Disclosures Common Medications in Pediatric Endocrinology I have nothing to disclose Carrie A. Tolman, CPNP Nationwide Children s Hospital Objectives The Endocrine System Review common endocrine disorders Discuss treatment options for common endocrine disorders in pediatrics The Endocrine System 5 Main Functions Produce hormones Regulate metabolism Maintain fluid and electrolyte balance in the blood Moderate growth and development, reproductive development Regulate the body s response to stress Diabetes Type 1 Diabetes Autoimmune condition that destroys beta cell function Become completely insulin dependent Type 2 Diabetes Inefficient use of insulin Insulin resistance Ultimately beta cell function failure 1
Diabetes Goals of Therapy Mimic physiologic insulin release Maintain normoglycemia as much as possible Prevent prolonged hyperglycemia Prevent acute hypoglycemia Hemoglobin A1C of <8%. Why Tight Control? MDI Insulin Therapy Basal Insulin Long acting insulin Usually given once daily Ideally 40-50% of daily insulin Bolus Insulin Rapid acting insulin Carb coverage at meal/snack time Requires carb counting ability Ideally given immediately BEFORE eating High blood glucose correction Bolus Calculation Basal/Bolus Therapy 2
Long-Acting Insulin Lantus/Basaglar (glargine) U-100 (100units/ml) Negligible Peak Up to 24 hour duration Levemir (detemir) Duration of action between 7.6 hrs and 24 hours Usually requires BID dosing Long-Acting Insulin Toujeo (glargine) U-300 (300 units/ml) More concentrated version of Lantus Advise patients to dial the same dose as their current dose, gives 3 times the dose in smaller quantity Approved in 18 years and older Tresiba (degludec) U100 and U200 Negligible Peak May last longer than 24 hours Makes it good for patients that may miss doses Approved in 18 years and older Rapid-Acting Insulin Humalog/Novolog Onset of action is immediate to 15 minutes Peaks at 1-2 hours Duration of Action 3-4 hours Apidra Children 4 years and older Onset of action is immediate Peaks at around 100 minutes Duration of action of 2-3 hours Methods of Delivery Vials Disposable Pens Reusable pen with disposable cartridges Insulin Pump Therapy Pump Models Continuous subcutaneous insulin infusion Decreases need for injections! Daily basal rate Bolus at meals/snacks and for corrections Meters communicate with the pump Moving closer to full closed loop system with continuous glucose monitor (CGM) 3
4/5/17 Glucagon Used in case of severe hypoglycemia Unconscious Unable to take po due to risk of choking Refusing oral treatment Acts on liver glycogen to release glucose into the blood stream Given IM <20 kg give 0.5 ml >20 kg give 1 ml May cause vomiting-roll patient to side after administration Mini-dose glucagon Type 2 Diabetes Increasing rates due to childhood obesity Limited options available in children Very few oral medications studied in pediatrics Lifestyle changes are first line treatment! Bariatric surgery is now viewed as a treatment Insulin is an option, but not usually 1st line Unfortunately, beta cell destruction is more rapid in youth than adult counterparts Type 2 Diabetes T2DM Treatments Insulin & Metformin are the only 2 FDA approved in pediatrics Biguanides: Decrease hepatic glucose output, increase hepatic & muscle sensitivity w/o direct effect on beta cell function Thiazolidenediones (TZDs): Improve peripheral insulin sensitivity Sulfonylureas: Increase insulin secretion (secretagogue) Meglitinide: Short term promotion of glucose stimulated insulin secretion Glucosidase inhibitors: slow CHO absorption Type 2 Diabetes Thyroid Due to side effects, dose should be titrated slowly. Before initiating therapy, need to assess renal and hepatic function 500 mg once daily for 2 weeks Increase in 500 mg increments every 1-2 weeks as tolerated Max daily dose 2000 mg daily XR form associated with fewer GI side effects Always take with food! Metformin is the only oral medication approved (down to age 10 years) Adequate monotherapy for about 50% of youth with T2DM Biguinide insulin sensitizer Binds in the liver to decrease hepatic glucose production Improves glucose uptake at the muscle and fat Most common side effects are GI-diarrhea, bloating, nausea Most severe side effect is lactic acidosis-rare in children and usually only in context of renal failure Converts iodine from food to T3 and T4 Controls metabolism Regulated by pituitary (TSH) through negative feedback 4
4/5/17 Hypothyroidism Congenital (CH) Found on newborn screen by TSH Indicates agenesis, dysgenesis, ectopy or non-functioning thyroid gland Autoimmune Hashimoto s thyroiditis Associated with other autoimmune conditions (diabetes, celiac) Genetic disorder Down Syndrome Turner Syndrome Panhypopituitarism Post-ablative/post-surgery Thyroid Replacement Levothyroxine (Synthroid, Levoxyl, Levothroid) For CH, need to start ASAP!! Dose at the same time of day Can be crushed and mixed in small amount of water, breastmilk, or non-soy formula Thyroid Dosing L-thyroxine Interactions TSH >10 Age appropriate dosing of levothyroxine (L-thyroxine) Age 1-3 years 4-6 mcg/kg/day Age 3-10 years 3-5 mcg/kg/day Age 1 and up 2-4 mcg/kg/day OR 100 mcg/m2/day TSH 4.5-10 (normal free T4) Mixed recommendations on treatment Consider retesting-70% retested are normal TSH <4.5 No recommendations support treatment of subclinical hypothyroid in children Foods Do not take L-thyroxine at the same time as: Soy/soybean products Espresso coffee Walnuts Grapefruit High fiber foods Cottonseed meal L-thyroxine Interactions Precocious Puberty Medications Iron supplements Calcium supplements Multivitamins SSRIs Vitamin K-Enhanced anticoagulant effect Centrally mediated-true pituitary driven puberty Pubertal development seen Before age 8 years in girls Before age 9 years in boys Concern is compromise of adult height 5
4/5/17 Precocious Puberty Depo-Lupron-PEDS Hypothalamic-Pituitary-Gonadal Axis GnRH agonist causes downregulation of gonadotropin secretion when given continuously IM injection Monthly dosing 7.5 mg, 11.25 mg, 15 mg dosing Every 3 months 11.25 mg or 30 mg dosing May see progression of puberty in the first May include vaginal bleeding in females Lasts usually a few weeks at most Most common side effects Injection site pain/swelling Headache Weight gain Supprelin-LA is a long-acting IMPLANT Also GnRH agonist Supprelin gives 65 mcg histrelin daily over a year Cortisol Deficiency Placed on the inner aspect of upper arm Outpatient procedure with local anesthesia Most common adverse events are minor Adrenal cortical hormone under the influence of ACTH from the pituitary Stress hormone Responsible for helping maintain BP, glucose levels, immune response Symptoms may be fatigue, hypoglycemia, low BP, slow to heal/recover from illness Bruising, redness, pain at insertion site May see progression of pubertal symptoms in first few weeks 6
Cortisol Deficiency Causes: Autoimmune Addison s Disease Genetic Congenital Adrenal Hyperplasia-on newborn screen Hypopituitarism Adrenal failure Steroid suppression of adrenal glands Cortisol Replacement Replace with hydrocortisone Cortef-TID dosing 10-15 mg/m 2 daily based on body surface area Prednisone or Dexamethasone-BID dosing Used only once skeletal maturation has been reached 5mg to 7.5 mg BID Stress Dose Stress Dosing-Oral Fever >101 Nausea, vomiting, diarrhea Infectious process-strep, pneumonia Prior to surgical procedure (contact Endocrinologist for instructions) Triple the oral dose until well Repeat dose x1 if emesis Stress Dose If unable to keep oral stress dose down, will need to give injectable Solu-Cortef Give in case of severe injury, unconscious Given IM Then call 911 or get to ED Patients with adrenal insufficiency should wear a MedicAlert ID Any Questions? 7