Acromegaly

Definition

Definition of Acromegaly
Acromegaly is a syndrome that results when the pituitary gland produces excess growth hormone (hGH) after epiphyseal plate closure at puberty. A number of disorders may increase the pituitary's GH output, although most commonly it involves a GH producing tumor called pituitary adenoma, derived from a distinct type of cell (somatotrophs).

Symptoms

Symptoms of Acromegaly
Soft tissue swelling visibly resulting in enlargement of the hands, feet, nose, lips and ears, and a general thickening of the skin. In particular the appearance of the hands can indicate to a knowledgeable person that a stranger may be developing acromegaly; there are documented instances of physicians warning strangers that they had acromegaly.

Soft tissue swelling of internal organs, notably the heart with attendant weakening of its muscularity, and the kidneys, also the vocal cords resulting in a characteristic thick, deep voice and slowing of speech.

Causes

Causes of Acromegaly
Pituitary Adenoma: In over 90 percent of acromegaly patients, the overproduction of growth hormones is caused by a benign tumor of the pituitary gland, called an adenoma. These tumors produce excess growth hormones and, as they expand, compress surrounding brain tissues, such as the optic nerves. This expansion causes the headaches and visual disturbances that often accompany acromegaly. In addition, compression of the surrounding normal pituitary tissue can alter production of other hormones, leading to changes in menstruation and breast discharge in women and impotence in men because of reduced testosterone production.
Other Tumors: In a few patients, acromegaly is caused not by pituitary tumors but by tumors of the pancreas, lungs, and adrenal glands. These tumors also lead to an excess of GH, either because they produce GH themselves or, more frequently, because they produce GHRH (Growth Hormone Releasing Hormone), the hormone that stimulates the pituitary to make GH. In these patients, the excess GHRH can be measured in the blood and establishes that the cause of the acromegaly is not due to a pituitary defect. When these non-pituitary tumors are surgically removed, GH levels fall and the symptoms of acromegaly improve.
Pituitary Gigantism: This condition of growth hormone excess is rare in and is referred to as pituitary gigantism, because the excessive growth hormone produces excessive growth of bones and the child can achieve excessive height; from 2.1 to 2.7 m (6'11" to 8'11") in stature by adulthood if left untreated.

Diagnosis

Diagnosis of Acromegaly
Frequent blood sampling with serum GH measurement shows that in normal subjects (left panel) GH can fluctuate between undetectable levels (most of the time) and peaks of up to 30 ?g/l (90 mIU/l), owing to the episodic nature of GH secretion, while in patients with acromegaly (an example is given on right panel), GH hypersecretion is continuous and GH never returns to undetectable levels.

Magnetic resonance image of a pituitary macroadenoma that caused acromegaly with compression of the optic chiasm.

Site of action of the different therapeutic tools in acromegaly. Surgery, radiotherapy, somatostatin analogues and dopamine agonists act at the level of the pituitary adenoma, while GH-receptor antagonists act in periphery by blocking the growth hormone receptor and thus impairing the effects of GH on the different tissues.

IGF1 provides the most sensitive and useful lab test for the diagnosis of acromegaly. A single value of the Growth hormone (GH) is not useful in view of its pulsatality (levels in the blood vary greatly even in healthy individuals).

An MRI of the brain focusing on the sella turcica after gadolinium administration allows for clear delineation of the pituitary and the hypothalamus and the location of the tumor.

Prognosis

Prognosis of Acromegaly
Treatments for acromegaly are successful in a significant number of people. Unfortunately, however, the disease is rarely caught early enough to prevent permanent damage or even premature death.

1. Bone changes of acromegaly are permanent.
2. Many of the soft-tissue changes, such as swelling, enlarged tongue, thickened skin, acne, and carpal tunnel syndrome are reversible with treatment. Depression and sexual problems also may improve with treatment. Goiter and other organ enlargement improve in some cases.
3. Complications such as high blood pressure, diabetes, and high triglycerides start to reverse when the levels of growth hormone and IGF-1 are normalized. If these changes are reversed, serious illness, such as heart disease and stroke or death can be prevented.

Treatment

Treatment of Acromegaly
The goals of treatment are to reduce GH production to normal levels, to relieve the pressure that the growing pituitary tumor exerts on the surrounding brain areas, to preserve normal pituitary function, and to reverse or ameliorate the symptoms of acromegaly. Currently, treatment options include surgical removal of the tumor, drug therapy, and radiation therapy of the pituitary.

Surgery is a rapid and effective treatment, of which there are two alternative methods. The first method, a procedure known as Endonasal Transphenoidal surgery, involves the surgeon reaching the pituitary through an incision in the nasal cavity wall. The wall is reached by passing through the nostrils with microsurgical instruments. The second method is Transsphenoidal surgery during which an incision is made into the gum beneath the upper lip. Further incisions are made to cut through the septum to reach the nasal cavity, where the pituitary is located. Endonasal Transphenoidal surgery is a less invasive procedure with a shorter recovery time than the older method of Transphenoidal surgery, and the likelihood of removing the entire tumor is greater with reduced side-effects. Consequently, Endonasal Transphenoidal surgery is often used as a first option, with Transphenoidal and other treatments, such as, medicinal therapy or radiostatic neurosurgery being used to reduce the remaining adverse effects of the remaining tumor.

These procedures normally relieve the pressure on the surrounding brain regions and lead to a lowering of GH levels. If the surgery is successful, facial appearance and soft tissue swelling improve within a few days. Surgery is most successful in patients with blood GH levels below 40 ng/ml before the operation and with pituitary tumors no larger than 10 mm in diameter. Success depends on the skill and experience of the surgeon. The success rate also depends on what level of GH is defined as a cure. The best measure of surgical success is normalization of GH and IGF-1 levels. Ideally, GH should be less than 2 ng/ml after an oral glucose load. A review of GH levels in 1,360 patients worldwide immediately after surgery revealed that 60 percent had random GH levels below 5 ng/ml. Complications of surgery may include cerebrospinal fluid leaks, meningitis, or damage to the surrounding normal pituitary tissue, requiring lifelong pituitary hormone replacement.

Prevention

Prevention of Acromegaly
There is no known way to prevent acromegaly. Early detection is the best hope of preventing severe symptoms and complications.