Considering hormoneinduced causes of diabetes

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Hormones that help to raise the blood glucose when it's too low may cause diabetes when present in very large amounts, such as when a tumor develops on the gland that makes a hormone. The important hormones that bring on diabetes under these circumstances are discussed in this section.

Acromegaly

Acromegaly is the disease that occurs when a benign tumor of the pituitary gland in the brain makes excessive quantities of growth hormone. (In Chapter 2, I discuss the hormones that help to raise the blood glucose when it's abnormally lowered and mention the role of growth hormone.) Growth hormone is essential to normal growth of the bones, but it causes diabetes among other abnormalities when it's present in excessive amounts.

^¡Je-OOCTj^ Unfortunately, because acromegaly is relatively rare, it sometimes takes " years before the diagnosis is finally considered. Fortunately, excessive growth hormone triggers a number of signs and symptoms that can help point doctors to the diagnosis of acromegaly. Following are some of these signs and symptoms of acromegaly:

^ Carpal tunnel syndrome (tingling and weakness in the hand due to squeezing of nerves in the wrist)

^ Coarsening of facial features (enlargement of facial bones and the nose)

^ Excessive sweating

^ Headaches

^ Infertility in women and erectile dysfunction in men ^ Swelling of hands and feet ^ Tiredness

Diabetes occurs in 40 percent of people with acromegaly, which is usually diagnosed in adults. It appears more like T2DM than T1DM, and it's usually mild and can be managed with oral diabetes agents if necessary.

Doctors diagnose acromegaly by obtaining multiple growth hormone blood tests and finding the average. In unafflicted people, growth hormone measurements throughout the day are usually undetectable, but people with acromegaly have measurable levels of growth hormone in all samples. The diagnosis is confirmed by an X-ray study of the pituitary gland, in which the tumor can be clearly seen.

Acromegaly is treated by surgically removing the tumor. If this can't be done or the patient refuses the procedure, several medications bring the growth hormone down to normal levels. Reducing the growth hormone level to normal will cure the patient's diabetes and either stop the rest of the symptoms from worsening or reverse them.

Cushing's syndrome

Cushing's syndrome, which is usually diagnosed in adults, involves an overproduction of the hormone cortisol from the adrenal glands on the kidneys. Cortisol is one of the hormones normally secreted to help raise blood glucose when it's low (see Chapter 2). When present in excessive amounts, cortisol can cause diabetes.

The excessive production of cortisol may be the result of one of these causes:

¡^ In 80 percent of cases, a benign tumor of the pituitary gland produces too much of the hormone adrenocortical stimulating hormone (ACTH), which stimulates the adrenals to make more cortisol.

¡^ In 20 percent of cases, a benign tumor in one of the adrenals stimulates the overproduction of cortisol.

The difference between these two causes is that there's a lot of measurable ACTH in the pituitary gland tumor and none in the adrenal gland tumor. Sometimes a cancer will produce a form of ectopic ACTH that stimulates overproduction of cortisol, but ectopic ACTH differs from normal ACTH in that it comes from outside the pituitary.

^¡jc.OOC^ The most obvious symptoms of Cushing's syndrome, such as a round face " and obesity of the trunk with wasting of the arms and legs, are rarely seen today because patients are diagnosed at a much earlier stage. The common signs and symptoms that suggest Cushing's syndrome today are

¡^ Acne ¡^ Depression ¡^ Easy bruising of the skin ¡^ Loss of sexual interest ¡^ Menstrual irregularity

¡^ Weakness and tiredness (weakness and tiredness that come on rapidly and severely suggest that a tumor is secreting ectopic ACTH)

Doctors diagnose Cushing's syndrome by finding high levels of cortisol in the blood both in the morning and at night. In a person without Cushing's, the blood contains much more cortisol in the morning than in the evening. Following the finding of abnormally high cortisol, several tests for ACTH are taken to determine if it's high or low:

¡^ If the ACTH is high, X-ray studies of the pituitary gland usually identify a tumor, which can be surgically removed. Radiation therapy to the pituitary also is used in some cases, especially when surgery fails to normalize the cortisol level.

A number of drugs that block the action of Cortisol may be used to prepare the patient for surgery so that he's in the best condition possible and to control the disease until radiation therapy can take effect.

1 If the ACTH is low, X-rays of the adrenals may point to a tumor in one of them, which can be removed surgically to cure the condition.

In people with Cushing's syndrome, X-rays of the chest and abdomen often reveal the source of ectopic production of ACTH, especially when it's a small cell carcinoma in the lungs. The carcinoma may or may not be operable.

The diabetes that occurs with Cushing's syndrome tends to be mild, which is in part due to earlier diagnosis. It presents more like T2DM in that it responds to oral agents, if necessary, but goes away if the underlying disease is cured.

The most common reason for high levels of cortisol and resultant diabetes is taking cortisol for its anti-inflammatory action. Cortisol is commonly prescribed to treat a variety of autoimmune diseases and to prevent rejection of transplanted organs. When the cortisol is essential, the diabetes is treated as necessary. I discuss other chemicals that may cause diabetes in the later section "Discovering drugs and chemicals that may cause or worsen diabetes."

Other causes

There are a number of other diabetes-causing conditions associated with overproduction of hormones, usually due to tumors. They're rarer than acromegaly and Cushing's syndrome, which I describe in the previous sections. Here's a rundown of what these other conditions are and who's most likely to get them:

1 Glucagonoma: This condition results from a tumor of the A cells of the pancreas, which make glucagon. Glucagon is a hormone that counteracts insulin and raises the blood glucose (see Chapter 2), and excess glucagon can cause T2DM. The signs and symptoms of glucagonoma are weight loss, diarrhea, and anemia. It tends to be malignant 75 percent of the time but fortunately is very rare. It's found in adults and is treated with surgery.

1 Hyperthyroidism: This disease is caused by excessive production of thyroid hormone, usually due to an autoimmune stimulation of the thyroid gland. Hyperthyroidism causes increased production of glucose from amino acids in the liver, more rapid uptake of glucose from the intestine, and increased insulin resistance. All these effects lead to hyperglycemia (high blood glucose) and possible diabetes, usually of the type 2 variety. Control of the hyperthyroidism eliminates the diabetes, and it's rare in the modern era to see hyperthyroidism go on long enough for T2DM to develop. Hyperthyroidism may be treated by antithyroid drugs, a dose of radioactive iodine that destroys the thyroid, or surgical removal of most of the thyroid. It's seen most often in adults.

1 Pheochromocytoma: This disease is caused by a tumor of the adrenal gland that causes it to make excessive amounts of norepinephrine. Excessive norepinephrine causes high blood pressure, headaches, and a rapid heartbeat, often in recurring episodes. Because this hormone also causes increased blood glucose, type 2 diabetes may be found in patients with pheochromocytoma. It's found in adults, usually, and is treated by surgical removal of the tumor.

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