocious Puberty Presence of secondary sexual development by age: 8 in a girl 9 in a boy

49. Approach to Precocious Puberty Growth Velocity Bone Age Premature Thelarche Estrogen Premature Adrenarche Androgens Normal variant Normal Central AndrogensEstrogen Peripheral Pathological Increased Precocious Puberty

50. Approach to Precocious Puberty: Females Premature Thelarche Estrogen Premature Adrenarche Androgens Normal Variant Normal Estrogen +/- androgens Central Ovary Adrenal Other Estrogen Ovary Adrenal Other Androgens Peripheral Pathological Increased Bone age, GV

51. Approach to Precocious Puberty: Males Premature Adrenarche Androgens Normal Variant Normal Testes > 4ml Central Testes Adrenal Other Androgens Testes Adrenal Other Estrogen Peripheral Pathological Increased Bone age, GV

52. Delayed Puberty Absence of secondary sexual development by age: 13 in a girl 14 in a boy

53. Constitutional Delay of Growth and Puberty Hypothalamic or Pituitary Cause Central Low Gonadal Failure Peripheral High LH, FSH Delayed Puberty Approach to Delayed Puberty

54. Delayed Puberty: Investigations Growth records Bone age LH, FSH Sex hormone levels - not needed Other hormones as clinically indicated (T4, TSH, GH, Prolactin, Cortisol)

55. Delayed Puberty: Treatment Constitutional Delay of Growth and Puberty Boys: Treat if psychologically distressed Depot testosterone 75-100 mg IM monthly x 3 Girls: Usually don’t treat (even low dose estrogens cause accelerated skeletal maturation)

56. Delayed Puberty: Treatment Hyper / Hypogonadotropic Hypogonadism Boys: Testosterone intramuscular injection, transdermal patch/gel or orally, gradually increasing to adult doses Girls: Start with low dose estrogen, increasing over 1-2 years, then begin cycling with estrogen and progesterone

57. Short Stature

58. Approach to Short Stature Growth velocity Target Height Familial Short StatureConstitutional Delay Normal Variant IUGR Dysmorphic syndromes Chromosomal disorders Prenatal Medications Chronic disease Endocrine Postnatal ProportionateDisproportionate Pathologic Short Stature Idiopathic Short Stature

59. Chronic Disease

60. Endocrinopathy