Question

Monica Williams is a 32-year-old woman who presents with a 3-month history of nervousness, tremor, palpitations, increased sweating, and discomfort with heat. She has lost 20 pounds over the last 3-months, despite a voracious appetite. Monica also complained of muscle weakness and fatigue with exercise at a level to which she was ordinarily accustomed. Physical exam revealed a heart rate of 110 beats/minute, respirations at 20/minute, and a blood pressure of 150/60. Her skin was warm and moist, her speech was rapid, her gaze had a stare quality, and her movements were hyperkinetic. She exhibited a tremor and very rapid reflexes. It was revealed her thyroid gland was diffusely enlarged.

Laboratory studies revealed:

Total serum T4 = 26 ug/dl (Normal 5 - 12)

Serum Free T4 = 4.1 ng/dl (Normal 0.8 – 2.4)

Serum Thyroid Stimulating Hormone (TSH) = 0.01 (Normal 0.5 – 5)

Pregnancy test = negative

1.         You suspect that Monica is suffering from hyperthyroidism. Based on your understanding of the hypothalamic-anterior pituitary-thyroid axis discuss each of the following as a possible cause of Monica’s hyperthyroidism.

                        a. Increased secretion of TRH from the hypothalamus

                        b. Increased secretion of TSH from the anterior pituitary

                        c. Primary hyperactivity of the thyroid gland

                        d. Ingestion of exogenous thyroid hormones

2.         To gain additional information about Monica’s thyroid condition, the activity of her thyroid gland was measured by a radioactive iodide (I^-) uptake test. When her gland 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 hyperthyroidism, as listed in Question #1, was ruled out by this result?

3.         A condition that causes hyperthryroidism is Graves’ Disease. Describe the pathophysiologic basis for how this condition leads to increased secretion of thyroid hormone. Include a discussion of the type of hypersensitivity disorder underlying Graves’ Disease.

4.         Monica’s thyroid condition was treated with a thiouracil drug, which inhibits the enzyme peroxidase. Based on your knowledge of the synthesis of thyroid hormone, explain the mechanism as to how this drug might benefit Monica.

After 4 weeks of treatment with thiouracil, Monica’s symptoms improved, and her

serum total T4 decreased to within normal range.   However, after 12 weeks of the

same dose of thiouracil, her serum T4 decreased further to below normal. At this time, Monica

complained of fatigue, lethargy, and intolerance to cold. Her weight had increased to 20

pounds over her usual healthy weight. Her thyroid gland, which had begun to decrease in size

with drug treatment, had now grown even larger than before treatment.

5.         Explain Monica’s symptoms at 12 weeks of continual therapy with maximal dose of thiouracil? What do you anticipate her serum TSH level to be at that point (12 weeks) and why? Why did her thyroid gland enlarge?

Answer 1

Hypertyroidism is hyper activity of thyroid gland with sustained increase and release of throid hormones. The most common form of hyperthyroidism is Grave's disease

Increased Thyroxine releasing Hormone: Increased Thyroxine Releasing hormones may be seen in toxic nodular goiters, and thyroid cancers

Increased Thyroid stimulating Hormone: as in case of pituitary adenomas there will be release of excessive TSH which stimulate Thyroid gland to produce more hormones

Primary Hyperactivity of Thyroid gland: due to autoimmune disorders like Grave's Disease body produces antibodies which binds with Thyroid Stimulating Hormone receptors and chronically stimulate it which inturn causes excessive production of thyroid hormones

Ingestion of exogenous Thyroid Hormones: Excessive intake may result in thyrotoxicosis due to high level of thyroid hormones

2. Radioactive re-uptake scan test: measures amount of iodine thyroid absorbs form the blood stream, if more iodine is absorbed it lead to the diagnosis of Grave's disease. It is confirmed by thyroid scan which shows how and where iodine is distributed in the thyroid. In Grave's disease entire thyroid is involved , so it will get distributed uniformly throughout the gland

3.Grave's disesase is characterised by excessive thyroid enlargement and thyroid hormone secretion. It produce autoimmune antibodies to TSH receptors . These antibodies attach to the receptors stimulate thyroid gland to produce more T3 and T4. Hence, the client will have low level of TSH in the blood stream.

Autoimmunity is an immune response against self in which immune system no longer differentiates between self and non-self. Exact cause is unknown In this autoantibodies and autosensitized T cells are responsible for  pathophysiologic tissue damge

Principal factors involved in autoimmunity are

1. Inheretance of susceptable genes which may contribute to failure of self tolerance
2. Initiation of autoreactivity by triggers such as viral infections

4. Prophyl thiouracil is a thyourea antithyroid agent inhibits iodine and peroxidase form their normal interaction with thyroglobulin to form T4 and T3 thus reducing thyroid hormone production

5. Low level of T3 and T4 causes hypothyroidism as a compensatory mechanism hypothalamus stimulate anterior pituitary to release more TSH. This is the side effect of the drug she is experiencing symptoms of hyper thyroidism