Evaluation of fatigue

Use of depression screening instruments may help exclude a depressive disorder when assessing a complaint of fatigue. The 2-question patient health questionnaire (PHQ-2) asks only how often the patient feels depressed and if he or she is able to experience any joy or pleasure.[99]Kroenke K, Spitzer RL, Williams JB. The patient health questionnaire-2: validity of a two-item depression screener. Med Care. 2003 Nov;41(11):1284-92. http://www.ncbi.nlm.nih.gov/pubmed/14583691?tool=bestpractice.com [ Depression (any) Screening by a Two Item PHQ-2 Opens in new window ] [ Depression (major) Screening by a Two Item PHQ-2 Opens in new window ]

Case-finding instruments for depression in primary care have on average a sensitivity of 84%, a specificity of 72%, and a likelihood ratio of 3.[123]Mulrow CD, Williams JW Jr, Gerety MB, et al. Case-finding instruments for depression in primary care settings. Ann Intern Med. 1995 Jun 15;122(12):913-21. http://www.ncbi.nlm.nih.gov/pubmed/7755226?tool=bestpractice.com Given a prior probability of 25%, the post-test probability that the patient has depression is 50% with a positive result instrument. Conversely, the negative likelihood ratio is 0.2, and therefore only 7% with a negative result instrument will have depression.

PHQ-9 is adapted from PRIME MD (The Primary Care Evaluation of Mental Disorders) as a brief screening instrument aiding in recognition of depression in the primary care setting. PRIME MD requires 8 minutes to complete, whereas the PHQ-9 takes <3 minutes.[100]Spitzer RL, Williams JB, Kroenke K, et al. Utility of a new procedure for diagnosing mental disorders in primary care: the PRIME-MD 1000 study. JAMA. 1994 Dec 14;272(22):1749-56. http://www.ncbi.nlm.nih.gov/pubmed/7966923?tool=bestpractice.com [101]Jackson JL, Houston JS, Hanling SR, et al. Clinical predictors of mental disorders among medical outpatients. Arch Intern Med. 2001 Mar 26;161(6):875-9. http://archinte.ama-assn.org/cgi/content/full/161/6/875 http://www.ncbi.nlm.nih.gov/pubmed/11268232?tool=bestpractice.com [102]Spitzer RL, Kroenke K, Williams JB; Patient Health Questionnaire Primary Care Study Group. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. JAMA. 1999 Nov 10;282(18):1737-44. http://jama.jamanetwork.com/article.aspx?articleid=192080 http://www.ncbi.nlm.nih.gov/pubmed/10568646?tool=bestpractice.com

Microcytic hypochromic anemia.

In menstruating females complaining of fatigue, iron treatment is recommended at a ferritin level <50 nanograms/mL (treatment goal: ferritin ≥50 nanograms/mL).[16]Verdon F, Burnand B, Stubi CL, et al. Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. BMJ. 2003 May 24;326(7399):1124. http://www.bmj.com/cgi/content/full/326/7399/1124 http://www.ncbi.nlm.nih.gov/pubmed/12763985?tool=bestpractice.com [17]Vaucher P, Druais PL, Waldvogel S, et al. Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial. CMAJ. 2012 Aug 7;184(11):1247-54. http://www.ncbi.nlm.nih.gov/pubmed/22777991?tool=bestpractice.com [30]Krayenbuehl PA, Battegay E, Breymann C, et al. Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration. Blood. 2011 Sep 22;118(12):3222-7. http://bloodjournal.hematologylibrary.org/content/118/12/3222.long http://www.ncbi.nlm.nih.gov/pubmed/21705493?tool=bestpractice.com In cases of hair loss the treatment goal may be as high as 70 nanograms/mL.[124]Rushton DH, Norris MJ, Dover R, et al. Causes of hair loss and the developments in hair rejuvenation. Int J Cosmet Sci. 2002 Feb;24(1):17-23. http://www.ncbi.nlm.nih.gov/pubmed/18498491?tool=bestpractice.com [125]Trost LB, Bergfeld WF, Calogeras E. The diagnosis and treatment of iron deficiency and its potential relationship to hair loss. J Am Acad Dermatol. 2006 May;54(5):824-44. http://www.ncbi.nlm.nih.gov/pubmed/16635664?tool=bestpractice.com

Presence of anterior Q waves suggests previous MI.

Anemia can exacerbate chronic heart failure. WBC count may be elevated in presence of comorbid lung infection.

Fasting blood glucose levels between 100 and 125 mg/dL suggest impaired fasting glucose rather than overt diabetes mellitus.

An initial screening test.​[133]American Diabetes Association Professional Practice Committee. 2. Diagnosis and classification of diabetes: standards of care in diabetes-2024. Diabetes Care. 2024 Jan 1;47(suppl 1):S20-42. https://diabetesjournals.org/care/article/47/Supplement_1/S20/153954/2-Diagnosis-and-Classification-of-Diabetes http://www.ncbi.nlm.nih.gov/pubmed/38078589?tool=bestpractice.com ​​​

Levels of 140 to 199 mg/dL indicate impaired glucose tolerance. Useful in evaluating patients with a normal or impaired fasting blood glucose but high level of clinical suspicion.

Confirms the presence of primary hypothyroidism. In subclinical disease, levels are only mildly elevated.

Low free T4 with an elevated TSH is diagnostic of primary hypothyroidism. However, free T4 may be normal in subclinical hypothyroidism, despite a mildly elevated TSH.

Test for heterophile antibody (Paul-Bunnell IgM). False negative common early in course. Antibodies usually persist for 3 months.

Indicated if monospot test is negative, to differentiate EBV infection from other infectious causes of mononucleosis. Helps differentiate acute disease from past infection.

Viral capsid antigen: IgM positive early infection, IgG positive for life. Early antigen: IgG appears within weeks, then disappears. EBV nuclear antigen (EBNA): positive for life.

There are no pathognomonic features of influenza and further testing is indicated only when the results are likely to affect diagnosis and treatment decisions and to provide community disease surveillance.[134]Centers for Disease Control and Prevention. Influenza signs and symptoms and the role of laboratory diagnostics. October 2016 [internet publication]. http://www.cdc.gov/flu/professionals/diagnosis/labrolesprocedures.htm

Not essential to make the diagnosis.[121]Centers for Disease Control and Prevention. Evaluating and caring for patients with post-COVID conditions: interim guidance. Jun 2021 [internet publication]. https://emergency.cdc.gov/coca/calls/2021/callinfo_061721.asp

The UK guidance recommends chest x-ray if respiratory symptoms persist for 12 weeks following acute COVID-19 infection.[122]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing the long-term effects of COVID-19. Jan 2024 [internet publication]. https://www.nice.org.uk/guidance/ng188 ​ Note that normal plain chest x-ray does not rule out lung disease.

Specialized test requested if symptoms indicate it is appropriate.[121]Centers for Disease Control and Prevention. Evaluating and caring for patients with post-COVID conditions: interim guidance. Jun 2021 [internet publication]. https://emergency.cdc.gov/coca/calls/2021/callinfo_061721.asp

Specialized test requested if symptoms indicate it is appropriate.[121]Centers for Disease Control and Prevention. Evaluating and caring for patients with post-COVID conditions: interim guidance. Jun 2021 [internet publication]. https://emergency.cdc.gov/coca/calls/2021/callinfo_061721.asp

Withdrawal of medication usually results in resolution of fatigue within 48 to 72 hours.

The AUDIT is a 10-item questionnaire and is especially helpful in identifying less severe drinking problems.[104]Babor TF, Higgins-Biddle JC, Saunders JB, et al. The alcohol use disorders identification test: guidelines for use in primary care. 2nd ed. World Health Organization. Department of Mental Health and Substance Dependence. Geneva, Switzerland: WHO; 2001. http://apps.who.int/iris/bitstream/10665/67205/1/WHO_MSD_MSB_01.6a.pdf [ Alcohol Consumption Screening AUDIT Questionnaire Opens in new window ]

CAGE questionnaire: Have you ever felt the need to cut down on drinking? Have you ever felt annoyed by criticism of your drinking? Have you ever had guilty feelings about your drinking? Do you ever take a "morning eye opener" (a drink first thing in the morning to steady your nerves or get rid of a hangover)?[103]Ewing JA. Detecting alcoholism: the CAGE questionnaire. JAMA. 1984 Oct 12;252(14):1905-7. http://www.ncbi.nlm.nih.gov/pubmed/6471323?tool=bestpractice.com

Further investigation must be initiated if a positive answer is given to any of the above questions.

Alcohol may cause bone marrow suppression.

Tool to identify possible chronic heavy alcohol consumption. Better performance than liver enzymes.[118]Anton RF, Moak DH. Carbohydrate-deficient transferrin and gamma-glutamyltransferase as markers of heavy alcohol consumption: gender differences. Alcohol Clin Exp Res. 1994 Jun;18(3):747-54. http://www.ncbi.nlm.nih.gov/pubmed/7943686?tool=bestpractice.com

Indicates recent drug use. Negative screens do not exclude misuse. Hair samples useful when chronic misuse suspected.

Indicates recent drug use. Negative screens do not exclude misuse. Hair samples useful when chronic misuse suspected.

Risk of infection high among people who misuse intravenous drugs.

Risk of infection high among people who misuse intravenous drugs.

Incidence is increasing worldwide. Therefore, all patients with FUO should be tested. Acute and chronic HIV disease commonly associated with FUO.

Positive even in early disease.

Rate may be very rapid: 350 to 450 bpm.

Decreased if underlying hyperthyroidism.

COPD is classified based on the patient's FEV1 and its percentage of the predicted FEV1.

May also show features of exacerbating condition: for example, pneumonia.

Elevated hematocrit may indicate long-term hypoxia. Elevated WBC count may suggest acute exacerbation or infection.

Evidence of unrecognized pulmonary TB or evidence of old healed TB (e.g., upper lobe fibrosis) may be present; such abnormalities should prompt sputum collection for smear, culture, and nucleic acid amplification testing

Testing of 3 specimens (minimum 8 hours apart, including an early morning specimen) is recommended in many countries; consult local guidance.[135]Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017 Jan 15;64(2):111-5. https://www.doi.org/10.1093/cid/ciw778 http://www.ncbi.nlm.nih.gov/pubmed/28052967?tool=bestpractice.com ​​​ Sputum specimen should be tested in patients with suspected extrapulmonary TB, as active pulmonary TB is seen in 15% to 20% of patients with extrapulmonary TB.[136]Geldmacher H, Taube C, Kroeger C, et al. Assessment of lymph node tuberculosis in northern Germany: a clinical review. Chest. 2002 Apr;121(4):1177-82. https://www.doi.org/10.1378/chest.121.4.1177 http://www.ncbi.nlm.nih.gov/pubmed/11948050?tool=bestpractice.com [137]Weir MR, Thornton GF. Extrapulmonary tuberculosis. Experience of a community hospital and review of the literature. Am J Med. 1985 Oct;79(4):467-78. https://www.doi.org/10.1016/0002-9343(85)90034-8 http://www.ncbi.nlm.nih.gov/pubmed/4050833?tool=bestpractice.com ​​​[138]Baydur A. The spectrum of extrapulmonary tuberculosis. West J Med. 1977 Apr;126(4):253-62. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1237539 http://www.ncbi.nlm.nih.gov/pubmed/855317?tool=bestpractice.com

Culture of Mycobacterium tuberculosis typically takes several weeks (up to 8), decisions on treatment are usually made before culture results are known.

Microscopy should be performed on specimens collected from sites of suspected extrapulmonary TB.[135]Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017 Jan 15;64(2):111-5. https://www.doi.org/10.1093/cid/ciw778 http://www.ncbi.nlm.nih.gov/pubmed/28052967?tool=bestpractice.com ​​​[139]Nataraj G, Kurup S, Pandit A, et al. Correlation of fine needle aspiration cytology, smear and culture in tuberculous lymphadenitis: a prospective study. J Postgrad Med. 2002 Apr-Jun;48(2):113-6. https://www.jpgmonline.com/article.asp?issn=0022-3859;year=2002;volume=48;issue=2;spage=113;epage=6;aulast=Nataraj http://www.ncbi.nlm.nih.gov/pubmed/12215692?tool=bestpractice.com Culture result may take several weeks.

NAAT should be performed on at least one respiratory specimen (or specimen collected from sites of suspected extrapulmonary TB) when a diagnosis of TB is being considered.​​​ NAAT may speed the diagnosis in smear-negative cases and may be helpful to differentiate nontuberculous mycobacteria when sputum is AFB smear positive but NAAT negative.[140]Centers for Disease Control and Prevention. Updated guidelines for the use of nucleic acid amplification tests in the diagnosis of tuberculosis. Jan 2009 [internet publication]. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5801a3.htm Genotyping might be considered useful in outbreaks of TB to identify transmission of TB, especially when contact had not been appreciated in the course of epidemiologic investigations.

Although NAATs were originally designed and approved for respiratory specimens, they may also be requested on specimens from other sites where involvement of TB is suspected (e.g., cerebrospinal fluid, lymph node aspirate, lymph node biopsy, pleural fluid, peritoneal fluid, pericardial fluid, synovial fluid, or urine).[135]Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017 Jan 15;64(2):111-5. https://www.doi.org/10.1093/cid/ciw778 http://www.ncbi.nlm.nih.gov/pubmed/28052967?tool=bestpractice.com ​​​[141]World Health Organization. WHO consolidated guidelines on tuberculosis. Module 3: diagnosis: rapid diagnostics for tuberculosis detection. Mar 2024 [internet publication]. https://www.who.int/publications/i/item/9789240089488 In the US, use of NAATs for extrapulmonary specimens is not approved by the Food and Drug Administration, and use would be off-label.

Several rapid NAATs are available for the diagnosis of TB and some are also able to detect genes encoding resistance to TB drugs.[141]World Health Organization. WHO consolidated guidelines on tuberculosis. Module 3: diagnosis: rapid diagnostics for tuberculosis detection. Mar 2024 [internet publication]. https://www.who.int/publications/i/item/9789240089488

Bronchoalveolar lavage may be indicated in patients in whom sputum induction is unsuccessful or in whom smear and NAAT are negative.

Bronchoscopy is useful when other diagnoses are strongly considered or in patients in whom pulmonary TB is still suspected after other methods proved nondiagnostic.

Transbronchial lung biopsies are useful in the diagnosis of miliary disease as granulomas may be visible.

One Cochrane review found the lateral flow urine lipoarabinomannan (LF-LAM) assay to have a sensitivity of 42% in diagnosing TB in HIV-positive individuals with TB symptoms, and 35% in HIV-positive individuals not assessed for TB symptoms.[142]Bjerrum S, Schiller I, Dendukuri N, et al. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in people living with HIV. Cochrane Database Syst Rev. 2019 Oct 21;10(10):CD011420. https://www.doi.org/10.1002/14651858.CD011420.pub3 http://www.ncbi.nlm.nih.gov/pubmed/31633805?tool=bestpractice.com [ ] What is the accuracy of lateral flow urine lipoarabinomannan (LF‐LAM) for detecting tuberculosis (TB) in symptomatic HIV‐positive adults?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2824/fullShow me the answer [ ] What is the accuracy of lateral flow urine lipoarabinomannan (LF‐LAM) for detecting tuberculosis (TB) in unselected HIV‐positive adults (symptomatic or asymptomatic)?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2825/fullShow me the answer​​​ WHO recommends that LF-LAM can be used to assist in the diagnosis of active TB in HIV-positive adults, adolescents, and children with signs and symptoms of TB, or in those with advanced HIV or who are seriously ill.[141]World Health Organization. WHO consolidated guidelines on tuberculosis. Module 3: diagnosis: rapid diagnostics for tuberculosis detection. Mar 2024 [internet publication]. https://www.who.int/publications/i/item/9789240089488 Culture would still be required for drug susceptibility testing (DST).

Bronchiectasis can be seen in chronic cases. Hemoptysis usually originates from bronchial arteries, but Rasmussen aneurysms from a pulmonary artery adjacent to a cavity can be the source of bleeding.

Residual bronchiectasis from old TB can cause hemoptysis.

If only IgG are positive, tests for the avidity of IgG antibodies may discriminate between recently acquired infection and those obtained in the more distant past.[145]Hedman K, Lappalainen M, Seppala I, et al. Recent primary toxoplasma infection indicated by a low avidity of specific IgG.J Infect Dis. 1989 Apr;159(4):736-40. http://www.ncbi.nlm.nih.gov/pubmed/2926163?tool=bestpractice.com

Typical symptoms of OSA include sleepiness, fatigue, insomnia, or other symptoms leading to impaired sleep-related quality of life (e.g., unrefreshing sleep, daytime sleepiness, fatigue or insomnia, awakening with a gasping or choking sensation, loud snoring, or witnessed apneas).[126]American Academy of Sleep Medicine. International classification of sleep disorders - third edition, text revision (ICSD-3-TR). Westchester, IL: American Academy of Sleep Medicine; 2023. Polysomnography is the definitive test.[127]Gibson GJ. Obstructive sleep apnoea syndrome: underestimated and undertreated. Br Med Bull. 2005 Mar 29;72:49-65. https://academic.oup.com/bmb/article/72/1/49/272854 http://www.ncbi.nlm.nih.gov/pubmed/15798032?tool=bestpractice.com ​ General parameters measured include electroencephalogram, electro-oculographic recording, air flow assessment, electromyogram, capnography, esophageal manometry, ECG, pulse oximetry, respiratory effort signals, synchronized polysomnography video, and body position.[128]American Academy of Sleep Medicine. The AASM manual for the scoring of sleep and associated events. Feb 2023 [internet publication]. https://aasm.org/clinical-resources/scoring-manual

Polysomnography may be a full night study or a split study.

Used for patients with higher probability of OSA and without complex comorbidities (e.g., cardiopulmonary disease, chronic opioid therapy, or neuromuscular disease). Portable tests typically include a smaller selection of channels than the polysomnogram (nasal pressure, oximetry, thoracoabdominal effort sensors, heart rate), but usually do not measure sleep. Portable tests may underestimate the REI as obstructions are measured for recording time, not sleep time.

May be used to screen for the presence of alveolar hypoventilation, but does not confirm the diagnosis.

Guidelines recommend serum bicarbonate levels for patients with low to moderate probability of having OHS (<20%) to decide when to measure PaCO₂.[129]Erratum: Evaluation and management of obesity hypoventilation syndrome. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2019 Nov 15;200(10):1326. https://www.doi.org/10.1164/rccm.v200erratum7

Awake resting PaCO₂ >45 mmHg at sea level (awake daytime hypercapnia), in the presence of obesity (BMI ≥30 kg/m²) and sleep disordered breathing defines OHS (after excluding other causes of hypoventilation)[129]Erratum: Evaluation and management of obesity hypoventilation syndrome. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2019 Nov 15;200(10):1326. https://www.doi.org/10.1164/rccm.v200erratum7 Measure first in patients strongly suspected of having OHS to confirm the diagnosis.[130]Mokhlesi B, Masa JF, Brozek JL, et al. Evaluation and management of obesity hypoventilation syndrome. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2019 Aug 1;200(3):e6-24. https://www.atsjournals.org/doi/10.1164/rccm.201905-1071ST http://www.ncbi.nlm.nih.gov/pubmed/31368798?tool=bestpractice.com

Identifies associated obstructive sleep apnea in patients with OHS.[131]Mokhlesi B, Tulaimat A, Faibussowitsch I, et al. Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea. Sleep Breath. 2007 Jun;11(2):117-24. http://www.ncbi.nlm.nih.gov/pubmed/17187265?tool=bestpractice.com ​ In addition, it may identify patients with OHS prior to developing awake elevations in PaCO₂.[132]Sivam S, Yee B, Wong K, et al. Obesity hypoventilation syndrome: early detection of nocturnal-only hypercapnia in an obese population. J Clin Sleep Med. 2018 Sep 15;14(9):1477-84. https://jcsm.aasm.org/doi/10.5664/jcsm.7318 http://www.ncbi.nlm.nih.gov/pubmed/30176974?tool=bestpractice.com

General parameters measured include electroencephalogram, electro-oculographic recording, air flow assessment, electromyogram, capnography, esophageal manometry, ECG, pulse oximetry, respiratory effort signals, synchronized polysomnography video, and body position.[128]American Academy of Sleep Medicine. The AASM manual for the scoring of sleep and associated events. Feb 2023 [internet publication]. https://aasm.org/clinical-resources/scoring-manual

Polysomnography may be a full night study or a split study.

False-negative results are found in IgA deficiency. Therefore, IgA immunoglobulin level should also be requested.

Test of choice for individuals with IgA deficiency.

Required for diagnosis.

Blood should be drawn between 8.00 am and 9.00 am, when cortisol levels peak.

A normal response to ACTH (250 micrograms as an intravenous bolus) is a rise in serum cortisol concentration after 30 or 60 minutes to a peak of 18 to 20 micrograms/dL (500 to 550 nanomol/L) or more.[143]Dickstein G, Shechner C, Nicholson WE, et al. Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test. J Clin Endocrinol Metab. 1991 Apr;72(4):773-8. http://www.ncbi.nlm.nih.gov/pubmed/2005201?tool=bestpractice.com

Useful for evaluation of premenopausal women.

Hypopituitarism may occur with large prolactinomas or interruption of the hypothalamic-pituitary axis.

Definitive test but associated with substantial risks.

Only if suspected diabetes insipidus.

Dehydration should be done with caution and by an expert.

Dehydration should be done with caution and by an expert.

Abnormalities include promyelocytes, myelocytes, metamyelocytes, and band forms.

Hypoproliferative anemia can be secondary to inflammation or bone marrow replacement, and often presents with normochromic, normocytic indices. Alternatively, anemia can result from autoimmune hemolysis (Coombs test positive) associated with an underlying lymphoma.

LDH is an important marker of disease activity and prognosis in lymphomas.

CT scan also provides important information about splenic and extranodal sites of involvement.

HIV patients are at high risk for development of lymphoma.

As with HIV, hepatitis B and hepatitis C infections correlate with an increased risk for the development of malignant lymphoma.

CT scan also provides important information about splenic and extranodal sites of involvement.

Acute infection suggested by presence of IgM.

Detects the presence of CMV proteins in the peripheral smear; most useful in immunocompromised patients.

Results take 3 weeks.

Results take 3 weeks.

May be required for localized infection.

Used to confirm the diagnosis if the IFA or ELISA is positive or equivocal.

May be used instead of a western blot to confirm the diagnosis if the IFA or first ELISA is positive or equivocal.[144]Mead P, Petersen J, Hinckley A. Updated CDC Recommendation for Serologic Diagnosis of Lyme Disease. MMWR Morb Mortal Wkly Rep. 2019 Aug 16;68(32):703. https://www.doi.org/10.15585/mmwr.mm6832a4 http://www.ncbi.nlm.nih.gov/pubmed/31415492?tool=bestpractice.com

Regarded as chronic renal disease stage 1 if GFR >90 mL/minute/1.73 m², stage 5 if <15 mL/minute/1.73 m² or patient on dialysis. Calculated based on Cockroft-Gault formula.[146]Perazella MA, Reilly RF. Chronic kidney disease: a new classification and staging system. Hospital Physician. 2003 Mar;39:18-45. [ Glomerular Filtration Rate Estimate by the IDMS-Traceable MDRD Study Equation Opens in new window ]

Diagnosis can be made if bradykinesia is present plus at least 1 of the following: muscular rigidity; 4 to 6 Hz rest tremor; postural instability not caused by visual, vestibular, cerebellar, or proprioceptive dysfunction.[147]Hughes AJ, Daniel SE, Kilford L, et al. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992 Mar;55(3):181-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1014720 http://www.ncbi.nlm.nih.gov/pubmed/1564476?tool=bestpractice.com

Nonspecific; DEXA reveals a decreased bone density in both osteoporosis and osteomalacia.

ANA is positive in almost all patients with SLE and confirms the diagnosis in the presence of relevant clinical findings. However, a positive ANA alone is not diagnostic, as it may be positive in other connective tissue diseases.

Anti-dsDNA and anti-Smith antibodies are specific for SLE and often confirm the diagnosis, if present.[148]Smeenk R, Brinkman K, van den Brink H, et al. Antibodies to DNA in patients with systemic lupus erythematosus: their role in the diagnosis, the follow-up and the pathogenesis of the disease. Clin Rheumatol. 1990 Mar;9(1 suppl 1):100-10. http://www.ncbi.nlm.nih.gov/pubmed/2203588?tool=bestpractice.com [149]Eaton RB, Schnneider G, Schur PH. Enzyme immunoassay for antibodies to native DNA. Specificity and quality of antibodies. Arthritis Rheum. 1983 Jan;26(1):52-62. http://www.ncbi.nlm.nih.gov/pubmed/6337594?tool=bestpractice.com

Presence of these antibodies is established by means of immunofluorescence or ELISA.

All active, unresolved, or suspected disease likely to cause fatigue, including psychotic disorders, melancholic or bipolar depression, dementia, anorexia or bulimia nervosa, alcohol or substance misuse, and severe obesity, are regarded as exclusion criteria.[18]Fukuda K, Straus SE, Hickie I, et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. 1994 Dec 15;121(12):953-9. http://www.ncbi.nlm.nih.gov/pubmed/7978722?tool=bestpractice.com Various laboratory tests may be ordered as a means of ruling out organic disease. Extensive laboratory testing is not indicated.