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An Endocrine Approach to the Overweight Patient

Endocrinology Rounds September 8, 2010 Selina Liu PGY5 Endocrinology. An Endocrine Approach to the Overweight Patient. Outline. Case Approach Confirm diagnosis Establish cause(s) and contributory factors Endocrine vs. other Assess severity, and presence of complications

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An Endocrine Approach to the Overweight Patient

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  1. Endocrinology Rounds September 8, 2010 Selina Liu PGY5 Endocrinology An Endocrine Approach to the Overweight Patient

  2. Outline • Case • Approach • Confirm diagnosis • Establish cause(s) and contributory factors • Endocrine vs. other • Assess severity, and presence of complications • Management

  3. Case – Mr. AB • 31 y M referred for morbid obesity • PMHx – previously healthy • PSHx – prior laparoscopic cholecystectomy • No medications • NKDA

  4. Approach CONFIRM THE DIAGNOSIS

  5. Definitions • obesity – derived from Latin • obesitas – “fatness, corpulence” • obesus – “that has eaten itself fat” • obedere – “to eat all over, devour” • ob – “over” + edere – “eat”

  6. Definitions • overweight & obesity: “ abnormal or excessive fat accumulation that presents a risk to health” http://www.who.int/topics/obesity/en/

  7. Statistics • 2009: 12 731 188 Canadians overweight or obese (age > 18 yrs) Statistics Canada Website http://www40.statcan.ca/l01/cst01/health81a-eng.htm

  8. Overweight vs. Obesity • Body Mass Index (Quetelet’s Index) Body mass index = kg m2

  9. Overweight vs. Obesity http://www.bodymassindexchart.org/bmi-chart/

  10. Overweight vs. Obesity http://www.who.int/features/factfiles/obesity/facts/en/index.html

  11. BMI and Mortality http://www.uptodate.com

  12. Limitations of BMI • does not take into account: • age, gender, race • body fat distribution • fat mass vs. muscle mass

  13. Waist Circumference • measure of central obesity • abdominal fat: predictor of obesity-related diseases Lau DCW et al. 2006Canadian clinical practice guidelines on the management and prevention of obesity in adults and children. 2007 CMAJ 176 (8 Suppl):S1-13

  14. Approach ESTABLISH CAUSE(S) AND CONTRIBUTORY FACTORS

  15. Causes of Obesity Genetics Environment Caloric intake > energy expenditure

  16. Genetic Causes • Monogenic • leptin gene mutations, leptin receptor mutations • POMC gene mutation • prohormone convertase 1 gene mutation • melanocortin 4 receptor mutation • TrkB gene mutation • Chromosomal Rearrangements • Prader-Willi Syndrome • obesity, developmental delay, short stature, secondary hypogonadism • SIM1 gene mutation (balanced translocation chromosome 1, 6) • paraventricular/supraoptic nuclei formation abnormality Kronenberg HM et al. Williams Textbook of Endocrinology. 11th edition. 2008 Saunders Elsevier.

  17. Genetic Causes • Pleiotropic Syndromes • ~30 syndromes with obesity as a clinical feature • associated with mental retardation, dysmorphic features, organ-specific developmental abnormalities i.e. Wilson-Turner syndrome (obesity, gynecomastia, tapering fingers, mental retardation) – X-linked • Polygenic Causes • >600 genes, markers, and chromosomal regions linked with obesity phenotypes Kronenberg HM et al. Williams Textbook of Endocrinology. 11th edition. 2008 Saunders Elsevier.

  18. Other Causes & Contributory Factors • Iatrogenic • drugs/medications, hypothalamic surgery • Diet • Lifestyle • physical activity, sleep deprivation, smoking cessation, social networks • Psychological factors • depression, seasonal affective disorder • Socioeconomic Class • Ethnicity • ENDOCRINE

  19. Endocrine Causes of Obesity • Cushings’ Syndrome • Hypothyroidism • Polycystic Ovarian Syndrome • Growth Hormone Deficiency • Hypothalamic Obesity • Insulinoma • Pseudohypoparathyroidism

  20. Cushings’ Syndrome • symptoms: • progressive obesity • dermatological manifestations • easy bruising, skin atrophy, striae, pigmentation • adrenal androgen excess (♀) • oily skin, acne, hirsutism, libido, virilization • muscle weakness, wasting • fractures (osteoporosis) • polydipsia, polyuria (dysglycemia)

  21. Cushings’ Syndrome

  22. Cushings’ Syndrome

  23. Hypothyroidism

  24. Polycystic Ovarian Syndrome • 2003 - Rotterdam criteria – 2 of 3 of: • unexplained clinical or biochemical hyperandrogenism • oligo-anovulation • polycystic ovaries Fertil Steril 2004 Jan;81(1):19-25 • 2006 - Androgen Excess and PCOS Society criteria • hyperandrogenism (clinical or biochemical) and • ovarian dysfunction (oligo-anovulation and/or polycystic ovaries) and • exclusion of other androgen excess or related disorders Fertil Steril 2009 Feb;91(2):456-88. Epub 2008 Oct 23

  25. Polycystic Ovarian Syndrome • association between PCOS and obesity • between 30-75% of women with PCOS are obese reviewed in Ehrmann DA 2005 N Engl J Med 352:1223-1236 • 60% of lean women with PCOS have increased body fat and central adiposity Kirchengast S & Huber J 2001. Hum Reprod 16(6):1255-60 • cause of obesity in PCOS is not known

  26. Growth Hormone Deficiency • in adults, GH deficiency is associated with  fat mass (especially abdominal adiposity) and  lean body mass • GH treatment in GH deficient adults has been shown to decrease fat mass and promote growth of lean tissue • but – no effect on overall weight reviewed in Rassmusen MH 2010 Mol Cell Endocrinol 316(2):147-153

  27. Hypothalamic Obesity • trauma/surgery/radiation • infection • tumour – i.e. craniopharyngioma • mechanisms: • hyperphagia, decreased voluntary energy expenditure • impaired satiety signalling • hyperinsulinemia

  28. Hypothalamic Obesity • History: • hyperphagia • local symptoms – headache, visual changes, N/V • hypothermia/hyperthermia • seizure, coma • symptoms of pituitary hormonal deficiencies • prior surgery/radiation/trauma

  29. Insulinoma • rare cause of obesity ~ 20-40% patients have hyperphagia & weight gain • present with episodes of hypoglycemia • usually fasting, but can be postprandial • neuroglycopenic & adrenergic symptoms

  30. Pseudohypoparathyroidism (PHP) • Albright’s hereditary osteodystrophy (AHO) • PHP Type 1a • decreased Gsa activity • renal unresponsiveness/resistance to PTH • hypocalcemia, hyperphosphatemia, PTH • obesity, short stature • shortened 4th/5th metacarpals • subcutaneous calcifications • developmental delay

  31. Pseudohypoparathyroidism (PHP) http://www.netterimages.com/ http://www.endotext.org/

  32. Case – Mr. AB • 31 y M referred for morbid obesity • PMHx – previously healthy • PSHx – prior laparoscopic cholecystectomy • No medications • NKDA • lives with 9 yr old son, not currently working

  33. Approach • Clinical assessment • History • Physical Exam • Investigations

  34. History • Past medical/surgical history • endocrine • psychiatric • Social history • EtOH • smoking vs. smoking cessation? • recreational drugs • Family history

  35. History • Medications • insulin, oral antihyperglycemics • glucocorticoids • anti-depressants • anti-pyschotics • anti-epileptics • b-blockers

  36. History • Weight history • onset/rapidity of weight gain • prior weight loss attempts – methods, success • Activity level • Nutrition history • frequency of eating (meals, snacks) • portion size, fat content • binge eating, night-time eating

  37. History • complications of obesity • endocrine & metabolic • Metabolic Syndrome, DM2, dyslipidemia • cardiovascular • HTN, CAD, cerebrovascular, thromboembolic • respiratory • OSA, restrictive lung disease, OHS • gastrointestinal • GERD, hepatobiliary disease, pancreatitis

  38. History • complications of obesity • MSK • OA, gout • neurologic • idiopathic intracranial hypertension • ophthlamologic • cataracts • malignancy

  39. Case – Mr. AB • weight history – in his early 20s, weighed 150 lbs • 2 yrs ago, was 210 lbs • gained 100 lbs within past 1 yr • activity history • jogs 7km/day x 7 months, but only lost 5 lbs • some weight training • nutrition history • trying to eat more healthy (saw nutritionist at gym)

  40. Case – Mr. AB • poor energy, fatigue • possible symptoms of sleep apnea • daytime somnolence, unrefreshing sleep, +snores • has had prior w/u for atypical chest pain • normal EST, MIBI • endocrine review of systems - noncontributory

  41. Physical Exam • height, weight, BMI +/- waist circumference • blood pressure, heart rate • cardiovascular, respiratory, abdominal exam • signs of endocrine causes • Cushings, hypothyroidism, PCOS • signs of complications • CHF, PVD, OSA, gout, OA

  42. Case – Mr. AB • ht 180 cm, wt 141.3 kg = BMI 43.6 • BP 130/92 left arm sitting, large cuff HR 66 reg • normal thyroid • cardiovascular, respiratory, abdomen all normal • no signs of Cushings’ syndrome • old photograph – face more round now, but no other significant change in features

  43. Investigations • fasting glucose, lipid profile • grade A, level 3 • renal function, urinalysis, liver enzymes • sleep study (if appropriate) • grade B, level 3 Lau DCW et al. 2006Canadian clinical practice guidelines on the management and prevention of obesity in adults and children. CMAJ 176 (8 Suppl):S1-13

  44. Investigations • TSH (+/- fT3, fT4 if concern re: central hypothyroidism) • 24 hr urine collection for urine free cortisol or p.m. salivary cortisol or low dose dexamethasone suppression test • other tests as suggested by history, physical

  45. Case – Mr. AB • random glucose 5.1, A1c 5.4% • creatinine 95 • normal liver enzymes • fasting lipids previously normal

  46. Case – Mr. AB • TSH 2.60, fT3 5.4 fT4 16 • IGF-1 155 (115-307) • 24 hr urine free cortisol 320 (106-346) • normal 24 hr urine volume, creatinine

  47. Management • Lifestyle • dietitian referral -  energy intake by 500-1000 kcal/day www.eatrightontario.ca • 30 min moderate intensity 3-5x/wk • eventually > 60 min on most days • consider cognitive-behavioural therapy if indicated • Pharmacological • sibutramine (Meridia) or orlistat (Xenical) • Surgical • bariatric surgery if BMI >40 or > 35 and comorbidities Lau DCW et al. 2006Canadian clinical practice guidelines on the management and prevention of obesity in adults and children. CMAJ 176 (8 Suppl):S1-13

  48. Increased risk of nonfatal MI or nonfatal CVA (but not of CV death or death from any cause)

  49. Case – Mr. AB • continued lifestyle modifications • discussed pharmacological treatments, but he was not interested at this point • briefly discussed bariatric surgery • referred for evaluation for sleep apnea

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