Weight Loss (Case 41)

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Chapter 49
Weight Loss (Case 41)

Pamela R. Schroeder MD, PhD

Case: A 34-year-old woman with a history of HIV infection presents complaining of an unintentional weight loss of 20 pounds in 3 months despite an increased appetite. She also has been experiencing diaphoresis, heat intolerance, palpitations, fatigue, hair loss, and a gritty feeling in her eyes. Before 3 months ago her weight had been stable. She denies difficulty swallowing or breathing, mood changes, voice changes, or difficulty concentrating. She has noted that her menses are lighter than usual, but they are regular, occurring every 28 days without skipping months. She is compliant with her antiretroviral medications. She has a 15 pack-year history of smoking cigarettes, but denies alcohol or illicit drug use. She does not get any regular exercise.

Differential Diagnosis

Cancer	Infection (e.g., HIV, tuberculosis)	Gastrointestinal causes (e.g., malabsorption, hepatitis)
Endocrine (e.g., uncontrolled diabetes, thyrotoxicosis)	Psychiatric (e.g. depression, anorexia, bulimia)	Chronic illness
Intense exercise	Cardiac (e.g., advanced heart failure)	Pulmonary (e.g., chronic obstructive pulmonary disease [COPD])
Substance abuse (e.g., opiates, cocaine, amphetamine, cannabinoids)	Heavy cigarette smoking	Medications (e.g., antidepressants, antiepileptics, exenatide, metformin, pramlintide, topiramate, digoxin, nonsteroidal anti-inflammatory drugs [NSAIDs])

Speaking Intelligently

Upon initially encountering a patient who reports weight loss, I first quantify the amount of weight lost over a specified time frame and determine whether this was intentional or unintentional weight loss. Clinically significant weight loss is defined as over 10 pounds or greater than 5% of body weight in 6 to 12 months. I like to know what kind of appetite the patient has. Causes of unintentional weight loss with an increased appetite usually involve either an underlying medical cause or a significant increase in rigorous exercise, leading to calorie loss despite increased appetite. Examples in this category include malabsorption, uncontrolled diabetes mellitus, and hyperthyroidism. I also like to find out if there is any history of cancer, if patients are up to date on their general medical screenings (e.g., Papanicolaou test, or PAP smear; mammogram; colonoscopy), and if there are gastrointestinal symptoms, fever, psychiatric symptoms, substance abuse or heavy smoking, rigorous exercise, medications, and chronic illnesses. As there is a broad differential diagnosis, the key is to narrow down the possible causes with a thorough history and physical exam.

PATIENT CARE

Tests for Consideration

• Use clinical judgment when ordering tests based on degree of clinical suspicion for the disease.
• CBC: WBC count is increased in infection.	$11
• Comprehensive chemistry panel: Liver function tests will be abnormal in hepatitis; renal function might be abnormal if taking a medication (e.g., NSAIDs) causing renal failure; electrolytes might be abnormal in multiple chronic illnesses; blood glucose will be elevated in uncontrolled diabetes.	$12
• TSH with reflex free thyroxine (T4): TSH is suppressed in thyrotoxicosis with elevated free T4.	$24, $9
• Erythrocyte sedimentation rate (ESR): If high and clinically likely, suspect tuberculosis (TB), then check sputum acid-fast smears, sputum culture, and purified protein derivative (PPD).	$4
• Brain natriuretic peptide (BNP): Elevated in CHF.	$45
• Prostate-specific antigen (PSA): Elevated in prostate cancer.	$26
• Urine toxicology screen: Evaluate for opiates, cocaine, amphetamine, and cannabinoids.	$21

IMAGING CONSIDERATIONS

→ Chest radiographs: Posteroanterior (PA) and lateral chest radiographs might show pulmonary venous congestion, cardiomegaly, and/or pleural effusion in patients with CHF. In patients with TB, chest radiograph might reveal hilar and paratracheal lymphadenopathy, cavitary lesions, and/or upper lobe infiltrates. In patients with COPD, diaphragms are flattened with hyperinflation. Large mass might be seen in smoker with lung cancer.	$45
→ Transthoracic echocardiogram: Evaluate left ventricular function and ejection fraction in patients with CHF.	$393
→ Thyroid uptake and scan: Evaluate degree of hyperthyroidism with uptake; pattern on scan can help with etiology (diffuse pattern in Graves disease or multiple hot nodules in toxic multinodular goiter).	$221
→ Mammogram: Evaluate for mass that might be seen in patients with breast cancer.	$130
→ Upper endoscopy/colonoscopy: Evaluate for gastrointestinal pathology (e.g., colon cancer).	$600, $655

Clinical Entities

Medical Knowledge

Congestive Heart Failure
Pφ	CHF occurs when the heart cannot adequately pump blood. Fluid builds up in the lungs, causing pulmonary edema. This condition can be due to systolic or diastolic dysfunction.
TP	Typical symptoms include shortness of breath at rest, orthopnea, paroxysmal nocturnal dyspnea, edema, jugular venous distension, and crackles. If advanced, weight loss can occur.
Dx	Diagnosis is made based on clinical symptoms, physical exam findings, elevated BNP, and chest radiographic findings of pulmonary congestion, pleural effusions, and cardiomegaly.
Tx	Treatment is focused on diuretics with strict input and output measurements with more fluid out than in, sodium and fluid restriction, morphine, nitrates, supplemental oxygen, and inotropic agents, if indicated. See Cecil Essentials 4, 6.

Cancer
Pφ	Cancer must be suspected, especially in an elderly patient who is losing weight unintentionally. The differential diagnosis of cancer is broad and beyond the scope of this chapter, as is the underlying pathophysiology of the different types of cancers.
TP	Different types of cancers present in different ways, but unintentional weight loss with a decreased appetite and cachexia is common to many types of cancer. Look for other symptoms and signs to help with the type of cancer (e.g., smoking history and shortness of breath in lung cancer or Hemoccult-positive pencil-thin stools in colon cancer).
Dx	Diagnosis of cancer is made with the clinical signs and symptoms and targeted lab and radiology tests. Examples include mammogram in breast cancer, chest radiograph or CT of the chest in lung cancer, PSA in prostate cancer, hematocrit, and stool guaiac and colonoscopy in colon cancer.
Tx	Treatment of cancer is beyond the scope of this chapter. Specifically for the weight loss, encourage the patient to eat frequent small meals and snacks, to drink meal supplements or shakes, and, if weight loss is severe, to take megestrol to stimulate appetite.

Thyrotoxicosis
Pφ	Thyrotoxicosis is the clinical syndrome associated with excess thyroid hormone, from either endogenous or exogenous sources. Hyperthyroidism is the endogenous production of too much thyroid hormone, such as occurs in Graves disease or with a toxic adenoma. Graves disease is caused by thyroid-stimulating immunoglobulins binding to and stimulating the thyroid to produce thyroid hormone. Toxic adenomas are often due to mutations in the Gs α-subunit or the TSH receptor, causing activation of the pathway leading to thyroid hormone production.
TP	Typically patients present with unintentional weight loss and increased appetite with other symptoms and signs of thyrotoxicosis, including heat intolerance, diaphoresis, tremors, palpitations, hyperdefecation, and difficulty concentrating.
Dx	The diagnosis is made clinically based on symptoms and signs and confirmed with thyroid function tests. Physical exam can be helpful. For example, if a diffuse goiter and exophthalmos are seen, this suggests Graves disease. A palpable nodule supports toxic adenoma. TSH should be suppressed with a high free T4 and/or total T3. Thyroid uptake and scan is helpful to determine the degree of overactivity from the uptake; the pattern from the scan confirms the etiology. There is a diffuse pattern in Graves disease and multiple hot nodules in toxic multinodular goiter.
Tx	Treatment of hyperthyroidism is with antithyroid medications, such as methimazole or propylthiouracil, or radioactive iodine; most experts prefer radioactive iodine. Most patients are also given β-adrenergic-blocking agents, unless contraindicated. Surgery is rarely indicated and is performed in cases refractory to medical therapy. See Cecil Essentials 66.

Anorexia Nervosa
Pφ	The underlying pathogenesis of anorexia nervosa is unclear, although psychological, genetic, and environmental factors are all thought to contribute to its development.
TP	Typically, patients present with disturbed body image, where they fear weight gain, are in denial about the illness, refuse to maintain a normal weight (for height and age), and have amenorrhea or oligomenorrhea in females after menarche.
Dx	The diagnosis is made with the clinical history meeting the Diagnostic and Statistical Manual IV of Mental Disorders (DSM-IV) criteria and a thorough physical exam looking for findings (e.g., on gastrointestinal or neurologic exam) to rule out other causes of chronic weight loss and vomiting (e.g., brain tumor, inflammatory bowel disease, new-onset diabetes mellitus). Basic laboratory values, as above, are also checked (e.g., BUN, creatinine, electrolytes, glucose, β-human chorionic gonadotropin [HCG]) to look for dehydration and rule out other causes.
Tx	Treatment includes weight gain, calcium supplements, daily multivitamins, and possible estrogen/progesterone replacement. Markedly underweight persons may require a hospital-based program to achieve weight restoration; if patients refuse to eat, nasogastric feeding may be used. Psychotherapy is the mainstay for treatment when adequate nutrition is restored. See Cecil Essentials 61.

a. Adrenal insufficiency occurs when the adrenal gland is not functioning (primary) or if the pituitary gland is not sending the signal (i.e., ACTH; secondary) to the adrenal gland to make cortisol. In primary adrenal insufficiency, patients are also deficient in the other hormones synthesized in the adrenal glands such as aldosterone. In addition to weight loss, patients may present with weakness, malaise, fatigue, myalgias, arthralgias, nausea, vomiting, abdominal pain, dizziness, and hypotension. In primary adrenal insufficiency, patients can also have hyperpigmentation. Laboratory findings can include hyponatremia, hyperkalemia, hypoglycemia, eosinophilia, lymphocytosis, and neutropenia. Although adrenal insufficiency is uncommon, clinical suspicion must be high, because administering corticosteroids may be lifesaving in acute adrenal insufficiency and will improve the symptoms of chronic adrenal insufficiency.

Practice-Based Learning and Improvement: Evidence-Based Medicine

Title
Oxandrolone in the treatment of HIV-associated weight loss in men: a randomized, double-blind, placebo-controlled study

Authors
Grunfeld C, Kotler DP, Dobs A, Glesby M, Bhasin S

Institution
University of California–San Francisco and Department of Veterans Affairs Medical Center, San Francisco

Reference
J Acquir Immune Defic Syndr 2006;41:304–314

Problem
Unintentional weight loss is a significant problem in HIV-infected individuals and may contribute to morbidity in this population.

Intervention
Patients received the anabolic steroid oxandrolone or placebo for 12 weeks, then open-label oxandrolone for another 12 weeks.

Quality of evidence
Level I

Outcome/effect
Oxandrolone administration is effective in promoting dose-dependent gains in body weight in HIV-infected men with weight loss.

Historical significance/comments
This study examined the effects of the administration of an anabolic steroid oxandrolone, which has been used to promote weight gain, to men with HIV-associated weight loss. The study included 262 subjects and 24 weeks of data. Because oxandrolone cannot be aromatized to estrogen, it does not cause side effects such as gynecomastia. It is therefore an important potential therapy in this population.

Interpersonal and Communication Skills

Avoid Unapproved Abbreviations That May Lead to Medical Errors

In this chapter we use some abbreviations, including HIV and CHF. In general, abbreviations constitute an acceptable means of medical communication, but certain abbreviations should be avoided in medical orders and progress notes, as they can lead to confusion and medical errors. Consider the following:

Abbreviation	Potential problem	Preferred terminology
U (units)	Mistaken as zero, four or cc	Write the word “units.”
IU (international units)	Mistaken as IV or 10	Write “international units.”
Q.D. and Q.O.D. (Latin abbreviations for once daily and once every other day)	Mistaken for each other. The period after “Q” can be mistaken for an “I,” and the “O” can be mistaken for an “I.”	Write “daily” and “every other day.”
Trailing zero (X.0 mg) Lack of leading zero (.X mg)	Decimal point is missed.	Never write a zero by itself following a decimal point (X mg), and always use a zero before a decimal point (0.X mg).
MS MSO4 MgSO4	Confused for one another. Can mean morphine sulfate or magnesium sulfate.	Write “morphine sulfate” or “magnesium sulfate.”
From Mann BD. Surgery: a competency-based companion. Philadelphia: Elsevier; 2009, p. 190.

Professionalism

Maintain Boundaries of Professional Care

There will be times in every career in medicine when the person with the serious illness is a family member or loved one. These are arguably the hardest cases for physicians. If the patient is a spouse, for example, it is important to maintain your role as spouse and not your role as doctor, despite your medical knowledge. Entrusting your loved one’s care to a capable and compassionate colleague is the right thing to do. Caring for family members crosses the boundary of self-care. Judgment is often clouded, and thus medical decision making may be affected. Knowing that there are some things that you simply cannot do or change is extremely important. It is equally important to know when to seek help for yourself.

Systems-Based Practice

Radiation Safety for Patients and Families

Though radioactive iodine has been used to treat patients with hyperthyroidism since the 1940s, there are a number of patient safety concerns regarding its use. Properly following safety instructions at the time of treatment should minimize radiation exposure to individuals other than the patient, such as family members and visitors. Patients who have been treated should be informed to avoid young children and pregnant women. Mothers with young children will often need to make special arrangements for child care following therapy. Patients may remain detectably radioactive for several days and even weeks and should carry a doctor’s note in case sensitive radiation detectors at airports or government buildings are triggered. As a precaution, pregnant or nursing women should not receive radiation, and women who are treated should not become pregnant for 6 to 12 months following treatment.