Acromegaly is a disease of growth hormone (GH) hypersecretion.
Usually, the source is the pituitary tumor. These are always benign
(non-cancerous) but often large and invasive. GH itself does not
promote growth. Instead, it induces production of yet another hormone,
IGF-I or somatomedin C (SmC) in virtually all organs and tissues.
High IGF-I in turn promotes somatic growth. Clinically, acromegaly
is associated with increased amount of soft tissues (large puffy
hands, rough facial features), bone overgrowth (protruding lower
jaw, frontal bossing) tall stature (if the disease began before
puberty). Other symptoms include headache, sweating, snoring, sleep
apnea, carpal tunnel syndrome and joint aches.
The development of the disease is insidious, and at the time of
diagnosis the patient usually recalls the existence of symptoms
for 5-10 years. Even family rarely notices the gradual development
of the disease. Often, the diagnosis is made by a stranger or by
a new physician during his/her first meeting with the patient.
Acromegaly is a potentially life-threatening disease: Life expectancy
in the patients is shortened on the average by
10-15 years. Heart disease, diabetes and sleep apnea all contribute
to excess mortality. It is also possible that certain cancers (colon,
breast, and prostate) may be more frequent.
The biochemical diagnosis rests on the finding of high GH and IGF-I
levels. Often, the reliance on GH confuses the picture: most laboratories
state that GH below 10 or 15 ng/ml is normal. Physicians who are
not experienced in pituitary diseases often tell the patient that
the diagnosis of acromegaly is excluded if plasma GH is “normal.”
In fact, active acromegaly may be accompanied by perfectly normal
GH levels, often as low as 0.5-1 ng/ml. Over the past 5 years we
have seen close to 20 such patients, whose diagnosis was missed
elsewhere because of “normal” GH. We often put such
patients in the Clinical Research Center to perform frequent blood
sampling and do certain dynamic tests to establish the diagnosis
with certainty. Currently, plasma IGF-I is the only valid measure
of biochemical activity of the disease. If it is elevated, the diagnosis
of acromegaly should be suspected. Similarly, only normalization
of IGF-I can serve as a valid parameter of cure.
Surgery is the first option for the patients. It should be done
by an experienced pituitary surgeon. A minimum of 20 pituitary surgeries
per year is a criterion suggested by some to indicate sufficient
experience and proficiency. In experienced hands, microadenomas
are totally removed in 80-90% of cases, while the success rate in
macroadenomas depends on the size and the invasiveness of the tumor.
The success rate of less experienced surgeons is about ½-1/3
as low as that and the incidence of complications is 3-4 times as
high. Very large and invasive tumors often cannot be removed surgically,
but a sufficient debulking is important to improve the efficacy
of subsequent treatments.
Swelling of the hands and feet
Facial features become coarse as bones grow
Body hair becomes coarse as the skin thickens and/or
Increased perspiration accompanied with body odor
Enlarged lip, nose, and tongue
Thickened ribs (creating a barrel chest)
Enlargement of other organs
Strange sensations and weakness in arms and legs
Fatigue and weakness
Loss of vision
Irregular menstrual cycles in women
Breast milk production in women
Impotence in men
surgery the patient stays in the hospital overnight. Only rarely
do we have to prolong hospitalization for another 2-3 days. Patients
usually return to light work within a couple of weeks, but strenuous
exertion is not recommended for a month. The recurrence rate is
Radiation is very effective in preventing tumor regrowth, but its
ability to normalize hormone levels is limited and takes years.
Stereotactic radiosurgery (gamma knife) is a confusing misnomer
as no surgery is involved. While it is becoming more popular, there
is still no evidence that it is any more effective than conventional
radiation in normalizing hormone levels. Also, it has a higher complication
Medical therapy is most often used if surgery does not result in a cure and sometimes to shrink large tumors before surgery. Three medication groups are used to treat acromegaly.
Somatostatin analogs (SSAs) are the first medication group used to treat acromegaly. They shut off GH production and are effective in lowering GH and IGF-I levels in 50 to 70 percent of patients. SSAs also reduce tumor size in around 0 to 50 percent of patients but only to a modest degree. Several studies have shown that SSAs are safe and effective for long-term treatment and in treating patients with acromegaly caused by nonpituitary tumors. Long-acting SSAs are given by intramuscular injection once a month.
Digestive problems-such as loose stools, nausea, and gas-are a side effect in about half of people taking SSAs. However, the effects are usually temporary and rarely severe. About 10 to 20 percent of patients develop gallstones, but the gallstones do not usually cause symptoms. In rare cases, treatment can result in elevated blood glucose levels. More commonly, SSAs reduce the need for insulin and improve blood glucose control in some people with acromegaly who already have diabetes.
The second medication group is the GH receptor antagonists (GHRAs), which interfere with the action of GH. They normalize IGF-I levels in more than 90 percent of patients. They do not, however, lower GH levels. Given once a day through injection, GHRAs are usually well-tolerated by patients. The long-term effects of these drugs on tumor growth are still under study. Side effects can include headaches, fatigue, and abnormal liver function.
Dopamine agonists make up the third medication group. These drugs are not as effective as the other medications at lowering GH or IGF-I levels, and they normalize IGF-I levels in only a minority of patients. Dopamine agonists are sometimes effective in patients who have mild degrees of excess GH and have both acromegaly and hyperprolactinemia—too much of the hormone prolactin. Dopamine agonists can be used in combination with SSAs. Side effects can include nausea, headache, and lightheadedness
Agonist: A drug that binds to a receptor of a cell and triggers a response by the cell, mimicking the action of a naturally occurring substance.
Antagonist: A chemical that acts within the body to reduce the physiological activity of another chemical substance or hormone.