Thyroid Gland - Pathophysiology

Thyroid Gland Pathophysiology

Here we'll learn the basic tenants of thyroid gland pathophysiology. We discuss thyroid hormone production and thyroid disorders, including Graves disease and Hashimoto Thyroiditis in more depth, elsewhere.*

Thyroid Hormones T3 & T4

Review thyroid hormone production

Thyroid hormones T3 and T4 are responsible for:

CNS development in infants
Bone growth and maturation in children
Proper functioning in multiple organ systems in adults

Pathology can be broadly categorized as hyperthyroidism, which produces thyrotoxicosis, or hypothyroidism, which produces myxedema. Goiter = an enlarged thyroid gland.

Goiter can be benign or a sign of underlying thyroid disease. In some countries, lack of iodine is the primary cause of goiter, but many countries, including the U.S., add iodine to salt and other foods so that deficiency is rare.

Thyroid Hormone Regulation

We show the structures of the Hypothalamic-Pituitary-Thyroid axis.

1. Thyrotropin-releasing hormone (TRH) is released from the hypothalamus and carried in the pituitary circulation. 2. In the anterior pituitary gland, TRH stimulates thyrotrophs (aka, tyrotropes) to release thyroid-stimulating hormone (TSH). 3. TSH travels in the systemic circulation to its target organ, the thyroid, where it triggers release of the thyroid hormones, T3 and T4. 4. Thyroid hormones travel to the peripheral tissues, where some T4 is deiodinated to T3. Recall that T3 is more biologically active than T4.

Via negative feedback at the hypothalamus and the anterior pituitary gland, thyroid hormones inhibit further secretion of TRH and TSH.

Additionally, because iodine is essential for thyroid hormone production, low levels of the element also down-shift thyroid hormone production.

In cases of excessive iodine exposure, the thyroid inhibits iodine organification, thereby avoiding over-production of thyroid hormone (the Wolff-Chaikoff effect). These regulatory details will return when we learn about treatments for thyroid disorders.

Thyroid Gland Functions

Promote CNS development in infants
Maintain ventilatory responses to hypoxia and hypercapnia
Chronotropic and inotropic effects on the heart (heart rate and contractility)
Stimulate LDL receptors in the liver
Promote GI motility and carbohydrate absorption
Promote lipolysis in adipose tissue
Promote protein breakdown in muscle
Promote normal bone growth and development in children
Promotes oxygen consumption in many tissue types.
Sympathetic nervous system: thyroid hormone increases beta adrenergic receptor numbers and sensitivity. This can help us predict the physiological roles of thyroid hormone and the pathology that results when there is too much or too little hormone activity.

Hyperthyroidism (thyrotoxicity) vs Hypothyroidism (myxedema)

We'll explore many of these signs and symptoms in more detail, elsewhere.

Hyperthyroidism Hyperthyroidism is characterized by elevated levels of T3 and T4, low LDL (due to increased LDL receptors in the liver), and, if in the case of primary hyperthyroidism, low levels of TSH due to negative feedback on the pituitary.

Hypothyroidism Conversely, hypothyroidism is characterized by low levels of T3 and T4, hypercholesterolemia, and, in the case of primary hypothyroidism, high TSH.

Effects By Body System:

Neuropsychiatric effects

Hyperthyroidism: hyperactivity, restlessness, anxiety, and insomnia. Patient have increased reflexes and fine motor tremors.
Hypothyroidism has the opposite effects: patients are hypoactive, fatigued, and experience weakness and depressed mood with slow reflexes.

Cardiovascular and respiratory effects

Hyperthyroidism: tachycardia with palpitations. Patients experience dyspnea and chest pain and have systolic hypertension.
Hypothyroidism: bradycardia with reduced cardiac output. Patients experience dyspnea on exertion and are at risk for hypoventilation.

Muscle

Hyperthyroidism: breaks down proteins and muscles, producing proximal weakness with normal levels of creatine kinase; hypothyroidism also produces proximal weakness, but with myalgia; creatine kinase levels are often elevated.
Hyperthyroidism: accelerates bone growth and tissue turnover; thus, patients are at risk for osteoporosis and bone fractures. Hypothyroidism in children produces impaired bone formation and growth.

GI tract

Hyperthyroidism: more bowel movements, possibly with diarrhea, and appetite is increased.
Hypothyroidism: constipation and reduced appetite.

Hair and Skin

Hyperthyroidism: vasodilation produces warm, moist skin; hair is often fine (thin diameter).
Hypothyroidism: patients have reduced blood flow with cool, dry skin. Hair is often coarse and brittle, and patients may have alopecia. Nails are brittle. Hypothyroidism is often characterized by nonpitting edema and puffy facies, due to water retention – thus its alternative name, myxedema.

Reproductive functioning

Hyperthyroidism: irregular or reduced menstrual flow, gynecomastia, lower libido, and possibly reduced fertility. - Hypothyroidism: similar effects, but gynecomastia is not common.

Metabolism

Hyperthyroidism: heat intolerance with increased sweating; patients have elevated basal metabolic rate with weight loss.
Hypothyroidism: cold intolerance and reduced sweating; patients have lower basal metabolic rates with weight gain, and possibly hyponatremia.

Ocular

Both hyper- and hypothyroidism: can produce periorbital edema.
Hyperthyroidism is also associated with exophthalmos, aka, proptosis, which is characterized by "bulging" eyeballs due to inflammation around the eyes. Lid retraction can also occur in hyperthyroidism due to increased sympathetic stimulation of the muscles of the eyelid.

Most common causes (United States)

Hyperthyroidism: in the US is Graves disease
Hypothyroidism: Hashimoto thyroiditis

Thyroid Gland - Pathophysiology

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