Sean Hamlett DO FACOI Endocrinology, Diabetes, and Metabolism Freeman Health System Joplin, MO

Transcription

1 Sean Hamlett DO FACOI Endocrinology, Diabetes, and Metabolism Freeman Health System Joplin, MO

2 I will not be discussing any off-label uses of medications. I am a paid speaker for: Amylin, BMS, BI, and AstraZeneca. I have no conflicts of interest regarding this presentation.

3 OSU-COM class of 1999 IM Residency at TRMC Endocrinology Fellowship at OU Board Certified in Endocrinology AOBIM Top Weight: 306 lbs Current Weight 180lbs Rise at 4:38AM Run and lift weights until 5:40AM daily Strict dietary plan: calories daily

4 I don t eat anything, and I can never lose weight..

5 Calories in = Calories out Weight gain = Caloric excess and/or change in body water content due to disease or medications First Law of Thermodynamics Energy is neither created nor destroyed Calories Out = resting metabolism (REE) + physical activity + the thermogenic effect of food You burn what you eat, you cannot spontaneously create energy to burn or to store as fat. When you burn less energy than you have supplied, then you gain weight.

6 To lose 1 pound of fat you must burn an extra 3500 calories. To lose 30 pounds you must create a deficit of 105,000 calories.

7 Hall, C. et al. Energy Expenditure of Walking and Running: Comparison with Prediction Equations. Medicine & Science in Sports and Exercise (Dec), 36(12): Running 1 mile: Men: burned 124 calories Women: burned 105 calories Walking 1 mile: Men: burned 88 calories Women: burned 74 calories

8 We have a 35 y.o. woman who is 5 feet 7 inches tall and weighs 170 pounds. She would like to lose 30 pounds. Her caloric consumption perfectly matches her basal energy expenditure (her calories in perfectly match her calories out per day at her normal daily activity level). She burns 64 calories per hour at baseline activity If she ran for 1 hour per day at a 10 minute per mile pace, she would run 6 miles and burn 630 calories in that hour. Net difference is 566 calories over that hour of running. To burn the 105,000 calories required to lose 30 pounds, she would have to run 1 hour per day (6 miles at a 10 minute per mile pace) for 185 days.

9 If you don t wake up every morning and know what you are going to eat that day, and when you are going to eat it, then you are not going to be successful at losing weight. Very few people can wing-it and be successful at losing weight.

10 But Dr. Hamlett, what do I do when I get hungry.. Stephen Covey (paraphrase): There is a moment between a thought (I am hungry and want to eat) and an action (eating a snack). You must act in that moment to choose to not eat the snack and prioritize your long-term goals over your short term desires

11 Both in their 20 s Annie Thorisdottir Crossfit games champion: 2011 and 2012 These lifestyles are not the same Adele

12 Rich Froning Crossfit Games Champion: 2011 and 2012 Is not undisciplined with his diet Is not in your office lamenting the fact that he can t lose weight.

13 Ava Cowan does not eat the same diet as the pleasant 40 year old women who come to your office complaining that they don t look like this fitness athlete.

14 I ve been criticized for being too basic with my lectures, but I keep getting consults that demonstrate that several of us don t understand the basics

15 38 y.o. woman seen in consultation: I am tired all the time and I have a really hard time losing weight. I looked on the internet and I think that I have hypothyroidism, but my doctor says that my thyroid levels are normal. I know that he/she is wrong. I wanted to come to a specialist to get a correct diagnosis.

16 Thyroid Physiology TSH T4 T3 In the absence of central hypothyroidism, if the TSH is normal, then the patient is EUTHYROID!!

17 Based on the medical literature, the amount of weight So, gain if you directly have attributable primary to hypothyroidism is. hypothyroidism, and you are 100 pounds overweight, the medical 5-15 pounds!! literature would suggest that the primary etiology is caloric excess. Blaming the hypothyroid condition is a state of denial. Hoogwerf BJ, et al. Long-term weight regulation in treated hyperthyroid and hypothyroid subjects. AM J Med (1984) 76:

18 Danish study whose aim was to investigate the association between thyroid function and BMI/Obesity in a normal population. A cross-sectional population study of 4649 subjects of whom only 4082 were analyzed after exclusion of those with over thyroid dysfunction. Knudsen, N, et al. JCEM (2005) 90(7):

19 The difference between lowest BMI and highest BMI was 1.9 kg/m². That corresponds to 12.1 lbs. Knudsen, N, et al. JCEM (2005) 90(7):

20 Those with the highest TSH gained approximately 11 pounds over a 5 year period. This is a gain of 2.2 pounds per year. Knudsen, N, et al. JCEM (2005) 90(7):

21 The proposed mechanism to explain the differences in weight between the groups Calories with lower In = Calories TSH values Out and higher TSH values was a difference in Resting Energy If Expenditure Calories In is (REE). constant and Calories Out decreases due to a diminution in REE, then Calories the result Out: is a net gain of energy (calories), (resting metabolism (REE) + physical activity + the which is then stored as fat. thermogenic effect of food) Knudsen, N, et al. JCEM (2005) 90(7):

22 Karmisholt J, et al. Weight loss after Therapy of hypothyroidism is Mainly Caused by Exretion of Excess Body Water Associated with Myxoedema. JCEM (2011) 96(1): E99-E103.

23 Small study of 12 newly diagnosed patients with autoimmune primary overt hypothyroidism who were treatment naïve. During the study (over 1 year), thyroid function was kept normal by adjustment of levothyroxine. Measurements of thyroid function were obtained at regular intervals for any necessary adjustment of Levothyroxine dosage. Karmisholt J, et al. Weight loss after Therapy of hypothyroidism is Mainly Caused by Exretion of Excess Body Water Associated with Myxoedema. JCEM (2011) 96(1): E99-E103.

24 DXA analysis scans, height measurements, and weight measurements were utilized to determine body composition over the course of the study. REE was measured with indirect calorimetry. Physical activity was studied utilizing step counting and questionnaires. A control group was included to validate the constancy of the measurement methods (10 patients treated with RAI for euthyroid goiter >1 year prior). Karmisholt J, et al. Weight loss after Therapy of hypothyroidism is Mainly Caused by Exretion of Excess Body Water Associated with Myxoedema. JCEM (2011) 96(1): E99-E103.

25 REE was measured with indirect calorimetry. Physical activity was studied utilizing step counting and questionnaires. A control group was included to validate the constancy of the measurement methods (10 patients treated with RAI for euthyroid goiter >1 year prior). Karmisholt J, et al. Weight loss after Therapy of hypothyroidism is Mainly Caused by Exretion of Excess Body Water Associated with Myxoedema. JCEM (2011) 96(1): E99-E103.

26 Karmisholt J, et al. Weight loss after Therapy of hypothyroidism is Mainly Caused by Exretion of Excess Body Water Associated with Myxoedema. JCEM (2011) 96(1): E99-E103.

27 Body weight decreased on average 9.46 lbs over the course of 1 year of Levothyroxine therapy. The decrease in total body weight was caused by a significant decrease of 8.36 lbs in the lean mass subcompartment. A small and insignificant decrease was observed in the fat mass subcompartment, and bone mass was equal between the two measurements. Karmisholt J, et al. Weight loss after Therapy of hypothyroidism is Mainly Caused by Exretion of Excess Body Water Associated with Myxoedema. JCEM (2011) 96(1): E99-E103.

28 REE increased significantly over the 1 year period despite no significant difference noted in physical activity. REE increased by 11.6% P = 0.41 Karmisholt J, et al. Weight loss after Therapy of hypothyroidism is Mainly Caused by Exretion of Excess Body Water Associated with Myxoedema. JCEM (2011) 96(1): E99-E103.

29 As expected, therapy of hypothyroidism was followed by a moderate decrease in body weight. Weight loss = 9.46 lbs Intuitively, it might be speculated that such weight loss was mainly caused by loss of body weight due to an increase in energy expenditure. Average increase in REE after 1 year of therapy was 215 kcal/24h. Karmisholt J, et al. Weight loss after Therapy of hypothyroidism is Mainly Caused by Exretion of Excess Body Water Associated with Myxoedema. JCEM (2011) 96(1): E99-E103.

30 However, DXA analysis demonstrated that the change in body weight was due to a change in lean body mass. Fat mass was unaltered. Lean body mass = water, proteins, glycogen, and minerals not tied to bone. Hypothyroid patients are known to retain water through various mechanisms (reduced capacity of renal free water excretion, increased AVP levels, and increased amounts of tissue glycosaminoglycans). Karmisholt J, et al. Weight loss after Therapy of hypothyroidism is Mainly Caused by Exretion of Excess Body Water Associated with Myxoedema. JCEM (2011) 96(1): E99-E103.

31 It is well established that patients with overt hypothyroidism who undergo therapy with thyroid hormones develop an increase in urine output. In this study, the loss of weight in treatment naïve patients with overt hypothyroidism who were rendered euthyroid with via therapy with Levothyroxine over a 1 year period, was due to loss of body water content and not loss of fat content. Karmisholt J, et al. Weight loss after Therapy of hypothyroidism is Mainly Caused by Exretion of Excess Body Water Associated with Myxoedema. JCEM (2011) 96(1): E99-E103.

32 Data suggest that weight gain associated with a hypothyroid state would approximate 5-15 pounds depending on the descriptive study. Higher TSH values are associated with a higher BMI amongst euthyroid subjects, seemingly due to a difference in REE. Thus intuitively, a lower TSH target could help patients with hypothyroidism from a weight management standpoint (conjecture).

33 Data suggest that weight gain associated with a hypothyroid state would approximate 5-15 pounds depending on the descriptive study. This is incongruous with the perception amongst lay-persons that their 100 lb weight excess is explainable solely by their hypothyroid state.

34 Higher TSH values are associated with a higher BMI amongst euthyroid subjects, seemingly due to a difference in REE. Thus intuitively, a lower TSH target could help patients with hypothyroidism from a weight management standpoint (conjecture).

35 In newly diagnosed patients with hypothyroidism in whom you initiate treatment, you can inform them that they can expect to potentially lose approximately 10 pounds, but that it will not likely be from fat mass, but rather from loss of water. Unless, of course, they make lifestyle changes involving caloric restriction and/or increased physical activity.

36 The thyroid explains a small portion of the problem, but the overwhelming issue remains Calories In = Calories Out

37 Briefly

38 40 y.o. woman with BMI of 40 kg/m². She has no discernible dietary plan (other than stating I try and watch what I eat ) and does not exercise on a regular basis. She states that she is here for consultation because I was on the internet and I have the symptoms of Cushing s syndrome. Then, I looked at some pictures, and they look just like me.

39 I can t seem to lose weight. I am tired all the time. I just have no energy.

40 HPA Axis Pituitary ACTH Adrenal Cortisol

41 Most common cause = exogenous glucocorticoids Endogenous pathologic hypercortisolism Cushing s Disease: Autonomous Corticotroph Adenoma secreting excessive ACTH (MC Endogenous cause: 65%). Adrenal Adenoma autonomously secreting excessive cortisol (20%). Ectopic

42 European population based studies reported an incidence of endogenous Cushing s Syndrome to be 1-2 cases per 1 million inhabitants per year This is truly an uncommon disorder Few, if any, features of Cushing s Syndrome are unique, but some features are more discriminatory than others. The Diagnosis of Cushing s Syndrome: An Endocrine Society Clinical Practice Guideline. JCEM (2008) 93:

43 Features that best discriminate Cushing s Syndrome: Easy bruising Facial Plethora Proximal myopathy (or proximal muscle weakness) Striae (especially if reddish purple and >1cm wide) The Diagnosis of Cushing s Syndrome: An Endocrine Society Clinical Practice Guideline. JCEM (2008) 93:

44 Features of Cushing s that are less useful in discriminating Cushing s, and are common in the general population: Fatigue Weight gain/obesity Dorsocervical fat pad ( buffalo hump ) Supraclavicular fullness Thin skin (more useful if onset at young age) Acne Hirsutism or female balding HTN DM type 2 The Diagnosis of Cushing s Syndrome: An Endocrine Society Clinical Practice Guideline. JCEM (2008) 93:

45 Pregnancy Depression and other psychiatric conditions ETOH dependence Morbid obesity Poorly controlled DM Some clinical features of Cushing s may be present The Diagnosis of Cushing s Syndrome: An Endocrine Society Clinical Practice Guideline. JCEM (2008) 93: Physical stress (hospitalization, surgery, pain) Malnutrition/anorexia Intense chronic exercise The presence of these conditions can make it difficult when screening for Cushing s Syndrome biochemically This is why you need a high index of clinical suspicion (presence of the best discriminating features) before committing to screening for Cushing s Syndrome Unlikely to have any clinical features of Cushing s

46 Recommendation 3.2: We recommend testing for Cushing s syndrome in the following groups: Patients with unusual features for age (e.g. osteoporosis, HTN) Patients with multiple and progressive features, particularly those that are more predictive of Cushing s Syndrome Patients with adrenal incidentaloma compatible with an adenoma. The Diagnosis of Cushing s Syndrome: An Endocrine Society Clinical Practice Guideline. JCEM (2008) 93:

47 Recommendation 3.3: We recommend against widespread testing for Cushing s syndrome in any other patient group. Obesity and/or difficulty losing weight without more discriminating features, is really not enough to warrant screening. The Diagnosis of Cushing s Syndrome: An Endocrine Society Clinical Practice Guideline. JCEM (2008) 93:

48 First, carefully review the patient s medication list and/or supplements to avoid testing in patients receiving exogenous glucocorticoids. 24 hour urine free cortisol At least two measurements Late-night salivary cortisol (two measurements) The Diagnosis of Cushing s Syndrome: An Endocrine Society Clinical Practice Guideline. JCEM (2008) 93:

49 Pituitary ACTH Adrenal Cortisol Cortisol <1.8 mcg/dl

50 1mg overnight Dexamethasone suppression test Dexamethasone 1mg at 11PM the night before your lab. 8AM fasting cortisol (I usually obtain Dexamethasone level concomitantly) Normal test: Serum Cortisol <1.8 mcg/dl The Diagnosis of Cushing s Syndrome: An Endocrine Society Clinical Practice Guideline. JCEM (2008) 93:

51 First law of thermodynamics Calories In = Calories Out Know the data regarding hypothyroidism and weight gain. Know the data regarding Levothyroxine replacement in overtly hypothyroid patients. Don t be afraid to be honest with patients about the most likely cause of their overweight/obesity

52 Be discriminatory about who you agree to screen for Cushing s. Make sure the clinical suspicion is truly high. Thank you, Understand the screening tests for Cushing s and apply them appropriately. Now Let s Go Eat!!