Interpretation of Selected Findings in Evaluating Fatigue

Anorexia, abdominal pain, weight loss, or steatorrhea

Undernutrition secondary to gastrointestinal tract disorder, cancer

Endoscopy, MRI of abdomen, MRCP

Anorexia, abdominal pain, weight loss, orthostatic hypotension, skin hyperpigmentation

Adrenal insufficiency

Blood electrolyte, cortisol, and ACTH levels; Sometimes synthetic ACTH 1-24 (Cortrosyn®) stimulation test

Fever, night sweats, or weight loss

Infection, rheumatologic disorder (including vasculitis)

Chest radiograph, CBC, ESR, blood or other cultures, rheumatoid factor and ANA

Dyspnea with cough or hemoptysis

HIV/late-stage HIV (with Pneumocystis jirovecii pneumonia), fungal pneumonia, tuberculosis, COVID-19

Chest radiograph, chest CT or PET-CT, HIV test, sputum cytology and/or culture, pulmonary function tests, PPD, molecular or antigen test for SARS-CoV-2

Dyspnea, orthopnea, and/or edema

Chronic kidney disease, heart failure

Chest radiograph, renal function tests, echocardiography (if orthopnea)

Dyspnea, Roth spots, Janeway lesions, new or changing heart murmurs, IV drug use

Endocarditis

Multiple blood cultures, echocardiography

Decreased exercise tolerance with dyspnea on exertion, pallor

Anemia

CBC

Generalized lymphadenopathy

HIV/late stage HIV, leukemia, lymphoma, mononucleosis

HIV test, CBC, EBV serologic tests

Combined arthritis, rash, and/or other organ involvement

Systemic rheumatic disease (including vasculitis)

CBC, ESR, rheumatoid factor, anti-CCP, ANCA, ANA

Jaundice, ascites, confusion

Hepatitis

Liver tests, viral hepatitis serologies

Polydipsia, polyuria, increased appetite, weight gain or loss

Diabetes

Fasting plasma glucose level, HbA1C, glucose tolerance testing

Cold intolerance, weight gain, constipation, coarse skin

Hypothyroidism, pituitary insufficiency

Thyroid function tests

Weight loss or atrial fibrillation in older adult

Hyperthyroidism (including apathetic)

Thyroid function tests

Fatigue worse with exposure to heat, past neurologic symptoms (eg, numbness, ataxia, weakness), particularly > 1 episode

Multiple sclerosis

Brain and/or spinal cord MRI with contrast

Headache, jaw claudication, temporal artery tenderness or thickening, and/or muscle pains in an older adult

Giant cell arteritis

ESR, brain MRI or CT, temporal artery biopsy

Anxiety, sadness, anorexia, unexplained sleep disturbance

Anxiety, depression, domestic violence, somatization disorder

Clinical evaluation

Recent sore throat, lymphadenopathy, splenomegaly

Mononucleosis, myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease

EBV serologic tests; CBC, ESR, TSH, chemistries (as for suspected chronic fatigue syndrome)

Lymphadenopathy, splenomegaly

CMV infection, lymphoma

EBV serologic tests, sometimes CMV antibody testing; flow cytometry, excisional biopsy of a lymph node

Frequent or opportunistic infections, candidiasis, lymphadenopathy, splenomegaly

HIV/late stage HIV

HIV testing

Chronic, widespread musculoskeletal extra-articular pain, trigger points, irritable bowel symptoms, migraines, anxiety

Fibromyalgia

ESR or C-reactive protein, CK, TSH, hepatitis C serology

Weight loss, steatorrhea, inadequate oral intake

Undernutrition, pancreatic insufficiency

Plasma albumin, total lymphocyte and CD4 counts, serum transferrin, serum vitamin B12, serum iron, serum folate, fecal elastase measurement

Constipation, lethargy, bone pain (eg, at night)

Hypercalcemia

Serum chemistries, including calcium

Postexertional malaise, unrefreshing sleep, difficulty with concentration or short-term memory, orthostatic intolerance, sore throat, myalgias, headaches

Myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease

CBC, ESR, TSH, serum electrolytes, glucose, calcium, renal and liver tests