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44. Laboratory assessment of the thyroid function

Hypothyroidism

(Overt) hypothyroidism refers to decreased production of T3 and T4 by the thyroid gland. It’s a common condition. Chronic hypothyroidism is almost always due to Hashimoto thyroiditis.

Subclinical hypothyroidism is very common, but despite being subclinical it may be associated with adverse outcomes on cardiovascular disease. Also, most patients with subclinical hypothyroidism progress into overt hypothyroidism.

Etiology

Thyroiditis, especially Hashimoto thyroiditis, is the most common cause of hypothyroidism. Secondary and tertiary hyperthyroidism are rare.

Diagnosis and evaluation

TSH is the most important biomarker in the evaluation of hypothyroidism as it’s much more sensitive than T3 and T4. T3 and T4 are only measured to diagnose subclinical hypothyroidism, the stage before overt hypothyroidism develops.

TSH Free T4 Free T3
Euthyroidism Normal Normal Normal
Subclinical hypothyroidism Increased Normal Normal
Overt hypothyroidism Increased Decreased Decreased

To find the etiology, measurement of anti-thyroid antibodies (anti-TPO and anti-Tg), ultrasound, and FNAB are used.

Anti-TPO and elevated in autoimmune thyroiditis. Anti-thyroglobulin may also be used in autoimmune thyroiditis, but is less sensitive and specific than anti-TPO, so anti-TPO is used instead.

Hyperthyroidism and thyrotoxicosis

Thyrotoxicosis or hyperthyroxinaemia is the state where the level of circulating free T3 and T4 is elevated, causing hypermetabolism. It is most commonly caused by hyperthyroidism, which is the state where the thyroid is overactive. However, thyrotoxicosis can also be caused by ectopic hormones or destruction of the thyroid. Because the most common cause of thyrotoxicosis is hyperthyroidism, the two terms are often used interchangeably.

Etiology

Thyrotoxicosis can be caused by many conditions:

  • Primary hyperthyroidism
  • Destruction of the thyroid gland – causes release of stored thyroid hormone in the early phase of disease
  • Secondary hyperthyroidism
    • Gestational thyrotoxicosis – hCG stimulates TSH receptors due to their structural similarity
    • Struma ovarii – an ovarian teratoma which produces thyroxine
    • TSH-producing pituitary adenoma

In regions without iodine deficiency, Graves disease is the most common cause of thyrotoxicosis. In iodine deficient regions, toxic adenoma and toxic multinodular goitre are more common.

Diagnosis and evaluation

The diagnosis of (primary) hyperthyroidism is based on the levels of TSH, the most sensitive biomarker. Free T4 and T3 are measured to look for subclinical hyperthyroidism.

TSH Free T4 Free T3
Euthyroidism Normal Normal Normal
Subclinical hyperthyroidism Decreased Normal Normal
Overt hyperthyroidism Decreased Increased Increased

The clinical features, including the thyroid size, consistency, nodularity, as well as the presence of eye symptoms, can help narrow the differential diagnosis. The following investigations are important in determining the etiology:

  • Autoantibodies against thyroid peroxidase (anti-TPO), thyroglobulin (anti-Tg), and TSH receptor (anti-TSHR)
    • Anti-TPO and elevated in autoimmune thyroiditis
    • Anti-thyroglobulin may also be used in autoimmune thyroiditis, but is less sensitive and specific than anti-TPO, so anti-TPO is used instead
    • Anti-TSHR is elevated in Graves disease
  • Ultrasound
  • Thyroid scintigraphy (nuclear imaging)

Hashimoto thyroiditis

Hashimoto thyroiditis, also called chronic autoimmune hypothyroidism is an autoimmune condition characterised by CD8-mediated destruction of the thyroid parenchyme. It’s the most common cause of chronic hypothyroidism in western countries, affecting 3 – 5 per 10 000. It mostly affects middle-aged females.

It’s associated with other autoimmune diseases and with HLA-DR5.

Diagnosis and evaluation

The following features are typical for Hashimoto:

  • Typical clinical features
  • Ultrasound findings (inhomogenous, hypoechogenic thyroid)
  • Normal leukocyte count
  • Moderately elevated ESR
  • Initial thyrotoxicosis followed by hypothyroidism
  • Elevated anti-thyroid antibodies (anti-TPO, anti-Tg)

The anti-thyroid antibodies are the main factors in the diagnosis of Hashimoto thyroiditis. Ultrasound is rarely indicated in the evaluation of Hashimoto thyroiditis.

Other stuff

  • Drugs which affect thyroid function
    • Lithium – decreases thyroid hormone release
    • Amiodarone – hypo or hyperthyroidism
    • SSRIs – increase TSH