Advanced Practice Education Associates. Endocrine

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1 Advanced Practice Education Associates Endocrine

2 Overview Diabetes Thyroid Disease 162 Copyright 2016 Advanced Practice Education Associates

3 DIABETES MELLITUS What is the BMI cut point for screening adults with one or more risk factors for diabetes? kg/m kg/m kg/m kg/m 2 Screening: ADA Recommends Annual screening for BMI > 25 kg/m 2 and one or more risk factors for DM Entire population > 45 years every 3 years if screening is normal DM Risk Factors Age > 45 years BMI > 25 kg/m 2 Family history FDR (first degree relative) Habitual physical inactivity HTN (140/90 or >) HDL < 35 and/or trigs > 250 Women with PCOS History of vascular disease Delivery of a macrosomic infant (9 pounds) or gestational diabetes African American, Hispanic, Native American, Asian-American, Pacific Islanders Previously identified A1C > 5.7%, Impaired glucose tolerance, IFG What about Asians? BMI cut point for screening overweight/obese Asians for Pre DM/DM: o 23 kg/m 2 American Diabetes Association. Classification and diagnosis of diabetes. Sec. 2. In Standards of Medical Care in Diabetes Diabetes Care 2015; 38 (Suppl. 1): S8-S16 ADA Diagnostic Criteria T2DM Pre-DM * 6.5% A1C % * 126 FPG mg/dl * > 200 mg/dl 2h GTT mg/dl > 200 mg/dl Random *Should be confirmed by repeat testing unless hyperglycemia is unequivocal. American Diabetes Association. Standards of Medical Care in Diabetes Care 2015.

4 Evidence Based Management Initial Management T2DM, IFG Set A1C goal Reduce cardiovascular risk factors Evaluate use of metformin Physical exam and monitoring Mr. Smith is 72 years old. He has been diagnosed with T2DM. What is a reasonable A1C goal for him? 1. A1C < 8% 2. A1C < 7% 3. A1C < 6% 4. A1C < 5% ADA Suggest A1C Goals by Age for T2DM A1C < 7% for most adults with Type 2 diabetes A1C < 8% for older patients A1C < 6% for Type 1 diabetes patients A1C < 6% for most pregnant patients Initial Management IFG Lifestyle, Lifestyle, Lifestyle!!! o Weight loss 7% body weight o Physical activity to at least 150 minutes per week of moderate activity For IFG consider Metformin if: o A1C % o Less than 60 years old o BMI 35 o Women with history of gestational diabetes Reducing Risks: T2DM, IFG Recommendations: o Increased physical activity o Weight loss as needed o Smoking cessation o Nutrition intervention: less saturated fat, more omega-3 and fiber o STATINS for T2DM! American Diabetes Association. Cardiovascular disease and risk management. Sec. 8. In Standards of Medical Care in Diabetes Diabetes Care 2015; 38 (Suppl. 1): S49-S Copyright 2016 Advanced Practice Education Associates

5 Exercise Recommendations Reduce sedentary time When sitting: Get up and move at least every 90 minutes Exercise of at least 8 weeks duration shown to decrease A1C 0.6% in T2DM even if no weight loss plus many other benefits! American Diabetes Association. Foundations of care: education, nutrition, physical activity, smoking cessation, psychosocial care, and immunization. Sec. 4. In Standards of Medical Care in Diabetes Diabetes Care 2015; 38 (Suppl. 1): S20-S30 Diastolic BP < 90 mm Hg Blood Pressure: < 140 SBP, DBP o Lower targets? (< 80 mmhg) may be appropriate for patients with long life expectancy o Those with chronic kidney disease o Elevated urine albumin excretion o harmonization with JNC 8 American Diabetes Association. Cardiovascular disease and risk management. Sec. 8. In Standards of Medical Care in Diabetes Diabetes Care 2015; 38 (Suppl. 1): S49-S57 DM Monitoring - History and Physical Exam Provider Frequency Comments Responsibility Ask about smoking Every visit Ask every patient at every visit; encourage cessation Blood Pressure Every visit < 140/80 if average risk for stroke Foot Exam Usually every 3 months; unless PVD or neuropathy Discuss importance of daily self-checks by patient present then every visit Dilated eye exam Annually at onset for T2DM, after 5 years of dx if T1DM Encourage patient to bring copy of report to PCP appointment Dental examination Annually Periodontal disease more severe in patients with DM DM Monitoring - Labs Provider Frequency Responsibility Fasting serum lipid Annually profile Comments Lifestyle modifications; Patients ages without additional CV risk factors, consider moderate intensity statin and lifestyle modifications; All patients of all ages with DM and overt CVD, high intensity statin therapy should be added to lifestyle Goal is <7% in most patients A1C Every 3 months if not at goal; otherwise, twice annually Urinary albumin to Annually At diagnosis for Type 2 Monitor 3-5 creatinine ratio years after diagnosis of Type 1 Serum Creatinine Initially As indicated depending on renal status

6 Medications ADA First Life Treatment Evidence Level: A Metformin is first choice for oral treatment unless there is a contraindication Metformin reduces CV risks!!! Mrs. Jones is a newly diagnosed T2DM. In which items(s) below would metformin be a safe choice for her? Choose all that apply. 1. Active Hepatitis C 2. Serum creatinine: Heart failure 4. Binge drinking Serum Cr > 1.4 females, > 1.5 males Metformin Metformin often chosen for: o Effect on glucose o Absence of weight gain or hypoglycemia o Low incidence of side effects o Low cost o Reduction in all cause mortality What are the two most common side effects of metformin? Mrs. Smith is a newly diagnosed T2DM. She has been started on metformin and is tolerating a dose of 1000 mg BID. How much is her A1C expected to decrease in the next 3 months? % % % 4. 3% Evidence Based Management: Second Agent Match patient characteristics with medication Additional Notes: 166 Copyright 2016 Advanced Practice Education Associates

7 Diabetes Medications Drug Class Biguanide Sulfonylurea Alpha glucosidase inhibitors DPP-4 inhibitor GLP-1 TZD SGLT2 Examples Metformin Glimepiride, glipizide, glyburide Acarbose (Precose), miglitol (Glyset) Alogliptin (Nesina), linagliptin (Tradjenta), saxagliptin (Onglyza), sitagliptin (Januvia) Exenatide (Byetta, Bydureon), Liraglutide (Victoza), Dulaglutide (Trulicity), Albiglutide (Tanzeum) Pioglitazone (Actos), Rosiglitazone (Avandia) Canagliflozin (Invokana), dapagliflozin, empagliflozin Metformin plus what else? Choose medication from another class based on patient characteristics, cost, side effects, tolerability, etc. Add a second agent, like a second oral agent, a glucagon-like peptide 1 (GLP-1) receptor agonist, or insulin. Level of evidence: A Diabetes Care Volume 37, Supplement 1, January 2014 Pharmacologic Management Sulfonylurea agents o Potentiate insulin secretion (secretagogue) o May cause hypoglycemia, tend to cause weight gain o Ideal use: insulinopenic patients, non-obese/mild obesity o Use in combo or as monotherapy o Reduces A1C about 1-2% o Cost: cheap! DPP-4 Agents o Dipeptidyl peptidase-4 inhibitor o Slows inactivation of the incretin hormones (which lowers BG) o Use in combo or as monotherapy, but not initial o Gliptins o Reduces A1C about 0.7% o Cost: $ /month GLP-1 Agonists o Glucagon like peptide o Increases production of insulin in response to elevated BG levels o Decreases A1C 1-1.5% o Almost never hypoglycemia o Average weight loss is 2-6 pounds

8 Comparison of GLP-1 Drug Dosing A1C Reduction Cost Albiglutide (Tanzeum) Once weekly 1% $330 Exenatide (Byetta) BID 1% $430 Exenatide ER (Bydureon) Once weekly 1.5% $440 Dulaglutide (Trulicity) Once Weekly 1.5% $500 Liraglutide (Victoza) Daily 1.5% $ Pharmacologic Management TZDs o Thiazolidinedione (Pioglitazone, rosiglitazone) o Preserves beta cell function, improves insulin o High dose associated with bone fractures, osteopenia o Contraindicated in heart failure o Reduces A1C about 0.7% o Cost: $ /month SGLT2 inhibitors o Dapagliflozin (Farxiga), Empagliflozin (Jardiance), Canagliflozin (Invokana) o Prevents reabsorption of renal glucose, increases glucose excretion o Increased risk of UTI, vaginal yeast infections, weight loss o Cost: $450/month SGLT-2 Inhibitor 90% glucose blocked by inhibiting SGLT-2 Additional Notes: 168 Copyright 2016 Advanced Practice Education Associates

9 The Medications Class Advantages Disadvantages Comments Sulfonylureas (SU) Cost, long history, reduction in micro/macro vascular events, reduces BG levels Causes weight gain and produces hypoglycemia DPP-4 (Dipeptidyl peptidase-4 inhibitors) GLP-1 (incretin mimetics) Thiazolidinedione TZDs SGLT2 Inhibitors Insulin (basal or NPH in evening); then meal time insulin with biggest meal No hypoglycemia, weight neutral, oral agent Weight loss, delays gastric emptying No hypoglycemia, improves insulin sensitivity Weight loss, lowers BP, glucose excreted in urine Long history, reduction in micro/macro vascular events, reduces BG levels Expensive, long term effects not known Must be injected, expensive, long term effects not known Expensive, weight gain, edema, high dose associated with bone fractures Expensive, Hyperkalemia, hypotension Weight gain, hypoglycemia Glimepiride or short acting glipizide at mealtime preferred Drug suffix is "gliptin" (Januvia Onglyza, Tradjenta) Enhances insulin secretion, (Byetta, Victoza) Pioglitazone, Do not use in heart failure! (Actos) CR Cl > 60 ml/min No long term data Stop SU when initiating meal time insulin What meds are safe when combined? Metformin Plus EVERYTHING! Insulin* Plus Any of these: Metformin, GLP-1 agonists, DPP-4 inhibitors, SGLT2 inhibitors Usually discontinue sulfonylureas, glitazones after initiating insulin. SU plus insulin is less efficacious, more weight gain; can use insulin alone and achieve same result for less cost Additional Notes:

10 Patient Scenarios Patient A1C 5.9%, newly diagnosed with IFG 55 y/o female, intolerant of metformin, A1C 10.2% 79 y/o male, A1C 8.9%, newly diagnosed DM 62 y/o female taking metformin, A1C 7.9%, fixed budget (A1C goal < 7%) 27 y/o male, A1C 6.9%, newly diagnosed T2DM 35 y/o obese female on metformin, A1C 8.9%, Cadillac insurance 79 y/o male on metformin with A1C 7.9%, needle phobic 55 y/o female, takes metformin plus glipizide, A1C 10.2% Do we need med? What Medication? When should you consider insulin? Consider initially when A1C > 10% Fasting glucose > 250 mg/dl After maxing out orals Symptoms of hyperglycemia Pregnant patients Consider it EARLY! Types of Insulin Regular and NPH insulin are available OTC Insulin Type Onset of Action Duration Examples Immediate <.25 minutes 2-4 hours Novolog, Humalog, Apidra 3-5 hours Regular 30 minutes 6-8 hours Humulin, Novolin Mixed (rapid plus long acting) Fast and Long hours NovoLog Mix 70/30 Humalog Mix 75/25, 50/50 Humulin 70/30 NPH 1-2 hours hours Novolin, Humulin Long Acting 1 hour 24 hours (peakless) Lantus, Levemir, Toujeo 170 Copyright 2016 Advanced Practice Education Associates

11 Basal Insulin Formulations Long Acting: Lantus, Toujeo (insulin glargine), Levemir (insulin detemir), NPH Peakless insulin Mimics basal insulin secretion Action is predictable from day to day (consistent absorption!) Greatly improved A1C levels!!!!! Duration up to 24 hours Expensive Initiating Basal Insulin Consider a bedtime basal insulin like NPH, basal insulin s (Lantus, Levemir) Start about u/kg as bolus at bedtime or 10 units Increase basil insulin by 2-3 units every 2-3 days until fasting glucose is at goal. What is the goal? Once you need better control Basal Plus: short acting insulin given before biggest meal usually Basal Bolus: bolus at each meal; frequent BG checks (motivated patient) THYROID DISEASE Thyroid Background T 4 is thyroxine It s called T 4 because it contains 4 iodine atoms (tetraiodothyronine) T 4 can be bound or free thyroxine Bound T 4 is attached to proteins and becomes too large to enter cells and be effective Free T 4 is NOT attached to proteins and so can enter target tissues and affect metabolism Thyroid Background T 3 is triiodothyronine It s called T 3 because it contains??? iodine atoms T 3 can be bound or free Most circulates as Bound T 3 (reverse T 3 ) 99.5% of T 3 is completely bound to carrier proteins WHY IS THIS SOOOO IMPORTANT? (serves as about a 1 week reserve of T 3 ); Activity: T 3 >>>>> T 4 FYI: T 3 is 5 times more active than T 4 Thyroid Stimulating Hormone TSH is produced by the anterior pituitary TSH is a messenger

12 Hypothyroidism Reduction in the amount of circulating free thyroid hormone Resistance to the action of thyroid hormone Common cause is Hashimoto s thyroiditis (autoimmune) 5-8 times more common in women (especially > 50 years) 2 nd most common endocrine problem (2-5 cases/100 persons in US) A 57 year old female has fatigue, weight gain. Thyroid disease is suspected. How should she be screened? 1. TSH only 2. TSH, T4 3. TSH, T3,T4 4. Complete thyroid panel TSH Considerations IF.. Serum TSH normal: no further testing Serum TSH increased: repeat, add free T4 Serum TSH decreased: repeat, add free T4 and T3 Suspected pituitary or hypothalamic disease present, TSH plus free T4 initially TSH normal and patient has convincing symptoms of hyper/hypo, then Free T4 Thyroid Summary TSH T4 T3 Primary Hypothyroidism Normal Subclinical Hypothyroidism Normal Normal Primary Hyperthyroidism Elevated Normal Primary Hypothyroidism: How do we replace? L-thyroxine (synthetic T4) PO daily, in AM, on empty stomach (30-60 mins) T4 is a prohormone and mostly inactive Deiodinated to become T3, the active form Adults need 1.6 mcg/kg/day Based on ideal body weight, not necessarily actual Start with full replacement dose in healthy, young patients Use clinical judgment when prescribing 172 Copyright 2016 Advanced Practice Education Associates

13 How do we replace? Pounds Kilograms Replacement mcg Levothyroxine Tabs: 25 mcg, 50 mcg, 75, 88, 100, 112, 125, 137, 150, 175, 200, 300 Replacement in Middle/Older Adults Patients years old: start at 50 mcg daily Older adults, multiple co-morbids, cardiac disease: consider 25 mcg daily Increase every 3-6 weeks by 25 mcg until normal TSH Small decreases in thyroid replacement dose may be needed as the patient ages Upper limit of normal in TSH in 80 year old 7.5 mu/l A 35 year old female complains of fatigue. Thyroid studies are ordered. What is your diagnosis? TSH: Norm: T4: Norm: Screening # Screening # 2 (6 weeks later) Primary hypothyroidism 2. Subclinical hypothyroidism 3. Primary hyperthyroidism 4. Subclinical hyperthyroidism Subclinical Hypothyroidism Treatment is controversial TSH > 10mU/L: Treat TSH : most do not recommend treatment; monitor 6-12 months unless patient becomes more symptomatic Additional Notes:

14 A 45 year old patient has subclinical hypothyroidism, TSH 6.2. What are the major risks of prescribing levothyroxine? 1. There are very few risks 2. Hyperlipidemia, atrial fibrillation 3. Accelerated bone loss, atrial fibrillation 4. She may develop hypertension and tachycardia A 55 year old patient was diagnosed with hypothyroidism 6 weeks ago. How should her levothyroxine dose be managed today? Normal TSH: mu/l Normal Serum Free T4: ng/dl Diagnosis TSH T4 Replacement levothyroxine 6 weeks ago mcg daily Today 18.4??? 1. Increase levothyroxine to 100 mcg 2. Increase levothyroxine to 75 mcg 3. Decrease levothyroxine to 25 mcg 4. Discontinue levothyroxine Levothyroxine Tabs: 25 mcg, 50 mcg, 75, 88, 100, 112, 125, 137, 150, 175, 200, 300 A patient has hypothyroidism. Her last TSH was 2.5. She takes her levothyroxine in the AM on an empty stomach. What will happen to her TSH in each of the following situations? Normal TSH: mu/l 1. Taking levothyroxine with food 2. Taking 2 pills daily instead of one 3. Taking levothyroxine with vitamins 4. Switching to a generic form of levothyroxine Follow Up Recheck TSH 4-6 weeks after replacement starts, and then after each dose change until euthyroid Monitor TSH annually unless symptoms develop 174 Copyright 2016 Advanced Practice Education Associates

15 Hyperthyroidism Body's tissues are exposed to an increased level of circulating thyroid hormone (T3 and T4) T3 and T4 are 99% protein bound and thus not active T3 >>>>> activity than T4 Most common cause is Grave's disease 0.5 cases/1000 persons in US A 27 year old male reports a recent 15 pound weight loss, extreme fatigue and inability to sleep at nighttime because he is too keyed up. What is the most appropriate action for the NP? Select all that apply. Normal TSH: mu/l Normal Serum Free T4: ng/dl 1. Refer to endocrinology 2. Initiate levothyroxine 88 mcg 3. Consider initiating propranolol for symptom management 4. Initiate RAI (radioactive iodine) Additional Notes: Measurement Results BP 150/90 HR 120/min Temp 99.5 F TSH 0.01 T4 3.4

16 CHECK YOUR KNOWLEDGE A 35 year old female as diagnosed with hypothyroidism 6 weeks ago and is being replaced with 88 mcg of levothyroxine daily. Based on today s labs, what action is appropriate? Normal TSH: mu/l Measurement Results Normal Serum Free T4: ng/dl TSH 1.4 mu/l 1. Increase the dose to 100 mcg 2. Increase the dose to 112 mcg 3. Decrease the dose 4. Continue the same dose Levothyroxine Tabs: 25 mcg, 50 mcg, 75, 88, 100, 112, 125, 137, 150, 175, 200, 300 T4 2.5 mu/l A 45 year old female has hypothyroidism. Which measures should be used to determine how much levothyroxine replacement she needs? Select all that apply. 1. Actual weight 2. Ideal body weight 3. BMI 4. TSH Measure Patient Actual Weight 155 lbs. Ideal Weight 122 lbs. BMI 26.6 TSH 35.6 The NP is initiating levothyroxine for primary hypothyroidism in a 75 year old female. Her projected levothyroxine needs are 88 mcg per day. What dose would be the most appropriate for initial therapy in this client? mcg per day mcg per day mcg per day mcg per day Additional Notes: 176 Copyright 2016 Advanced Practice Education Associates