Endocrine Pathophysiology › Thyroid Gland

Hypothyroidism

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Hypothyroidism

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Hypothyroidism

Please see our separate tutorial on Hyperthyroidism.

Goiter
Enlarged thyroid gland.
Goiter may be a sign of hyper- or hypothyroidism, or may occur in the absence of thyroid hormone disorders.

Smooth/diffuse goiter
The thyroid gland is more or less uniformly enlarged (we show the normal thyroid gland size with a dotted line):

Nodules
These are specific areas of the thyroid gland that are hypertrophic/hyperplastic.

Euthyroid sick syndrome
Occurs when thyroid hormone levels are reduced in the presence of systemic illness; generally we treat the underlying illness rather than focus on the hypothyroidism.

Hypothyroidism: Clinical Manifestation

Hypothyroidism
Characterized by low levels of T3 and T4.

Hypometabolic state
Decreased basal metabolic rate with weight gain but reduced appetite.

Goiter can develop.

Skin, face, and hair changes:
Cold intolerance with reduced sweating and cool, dry, flaky skin; cutaneous changes are due to the accumulation of glycosaminoglycans in the skin.
Hair loss is common.
Non-pitting edema, most notable in the extremities, is due to water retention and the deposition of hyaluronic acid.
Puffy face and eyelids.

Neuropsychiatric and neuromuscular changes:
Patients often experience some degree of depression, with slower speech and mental functioning, which may present as mild confusion.
Patients are often fatigued and feel lethargic, with slower reflexes.
Proximal myalgia is more likely associated with elevated levels of creatine kinase, unlike the myalgia in hyperthyroidism.
Carpal tunnel syndrome and other entrapment disorders can result from fluid retention and swelling around the tissues.

Cardiovascular effects:
Cardiovascular effects are opposite those in hyperthyroidism: bradycardia and reduced cardiac output. Patients may be hypertensive, though, because peripheral resistance is increased due to changes in the vasculature.

Ventilatory effects:
Ventilatory responses are also reduced.

Myxedema madness:

Characterized by delusions, hallucinations, and delirium.
Though rare, we should look for this in patients who present with psychosis and other signs or symptoms of hypothyroidism (puffy face, lethargy, etc.).
Fortunately, thyroid hormone administration can treat this "madness."

Myxedema Crisis/Coma:

Potentially fatal situation characterized by extreme lethargy, stupor, or coma with hypothermia.
Treat with thyroid hormone immediately. Like thyroid storm in hyperthyroidism, these signs and symptoms reflect organ dysfunction and decompensation, and the condition is often precipitated by additional insults, such as hypothermia, infection, drugs or other traumas.

Hypothyroidism: Causes

Now, let's learn some causes of hypothyroidism; we'll focus on primary disorders where the dysfunction arises int eh thyroid gland.

Hashimoto's thyroiditis
The leading cause of hypothyroidism in the United States and many other countries.

  • Like Graves' disease, this is a chronic autoimmune disorder in which antibodies and lymphocytes are involved.
  • However, instead of stimulating thyroid hormone production, the antibodies in Hashimoto's thyroiditis block receptors in the thyroid gland, inhibiting thyroid hormone production.
  • Antibodies involved include Thyroid peroxidase antibody (TPOAb, which is also implicated in Graves' disease) and Thyroglobulin antibody (which we also see in Thyroid cancer).
  • Histopathology: Germinal centers with lymphocytic infiltrates and thyroid follicle atrophy with absent colloid. Fibrosis is common. Be aware that there is a fibrosing variant of Hashimoto's in which the fibrosis is extensive and thyroid follicles are nearly absent; this may represent the end stage of Hashimoto's thyroiditis rather than a separate pathology.

Treatments for hyperthyroidism
Hyperthyroidism treatments are another significant cause of hypothyroidism in many– radioactive iodine or surgery results in too little thyroid hormone production.

Iodine deficiency
Worldwide, iodine deficiency is the most common cause of hypothyroidism; recall that iodine is a rate-limiting ingredient in thyroid hormone production.
In the US and many other countries, iodine is added to many foods, including table salt, to prevent hypothyroidism.

Inflammatory diseases:

Patients with inflammatory infections often initially experience hyperthyroidism due to the dumping of large quantities of thyroid hormone in response to lymphocytic attack, but, as thyroid stores are diminished, hypothyroidism sets in.

Treatments: with anti-inflammatories, and the thyroiditis generally resolves on its own within a few months.

Subacute granulomatous thyroiditis typically follows viral illness, with pain that can spread to the neck, jaw, and other surrounding structures.
Be aware that this form of hypothyroidism is also called de Quervain thyroiditis and giant cell thyroiditis.

Riedel thyroiditis is a rare chronic disease with inflammatory infiltrate and fibrosis of the thyroid gland and nearby structures; recent research implicates an autoimmune response. Dense fibrosis turns the thyroid gland into a hard, painless structure that can compress other structures to produce hoarseness and difficulty breathing and swallowing.

Congenital hypothyroidism (formerly referred to as "cretinism") is a significant but preventable cause of intellectual disability.

  • Because maternal thyroid hormone may have been sufficient in uteruo or the fetus may have been able to produce small quantities of hormone, there are often no signs of hypothyroidism at birth.
  • Thus, screening is key for early detection and treatment with exogenous thyroid hormone.
  • When present, signs and symptoms include jaundice, difficulty or reluctance feeding, constipation, lethargy, tongue protrusion and umbilical herniation/abdominal extension.
  • Congenital hypothyroidism may be due to thyroid dysgenesis (defective, including ectopic, development of the gland), mutations causing TSH resistance, or defects in thyroid hormone production.

Secondary/Central causes:
TSH and TRH deficiencies; these are rare.

Treatment for hypothyroidism typically includes replacement of thyroid hormone with Levothyroxine.

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Textbooks:

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