Tuesday, December 11, 2012

Factors affecting thyroid function


FACTORS THAT AFFECT THYROID FUNCTION

a. Age
The level of TSH and thyroid hormones are higher in neonates and children which is required for growth and development. In old age slight decrease is seen.

b .Pregnancy
In pregnancy due to effect of estrogen and diminished clearance there is increase in TBG. Also there is increase in deiodination of thyroid hormones in developing placenta. So, during pregnancy there is increase in requirement for iodine (200µg/day) and more T4 and T3 is produced to compensate for overutilization. In early pregnancy due to thyroid stimulating action of hCG there is slight rise in fT3 and fT4, and this suppresses TSH but as pregnancy progress this pattern subsides since hCG also falls thus TSH rises.

c. Non-thyroidal illness
Patients in hospital with NTI have abnormalities in thyroid function tests. A low T3 may be found even though patients are clinically euthyroid; this has been termed as sick euthyroid syndrome. Several mechanisms are involved, including:

  1. Hypothalamic-pituitary-thyroidal malfunction leading to decrease store of TRH and  suppression of TSH due to increased concentration of dopamine, cytokine, cortisol, etc. 
  2. Alteration in plasma concentration and affinity of binding proteins (usually reduced concentration and affinity). High concentration FFA can compete with thyroid hormone binding to plasma proteins so there may be slight rise in T4.
  3. Impaired uptake of thyroid hormones in tissue
  4. Decreased conversion of T4 to T3 in peripheral tissue and receptor dysfunction. This cause marked decline in T3 and slight increase in T4. Excess T4 is converted to rT3 which is metabolically inactive and there is marked increase in rT3.

TSH is the most reliable test of thyroid function in hospitalized patients. Normalization of thyroid parameters occurs during recovery from NTI or refeeding after starvation. These changes in TSH helps in differential diagnosis of thyroid disorder which lead to hyper and hypothyroidism. In NTI plasma proteins are altered, since thyroid hormones are bound by proteins, so measurement of T3, T4 would not indicate exact picture.


In non-thyroidal illness 5’-mono-deiodination (D1) is impaired leading to a decreased production of T3 but increased rT3 due to impaired clearance; however total T4 remains unchanged.

Assessment of thyroid illness in ill patient should be postponed until the illness resolves.

Hypothyroidism in euthyroid sick syndrome shows a reduced total T4 and a slightly subnormal FT4. Serum TSH is probably the best single test to distinguish between euthyroid sick syndrome and hypothyroidism (in the absence of suspected pituitary or hypothalamic disease or medications, such as dopamine or glucocorticoids). A clear elevation of the TSH concentration (>20 mIU/L) would indicate hypothyroidism. Lesser TSH elevations may be seen transiently in euthyroid sick syndrome patients during recovery. If the question of hypothyroidism in acutely ill patients cannot be resolved with TSH and FT4 testing, measurement of rT3 may help (rT3 being low in hypothyroidism and normal or high in euthyroid subjects). Documentation of a normal serum cortisol may help-distinguish euthyroid sick syndrome patients from those with hypothalamic or pituitary hypothyroidism.

Hyperthyroidism in euthyroid sick syndrome shows subnormal TSH values often associated with the acute phase of illness or with glucocorticoid or dopamine therapy. In these ill patients TSH level is mildly suppression in 0.05 to 0.1 mIU/L range as compared to hyperthyroid patients where TSH is highly suppressed.

d. Drugs
Dopamine, glucocorticoid, cytokine decreases TSH secretion. Lithium, iodide decrease or increase thyroid hormone secretion; Propylthiouracil, carbimazole decrease thyroidal synthesis; Oestrogens increases TBG whereas androgen, glucocorticoid decreases TBG. NSAIDs, Phenytoin, carbamazepine, furosemide and salicylate compete with thyroid hormone binding to plasma binding proteins and may increase plasma fT4 concentration.

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