Downloaded 130 times
More Related Content
Similar to Sick euthyroid syndrome
More from Shivshankar Badole
Sick euthyroid syndrome
- 1. Sick Euthyroid Syndrome Guide: Dr Rajesh Verma Sir Candidate : Dr Sagar Dagdiya
- 2. Sick Euthyroid Syndrome •Abnormal findings in thyroid function tests • Occur in the setting of a non thyroidal illness(NTI) • Without pre-existing hypothalamic-pituitary- thyroid gland dysfunction.
- 3.
- 5. Function of DeiodinaseEnzyme Parameters D1 D2 D3 Act on rT3 ,T4 T4 ,rT3 T3,T4 Tissue location Liver ,Kidney Thyroid ,Pituitary CNS, Pituitary Skeletal muscle, Placenta, Thyroid, Heart Placenta,CNS Hemangiomas, skeletal muscle liver Function Degradation of rT3 and T3 Synthesis Main source of T3 Inactivation of T3 and T4
- 6. • Normally T3,T4 and TSH levels are well regulated • Most prominent are low T3 & elevated rT3 • Leading to the term “low T3 syndrome.” • As the severity of non thyroidal illness increases, both T3 and T4 levels drop that usually normalizes as the underlying illness recovers.
- 7. Mechanisms • Cytokines particularlyIL-1, IL-6, TNF-α and Interferon-β. • Impaired peripheral deiodination of T4 to T3. • Decreased clearance of rT3. • Inhibition of thyroid hormone binding to thyroid hormone binding proteins and tissues. • Insufficient levels of thyroid hormone binding proteins(TBG, TBPA & TBA).
- 8. • During inflammatorystates, there is increase in Reactive Oxygen Species(ROS). • The active centers of both D1 & D2 are intracellular, and that of D3 is extracellular, which do not pass easily through the cell membrane.
- 9. • D1 &D2 inactivated • However D3 is spared {and Type 2 Deiodinase in Tanycytes is also spared} • Leading to decreased T3 & Increased rT3 • Reduced clearance of rT3 due to reduced activity of D1 & D2
- 10. • D2 isthought to be negatively regulated by thyroid hormone • Normal to increased production of T3 via increased activity of D2 in Tanycytes (Speciliased cells in the wall of 3rd Ventricle).
- 11. • Cytokines likeIL-1, IL-6, TNF-α & Interferon-γ also affect hypothalamus, pituitary and other tissues. • Interferon-γ inhibits TSH & cAMP induced up- regulation of TSH receptors on thyroid cells.
- 12. • Interferon-γ andTNF-α inhibits TSH induced mRNA expression and thyroid hormone & thyroglobulin secretion. • Interferon-γ inhibits TSH induced increase in sodium iodide symporter (NIS) expression • Diminished iodide uptake.
- 13. • Prolonged criticalillness there is decreased food intake • Decreased level of hormone leptin • Cytokines, cortisol and leptin alters secretion of TRH and TSH • Reduction in leptin levels cause increase in Type 3 Deiodinase activity.
- 14. Effect of NTIon T3 & rT3 MCR : Metabolic Clearance Rate PR : Production Rate
- 15. Diagnosis • Low T3and T4 levels. • TSH : can be Low, Normal or slightly Elevated. • Reverse T3(rT3) : Elevated. • Sr. Cortisol levels : Usually Elevated.
- 16. Systemic and NTI ConditionT3 rT3 T4 FT4 TSH Fasting = = Mild illness = =, = Critical illness =, Trauma /Burn =, CRF = =, =, =, Hepatitis =, =, =, =, = HIV infection = = =, =, Depression =, =, =, =, =,
- 17. Differential Diagnosis Hypothyroidism :Low T3 & T4 with markedly increased TSH with low Cortisol. Acute exposure to heat : Low T3 (free & total) with increased rT3 and TSH. Fasting/Starvation : Total T4 usually unchanged, free T4 normal or elevated due to increase in FFA. Total & free T3 decreased. Elevated rT3 with diminished response of TSH to TRH.
- 18. Surgery : TotalT3 level falls, free T3 level increases on the day of surgery that eventually falls postoperatively. T4 & TSH levels are usually unaltered. Myocardial Infarction : In 1-3 days post infarction, total T3 low, rT3 elevated and TSH may be normal or elevated.
- 19. CKD : Total& Free T4 normal or decreased, Total & Free T3 reduced, rT3 unchanged, Basal TSH unchanged or reduced. Low FT3 is an independent predictor of death in hemodialysis patients. Liver Disease : Total T4 unchanged or increased, Free T4 unchanged or reduced, Free T3 reduced or unchanged, rT3 elevated, TSH reduced, normal or slightly elevated.
- 20. HIV Infection :Patients with asymptomatic HIV infection have TFT results WNL or slightly increased TSH levels. Psychiatric Illness : In acute psychosis, there is elevated T4. Patients with PTSD may have slightly high serum T3 concentrations, but their serum FT3, FT4, and TSH are normal.
- 21. Severity of Illnessand Pattern of Sick Euthyroid Syndrome • The changes in hormonal status depends upon the duration of the illness -Acute illness -mild ,moderate ,severe -Chronic illness • Magnitude of change in T3 and rT3 reflects severity of illness • Total T3 fall is faster than FT3, T4 level is generally within normal range, however T4 level may fall as the severity of NTI increases.
- 22. • Low T3- D2,D1 in peripheral tissue • TSH (N) with T3 : Suppression of TSH by T3 produced by D2 located in tanycytes TRH TSH (N) FT4 (N) FT3 rT3 T2 D2,D1 D1,D2 D3 Free T3 Free T4 RT3 TSH Cause N (2 -3 fold) N D2,D1 D350% Mild Illness (acute illness)
- 23. Moderate To SevereIllness (Acute Illness) • TSH - cytokine ,drugs suppress H-P level • FT4 ( ,N) even with TSH FFA and other substances reduce the binding to TBG • in Tissue FT3 similar that of serum FT3 TRH TSH FT4 FT3 rT3 T2 D2 ,D1 D3 (N , , ) D1,D2D3 Free T3 Free T4 RT3 TSH Cause N, (2 -3 fold) N , D2,D1 ,D3 (N, ) 50-70%
- 24. Changes in ChronicCritical Illness TRH TSH FT4 FT3 rT3 T2 Free T3 Free T4 RT3 TSH Cause D2,D1, D3 • FT4 and TSH marked reduced • FT3 marked reduced ,barely detected in tissue level
- 25. Changes in ThyroidHormone Levels During Illness Severity of Illness Free T3 Free T4 Reverse T3 TSH Probable Cause Mild N N D2,D1 Moderate N, , N, D2,D1, ? D3 Severe D2,D1, D3 Recovery ?
- 26. Thyroid Hormone ConcentrationIn In-Patients Severity Of Illness : Mild Moderate Severe
- 27. Treatment • Treatment withThyroid Hormone Replacement is controversial. • Whether there is any beneficial role behind these alterations is still not clear. • When the underlying illness is treated, results of thyroid tests usually normalize of its own.
- 28. • The onlypositive outcomes of T3 treatment is seen in patients undergoing cardiac surgery. • Postoperative intravenous T3 therapy increases cardiac index • No difference in mortality benefit
- 29. • Co-infusion ofGHRH plus TRH is better • Induce restoration of pulsatile growth hormone and TSH release • Near-normal serum T4 and T3 values • Shift from catabolism towards anabolism • Rise in circulating rT3 avoided.