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مخاطبین محترم : رزیدنتهای داخلی و فلوهای غدد

مختصر و مفید از:

UPTODATE 21.2

 

euthyroid-sick :

INTRODUCTION —

Previously, these patients were thought to be euthyroid, and the term euthyroid-sick syndrome was used to describe the laboratory abnormalities . However, there is some evidence that these patients may have acquired transient central hypothyroidism .

There are two important general principles :

  • Thyroid function should not be assessed in seriously ill patients unless there is a strong suspicion of thyroid dysfunction.
  • When thyroid dysfunction is suspected in critically ill patients, measurement of serum TSH alone is inadequate for the evaluation of thyroid function.

LOW SERUM T3 —

80 percent of circulating T3 is produced by the peripheral 5′-deiodination of T4 to T3, in organs such as the liver and kidney

5′-monodeiodination decreases whenever caloric intake is low and in any nonthyroidal illness, even mild illness .

there is reduced 5′-monodeiodinase activity and increased 5-monodeiodinase activity (which converts T4 to rT3

Patients with fatal illness have low tissue T4 and T3 concentrations .

Several mechanisms for inhibition of 5′-monodeiodination in nonthyroidal illness :

High endogenous serum cortisol concentrations and exogenous glucocorticoid therapy

Circulating inhibitors of deiodinase activity, such as free (non-esterified) fatty acids

impair uptake of T4 into hepatocytes, thereby reducing the availability of substrate for conversion to T3 .

  • drugs :  amiodarone and high doses of propranolol.
  • Cytokines (TNF , INF-alfa, NF-kB, and IL-6)

When to measure Reverse T3  —

The clearance of rT3 to diiodothyronine (T2) is reduced in nonthyroidal illness

 serum rT3 concentrations are high in patients with nonthyroidal illnesses, except in those with renal failure and some with AIDS .

 Measurement of serum rT3 is occasionally useful in hospitalized patients to distinguish between nonthyroidal illness and central hypothyroidism( rT3 are low) .

In patients with mild hypothyroidism, rT3 may be NL or even slightly high .

Thyroxine sulfate (T4S) is also elevated in critical nonthyroidal illness .

LOW SERUM T4 —

From 15 to 20 % of hospitalized patients and up to 50 % of patients in ICU  have low serum T4 concentrations (low T4 syndrome).

The concentrations are low primarily because of reductions in the serum concentrations of one or more of the three thyroid hormone-binding proteins: thyroxine-binding globulin (TBG), transthyretin (TTR, or thyroxine-binding prealbumin [TBPA]), and albumin.

Since TBG is the major binding protein, low serum T4 values are likely the result of decreased production of normal TBG or production of TBG that binds T4 poorly because it is abnormally glycosylated or is cleaved in the circulation .

Free T4 —

 free T4 index are usually normal in patients whose illness is not severe.

in  more critical illness have circulating substances that inhibit T4 binding to the binding proteins .

 free T4 fraction measured by equilibrium dialysis may be normal or even slightly high in these patients .

Possible contributing factors for decreased T4 and free T4: inhibitors of T4 binding —

Some data support the possibility that high serum free fatty acid ( is high in critically ill patients)  inhibit T4 binding to serum proteins

effect of FFA on T4 binding may be increased because of hypoalbuminemia, because albumin is the major carrier of free fatty acids in serum

Inhibitors may also interfere with the T3-resin uptake test by interacting with the solid matrices used in the test .

Transient central hypothyroidism —

Patients with severe nonthyroidal illness may have acquired transient central hypothyroidism

SERUM TSH — Serum TSH assays that have a detection limit of 0.01 mU/L should be used in assessing thyroid function in critically ill patients . TSH results should be interpreted as follows:

Low but detectable —

Almost all patients who have a subnormal but detectable serum TSH concentration (greater than 0.05 mU/L and less than 0.3 mU/L) will be euthyroid when reassessed after recovery from their illness.

Undetectable —

 In contrast, approximately 75 % of patients with undetectable serum TSH concentrations (<0.01 mU/L) have hyperthyroidism.

High —

 As noted above, some hospitalized patients have transient elevations in serum TSH concentrations (up to 20 mU/L) during recovery from nonthyroidal illness , Few of these patients prove to have hypothyroidism .

Patients with TSH > 20 mU/L usually have permanent hypothyroidism .

EFFECTS OF DRUGS —

 Dopamine, dobutamine, glucocorticoids, furosemide, NSAIDS , heparin, anticonvulsants, metformin, and drugs that affect TBG can alter thyroid function tests.

Specific nonthyroidal illnesses —

acute hepatitis, hepatoma, acute intermittent porphyria, acromegaly, nephrotic syndrome, Cushing’s syndrome, acute psychosis, and depression.

Psychiatric illness —

 Some patients with acute psychiatric illnesses, particularly schizophrenia, have transient elevations in serum T4 concentrations with or without low serum TSH concentrations

Patients with severe depression may have changes similar to those of patients with glucocorticoid excess

PROGNOSIS —

serum free T4 index value correlates with outcome; values under 3 have been associated with mortality rates in excess of 85 percent

high rT3 and a low T3/rT3 ratio on the first day in an ICU correlated with increased mortality

TREATMENT

Thyroid hormone replacement —

treatment of these patients with thyroid hormone, while controversial, appears to be of little benefit, and may be harmful

 Thyroid hormone replacement has not been shown to be effective for patients with critical illness and low T3 and/or T4, or for patients undergoing cardiopulmonary bypass.

Thyroid hormone during fasting —

 During fasting, there is an associated decrease in serum T3 concentrations that spares muscle protein. T3 replacement results in increased catabolism with breakdown of skeletal muscle

Critical illness —

 Thyroid hormone replacement does not appear to be beneficial for critically ill patients with low serum T3 and/or low T4 concentrations.

CABG —

During and after cardiopulmonary bypass, there is a transient decrease in serum T3 concentrations,

In summary, there is no evidence that thyroid hormone replacement is beneficial for patients with critical illness who have low serum T4 or T3 concentrations, or for patients undergoing CABG, whose serum T3 concentrations are known to decrease in the perioperative period. If, however, there is evidence to support a diagnosis of hypothyroidism (such as a TSH over 20 mU/L with low free T4 and/or history, symptoms, and signs of hypothyroidism), cautious administration of thyroid hormone is appropriate.

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