Environmental conditions
Cold exposure and stay at high altitude may lead to type 1 or type 2 phenotype, depending on duration and other boundary conditions (which determine whether or not stress is associated with energy deprivation). Diagnosis
Affected patients may have normal, low, or slightly elevated TSH depending on the spectrum and phase of illness. Total T4 and T3 levels may be altered by binding protein abnormalities, and medications. Reverse T3 levels are generally increased, while FT3 is decreased. FT4 levels may have a transient increase, before becoming subnormal during severe illness. Correspondingly, in the majority of cases calculated sum activity of peripheral deiodinases (SPINA-GD) is reduced. Generally the levels of free T3 will be lowered, followed by the lowering of free T4 in more severe disease. Several studies described elevated concentrations of 3,5-T2, an active thyroid hormone, in NTIS. 3,5-T2 levels were also observed to correlate with concentrations of rT3 (reverse T3) in patients with euthyroid sick syndrome. NTIS is a component of a complex endocrine adaptation process, so affected patients might also have hyperprolactinemia and elevated levels of corticosteroids (especially cortisol) and growth hormone. NTIS can be difficult to distinguish from other forms of thyroid dysfunction in the hospital setting. Both NTIS and primary hypothyroidism may have reduced fT3 and fT4, and elevated TSH (which is common in the hospital, during the recovery phase of NTIS). Prescribing thyroxine to treat this may lead to lifelong thyroid overtreatment.Hyperthyroidism may be assumed due to decreased TSH and a transient fT4 increase.
In some cases, this can be distinguished from NTIS by a thyroid ultrasound, which is commonly available in the hospital intensive care unit.NTIS looks similar to central hypopituitarism; both frequently have reduced TSH and thyroid hormone levels. Treatment
Debate is ongoing as to whether NTIS is an adaptive or maladaptive mechanism in response to physiological stress. Some sources indicate that NTIS is beneficial as an acute-phase response, but detrimental during the chronic phase of illness. Several trials have investigated a possible therapy for NTIS, but they yielded inconsistent and partly contradictory results. This may be due to the heterogeneity of investigated populations, and to the lack of a consistent definition of NTIS.Administering exogenous T3 and T4 has variable results, but overall seems to confer no improvements to health outcome. Administering TRH to patients with chronic illness, however, seems to normalize thyroid levels and improve catabolic function.When NTIS is caused by the normal fasting response to illness, early parenteral nutrition has been shown to attenuate alterations in thyroid hormone (TSH, T3, T4, rT3) levels, whereas late parenteral nutrition exacerbates it. Late parenteral nutrition, though,  also reduced complications and accelerated recovery in one study. History
In 1968, a reduced T4 half-life in athletes was discovered. This was the first awareness of thyroid hormone concentration alterations that were not a result of thyroid gland or pituitary dysfunction. In 1971, they also found a transient increase in T4 during bicycle training.In 1973, Rothenbuchner et al. discovered that starvation is correlated with reduced T3 concentration.