Thyroid Physiology in Nonthyroidal Illness (Euthyroid Sick Syndrome)

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • The evaluation of a chronically ill or hospitalized patient with abnormal serum thyroid function tests:
    • Can often be challenging
  • Nonthyroidal illness is not considered a primary thyroid disorder:
    • Its pathophysiology is not completely understood:
      • Although it is known that the elevation of cytokines and hypoxia plays a significant role
    • It is generally recommended to avoid measuring serum thyroid function tests during acute illness:
      • Unless thyroid dysfunction is thought to be a significant contributor to the illness
  • Severe nonthyroidal illness:
    • Is accompanied by significant alterations in thyroid physiology
  • Due to the decreased availability in all of the thyroid binding proteins (thyroxine bindings globulin, transthyretin, albumin):
    • Serum total T4 and total T3 levels are reduced:
      • Whereas free levels are usually normal or slightly low (Figure)
    • Total T3 levels are further decreased:
      • Due to reduced Dio1 activity:
        • Which converts T4 to T3
    • A relatively greater amount of T4 is metabolized to the inactive metabolite:
      • Reverse T3 (rT3):
        • By Dio3
      • Although measurement of rT3 does not reliably distinguish nonthyroidal illness from primary hypothyroidism
      • The degree of serum rT3 elevation, depressed T3 / rT3 ratio, and decreased FT3 and FT4 concentrations:
        • Have been associated with higher mortality among patients in the intensive care unit (ICU):
          • Treatment with T4 or T3, however, does not consistently improve outcome
      • Whether other T4 metabolites, including 3,3′-diiodothyronine (3,3′-T2); 3,5-diiodothyronine (3,5-T2); and 3-iodothyronamine (3-T1AM):
        • Have functional roles in nonthyroidal illness remains unclear
Alternations in Serum Thyroid Hormone Concentrations During Acute Nonthyroidal Illness and Recovery.
The degree of change in hormone concentrations relates to the severity and duration of the illness. Thyroid-stimulating hormone (TSH) may also be suppressed during severe illness and transiently rise moderately above the reference range before returning to normal with recovery. Mortality correlates inversely with the degree of reduction in total T4 concentration. (From Farwell AF. Sick euthyroid syndrome in the intensive care unit. In: Irwin RS, Rippe JM, eds. Intensive Care Medicine. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2003.)
  • It is important that the diagnosis of primary thyroid dysfunction:
    • Is not established during severe illness based solely on an abnormal serum TSH
  • In nonthyroidal illness:
    • Serum TSH concentrations may be low, normal, or high:
      • Due to the TSH-lowering effects of commonly used medications (glucocorticoids, ipodate, amiodarone, dopamine) in patients managed for a nonthyroidal illness or from a reversible form of acquired central hypothyroidism in severe nonthyroidal illness
  • During the recovery phase of nonthyroidal illness:
    • The TSH may briefly rise above the upper reference range, as suppression of TSH lessens, before it normalizes
    • When possible, thyroid evaluation after recovery from an acute illness is recommended in patients suspected of having intrinsic thyroid disease
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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