Take-Home Messages and Clinical Pearls

Transcription

1 Take-Home Messages and Clinical Pearls Carolyn Becker MD Master Clinician Educator Division of Endocrinology, Diabetes and Hypertension Brigham and Women s Hospital Associate Professor of Medicine Harvard Medical School

2 Disclosures Royalties from UpToDate for 2 chapters on Premenopausal Osteoporosis ($1800/yr)

3 Topics to be Reviewed Diabetes/Obesity Thyroid Adrenal Pituitary Hypoglycemia

4 Case 1 A 54 year old man presents to you for follow up of T2DM, HTN, hyperlipidemia, and obesity (BMI 44 kg/m2). Six months ago, you added sitagliptin to metformin and glipizide for HgbA1C of 8.2%. A1C improved to 7.6% but he wants help with weight loss. He refuses to consider bariatric surgery. In addition to prescribing a diet and exercise program, you plan to switch from sitagliptin to liraglutide 3.0 mg daily to help him lose weight.

5 Current Medications Metformin 1000 mg twice daily with meals Glipizide 5 mg twice daily with meals Sitagliptin 100 mg once daily to be stopped and switched to liraglutide 3.0 mg daily Lisinopril 20 mg daily Atorvastatin 40 mg daily

6 If You Make No Other Medication Changes After Switching to Liraglutide, What is the Patient At Greatest Risk For? A. Rhabdomyolysis B. Hypotension C. Hypoglycemia D. Hypertriglyceridemia E. Hyperkalemia

7 If You Make No Other Medication Changes After Switching to Liraglutide, What is the Patient At Greatest Risk For? A. Rhabdomyolysis B. Hypotension C. Hypoglycemia D. Hypertriglyceridemia E. Hyperkalemia Davies MJ JAMA 314:687 Pi-Sunyer X NEJM 371:11

8 Proper Use of GLP-1 Agonists GLP-1 agonists (eg. liraglutide) are used at a dose of 1.8 mg daily to improve glycemic control in patients with T2DM. At a dose of 3.0 mg daily, liraglutide also is approved for weight loss and can be an adjunct to diet and exercise However, in patients with T2DM on other glucoselowering medications there is a significantly higher risk of hypoglycemia when liraglutide 3.0 mg is added. Hypoglycemic risk was ~25% for either metformin or pioglitazone and ~43% with a sulfonylurea + liraglutide 3.0 mg daily Take home message: reduce sulfonylurea by 50% (or stop completely) when starting high dose liraglutide to help in weight loss in patients with T2DM

9 Case 2 A 28 year old woman comes to you for help in losing weight. She gained 20 lbs after college due to a more sedentary lifestyle and increased caloric intake She gained another 30 lbs in the past year despite trying to cut back on food and increase exercise. Her only medication is paroxetine for depression. She started paroxetine 18 months ago

10 After Stopping Paroxetine, Which of the Following Would You Begin for her Depression? A. Amitriptyline B. Mirtazapine C. Venlafaxine D. Fluoxetine E. Sertraline

11 After Stopping Paroxetine, Which of the Following Would You Begin for her Depression? A. Amitriptyline B. Mirtazapine C. Venlafaxine D. Fluoxetine E. Sertraline

12 Obesity and Anti-Depressants The SSRI paroxetine (Paxil) is associated with the greatest weight gain in this list Of the tricyclics, amitriptyline (Elavil) promotes the greatest weight gain. Mirtazapine (Remeron), venlafaxine (Effexor), and duloxetine (Cymbalta) can all promote weight gain though milder Sertraline (Zoloft), citalopram (Celexa), and escitalopram (Lexapro) are weight neutral Fluoxetine (Prozac) and buproprion (Wellbutrin) promote weight loss

13 When Lifestyle Fails: Weight Loss Medications for Obesity Phentermine (Adipex) Phentermine/topiramate (Qysmia) Orlistat (Xenical) Lorcaserin (Belviq) Naltrexone/bupropion (Contrave) Liraglutide (Saxenda)

14 Thyroid Case A 30 year old woman presents with mild fatigue, 5-lb weight gain, and occasional constipation She is 2 months postpartum and plans to breastfeed for 1 year Her only medication is a prenatal MVI FH is positive for hypothyroidism in her mother On exam, she appears well, though tired Wt 130 lbs (60 kg), BMI 22, pulse 70 and regular Thyroid gland: normal in size and consistency Labs: TSH 30 mu/l (nl ), free T4 1.2 (nl )

15 What Would You Do Next? A. Order a radioiodine scan and uptake B. Begin levothyroxine 50 mcg daily C. Begin levothyroxine 100 mcg daily D. Ask her to return for a repeat TSH in 1 month E. Check anti-thyroid antibodies

16 What Would You Do Next? A. Order a radioiodine scan and uptake B. Begin levothyroxine 50 mcg daily C. Begin levothyroxine 100 mcg daily D. Ask her to return for a repeat TSH in 1 month E. Check anti-thyroid antibodies

17 Postpartum Thyroiditis A.RAI scan and uptake is indicated for evaluation of thyrotoxicosis, not hypothyroidism, and is contraindicated during lactation B. and C. In a symptomatic hypothyroid patient, levothyroxine 100 mcg/d (or 0.8 mcg/lb) would be a good starting dose. Given her normal free T4, a lower starting dose such as 50 mcg/d might be considered.

18 Postpartum Thyroiditis D. In the postpartum setting with minimal symptoms, no goiter, and normal free T4, the most likely diagnosis is postpartum thyroiditis which will resolve 50% of the time without rx. Monitoring TSH in this case is reasonable. E. Positive anti-thyroid antibodies can be present in both postpartum thyroiditis and Hashimoto s so will not help distinguish between the 2 possibilities.

19 Case 3 A 60 year old Caucasian woman admitted with acute abdominal pain and sepsis is found to have a ruptured appendix. She is treated with antibiotics and emergency appendectomy via laparotomy and does well intraoperatively. Over the next 48 hours, she experiences nausea, vomiting and hypotension requiring intravenous saline and pressors.

20 Case (cont) Her PMH is positive for arthritis of both knees and spinal stenosis. She denies any history of oral prednisone use. ROS: She noted some fatigue and mild decreased appetite over the past 2 months months. PE: she has generalized obesity with mild facial plethora

21 Case (cont) Labs as outpatient prior to surgery: Normal complete metabolic panel, TSH, free T4 and FSH 55 (c/w menopause) Now: serum Na+ 130, K+ 3.8, serum cortisol 1.8 mcg/dl, ACTH < 10 pg/ml. After 250 mcg of cosyntropin IV, her serum cortisol rises from 2.0 to 3.5 mcg/dl at 60 minutes.

22 Which Diagnosis is Most Likely to Explain Her Adrenal Insufficiency? A. Bilateral adrenal hemorrhage B. Perioperative opiate exposure C. Acute pituitary infarction D. Exogenous glucocorticoids E. Addison s disease

23 Which Diagnosis is Most Likely to Explain Her Adrenal Insufficiency? A. Bilateral adrenal hemorrhage B. Perioperative opiate exposure C. Acute pituitary infarction D. Exogenous glucocorticoids E. Addison s disease

24 Exogenous Glucocorticoids This patient had received multiple injections of methylprednisolone into her spine and several joints over the past 15 months. When asked about taking prednisone, she did not associate this with her steroid injections. Following her last injection 4 months ago, she had mild symptoms of steroid withdrawal but compensated until her acute sepsis, surgery and anesthesia when she decompensated.

25 Exogenous Glucocorticoids Her labs are consistent with chronic secondary adrenal insufficiency. Opiates can transiently suppress the HPA axis but cortisol post-cosyntropin should have stimulated normally. ACTH would be HIGH in both adrenal hemorrhage and Addison s as these cause primary adrenal insufficiency Acute pituitary infarction should have impacted the other anterior pituitary hormones and cosyntropin stimulation would be normal.

26 ACUTE Secondary Adrenal Insufficiency H CRH Manifestations/Characteristics: ACTH P Labs: low basal cortisol inappropriately low ACTH ± hyponatremia Normal K and aldosterone regulation Adrenal Physical: Cortisol completely normal mild, progressive, fatigue at baseline severe fatigue, orthostasis, hypotension, in situations of stress Glucocortic Recepto Mineralocorticoid Receptor Target Organ Cell

27 ACUTE Secondary Adrenal Insufficiency H ACTH P CRH Adrenal Response to Cosyntropin: NORMAL EXAMPLE: Cosyntropin Morning ACTH (pg/ml) 10 Cortisol 60 mins following 250 µg cosyntropin Cortisol (µg/dl) Glucocortic Recepto Mineralocorticoid Receptor Target Organ Cell

28 CHRONIC Secondary Adrenal Insufficiency H CRH With chronic ACTH deficiency, adrenal cortex (ZF) will atrophy, and will progressively respond less to cosyntoprin stimulation ACTH P EXAMPLE: Cosyntropin Morning 60 mins following 250 µg cosyntropin Cortisol (µg/dl) ACTH (pg/ml) 10 Adrenal Cortisol Glucocortic Recepto Mineralocorticoid Receptor Target Organ Cell

29 Causes of Hyperprolactinemia I. Physiologic Menstrual cycle Pregnancy Nursing Nipple stimulation Stress II. Pharmacologic Dopamine antagonists - phenothiazines - haloperidol - risperidone - metoclopromide - domperidone Amitriptyline Antihypertensives - methyldopa - reserpine Verapamil Cimetidine Estrogens III. Pathophysiologic Primary hypothyroidism Chronic renal failure Chest wall lesions Polycystic ovary syndrome Idiopathic Macroprolactinemia Hypothal/pituitary lesions Prolactinoma Other medications? Birth control pills? Check TSH Stalk compression?

30 Evaluation of the Non-Diabetic Patient with Low Glucose & Symptoms Must get labs when the glucose is LOW Glucose Insulin C-peptide Sulfonylurea (SFU) screen Others

31 Proinsulin is Cleaved into Insulin and C-Peptide and Secreted Proinsulin B Chain C-peptide A Chain Insulin A Chain C-peptide C-peptide S S + B Chain

32 When Glucose is Low (<50) INSULIN HIGH C-peptide high SFU negative insulinoma SFU positive sulfonylurea effect C-peptide low surreptitious insulin use INSULIN LOW Liver, heart, or kidney failure; sepsis, ETOH, Cortisol or GH deficiency, nonpancreatic tumors, inborn errors of metabolism, inanition

33 Disclosures Royalties from UpToDate for 2 chapters on Premenopausal Osteoporosis ($1800/yr) THANK YOU!