Case Study 1

To cause high levels of thyroid hormone, the genes responsible for TGB production must have been overexpressed. These genes are located in follicular cells.

Enhanced expression of myosin heavy chain alpha genes and repression of myosin heavy chain beta genes increases the velocity of myocardial contraction. The increase in basal oxygen utilization is partly caused by enhanced expression of the Na+, K+-ATPase gene. Overactivity of the sympathetic nervous system is partly caused by enhanced expression of the beta adrenergic receptor gene. (See pp. 942 and 943 in Physiology 3rd ed.)

The patient’s serum TSH was low because such high levels of T3 & T4 wouldn’t stimulate the secretion of TRH, and subsequently TSH. Secretion of TRH is stimulated by LOW levels of T3 and T4.

Excess secretion of thyroid hormone almost always results from disease intrinsic to the thyroid gland, and therefore such secretion is autonomous and independent of TSH stimulation of the gland. The resultant high serum T4 and T3 levels inhibit TSH secretion by blocking the effect of TRH on the pituitary thyrotrophs. The serum TSH level is therefore low. (See pp. 903-904 in Physiology 3rd ed.)

The relative serum level of T3 would likely be lower than T4, but T3 is more potent. I don’t believe this would contribute to her clinical state in any way different than the effects of the stated levels of T4 because these concentrations are related.

The serum TSH level would be elevated. This is largely attributable to the high serum level of T4, from which most T3 is derived by peripheral conversion. To a lesser extent T3 secretion is increased by the enlarged thyroid gland. T3 is the active metabolite of T4, and it binds with tenfold greater affinity to the nuclear thyroid hormone receptor. Therefore increased T3 accounts for most of the patient’s clinical signs. (See pp. 940 and 941 in Physiology 3rd ed.)

If the patient were pregnant, her serum thyroid levels would likely be increased.

Normal pregnancy is accompanied by high levels of estrogenic hormones. Estrogen increases the level of serum thyroid-binding globulin and therefore increases binding capacity. Consequently, total serum T4 rises but free T4 remains essentially normal, and the pregnant woman is basically euthyroid. The negative pregnancy test eliminates this consideration in the patient. In addition, the serum free T4 was clearly elevated. (See p. 1017 in Physiology 3rd ed.)

Any condition which would increase dmand for ATP. These include cold environment, hypoglycemia, high altitude, and pregnancy.

The serum TSH level would be elevated only in the rare case in which hypothyroidism was caused by excessive release of TRII or by secretion of TSH from a pituitary neoplasm.

The patient’s elevated radioactive iodine uptake was significant because it suggests that the patient’s iodine reserves were severely depleted.

An increased rate of synthesis of T4 requires increased availability of iodide to the thyroid gland. If the total body pool of iodide stays normal, then a larger than normal percentage of that pool must be taken up by the thyroid gland each day to maintain a high level of thyroid hormone synthesis and release. (See p. 934 in Physiology 3rd ed.)

Thiouracil depresses the function of the thyroid gland.

Thiouracil drugs inhibit the enzyme peroxidase which catalyzes all steps in thyroid hormone synthesis from iodide and tyrosine. In addition to reducing T4 synthesis and release, thiouracil drugs inhibit the enzyme 5′ monodeiodinase and thereby decrease the peripheral production of T3 from T4. (See pp. 934, 935, 938, and 940 in Physiology 3rd ed.)

Hypothyroidism, goiter, and myxedema resulted from excessive treatment with uracil.

When the patient developed hypothyroidism, the operation of negative feedback caused an elevation in the serum level of TSH. Low serum T4 and T3 levels elicit overstimulation of the pituitary thyrotrophs by TRH. (See p. 903 in Physiology 3rd ed.)

The patient’s serum TSH level would likely be high, because low concentrations of T3 would stimulate release of TRH and TSH. Negative feedback inhibition is involved in this relationship.

When the patient developed hypothyroidism, the operation of negative feedback caused an elevation in the serum level of TSH. Low serum T4 and T3 levels elicit overstimulation of the pituitary thyrotrophs by TRH. (See p. 903 in Physiology 3rd ed.)

The patient’s thyroid gland reenlarged (the patient developed a goiter) due to hypothyroidism caused by excessive treatment with thiouracil.

The thyroid gland was initially enlarged because of hyperthyroidism (Graves’ disease). The later reenlargement of the thyroid gland during thiouracil therapy reflected the trophic action of excess TSII acting through its thyroid plasma membrane receptor to stimulate DNA, RNA, and protein synthesis. (See p. 937 in Physiology 3rd ed.)

The excess thyroid hormones act to increase the basal metabolic rate, and induce the calorigenic effect to produce this patient’s symptoms. Her cardiac output and vascular resistance were elevated due to the enhanced actions of catecholamines, which up-regulate beta receptors.

Loss of weight despite normal food intake indicates negative caloric balance caused by energy expenditure exceeding energy intake. An excess level of thyroid hormone has increased the patient’s basal or resting metabolic rate, that is, the rate of oxygen utilization above normal. In addition, thyroid hormone excess has caused a negative nitrogen balance, with the rate of protein degradation exceeding the rate of protein synthesis, so that lean body mass and bone mass have declined along with adipose tissue. The high basal metabolic rate induced by thyroid hormone is accompanied by increased heat production, which causes intolerance to high environmental temperatures and stimulates mechanisms of heat loss, such as sweating and hyperventilation. Nervousness, tremor, rapid reflexes, and tachycardia reflect increased adrenergic nervous system activity. Muscle weakness is caused by a loss of muscle mass that results in enhanced proteolysis. Increased fatigability with exercise is caused by inefficient generation of ATP and reduces stores of creatine phosphate. The patient’s cardiac output has been increased through thyroid hormone-induced increases in preload, cardiac contractility, and stroke volume. Systemic vascular resistance is decreased; this is attributable to local vasodilation caused by increased rates of tissue metabolism. (See pp. 254-256, 483, 518, 833, 834, 841, and 942-945 in Physiology 3rd ed.)