The idea of a "Set-Point" for temperature control is that at a basic core body temperature of about 37.1 degrees C (98.8 degrees F), intense changes happen in the paces of both heat loss and heat production. At temperatures over this level, the pace of heat loss is more prominent than that of heat production, so the internal heat level falls and approaches the 37.1 degrees C level.

At temperatures beneath this level, the pace of heat production is more prominent than that of heat loss, so the internal heat level ascents and again moves toward the 37.1 degrees C level. This significant temperature level is known as the "set-point" of the temperature control component. In this way, all the temperature control processes constantly endeavor to take the internal heat level back to this set-point level.

The quick change in the set point in the hypothalamic thermostat causes an elevation in core body temperature by triggering several physiological reactions. Temperature-increasing mechanisms incorporate the following:

1. Posterior hypothalamic sympathetic center stimulation causes skin vasoconstriction all through the body.
2. Piloerection, which is hairs "raising on end." The excitement of the sympathetic system causes the contraction of the arrector pili muscles, which results in a standing position of the hairs. This process is significant in lower creatures, which permits them to capture a layer of non-conducting air close to the skin, which significantly depresses the heat transfer to surroundings.
3. Heat production or thermogenesis increases through shivering, sympathetic stimulation, and thyroxine discharge.

A diagnostic approach to fever or hyperthermia includes the following:

History and physical examination:

Diagnostic testing:

• ESR and CRP
• Procalcitonin-elevated in certain bacterial infections
• Tuberculin skin test
• HIV
• Serum LDH
• Routine blood cultures
• RF, ANA, heterophile antibody in children and young adults
• CPK
• Serum protein electrophoresis
• Imaging studies like CT chest, abdomen based on history
• CNS signs should prompt for Lumbar puncture
• In a person with travel history to malaria-endemic areas should be tested with thick and thin peripheral smears.
• In IV drug abuse rule out thrombophlebitis and infective endocarditis

Several other specific tests can be performed based on the history and physical exam findings in different patients of varying age groups.

The most crucial component initiating fever in the human body is the presence of a pyrogen. A pyrogen is a substance that physiologically induces fever in the body [6]. Pyrogens can be classified as endogenous or exogenous depending on whether they originate from inside the body or a fever triggering component from outside the body (e.g., toxins).[7] 

Many infectious pathogens normally trigger exogenous pyrogens as a part of their virulence. For example, the cause of a febrile response in a Neisseria Meningitidis infection is commonly triggered by the lipopolysaccharide (LPS) component of this bacteria's cell wall, which subsequently induces the production of the cytokine prostaglandin-E2.[8] Cytokines, natural mediators of the body's immunological response, operate as endogenous pyrogens to trigger the activation of the fever response. Common cytokines known to induce the febrile response include but are not exclusive to IL-1, IL-6, and TNF.[9]

After the release of cytokine or exogenous pyrogens into the circulatory system, they bind to specific receptors on the epithelial, vascular system. This process subsequently causes the production and release of prostaglandin-E2 (PGE2), which is the ultimate inflammatory mediator associated with many of the effects and symptoms related to the febrile response.[10] In the brain, the presence of the PGE2 stimulates the increase in the set-point temperature of the hypothalamus and enables the increase in the core body temperature.[11]

The normal internal heat level is low in the early morning and high at night, shifting 0.5 degrees C (0.9 degrees F) through the span of the day, controlled in the thermoregulatory focus situated in the anterior hypothalamus.

• Fever occurs when there is an elevation in the body's thermoregulatory set-point either by endogenous or by exogenous pyrogen. In hyperthermia, the set-point is unaltered, and the body temperature becomes elevated in an uncontrolled fashion due to exogenous heat exposure or endogenous heat production.
• Hyperpyrexia is the term for an exceptionally high fever (>41.5 degrees C), which can occur in patients with serious infections; however, most ordinarily happen in patients with CNS hemorrhages.
• Inhibitors of cyclooxygenases, for example, aspirin and acetaminophen help reduce fever[12]
• Observation of a pattern of fever can be helpful in certain conditions; for example, a fever that occurs every 48 to 72 hrs in certain types of malaria, evening rise of temperature occurs in tuberculosis.
• For instance, the everyday highs and lows of typical temperatures are emphasized in many fevers. However, these variations might be turned around in typhoid fever and disseminated tuberculosis. Temperature-pulse dissociation occurs in typhoid fever, brucellosis, leptospirosis, some medication prompted fevers, and factitious fever. In healthy people, the temperature-pulse relationship is directly proportional with an expansion in the pulse of 4.4 beats/minute for each 1 degree C (2.44 beats/minute for each 1 degree F) an increase in core temperature.
• During infections, fever may not be observed in babies, older adults, patients with CKD, and in patients taking corticosteroids; on the contrary, hypothermia may be present.