Acromegaly: Causes, Diagnosis, Signs, and Treatment

Introduction 

Acromegaly is a rare hormonal disorder that comes about when the pituitary hormone malfunctions to produce excessive growth hormone during adulthood. The effect on the body is that the bones markedly increase in size including those on the feet, face, and hands. Acromegaly is a severe disease that is normally diagnosed late, and its rates of morbidity and mortality are high given that it is closely associated with other pathologies such as cerebrovascular, cardiovascular, and respiratory malignancies. Most people are diagnosed with the disease at the age of between 30 and 50, but it can attack people at any particular age. When the disease develops in a person before puberty, it is referred to as gigantism. The discussion will analyze the etiology, diagnosis, signs and symptoms, and treatment of the disease. 

Etiology 

In 99% of the cases, Acromegaly is as a result of an adenoma of the pituitary somatotroph. In about 25%-30% of the patients, prolactin is also co-secreted by either a combined effect of somatotroph tumor and mixed lactotroph or a mammosomatotroph tumor. The somatotroph hyperplasia associated with Acromegaly patients occurs due to neuroendocrine tumors that lead to the overproduction of the growth hormone-releasing hormone (GHRH). One major cause of the overproduction of the growth hormone is the pituitary adenoma. A close analysis of the X chromosome has postulated that the pituitary adenomas have an origin that is monoclonal. Therefore, this means that tumors in the pituitary are as a result of the proliferation of a single cell. The disease begins with the activation of mutation in GNAS1 gene, which subsequently leads to the activation of the GHRH receptors. The resultant effect is the activation of what is known as the adenylyl cyclase which leads to the proliferation of the somatotroph and finally the hypersecretion of the growth hormone. 

Diagnosis 

Laboratory Diagnosis 

The diagnosis of Acromegaly requires two important tests, one to check to assess the insulin-like growth factor-1 (IGF-1) level and secondly oral glucose tolerances test (OGTT). The IGF-1 hormone is closely related to the growth hormone. The growth hormone instructs the body to make IGF-1 which thereafter causes tissue growth in the body. In a normal person, high IGF-1 levels in the body signal the body to stop producing the growth hormone. However, the case is different for a person with Acromegaly as the body continues with the production of the growth hormone regardless of the amounts of IGF-1 levels. Blood tests are therefore taken to measure the IGF-1 levels because their levels are much constant throughout the day as opposed to the GH levels. When the levels of IGF-1 are found to be elevated, then this might be a sign of Acromegaly. 

Another important laboratory test to diagnose Acromegaly is the OGTT. This is because there is a close connection between the levels of blood glucose and growth hormone ( Ribeiro-Oliveira & Barkan, 2012). In people suffering from Acromegaly, high blood glucose levels will initiate the body to stop secreting the growth hormone. Therefore, the doctor will deliberately raise the patient's blood sugar levels using the OGTT and thereafter monitor how the growth hormone responds. The patient will be made to drink a glucose solution, and the doctor will measure the glucose levels after every 30 minutes for 2 hours. If the growth hormone levels fail to drop below the 1ng/ml mark during the cause of the test, then there is a high likelihood that the person is suffering from Acromegaly. Naturally, an increase in the glucose levels in the body should result in the dropping of the growth hormone levels. So if this does not happen, it means that the body has failed to respond to its signals hence predicting the interruption of the body’s endocrine system. Other hormones that can be tested in the blood include the GHRH and testosterone hormones. 

Radiology Tests 

A majority of the Acromegaly disorders are caused due to the malfunctioning of the pituitary tumor. The doctor will, therefore, request a magnetic resonance imaging (MRI) scan to be done on the pituitary gland. The imaging will reveal to the doctor the position of the tumor and the possible size. If the doctor cannot see the tumor, then the likelihood is that the patient is suffering from a rare form of Acromegaly that is as a result of a non-pituitary tumor. A computerized tomography (CT) test can also be employed to locate the possible sites of the tumor. The possible locations for the CT scan include the abdomen and the chest. 

Signs and Symptoms of Acromegaly 

According to Krysiak et al . (2012), the most common signs of the disease include the enlargement of hands and feet. The shape of the face might begin to distort with the protrusion of the lower jaw and the enlargement of the nose. The lips may also begin to thicken, and wider spaces between the teeth may also develop. The symptoms of the disease progress at a slow rate and hence it can only be noticed after several years. Other common symptoms associated with the disease include thickened, oily, and coarse skin, excessive sweating and the development of body odor, and fatigue. Muscle weakness, impaired vision, headaches, enlarged tongue, erectile dysfunction, and menstrual cycle irregularities may also follow. Lugo et al . (2012) asserted that major complications could also arise from the disease. They include high blood pressure, diabetes mellitus, goiter, precancerous growths, uterine fibroids, compressions of the spinal code, and loss of vision. Early treatment can prevent the onset of the complications. 

Acromegaly vs. Gigantism 

Acromegaly and gigantism are two disorders with a similar disease mechanism and presentations but have different outcomes because of the difference in the age of onset. Acromegaly begins after puberty while gigantism, on the other hand, begins at childhood as asserted by Rostomyan et al . (2015). Both the two conditions have a majority of similar presentations that might include a headache, visual disturbances, and excessive sweating among others. Most of the methods used for diagnosis are similar in both cases. However, certain differences might be noticed between the two diseases. Acromegaly, as stated earlier, begins in puberty while gigantism begins in childhood. Whereas Acromegaly is a common disease, gigantism is a rare disease which has only seen 100 cases reported so far. Acromegaly has a relatively higher mortality rate in comparison to gigantism. Gigantism has been postulated to begin anytime before the epiphyseal fusion while Acromegaly begins at around the third decade of life. Regarding the presentation, gigantism may feature excessive tallness while Acromegaly may be depicted by an excessive growth of the finger ends, lower jaw, and the tongue. 

Treatment 

The treatment initiatives target the symptoms that are presented in an individual. In most cases, the treatment requires a coordinated team of specialists. Chanson and Kamenický (2012) asserted that the interventions aim to return the functioning of the growth hormone levels to normal. Giustina et al . (2014) believe that focus is also geared towards reducing the size of the pituitary adenoma hence relieving pressure on the nearby tissues hence restoring normal pituitary function. The treatment mechanism for Acromegaly involves surgery, radiation therapy, and medications. Each patient might require a medical intervention that is different from the other depending on signs and symptoms, age, general health, size and location of the pituitary adenoma among others. The mode of intervention chosen should be decided by the medical team in association with the patient and also in consideration of factors such as the side-effects and long-term effects. 

Transsphenoidal surgery is a treatment intervention for Acromegaly where part or the entire tumor is removed. The removal of the therapy can result in therapeutic responses such as relieving pressure on the surrounding tissues and also lowering the growth hormone levels. Medications might also be prescribed to treat individual presentation of Acromegaly. The three classes of medications used in treatment include somatostatin analogs, receptor antagonists, and dopamine antagonists. According to Robbins (2012), the Food and Drug Association (FDA) has also approved certain drugs that can be used in the treatment of Acromegaly including pasireotide and octreotide acetate. In case surgery has failed to reduce the size of the tumor sufficiently, then the third method of intervention which is radiation therapy can be used. 

Genetic component of Acromegaly 

Acromegaly is not a genetic disease, but certain explanations have been postulated to show genetic implications in the disease. In about 5% of the cases, that mostly includes the young; Acromegaly is as a result of a genetic defect ( Hannah-Shmouni et al . 2016). The genetic defects target the pituitary glands hence activating the oncogenes which subsequently result in overproliferation of the glands and the overproduction of the growth hormone. Other types of mutations such as the X-linked acro gigantism which is a result of a genomic duplication known as Xq26.3 can also result in Acromegaly ( Trivellin et al . 2014). 

Conclusion 

In conclusion, Acromegaly is a hormonal disorder that mainly affects the proper function of the pituitary gland leading to over production of the growth hormone. The subsequent effect is the enlargement of the limbs, face, and the tongue. It is diagnosed in the laboratory through tests such as OGTT and IGF-1 and imaging tests such as MRI and CT scan. Treatment can be done by medication, surgery or use of radiation. 

References 

Chanson, P., & Kamenický, P. (2012, April). Treatment of acromegaly: a critical analysis of the last ten years. In Annales d'endocrinologie (Vol. 73, No. 2, pp. 99-106). 

Giustina, A., Chanson, P., Kleinberg, D., Bronstein, M. D., Clemmons, D. R., Klibanski, A., ... & Casanueva, F. F. (2014). Expert consensus document: a consensus on the medical treatment of acromegaly. Nature Reviews Endocrinology , 10 (4), 243-248. 

Hannah-Shmouni, F., Trivellin, G., & Stratakis, C. A. (2016). Genetics of gigantism and acromegaly. Growth Hormone & IGF Research , 30 , 37-41. 

Krysiak, R., Okopień, B., & Marek, B. (2012). Current views on etiology, pathophysiology and clinical manifestations of acromegaly. Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego , 32 (188), 123-128. 

Lugo, G., Pena, L., & Cordido, F. (2012). Clinical manifestations and diagnosis of acromegaly. International Journal of Endocrinology , 2012 . 

Ribeiro-Oliveira Jr, A., & Barkan, A. (2012). The changing face of acromegaly—advances in diagnosis and treatment. Nature Reviews Endocrinology , 8 (10), 605-611. 

Robbins, R. J. (2012). Acromegaly: a century of scientific and clinical progress . Springer Science & Business Media. 

Rostomyan, L., Daly, A. F., Petrossians, P., Nachev, E., Lila, A. R., Lecoq, A. L., ... & Holdaway, I. (2015). Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients. Endocrine-related cancer , 22 (5), 745-757. 

Trivellin, G., Daly, A. F., Faucz, F. R., Yuan, B., Rostomyan, L., Larco, D. O., ... & Castermans, E. (2014). Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation. New England Journal of Medicine , 371 (25), 2363-2374.