57: Thyroid Pharmacology Flashcards
- Explain the pathophysiology and treatment of thyroid hormone excess, especially as observed in Grave’s disease.
Graves’ disease is an autoimmune disease. It most commonly affects the thyroid, frequently causing it to enlarge to twice its size or more (goiter), become overactive, with related hyperthyroid symptoms such as increased heartbeat, muscle weakness, disturbed sleep, and irritability. It can also affect the eyes, causing bulging eyes (exophthalmos). It affects women more.
Symptoms of Graves disease include: warm moist skin, elevated BMR, heart palpitations, heat intolerance, muscle wasting, nervousness/ anxious/ irritable, diarrhea, decreased TSH & TRH. They have toxic goiter (hyperthyroidism)—if surgically manipulated, the toxins in the gland could be released.
The Immunoglobulin G antibody also called thyroid stimulating antibodies recognizes and binds to the thyrotropin receptor (TSH receptor). It mimics the TSH (but does its job better & longer) to that receptor and activates the secretion of thyroxine (T4) and triiodothyronine (T3), and the actual TSH level will decrease in the blood plasma.
The TSH levels fall because the hypothalamus-pituitary-thyroid negative feedback loop is working. The result is very high levels of circulating thyroid hormones and the negative feedback regulation will not work for the thyroid gland. Hence, patients have elevated T3, elevated T4, & elevated TSH receptor antibodies.
Treatment of Graves’ disease includes antithyroid drugs which reduce the production of thyroid hormone; radioiodine (radioactive iodine I-131); and thyroidectomy (surgical excision of the gland).
Primary hyperthyroidism = graves disease (thyroid gland defect) = high T3 & T4 feedback highly in hypothalamus to decrease TRH & TSH.
Secondary hyperthyroidism (anterior pituitary defect) = high T3 & T4 neg feedback= high TSH (anterior pituitary defect) & low TRH
TH excess or hyperthyroidism is a common pathology. Patients have an elevated BMR, tachycardia, sweating, heat-intolerance, nervousness, muscle wasting and weakness, tremor, difficulty sleeping, changes in hair growth and skin texture. Patients develop toxic goiter (enlarged thyroid containing increased amounts of THs on TG). The most common form is Graves disease (seen in 2% of females).Thyroid-stimulating immunoglobulins are present in circulation and cause hypertrophy of thyrocytes, resulting in goiter. Increased circulating TH leads to decreased TSH release from anterior pituitary by a negative feedback effect. However, the stimulatory immunoglobulins continue to stimulate secretion of high amounts of TH by acting directly on TSH receptors in the follicle cells. Some patients also experience exophthalmos and eyelid retraction. Thyroid storm, an exacerbation of hyperthyroidism, is a medical emergency.
Clinical Symptoms of Hyperthyroidism A. Hyperthyroidism, such as seen in Grave’s disease, affects most physiologic systems and can increase the metabolic rate by 30% to 60% over normal. The elevated thyroid hormone causes a wide variety of symptoms as illustrated above. B. Goiter. Enlargement of the thyroid gland (goiter) can be caused by both hypothyroid and hyperthyroid conditions and results from TSH, or immunoglobulin- mediated stimulation of hyperplastic growth of the thymocytes .
Thyrotoxicosis = Grave’s disease
- Explain the pathophysiology and treatment of thyroid hormone deficiency, especially as observed in autoimmune thyroiditis (Hashimoto’s).
Non-toxic goiter = hypothyroidism type 1 of hashimoto.
TH deficiency (aka hypothyroidism or myxedema) is a common pathology.
Patients have a low BMR, cold-intolerance (not me), lethargy, increased fat deposition, hypotension, nonpitting edema, headache, skin changes, constipation.
Patients can develop non-toxic goiter (enlarged thyroid due to fibrosis & lymphocytic infiltration).
Hashimotos (primary hypothyroidism) patients have reduced TH, which leads to INCREASED TSH due to reduced negative feedback. However, the thyroid gland cannot respond to TSH bc it is being destroyed by the antithyroid antibodies. Hashimoto’s patients are typically treated with thyroxine. In in hypothyroidism there is a deposition of mucoprotein in the subcutaneous and extracellular spaces that causes edema = mixedema non pitting edema seen in Hashimoto’s.
Hypothyroid individuals (another type of case) who are iodine deficient (secondary hypothyroidism) are treated with dietary iodine. These patients have goiters.
She will not ask us anything about nitrogen balance if the questions of this lecture.
Patients with myxedema are somnolent (near sleep). Patients with Hashimotos have elevated serum TSH & thyroid (destroying) antibodies.
Patients with a deficiency in iodine intake have increased synthesis of thyroglobulin—but you do not have the iodide associate with the tyrosine residues to make thyroid hormone.
Causes of hypothyroidism include autoimmune thyroiditis (hashimoto’s), surgery for hypothyroidism causes hypothyroidism, iodide deficiency, decreased TRH or TSH.
TRH is made in hypothalamus & controls TSH secretion by anterior pituitary.
Pregnancy (high estrogen) increases TBG in the liver—thyroid binding globulin. TBG binds most circulating thyroid hormone in circulation—this binds free T4 & T3 & the feedback will correct for that by pituitary increasing amount of TSH & TRH to get to euthyroid status (pituitary = sensor).
Non-objective important stuff
Goiters are associated with hyperthyroidism, hypothyroidism, euthyroidism (normal).
Large amounts of iodide supress thyroid hormone release via wolf-trychoff effect & thyroid gland becomes firmer.
