What is the differential diagnosis for night sweats?

Differential Diagnosis for Night Sweats

The differential diagnosis for night sweats should prioritize life-threatening conditions first—tuberculosis, lymphomas (Hodgkin and non-Hodgkin), and HIV—followed by common benign causes including menopause, gastroesophageal reflux disease, hyperthyroidism, medications, and mood disorders. 1, 2

Life-Threatening Causes (Rule Out First)

Infectious Diseases

• Tuberculosis remains a critical diagnosis, particularly in high-risk populations, where night sweats appear alongside cough, fever, hemoptysis, and weight loss 3
• HIV infection must be considered, especially with associated fever and weight loss 3, 1, 2
• Hepatitis B and C should be screened when risk factors are present 4
• Geographic and exposure-specific infections warrant testing based on patient history 4

Malignancies

• Classical Hodgkin Lymphoma characteristically presents with B symptoms (fever, night sweats, weight loss >10% body weight over 6 months) and requires tissue diagnosis through excisional lymph node biopsy 3, 5
• Non-Hodgkin Lymphomas including Diffuse Large B-Cell Lymphoma and Marginal Zone Lymphomas frequently manifest with night sweats 5
• Waldenström's Macroglobulinemia often presents with night sweats and requires serum immunoglobulin level assessment 5, 4
• The presence of night sweats combined with fever and weight loss substantially increases suspicion for lymphoma 4

Common Benign Causes

Endocrine Disorders

• Menopause represents the most frequent hormonal cause of night sweats in women 1, 6
• Hyperthyroidism is a common endocrinologic etiology requiring thyroid-stimulating hormone testing 1, 2, 6
• Hypoglycemia should be considered in appropriate clinical contexts 2
• Hypogonadism in aging males is rare but must be associated with sexual dysfunction and low morning testosterone 6

Gastrointestinal and Sleep Disorders

• Gastroesophageal reflux disease (GERD) is an underrecognized but important cause, with excellent response to anti-reflux treatment 1, 7
• Obstructive sleep apnea warrants consideration, particularly when sleep disturbances are present 2
• Panic attacks and mood disorders frequently cause night sweats and should be explored 1, 6

Medications and Substances

• Antihypertensives and antipyretics commonly cause night sweats 2
• Serotonin reuptake inhibitors are associated with night sweats (alpha-adrenergic blockers may provide relief) 8
• Alcohol and heroin abuse should be considered 2

Diagnostic Evaluation Algorithm

Initial Assessment

• Duration and pattern of night sweats (drenching sweats requiring bed clothes change) 8, 7
• Associated B symptoms: fever, weight loss >10% over 6 months 3, 5
• Examination of all lymphoid regions, spleen, and liver 5
• Medication review and substance use history 2
• Menstrual history in women and sexual function in men 6

First-Line Laboratory Studies

• Complete blood count to screen for hematologic malignancies 1, 2
• Tuberculosis testing (purified protein derivative or interferon-gamma release assay) 1, 2
• Thyroid-stimulating hormone for hyperthyroidism 1, 2
• HIV testing in all patients without recent negative results 1, 2
• C-reactive protein or erythrocyte sedimentation rate for inflammatory conditions 1, 2
• Comprehensive metabolic panel for liver and kidney function 4

First-Line Imaging

• Chest radiography is essential for tuberculosis and lymphoma screening 1, 2

Second-Line Studies (When Initial Workup Negative)

• Contrast-enhanced CT chest and/or abdomen if malignancy suspected 5, 2
• PET/CT scan for lymphoma staging when indicated 5
• Serum immunoglobulin levels if Waldenström's macroglobulinemia suspected 4
• Polysomnography for suspected sleep apnea 1
• Bone marrow biopsy reserved for specific hematologic concerns 1, 2

Critical Clinical Pearls

• Most patients with persistent night sweats in primary care do not have serious underlying disease, but systematic evaluation is mandatory 1, 8
• Night sweats alone do not indicate increased mortality risk in the absence of other concerning features 1
• Prevalence ranges from 10% in older primary care patients to 60% in hospitalized obstetric patients 8
• If initial history and physical examination suggest a specific benign diagnosis (e.g., GERD, menopause), a 4-8 week therapeutic trial is reasonable before extensive testing 1
• When all testing is negative and no additional disorders are suspected, reassurance and continued monitoring are appropriate 1