Acromegaly

Acromegaly is characterized by excessive secretion of growth hormone, usually caused by a somatotroph pituitary adenoma.

The incidence rate of this disease is defined as approximately 0 / 100.000.

Presentation

The diagnosis of acromegaly is frequently delayed due to the slow progression of signs and symptoms. Patients with large tumors may experience symptoms due to the local mass effects of the pituitary lesion. These include headaches, visual abnormalities, typically bitemporal hemianopsia, and cranial nerve palsies. Hypersecretion of prolactin occurs if its inhibitory feedback from the hypothalamus is disturbed. Pituitary adenomas may also result in decreased secretion of other hormones by the pituitary gland.

Oversecretion of GH and IGF-1 causes acral and soft tissue overgrowth with skin thickening and organomegaly leading to arthritis, abnormal development of facial features, diabetes mellitus, hypertension and other cardiovascular diseases, carpal tunnel syndrome, obstructive sleep apnea, and various other symptoms. Patients present with increased foot size due to abnormal development of feet and increased ring size due to excessive fingers growth. Hyperhidrosis may also occur. Increased urinary secretion of calcium and phosphate is also associated with acromegaly.

Workup

Measurement of:

  • GH
  • GHRH
  • TRH
  • Oral glucose
  • IGF-1
  • Prolactin

Imaging studies include MRI, CT scanning and radiography. Radiography reveals increase in length and thickness of certain bones like mandible and ribs. Mainly membranous bones are increased in size in radiographs of acromegalic patients. Increased cartilage growth is also evident. Histological findings are also important diagnostic tool and reveal different types of tumors in acromegaly.

Treatment

Acromegaly can be treated surgically as well as by medications. Surgical removal of adenomas is quite successful nowadays [11] [12]. If surgery is not successful regarding GH hypersecretion then radiation therapy is used. Medications include mostly analogues of somatostatin like octreotide, which decrease the secretion of growth hormones and IGF-1, because somatostatin has an inhibitory effect on GH [13]. Dopamine agonists like bromocriptine are also employed as a pharmacological treatment because they bind to dopamine type 2 receptors in the pituitary gland and cause depressed secretion of GH [14].

Transsphenoidal surgery is used to completely remove the tumor. It is an efficient procedure and uses nasal approach to remove the tumor. After treatment, patients should be monitored throughout their life for their GH and IGF-1 levels. Also, patients should be evaluated for severe GH deficiency after surgery [15].

Prognosis

Mortality and morbidity rates are increased in acromegaly. Increased secretion of GH and IGF-1 has somatic and metabolic effects affecting all organ systems and patients may develop sleep apnea, hypertension, cardiomyopathy, nerve root compression, carpal tunnel syndrome, diabetes mellitus, and various other cerebrovascular, cardiovascular, and respiratory disorders [10]. In addition, the pituitary lesion may cause symptoms including headache and visual field defects. Early diagnosis and management of complications improves the long-term outcome [10].

Etiology

Acromegaly is caused by:

  • Increased secretion of growth hormone (GH) caused by pituitary adenomas in most cases.
  • Hypothalamic tumors which result in increased secretion of growth hormone releasing hormone (GHRH).
  • IGF-1 (insulin-like growth factor 1) oversecretion, which is a growth regulating substance produced by the liver under the effect of growth hormone [2].
  • In some instances, tumors of the adrenal glands or lungs may cause ectopic secretion of GH, rarely of GHRH.

Epidemiology

The prevalence of acromegaly in Europe has been reported to be 30-70:1,000,000 [3] [4], however, recent studies observed higher numbers [4] [5] [6]. Acromegaly affects both males and females equally. The mean age for diagnosis is 40 years in males and 45 years in females.

Sex distribution
Age distribution

Pathophysiology

Growth hormone, which is released by the adenohypophysis, is regulated by the hypothalamus through growth hormone releasing hormone and somatostatin. GH exhibits its regulatory effects by insulin-like growth factor I, which is produced by the liver under the influence of GH. Most cases of acromegaly are caused by pituitary adenomas, resulting in increased secretion of GH and insulin-like growth factor I subsequently. Both cause increased growth of soft tissues, bones and viscera. Because somatostatin decreases the secretion of GH, drugs mimicking the actions of somatostatin are given to acromegalic patients to decrease GH.

Extrapituitary tumours including neuroendocrine tumors are rare causes and may also increase the secretion of GH in the same way and causing the same results [7] [8] [9]. Tumors associated with GHRH production such intracranial gangliocytomas and disruption of the somatostatin feedback pathway also lead to acromegaly.

Prevention

Acromegaly can not be prevented. Early diagnosis should is important to avoid severe complications.

Summary

Acromegaly is most often caused by adenomas of the pituitary gland. If the tumour occurs before puberty, linear growth increases, a condition known as pituitary gigantism. After adolescence, when the fusion of the epiphyseal growth plates has occured, acromegaly develops. The disorder causes acral and soft tissue overgrowth, characterized by markedly increased growth of hands and feet. Also, bones and viscera increase in size including nose, cranium, supraorbital ridges, forehead and vertebrae, causing symptoms such as macrognathia, kyphosis, goiter and left ventricular hypertrophy [1].

Patient Information

Definition

Acromegaly is usually caused by a tumor of the pituitary gland which results in increased growth hormone secretion. This leads to secondary effects due to growth hormone overproduction.

Cause

The common cause of acromegaly is a pituitary adenoma that causes increased growth hormone (GH) and subsequent insulin-like growth factor 1 (IGF-1) secretion.

Signs and symptoms

The symptoms by which the acromegaly patient can be recognized are increased bone growth, hunched back, increased blood pressure, protrusion of jaw and forehead and increased growth of extremities.

Diagnosis

Diagnosis is made by measuring levels of GH and IGF-1 in the blood. Also radiographic and other imaging techniques are used.

Treatment

Acromegaly can be treated medically as well as surgically. Medical treatment is by use of somatostatin analogues, dopamine agonists and growth hormone antagonists. Radiation is also used.

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References

  1. Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva FF, et al. A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab. Jul 2010;95(7):3141-8.
  2. Soares BS, Eguchi K, Frohman LA. Tumor deletion mapping on chromosome 11q13 in eight families with isolated familial somatotropinoma and in 15 sporadic somatotropinomas. J Clin Endocrinol Metab. Dec 2005;90(12):6580-7.
  3. Bengtsson BA, Edén S, Ernest I, et al. Epidemiology and long-term survival in acromegaly. A study of 166 cases diagnosed between 1955 and 1984. Acta Med Scand 1988; 223:327.
  4. Ribeiro-Oliveira A Jr, Barkan A. The changing face of acromegaly--advances in diagnosis and treatment. Nat Rev Endocrinol 2012; 8:605.
  5. Fernandez A, Karavitaki N, Wass JA. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf) 2010; 72:377.
  6. Daly AF, Rixhon M, Adam C, et al. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab 2006; 91:4769.
  7. Melmed S, Ezrin C, Kovacs K, et al. Acromegaly due to secretion of growth hormone by an ectopic pancreatic islet-cell tumor. N Engl J Med 1985; 312:9.
  8. Beuschlein F, Strasburger CJ, Siegerstetter V, et al. Acromegaly caused by secretion of growth hormone by a non-Hodgkin's lymphoma. N Engl J Med 2000; 342:1871.
  9. Altstadt TJ, Azzarelli B, Bevering C, et al. Acromegaly caused by a growth hormone-releasing hormone-secreting carcinoid tumor: case report. Neurosurgery 2002; 50:1356.
  10. Melmed S, Casanueva FF, Klibanski A, Bronstein MD, Chanson P, Lamberts SW, et al. A consensus on the diagnosis and treatment of acromegaly complications. Pituitary. 2013 Sep. 16(3):294-302.
  11. Ross DA, Wilson CB. Results of transsphenoidal microsurgery for growth hormone-secreting pituitary adenoma in a series of 214 patients. J Neurosurg 1988; 68:854.
  12. Fahlbusch R, Honegger J, Buchfelder M. Surgical management of acromegaly. Endocrinol Metab Clin North Am 1992; 21:669.
  13. Shimon I, Yan X, Taylor JE, et al. Somatostatin receptor (SSTR) subtype-selective analogues differentially suppress in vitro growth hormone and prolactin in human pituitary adenomas. Novel potential therapy for functional pituitary tumors. J Clin Invest 1997; 100:2386.
  14. Sandret L, Maison P, Chanson P. Place of cabergoline in acromegaly: a meta-analysis. J Clin Endocrinol Metab. 2011 May. 96(5):1327-35.
  15. Ronchi CL, Giavoli C, Ferrante E, et al. Prevalence of GH deficiency in cured acromegalic patients: impact of different previous treatments. Eur J Endocrinol 2009; 161:37.

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