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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2892_Библиотеки_им_академика_М_И_Перельмана
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360 CASE FILES: FAMILY MEDICINE
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CLINICAL PEARLS
» Consider a broad differential diagnosis in patients who present with
“memory problems” and be sure to perform a thorough history and
physical examination, cognitive testing, laboratory studies, and imaging
diagnostic workup.
» The presentation of acutely altered mental status (delirium) should
prompt an aggressive workup for an underlying cause, as treatment may
result in correction of the mental status.
» Alzheimer disease is a disease of the family, not just the individual. It is
critical to treat the patient while giving support to the caregivers.
REFERENCES
Alzheimer’s Association. Home page: https://www.alz.org
American Geriatric Society website: https://www.americangeriatrics.org
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed.
Arlington, VA: American Psychiatric Association; 2013.
Cardarelli E, Kertesz A, Knebl JA. Frontotemporal dementia: a review for primary care physicians.
Am Fam Physician. 2010;82(11):1372-1377.
Falk N, Cole A, Meredith TJ. Evaluation of suspected dementia. Am Fam Physician. 2018;97(6):398-405.
Neef D, Walling AD. Dementia with Lewy bodies: an emerging disease. Am Fam Physician.
2006;73(7):1223-1230.
Seeley WW, Miller BL. Alzheimer’s Disease. In: Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL,
Loscalzo J. eds. Harrison’s Principles of Internal Medicine, 20e New York, NY: McGraw Hill.
http://accessmedicine.mhmedical.com/content.aspx?bookid=2129§ionid=192532255. Accessed
May 19, 2020.
CASE 33
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A 20-year-old woman comes to clinic for an annual physical examination. She has
no complaints. She has no significant medical or surgical history. She is currently
taking oral contraceptive pills because of irregular menstrual cycles. She attained
menarche at age 13 years and has had irregular cycles since. She has never been
sexually active. Her family history is positive for hypertension, diabetes, and
obesity in her parents. On examination, her blood pressure is 120/85 mm Hg,
her pulse is 78 beats/min, and her respiratory rate is 14 breaths/min. Her weight
is 188 lb, and she is 63 inches tall. Her physical examination is unremarkable
except for a brownish/black, velvety thickening of the skin on the back of her
neck, hirsutism, and abdominal obesity. Her laboratory test results included total
cholesterol of 202 mg/dL, high-density lipoprotein (HDL) cholesterol of 35 mg/dL,
low-density lipoprotein (LDL) cholesterol of 120 mg/dL, and triglycerides of
172 mg/dL. Her fasting glucose was 104 mg/dL, and she had normal renal and
liver function tests.
▶ What are the clinical issues that need to be addressed during this
preventive visit?
▶ What is your next step in the evaluation of this patient?
▶ What are the therapeutic options available for this patient?
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ANSWERS TO CASE 33:
Obesity
Summary: A 20-year-old woman presents with
Obesity—body mass index (BMI) of 33.5 kg/m
History of menarche at age 13 years and irregular cycles since then
Acanthosis nigricans and hirsutism
Total cholesterol of 202 mg/dL, HDL cholesterol of 35 mg/dL, LDL cholesterol of
120 mg/dL, triglycerides of 172 mg/dL, and fasting glucose of 104 mg/dL
Family history of hypertension, diabetes, and obesity in her parents
Clinical issues to address: Obesity and possible polycystic ovarian disease.
Next step in evaluation: Calculate a BMI, measure waist circumference, and repeat
blood pressure evaluation. Order laboratory testing to measure thyroid-stimulating
hormone (TSH).
Therapeutic options: Ask about her interest in losing weight. Advise on the health
benefits of weight loss, address other risk factors, and collaborate with the patient
to devise weight-loss goals; advise on diet and physical activity to achieve these
goals. Assess her ability and desire to follow the plan developed together and
explore options to achieve goals. Arrange follow-up. At subsequent visits, you can
consider adding pharmacotherapy as an adjunct to diet and exercise.
2
ANALYSIS
Objectives
1. Be able state the etiology and pathogenesis of obesity. (EPA 12)
2. Be able to state other comorbid conditions associated with obesity. (EPA 12)
3. Be able to state the diagnostic criteria for obesity and metabolic syndrome.
(EPA 3)
4. Be able to state the therapeutic options available for the management of
obesity. (EPA 4)
Considerations
Obesity is a chronic and stigmatizing disease that begins early in life. Increased
caloric intake, types of foods consumed, decreased physical exertion, and genetic
predisposition are common causes of obesity. Routine physical examination visits serve as a good platform to address issues related to obesity and its associated
comorbid conditions. This visit should be taken as an opportunity to address obesity, metabolic risk, and its management.
Increased body weight is a major risk factor for the development of disease
and for premature death. Metabolic syndrome is an important risk factor for the
subsequent development of type 2 diabetes and cardiovascular disease (CVD).
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Metabolic syndrome is more common in overweight and obese patients and has a
higher prevalence in those age ≥ 60. It is a worldwide health issue and is present
in approximately one-third of Americans age 18 and over. This patient has metabolic syndrome based on her abdominal circumference, increased triglycerides, low
HDL, and mildly elevated LDL cholesterol levels. She may also need further investigation for the presence of polycystic ovary syndrome (PCOS) because of her obesity, hirsutism, and history of irregular cycles. PCOS should be a consideration in
patients with chronic anovulation, ovarian cysts, and evidence of hyperandrogenism. Both metabolic syndrome and PCOS are very closely associated with obesity
and insulin resistance.
Based on the provided information, in this situation, the key clinical implication
of these diagnoses is identification of a patient needing aggressive lifestyle modification focused on weight reduction and increased physical activity.
APPROACH TO:
Obesity
DEFINITIONS
BODY MASS INDEX: A measurement of the relative composition of lean body
mass and body fat; calculated as (Weight in kilograms)/(Height in meters)2.
METABOLIC SYNDROME SYNDROME X, INSULIN RESISTANCE
SYNDROME): A constellation of metabolic abnormalities that confer increased
risk of CVD and diabetes mellitus. Major features include central obesity, hypertriglyceridemia, low HDL cholesterol, hyperglycemia, and hypertension.
OBESITY: A state of excess adipose tissue mass. Defined by most authorities as
BMI of ≥ 30 kg/m2. Morbid obesity is defined as a BMI ≥ 40 kg/m2. Super obesity
is defined as a BMI ≥ 50 kg/m2.
OVERWEIGHT: Defined as BMI ≥ 25 kg/m2, the point at which all-cause, meta-
bolic, cancer, and cardiovascular morbidity begin to rise.
SATIATION: Level of fullness during a meal.
SATIETY: Level of fullness/satisfaction (lack of hunger) after a meal.
CLINICAL APPROACH
Epidemiology
Obesity is a chronic and easily diagnosed disease that is associated with lifethreatening morbidity and mortality. Data from the National Health and Nutrition Examination Surveys (NHANES) show that in 2015 to 2016, obesity
affected 18.5% of 2- to 19-year-olds and 39.8% of adults aged 20 years or older.
The prevalence of obesity was higher in middle-aged adults (42.8%) compared to
young adults (35.7%).
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Table 33–1 • DIAGNOSTIC CRITERIA FOR METABOLIC SYNDROME
Three of more of the following:
Waist circumference > 102 cm (male) or > 88 cm (female)
Hypertriglyceridemia Triglycerides ≥ 150 mg/dL or specific medication
Low HDL cholesterol < 40 mg/dL (male) or < 50 mg/dL (female) or specific medication
Hypertension ≥ 130 mm systolic or ≥ 85 mm diastolic or specific medication
Fasting plasma glucose ≥ 100 mg/dL or specific medication or previously diagnosed
type 2 diabetes
HDL, high-density lipoprotein.
Metabolic Syndrome. Current minimum estimates are that the prevalence of
metabolic syndrome in the United States is at least 34.5% using the National
Cholesterol Education Program’s 3rd Adult Treatment Panel (ATP III) criteria
(Table 33–1). Metabolic syndrome is an important risk factor for subsequent
development of type 2 diabetes and CVD. Thus, the key clinical implication of
a diagnosis of metabolic syndrome is identification of a patient needing aggressive lifestyle modification focused on weight reduction and increased physical
activity.
Pathophysiology
Energy balance is the relationship of energy intake to energy expenditure. When
more energy is expended than taken in, weight loss ensues. When the intake of
energy exceeds the amount expended, weight gain occurs. Thus, obesity is caused
by positive caloric balance and quality of food ingested, and it is relative to the amount
of energy expended through physical activity. Risk of obesity is affected by genetic,
physiologic, and environmental factors. A positive energy imbalance results in
weight gain and obesity, but the possible causes of positive energy imbalance are
not well understood and are likely different for different people.
It has been estimated that genetic background can explain 40% or more of the
variance in body mass in humans. The genetic component is complex and involves
the interaction of multiple genes. However, the marked increase in obesity cannot be completely attributed to genetics. Social factors such as lower education
level, lower socioeconomic class, and diet composition are all associated with a high
risk of obesity. Likewise, physiologic factors such as various gut hormones, level of
spontaneous physical activity (fidgeting), and age-related decline in energy expenditure are key determinants in regulation of food intake and energy expenditure.
An increase in energy consumption with a decrease in physical activity is thought to
be the main contributor to the current obesity epidemic. Additionally, the availability
of convenience foods and the increase in palatability and serving size, compounded
with industrialization leading to a sedentary lifestyle, have led to an altered energy
balance.
Screening. The US Preventive Services Task Force recommends screening all
adult patients for overweight and obese statuses by measuring height and weight
and calculating BMI as part of the routine physical examination. BMI is used as
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Table 33–2 • DEFINITION OF OBESITY BASED ON BMI
BMI (kg/m2) Obesity Class
Underweight < 18.5
Normal 18.5-24.9
Overweight 25.0-29.9
Obesity
Extreme obesity (also called morbid or severe obesity) > 40 III
Super obesity > 50 III
30.0-34.9
35.0-39.9
I
II
a measure of weight status and as a tool to predict risk of disease, as it generally
correlates well as an estimate of total body fat. However, BMI is not as accurate a
measure of being overweight/obese in patients with heart failure, pregnant women,
bodybuilders, professional athletes, elderly patients, and certain ethnic groups. More-
over, abdominal obesity is associated with increased risk for hypertension, heart
disease, dyslipidemia, and diabetes. Additional measurements, like waist circumference and waist-to-hip ratio, need to be used to accurately identify the population
at risk. Direct measurement of percentage of body fat may also provide additional
information. Table 33–2 lists the classification of overweight/obese statuses based
on BMI.
Along with the measurements mentioned, a health history, physical examination, and focused laboratory workup should be performed to look for complications and comorbid conditions. Any previous weight-loss efforts, recent smoking
cessation, daily physical activity levels, and eating habits should be assessed to identify factors that might be contributing to weight gain and obesity.
Laboratory Workup. A fasting glucose and glycosylated hemoglobin level should
be measured to evaluate for diabetes mellitus and impaired glucose tolerance. The
presence of acanthosis nigricans—a velvety, hyperpigmented thickening of the skin
commonly found on the neck and axillary regions—may also be a sign of insulin
resistance. Fasting lipids should also be measured, both to evaluate for the pres-
ence of metabolic syndrome and for the assessment of the patient’s risk for CVD.
TSH should be measured to screen for hypothyroidism. Liver enzymes should be
requested, as abnormal results may indicate the development of a fatty liver.
Treatment
The goal of therapy is to prevent, treat, or reverse the complications of obesity
and improve quality of life. Treatment of obesity should begin in patients with a
BMI greater than 25 kg/m2 or who have visceral obesity, documented by increased
waist circumference greater than 40 inches in men and greater than 35 inches in
women, or a waist-to-hip ratio greater than 0.9 in men and greater than 0.85 in
women. Weight loss of as little as 5 pounds (2.3 kilos) reduces the risk of developing comorbid conditions. Developing a treatment plan for obesity is complex and
should use a combination of dietary/caloric modifications, increased physical activity,
and behavior therapy as a gold standard.
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Dietary Changes. Dietary intervention is the cornerstone of weight-loss therapy. Most diets work in two principal dimensions: energy content and nutrient
composition. The National Heart, Lung, and Blood Institute recommends initiating treatment with a calorie deficit of 500 to 1000 kcal/d compared with the
patient’s habitual diet. This reduction produces a weight loss of 1 to 2 lb/wk
(0.45 to 0.91kg/wk). Loss of more than 5% of initial body weight can improve CVD
risk. There are different kinds of specific dietary modifications recommended, but
they all work based on caloric expenditure greater than intake through portion
control. The selection of a diet should be based upon patient preferences to promote optimal dietary adherence, a key determinant of weight loss irrespective of
the type and nutrient composition of the diet. Portion control should not compromise the nutrient content of the diet; patients should still aim for a balanced meal.
Most diets (both low carbohydrate and low fat) have good short-term results but
limited long-term efficacy, with patients typically losing 5% of body weight over the
first 6 months, then returning to the initial weight by 12 to 24 months. A “Mediterranean” diet or low-carbohydrate diet may be more effective for modest long-term
weight loss compared to a low-fat diet.
Physical Activity. The addition of exercise training to a diet program can add to
the weight loss. Physical activity alone is not an effective method for achieving weight
loss, although it is very important for long-term weight management and cardiovascular health benefits. Physical activity can improve insulin sensitivity and glycemic
control, decrease abdominal fat, and reduce cardiovascular risk. Patients should
engage in moderate-to-vigorous physical activity for at least 30 min/d, 5 to 7 d/wk,
both to maintain weight loss and for the independent health benefits of exercising.
Other Lifestyle Modifications. The purpose of behavior modification therapy is
to help patients identify and make long-term changes in their eating and physical activity habits that contribute to obesity. The targets of behavior modification
are avoiding triggers, maintaining dietary diaries, using portion-controlled plates,
slowing the rate of eating to enhance satiation, avoidance of high-risk situations,
increasing physical activity, and breaking repetitive behaviors, such as watching TV
while eating.
Pharmacotherapy. Table 33–3 lists the medications commonly used in the
treatment of obesity. Pharmacologic therapy may be offered to those with a BMI
greaterthan 30 kg/m2 or BMI of 27 to 30 kg/m2 with comorbid conditions.
Orlistat, lorcaserinphenteramine/topiramate, naltrexone ER (extended release)/
bupropion ER and liraglutide are US Food and Drug Administration (FDA)
approved for long-term weight-loss management. All of these approved medications have generally been found to have modest weight loss over placebo and often
are limited in efficacy due to side effects and/or cost.
With the exception of orlistat, which inhibits the absorption of dietary fat by
inhibiting pancreatic lipases, all medications approved for obesity act as anorexiants. Anorexiant medications increase satiation, satiety, or both. Increasing satiation results in a reduction in the amount of food eaten, and increasing satiety
reduces the frequency of eating. FDA-approved medications are generally recommended to be used as short-term adjuncts to diet, exercise, and behavioral modification. Their use should be tapered off after prolonged use or if there is lack of efficacy.
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Table 33–3 • MEDICATIONS USED IN THE TREATMENT OF OBESITY
Drug Name
(Trade Name) Mechanism of Action Notes
Bupropion-naltrexone
(Contrave)
Dextroamphetamine
(Dexedrine, Dextrostat)
Phendimetrazine
(Bontril)
Diethylpropion
(Tenuate)
Phentermine (Fastin,
Pro-Fast, Ionamin,
Adipex-P)
Phenterminetopiramate (Qsymia)
Lorcaserin (Belviq) Serotonin receptor
Orlistat (Xenical, Alli) Selective inhibitor of
Liraglutide (Saxenda) Glucagon-like peptide-1
Antidepressant and
opioid antagonist
Sympathomimetic
(increased
norepinephrine release)
Sympathomimetic
(increased
norepinephrine release)
Sympathomimetic
(increased
norepinephrine release)
Sympathomimetic
(increased
norepinephrine release)
Sympathomimetic
(increased
norepinephrine release)
and anticonvulsant
agonist
pancreatic lipase, results
in reduced intestinal
digestion of fat and
increased fecal fat
excretion
(GLP-1) agonist causing
appetite suppression
Not recommended as first line. Can be used
in obese smokers who want to quit. Full
cardiovascular effects are unknown, but
this should not be used with uncontrolled
hypertension. Warn about suicidal ideation
in young adults.
Numerous drug interactions; stimulant
side effects include insomnia, agitation,
tachycardia, hypertension; additive effects
with other stimulants (caffeine, cold
medications, etc); can be addicting; avoid
with monoamine oxidase (MAO) inhibitors;
all indicated for short-term (generally
interpreted as up to 12 weeks) use only.
Significant side effects of topiramate include
paresthesias, somnolence, and difficulty concentrating. Topiramate has also been
associated with metabolic acidosis.
Selective serotonin 2C receptor agonist
(less cardiac side effects than nonselective
serotonin agonists).
Recommended as first-line pharmacotherapy
along with behavioral and dietary changes.
Gastrointestinal side effects common:
diarrhea, fecal incontinence, bloating,
cramps, gas, oily stools; must follow low-fat
diet to reduce side effects; may give vitamin
supplements for decreased absorption of
fat-soluble vitamins (A, D, E) and betacarotene; indicated for short- or long-term
use.
3-mg subcutaneous injection once daily
(after 4-week escalation); inform patient of
unconfirmed risk of thyroid tumors; risk of
pancreatitis. Common side effects include
nausea, vomiting, diarrhea, and increased
heart rate.
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Metformin and glucagon-like peptide-1 (GLP-1) receptor agonists (medications
approved for treatment of type 2 diabetes mellitus) may be a useful adjunct for
weight loss in patients with comorbid obesity. Metformin can also help with weight
loss in patients with PCOS.
Many previously approved medications for weight loss have been removed from
the market due to significant risks greater than benefits. Over-the-counter weightloss medications and supplements have similar risk-benefit profiles or have limited
research for safety and efficacy.
Bariatric Surgery. Patients with a BMI greater than 40 kg/m2 who have failed
diet and exercise (with or without drug therapy), or greater than 35 kg/m2 with
serious comorbid conditions, are potential candidates for surgical treatment of
obesity. Weight-loss surgeries fall into one of two categories: restrictive and
restrictive-malabsorptive. Restrictive surgeries, such as laparoscopic adjustable
gastric banding, limit the amount of food the stomach can hold and slow the
rate of gastric emptying. Restrictive-malabsorptive bypass procedures, such as
the Roux-en-Y gastric bypass, combine the elements of gastric restriction and
selective malabsorption.
The two most common surgeries done are Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding, or “lap banding.” The Roux-en-Y procedure
involves the construction of a small (10- to 30-mL) gastric pouch that empties into
a segment of jejunum. With the small pouch and the small outlet to limit caloric
intake, the Roux-en-Y is mostly a restrictive procedure with some degree of associated malabsorption. The surgical mortality rate from bariatric surgery is generally
< 1% but varies with the procedure, patient’s age and comorbid conditions, and
experience of the surgical team. The most common surgical complications include
stomal stenosis or marginal ulcers (occurring in 5% to 15% of patients) that present as prolonged nausea and vomiting after eating or inability to advance the diet
to solid foods.
In lap banding, an adjustable silicone gastric band is laparoscopically placed
around the upper stomach just distal to the gastroesophageal junction. The band
has a balloon connected to a subcutaneously implanted port, which can be inflated
or deflated to reduce the circumference of the band. Complications of the banding
procedure are less common and less severe than in gastric bypass, but the longterm weight loss may also be less. The adjustable band allows for the flexibility of
addressing various nutritional demands after the surgery. For example, the band
can be adjusted to have the stoma widened to accommodate a greater demand for
caloric and fluid intake when a patient becomes pregnant.
Complications
Obesity is a risk factor for the development of diabetes and CVD, as well as numerous other medical conditions (Table 33–4). In general, greater BMI is associated
with more health complications, and grade II or higher obesity is associated with
greater risk of mortality. Also, the more complications that develop, the more difficult
it becomes to manage the underlying obesity. For example, a person with degenerative arthritis and heart disease may have significant symptoms during exercise,
impairing his or her ability to expend more energy in an effort to lose weight.
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Table 33–4 • COMMON MEDICAL COMPLICATIONS OF OBESITY
Cardiovascular disease
Cerebrovascular disease
Cholelithiasis
Chronic kidney disease
Degenerative joint disease
Eating disorders
Hyperlipidemia
Hypertension
Infertility/reduced fertility
Malignancies
Menstrual cycle irregularities
Mood disorders
Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis
Polycystic ovary syndrome
Psychosocial dysfunction
Sleep apnea
Type 2 diabetes mellitus
CASE CORRELATION
See also Case 15 (Thyroid Disorders), Case 35 (Hyperlipidemia), and
Case 50 (Menstrual Cycle Irregularity).
COMPREHENSION QUESTIONS
33.1 A 35-year-old man presents to the clinic stating that he has been experiencing
chest pain and shortness of breath and is having increased episodes of asthma
exacerbation. He is 5 ft 10 inches and weighs 399 lb. An electrocardiogram
in the office shows a normal sinus rhythm. He performs very little physical
activity due to his weight. He has friends but has some esteem issues because
of his weight issue. He has tried to lose weight but has not been successful in
many attempts at dieting. He asks about who would be candidates for bariatric surgery. Which of the following patients has the best evidence to be a
candidate for bariatric surgery as initial treatment for obesity?
A. A man with a BMI of 32 kg/m2 and arthritis of the knees.
B. A woman with a BMI of 33 kg/m2 and type 2 diabetes.
C. A woman with a BMI of 42 kg/m2 but no identifiable complications.
D. Any obese patient who desires bariatric surgery should have it offered.
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