Tag Archives: Acromegaly

Acromegaly

Other Names: Somatotroph adenoma; Growth hormone excess; Pituitary giant

Definition:-
Acromegaly is a chronic metabolic disorder in which there is too much growth hormone and the body tissues gradually enlarge.
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It 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).

Acromegaly most commonly affects adults in middle age,  and can result in severe disfigurement, serious complicating conditions, and premature death if unchecked. Because of its insidious pathogenesis and slow progression, the disease is hard to diagnose in the early stages and is frequently missed for many years, until changes in external features, especially of the face, become noticeable.

Acromegaly is often also associated with gigantism.

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Symptoms:-
Features that result from high level of GH or expanding tumor include:

*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

*Generalized expansion of the skull at the fontanelle

*Pronounced brow protrusion, often with ocular distension

*Pronounced lower jaw protrusion with attendant macroglossia (enlargement of the tongue) and teeth gapping

*Hypertrichosis, hyperpigmentation, and hyperhidrosis may occur in these patients

Observations:

•Body odor
•Carpal tunnel syndrome
•Decreased muscle strength (weakness)
•Easy fatigue
•Enlarged bones of the face
•Enlarged feet
•Enlarged hands
•Enlarged glands in the skin (sebaceous glands)
•Enlarged jaw (prognathism) and tongue
•Excessive height (when excess growth hormone production begins in childhood)
•Excessive sweating
•Headache
•Hoarseness
•Joint pain
•Limited joint movement
•Sleep apnea
•Swelling of the bony areas around a joint
•Thickening of the skin, skin tags
•Widely spaced teeth
•Widened fingers or toes due to skin overgrowth with swelling, redness, and pain

Other symptoms that may occur with this disease:
•Excess hair growth in females...click & see
•Weight gain (unintentional)……click & see

Causes:-

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. The pituitary gland, which is located just below the brain, controls the production and release of several different hormones, including growth hormone.

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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.

There is a marked variation in rates of GH production and the aggressiveness of the tumor. Some adenomas grow slowly and symptoms of growth hormone excess are often not noticed for many years. Other adenomas grow rapidly and invade surrounding brain areas or the sinuses, which are located near the pituitary. In general, younger patients tend to have more aggressive tumors.

Most pituitary tumors arise spontaneously and are not genetically inherited. Many pituitary tumors arise from a genetic alteration in a single pituitary cell which leads to increased cell division and tumor formation. This genetic change, or mutation, is not present at birth, but is acquired during life. The mutation occurs in a gene that regulates the transmission of chemical signals within pituitary cells; it permanently switches on the signal that tells the cell to divide and secrete growth hormones. The events within the cell that cause disordered pituitary cell growth and growth hormone oversecretion currently are the subject of intensive research.

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.

In patients with GHRH-producing, non-pituitary tumors, the pituitary still may be enlarged and may be mistaken for a tumor. Therefore, it is important that physicians carefully analyze all “pituitary tumors” removed from patients with acromegaly in order not to overlook the possibility that a tumor elsewhere in the body is causing the disorder.

Pituitary gigantism
This condition of growth hormone excess is rare in children 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. As an affected child becomes an adult, many of the adult problems can gradually develop. The distinction between gigantism (occurring in children) and acromegaly (occurring in adults) can be made by the occurrence of the adenoma in relation to the closure of the epiphyses. If elevated growth hormone levels occur before the closure of the epiphyses (i.e. in prepubertal children), then gigantism ensues. If it occurs after the closure of the epiphyses (i.e., in adults) then acromegaly ensues.

Diagnosis:
If acromegaly is suspected, medical imaging and medical laboratory investigations are generally used together to confirm or rule out the presence of this condition.

*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). GH levels taken 2 hours after a 75 or 100 gram glucose tolerance test are helpful in the diagnosis: GH levels are suppressed below 1 ?g/L in normal people, and levels higher than this cutoff are confirmatory of acromegaly.

*Other pituitary hormones have to be assessed to address the secretory effects of the tumor as well as the mass effect of the tumor on the normal pituitary gland. They include TSH (thyroid stimulating hormone), gonadotropic hormones (FSH,LH), ACTH (adrenocorticotropic hormone), prolactin.

Exams and Tests
*High growth hormone level
*High insulin-like growth factor 1 (IGF-1) level
*Spine x-ray shows abnormal bone growth
*Echocardiogram may show an enlarged heart, leaky mitral valve, or leaky aortic valve
*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.

This disease may also change the results of the following tests:

*Fasting plasma glucose
*Glucose tolerance test

Treatment:
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.

Once the diagnosis has been confirmed by blood tests and scans, treatment can be provided. This may include a combination of surgery to remove the tumour, radiotherapy to destroy any tumour cells and drugs to suppress the production of GH.

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.

Even when surgery is successful and hormone levels return to normal, patients must be carefully monitored for years for possible recurrence. More commonly, hormone levels may improve, but not return completely to normal. These patients may then require additional treatment, usually with medications.

The primary current medical treatment of acromegaly is to use somatostatin analogues — octreotide (Sandostatin) or lanreotide (Somatuline). These somatostatin analogues are synthetic forms of a brain hormone, somatostatin, which stops GH production. The long-acting forms of these drugs must be injected every 2 to 4 weeks for effective treatment. Most patients with acromegaly respond to this medication. In many patients, GH levels fall within one hour and headaches improve within minutes after the injection. Several studies have shown that octreotide and lanreotide are effective for long-term treatment. Octreotide and lanreotide have also been used successfully to treat patients with acromegaly caused by non-pituitary tumors.

Somatostatin analogues are also sometimes used to shrink large tumors before surgery.

Because octreotide inhibits gastrointestinal and pancreatic function, long-term use causes digestive problems such as loose stools, nausea, and gas in one third of patients. In addition, approximately 25 percent of patients develop gallstones, which are usually asymptomatic. In rare cases, octreotide treatment can cause diabetes. On the other hand, scientists have found that in some acromegaly patients who already have diabetes, octreotide can reduce the need for insulin and improve blood sugar control.

For those who are unresponsive to somatostatin analogues, or for whom they are otherwise contraindicated, it is possible to treat using one of the dopamine agonists, Bromocriptine (Parlodel) or Cabergoline. These have the advantage of being tablets rather than injections, and cost considerably less. These drugs can also be used as an adjunct to somatostatin analogue therapy. They are most effective in those whose pituitary tumours cosecrete prolactin. Side effects of these dopamine agonists include gastrointestinal upset, nausea, vomiting, light-headedness when standing, and nasal congestion. These side effects can be reduced or eliminated if medication is started at a very low dose at bedtime, taken with food, and gradually increased to the full therapeutic dose. However, bromocriptine lowers GH and IGF-1 levels and reduces tumor size in fewer than half of patients with acromegaly. Some patients report improvement in their symptoms although their GH and IGF-1 levels still are elevated.

The latest development in the medical treatment of acromegaly is the use of growth hormone receptor antagonists. The only available member of this family is pegvisomant (Somavert). By blocking the action of the endogenous growth hormone molecules, this compound is able to control disease activity of acromegaly in virtually all patients. Pegvisomant has to be administered subcutaneously by daily injections. Combinations of long-acting somatostatin analogues and weekly injections of pegvisomant seem to be equally effective as daily injections of pegvisomant.

Radiation therapy has been used both as a primary treatment and combined with surgery or drugs. It is usually reserved for patients who have tumor remaining after surgery. These patients often also receive medication to lower GH levels. Radiation therapy is given in divided doses over four to six weeks. This treatment lowers GH levels by about 50 percent over 2 to 5 years. Patients monitored for more than 5 years show significant further improvement. Radiation therapy causes a gradual loss of production of other pituitary hormones with time. Loss of vision and brain injury, which have been reported, are very rare complications of radiation treatments.

No single treatment is effective for all patients. Treatment should be individualized depending on patient characteristics, such as age and tumor size. If the tumor has not yet invaded surrounding brain tissues, removal of the pituitary adenoma by an experienced neurosurgeon is usually the first choice. After surgery, a patient must be monitored for a long time for increasing GH levels. If surgery does not normalize hormone levels or a relapse occurs, a doctor will usually begin additional drug therapy. The current first choice is generally octreotide or lanreotide. However, bromocriptine or cabergoline are much cheaper and easier to administer. With both types of medication, long-term therapy is necessary because their withdrawal can lead to rising GH levels and tumor re-expansion. Radiation therapy is generally used for patients whose tumors are not completely removed by surgery; for patients who are not good candidates for surgery because of other health problems; and for patients who do not respond adequately to surgery and medication.

The following medications may be used to treat acromegaly:

*Octreotide (Sandostatin) or bromocriptine (Parlodel) may control growth hormone release in some people.
*Pegvisomant (Somavert) directly blocks the effects of growth hormone, and has been shown to improve symptoms of acromegaly.

These medications may be used before surgery, or when surgery is not possible.

After treatment, periodic evaluation is necessary to ensure that the pituitary gland is working normally. Yearly evaluations are recommended.

Possible Complications:-
*Arthritis
*Cardiovascular disease
*Carpal tunnel syndrome
*Colonic polyps
*Glucose intolerance or diabetes
*High blood pressure
*Hypopituitarism
*Sleep apnea
*Spinal cord compression
*Uterine fibroids
*Vision abnormalities
*Severe headache
*Enlarged heart
*Hypertension
*Diabetes mellitus
*Heart failure
*Kidney failure
*Compression of the optic chiasm leading to loss of vision in the outer visual fields (typically bitemporal hemianopia)
*Increased palmar sweating and sebum production over the face (seborrhea) are clinical indicators of active growth hormone (GH) producing pituitary tumors. These symptoms can also be used to monitor the activity of the tumor after surgery although biochemical monitoring is confirmatory.

Prognosis :
Pituitary surgery is successful in most patients, depending on the size of the tumor and the experience of the surgeon.

Without treatment the symptoms will get worse, and the risk of cardiovascular disease increases.

Prevention:
There are no methods to prevent the condition, but early treatment may prevent complications of the disease from getting worse.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://www.nlm.nih.gov/medlineplus/ency/article/000321.htm
http://www.bbc.co.uk/health/physical_health/conditions/acromegaly1.shtml
http://en.wikipedia.org/wiki/Acromegaly

http://www.sd-neurosurgeon.com/diseases/pit_tumors.html

http://www.elp.manchester.ac.uk/pub_projects/2002/MNBY9APB/THEPITUITARYCLINICAL.htm

http://commons.wikimedia.org/wiki/File:Endocrine_growth_regulation.svg

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Growth Disorders

Overview:
Growth is one of the complex and amasing facts of life that most people take for granted, but it can be a cause for concern for parents who have a child who’s shorter than others of the same age and doesn’t appear to be growing any taller.

Children of the same age vary greatly in height due to factors such as diet, genetics, and ethnic background. In most cases, tall or short stature is not abnormal and is due to a family tendency to be taller or shorter than average or to reach final height later than usual. Tall or short stature is a cause for concern only if the child’s height is well outside the average range for his or her age. Abnormally short or tall stature may be caused by a number of disorders.

What are the types?
Normal growth depends on a nutritionally adequate diet and good general health and is controlled by specific hormones. disruption of any of these three important factors may lead to a growth disorder that results in a child having abnormally short or tall stature.
short stature:
A child may be shorter than normal if his or her diet is inadequate. a chronic illness, such as cystic fibrosis or severe asthma, may also result in poor growth. crohn’s disease, a type of inflammatory bowel disease, is another example of a chronic illness that may lead to short stature. babies who have intrauterine growth retardation may reach a shorter than average height i later life.

Sometimes, short stature is caused by insufficient production of the hormones that are necessary for normal growth. in some children, the pituitary gland does not produce enough growth hormone. insufficient production of thyroid hormones is another cause of poor growth.

short stature is also a characteristic feature of tuner syndrome, a genetic disorder that only affects girls. in addition, short stature may occur as a result of a skeletal abnormality such as achondroplasia, an inherited disorder in which the bones of the legs and arms are shorter than normal.

Tall stature:
children may be temporarily taller than others of the same age and sex if puberty occurs early. however, in such children, the final height is usually normal. in very rare cases, exaggerated growth caused by the overproduction of growth hormone results in excessive height known as gigantism. the overproduction may be due to pituitary gland tumor. boys with the chromosome disorder klinefelter syndrome may also grow taller than normal at puberty.

Causes of delayed growth:
There are a large number of medical, genetic and external factors that can delay or inhibit normal growth. These include conditions such as Growth Hormone Deficiency (GHD) in children, Turner’s syndrome, Down’s syndrome, achondroplasia (defective growth of cartilage cells in the bones of the limbs) and various malfunctions of the endocrine system.

Chronic diseases and illnesses can also have a detrimental effect on growth including Inflammatory Bowel Disease IBD, chronic renal insufficiency and heart disease, as too can factors such as malnutrition, drug and alcohol abuse, neglect, chronic stress and lack of exercise. However, in many cases the cause of delayed or restricted growth is not known.

Many children are smaller than average during childhood yet end up reaching a normal adult height. But for some, a more normal adult height will not be achieved without treatment with supplemental human growth hormone (hGH). These include children with GHD and Turner’s syndrome.
A more common growth disorder is growth hormone deficiency (GHD). This is the condition of having too little GH. There are several possible explanations for its occurrence:

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A child can be born with GHD.
The condition also may arise because of damage to the hypothalamus or pituitary gland as a child or adult because of a tumor, an infection, or radiation to the brain — usually for the treatment of a tumor.
A deficiency in GH may also have an undefined cause. (In this case, it is said to be of idiopathic origin.)
Pituitary disorders, such as GH excess or GHD, are evaluated and treated by endocrinologists — medical specialists in hormone-related conditions. Because the diagnosis and treatment of such disorders require special expertise, primary care physicians who suspect patients have GH abnormalities should refer them to an endocrinologist.

One out of 2,500 to 5,000 children is born with a deficient growth hormone production resulting in impaired physical development, and another one in 2,000 to 2,500 girls are born with the genetic defect Turner’s syndrome. Both disorders may result in decreased final height, which may be improved by supplemental somatropin.

Growth Hormone Deficiency (GHD):-

In children
A child with an inadequate production of growth hormone (reduced or non-existent) may have a normal height and weight at birth, but the child’s physical development following birth is severely impaired.

The under-secretion of human growth hormone during childhood and puberty slows bone growth and teeth development, and also causes the growing plates of the long bones to close before normal height is reached. In addition, other organs of the body fail to grow and the body proportions remain childlike.

Without treatment the child with GHD risks the development of a range of complications, as well as having a short stature.

Turner’s syndrome
Turner’s syndrome is a common genetic defect that affects girls and women and occurs in about one out of every 2,000 to 2,500 female births.

In Turner’s syndrome all or part of one of the two X-chromosomes is missing, but the reason why this happens is not known. This defect can cause a number of physical and medical problems and in some cases creates educational and behavioural concerns.

Characteristics of Turner’s syndrome
As the extent of the defect to the chromosome varies, every case of Turner’s syndrome is individual and each affected girl may have only a few of the possible characteristics that can be associated with the syndrome.

Short stature is a common characteristic of Turner’s syndrome resulting in a decreased final adult height and is generally accompanied by a failure of the ovaries and infertility.

Growth failure in Turner’s syndrome
The reasons for the growth retardation in Turner’s syndrome are not entirely understood, but patients are generally not deficient in growth hormone. The pituitary gland produces adequate amounts but the long bones do not respond.

The growth plates appear to be resistant to the action of the body’s GH, yet the hormone functions normally in controlling metabolism and organ development. By treating with supplemental hGH the resistance can be overcome, creating growth in the long bones. Female hormones may need to be given as well.

Being a genetic problem the affected individual will be faced with the consequences of the syndrome all her life, but can expect to lead a healthy life with appropriate care and treatment.

Growth Hormone Excess:
Excess growth hormone (GH) in children (gigantism) is extremely rare, occurring in fewer than 100 children in the United States.

Excess GH in adults (acromegaly) most commonly occurs in middle-aged men and women. Approximately 60 out of every million Americans have acromegaly.

Very infrequently, GH excess may run in families, or be one manifestation of a number of rare syndromes.

Frequent Sign & Symptoms:

The signs and symptoms depends upon the type of growth disorder. A child with a growth problem needs to be evaluated by a health care provider to determine the underlying health issues involved.

How is it diagnosed?
Your child’s height will be measured during routine checkups. if his or her height is consistently either lower or higher than the normal range, he or she will need to be measured frequently. If growth rates continue to be normal, tests may be performed to check hormone levels and to look for underlying disorders, such as genetic abnormality. in some cases, maturity of a child’s bones may be assesses by taking x-rays of the hand and wrist.

What is the treatment?
Treatment for growth disorders is most successful if started well before puberty when bones still have the potential for normal growth. short stature caused by an inadequate diet usually improves if the diet is modified while the child is still growing. If the growth disorder is a chronic illness, careful control of the illness can sometimes result in normal growth. growth hormone deficiency is usually treated by replacement of growth hormone. hypothyroidism is treated by replacing thyroid hormone.

Abnormal early puberty may be treated using drugs to halt the advancement gland tumor may be treated by removal of the tumor.

Treated early, most children with a growth disorder reach a relatively normal height, but, if treatment is delayed until puberty, normal height is more difficult to achieve. Abnormal stature may cause a child to be self-conscious and unhappy, and he or she may need support such as counseling.

Growth Hormone Excess: Treatment Options
Because excess GH — acting alone or together with excess IGF-1 — produces adverse health effects, reducing the levels to normal is desirable. Surgery, medication and/or irradiation of the pituitary gland may be appropriate to achieve these goals.

Growth Disorders Lifestyle and Prevention:
For children:
Because growth hormone is taken for years, it is good for parents of children with GHD to be aware of some safety precautions:

Carefully follow the directions for taking GH
Tell all doctors who care for your child that he or she is taking growth hormone
Make sure your child takes any other prescription drugs exactly as prescribed
Contact your child’s doctor immediately if you have any questions about treatment or signs or symptoms which suggest a complication of GH treatment.
In addition, encourage your child to have a healthy lifestyle. Eating a variety of healthy foods will help your child to grow and respond to growth hormone treatment. Be sure that your child gets regular exercise and plenty of sleep, too.

For adults:

Adults receiving GH treatment should also eat a balanced diet, get regular exercise, and plenty of sleep.

Some adults find their lives are much better after taking GH alone. Others may find they still need some help, particularly with the psychological symptoms of GHD. You may need medication to control anxiety or lift your mood.

Counseling may be helpful too. Some forms of therapy, such as cognitive-behavior therapy, can allow you to correct negative thoughts you may be having. You also may want to join a support group with other adults who have GHD. Talking to others who have been through the same thing can be healing.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://www.charak.com/DiseasePage.asp?thx=1&id=344
http://www.ferring.com/en/therapeutic/endo/About+Growth+Disorders/
http://www.hormone.org/Growth/overview.cfm

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