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Table 1. Differential Diagnosis of Involuntary Weight Loss (IWL)
Disease Notes
Cancer Percent of patients with cancer and a physical cause of IWL, 30%-55%; percent of all patients with IWL, 16%-38%. Gastrointestinal disorders Percent of patients with a gastrointestinal disorder and a physical cause of IWL, 22%-25%; percent of all patients with IWL,
10%-18%.
Endocrine disorders Percent of patients with an endocrine disorder and a physical cause of IWL, 6%-9%; percent of all patients with IWL, ~5%. Infections Percent of patients with an infection and a physical cause of IWL, 6%-9%; percent of all patients with IWL, ~5%. Pulmonary disorders Percent of patients with a pulmonary disorder and a physical cause of IWL, 8%; percent of all patients with IWL, 6%. Medications Percent of patients with physical cause of IWL due to medication, 3%-18%; percent of all patients with IWL, 2%-9%. Cardiovascular diseases Percent of patients with cardiovascular disease and a physical cause of IWL, 13%; percent of all patients with IWL, ~9%. Renal disease Percent of patients with renal disease and a physical cause of IWL, 6%; percent of all patients with IWL, 4%.
Neurologic disease Percent of patients with neurological disease and a physical cause of IWL, 2%-13%; percent of all patients with IWL, 2%-7%. Depression Percent of all patients with IWL, 9%-18%.
anticholinergic agents, and dopaminergic agents such as L-dopa and metoclopramide.
Weight loss is commonly associated with psychiatric disorders, especially depression. Dementia may cause weight loss that pre- cedes the diagnosis of the underlying cognitive disorder. Eating disorders such as anorexia and substance abuse disorders such as alcoholism cause weight loss. Socioeconomic and functional prob- lems may cause or exacerbate weight loss. Examples include diffi- culty in obtaining food because of functional disabilities, lack of financial resources, and social isolation and loneliness.
Evaluation
Because a substantial proportion of patients who report weight loss may not have experienced it, use documented weight meas- urements or objective evidence of weight loss, such as change in fit of clothes or corroboration by a trusted observer, before pur- suing an evaluation. Then, confirm that changes in total body water are not the cause of weight loss. Dramatic weight changes can occur with gain or loss of total body water, which occur more quickly and erratically than changes in lean body mass.
Although the differential diagnosis of weight loss is wide rang- ing, it is clear from the literature that a carefully performed histo- ry and physical examination, followed by targeted use of diag- nostic studies, is most likely to discover the etiology. An often overlooked clinical pearl is that the chief complaint frequently points to a specific etiology. Look for information that suggests chronic diseases such as malignancy, gastrointestinal disorders, endocrinologic disorders, infections, or severe cardiopulmonary conditions. Take a careful medication history with particular emphasis on medications known to affect appetite or whose use is temporally related to weight loss. Be certain to assess the patient’s affective and cognitive state. Standard tools based on DSM IV criteria to assess for depression or the Mini-Mental State Examination to assess cognition can be very helpful in this regard.
Obtain a history of dietary practices, dietary intake, and supple- ment use. Inquire about the living environment, functional sta- tus, dependency, caregiver status, alcohol or substance abuse, social support, and resources. It is important to question rela- tives and caregivers.
Initial diagnostic testing is limited to basic studies unless the history and physical examination suggest a specific cause (Table 2). The following studies should be obtained in most patients: com- plete blood count, erythrocyte sedimentation rate or C-reactive protein, serum chemistry tests including calcium and liver tests, thyroid stimulating hormone level, urinalysis, chest radi- ograph, and stool occult blood. In patients with gastrointesti- nal symptoms or abnormalities in blood counts or liver tests, obtain an upper gastrointestinal series, abdominal ultrasonog- raphy, abdominal CT scan, or esophagogastroduodenoscopy, as appropriate. Indiscriminate imaging of the thorax and abdomen with CT or MRI in the absence of supporting history, physical examination, or laboratory findings is not helpful. Truly occult malignancy is not common.
It may be difficult to establish a definitive diagnosis for weight loss, and perhaps a quarter or more of patients will not have a diag- nosis after an appropriate initial evaluation. For such patients, care- ful reevaluation over time is an appropriate course; if serious dis- ease is present, the cause is likely to become evident within 3 to 6 months. If an etiology cannot be established over time, the prog- nosis is favorable.
Treatment
Once a specific diagnosis is made, treatment should, in most patients, alleviate weight loss. If weight loss continues, the puta- tive diagnosis may not be correct or completely responsible. Consider medication and lifestyle changes for some patients. Change or eliminate medications that may be associated with anorexia and/or temporally related to weight loss. Address issues
122 • General Internal Medicine
Table 2. Laboratory and Other Studies for Involuntary Weight Loss
Test Notes
CBC Anemia is present in 14% with a physical cause of weight loss.
Electrolytes, blood urea nitrogen, The combination of decreased albumin and elevated alkaline phosphatase is 17% sensitive and 87% creatinine, glucose, liver tests specific for cancer. Adrenal insufficiency is associated with electrolyte disturbances in 92% of patients. ESR Increased in patients with neoplasia (mean ESR 49 mm/h) compared with those with psychiatric
(mean ESR 19 mm/h) and unknown cause (mean ESR 26 mm/h) of IWL. Thyroid-stimulating hormone To look for “apathetic” hyperthyroidism.
Chest radiography A useful test overall in individuals with a physical cause of IWL. HIV If risk factors are present.
Upper GI x-ray series, EGD, abdominal Upper GI has the highest yield in disclosing a pertinent abnormality beyond basic screening tests ultrasonography, or abdominal CT scan among persons with physical cause of weight loss if GI symptoms are present. Among patients
diagnosed with cancer, the following were the most useful follow-up tests to make a diagnosis: for patients who had only an isolated abnormality in the CBC, abdominal CT scan, abdominal ultrasonography, and endoscopy; for patients who had only an isolated abnormality in liver tests, abdominal ultrasonography and abdominal CT scan; and for patients who had normal liver tests and CBC, upper endoscopy and abdominal CT scan.
CBC = complete blood count; CT = computed tomography; EGD = esophagogastroduodenoscopy; ESR = erythrocyte sedimentation rate; GI = gastrointestinal; HIV = human immunodeficiency virus; IWL = involuntary weight loss.
of social isolation and poor eating environments, if applicable. Ensure that oral health is adequate and that the patient has access to food and is able to eat it. Address personal and ethnic food pref- erences in the promotion of oral dietary intake. Assist those who need help with eating by seeking to improve their functional sta- tus or making certain they obtain help to eat. Eliminate restrictive diets, where appropriate.
The proven benefit of oral nutritional supplementation for weight loss is limited. In fact, the amount of regular food intake is sometimes decreased by oral nutritional supplement use. However, nutritional supplementation may be useful when access to calories is an issue due to functional impairments. Appetite stim- ulants are often recommended but are of limited benefit in patients not responding to treatment of the primary cause or if the cause of weight loss is unknown. Appetite-stimulant therapy has been studied mainly in patients with AIDS or cancer cachexia. In these patients, certain agents (e.g., megestrol acetate, human growth hormone) have been shown to promote weight gain. However, a survival benefit has never been demonstrated, and in some trials
patients who received such agents have experienced an increase in mortality.
Book Enhancement
Go to www.acponline.org/essentials/general-internal-medicine -section.html to access tables on drug treatment, important his- tory and physical examination elements for involuntary weight loss, nutritional syndromes, and a patient administered nutrition checklist for older adults. In MKSAP for Students 4, assess your- self with items 40-41 in the General Internal Medicine section.
Bibliography
Leff B.Weight Loss. http://pier.acponline.org/physicians/diseases/d244. [Date accessed: 2008 Jan 22] In: PIER [online database]. Philadelphia: American College of Physicians; 2008.
Vanderschueren S, Geens E, Knockaert D, Bobbaers H. The diagnostic spectrum of unintentional weight loss. Eur J Intern Med. 2005;16:160- 164. [PMID: 15967329]
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D
isorders of menstruation are common, ranging from the complete absence of menstrual blood flow (amenorrhea) to irregular or heavy bleeding (abnormal uterine bleed- ing), and later in the life cycle culminate in the menopause. The normal menstrual cycle depends on a tightly regulated system that includes the central nervous system, hypothalamus, pituitary, ovaries, uterus, and vaginal outflow tract. Disruption of the axis at any level can cause a variety of menstrual disorders (Table 1).The menstrual cycle is regulated by the pituitary-hypothalamic axis. The hypothalamus releases gonadotropin-releasing hormone (GnRH) in a pulsatile fashion, stimulating release of follicle- stimulating hormone (FSH) and leuteinizing hormone (LH) from the pituitary. FSH causes the development of multiple ovar- ian follicles, which in turn release estradiol. Estradiol inhibits FSH release, allowing only one or two dominant follicles to sur- vive, and stimulates LH secretion. LH promotes progesterone