Introduction

Both night sweats and weakness or fatigue are common medical symptoms found in a range of illnesses of varying severity. The reporting of night sweats as a symptom is incredibly frequent, with one study finding that between 10-41% of middle-aged patients had complained of night sweats to their general practitioner.¹ Sweating is a mechanism used by the body to lower temperature when the core body temperature rises above the normal range - the so-called thermoneutral zone (TNZ). The release of inflammatory chemicals in the body in response to infections, cancers, and autoimmune diseases causes a rise in body temperature, provoking sweating. Many of these illnesses also cause daytime feelings of weakness and fatigue. However, despite the extensive list of conditions that can potentially cause night sweats, in many cases, no underlying cause is found.¹ Because the number of conditions that theoretically cause both night sweats and fatigue is vast, this article focuses on some of the most common and clinically important, but it is by no means an exhaustive list.

Underlying conditions causing both night sweats and daytime weakness (fatigue)

Infections

Tuberculosis (TB)

Tuberculosis is a disease caused predominantly by the bacterium mycobacterium tuberculosis (although it may be caused less commonly by other strains of mycobacterium). Before the COVID pandemic, TB was the world’s most prevalent disease and accounted for 1.3 million deaths worldwide in 2022. TB is a chronic disease, and whilst the primary focus of active TB is often the lungs, any organ of the body can be affected. Pulmonary TB typically presents with general symptoms including a productive cough, with or without coughing up blood, weight loss, fatigue, night sweats, poor appetite, and swelling of the lymph nodes. Patients with Human Immunodeficiency Virus (HIV) have a 19% greater chance of contracting TB.²  

HIV/AIDS

HIV was first identified 42 years ago. The human immunodeficiency virus (HIV) attacks the body’s immune system. According to the WHO, 39.9 million people are living with HIV (end of 2023), although adult deaths have fallen to 560,000 in 2023. Advances in antiretroviral treatment have enabled long-term suppressed viral loads in patients with HIV, however, the WHO claims that 72% of people living with HIV have suppressed viral loads, meaning there is still a target to be reached in testing and treating the remaining patients. Clinically, there are different stages of HIV infection. Acute HIV occurs 2-4 weeks after the primary infection and comprises headache, fever, malaise, rash, tender enlargement of the lymph nodes, and night sweats may occur. This phase typically lasts about 2 weeks. This is followed by a long latent phase, during which there may be no symptoms. In the later stages of the illness and progression to AIDS (Acquired Immune Deficiency Syndrome), generalised symptoms including fatigue, night sweats, weight loss, chronic diarrhoea, swollen lymph nodes, sore throat, and lesions in the mouth occur. When the CD4+T-cell count has dropped below 200 per microlitre of blood, AIDS is diagnosed. Opportunistic infections and other diseases, such as Kaposi's sarcoma and lymphoma begin to occur at this stage.³ 

Endocarditis

Endocarditis is an infection of the interior surface of the heart (the endocardium). Infection is commonly with bacteria, but in rarer cases can be fungal. Affecting 15 in every 100,000, infective endocarditis is uncommon but ‌a serious and potentially fatal disease. Infection of the endocardium leads to the formation of growths on the heart valves and surfaces, known as vegetations. This can also lead to abscess formation and infection, and inflammation of the heart muscle and outer lining (pericardium) known as myopericarditis. Pieces of the vegetation can break off and travel in the bloodstream as mycotic emboli. When they lodge in a blood vessel, in say, the brain, this leads to weakening and bulging of these vessels due to infection, known as a mycotic aneurysm. People most at risk of infective endocarditis are those who have had rheumatic heart disease, people with congenital heart defects, people with artificial heart valves, enlarged heart (hypertrophic cardiomyopathy) and intravenous drug users. Infective endocarditis is subdivided into acute, sub-acute and chronic forms. Generalised symptoms of infective endocarditis include a high temperature, chills, headache, night sweats, fatigue, muscle and joint pain, and shortness of breath. There are some specific signs, such as splinter haemorrhages (small linear bleeds under the nails) and Osler’s nodes and Janeway lesions in the hands. New cardiac murmurs may be heard upon listening to the heart.⁴

Other infections

Besides the conditions described in more detail above, night sweats and fatigue may be features of the following infections:⁵

• Malaria
• Infectious Mononucleosis
• Certain types of pneumonia
• Cysticercosis
• Babesiosis

Endocrine Disorders

A combination of night sweats and daytime weakness occurs in several endocrine disorders:

Hyperthyroidism

Hyperthyroidism, or thyrotoxicosis, is not a single illness; rather, it is the result of one of several conditions that cause the thyroid gland to produce excessive amounts of thyroid hormone. The prevalence of thyrotoxicosis is around 1.6% in the US. Clinically, thyrotoxicosis presents with weight loss, muscle weakness, tremor, malaise and tiredness, sensitivity to heat, thirst, hyperactivity, anxiousness, itching, and eye symptoms. The typical signs associated with thyrotoxicosis are a goitre (swelling in the neck), tremor, excessive sweating (including night sweats), an irregular fast pulse (atrial fibrillation), red palms and patchy hair loss, exophthalmos (bulging of the eyes) may occur in thyrotoxicosis caused by Graves' disease. As stated, the causes of an overactive thyroid are multiple. Most commonly, it is caused by Graves' disease (an autoimmune condition of the thyroid gland), toxic multinodular goitres and toxic adenoma. Less commonly, it can be caused by iodine present in certain medicines, viral thyroiditis, pituitary adenomas and thyroid cancer.⁶

Menopause (Ovarian Failure)

Most people are aware of the association between sweating and menopause. The menopause occurs when the ovarian follicles no longer function and is said to have occurred 12 months after the final menstrual period. The average age of menopause is 51, although about 7% of women experience this at age 40-45. Symptoms of the perimenopausal transition include changes in the menstrual cycle, vaginal dryness/painful intercourse, “hot flashes”, fatigue, central weight gain, and decreased libido. Night sweats are a common complaint, not only because they occur but also because sleep disturbance associated with the menopause may make women more aware of nocturnal symptoms.⁷

Other endocrine conditions associated with night sweats and fatigue

Diabetes Mellitus (with nocturnal hypoglycemia)

In diabetes, hypoglycemia associated with the administration of too much insulin can cause sweating and fatigue. This may be a problem during the night, as the person is not eating at night and the evening insulin dose may be too high, which leads to dips in blood sugar levels during the night, resulting in night sweats and fatigue.⁸

Endocrine tumours (Pheochromocytoma and Carcinoid syndrome)

Both pheochromocytoma, a hormone-producing tumour of the adrenal glands, and carcinoid syndrome, caused by rare tumours of the neuroendocrine system, can cause night sweats and fatigue, among other symptoms. Both are rare.⁸

Cancer

Lymphoma (Hodgkin’s and non-Hodgkin’s)

Lymphoma is a cancer of the body’s immune cells called lymphocytes. Traditionally, lymphomas are classified as either Hodgkin’s or non-Hodgkin’s types, although around 90 different subcategories exist. The distinction between Hodgkin’s and non-Hodgkin’s lymphoma is still important, as they affect different age groups and respond to differing chemotherapy regimes. Lymphomas comprise 4.7% of all cancer diagnoses and account for 3.5% of all cancer deaths. The typical presentation of lymphoma is painless swelling of the lymph nodes, accompanied by weight loss, fatigue, and night sweats. Surgical biopsy of the enlarged lymph nodes makes the diagnosis of lymphoma.⁹

Leukaemia

Leukaemias are a range of cancers of the blood - forming cells in the bone marrow, which lead to the formation and proliferation of abnormal white blood cells and abnormalities in the levels of other blood cell components. There are four chief sub-types of leukaemia:

• Acute myeloid leukaemia
• Acute lymphoblastic leukaemia
• Chronic myeloid leukaemia
• Chronic lymphocytic leukaemia

Leukaemia accounts for 3.2% of newly diagnosed cancers. The symptoms of leukaemia are dependent on the subtype involved. In acute leukaemia, abnormal bleeding and bruising occur along with fever, often accompanied by night sweats, lethargy, and malaise. The liver and spleen may also enlarge. These constitutional symptoms are less common in chronic leukaemias.¹⁰

Solid tumours (e.g., breast, lung)

Whilst night sweats and fatigue are most commonly associated with the cancers mentioned above, they may also be a feature of so-called solid tumours, e.g. lung cancer, or these symptoms can occur because of certain treatments for solid tumours.

Chronic Inflammatory Conditions

Night sweats and fatigue may accompany flare-ups of rheumatoid arthritis besides the typical swelling and stiffness of the joints. Other rheumatological conditions, such as systemic lupus erythematosus (SLE), may also feature night sweats and fatigue among their symptom clusters because of the effect inflammatory chemicals within the body have on core body temperature.¹¹ Two inflammatory conditions mentioned specifically in the medical literature on night sweats are Takayasu’s arteritis and temporal cell arteritis, inflammatory conditions of the blood vessels.⁸

Sleep Disorders

There is an established link between sleep disorders and night sweats; in addition, patients with sleep disorders commonly complain of daytime fatigue.¹² Sleep disorders, including OSAHS (obstructive sleep apnoea hypopnoea syndrome), are more complex than once thought, and various types of OSAHS have been identified. During sleep apnoea, there are short periods in the night where the person stops breathing, known as apnoeas. The causes of sleep apnoea are multifactorial and include obesity, smoking, and upper airway anatomy. Sleep apnoea is incredibly common, with incidence increasing with age, estimated to affect 27% of people assigned female at birth and as much as 43% of those assigned male at birth in the 50-70-year-old age range.¹³ Assessment of sleep apnoea is via a sleep study, during which breathing is observed overnight and usually performed after a full assessment by a sleep medicine specialist.

Medications

In addition to the above conditions, many prescribed medications may cause both night sweats and fatigue as side effects. Examples include: SSRI antidepressants,¹⁴ certain antiviral drugs, anti-dementia drugs and certain types of chemotherapy, including interferon.⁸

Approach to Diagnosis

Given the wide range of potential causes of night sweats and daytime weakness, diagnosis of the cause can be challenging. A detailed clinical history may reveal risk factors for certain infections, such as foreign travel to TB endemic areas, risky sexual behaviours or intravenous drug use for HIV, or a history of rheumatic heart disease, artificial heart valves or intravenous drug use for endocarditis, or other associated symptoms such as irregular menstrual periods in menopause or bleeding or bruising in leukaemia. Likewise, specific findings may be present on examination, such as lymphadenopathy (swollen lymph nodes) in lymphoma and TB, splinter haemorrhages, Osler's nodes and Janeway lesions found in endocarditis. However, if no specific indicators are found, a full blood count, purified protein derivative test for TB, test for thyroid-stimulating hormone (TSH) and test of blood inflammatory markers are reasonable first-line investigations. If these are normal, some authors recommend a trial of anti-acid reflux medications. If there are spikes in the nocturnal temperature associated with the night sweats, blood cultures for the HACEK group of bacteria (haemophilus, actinobacillus, cardiobacterium, eikenella and kingella), which cause endocarditis, are indicated. CT scan of chest and abdomen and bone marrow biopsy may be considered in persistent symptoms, with or without spikes in nocturnal temperature.⁸

Conclusion

The symptoms of night sweats and daytime weakness/fatigue represents a diagnostic challenge as they may be caused by many vastly different underlying conditions. These conditions vary in prevalence and severity, range from infections to hormonal to inflammatory, and malignant conditions. Whilst classically, illnesses such as TB, HIV, and lymphoma are associated with night sweats and fatigue, the reality is that serious causes are often not found in patients presenting to their GP with these symptoms. A systematic approach to diagnosis can help identify serious causes of these symptoms.