Hashimoto Thyroiditis Workup

Up to 15% of patients aged 65 years or older may have subclinical hypothyroidism (mild thyroid failure, as evidenced by an elevated TSH above 4.0 μ IU/mL and normal free T4 levels), with few if any symptoms suggestive of hypothyroidism. These patients have a decreased thyroid reserve.

The best marker of progression to overt hypothyroidism is a combination of an elevated TSH level with the presence of thyroid autoantibodies, namely anti-TPO and anti-Tg antibodies. The rate of progression to overt hypothyroidism is estimated to be about 5% per year.

Patients with positive thyroid autoantibodies but a normal TSH level should be followed up periodically to monitor for symptoms of hypothyroidism and to detect any rise in their TSH or cholesterol levels. Checks can usually be performed every 6-12 months. These patients should be treated if the TSH level continues to rise, even if the level is at the upper limit of the reference range.

Iodine uptake and scan

Iodine uptake and scan usually are not indicated for the diagnosis of Hashimoto thyroiditis. The usefulness of radioactive iodine and scan is in classifying a nodule as either hot or cold. A cold thyroid nodule would indicate a higher risk for malignancy and therefore a need for fine-needle aspiration.

Fine-needle aspiration

Perform fine-needle aspiration of any dominant or suspicious thyroid nodules to exclude malignancy or the presence of a thyroid lymphoma in fast-growing goiters. ^[2]

A literature review by Travaglino et al found that with regard to evidence of the presence of Hashimoto thyroiditis, the pooled prevalence was 78.9% in patients with primary thyroid lymphoma. A significantly higher prevalence of Hashimoto thyroiditis was found in patients with mucosa-associated lymphoid tissue (MALT) lymphoma or with mixed MALT/diffuse large B-cell lymphoma (DLBCL) than in those with DLBCL alone. ^[26]

Histologic findings

Hashimoto thyroiditis is a histologic diagnosis. Typically, the thyroid gland shows diffuse lymphocytic and plasma cell infiltration with formation of lymphoid follicles from follicular hyperplasia and damage to the follicular basement membrane. Atrophy of the thyroid parenchyma is usually evident. Correlation with the presence of thyroid autoantibodies, namely anti-TPO and anti-Tg, is helpful in confirming the diagnosis.

In the presence of suggestive symptoms and physical findings, a serum TSH test is needed for the diagnosis of primary hypothyroidism, and it serves to assess the functional status of the thyroid.

This is a sensitive test of thyroid function; levels are invariably raised in hypothyroidism due to Hashimoto thyroiditis and in primary hypothyroidism from any cause.

The TSH level is also elevated in subclinical hypothyroidism and is usually the initial laboratory abnormality detected as the pituitary gland attempts to increase thyroid hormone production from the failing thyroid gland. The total T4 or free T4 usually remain within reference ranges in subclinical hypothyroidism. The TSH level may also be elevated in the recovery phase of euthyroid sick syndrome.

In the outpatient setting, when there is no cause to suspect hypothalamic or pituitary disease and in the absence of nonthyroidal illness and of medications that suppress TSH production in the inpatient setting, a normal TSH level excludes primary hypothyroidism from any cause.

Medications that suppress TSH production include steroids, dopamine, dobutamine, and octreotide.

Free T4 test

A free T4 is usually needed to correctly interpret the TSH in some clinical settings. A low total T4 or free T4 level in the presence of an elevated TSH level further confirms the diagnosis of primary hypothyroidism.

When a total T4 study, rather than a free T4 study, is performed, a T3 resin uptake helps to correct the total T4 and T3 values for protein binding, especially thyroid hormone–binding globulin (TBG) abnormalities, but the free T4 is typically the test of choice.

When the serum TSH and the free T4 levels are low in the outpatient setting, the case for central hypothyroidism is strengthened. However, in the acutely ill patient, nonthyroidal illness (euthyroid sick syndrome) is the more likely possibility. The TSH level cannot be reliably used in some clinical settings to distinguish central hypothyroidism from nonthyroidal illness. Physical findings suggestive of thyroid disease, as well as the presence of obvious or subtle clinical features of hypothyroidism, become pivotal in establishing the correct diagnosis.

T3 test

A low T3 level and a high reverse T3 level may be of additional help in the diagnosis of nonthyroidal illness.

T3 levels are most often maintained within reference ranges (even in the very late stages of hypothyroidism), and T3 measurement has little value in the diagnosis of hypothyroidism. Furthermore, T3 levels may be low in up to 70% of hospitalized patients without hypothyroidism or any thyroid disease, as is the case with nonthyroidal illness.

Thyroid autoantibodies

The presence of thyroid autoantibodies, typically anti-TPO and also anti-Tg antibodies, delineates the cause of hypothyroidism as Hashimoto thyroiditis or its variant. However, 10-15% of patients with Hashimoto thyroiditis may be antibody negative.

Although features of Hashimoto thyroiditis are usually identifiable on an ultrasonogram, a thyroid ultrasonogram is usually not necessary for diagnosing the condition. However, it is useful for assessing thyroid size, echotexture, and, most importantly, whether thyroid nodules are present. ^[27] Ultrasonographic study aids in confirming the presence of a thyroid nodule, in defining a nodule as solid or cystic, and in defining features suggestive of malignancy, such as irregular margins, a poorly defined halo, microcalcification, and increased vascularity on Doppler interrogation.

Ultrasonography is useful in facilitating fine-needle aspiration of nodules in general and, in particular, small or poorly defined nodules when indicated and in patients with distorted neck anatomy. A definite diagnosis of benign versus malignant thyroid lesion can be confirmed only by cytologic or histologic examination of thyroid tissue.

The following tests are not necessary for the diagnosis of primary hypothyroidism but may be performed to evaluate complications of hypothyroidism in some patients, when clearly indicated.

Complete blood count

Up to 30-40% of patients with hypothyroidism have anemia, usually from decreased erythropoiesis. In 15% of patients, the anemia is of the iron deficiency type, with microcytosis and hypochromia. Although this can be a normocytic normochromic anemia, the most common morphologic abnormality is a macrocytic anemia that may be partially due to insufficient vitamin B-12 and folate intake.

Total and fractionated lipid profile

Total cholesterol, LDL, and triglyceride levels may be elevated in hypothyroidism and may be responsive to levothyroxine replacement.

Basic metabolic panel

Glomerular filtration rate, renal plasma flow, and renal free water clearance are all decreased in hypothyroidism and may result in hyponatremia.

Creatine kinase

Creatine kinase levels, predominantly the MM isoenzyme from skeletal muscle and the aldolase enzyme, are frequently elevated in severe hypothyroidism.

Prolactin

Prolactin may be elevated in primary hypothyroidism. This is thought to be caused by overlap secretion due to stimulation of the lactotroph by the elevated TRH level. The decreased clearance of prolactin in hypothyroidism may also play a contributory role. The elevated prolactin level leads to decreased gonadotropin secretion and decreased responsiveness to GnRH. The result of this is anovulatory cycles with menstrual abnormalities, galactorrhea, and infertility in some patients.

Additional studies

Other studies may be performed in the evaluation of complications of primary hypothyroidism (when indicated). These tests are usually not performed and are not necessary in routine diagnosis or evaluation of hypothyroid patients.

• Chest radiograph - May show small pleural effusions

• Electrocardiogram (ECG) - May show low-voltage QRS tracing, nonspecific ST-wave changes, and premature ventricular contractions; prolongation of the QT interval with torsade de pointes and ventricular tachycardia may be noted

• Echocardiogram - May show some pericardial effusion in severe cases of hypothyroidism