Acromegaly is a disorder caused by excessive production of growth hormone from the anterior pituitary gland, resulting in excessive growth of body tissues and other metabolic dysfunctions. Adult patients with acromegaly have the characteristic facial features of a large lower jaw, prominent forehead, and large hands and feet. This takes place after the growth plates are fused, distinguishing acromegaly from gigantism which occurs before fusion of growth plates.
Despite the slow growth, acromegaly is a life-threatening condition for which there is no cure, but with present-day treatment, most patients can have a good quality of life.
Pituitary Tumor: In more than 95% of cases, the excessive growth hormone is caused by a pituitary tumor, usually a benign microadenoma of the pituitary gland.
Non-Pituitary Tumor: Tumors of the adrenals, lungs, and pancreas are implicated in a few cases. These tumors secrete growth hormone or growth hormone releasing Hormone (GH-RH).
Elevated levels of growth hormone stimulate the liver to produce Insulin-like growth factor-1 (IGF-1). Elevated levels of Insulin-like growth factor-1 stimulate the excessive growth of body tissues.
In about 95% of cases, acromegaly is associated with a pituitary microadenoma, while the remaining 5% are from non-pituitary ectopic sources of growth hormone or GH-RH. The common effect of the abnormal rise in growth hormone is the production of Insulin-like growth factor-1 (IGF-1) from the liver. The effect of IGF-1 on body tissues results in the multisystemic manifestation of acromegaly. IGF-1 also known as Somatomedin C is encoded by the IGF-1 gene on chromosome 12q23.2.
The pathologic effect of IGF-1 after fusion of the growth plates resulting in the acral growth spurts manifested as large hands and feet and a prominent jaw and forehead. It is clearly different from the linear size increase that occurs in gigantism in which the effect of elevated IGF-1 occurs before the closure of the growth plate.
Acromegaly leads to elevated IGF-1 that affects the following pathways of metabolism:
IGF-1 is an insulin-like protein produced majorly in the liver. It is a single chain of 70 amino acids and three disulfide bridges with a molecular weight of approximately eight kilodaltons. IGF-1 level peaks around puberty, with low levels at extreme ages.
Synthetic IGF-1 analog is used in the treatment of growth disorders, for example, dwarfism.
IGF-1 almost always exists in the bound form. It is bound by the IGF-binding proteins (IGF-BPs), and the most abundant of them is IGFBP-3.
Nutrition also plays some role, as high protein intake tends to increase growth hormone and IGF-1 levels.
Acromegaly is usually a slow progressing disorder, with onset usually in the third or fourth decade of life. The presenting complaints include the following:
Signs upon physical examination include the following:
Visual field examination
GH suppression test:
Growth Hormone Releasing Hormone (GHRH) Levels
Skull x-ray: thickened calvaria, enlarged sella, long and thick mandibles, exaggerated ridges, dilated sinuses
Chest x-ray: barrel rib cage with long ribs
Hand x-ray: cortical thickening, ungal tufting, wide distal phalangeal bases, osteophytes, and soft tissue hypertrophy
Minoxidil use has been associated with a condition characterized by facial features of acromegaly, but with normal growth hormone and IGF-1 blood levels. This condition is known as pseudoacromegaly.
Acromegaly is not a common disorder in North America, but when it presents, it is associated with very high morbidity and mortality rates. Because the presentation of acromegaly is systemic, an interprofessional team approach is necessary. There is no cure for acromegaly and the current treatments only manage the symptoms.
In particular, a cardiologist, oncologist, neurologist, and a pulmonologist should be involved as the disorder is associated with malignancies, adverse cardiac, CNS and pulmonary events.
The nurse practitioner should ensure that the patients are not showing signs of hypopituitarism after treatment and during followup appointments and report to the clinician as concerns arise. Levels of GH and IGF need to be monitored for life. Because of the risk of cancer, these patients should be referred to the appropriate specialist on a timely basis. Patients need to be educated about the importance of follow up because the morbidity from cardiac and respiratory complications are very high. Because of joint dysfunction, early physical therapy is recommended. Many of these individuals are not gainfully employed and thus social work should be involved in helping to manage their financial status. Due to the challenges of managing medical therapy, a pharmacist should be involved in assisting in drug reconciliation and evaluating for toxicity. Any concerns should be reported to the clinical team. [Level V]
The mortality rates of patients with acromegaly are 3 times the general population, with most dying from respiratory and cardiac complications. These patients also develop several types of tumors including prostatic hypertrophy, uterine myomas, and skin tags. The overall outcome depends on whether the cause of acromegaly can be treated. even after surgical removal of a pituitary tumor, some patients may need treatment as a result of residual disease. The quality of life in these patients is poor. Thus, it is also important not to subject these patients to unnecessary procedures, when medical treatment will suffice. The goal is not to harm the patient.
|||Drewes AM,Arlien-Søborg MC,Lunde Jørgensen JO,Jensen MP, [Acromegaly and symptoms of the motor apparatus]. Ugeskrift for laeger. 2018 Nov 12 [PubMed PMID: 30417820]|
|||Pazarlı AC,Köseoğlu Hİ,Kutlutürk F,Gökçe E, Association of Acromegaly and Central Sleep Apnea Syndrome. Turkish thoracic journal. 2017 Nov 29 [PubMed PMID: 30407161]|
|||Postma MR,Wolters TL,van den Berg G,van Herwaarden AE,Muller-Kobold A,Sluiter WJ,Wagenmakers MA,van den Bergh ACM,Wolffenbuttel BHR,Hermus A,Netea-Maier R,van Beek AP, Postoperative use of somatostatin analogs and mortality in patients with acromegaly. European journal of endocrinology. 2018 Oct 1 [PubMed PMID: 30400068]|
|||Matyjaszek-Matuszek B,Obel E,Lewicki M,Kowalczyk-Bołtuć J,Smoleń A, Prevalence of neoplasms in patients with acromegaly - the need for a national registry. Annals of agricultural and environmental medicine : AAEM. 2018 Sep 25 [PubMed PMID: 30260174]|
|||Sharma AN,Tan M,Amsterdam EA,Singh GD, Acromegalic cardiomyopathy: Epidemiology, diagnosis, and management. Clinical cardiology. 2018 Mar [PubMed PMID: 29574794]|
|||Pasupulati AK,Menon RK, Growth hormone and chronic kidney disease. Current opinion in nephrology and hypertension. 2018 Nov 1 [PubMed PMID: 30394899]|
|||Buchman M,Bell S,Kopchick JJ, Growth Hormone Discovery and Structure. Pediatric endocrinology reviews : PER. 2018 Sep [PubMed PMID: 30378777]|
|||Granada ML, Biochemical following-up of treated acromegaly. Limitations of the current determinations of IGF-1 and perspective. Minerva endocrinologica. 2018 Oct 10 [PubMed PMID: 30311754]|
|||Leonart LP,Borba HHL,Ferreira VL,Riveros BS,Pontarolo R, Cost-effectiveness of acromegaly treatments: a systematic review. Pituitary. 2018 Dec [PubMed PMID: 30159696]|
|||Ahmad MM,Buhary BM,Al Mousawi F,Alshahrani F,Brema I,Al Dahmani KM,Beshyah SA,AlMalki MH, Management of acromegaly: an exploratory survey of physicians from the Middle East and North Africa. Hormones (Athens, Greece). 2018 Sep [PubMed PMID: 29971605]|
|||Buchfelder M,van der Lely AJ,Biller BMK,Webb SM,Brue T,Strasburger CJ,Ghigo E,Camacho-Hubner C,Pan K,Lavenberg J,Jonsson P,Hey-Hadavi JH, Long-term treatment with pegvisomant: observations from 2090 acromegaly patients in ACROSTUDY European journal of endocrinology. 2018 Oct 1 [PubMed PMID: 30325178]|
|||He W,Yan L,Wang M,Li Q,He M,Ma Z,Ye Z,Zhang Q,Zhang Y,Qiao N,Lu Y,Ye H,Lu B,Shou X,Zhao Y,Li Y,Li S,Zhang Z,Shen M,Wang Y, Surgical outcomes and predictors of glucose metabolism alterations for growth hormone-secreting pituitary adenomas: a hospital-based study of 151 cases. Endocrine. 2018 Sep 20 [PubMed PMID: 30238327]|
|||Rick J,Jahangiri A,Flanigan PM,Chandra A,Kunwar S,Blevins L,Aghi MK, Growth hormone and prolactin-staining tumors causing acromegaly: a retrospective review of clinical presentations and surgical outcomes. Journal of neurosurgery. 2018 Sep 14 [PubMed PMID: 30215558]|