Question

1. A 48-year-old man complaining of impotence sought medical attention. Over the years, he has experienced increased difficulty with maintaining and, more recently, achieving an erection. Further questioning revealed that his shoe size has increased from a 9-C to 11-EEE over the past 5 years, and his dental plate had to be altered 3 times in 6 years. Recently friends have remarked on changes in his appearance. The patient also admitted to a tingling sensation in his fingers and joint pains. On physical examination, he had coarse facial features with a bulbous nose and a beetle-browed look. His hands, feet, and liver were enlarged. Laboratory studies revealed a fasting blood glucose level of 150 mg/dl.

       A). Why did the physician measure the plasma GH level? (Hint: What disease does the physician suspect this man has?)

       B). The concentration of what other peptide hormone that is secreted in direct response to GH is certainly elevated in this patient’s plasma, and where is that peptide primarily produced?

       C). What has caused the changes in the patient’s facial features, hands, feet and liver?

       D). What has caused the neurologic and joint symptoms?

       E). Why is the fasting blood glucose level elevated, and what changes in the plasma insulin level would you expect to find?

       F). What is the most likely cause of the patient’s impotence, and what hormonal abnormalities explain it?

2. A 30-year old woman sustained multiple injuries, including a skull fracture, in an automobile accident. Although initially in a coma, she gradually regained consciousness. Five days later she abruptly developed frequent urination and thirst, with a subsequent fluid intake and output of 8L/day. Vital signs were normal. Routine urinalysis was normal; no red blood cells were present. There was no glucose in her urine. Urine osmolarity was 75 mOsm/kg (i.e very dilute; high water concentration and low solute concentration). After depriving her of water, she continued to excrete 150 ml/hr and urine osmolarity stabilized at 125 mOsm/kg (serum osmolarity was 325 mOsm/kg --normal is 300 mOsm/kg; and serum sodium was 158 mEq/L—normal is about 145-150 mEq/L).

       C). What regulates water reabsorption and how does it act on its target cells?

       D). How and where is this regulatory substance synthesized and stored?

       E). What stimuli normally influence the secretion of this substance?

3. A person that has a diet deficient in iodine begins to experience weight gain, low blood pressure, and an intolerance to cold. The person also has a goiter (i.e. enlarged thyroid gland).

       A). What causes the weight gain, low blood pressure, and intolerance to cold?

       B). Why does this person have a goiter?

       C). How is iodine typically introduced in the diet?

Answer 1

Question 1.

A) The physician is suspecting a diasease called acromegaly in this 48 years old man. Acromegaly is caused by over secretion of growth hormones (GH) by the anterior pituitary gland during adult life. Hence, plamsa growth hormone level was measured to look for over secretion of growth hormone.

Ideally, plamsa growth hormone level is measured after administration of 75-100 grams of glucose orally and the supression of growth hormone is measured. In normal individuals, the level of GH should be less than 1microgram/liter. Any value of GH more than this after administration of 75 grams of glucose orally in an adult should raise the suspicion of growth hormone over secretion.

GH is secreted by somatotropic cells of anterior pituitary gland which helps in overall growth of the organs and body. Due to a pituitary tumor known as adenoma, there can be an increased production of GH from the pituitary gland. If this over secretion of GH occurs in a child it leads to gigantism and in an adult it leads to acromegaly.

B) The concentration of insulin like growth factor-1 (IGF-1) is also measured in the plasma to diagnose a case of acromegaly. IGF-1 is primarily produced in liver in response to growth hormone (GH) stimulation. The action of growth hormone in the growth of bones, cartilages, muscles, tendons, skin, visceral organs is mediated by IGF-1.

Hence, in this patient of acromegaly, IGF-1 levels in the plasma is also measured to look for its its overproduction as the oversecretion of growth hormone leads to overproduction of IGF-1 in the liver thereby causing abnormal enlargement of various tissues in the body.

C) The patient is suffering from acromegaly. Acromegaly literally means abnormal enlargement of the extremities (acro- extremities; megaly- abnormal enlargement).

In acromegaly there is over secretion of growth hormones due to pituitary tumor known as pituitary adenoma. This leads to over production of the hormone IGF-1 in the liver. Through the over activity of IGF-1 in the body, there is abnormal enlargement of bones in the hands, feet, face and also internal organs like liver and heart are also abnormally enlarged.

Due to overgrowth of facial bones, there can be prognathism (over growth of mandible bone), enlargement of maxilla and malocclusion of teeth in the sockets, frontal bossing due to enlarged frontal bones. There is also an enlargement of tongue (macroglossia).

Due to abnormally increased growth of soft tissues in the hands and feet, there is abnormal enlargement of the extremities.

D) The neurologic and joint symptoms like tingling, numbness and joint pain are caused by abnormal and excessive growth of soft tissues in this patient in response to over secretion of growth hormone and IGF-1. A classic example is carpal tunnel syndrome seen in patients of acromegaly in which the median nerve in the carpal tunnel of the wrist is compressed due to over growth of tissues in the wrist joint. Various other nerves can also be compressed and joint spaces can be abnormally enlarged due to overgrowth of bones or over growth of soft tissues in joint spaces, which leads to neurologic and joint symptoms.

E) Growth hormone increases the metabolism of glucose and fats to cause the overall growth of the body. Thus, growth hormone causes hyperglycemia (increased blood glucose level) and increased fatty acid levels in the blood.

In this patient of acromegaly as there is oversecretion of growth hormones by the pituitary gland, there is increased fasting blood glucose level (fasting hyperglycemia) which can eventually lead to diabetes mellitus.

As there is chronically increased blood glucose level in patient of acromegaly, it leads to insulin resistance. Although the body produces plenty of insulin to counter the hyperglycemia, it fails to do so due to insulin resistance. Insulin resistance is also added by chronic lipolysis and increased fatty acids in the blood in response to overactivty of growth hormone.

Thus, in this patient of acromegaly, there is increased plamsa level of growth hormone, IGF-1, insulin but due to insulin resistance (since there is chronic hyperglycemia and lipolysis), the patient can develop diabetes mellitus eventually.

F) Importence is caused by reeudced testosterone levels in the body. Acromegaly is caused by pituitary adenoma which causes over secretion of growth hormones from anterior pituitary gland in an adult. The pituitary tumor (adenoma) can gradually grow and alter the production of follicular stimulating hormone (FSH) and luteinizing hormone (LH) together called as gonadotropins since these gonadotropins are also secreted by the anterior pituitary gland.

Testosterone is synthesized by the interstitial cells of the testes in response to LH from the anterior pituitary gland. In acromegaly, the pituitary tumor can gradually impair the cells of anterior pituitary gland producing FSH and LH. Thus, reduced LH secretion from the anterior pituitary gland leads to reduced synthesis of testosterone from the interstitial cells (leydig cells) of the testes causing impotence.

As FSH secretion is also reduced, the patient can also suffer from decreased sperm counts and infertility as FSH controls the process of spermatogenesis in the testes.

In women, suffering from acromegaly, due to gradual decrease in FSH and LH levels, there can be impaired oogenesis and ovulation as FSH controls oogenesis and LH controls ovulation. Menstrual cycle is also altered due to the hormonal imbalance.