DEFINITION
Acromegaly is a chronic progressive disease that originates from an increased secretion of insulin-like grow factor (IGF-1), in turn due to high production of grow factor (GH), caused by a pituitary adenoma. This disease causes acral and soft tissue overgrowth.
Hand measurements in the follow-up of acromegaly,2013
EPIDEMIOLOGY
Acromegaly is a disease that is often diagnosed in adults who are already of a certain age, between the twentieth and the fortieth year, although symptoms can appear at any time during the life of an individual. The cause is pituitary adenoma which, by growth hormones’ hyper-expression, alters the body. They were also checked connections between vitamin D (calcitriol) circulating and the release of growth hormone. If calcitriol is high it will have little amount of GH.
The incidence of disease changes depending on the country, even though the average was calculated to be between 3 and 5 cases per million population per year. When the excessive production of GH occurs during childhood, you are suffering from gigantism rather than acromegaly.
Growth hormone and Klotho,2013
SYMPTOMS
Clinical manifestations in each patient depend on the levels of GH and IGF -1, age, tumor size, and the delay in diagnosis. The typical features of acromegaly develop slowly over years, and about 40% of acromegalic patients are diagnosed by various specialists such as physicians, dentists and ophthalmologists. The growth of pituitary adenoma may compress local structures can cause neurological symptoms and visual disturbances. Changes in appearance are derived from skeletal growth and enlargement of soft tissues, which is mild in the early stages of the disease. Visceromegalies as hepatomegaly, splenomegaly, and macroglossia are common. Facial changes include enlargement of lips and nose, drafts frontal skull and cranial ridges, overgrowth of the jaw with maxillary prognathism, widening the separation between the teeth.
Skin manifestations
The clinical manifestations of acromegaly include skin changes such as hyperhidrosis, oily skin, and unpleasant odor, which are due to the deposition of glycosaminoglycans.
Pigmented skin tags are common on the trunk, but it is unclear if GH / IGF -1 in excess to cause these changes in the skin, or arise as a consequence of insulin resistance and dyslipidemia. In patients with acromegaly develop severe nigricans, where the skin under the arms and the back of the neck become dark, soft and velvety with delicate folds and papillae. This phenomenon is caused by the increased amount of extracellular matrix of the skin, with edema. The skin microcirculation is impaired.
Cardiovascular manifestations
They occur in 60% of patients and has an involvement with hypertrophy of the heart that causes diastolic dysfunction and, subsequently, the failure of systole, coronary heart disease and valvular malfunction. This clinical picture is further compounded in case of hypertension, diabetes or exercise. It may have, also the change of atherosclerotic plaques.
You may create a vicious circle, since the high GH concentration alters the properties of insulin, increasing the severity of diabetes.
Respiratory manifestations
Acromegaly, modifying the structure of the skull, soft tissues such as the lining of the chest, causes problems with breathing. These failures can be summarized as sleep apnea and impaired respiratory function. In the first case, given the small amount of air inhaled, take the patient to snore and have excessive daytime sleepiness, and the second case, however, is due to the changes that have affected the device.
Endocrine manifestations
Endocrine manifestations may be different and may hit a certain percentage of patients: hyperprolactinemia caused by compression of the pituitary stalk (30%), hypopituitarism in 40% of patients, causes goiter and is caused by a compression of healthy tissue by the tumor; hypercalcemia, up to 77% of patients.
Gastrointestinal manifestations
In lower part of human body may develop polyps and carcinomas. The most frequent cancers are in colon, breast and prostate, the mechanisms leading to their development are not yet clear, but, is thought, to be caused to the large presence of hormones and diabetes. In addition, since the colon and gallbladder are very similar, there is the possibility of polyps at the level of gallbladder.
Osteoarticular manifestations
They are the most common symptoms of the disease, present in 70% of patients, as GH and IGF-1 promote the growth of articular cartilage, ligaments and also have the ability to stimulate osteoblasts. This uncontrolled increase swells joints, making them painful and limiting their ability to move. The carpal tunnel syndrome is due to the increase in fluid around the nerves that pass there. Edema, growing continuously, press more and more causing more pain. Finally, even the spine is subjected to change from one posture to incorrect.
Clinical Manifestations and Diagnosis of Acromegaly,2008
DIAGNOSIS
The diagnosis of acromegaly is made with two different methods , but related . It may also make a series of blood tests and, thereafter , the physician goes to check the level of circulating GH ; however, a single measurement does not suffice because the growth hormone is produced in waves and its concentration can vary all times. It thus tends to create the conditions under which , in the case of normality , the hormone GH should be inhibited . It is used as the oral glucose tolerance test (OGTT ): the patient should drink 75-100 grams of glucose solution than in healthy persons would lead to lower levels of growth hormone below the threshold of 1 ng / ml, if you are in the case of overproduction of GH, this test is bound to fail. It is also possible to search the levels of IGF - 1 which, being more stable throughout the day , is easier to indicate the presence of disease: if hormone levels are high, the patient is suffering from acromegaly . However, there are cases where the levels of IGF -1 are unpacked as in pregnant women (2-3 times higher than normal ) , in older people ( levels drop with age) , in individuals with diabetes or kidney or liver (IGF-1 very low).
The second method of diagnosis provides a further clarification : after acromegaly has been found through blood tests , it does make the patient a magnetic resonance imaging ( MRI) to see if the size of the pituitary tumor that creates this increased GH . In cases where patients can’t sustain a MRI is obvious to this problem with a CAT . It may present the cases in which the increase of GH is not caused by the pituitary , but from other tumors in the chest , abdomen, or pelvis . Their presence can be diagnosed by measuring GHRH hormone in the blood and a CAT scan to see their location .
Acromegaly is one of those diseases that if diagnosed and treated early in his course leaves no problem to the patient.
PATHOGENESIS
Acromegaly was described for the first time in 1886 and, as mentioned earlier, is caused by an increase of GH, with a consequent increase of IGF-1. This increase is created, for the 95% of cases by a pituitary tumor, very often a macroadenoma with a diameter greater than 1 cm. Depending on the location of the tumor can going to affect the surrounding brain structures. There are also cases in which the increase of GH is caused by non-pituitary tumors, but present in chest or pelvic area.
Acromegaly,2008
THERAPY
The goal of therapy against acromegaly is to normalize the secretion of hormones (GH and IGF-1), so that to reduce the symptoms and clinical signs of the disease. This should be achieved without affecting the function of the pituitary and without causing side effects.
As a first treatment in case of acromegaly is scheduled the surgery using the technique TSS. With an endoscope or a microscope, or both, the surgeon, passing from the nose and, later, through the sphenoid sinus, reach more easily pituitary gland and is thus able to export the tumor. If the tumor is small, the surgery succeeds more easily.
Endoscopic transsphenoidal surgery,2013
In case in which this technique fails is used to radiotherapy. Although its most effect may not last many years. Radiation therapy however may be detrimental to surrounding tissue to the tumor, and there are certain parameters that must be fulfilled (the tumor must be at least 5 mm from the optic chiasm). Another side effect is hypopituitarism.
At the same time it develops a drug therapy that aims to control the growth hormones in circulation. There are three different families:
- Somatostatin analogs. These drugs haven’t a long life and you need to inject them with an intramuscular injection once a month and are also active against non-pituitary tumors. They improve the clinical symptoms in 85% of patients, reduce the GH hormone circulating in 50-70% of cases and they regress the tumor. The best known of these is octreotide.
- The dopamine agonists. They have much milder effects, normalizing the effects of IGF-1 in a minority of patients and not reducing pituitary tumors. Among them is bromocriptine.
- GH receptor antagonists. These drugs normalize the levels of IGF-1, but not those of GH. They are taken by injection once a day. They are still under study.
How effective are current therapies for acromegaly?, 2003
Treatment of acromegaly with octreotide, a synthetic analog of somatostatin with extended action,1990
[The images have been taken from sites of public broadcasting]
