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A 45-year-old woman comes to clinic because of a resting hand tremor for the past 2 days. She says she has dealt with palpitations, unintentional loss of 9.1-kg (20-lb), and feelings of increased irritability towards her coworkers over the past 3 months. Her medical, family, and social histories are noncontributory. Her temperature is 36.6°C (98°F), pulse is 110/min, respirations are 15/min, and blood pressure is 120/80 mm Hg. Physical examination shows that the patient appears anxious and diaphoretic. Her eyelids are retracted with evidence of exophthalmos and thyroid is enlarged with no palpable masses. She shows occasional tremors in both hands and has an erythematous, thickened rash on both shins. Laboratory tests show an undetectable amount of thyroid stimulating hormone and elevated concentrations of anti-thyroid peroxidase antibodies. ECG shows tachycardia, but is otherwise within normal limits. Which of the following is the most likely diagnosis?
Content Reviewers:Rishi Desai, MD, MPH
Normally, the hypothalamus, which is located at the base of the brain, detects low blood levels of thyroid hormones and releases thyrotropin-releasing hormone into the hypophyseal portal system - which is a network of capillaries linking the hypothalamus to the anterior pituitary.
The anterior pituitary then releases thyroid-stimulating hormone, also called thyrotropin or simply TSH.
TSH stimulates the thyroid gland which is a gland located in the neck that looks like two thumbs hooked together in the shape of a “V”.
The thyroid gland is made up of thousands of follicles, which are small spheres lined with follicular cells.
Follicular cells convert thyroglobulin, a protein found in follicles, into two iodine-containing hormones, triiodothyronine or T3, and thyroxine or T4.
Once released from the thyroid gland, these hormones enter the blood and bind to circulating plasma proteins.
Only a small amount of T3 and T4 will travel unbound in the blood, and these two hormones get picked up by nearly every cell in the body.
Once inside the cell T4 is mostly converted into T3, and it can exert its effect.
T3 speeds up the basal metabolic rate.
It’s as if the cells are in a bit of frenzy.
T3 increases cardiac output, stimulates bone resorption - thinning out the bones, and activates the sympathetic nervous system, the part of the nervous system responsible for our ‘fight-or-flight’ response.
Thyroid hormone is important - and the occasional increase is like getting a boost to fight off a hungry predator or to stay warm during a snowstorm!
Now, in Graves disease, the trigger is unclear, but for some reason the B cells start to produce a few different types of antibodies against thyroid proteins.
The most common antibody is the thyroid-stimulating immunoglobulin, which binds to the TSH receptor on thyroid cells, imitating TSH, and stimulating the thyroid cells to release more T3 and T4.
But the effects of thyroid-stimulating immunoglobulins can also directly affect certain tissues.
First, there’s thyroid hypertrophy, meaning growth in the interstitium of the tissue, and there’s hyperplasia, meaning an increased number of follicular cells, both of which causes the thyroid to enlarge.
The follicle cells also change shape - becoming taller than in a healthy thyroid as they crowd together.