Answer case study- Exophthalmos- A 50-year-old woman complains of feeling warm all the time…

Case details

A 50-year-old woman complains of feeling warm all the time. Her eyes appear as they are bulging out of their sockets (exophthalmos). She sees a family physician to evaluate her condition. Her labs demonstrate a decreased level of TSH. Which of the following would you expect in this patient?

A. Reduced blood pressure

B. Weight gain

C. Increased basal metabolic rate

D. Reduced heart rate

E. Excess sleep

Answer- The patient presents with signs and lab reports consistent with hyperthyroidism (thyrotoxicosis).

Hence the right option is – C- Increased basal metabolic rate.Thyroid hormone is an important regulator of basal metabolic rate. Thus increased levels of thyroid hormone with subsequent decrease in TSH, result in an increased metabolic rate. Increased basal metabolic rate is associated with increased heat production and that is the cause of heat intolerance in patients with hyperthyroidism.

The term “thyrotoxicosis” refers to the clinical manifestations associated with serum levels of T4 or T3 that are excessive for the individual (hyperthyroidism). Serum TSH levels are suppressed in primary hyperthyroidism- see figure-1.

Release of thyroid hormone

Figure-1- Neurons in the hypothalamus secrete thyroid releasing hormone (TRH), which stimulates cells in the anterior pituitary to secrete thyroid-stimulating hormone (TSH). TSH binds to receptors on epithelial cells in the thyroid gland, stimulating synthesis and secretion of thyroid hormones, which affect probably all cells in the body. When blood concentrations of thyroid hormones increase above a certain threshold, TRH-secreting neurons in the hypothalamus are inhibited and stop secreting TRH.This is an example of “negative feedback”. Inhibition of TRH secretion leads to shut-off of TSH secretion, which leads to shut-off of thyroid hormone secretion. As thyroid hormone levels decay below the threshold, negative feedback is relieved, TRH secretion starts again, leading to TSH secretion.

Graves’ disease (known as Basedow’s disease in Europe) is the most common cause of thyrotoxicosis. It is an autoimmune disorder affecting the thyroid gland, characterized by an increase in synthesis and release of thyroid hormones; the thyroid gland is typically enlarged (figure-2) .

Enlarged thyroid gland in Grave's disease


Figure-2-Enlarged thyroid gland in Grave’s disease

Graves’ disease is much more common in women than in men (8:1), and its onset is usually between the ages of 20 and 40 years. It may be accompanied by infiltrative ophthalmopathy (Graves’ exophthalmos)- figure-3



Figure-3- Grave’s Exophthalmos

The pathogenesis of the hyperthyroidism of Graves’ disease involves the formation of auto antibodies that bind to the TSH receptor in thyroid cell membranes and stimulate the gland to hyperfunction.

The infiltrative exophthalmos that is frequently encountered has been explained by postulating that the thyroid gland and the extra ocular muscles share a common antigen which is recognized by the antibodies. Antibodies binding to the extra ocular muscles would cause swelling behind the eyeball.

Thyrotoxicosis due to any cause produces many different manifestations of variable intensity among different individuals. Patients may complain of nervousness, restlessness, heat intolerance, increased sweating, fatigue, weakness, muscle cramps, frequent bowel movements, or weight change (usually loss). There may be palpitations or angina pectoris. Women frequently report menstrual irregularities.

Cardiovascular, dermatological and gastrointestinal manifestations are commonly observed. The two signs that are truly ‘diagnostic’ of Graves’ disease (i.e., not seen in other hyperthyroid conditions) are exophthalmos and non-pitting edema, over the anterior and lateral aspects of the lower leg , (hence the term pretibial myxoedema).

Laboratory investigations include- Estimation of T3, T4, TSH, Protein bound iodine and Radio labeled iodine uptake test. Thyroid-stimulating antibodies may also be detected serologically.

The hyperthyroidism of Graves’ disease is treated by reducing thyroid hormone synthesis, using antithyroid drugs, or reducing the amount of thyroid tissue with radioiodine (131I) treatment or by thyroidectomy.

In the given case, the other choices including reduced blood pressure, reduced heart rate, weight gain and excess sleep are all seen with hypothyroidism.

For further reading follow the book-

A Case Oriented Approach Towards Biochemistry- By Namrata Chhabra

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