Euthyroid sick syndrome (nonthyroidal illness syndrome)
Euthyroid sick syndrome, also called nonthyroidal illness syndrome, is the pattern of low triiodothyronine, low or normal thyroxine, and a suppressed but detectable thyrotropin seen in hospitalized or critically ill patients without intrinsic thyroid disease. Diagnosis rests on recognizing the pattern in the right clinical setting; management withholds thyroid hormone treatment and treats the underlying illness.
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What this article covers
- Overview
What it is: euthyroid sick syndrome, also called nonthyroidal illness syndrome (NTIS), is a pattern of abnormal thyroid function tests, low triiodothyronine, variably low thyroxine, and a suppressed…
- Epidemiology
Extremely common in hospitalized patients: up to 75% of hospitalized patients have some physiologic abnormality on thyroid function testing, most attributable to nonthyroidal illness syndrome rather than intrinsic thyroid disease.
- Risk factors
Severity and duration of critical illness: the more severe and prolonged the systemic process, the deeper the fall in triiodothyronine and, later, thyroxine.
- Pathophysiology
Central suppression: systemic illness suppresses hypothalamic thyrotropin-releasing hormone, lowering the drive to secrete TSH; TSH runs suppressed but stays detectable, unlike the frank elevation of…
- Clinical features
No thyroid-specific symptoms: the fatigue, cold intolerance, or bradycardia of primary hypothyroidism are not attributable to the pattern itself; findings reflect the precipitating illness.
- Differential diagnosis
Primary hypothyroidism: low free thyroxine with an elevated TSH, often 20 mU/L or higher, frequently with a positive thyroid peroxidase antibody titer and a goiter, unlike this syndrome, where TSH stays suppressed but detectable.
- Diagnosis
What establishes the diagnosis: recognizing the pattern, low or normal free thyroxine, low triiodothyronine, elevated reverse triiodothyronine, and a suppressed but detectable TSH, in a hospitalized…
- Management
First step, do not test reflexively: do not order thyroid function tests in a hospitalized patient absent a specific clue such as a goiter, exophthalmos, a new arrhythmia, or hypopituitarism…
- Complications
Inappropriate thyroid hormone treatment: mistaking the pattern for hypothyroidism and giving levothyroxine or liothyronine adds metabolic demand in an already catabolic patient, a recognized theoretical harm with no offsetting trial benefit.
- Prognosis
Tracks the underlying illness rather than an independent thyroid problem: the abnormalities correlate with illness severity and resolve as that illness resolves; a deeper fall in triiodothyronine…
- Prevention
If thyroid function is tested and found abnormal, do not treat it prophylactically: the finding alone, without an undetectable or 20-mU/L-or-higher TSH, should not trigger thyroid hormone treatment.
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Related articles
- Hypothyroidism
Hypothyroidism is thyroid hormone deficiency, most commonly caused by autoimmune (Hashimoto) thyroid failure in iodine-sufficient countries, diagnosed by an elevated thyroid-stimulating hormone with a low or normal free thyroxine. First-line treatment is levothyroxine dosed at 1.6 mcg/kg lean body weight orally once daily, titrated using thyroid-stimulating hormone rechecked no sooner than 6 weeks after any dose change.
- Hyperthyroidism
Hyperthyroidism is the clinical syndrome of thyroid hormone excess, produced by a range of causes from Graves disease and autonomously functioning nodules to destructive thyroiditis and exogenous hormone ingestion. Diagnosis begins with a suppressed thyroid-stimulating hormone and elevated free thyroxine, followed by radioactive iodine uptake testing or antibody measurement to identify the cause, and first-line treatment is a beta blocker for symptom control while the underlying cause directs thionamide, radioactive iodine ablation, or thyroidectomy therapy.
- Myxedema coma
Myxedema coma is a rare, life-threatening decompensation of severe, longstanding untreated hypothyroidism with hemodynamic compromise and mortality up to 30-40%, typically precipitated by cold exposure, infection, or another acute illness. First-line treatment is empiric intravenous glucocorticoids followed immediately by intravenous levothyroxine (300-500 mcg load, then 1.6 mcg/kg/day), with aggressive supportive care in the ICU.
- Thyroid storm
Thyroid storm is a rare, life-threatening exaggeration of thyrotoxicosis with multiorgan dysfunction and mortality up to 30%, most often precipitated by discontinuation of antithyroid drugs, infection, surgery, or trauma in a patient with underlying hyperthyroidism. It is a clinical diagnosis treated emergently in the ICU with intravenous beta-blockade, a thionamide (propylthiouracil transitioning to methimazole), potassium iodide given only after the thionamide, and high-dose glucocorticoids.
- Sepsis
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, identified by an acute rise in SOFA score of 2 points or more in a patient with known or suspected infection. Survival depends on recognizing the pattern early and completing the hour-1 bundle: lactate, blood cultures before antibiotics, broad-spectrum antibiotics such as cefepime 2 g IV every 8 hours, and 30 mL/kg crystalloid for hypotension or a lactate of 4 mmol/L or higher.
- Secondary adrenal insufficiency
Secondary adrenal insufficiency is ACTH deficiency from pituitary or hypothalamic disease, or most commonly from withdrawal of prolonged exogenous glucocorticoid therapy, causing isolated cortisol deficiency without hyperpigmentation or hyperkalemia because aldosterone secretion is preserved. Lifelong glucocorticoid replacement with hydrocortisone, with dose increases during illness, prevents adrenal crisis.
- Hashimoto thyroiditis
Hashimoto thyroiditis is a chronic autoimmune process in which lymphocytic infiltration destroys the thyroid, and is the most common cause of hypothyroidism in iodine-sufficient regions such as the United States. Diagnosis rests on an elevated thyroid-stimulating hormone with a low or normal free thyroxine, and first-line treatment is lifelong levothyroxine replacement dosed to normalize thyroid-stimulating hormone.