Introduction:
Euthyroid hyperthyroxinemia is a condition in which the patient remains euthyroid (normal functioning of the thyroid gland) despite elevated levels of serum total thyroxine and triiodothyronine, the two thyroid hormones. The condition is asymptomatic, making it difficult to be diagnosed or be incorrectly diagnosed as hyperthyroidism. Acquired and inherited abnormalities of serum thyroid-binding proteins, opposition or resistance to thyroid hormones, acute systemic illness, acute psychiatric issues, and several drug-induced conditions associated with non-thyrotoxic elevations of serum thyroxine are among the causes of euthyroid hyperthyroxinemia. Many of these disorders are also accompanied by abnormalities in triiodothyronine and free thyroid hormone levels, as well as thyroid-stimulating hormone unresponsiveness to the thyrotropin-releasing hormone, all of which can lead to a false thyrotoxicosis diagnosis. Since the patient remains euthyroid, the condition generally does not require any treatment.
What Is the Thyroid Gland?
The thyroid is a small endocrine gland located in front of the neck. The thyroid is a vascular gland shaped like a butterfly, consisting of two lobes. Both the lobes of the thyroid are bridged by a band of tissues known as the isthmus. Although the thyroid is a small gland, it is crucial for the regulation of various functions of the body. Primarily, the thyroid is involved in the production and release of thyroid hormones. These hormones are thyroxine (T4), triiodothyronine (T3), and calcitonin. The thyroid hormones are responsible for the growth, development, and regulation of other metabolic activities in the body. Any imbalance in the thyroid hormone levels can throw the body at risk of developing thyroid disorders like hypothyroidism (underactive thyroid), hyperthyroidism (overactive thyroid), goiter (lump in the thyroid gland), etc.
What Is Euthyroid Hyperthyroxinemia?
Euthyroid hyperthyroxinemia is a condition characterized by elevated levels of serum total thyroxine (T4) and triiodothyronine (T3), along with normal levels of thyroid-stimulating hormone (TSH). The condition is usually asymptomatic, which means the patient does not show any physical signs or symptoms of elevated levels of thyroid hormones. Euthyroid hyperthyroxinemia can be a temporary or permanent condition depending upon its cause.
How Does Euthyroid Hyperthyroxinemia Occur?
Thyroxine (T4) and triiodothyronine (T3) primarily bind with three separate binding proteins in the bloodstream; thyroxine-binding globulin, thyroxine-binding prealbumin, and albumin. Approximately 99.7 percent of circulating thyroxine and triiodothyronine bind to these proteins. Out of which, thyroid-binding globulin carries 75 percent of the circulating thyroxine and triiodothyronine. Thyroid-binding prealbumin binds mainly with thyroxine and carries a total of 15 percent of these hormones. Albumin binds to only 10 percent of the thyroid hormones. Both bound and free (unbound) hormones are measured in serum total thyroxine (T4) and triiodothyronine (T3) assays. As a result, even if serum total free T4 and T3 levels do not change and the patient is euthyroid (shows normal thyroid functioning), factors that alter binding protein concentrations significantly impact serum total T4 and T3 concentrations.
Is Euthyroid Hyperthyroxinemia a Common Condition?
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The incidence rate of euthyroid hyperthyroxinemia is unknown because the condition is associated with multiple disorders and is often misdiagnosed as hyperthyroidism or thyrotoxicosis. However, familial dysalbuminemic hyperthyroxinemia is one of the most common causes of euthyroid hyperthyroxinemia, and its prevalence rate is around 0.08 to 0.17 percent.
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Euthyroid hyperthyroxinemia affects both men and women equally, and it is also common in pregnant women.
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Euthyroid hyperthyroxinemia can occur at any age and has no average age of onset.
What Causes Euthyroid Hypethyroxinemia?
The causes of euthyroid hyperthyroxinemia are variable, ranging from physiologic conditions like pregnancy to side effects of certain drugs.
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Physiologic Conditions: Pregnancy is the most common cause of euthyroid hyperthyroxinemia occurring due to increased thyroxine-binding globulin concentrations. During pregnancy, estrogen levels are elevated, stimulating the production of thyroxine-binding globulins by the liver. Total T4 and triiodothyronine (T3) levels rise as a result, while T3 resin uptake falls, resulting in normal free T4 and T3 levels.
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Hereditary Causes: Hereditary conditions are diseases or medical conditions that are passed down from parents to their children and are inherited from generation to generation. Several hereditary conditions associated with thyroid-binding protein abnormalities are responsible for the development of euthyroid hyperthyroxinemia. Increased thyroid-binding globulin is an x-linked dominant disorder, and it is the most common binding protein abnormality. In this condition, the production of thyroid-binding globulin (TBG) is increased, which, in turn, increases the concentrations of T4 and T3 (because TBG has an affinity for T3 and T4). Increased thyroxine-binding prealbumin (TBPA) is another binding protein abnormality resulting in euthyroid hyperthyroxinemia. TBPA carries T4 more than T3. Therefore, falsely elevated free T4 index results from this condition. Familial dysalbuminemic hyperthyroxinemia (FDH) is the most common cause of euthyroid hyperthyroxinemia due to elevated total T4.
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Drug-Induced Hyperthyroxinemia: The abuse of heroin, Methadone, Clofibrate, Perphenazine, and 5-fluorouracil increase the secretion of thyroid-binding globulin and ultimately increase their serum concentrations. In addition, drugs like Amiodarone, Iopanoic acid, and Ipodate block the conversion of T4 into T3, leading to the elevation of the T4 levels.
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Hyperthyroxinemia of Systemic Illness: Because of increased synthesis and decreased clearance caused by functional hyperestrogenemia, liver disorders produce high levels of thyroid-binding globulins. These liver diseases include hepatitis (a condition where the liver becomes inflamed), cirrhosis (a condition where the healthy liver is scarred), etc. The thyroid-binding globulin levels also rise due to increased liver synthesis in estrogen-secreting tumors, acute intermittent porphyria (a rare genetic disease), and HIV (human immunodeficiency virus) infection. Moreover, in 1 to 10 percent of patients with acute psychosis, total and free serum T4 concentrations are slightly elevated.
What Are the Symptoms of Euthyroid Hyperthyroxinemia?
In euthyroid hyperthyroxinemia, the patient remains euthyroid, which means there are no signs and symptoms of hormonal imbalance in the body. Therefore, an individual with euthyroid hyperthyroxinemia will not develop any symptoms pertaining to the condition.
How Is Euthyroid Hyperthyroxinemia Diagnosed?
The diagnosis of euthyroid hyperthyroxinemia is very difficult, and the condition is often misdiagnosed as hyperthyroidism or thyrotoxicosis. However, the diagnosis is confirmed with several laboratory tests, and no imaging tests are required.
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In addition to laboratory tests, a detailed medical history and clinical evaluation are necessary to rule out the presence of other medical conditions. It is also helpful in determining whether a patient has a history of drug abuse or a family history of protein-binding abnormalities.
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Blood samples are collected, and the levels of the thyroid-stimulating hormone are checked.
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Free T4 levels are also evaluated with the help of equilibrium dialysis.
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Serum thyroxine and triiodothyronine levels are also checked.
How Is Euthyroid Hyperthyroxinemia Treated?
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Individuals affected by familial euthyroid hyperthyroxinemia do not require any treatment generally.
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If the condition is caused by the use of a certain drug, then the specific drug should be avoided, or a substitute of the medicine should be used instead.
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Since euthyroid hyperthyroxinemia is clinically asymptomatic and does not cause any health issues, the condition does not require medicinal therapy or surgery. However, the doctor may advise regular follow-ups to keep a check on the patient’s thyroid functioning.
Conclusion:
Although euthyroid hyperthyroxinemia is a relatively harmless condition with no clinical symptoms, it is also important to do regular follow-ups with the doctor to ensure normal thyroid functioning. If any change in thyroid functioning is noticed, immediate diagnosis and treatment should be made. For patients with chronic systemic diseases who develop euthyroid hyperthyroxinemia, it is crucial to do regular follow-ups because the underlying disease that is the cause of euthyroid hyperthyroxinemia may aggravate and worsen the condition. With regular checkups and follow-ups, the prognosis of euthyroid hyperthyroxinemia is excellent.
