Back

Free One-Month! Institutional (.edu or .org) email required

Hyperthyroidism (Graves' Disease, others)

Hyperthyroidism

Please see our separate tutorial on Hypothyroidism.

General pathophysiology of thyroid hormone.

Goiter

Overview

Too much or too little thyroid hormone has systemic effects.

Patients can move from hyperthyroidism to hypothyroidism in some disorders – thus, we draw a see-saw to remind us that healthy functioning is the result of a balance of thyroid hormone.

Thyroid hormone disorders are often due to autoimmunity, and, as such, are often associated with other autoimmune disorders.

Thyroid disorders are caused by both genetic and environmental factors, and are most common in women over 40.

Diagnosis When thyroid hormone imbalance is suspected, we can measure serum TSH (thyroid -stimulating hormone) and thyroid hormone levels;

We can look for the presence of certain antibodies, such as Thyroid-stimulating hormone receptor antibodies (TSHRAb) and Thyroid peroxidase antibodies (TPO), which can tell us if autoimmunity is involved;

We can do radioactive iodine uptake tests to visualize thyroid functioning.

When testing thyroid hormone levels, be aware that several drugs can alter them, including: estrogens, glucocorticoids, amiodarone, lithium, and heparin.

We can look for serum antibodies in diagnosing thyroid disorders.

In Graves' disease, we look for Thyroid stimulating hormone receptor antibody (TSHRAb, aka, Thyroid stimulating immunoglobulin, thyroid stimulating antibody) and Thyroid Peroxidase Antibody (TPOAb, which is also present in Hashimoto thyroiditis).

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

Smooth/diffuse goiter The thyroid gland is more or less uniformly enlarged.

Nodules These are specific areas of the thyroid gland that are hypertrophic/hyperplastic: Toxic and non-toxic multinodular goiter (which we show here, with multiple nodules), thyroid adenoma (which is solitary), thyroid cancer, and thyroid cysts.

Radioactive iodine uptake tests (RIUT) Visualize thyroid hormone production in the gland.

In Graves' disease, the test shows diffuse, symmetrical "hot" areas of thyroid overproduction.
In Toxic Mutlinodular Thyroid Goiter, we see see several "hot" nodules throughout the thyroid gland.

Hyperthyroidism: Clinical Manifestations

Characterized by elevated levels of T3 and T4. Be aware that there is also a form in which only T3 is elevated.

Hperthyroidism puts patients in a hypermetabolic state with increased beta adrenergic responses; this will help us to remember key signs and symptoms, which we'll group by type:

Increased basal metabolic rate - patients experience weight loss with increased appetite.

Goiter which is common, whether it's due to overstimulation of the thyroid cells or other causes.

Skin, face, and hair changes:

Heat intolerance and increased sweating, with warm, moist, "velvety" skin, and hair thinning and loss (diffuse alopecia).
Graves' disease, in particular, is associated with dermopathy, often referred to as pretibial myxedema (a term we'll avoid due to the association of myxedema with hypothyroidism).

Areas of the skin, typically on the anterior legs, turn pink or dark purple with small lesions that render an "orange skin" appearance; nodules may also form.

The eyes may be affected in several ways including eyelid retraction and irritation of the eyeball (mostly due to adrenergic overstimulation).
Graves' ophthalmopathy is characterized by proptosis (aka exophthalmos) caused by inflammation and edema of the extraocular muscles and periorbital tissues. Double vision or blindness can result.

Neuropsychiatric and neuromuscular changes:

Nervousness and anxiety, and patients often report insomnia.
Fine-motor tremor, fast and strong tendon reflexes, and proximal myalgia.

Cardiovascular effects:

Patients may have heart palpitations with elevated cardiac output (again, due to adrenergic overstimulation) and hypertension. Be aware that this can worsen angina or heart failure.

GI effects:

Frequent bowel movements.

Thyroid storm: Aka, thyrotoxic crisis. State of organ decompensation resulting from excessive thyroid hormone exposure. It is most commonly associated with Graves' disease, and follows additional insults, such as infection or trauma.

Though rare, mortality rates are high, so watch for signs of organ failure, including: Fever, neuropsychiatric changes such as agitation or delirium, seizure, coma, GI effects or jaundice, and cardiovascular changes including tachycardia, congestive heart failure, and fibrillation.

Treatment: Thyroid storm treatment includes beta-blockers, thionamide to block thyroid hormone synthesis, iodine to block thyroid hormone release, glucocorticoids to reduce peripheral conversion of T4 to T3, and, possibly, bile acid sequestrants that reduce thyroid hormone enterohepatic recycling.

Hyperthyroidism: Causes

Primary hyperthyroidism: The thyroid gland itself is hyper-productive; negative feedback on the pituitary and hypothalamus suppresses TSH.

Graves' disease is the most common cause of hyperthyroidism in many countries, including the United States.

Recall that the thyroid gland is activated by Thyroid Stimulating Hormone (TSH), which is released by the pituitary.
In Graves' disease, antibodies bind and activate the TSH receptor, inducing thyroid hormone production and release.
Histology: in Graves' disease, hyperplastic folds of tall epithelial cells develop, with clear vacuoles that create "scalloped" edges from increased thyroid production. B- and T-cells infiltrate the stroma, and the colloid is scant. Although not shown here, Graves' disease is associated with increased vascularity, which can lead to hemorrhaging, inflammation, necrosis, and fibrosis.

Toxic multinodular goiter & Solitary thyroid adenomas

Toxic multinodular goiter is also called Plummer's disease.
Autonomous nodules in the thyroid gland produce excessive amounts of thyroid hormone; they are associated with genetic factors and low dietary iodine.

Thyroiditis is inflammation of the thyroid gland.

Can initially cause hyperthyroidism but patients may become hypothyroidic, as the inflammation causes the release of stored hormone.
Causes of inflammation include infection, autoimmune destruction, radiation, and drugs.

Too much iodine - this is called the Jod-Basedow effect, and can occur after iodine administration, for example.

Note that this represents an "escape" from the Wolff-Chaikoff effect

Wolff-Chaikoff effect: The thyroid responds to excessive iodine exposure by inhibiting iodine organification, thereby avoiding over-production of thyroid hormone.

Pregnancy: In the first trimester of pregnancy, excess human chorionic growth hormone can stimulate the thyroid gland and cause hyperthyroidism; however, later in gestation, this may shift to hypothyroidism.

Other causes (Secondary/Central): A TSH-secreting pituitary tumor or struma ovarii (teratoma with thyroid tissue in the ovary). These conditions are rare.

Treatments Treat hyperthyroidism with antithyroid drugs (the thionamides, which inhibit thyroid hormone production or iodines, which block thyroid hormone release), radioactive iodine therapy, or surgical removal of the thyroid. Beta blockers can be given to treat the adrenergic symptoms and prevent cardiovascular complications.

Hyperthyroidism (Graves' Disease, others)

Related Tutorials