Department of Pharmacology and Toxicology Small Group Discussion Thyroid Drugs A 20 year-old female college student is admitted to the

hospital with complaints of excessive sweating, extreme fatigue and a tingling or numbness in her fingers. She was in good health until 4 weeks ago when she began awakening at 2:00 a.m. and eating a snack each night. Afterwards she is unable to fall back to sleep, although she feels very tired. "Everything is wrong." She had broken up with her boyfriend; she was failing classes; she had fought with her roommates. Her grandmother had Type II diabetes and some other gland diseases. She admits to having frequent headaches, but has no trouble swallowing. She feels that her heart is racing out of control". She has loose stools, but with no complains of constipation or urinary tract problems. Her temperature is 38. 3C (101F), blood pressure is 130/60 mm Hg and pulse rate is 124/min. Her eyelids show a slowness to elevate on upward gaze, and there is sclera showing above and below the iris. Her thyroid gland measures 4.0 cm at the isthmus; 5.0 cm from top of right lobe to the bottom of the isthmus and 6.0 cm from top of left lobe to bottom of isthmus. Her chest is clear. Her heartbeat is irregular with respiration. Her abdomen is soft. Bowel sounds are hyperactive. On neurological exams, her reflexes are very quick and she has difficulty standing from a squatting position. You diagnose her condition as thyrotoxicosis and institute therapy with an antithyroid drug. In the next four to six weeks, she gradually improves symptomatically and her thyroid gland diminishes in size. You take her off the antithyroid drug. One month after therapy is discontinued, she notes a gradual return of her initial symptoms of hyperthyroidism. One month later, you admit her a second time for radioactive iodine thyroidectomy. Two months later, the patient is euthyroid and for the next two years shows no signs of thyrotoxicosis.

STUDY GUIDELINES 1. You should be able to describe how inappropriate hormone secretion could produce these same symptoms (differential diagnosis). Discuss the physiology and mechanism of thyroid hormone secretion that could cause these symptoms. Relate the hormone hypersecretion to the patient's signs and symptoms. Explain the mechanism by which the signs are produced. Discuss other signs and symptoms of excess secretion of this hormone and explain how testing is utilized to diagnose this condition. Describe the treatments available for this patient and explain the mechanisms of action of each treatment, as well as adverse effects, recurrence rates, and drug-drug interactions. Be able to explain the advantages and disadvantages of one treatment versus another. Based on the information available, recommend a plan of treatment. Discuss the long-term outcome of each of the potential treatments, necessary precautions to be used, and the use of laboratory testing to monitor the outcome. Explain the mechanism of action of each treatment and indicate probable adverse effects and potential drug-drug interactions.

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DISCUSSION QUESTIONS 1. Describe the physiology and biochemistry of thyroxin production and secretion. Indicate factors that regulate thyroxin production. 2. Describe 3 mechanisms by which excess thyroid secretion can be produced. 3. Explain how excessive thyroid hormone causes each of the patient's signs and symptoms. What effect does excessive thyroid hormone have on the sympathetic system? What other symptoms of hyperthyroidism may be observed? 4. How can thyroid function be measured? What test values would be expected in this patient? 5. What drugs can interfere with thyroid function tests? 6. What drugs are available to treat hyperthyroidism? Describe their mechanisms of action. Describe the chief adverse effects of the antithyroid drugs. 7. What is the best treatment for hyperthyroidism in pregnant women? Breastfeeding? 8. What adjuncts are available for the treatment of hyperthyroidism? What is thyroid storm and what drugs are used to treat it? 9. Initially the patient had a good response to therapy with the antithyroid drug. What may be the cause of her clinical relapse when therapy was discontinued? 10. Compare the advantages and disadvantages of radioactive iodine therapy with surgical thyroidectomy for this patient's condition. What are the general limitations to its use? 11. Discuss the possibility of hypothyroidism developing after radioiodine therapy and describe the symptomatology that might signify its onset. What thyroid function test values would be expected in this

state? If it does occur, what agents are available to treat it? 12. Discuss why thyroid hormone replacement must be done cautiously in a patient with coronary heart disease.