George is a thirty five year old hardware clerk. During his routine physical he

Question

George is a thirty five year old hardware clerk. During his routine physical he casually mentions to his physician that he seems to be sweating more profusely than normal and most rooms that once were comfortable are now too "hot". At home a room that his wife and children find to be comfortable causes him to sweat profusely. George also reports that he seems to be losing weight even though his appetite has increased. He also complains that he has a shortened attention span and that he always wants to be moving around. Despite the fact that he feels fatigued, George claims to have difficulty sleeping and seems to have more frequent bowel movements, occasionally accompanied by diarrhea. The physician discovers George has lost 15 pounds since his last physical. In checking his chart, the physician finds that George has a negative history for chronic illnesses, does not smoke, and has a low risk for cardiovascular disease. He does however have a positive family history for autoimmune diseases. His father suffers from idiopathic thrombocytopenia, his mother has been diagnosed with rheumatoid arthritis and his oldest sister was recently diagnosed with systemic lupus erythematosus.

Results of George's physical examination were within normal ranges with the exception of the following: he demonstrated tachycardia, loud heart sounds, and apparent cardiac arrhythmias accompanied by slight hypertension. These arrhythmias were confirmed by electrocardiogram to be supraventricular in origin. George's eyeballs appeared large and protruding and his hair was fine and soft. He was also beginning to demonstrate some degree of alopecia. George was also observed to have palmar erythema. palpation of the neck revealed the presence of goiter. Results of blood tests indicated elevated concentrations of thyroid hormones (thyroxin and triiodothyronine), hypercalcemia, and decreased circulating concentrations of lipids. Based on the physical characteristics and the results of the blood tests, George's physician suspected that George was suffering from some form of hyperthyroidism and sent him to an endocrinologist to confirm the initial diagnosis.

Following the initial consultation and examination, the endocrinologist ordered tests to determine whether George was indeed hyperthyroid. The test results indicated an elevation in the concentration of thyroid hormones in the blood and the presence of thyroid-stimulating antibodies. These antibodies specifically stimulate the thyroid gland by binding with the thyroid stimulating hormone receptor located on the plasma membrane of the follicular cells of the thyroid gland. Based on these results, the endocrinologist concluded that George had Grave's disease, a form of hyperthyroidism believed to be autoimmune in nature. George was presented with a number of possible treatment options. These included treatment with chemicals (propylthiouracil and methimazole) that decrease the production of thyroid hormones by the thyroid gland, radioisotopic destruction of the thyroid gland by the use of 131I, and surgical removal of the thyroid gland. After considering all the options, especially the possible effects of radiation on gamete development, George chose surgery. Following successful surgery, George was prescribed synthetic thyroid hormone to ensure that his body was receiving adequate thyroid hormone and told to return within 2 months for a follow-up evaluation of circulating thyroid hormone concentrations. He was also cautioned to carefully monitor his calcium intake.

DISCUSSION QUESTIONS Case Study #5a: Choose 4 to answer. SHORTLY SUMMARIZE EACH ANSWER

1. Thyroid hormones exert their effects on cells in a manner similar to steroid hormones; describe the mechanism of action of thyroid hormones.

Thyroid hormones diffuse through the plasma membrane of a target cell and enter the nucleus of the cell. Once in the nucleus, the thyroid hormone binds to a specific receptor for the hormone located in the nucleus, forming a thyroid hormone-receptor complex. This complex then binds to a specific region of DNA known as a responsive element. These responsive elements are unique for the different hormone-receptor complexes that can form. Binding of the thyroid hormone-receptor complex to the responsive element results in an increase in transcription of specific genes. The increase in gene transcription results in an increase in the amount of mRNA for the gene in the cytoplasm of the cell. This mRNA will be translated in the cytoplasm resulting in an increase in the amount of protein in the cell. Increasing the cellular concentration of protein will bring about the cellular responses specific for thyroid hormone in that specific cell.

2. Why would an imbalance in thyroid hormones have such widespread effects on the body?

Thyroid hormones have numerous roles within the organism. These hormones are essential in regulating the metabolism of carbohydrates, proteins, and lipids with the body. In addition to this role, thyroid hormones are required for the normal growth and development of an individual, the development of the nervous system, and for regulating the basal metabolic rate of the individual. Since these effects are not localized to a single tissue or organ, the effects of an imbalance in thyroid hormones would be expected to have widespread effects. In addition to the effects of an imbalance of thyroid hormone that would occur directly, additional effects would be noted as the body attempted to compensate and maintain homeostasis.

3. Why was goiter observed in George’s case?

Goiter was observed in George’s case because the thyroid gland was producing an excessive amount of thyroid hormones due to stimulation by the antibodies present in his blood. Since these antibodies bind to the thyroid stimulating hormone receptor they induce the same effects as elevated concentrations of thyroid stimulating hormone. This hormone stimulates an increase in thyroid gland size, increase in colloid synthesis, an increased thyroid hormone synthesis and secretion. The goiter that results is due to increased gland size.

4. Why would calcium homeostasis be impaired in response to removal of the thyroid gland?

Calcium homeostasis would be impaired when the thyroid was surgically removed because of the loss of both the extrafollicular cells and the parathyroid glands. The extrafollicular cells are those cells in the thyroid gland that lies in the interstitial spaces between the follicles. These cells synthesize and secrete calcitonin. Calcitonin is secreted when circulating concentrations of calcium are elevated to stimulate decreases in serum calcium by stimulating osteoblast activity and increasing renal calcium excretion. The parathyroid glands are located on the posterior aspect of the thyroid gland so removal of the thyroid gland would result in the removal of the parathyroid glands. These glands secrete parathyroid hormone when circulating concentrations of calcium are decreased. The actions of parathyroid hormone on the body are to elevate circulating calcium concentrations by increasing osteoclast activity, stimulating renal calcium reabsorption, and increasing the renal activation of vitamin D. Vitamin D stimulates an increase in calcium absorption by the intestinal mucosa.

5. Why could 131I be used to specifically destroy the thyroid gland and have minimal effects on other cells and tissues in the body?

Radioactive iodine is the most widely recommended permanent treatment of hyperthyroidism. This treatment takes advantage of the fact that thyroid cells are the only cells in the body which have the ability to absorb iodine. In fact, thyroid hormones are experts at doing just that. By giving a radioactive form of iodine gives off a poisonous type of radiation, the thyroid cells which absorb it will be damaged or killed. Because iodine is not concentrated by any other cells in the body, there is very little radiation exposure (or side effects!) for the rest of the body. Radioiodine can be taken by mouth without the need to be hospitalized. This form of therapy often takes one to two months before the thyroid has been killed, but the radioactivity medicine is completely gone from the body within a few days. The majority of patients are cured with a single dose of radioactive iodine. The only common side effect of radioactive iodine treatment is underactivity of the thyroid gland. The problem here is that the amount of radioactive iodine given kills too many of the thyroid cells so that the remaining thyroid does not produce enough hormone, a condition called hypothyroidism. There is no evidence that radioactive iodine treatment of hyperthyroidism causes cancer of the thyroid gland or other parts of the body, or that it interferes with a woman's chances of becoming pregnant and delivering a healthy baby in the future. It is also important to realize that there are different types of radioactive iodine (isotopes). The type used for thyroid scans (iodine scans) gives up a much milder type of radioactivity which does NOT kill thyroid cells."

Explanation / Answer

Question 1: Thyroid hormones exert their effects on cells in a manner similar to steroid hormones; describe the mechanism of action of thyroid hormones?

Ans: The steroid hormone diffuses through the plasma membrane and binds to an intracellular receptor ? the hormone-receptor complex enters the nucleus ? Binds a hormone response element ? Binding initiates transcription of mRNA ? mRNA directs protein synthesis.

Question 2: Why would an imbalance in thyroid hormones have such widespread effects on the body?

Ans: Thyroid hormones are essential in regulating the metabolism of carbohydrates, proteins, lipids also required for the normal growth and development of an individual also the development of the nervous system, and for regulating the basal metabolic rate of the individual. Since these effects are not localized to a single tissue or organ, the effects of an imbalance in thyroid hormones would be expected to have widespread effects.

Question 3: Why was goiter observed in George’s case?

Ans: Goiter was observed in George’s case because the thyroid gland was producing an excessive amount of thyroid hormones due to stimulation by the antibodies present in his blood. The goiter that results is due to increased gland size.

Question 4:

Why would calcium homeostasis be impaired in response to removal of the thyroid gland?

Ans: Calcium homeostasis would be impaired when the thyroid was surgically removed because of the loss of both the extra follicular cells and the parathyroid glands. The extra follicular cells are those cells which synthesize and secrete calcitonin.

The parathyroid glands secrete parathyroid hormone. The actions of parathyroid hormone on the body are to elevate circulating calcium concentrations by increasing osteoclast activity.

Question 5: Why could 131I be used to specifically destroy the thyroid gland and have minimal effects on other cells and tissues in the body?

Ans: This treatment takes advantage of the fact that thyroid cells are the only cells in the body which have the ability to absorb iodine. Because iodine is not concentrated by any other cells in the body, there is very little radiation exposure for the rest of the body.

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