Endocrinology RoundsSeptember 8, 2010

Selina LiuPGY5 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

Management

Case – Mr. AB

31 y M referred for morbid obesity

PMHx – previously healthy

PSHx – prior laparoscopic cholecystectomy

No medications

NKDA

Approach

CONFIRM THE DIAGNOSIS

Definitions

obesity – derived from Latin

obesitas – “fatness, corpulence”

obesus – “that has eaten itself fat”

obedere – “to eat all over, devour”

ob – “over” + edere – “eat”

Definitions

overweight & obesity:

“ abnormal or excessive fat accumulation that presents a risk to

health”

http://www.who.int/topics/obesity/en/

Statistics

2009:

12 731 188 Canadians overweight or obese

(age > 18 yrs)

Statistics Canada Websitehttp://www40.statcan.ca/l01/cst01/health81a-eng.htm

Overweight vs. Obesity

Body Mass Index (Quetelet’s Index)

Body mass index = kg m2

Overweight vs. Obesity

http://www.bodymassindexchart.org/bmi-chart/

Overweight vs. Obesity

http://www.who.int/features/factfiles/obesity/facts/en/index.html

BMI and Mortality

http://www.uptodate.com

Limitations of BMI

does not take into account:

age, gender, race

body fat distribution

fat mass vs. muscle mass

Waist Circumference

measure of central obesity

abdominal fat: predictor of obesity-related diseases

Lau DCW et al. 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children. 2007 CMAJ 176 (8 Suppl):S1-13

Approach

ESTABLISH CAUSE(S) AND CONTRIBUTORY FACTORS

Causes of Obesity

Caloric intake > energy expenditure

Genetics Environment

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.

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.

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

Endocrine Causes of Obesity

Cushings’ Syndrome Hypothyroidism Polycystic Ovarian Syndrome

Growth Hormone Deficiency Hypothalamic Obesity Insulinoma Pseudohypoparathyroidism

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)

Cushings’ Syndrome

Cushings’ Syndrome

Hypothyroidism

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

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

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

Hypothalamic Obesity

trauma/surgery/radiation infection tumour – i.e. craniopharyngioma

mechanisms: hyperphagia, decreased voluntary energy expenditure impaired satiety signalling hyperinsulinemia

Hypothalamic Obesity

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

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

Pseudohypoparathyroidism (PHP) Albright’s hereditary osteodystrophy (AHO)

PHP Type 1a decreased Gs activity

renal unresponsiveness/resistance to PTH hypocalcemia, hyperphosphatemia, PTH obesity, short stature shortened 4th/5th metacarpals subcutaneous calcifications developmental delay

Pseudohypoparathyroidism (PHP)

http://www.endotext.org/http://www.netterimages.com/

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

Approach

Clinical assessment

History Physical Exam Investigations

History

Past medical/surgical history endocrine

psychiatric

Social history EtOH

smoking vs. smoking cessation?

recreational drugs

Family history

History

Medications insulin, oral antihyperglycemics

glucocorticoids

anti-depressants

anti-pyschotics

anti-epileptics

-blockers

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

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

History

complications of obesity MSK

OA, gout

neurologic

idiopathic intracranial hypertension

ophthlamologic

cataracts

malignancy

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)

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

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

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

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. 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children. CMAJ 176 (8 Suppl):S1-13

Investigations

TSH (+/- fT3, fT4 if concern re: central hypothyroidism)

24 hr urine collection for urine free cortisolor

p.m. salivary cortisolor

low dose dexamethasone suppression test

other tests as suggested by history, physical

Case – Mr. AB

random glucose 5.1, A1c 5.4%

creatinine 95

normal liver enzymes

fasting lipids previously normal

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

Management Lifestyle

dietitian referral - energy intake by 500-1000 kcal/daywww.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. 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children. CMAJ 176 (8 Suppl):S1-13

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

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

Summary – Approach

Confirm diagnosis – overweight vs. obese

Establish cause – rule out endocrine etiologies also other treatable/reversible contributory causes

Assess severity, and presence of complications

Treatment & management lifestyle modification +/- pharmacological +/- surgical

References

Lau DCW et al. 2007. CMAJ 176 (8 Suppl):S1-13 Kronenberg HM et al. Williams Textbook of Endocrinology. 11th edition. 2008 Saunders Elsevier. Fertil Steril 2004 Jan;81(1):19-25 Azziz R et al. 2009. Fertil Steril Feb;91(2):456-88. Epub 2008 Oct 23 Ehrmann DA 2005 N Engl J Med 352:1223-1236 Kirchengast S & Huber J 2001. Hum Reprod 16(6):1255-60 Rassmusen MH 2010 Mol Cell Endocrinol 316(2):147-153 http://www.who.int/topics/obesity/en/ http://www40.statcan.ca/l01/cst01/health81a-eng.htm http://www.bodymassindexchart.org/bmi-chart/ http://www.who.int/features/factfiles/obesity/facts/en/index.html http://www.uptodate.com http://www.netterimages.com http://www.endotext.org