endocrinology rounds september 8, 2010 selina liu pgy5 endocrinology an endocrine approach to the...
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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
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
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
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)
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
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
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
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