Acromegaly

Acromegaly is an endocrinological syndrome causing an overgrowth of some organs, bones and joints. Read on to find out all about the disease as well as its causes, symptoms, diagnosis and treatment.

What is Acromegaly?

It is an abnormal condition of the pituitary gland resulting in excessive production of growth hormone, abbreviated as GH. This is a serious disorder as the tissues in the body continue to grow at an uncontrollable rate even after puberty.

Acromegaly Incidence

Nearly 4,676 cases of the disorder are reported every year per million people. It is typically observed in adults between the ages of 40 and 45.

Acromegaly Symptoms

Increased secretion of growth hormone manifests in the form of abnormal physical changes in the body. Few cases of the hormonal disorder are associated with abrupt increase in body growth. Here, the clinical features are more distinct and develop rapidly. In remaining cases, there is a delay in the presentation of symptoms and may take several years to appear.

Picture 1 – Acromegaly

Some of the fairly common symptoms of the condition are:

• Enlargement of the hands and feet
• Sausage-like fingers
• Distinct facial characteristics, including broad lips and nose
• Thickened ears
• Coarsening and thickening of the skin, especially on the palms and soles
• Hyperpigmentation of the skin
• Excessive lubrication of the skin, causing acne
• Formation of benign skin tags
• Swollen tongue and neck
• Profuse sweating
• Increased prominence of the lower jaw with gaps between the teeth
• Bulging eyes
• Visual impairment
• Headaches
• Enlarged head
• Protruding forehead
• Extensive hair growth all over the body
• Numbness and tingling sensations in the thumb and fingers due to Carpal Tunnel Syndrome
• Pain, inflammation and stiffness in the joints
• Swollen vocal cords, resulting in
• Sleep interruption
• Irregular menstruation in females
• Impotency in males

In aggressive cases, the muscles of the heart, kidneys, spleen and liver get severely affected with few patients having insulin deficiency as an additional endocrinological illness. Anomalies in these vital organs give rise to problems like:

• Shortness of breath
• Fatigue
• Irritability
• Excessive thirst
• Frequent urination
• Chest pain
• Weakness
• Increased heart beat
• Exercise intolerance
• Fainting

Acromegaly Causes

The pituitary gland is a tiny structure in the head. It is the master gland of the endocrine system known for producing hormones, including GH, that regulate other glands and control various body functions. The presence of GH in blood stimulates the liver to release insulin-like growth factor 1 (IGF-1), which in turn triggers cellular growth and division. The pituitary is divided into anterior and posterior sections. The anterior pituitary forms the front portion of the gland and secretes hormones that affect the following:

• Growth
• Development of the sex organs
• Pigmentation of the skin
• Functioning of the cortex of adrenal glands

The back portion of the gland constitutes the posterior pituitary, which produces hormones for increased uterine contractions and reabsorption of water by the kidneys. Interestingly, the pituitary gland is stimulated to release GH by growth hormone-releasing hormone (GHRH) produced by the hypothalamus of the brain. In order to inhibit the secretion of excess GH, the hypothalamus produces another important hormone called Somastatin. Under normal circumstances the levels of GHRH, GH, Somastatin and IGF-1 are properly maintained by a well-regulated feedback loop in the body. However, the defect in this condition lies in the anterior pituitary, which causes disruption of the feedback loop and leads to overproduction of growth hormone in adults. The overfunction of the anterior pituitary, resulting in excessive release of GH, can be attributed to the following causes:

Pituitary adenoma

The condition is marked by noncancerous tumors in the pituitary gland. Carcinoma of the pituitary has a minimum possibility. More than 90% of patients have a dysfunctional pituitary due to an adenoma. The benign lesions influence the secretion of GH, which in turn raises the level of IGF-1 in the blood. This results in uninterrupted growth of bones and cartilages, causing physical changes. The inability of the feedback loop to neutralize the level of IGF-1 also contributes to the rapid buildup of the hormone. The tumors turn more lethal when they increase in size and begin to invade the nearby brain tissues. The benign growths preferably compress the optic nerve, a cranial nerve transmitting visual information from the retina to the brain. This explains the cause of headaches and ocular impairment. The damaging effects of the tumors create a hormonal imbalance, causing menstrual irregularities and reduced libido in males.

The late appearance of symptoms in some patients can be related to a slow growth of the adenomas. The invasive type of the tumor is the one, which deteriorates the surrounding tissues of the brain. The variance in size of the lesions determines the rate of GH production. Medical experts believe that a genetic mutation in one of the pituitary cells causes adenomas. The gene mainly transmits chemical signals within pituitary cells to trigger cellular division required for secretion of GH. The genetic condition is not a congenital defect but normally occurs during life. In other cases, the noncancerous tumors form without a known cause.

Gigantism

Chronic overactivity of the anterior pituitary gland can cause increased secretion of growth hormone before the end of adolescence. Affected children become abnormally tall and could be 7 or 8 feet in height. In the absence of treatment, such patients face the other problems of the hormonal disorder when they reach adulthood. Excessive production of GH after puberty does not induce gigantism but only causes enlargement of the bones.

Non-pituitary tumors

Malfunctioning of the anterior pituitary cannot always be ascribed to adenomas. Such localized tumors can develop in lungs, pancreas and adrenal glands that stimulate the hypothalamus to produce adequate amount of GHRH, which in turn leads to elevated GH levels. In contradictory cases, the affected organs may themselves produce GH. In such a situation, the underlying problem is not present in the pituitary gland.

Acromegaly in cats

This hormonal disorder can also occur in cats and is known as Feline acromegaly. It is more common in cats aged between 8-14 years. Affected animals exhibit enlarged extremities, uncontrolled diabetes mellitus, increased urine output and difficulty in swallowing.

Acromegaly Diagnosis

Many physicians may misinterpret the condition as an ordinary inflammation of the upper and lower extremities due to some infection. The symptoms may not be intense enough to get easily recognized. However, the condition is more evident in severely affected patients. The anomalous physical features and functional problems in the internal organs may warrant standard diagnostic tests like:

Blood test

This laboratory exam assists in measuring the level of growth hormone in the blood. However, the presence of GH does not confirm the disorder as the hormone has a tendency to fluctuate. Identification of the disorder can be done by checking the IGF-1 level. If a patient shows elevated quantity of IGF-1 and GH in the blood then this suffice the preliminary diagnosis of an impaired pituitary. Measurement of the amount of IGF-binding protein-3, which normally binds to IGF-1, implies functional abnormality of the master gland. In addition to these entities, high levels of cholesterol and triglyceride also indicate an underlying endocrine disorder. The test can even find out whether the adenomas are eliciting the release of hormones other than GH. These include:

• Gonadotropic hormones
• Prolactin
• Adrenocorticotropic hormone
• Thyroid stimulating hormone

X-ray

Unusual elongation of the bones with respect to the age of the patient signify hormonal imbalance.

Imaging procedures

An MRI or CT scan of the brain after the infusion of a luminescent material called gadolinium shows the presence, type and location of the pituitary tumor. When the examiner does not find an adenoma then the chest, abdomen and pelvis are scanned for tumors.

Echocardiogram

The movement of the heart can be properly monitored with the help of an ultrasound. Affected patients normally show an abnormal heart rhythm. The condition of the valves and blood vessels should also be evaluated for any other cardiac disorder.

Acromegaly Treatment

A patient’s suitability for a particular kind of treatment is judged by the following factors:

Picture 2 – Acromegaly Image

• Age
• Cause
• Severity of the symptoms

After assessing the condition of patients, the appropriate treatment method is accomplished, which aims at alleviating the symptoms, correcting the GH levels and restoring the normal function of the pituitary. Some of these are:

Surgery

Abnormal levels of GH in the body and its consequences are detrimental to the health of the patients. Therefore, irrespective of the cause, surgery should be the first therapeutic approach for this condition. Endonasal Transphenoidal surgery is the first procedure used to remove adenomas. Here, an incision is made in the nasal cavity wall through which the small surgical instruments are inserted to remove the tumor. Transsphenoidal surgery is the second opted method for remission of the symptoms caused by the tumors. In this procedure, an incision is made in the gum beneath the upper lip. The next step involves the incision of the septum in order to reach the nasal cavity and excise the tumor. Elimination of the pituitary lesions reduces the pressure exerted on the surrounding brain tissues and decreases the GH levels.

Drug therapy

Octreotide or lanreotide, which are the artificial preparations of the hormone called somatostatin, can inhibit the production of GH. These somatostatin analogues usually show promising results and need to be injected every 2 to 4 weeks. Symptomatic relief is quickly achieved following the administration of the drugs. Somatostatin analogues directly act on both pituitary and non-pituitary tumor by diminishing its size. Regular intake of the drug can lead to many gastrointestinal side effects like bloating, nausea and loose motions. Patients who do not respond well to somatostatin shots can be administered with dopamine antagonists like Bromocriptine or Cabergoline. These medicines are affordable, owing to its availability in the form of tablets. Like every drug, dopamine antagonists also produce side effects like dizziness, stomach upset, sinus congestion and nausea. Therefore, to prevent this, low dose of the drug is advisable.

Growth hormone receptor blockers have been recently discovered as the most effective drugs for treating the anomalous condition of the pituitary. These drugs block the site on the cells where GH normally attaches and triggers their growth and division. Pegvisomant (Somavert) is the only GH receptor that has been approved by the US Food and Drug Administration. Fatigue, sweating and headache are some of its side effects.

Radiation therapy

The use of radiation treatment is apt for older patients who cannot undergo surgery due to other underlying illnesses. External beam therapy is one type of the method. Here, a single or several beams of high energy X-rays from a linear accelerator is focused on the causative tumor. The second type is stereotactic radiotherapy, which requires a number of ionizing beams from various directions to be targeted at the site of tumor. The procedure can be, however, risky for some patients and may result in growth of secondary tumors.

Acromegaly Prognosis

The outlook following a surgical procedure is generally good but may cause some complications. The size of the tumor determines how well the patients respond to the treatment. Nearly 80-85% of patients with small size tumors recover fast as opposed to large lesions in which the success rate is 50-65%. The life expectancy of such patients post treatment is high. However, untreated patients can only survive up to 50 years.

Acromegaly Complications

Some of the severe complications of the disorder are:

• Hypertension
• Renal failure
• Cardiac failure
• Enlarged heart
• Complete vision loss

Acromegaly Support groups

Many online support groups help affected patients and their family members to deal with the disease. These kinds of communities encourage interaction with other patients who are facing similar difficulties. Some of the well-renowned organizations are:

The Pituitary Network Association (PNA)

Email: www.pituitary.org

The Endocrine Society

Email: www.endo-society.org

AcromegalySupport.com

Email: www.acromegalysupport.com

Early detection and appropriate treatment can reduce the morbidity and fatality associated with Acromegaly. Immediate visit to a healthcare expert is necessary in cases where the symptoms last for more than a few weeks.

References:

http://en.wikipedia.org/wiki/Acromegaly

http://www.patient.co.uk/doctor/Acromegaly.htm

http://emedicine.medscape.com/article/116366-overview

http://www.mayoclinic.com/health/acromegaly/DS00478