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Evaluation of the patient with night sweats or generalized hyperhidrosis

Evaluation of the patient with night sweats or generalized hyperhidrosis
Literature review current through: Jan 2024.
This topic last updated: May 10, 2023.

INTRODUCTION — Episodes of generalized sweating, occurring either during the day or night (or both) is a common presenting symptom in primary care. While the cause may be evident after history-taking, often no etiology is immediately apparent. In such cases, clinicians face the challenge of pursuing a thoughtful, cost-effective yet comprehensive diagnostic strategy.

The evaluation of the patient with night sweats or generalized hyperhidrosis is discussed here. The management of benign excessive sweating limited to certain areas of the body (primary focal hyperhidrosis) is discussed separately. (See "Primary focal hyperhidrosis".)

Although hot flashes and flushing are discussed here as they relate to the diagnostic evaluation of night sweats, they are reviewed in greater detail elsewhere. (See "Menopausal hot flashes", section on 'Clinical manifestations' and "Clinical manifestations and diagnosis of menopause", section on 'Hot flashes' and "Approach to flushing in adults".)

DEFINITIONS

Excessive sweating, or generalized hyperhidrosis, is the secretion of sweat in excess of that needed to control body temperature. It may be primary (idiopathic) or secondary (due to an underlying cause). When sweating is limited to certain areas of the body, it is called primary focal hyperhidrosis; this is reviewed in detail elsewhere. (See "Primary focal hyperhidrosis".)

Night sweats (sleep hyperhidrosis) are episodes of generalized hyperhidrosis that occur during sleep and may range in severity from moderate diffuse sweating to drenching sweats that require changing bedclothes and even bed sheets. An overheated room or too many bed coverings may be a simple cause for an increase in sweating at night, but sweating in these circumstances does not necessarily represent sleep hyperhidrosis.

Hot flashes may be difficult to distinguish from night sweats, although the former have several distinctive features. Hot flashes may begin with an unpleasant heat sensation in the chest, neck, or abdomen. A sudden warmth and visible skin redness in the chest, head, and neck follows, which may be visible to observers [1]. The sensation of warmth lasts for three to four minutes and is typically followed by sweating in the same areas. (See "Menopausal hot flashes".)

Flushing, an increased cutaneous blood flow due to vasodilation, is experienced as a warmth and redness of the face and occasionally the trunk, which may be associated with sweating. It sometimes may be difficult to distinguish flushing with increased sweating from sweating due to hot flashes or night sweats. (See "Approach to flushing in adults".)

EPIDEMIOLOGY — There are limited high-quality data on the incidence of night sweats; only a few small series describe these patients and their ultimate diagnoses [2-4].

In a study of over 2000 patients presenting to primary care clinicians, 41 percent reported experiencing night sweats within the last month; 23 percent had night sweats only and 18 percent experienced both day and night sweats [5].

In a random sample of 174 hospital inpatients, 32 percent of non-obstetric patients and 60 percent of obstetric patients reported night sweats within the prior three months [2].

In a cross-sectional study of 360 patients visiting a primary care clinic, 24 percent of patients experienced night sweats in the previous month and half of these reported severe (drenching) sweats [6].

In a large cross-sectional population analysis, 4 percent of 4680 persons living in Bangkok, Thailand reported night sweats [7].

The presence of night sweats does not necessarily portend a poor prognosis or risk of increased mortality. As an example, in one study of 1500 older adults, those reporting night sweats at baseline were no more likely to die over the next seven years than those without night sweats [8]. While this does not diminish the importance of a careful evaluation of patients with night sweats, it does suggest that most patients with night sweats may have a benign course.

INITIAL ASSESSMENT OF ALL PATIENTS — Given the myriad possible causes of night sweats and conditions (hot flashes, generalized hyperhidrosis, and flushing) that may present with nighttime sweating symptoms, the challenge is to correctly identify those patients with a serious underlying cause while minimizing unnecessary diagnostic testing.

There are no high-quality data to guide the diagnostic evaluation to generalized hyperhidrosis and night sweats, and reasonable clinicians may have different approaches. Our approach is based upon our clinical experience, taking into account the likelihood of certain conditions in a primary care setting, the diagnostic value of a careful history and physical examination, and the tradeoff between delay of diagnosis with a conservative approach versus the cost and risk of diagnostic testing.

Elements of the medical history to ascertain — A detailed medical history is the most important element in the evaluation of a patient with generalized hyperhidrosis or night sweats (table 1).

Characteristics of the sweating – The exact details of the sweating episodes are essential to clarify and include the severity and frequency of the events. Mild sweats are typically less concerning for underlying serious disease or infection than are drenching night sweats that cause the patient to change their bedclothes and sheets. In addition, the frequency of sweats, including daytime symptoms, should be determined. As an example, night sweats occurring every night versus once monthly raise more concern for a serious underlying cause.

Fevers – Fever should be excluded with certainty when evaluating a patient with night sweats; if there is any concern for concurrent fever, patients should take and record daily temperatures during and after sweating episodes and at other random times (once to twice daily). When a documented fever occurs in association with night sweats, infection and malignancy become more likely diagnostic possibilities. Additionally, if fevers are present, the patient should be questioned about rigors.

Risk factors for tuberculosis – The patient should be evaluated for risk factors for tuberculosis (TB); including a prior positive TB skin test or interferon-gamma release assay, HIV infection, hemodialysis, gastrectomy, solid organ transplantation, exposure to an individual with TB, being homeless or living in an institutionalized setting, immigration from an endemic area, working in a health care setting, or symptoms of active TB [cough, sputum, fatigue, and weight loss]). (See 'Infections' below.)

Constitutional symptoms, lymphadenopathy, or known history of malignancy – We ask about unintentional weight loss, fatigue, and pruritus, which may suggest the presence of a malignancy such as lymphoma. In addition, we inquire about any known history of malignancy, or the presence of enlarged lymph nodes; if any of these are present, a diagnosis of malignancy is also suspected. (See 'Malignancies' below.)

Risk factors for HIV infection – We also ask about risk factors for HIV infection, including injection drug use, men who have sex with men, sexual activity with multiple partners, or commercial sex work. Other relevant medical history includes thrush, diarrhea, unintentional weight loss, or a report of enlarged lymph nodes. (See 'Infections' below.)

Assess for bacterial infection – We assess for likelihood of bacterial infection, including the patient's risk factors for bacteremia (eg, chronic indwelling vascular catheter, injection drug use, prior history of endocarditis, recent dental work with risk factors for endocarditis, immunosuppression). We ask about any localized pain, especially back or joint pain, which (particularly if accompanied by fever) might suggest endocarditis, bacteremia, or spinal infection including vertebral osteomyelitis and discitis. (See 'Infections' below.)

Geographic infection risk – We assess the patient's geographic region of residence and also inquire about travel history. Specifically, we consider residence in or any recent travel to areas where certain infections such as malaria, typhoid fever, and tick-borne diseases are endemic. While fever and other symptoms are often present with these infections, night sweats may be the first clinical feature. We ask about known or suspected mosquito or tick bites, food and water hygiene, use of chemoprophylaxis for malaria (if indicated), and country-specific vaccination status. We ask about residence in the Southwest of the United States, particularly Arizona and the San Joaquin Valley of California, and travel to Mexico and parts of Central and South America, due to the risk of coccidioidomycosis. (See "Evaluation of fever in the returning traveler" and 'Infections' below and "Primary pulmonary coccidioidal infection".)

COVID-19 exposure – In the pandemic era, nearly all patients around the globe live in countries where person-to-person transmission of coronavirus disease 2019 (COVID-19) is a potential risk. According to the Centers for Disease Control and Prevention (CDC) definition, risk exists for close-range contact (<2 meters) with a person of unknown COVID-19 status for a cumulative total of at least 15 minutes in a 24-hour period [9]. Risk is increased for household contacts of patients with known COVID-19, for health care workers who may be exposed to COVID-19 patients and who do not follow proper personal protective equipment precautions, for first responders, and for others with regular exposure to members of the community such as pharmacy technicians and grocery store clerks. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Transmission'.)

Hormonal (estrogen and androgen) status – For female patients, we consider age and menopausal (surgical, chemical or natural) status. We also inquire about the use of estrogen-containing products and recent obstetric history. For male patients, any history of androgen deprivation therapy (chemical or surgical) is assessed and, if relevant, the temporal relationship to the onset of sweats. (See 'Endocrine causes' below and 'Medications' below.)

Other endocrine symptoms – We question the patient about episodic flushing, diarrhea, wheezing, palpitations, or headache which might suggest a neuroendocrine etiology. In addition, weight loss in association with heat intolerance and tremor may suggest hyperthyroidism. (See 'Endocrine causes' below.)

Medication use – Medication history should include both prescription and over-the-counter supplements; a temporal relationship between initiation of a new medication known to be associated with generalized hyperhidrosis and the onset of symptoms increases the likelihood of the medication as the cause (table 2). (See 'Medications' below.)

Neurologic history – We evaluate for a history of a spinal cord injury, stroke, or other neurologic disorder which may be associated with autonomic dysreflexia. (See 'Neurologic causes' below.)

Focused physical examination — While the medical history is the cornerstone of the clinical evaluation of patients with night sweats, a focused physical examination may provide additional diagnostic information (table 1).

General appearance; observe overall health including nutritional status.

Temperature, heart rate, blood pressure, and weight. If available, we compare current weight with a previous weight.

If sweating is present at the time of the examination, we make note of the sweating pattern (degree and location) and any skin flushing.

Examine all lymph node chains in search of any pathologically enlarged nodes. (See "Evaluation of peripheral lymphadenopathy in adults", section on 'Evaluation'.)

Examine the oropharynx for thrush, and the mucous membranes for petechiae or pallor. (See "The natural history and clinical features of HIV infection in adults and adolescents", section on 'Clinical presentation' and "The natural history and clinical features of HIV infection in adults and adolescents", section on 'AIDS-defining conditions' and "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Symptoms and signs'.)

Evaluate the eyes for lid-lag or exophthalmos, check for brisk peripheral reflexes, and examine the thyroid for thyromegaly or nodule(s). (See "Diagnosis of hyperthyroidism", section on 'Clinical manifestations'.)

Examine the abdomen for masses and/or splenomegaly. (See "Clinical presentation and initial evaluation of non-Hodgkin lymphoma", section on 'Abdomen and pelvis'.)

Perform a cardiovascular examination for new or changed heart murmur, particularly a regurgitant valvular murmur. Examine the skin and fingernails for peripheral stigmata of endocarditis. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Clinical manifestations' and "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Symptoms and signs'.)

Perform a lung examination for adventitious sounds or other abnormalities. (See "Pulmonary tuberculosis: Clinical manifestations and complications", section on 'Physical findings'.)

Conduct a focused neurologic examination if indicated by the medical history. (See "Chronic complications of spinal cord injury and disease", section on 'Autonomic dysreflexia'.)

OUR DIAGNOSTIC STRATEGY — Our next step in the diagnostic approach to the patient with generalized hyperhidrosis or night sweats depends upon the information collected in the history and physical examination. At no point in the evaluation do we treat with empiric antibiotic therapy.

Patients with history and physical findings suggesting a specific etiology — If an etiology is apparent after the clinical history and/or physical examination, then the appropriate next steps are taken for treatment or further evaluation of that specific cause (table 1). As examples:

If tuberculosis (TB) is suspected, testing (including TB skin test or interferon-gamma release assay, chest imaging, and sputum collection) should be performed and appropriate infection control precautions instituted. (See "Tuberculosis transmission and control in health care settings", section on 'Clinical triaging' and "Diagnosis of pulmonary tuberculosis in adults" and "Clinical manifestations, diagnosis, and treatment of miliary tuberculosis".)

If lymphoma is suspected, further appropriate diagnostic workup should be pursued. This may include computed tomography (CT) or positron emission tomography (PET) scanning of the torso, biopsy of an enlarged lymph node, appropriate blood testing, and bone marrow biopsy. (See "Clinical presentation and initial evaluation of non-Hodgkin lymphoma" and "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults".)

For patients with a known history of a tick bite, who live in a region or with recent travel to a region where tick-borne illness is endemic, we perform light microscopy on a thick blood smear for babesiosis and serologic tests for ehrlichiosis, anaplasmosis, and Lyme disease. For those living in areas or returning from travel where malaria is endemic, we perform light microscopy on a thick blood smear to evaluate for malaria. (See "Babesiosis: Clinical manifestations and diagnosis", section on 'Diagnosis' and "Human ehrlichiosis and anaplasmosis", section on 'Diagnosis' and "Diagnosis of Lyme disease" and "Evaluation of fever in the returning traveler" and "Laboratory tools for diagnosis of malaria".)

Sweats associated with hormone deficiency (including testosterone reduction or blocking therapy or menopause) are sufficiently characteristic that, in general, clinicians may make a diagnosis based upon history or selected diagnostic tests. If symptoms are not sufficiently characteristic to establish a diagnosis of menopausal hot flashes, measurement of serum follicle-stimulating hormone (FSH) can help to suggest the diagnosis. (See "Side effects of androgen deprivation therapy", section on 'Vasomotor symptoms' and "Menopausal hot flashes" and "Clinical manifestations and diagnosis of menopause".)

If a patient is taking a medication known to cause excessive sweating, the medication should be withdrawn, if possible, as a diagnostic trial (table 2). Depending on the medication, it may take one to two weeks for the sweats to resolve if the medication is the cause. If this is not possible, we consider a reduction in dose, change to an extended-release formulation of the medication, or substitute with a drug less likely to cause sweating [10]. (See 'Medications' below.)

Patients with fever as the only finding on history and physical — If no specific etiology is suggested by the clinical history and physical examination, but objective fever is documented, there is a higher likelihood of occult infection or malignancy (algorithm 1). The evaluation of a patient with a fever of unknown origin is discussed elsewhere. (See "Fever of unknown origin in adults: Evaluation and management".)

Patients with no findings suggesting a specific etiology and no fevers — If no cause is identified by the clinical history and/or physical examination and objective fever is excluded, our next step in the evaluation is determined by the character (severity and pattern) of their sweating (algorithm 1).

Less severe sweats — For patients without documented fevers and less severe episodes of sweating, no additional evaluation or treatment is immediately needed. Patients should be counseled to monitor for fever, any increased severity in their sweating or sweating pattern, or new symptoms (such as unintentional weight loss) that might suggest a specific diagnosis.

Severe, drenching sweats — For patients without fevers but with severe, drenching sweats that require changing bedclothes, further evaluation is warranted; fever may be absent among some immunosuppressed patients despite the presence of malignancy or systemic infection.

At each step of the following evaluation, it is important to repeat a careful history as new diagnostic symptoms often emerge over time:

We perform an initial evaluation for possible TB (with a chest radiograph in conjunction with a TB skin test or interferon-gamma release assay). In addition, we check a complete blood count (CBC), thyroid-stimulating hormone (TSH), HIV serology, C-reactive protein (CRP), urinalysis, liver function tests, and blood cultures.

If these tests are normal, and drenching night sweats persist, then CT or PET scan of the torso (chest, abdomen, and pelvis) should be obtained to evaluate for lymphoma, solid tumor, or abscess.

If the above studies are normal and drenching night sweats persist, we check a transthoracic echocardiogram as a screening test to evaluate for culture negative endocarditis. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Culture-negative endocarditis'.)

If no diagnosis is apparent at this stage of the evaluation, and severe night sweats persist, then further evaluation typically includes a bone marrow biopsy.

If no cause has been identified after a bone marrow biopsy, and severe generalized hyperhidrosis or night sweats persist beyond eight weeks (even in the absence of other signs and symptoms), we check a 24-hour urine collection for 5-hydroxyindoleacetic acid (5-HIAA), metanephrine, and catecholamines to exclude carcinoid and pheochromocytoma. (See "Patient education: Collection of a 24-hour urine specimen (Beyond the Basics)".)

If this evaluation is negative, and severe hyperhidrosis or night sweats persist, no further evaluation is indicated in the absence of new symptoms or development of fevers. If new symptoms or documented fevers develop, however, previous testing, including CT imaging, bloodwork (including blood cultures), and echocardiography should be repeated. (See 'Patients with history and physical findings suggesting a specific etiology' above and 'Patients with fever as the only finding on history and physical' above.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of generalized hyperhidrosis and night sweats includes infection, malignancy, medications, endocrine causes, neurologic disease, and idiopathic hyperhidrosis (table 1 and table 3).

Infections — Infections (acute and chronic) may cause generalized hyperhidrosis and night sweats. While localizing features are typically present, in some cases sweats may the sole presenting symptom (table 1).

Tuberculosis – Tuberculosis (TB) is frequently associated with sweats, particularly night sweats; both pulmonary and extrapulmonary infections are associated with this symptom. In one prospective study of 310 adults with TB, 48 percent of patients experienced sweats, with 29 percent reporting sweats of at least two weeks’ duration [11]. Among these patients, sweats were more common among patients with extrapulmonary disease than among those with pulmonary disease (54 versus 46 percent). By contrast, in a retrospective study of 370 patients with TB, night sweats were more common among those with pulmonary compared with extrapulmonary disease (46 percent versus 24 percent) [12]. In a study of 145 patients seen in emergency departments in whom TB was suspected, night sweats were significantly more common among those with a positive sputum TB test than those with a negative test (46 versus 26 percent, odds ratio [OR] 2.51, 95% CI 1.07-5.90) [13]. In a South African population of 701 patients with confirmed TB, 414 (59 percent) reported night sweats, as opposed to only 23 percent of 686 patients with suspected TB who turned out not to have the disease [14]. (See "Pulmonary tuberculosis: Clinical manifestations and complications", section on 'Symptoms and signs' and "Clinical manifestations, diagnosis, and treatment of miliary tuberculosis", section on 'Clinical manifestations'.)

HIV infection – Individuals with HIV infection may experience sweats due to acute seroconversion, constitutional symptoms related to advanced disease, opportunistic infection [15-17], or HIV-related malignancies. The clinical manifestations and the complications of HIV infection are discussed in detail elsewhere. (See "Acute and early HIV infection: Clinical manifestations and diagnosis", section on 'Constitutional symptoms' and "Overview of prevention of opportunistic infections in patients with HIV", section on 'Epidemiology of opportunistic infections' and "HIV-related lymphomas: Clinical manifestations and diagnosis", section on 'Clinical manifestations'.)

Bacterial infections – Subacute bacterial infections such as endocarditis, osteomyelitis, and pyogenic abscess may present with sweats or night sweats. In such cases, fever will typically be present, and localizing signs or symptoms may indicate one of these diagnoses. As an example, back pain in the presence of new heart murmur and recent dental work suggests endocarditis and/or vertebral osteomyelitis, and localized gingival pain raises the possibility of a dental abscess. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Complications as initial presentation' and "Vertebral osteomyelitis and discitis in adults", section on 'Epidemiology' and "Fever of unknown origin in adults: Etiologies".)

COVID-19 infection – The clinical manifestations of COVID-19 are described in detail elsewhere (see "COVID-19: Clinical features"). Although fever is a common symptom, reports of night sweats among patients with COVID-19 are infrequent. This was confirmed in a convenience review of 164 patients with laboratory confirmed COVID-19; only 2 percent of patients described night sweats. By contrast, fever was present in 80 percent of patients [18]. Therefore, in a patient with isolated night sweats, without any of the more characteristic symptoms described above, COVID-19 is unlikely. Decisions regarding testing for active COVID-19 and/or quarantining must be made according to Centers for Disease Control and Prevention (CDC) and local guidelines. (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection" and "COVID-19: Epidemiology, virology, and prevention".)

Brucellosis – Brucellosis is a zoonotic disease that primarily affecting those who work with domestic animals or animal products, or people whose diet includes raw milk or unpasteurized cheese. It is a well-documented cause of fever of unknown origin and is characterized by nonspecific symptoms, including joint pain, fatigue, weight loss, malodorous perspiration and night sweats [19]. Brucellosis is reviewed in detail elsewhere. (See "Brucellosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

Malaria – Malaria is among the common causes of fever in the returning traveler [20]. Some patients may have not measured temperature and may instead characterize their initial symptom of malaria as night sweats. (See "Malaria: Epidemiology, prevention, and control" and "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children".)

Babesiosis – Babesiosis is an infection caused by protozoa of the genus Babesia; it is transmitted to humans primarily through tick bites and less often through transfusion of infected blood. Common symptoms among those with mild to moderate infection include fevers, chills, sweats and myalgias [21,22]. Risk factors for babesiosis include residence in or travel to an endemic area within the previous six weeks or blood transfusion within the previous six months. (See "Babesiosis: Clinical manifestations and diagnosis", section on 'Clinical manifestations' and "Babesiosis: Microbiology, epidemiology, and pathogenesis", section on 'Risk factors'.)

Human ehrlichiosis and anaplasmosis – Human ehrlichiosis and anaplasmosis are similar tick-borne infections which vary in severity from asymptomatic to severe. Among patients with symptomatic infections, fever, chills, malaise, myalgia, and headache are commonly seen. The tick responsible for transmitting anaplasmosis is also a vector for the causative agents of Lyme disease as well as babesiosis [23,24]; coinfection with these organisms should be considered for all patients with anaplasmosis. (See "Human ehrlichiosis and anaplasmosis".)

Coccidioidomycosis – This fungal infection with predominantly pulmonary involvement is common in parts of the Southwestern United States, Mexico, and Central and South America. Fever, drenching night sweats, and weight loss are common extrapulmonary manifestations. (See "Primary pulmonary coccidioidal infection".)

Malignancies — Sweats, particularly night sweats, may be an early feature of many different cancers, and malignancy should always be considered in the evaluation of a patient with night sweats (table 1).

Lymphoma (Hodgkin and non-Hodgkin) – The malignancy most commonly associated with night sweats is lymphoma.

Night sweats and fevers are frequently present in patients with Hodgkin lymphoma, although the frequency is variable and may depend upon the stage of disease. Additional symptoms that may suggest Hodgkin lymphoma as the cause for night sweats include fatigue, pruritus, and pain (at sites of tumor involvement) after alcohol consumption. The physical examination may be normal or may reveal lymphadenopathy or splenomegaly. (See "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults", section on 'B symptoms'.)

Patients with non-Hodgkin lymphoma may also report night sweats as an early constitutional symptom. (See "Clinical presentation and initial evaluation of non-Hodgkin lymphoma", section on 'Systemic "B" symptoms'.)

Solid (nonhematologic) malignancies – Patients with solid tumors may also experience night sweats. Common cancers associated with night sweats include prostate cancer, renal cell cancer, and germ cell tumors. Advanced medullary carcinoma of the thyroid may cause flushing and sweating due to calcitonin secretion.

Medications — Medications are a common cause of increased sweating and night sweats. Although the exact incidence cannot be determined given the lack of epidemiologic data, medications are frequently the cause of night sweats when there is no other immediately apparent etiology. The list of medications known to cause increased sweating or sweating due to flushing is extensive, and the causal mechanism differs by drug class (table 2). [10].

Antidepressants – Antidepressants are the most common medication-related cause of sweating, occurring in approximately 10 to 15 percent of patients taking these medications [10]. Antidepressants cause a generalized increase in sweating, with some patients more aware of episodes at night, therefore presenting with complaints of night sweats. Sweating usually occurs within several weeks of initiation of these medications. In our practice, we have observed rates of sweating greater than described in the US Food and Drug Administration (FDA) drug package inserts.

All classes of antidepressants have been implicated, including tricyclics and selective serotonin reuptake inhibitors (SSRIs). However, tricyclics, bupropion, and venlafaxine cause sweating more frequently than SSRIs [10,25]. Sweating is the most common side effect of desipramine and duloxetine [26].

The atypical antipsychotic medication clozapine has also been associated with generalized hyperhidrosis.

Cholinergic agents – Cholinergic agonists (such as pilocarpine and bethanechol) cause sweating through direct stimulation of peripheral muscarinic receptors in sweat glands. In addition, exposure to cholinesterase inhibitors such as organophosphate pesticides cause prominent sweating. (See "Organophosphate and carbamate poisoning", section on 'Cholinergic excess'.)

Hypoglycemic agents – Patients being treated for diabetes mellitus with hypoglycemic agents can experience low blood sugars, and sweats may be the most prominent or even the sole symptom. Nocturnal sweating may be the only symptom depending upon the pattern of blood sugar fluctuations. For patients with sweating episodes being treated with these agents, clinicians should be mindful of hypoglycemia as a possible etiology and ask patients to check blood sugars during events to rule out hypoglycemia. (See "Hypoglycemia in adults with diabetes mellitus", section on 'Symptoms' and "Hypoglycemia in adults without diabetes mellitus: Clinical manifestations, causes, and diagnosis", section on 'Assessment in symptomatic individuals'.)

Estrogen/androgen modulating agents – All medications that modulate estrogen or androgen levels or hormone receptor binding have the potential to cause hot flashes with episodes of sweating during the day and night. Such medications include gonadotropin-releasing hormone (GnRH) agonists, aromatase inhibitors (AIs), selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene, and androgen receptor blockers such as bicalutamide. (See "Adjuvant endocrine therapy for premenopausal women with hormone receptor-positive breast cancer", section on 'Toxicity' and "Side effects of androgen deprivation therapy", section on 'Vasomotor symptoms'.)

Other medications – Other commonly used medications may cause generalized hyperhidrosis, and symptoms can be experienced during the day or night. Among patients on methadone therapy, diffuse, excessive sweating is a common complaint. Diffuse sweating may be also be seen, but with less frequency, with other opioid drugs. Diffuse sweating is seen infrequently among patients using albuterol (and other sympathomimetics) as well as cyclosporine.

In addition, withdrawal from alcohol, opioids, and cocaine may cause sweating. (See "Alcohol withdrawal: Epidemiology, clinical manifestations, course, assessment, and diagnosis", section on 'Clinical presentation and course' and "Opioid withdrawal: Clinical features, assessment, and diagnosis", section on 'Clinical manifestations' and "Cocaine use disorder: Epidemiology, clinical features, and diagnosis" and "Cocaine use disorder: Epidemiology, clinical features, and diagnosis", section on 'Withdrawal symptoms'.)

Endocrine causes — Generalized hyperhidrosis due to hot flashes or flushing is a central feature of several endocrine causes, including menopause, and disorders such as pheochromocytoma, carcinoid syndrome, and hyperthyroidism (table 1) [27].

Menopause – The distinction between perimenopausal hot flashes with generalized hyperhidrosis and night sweats due to another cause is not always clear.

The median age of menopause in the United States is 51 years [28]. The first menopausal symptoms, usually hot flashes, occur a median of 3.8 years earlier and typically precede the onset of menstrual irregularities. The peak occurrence of hot flashes is during the year before the final menstrual period, and women may experience hot flashes for more than 10 years after menopause. (see "Clinical manifestations and diagnosis of menopause", section on 'Hot flashes' and "Menopausal hot flashes", section on 'Typical symptoms')

Clinicians, however, should not immediately conclude that sweating episodes in women of typical perimenopausal age represent hot flashes. We obtain a thorough history in all women with generalized hyperhidrosis symptoms; if there are concerning associated symptoms (eg, weight loss, pruritus, full body sweating) or localizing symptoms are present, we perform a directed physical examination and pursue further diagnostic studies as appropriate.

Endocrine disorders – Several endocrine disorders classically present with sweating, or flushing that can be accompanied by diffuse sweating.

Hyperthyroidism – Increased sweating and heat intolerance are prominent features of hyperthyroidism. In one review, sweating occurred in 50 to 91 percent of hyperthyroid patients, and heat intolerance occurred in 41 to 89 percent [29]. The sweating, however, is usually persistent and not paroxysmal. In addition, in the majority of patients, other typical clinical features of hyperthyroidism will be present. (See "Overview of the clinical manifestations of hyperthyroidism in adults".)

Pheochromocytoma – The classic triad of symptoms in patients with a pheochromocytoma consists of episodic headache, sweating, and tachycardia in a patient with sustained or intermittent hypertension. In a series of 108 pheochromocytomas in 104 patients, sweating was present in 37 percent of patients and flushing in 18 percent [30]. In a review of 95 pheochromocytoma patients from a single institution, sweating was present in 52 percent of patients; 88 percent of affected patients were hypertensive [31]. (See "Clinical presentation and diagnosis of pheochromocytoma".)

Carcinoid syndrome – Flushing is the hallmark of the carcinoid syndrome, occurring in 84 percent of affected patients; sweating may occur concurrent with the flushing. Other classic symptoms are diarrhea and wheezing. (See "Clinical features of carcinoid syndrome", section on 'Clinical features'.)

Insulinoma – Insulinoma may cause night sweats due to nocturnal hypoglycemia. (See "Insulinoma", section on 'Clinical features'.)

Acromegaly – Patients with acromegaly commonly describe malodorous hyperhidrosis; this is due to increased sweating and enlargement of sebaceous glands with excessive production of sebum [32,33]. (See "Causes and clinical manifestations of acromegaly", section on 'Metabolic'.)

Neurologic causes — Neurologic conditions (particularly spinal cord injury and syringomyelia) causing autonomic dysreflexia and autonomic neuropathy may cause episodic generalized hyperhidrosis and night sweats (table 1).

Autonomic dysreflexia – Autonomic dysreflexia is a syndrome of acute autonomic instability that occurs in patients with cervical or high thoracic spinal cord injuries (above the T6 level). The most common precipitant of acute episodes is bladder distension; it may also occur after rectal distension, urologic or rectal procedures, or any painful stimuli [34]. Common clinical features include sweating of the forehead or generalized sweating along with headache, gooseflesh, cutaneous vasodilation, increased muscle spasticity, an acute rise in blood pressure, and a desire to void. This distinctive symptom constellation in the context of a patient with a spinal cord injury is not easily confused with other causes of sweating spells [35]. (See "Chronic complications of spinal cord injury and disease", section on 'Autonomic dysreflexia'.)

Syringomyelia – Posttraumatic or idiopathic syringomyelia can cause episodes of generalized increase in sweating. The sweating may be affected by posture and may be generalized or segmental [36]. (See "Disorders affecting the spinal cord", section on 'Syringomyelia'.)

Sleep disorders — Sleep disorders are more common among patients with night sweats, although it is unclear if sleep disorders are a cause of night sweats or if sleep disorders are identified more commonly in patients who awaken because of night sweats. In a series of patients in a primary care practice reporting night sweats, symptoms positively associated with sweating included daytime tiredness (odds ratio [OR] 1.99, CI 1.12-3.53) and legs jerking during sleep (OR 1.78, CI 1.05-3.00) [6]. (See "Classification of sleep disorders".)

Among those with established sleep disorders, night sweats are common, and treatment for the sleep disorder may decrease night sweats. In a study evaluating night sweats in patients with diagnosed obstructive sleep apnea (OSA), approximately 33 percent of patients reported having night sweats at least three times a week; with continuous positive airway pressure (CPAP) treatment, the percentage reporting night sweats decreased to 12 percent [37]. In a report from Thailand, 14.4 percent of a population sample that reported habitual snoring and excessive daytime sleepiness also reported night sweats [7]. In this study, night sweats independently predicted the presence of OSA in a multivariate analysis (adjusted OR 2.33, 95% CI 1.32-4.13).

Other causes — A number of other less common diagnoses may result in generalized hyperhidrosis or night sweats. They include gastroesophageal reflux [6], temporal arteritis [38], arginine vasopressin deficiency (previously called central diabetes insipidus) [39], sarcoidosis [40], myalgic encephalomyelitis/chronic fatigue syndrome [41,42], and mercury poisoning. (See "Mercury toxicity".)

SUMMARY AND RECOMMENDATIONS

Definitions – Excessive sweating, or generalized hyperhidrosis, is the secretion of sweat in excess of that needed to control body temperature. It may be primary (idiopathic) or secondary (due to an underlying cause). When sweating is limited to certain areas of the body, it is called primary focal hyperhidrosis. Night sweats are episodes of generalized hyperhidrosis that occur during sleep and may range in severity from moderate diffuse sweating to drenching sweats that require changing bedclothes and even bed sheets. Hot flashes and flushing with associated sweating may be difficult to distinguish from generalized hyperhidrosis and night sweats. (See 'Definitions' above.)

Medical history – A detailed medical history is the most important element in the evaluation for all patients with generalized hyperhidrosis or night sweats (table 1) (see 'Elements of the medical history to ascertain' above). Essential components of the relevant history include:

Severity and frequency of the sweating episodes

Fever, which should be excluded with certainty

Risk factors for tuberculosis (TB) or symptoms of active TB

A history of unintentional weight loss, fatigue, pruritus, and known history of malignancy or enlarged lymph nodes

Risk factors for HIV infection

Risk factors for bacteremia or other infection

Risk factors for COVID-19

Geographic infection risk, including region of residence or recent travel to area with endemic infections (eg, malaria and tick-borne infections)

Risk factors for estrogen or testosterone deficiency

Symptoms consistent with an endocrine or neuroendocrine etiology, including heat intolerance, palpitations, tremor, flushing, diarrhea, wheezing, palpitations, or headache

Medication use with attention to any temporal relationship between initiation of a new medication known to be associated with generalized hyperhidrosis and the onset of symptoms (table 2)

Prior spinal cord injury, stroke, or other neurologic disorder that may be associated with autonomic dysreflexia

Physical examination – For all patients, we perform a focused physical examination. (See 'Focused physical examination' above.)

Likely etiology apparent – If an etiology is apparent after the clinical history and physical examination, then the appropriate next steps are taken for treatment or further evaluation of that specific cause (table 1). (See 'Patients with history and physical findings suggesting a specific etiology' above.)

No obvious etiology

Objective fever – If no specific etiology is suggested by the clinical history and physical examination, but objective fever is documented, there is a higher likelihood of occult infection or malignancy. In this case, evaluation for fever of unknown origin should be pursued (algorithm 1). We do not treat with empiric antibiotic therapy. (See 'Patients with fever as the only finding on history and physical' above.)

No objective fever – If no cause is identified by the clinical history and physical examination, and objective fever is excluded, our next step in the evaluation is determined by the severity and pattern of the sweating (algorithm 1). (See 'Patients with no findings suggesting a specific etiology and no fevers' above.)

-For patients without documented fevers and less severe episodes of sweating, no additional evaluation or treatment is immediately needed. (See 'Less severe sweats' above.)

-For patients without fevers, but with severe, drenching sweats that require changing bedclothes, further evaluation is warranted; fever may be absent among some immunosuppressed patients despite the presence of malignancy or systemic infection. (See 'Severe, drenching sweats' above.)

Differential diagnosis – The differential diagnosis of hyperhidrosis and night sweats includes infection (most commonly TB, HIV, and bacterial infections), malignancy (lymphomas and non-hematologic malignancies), medications (most frequently antidepressants), endocrine causes (including estrogen and androgen deficiency, neuroendocrine syndromes and tumors, hyperthyroidism, and acromegaly), autonomic dysreflexia, and other less common causes (table 3). (See 'Differential diagnosis' above.)

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References

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