Physiology

Case One

Natasha Schick is a 19-year-old aspiring model who has always dieted to keep her weight in an “acceptable” range. However, within the past 3 months, she has lost 20 lb despite a voracious appetite. She complains of nervousness, sleeplessness, heart palpitations, and irregular menstrual periods. She notes that she is “always hot” and wants the thermostat set lower than her apartment mates. On physical examination, Natasha was restless and had a noticeable tremor in her hands. At 5 feet, 8 inches tall, she weighed only 110 lb. Her arterial blood pressure was 160/85, and her heart rate was 110 beats/min. She had a wide-eyed stare, and her lower neck appeared full; these characteristics were not present in photographs taken 1 year earlier. Based on her symptoms, the physician suspected that Natasha had thyrotoxicosis, or increased circulating levels of thyroid hormones. However, it was unclear from the available information why her thyroid hormone levels were elevated. Laboratory tests were performed to determine the etiology of her condition

1. Based on her symptoms, Natasha’s physician suspected thyrotoxicosis (elevated levels of thyroid hormone). Why is each of the following symptoms consistent with increased levels of thyroid hormones? (i) Weight loss (ii) Heat intolerance (iii) Increased heart rate (iv) Increased pulse pressure (v) Increased arterial blood pressure 2. The physician considered the following possible causes of thyrotoxicosis, based on his understanding of the hypothalamic–anterior pituitary–thyroid axis: (i) increased secretion of thyrotropinreleasing hormone (TRH) from the hypothalamus; (ii) increased secretion of thyroid-stimulating hormone (TSH) from the anterior pituitary; (iii) primary hyperactivity of the thyroid gland (e.g., Graves’ disease); and (iv) ingestion of exogenous thyroid hormones (factitious hyperthyroidism). Using the laboratory findings and your knowledge of the regulation of thyroid hormone secretion, include or exclude each of the four potential causes of Natasha’s thyrotoxicosis. 3. Natasha’s physician performed a radioactive I− uptake test to measure the activity of her thyroid gland. When her thyroid was scanned for radioactivity, I− uptake was increased uniformly throughout the gland. How did this additional information help refine the diagnosis? Which potential cause of thyrotoxicosis discussed in Question 2 was ruled out by this result

4. The triiodothyronine (T3) resin uptake test measures the binding of radioactive T3 to a synthetic resin. In the test, a standard amount of radioactive T3 is added to an assay system that contains a sample of the patient’s serum and a T3-binding resin. The rationale is that radioactive T3 will first bind to unoccupied sites on the patient’s thyroid-binding globulin (TBG) and any remaining, or “leftover,” radioactive T3 will bind to the resin. Thus, T3 resin uptake is increased when circulating TBG levels are decreased (e.g., liver disease; fewer TBG-binding sites are available) or when endogenous free T3 levels are increased (endogenous hormone occupies more sites on TBG). Conversely, resin uptake is decreased when circulating TBG levels are increased (e.g., pregnancy) or when endogenous T3 levels are decreased. Natasha’s T3 resin uptake was increased. Using all of the information you have been given thus far, explain this finding. 5. Based on Natasha’s symptoms and laboratory findings, Natasha’s physicians concluded that she had Graves’ disease. Why did they reach this conclusion? Describe the etiology and pathophysiology of this disease. 6. Natasha’s thyroidectomy was successful, and she was recovering well. Her nervousness and palpitations disappeared, she was gaining weight, and her blood pressure returned to normal. However, she began to experience alarming new symptoms, including muscle cramps, tingling in her fingers and toes, and numbness around her mouth. She returned to her endocrinologist, who noted a positive Chvostek sign (in which tapping on the facial nerve elicits a spasm of the facial muscles). Her total blood Ca2+ concentration was 7.8 mg/dL, and her ionized Ca2+ concentration was 3.8 mg/dL, both of which were lower than normal (hypocalcemia). What caused Natasha to become hypocalcemic? How did hypocalcemia cause her new symptoms? 8. How was this new problem treated?

Case Two

Shirley Tai is a 43-year-old elementary school teacher. At her annual checkup, Shirley complained that, despite eating less, she had gained 16 lb in the past year. Her physician might have attributed this weight gain to “getting older” except that Shirley also complained that she has very little energy, always feels cold (when everyone else is hot), is constipated, and has heavy menstrual flow every month. In addition, the physician noticed that Shirley’s neck was very full. The physician suspected that Shirley had hypothyroidism and ordered laboratory tests

Based on the physical findings and laboratory results, Shirley’s physician concluded that Shirley had autoimmune (Hashimoto) thyroiditis and prescribed oral administration of synthetic T4 (L-thyroxine). The physician planned to determine the correct dosage of T4 by monitoring the TSH level in Shirley’s blood.

1. How were Shirley’s symptoms of weight gain and cold intolerance consistent with a diagnosis of hypothyroidism? 2. Review the regulation of thyroid hormone secretion by the hypothalamic–anterior pituitary– thyroid axis. List the potential mechanisms that could result in decreased secretion of thyroid hormones. How might you distinguish between these mechanisms as potential causes for her hypothyroidism? 3. Based on the laboratory results, what is the etiology of Shirley’s hypothyroidism? Why was her T4 level decreased? 4. Why was the triiodothyronine (T3) resin uptake decreased? 5. Why was her thyroid-stimulating hormone (TSH) level increased? 6. Shirley’s neck appeared full because she had an enlarged thyroid gland (goiter). If Shirley had hypothyroidism, why was her thyroid gland enlarged? 7. Shirley is receiving hormone replacement therapy in the form of synthetic T4. How does her body process this T4? How is synthetic T4 expected to ameliorate her symptoms? 8. How was Shirley’s serum TSH level used to adjust the dosage of synthetic T4? 9. What symptoms might Shirley experience if the dosage of T4 is too high?