The Circadian Rhythm of Body Temperature
Normal body temperature follows a diurnal pattern, peaking in mid-afternoon around 3 to 4 p.m. and reaching its nadir around 3 to 4 a.m. This decrease in body temperature is partially mediated by evaporation, through the process of sweating. As an adaptive process, an increase in the degree of sweat production is necessary in most instances for an elevated temperature to reach the nocturnal nadir. This sweating reaction has been observed to be disproportionate; most of the sweating occurs in the first half of the night. One possible explanation is that sweating thresholds in humans are lowered during the early phases of sleep . When nocturnal sweating reaches eight-fold the normal baseline sweating, it becomes perceivable to the patient as night sweats. Throughout the literature, night sweats have often been described as drenching sweats inducing the need to change pajamas and/or bedclothes.
Febrile Versus Nonfebrile Night Sweats
Night sweats can be conceptually divided into two groups: febrile night sweats (FNSs) and nonfebrile night sweats (NFNSs) (Table 1). For the purposes of our discussion, FNSs are defined as night sweats resulting from an exaggeration of the normal circadian temperature rhythm. FNSs are secondary to an increased body temperature that provokes the adaptive sweating response. We define NFNSs as night sweats induced by endocrine or autonomic abnormalities, most likely resulting in dysfunction of the hypothalamic temperature control without an elevated body temperature, although this has not been proven.
Febrile Night Sweats
FNSs are due to either infectious or noninfectious disorders, which lead to elevated body temperature and may be associated with symptoms of an indolent disease course. The patient experiencing FNSs may be unaware of temperatures as high as 39.4°C. FNSs may be categorized further by cause into two major classes: infectious and noninfectious. Although infectious causes may already be well understood to cause elevated body temperatures secondary to cytokine production, the mechanism by which elevated body temperature subsequently leads to night sweats in the noninfected patient is not known.
FNSs have been noted in many infectious diseases such as tuberculosis, brucellosis, lung or liver abscess, subacute infective endocarditis, HIV disease, and mononucleosis. Whereas other symptoms in addition to night sweats may be noted in association with many of the above infectious causes, diagnosis of the noninfectious diseases initially presenting with night sweats is much more difficult.
FNSs have been noted in association with several malignancies. In a study by Gobbi et al., patients with Hodgkin’s disease who had night sweats as a predominant symptom were seen to have a documented increase in temperature prior to the sweating episode . These febrile pulses were temporally related to the sweating episode, and the sweating response subsequently led to a rapid decrease in body temperature while causing the patient to awake from sleep. In addition to their occurrence with Hodgkin’s disease and other lymphomas, night sweats have been noted to occur in patients with prostate cancer .
Pharmacologic agents have also been implicated as causes of night sweats. Babbott and Pearson described a patient receiving sertraline therapy who reported a 3-month history of dry cough and night sweats, which resolved within 4 days of discontinuation of the therapy . Night sweats with or without hot flashes have also been associated with the use of cholinergic agonists, meperidine, tamoxifen citrate, leuprolide acetate, and niacin .
Night sweats as a presenting symptom have also been noted in systemic cases such as sarcoidosis , Castleman’s disease , and giant cell arteritis . Isolated occurrences of night sweats with medical conditions such as chronic aortic dissection , ankylosing spondylitis associated with pulmonary findings on chest radiography , Prinzmetal’s angina , and gastroesophageal reflux  also have been described. Letters have also mentioned posttraumatic spinal cord syrinx  and obstructive sleep apnea [14,15] as possible causes of night sweats.
Nonfebrile Night Sweats
In our categorization, NFNSs are night sweats due to misinterpretation of the circadian temperature rhythm, secondary to endogenous endocrine or metabolic abnormalities.
The mechanism of night sweats in many of these conditions is not known, and they present in only a small fraction of these patients with certain conditions. Perhaps some of the more commonly known endocrine causes of night sweats are carcinoid syndrome, pheochromocytoma, hyperthyroidism/thyrotoxicosis, and menopause . The presenting symptoms in addition to the night sweats are the clues to further workup; night sweats alone are a relatively nonspecific symptom in these cases.
Pheochromocytoma will present with a more paroxysmal course of sweating than will thyrotoxicosis, and the constellation of signs with paroxysmal headache, anxiety, and palpitation will more likely suggest pheochromocytoma as the cause. Menopause often leads to night sweats in the context of hot flashes and in females with characteristic new-onset menstrual changes.
Nocturnal hypoglycemia has been reported as an easily identifiable cause of night sweats. In one diabetic patient reporting night sweats of 4 weeks’ duration and fearing the possibility of being HIV-positive, nocturnal hypoglycemia secondary to failure to readjust insulin dosage was found to be the cause . The author reporting that case mentioned how the occurrence of night sweats alone, coupled with the intense media coverage of HIV disease, caused significant distress to this patient. Night sweats have also been described as a dominant symptom of diabetes insipidus .
Although FNSs and NFNSs are relatively nonspecific symptoms that may be attributed to a wide variety of medical conditions, their presence alone can narrow the differential, and in conjunction with other symptoms they can provide a strong clue to a specific diagnosis. When night sweats are reported by a patient, certain information should be obtained to guide the differential diagnosis: medications, menopause status, reflux symptoms, weight loss, cough/sputum, HIV/ tuberculosis exposure, and exertional symptoms such as chest pain and dyspnea . In addition, if the patient is diabetic, questions pertaining to insulin dosage and regulation may be pertinent.
Finally, certain red-flag physical examination signs that should be noticed include fever, adenopathy, hypertension that is episodic and difficult to control, and any neurological abnormalities . Patients should also be asked to measure their temperature when experiencing an episode of night sweats.
The workup of a patient with night sweats should be dictated by the constellation of symptoms and relevant physical examination findings. Should the patient have FNSs, then a work-up to identify a possible infection or malignancy is completely appropriate. Likewise, a work-up for endocrine abnormalities in the patient with NFNSs may yield better results.
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