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Mayo Clinic Proceedings Feb 2022Acromegaly is typically caused by a growth hormone-secreting pituitary adenoma, driving excess secretion of insulin-like growth factor 1. Acromegaly may result in a... (Review)
Review
Acromegaly is typically caused by a growth hormone-secreting pituitary adenoma, driving excess secretion of insulin-like growth factor 1. Acromegaly may result in a variety of cardiovascular, respiratory, endocrine, metabolic, musculoskeletal, and neoplastic comorbidities. Early diagnosis and adequate treatment are essential to mitigate excess mortality associated with acromegaly. PubMed searches were conducted using the keywords growth hormone, acromegaly, pituitary adenoma, diagnosis, treatment, pituitary surgery, medical therapy, and radiation therapy (between 1981 and 2021). The diagnosis of acromegaly is confirmed on biochemical grounds, including elevated serum insulin-like growth factor 1 and lack of growth hormone suppression after glucose administration. Pituitary magnetic resonance imaging is advised in patients with acromegaly to identify an underlying pituitary adenoma. Transsphenoidal pituitary surgery is generally first-line therapy for patients with acromegaly. However, patients with larger and invasive tumors (macroadenomas) are often not in remission postoperatively. Medical therapies, including somatostatin receptor ligands, cabergoline, and pegvisomant, can be recommended to patients with persistent disease after surgery. Select patients may also be candidates for preoperative medical therapy. In addition, primary medical therapy has a role for patients without mass effect on the optic chiasm who are unlikely to be cured by surgery. Clinical, endocrine, imaging, histologic, and molecular markers may help predict the response to medical therapy; however, confirmation in prospective studies is needed. Radiation therapy is usually a third-line option and is increasingly administered by a variety of stereotactic techniques. An improved understanding of the pathogenesis of acromegaly may ultimately lead to the design of novel, efficacious therapies for this serious condition.
Topics: Acromegaly; Cardiovascular Diseases; Growth Hormone-Secreting Pituitary Adenoma; Hormone Antagonists; Human Growth Hormone; Humans
PubMed: 35120696
DOI: 10.1016/j.mayocp.2021.11.007 -
The Lancet. Diabetes & Endocrinology Nov 2022Growth hormone-secreting pituitary adenomas that cause acromegaly arise as monoclonal expansions of differentiated somatotroph cells and are usually sporadic. They are... (Review)
Review
Growth hormone-secreting pituitary adenomas that cause acromegaly arise as monoclonal expansions of differentiated somatotroph cells and are usually sporadic. They are almost invariably benign, yet they can be locally invasive and show progressive growth despite treatment. Persistent excess of both growth hormone and its target hormone insulin-like growth factor 1 (IGF-1) results in a wide array of cardiovascular, respiratory, metabolic, musculoskeletal, neurological, and neoplastic comorbidities that might not be reversible with disease control. Normalisation of IGF-1 and growth hormone are the primary therapeutic aims; additional treatment goals include tumour shrinkage, relieving symptoms, managing complications, reducing excess morbidity, and improving quality of life. A multimodal approach with surgery, medical therapy, and (more rarely) radiation therapy is required to achieve these goals. In this Review, we examine the epidemiology, pathogenesis, diagnosis, complications, and treatment of acromegaly, with an emphasis on the importance of tailoring management strategies to each patient to optimise outcomes.
Topics: Humans; Acromegaly; Insulin-Like Growth Factor I; Quality of Life; Human Growth Hormone; Growth Hormone; Adenoma
PubMed: 36209758
DOI: 10.1016/S2213-8587(22)00244-3 -
Orphanet Journal of Rare Diseases Jun 2008Acromegaly is an acquired disorder related to excessive production of growth hormone (GH) and characterized by progressive somatic disfigurement (mainly involving the... (Review)
Review
Acromegaly is an acquired disorder related to excessive production of growth hormone (GH) and characterized by progressive somatic disfigurement (mainly involving the face and extremities) and systemic manifestations. The prevalence is estimated at 1:140,000-250,000. It is most often diagnosed in middle-aged adults (average age 40 years, men and women equally affected). Due to insidious onset and slow progression, acromegaly is often diagnosed four to more than ten years after its onset. The main clinical features are broadened extremities (hands and feet), widened thickened and stubby fingers, and thickened soft tissue. The facial aspect is characteristic and includes a widened and thickened nose, prominent cheekbones, forehead bulges, thick lips and marked facial lines. The forehead and overlying skin is thickened, sometimes leading to frontal bossing. There is a tendency towards mandibular overgrowth with prognathism, maxillary widening, tooth separation and jaw malocclusion. The disease also has rheumatologic, cardiovascular, respiratory and metabolic consequences which determine its prognosis. In the majority of cases, acromegaly is related to a pituitary adenoma, either purely GH-secreting (60%) or mixed. In very rare cases, acromegaly is due to ectopic secretion of growth-hormone-releasing hormone (GHRH) responsible for pituitary hyperplasia. The clinical diagnosis is confirmed biochemically by an increased serum GH concentration following an oral glucose tolerance test (OGTT) and by detection of increased levels of insulin-like growth factor-I (IGF-I). Assessment of tumor volume and extension is based on imaging studies. Echocardiography and sleep apnea testing are used to determine the clinical impact of acromegaly. Treatment is aimed at correcting (or preventing) tumor compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. Transsphenoidal surgery is often the first-line treatment. When surgery fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogs and/or radiotherapy can be used. The GH antagonist (pegvisomant) is used in patients that are resistant to somatostatin analogs. Adequate hormonal disease control is achieved in most cases, allowing a life expectancy similar to that of the general population. However, even if patients are cured or well-controlled, sequelae (joint pain, deformities and altered quality of life) often remain.
Topics: Acromegaly; Adult; Female; Human Growth Hormone; Humans; Male; Middle Aged; Pituitary Neoplasms; Prevalence; Radiography
PubMed: 18578866
DOI: 10.1186/1750-1172-3-17 -
The Journal of Clinical Endocrinology... Apr 2020The aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013.
OBJECTIVE
The aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013.
PARTICIPANTS
The Consensus Group, convened by 11 Steering Committee members, consisted of 45 experts in the medical and surgical management of acromegaly. The authors received no corporate funding or remuneration.
EVIDENCE
This evidence-based consensus was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence following critical discussion of the current literature on the diagnosis and treatment of acromegaly comorbidities.
CONSENSUS PROCESS
Acromegaly Consensus Group participants conducted comprehensive literature searches for English-language papers on selected topics, reviewed brief presentations on each topic, and discussed current practice and recommendations in breakout groups. Consensus recommendations were developed based on all presentations and discussions. Members of the Scientific Committee graded the quality of the supporting evidence and the consensus recommendations using the GRADE system.
CONCLUSIONS
Evidence-based approach consensus recommendations address important clinical issues regarding multidisciplinary management of acromegaly-related cardiovascular, endocrine, metabolic, and oncologic comorbidities, sleep apnea, and bone and joint disorders and their sequelae, as well as their effects on quality of life and mortality.
Topics: Acromegaly; Comorbidity; Consensus; Humans; Practice Guidelines as Topic; Quality of Life
PubMed: 31606735
DOI: 10.1210/clinem/dgz096 -
The Journal of Clinical Investigation Nov 2009Dysregulated growth hormone (GH) hypersecretion is usually caused by a GH-secreting pituitary adenoma and leads to acromegaly - a disorder of disproportionate skeletal,... (Review)
Review
Dysregulated growth hormone (GH) hypersecretion is usually caused by a GH-secreting pituitary adenoma and leads to acromegaly - a disorder of disproportionate skeletal, tissue, and organ growth. High GH and IGF1 levels lead to comorbidities including arthritis, facial changes, prognathism, and glucose intolerance. If the condition is untreated, enhanced mortality due to cardiovascular, cerebrovascular, and pulmonary dysfunction is associated with a 30% decrease in life span. This Review discusses acromegaly pathogenesis and management options. The latter include surgery, radiation, and use of novel medications. Somatostatin receptor (SSTR) ligands inhibit GH release, control tumor growth, and attenuate peripheral GH action, while GH receptor antagonists block GH action and effectively lower IGF1 levels. Novel peptides, including SSTR ligands, exhibiting polyreceptor subtype affinities and chimeric dopaminergic-somatostatinergic properties are currently in clinical trials. Effective control of GH and IGF1 hypersecretion and ablation or stabilization of the pituitary tumor mass lead to improved comorbidities and lowering of mortality rates for this hormonal disorder.
Topics: Acromegaly; Animals; Growth Hormone; Growth Hormone-Secreting Pituitary Adenoma; Humans; Insulin-Like Growth Factor I; Morbidity; Signal Transduction
PubMed: 19884662
DOI: 10.1172/JCI39375 -
Archives of Medical Research Dec 2023Acromegaly is a chronic and rare disease. The diagnosis usually takes several years. Multiple comorbidities are associated with acromegaly. Long-term exposure to growth... (Review)
Review
Acromegaly is a chronic and rare disease. The diagnosis usually takes several years. Multiple comorbidities are associated with acromegaly. Long-term exposure to growth factors may lead to complications such as the development of benign or malignant tumors. However, the association between acromegaly and cancer remains a matter of debate due to multiple limitations in epidemiological data. There is controversy between acromegaly and mortality, but evidence shows a significant improvement in mortality rates with disease control and careful management of comorbidities. Older age, increased growth hormone levels (GH) at last follow-up, higher insulin-like growth factor-1 (IGF-1) levels at diagnosis, malignancy and radiotherapy were proposed as independent predictors of mortality. In this review we summarize the current state of knowledge in this field. Incidence of different cancer types is described. Rigorous surveillance of endocrine diseases may contribute to increased tumor detection. Personalized screening should probably be recommended.
Topics: Humans; Acromegaly; Neoplasms; Comorbidity; Insulin-Like Growth Factor I; Incidence
PubMed: 38007382
DOI: 10.1016/j.arcmed.2023.102914 -
Endocrine Apr 2020Acromegaly is a rare disease characterized by a chronic exposition to growth hormone (GH) and insulin-like growth factor-1 (IGF-1), caused in most cases by a pituitary... (Review)
Review
BACKGROUND
Acromegaly is a rare disease characterized by a chronic exposition to growth hormone (GH) and insulin-like growth factor-1 (IGF-1), caused in most cases by a pituitary GH-secreting adenoma. Chronic GH excess induces systemic complications (metabolic, cardiovascular, respiratory, neoplastic, and musculoskeletal) and increased mortality if not appropriately treated. Recent epidemiological data report an improved life span of patients with acromegaly probably due to better acromegaly management; additionally, the number of pituitary incidentaloma in general population also increased over time due to more frequent imaging. Therefore, the number of elderly patients, newly diagnosed with acromegaly or in follow-up, is expected to grow in the coming years and clinicians will need to be aware of particularities in managing these patients.
PURPOSE
This review aims to explore different aspects of acromegaly of the elderly patients, focusing on epidemiology, diagnosis, clinical presentation, complications, and management options.
METHODS
Available literature has been assessed through PubMed (data until August 2019) by specific keywords.
CONCLUSIONS
Available data on acromegaly in the elderly patient are sparse, but point to important differences. Further studies are needed comparing elderly with younger patients with acromegaly to better define a tailored diagnostic and therapeutic management.
Topics: Acromegaly; Adenoma; Aged; Growth Hormone-Secreting Pituitary Adenoma; Human Growth Hormone; Humans; Insulin-Like Growth Factor I
PubMed: 32060689
DOI: 10.1007/s12020-020-02206-7 -
The Journal of Clinical Endocrinology... Nov 2014The aim was to formulate clinical practice guidelines for acromegaly.
OBJECTIVE
The aim was to formulate clinical practice guidelines for acromegaly.
PARTICIPANTS
The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), five experts in the field, and a methodologist. The authors received no corporate funding or remuneration. This guideline is cosponsored by the European Society of Endocrinology.
EVIDENCE
This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews.
CONSENSUS PROCESS
One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society and the European Society of Endocrinology reviewed drafts of the guidelines.
CONCLUSIONS
Using an evidence-based approach, this acromegaly guideline addresses important clinical issues regarding the evaluation and management of acromegaly, including the appropriate biochemical assessment, a therapeutic algorithm, including use of medical monotherapy or combination therapy, and management during pregnancy.
Topics: Acromegaly; Combined Modality Therapy; Endocrinology; Evidence-Based Medicine; Female; Humans; Male; Pregnancy
PubMed: 25356808
DOI: 10.1210/jc.2014-2700 -
Archives of Endocrinology and Metabolism 2019Acromegaly is an insidious disease, usually resulting from growth hormone hypersecretion by a pituitary adenoma. It is most often diagnosed during the 3rd to 4th decade... (Review)
Review
Acromegaly is an insidious disease, usually resulting from growth hormone hypersecretion by a pituitary adenoma. It is most often diagnosed during the 3rd to 4th decade of life. However, recent studies have shown an increase in the incidence and prevalence of acromegaly in the elderly, probably due to increasing life expectancy. As in the younger population with acromegaly, there is a delay in diagnosis, aggravated by the similarities of the aging process with some of the characteristics of the disease. As can be expected elderly patients with acromegaly have a higher prevalence of comorbidities than younger ones. The diagnostic criteria are the same as for younger patients. Surgical treatment of the pituitary adenoma is the primary therapy of choice unless contraindicated. Somatostatin receptor ligands are generally effective as both primary and postoperative treatment. The prognosis correlates inversely with the patient's age, disease duration and last GH level. Arch Endocrinol Metab. 2019;63(6):638-45.
Topics: Acromegaly; Aged; Aged, 80 and over; Female; Humans; Male; Prognosis
PubMed: 31939489
DOI: 10.20945/2359-3997000000194 -
Minerva Endocrinologica Jun 2018Growth hormone (GH) and insulin-like growth factor-I (IGF-I) have pleiotropic effects on the skeleton throughout the lifespan by influencing bone formation and... (Review)
Review
Growth hormone (GH) and insulin-like growth factor-I (IGF-I) have pleiotropic effects on the skeleton throughout the lifespan by influencing bone formation and resorption. Despite these positive effects on skeletal metabolism, in presence of GH and IGF-I excess, bone turnover increases excessively leading to deterioration of bone microarchitecture and high risk of fragility fractures, thereby impairing quality of life. Coexistent hypogonadism, diabetes mellitus, hypovitaminosis D, hyperparathyroidism, and over-replacement with glucocorticoids impair bone framework, however, the effects of acromegaly on bone mineral density (BMD) are still controversial and despite normalization of bone turnover after treatment, the risk for fractures remains increased. As a matter of fact, a major clinical aspect emerging from the studies published so far is the lack of clinical-diagnostic tools able to reliably predict the appearance of fractures in patients with acromegaly occurring even in the presence of normal or low-normal BMD. New radiological software and clinical devices have been employed in acromegaly patients highlighting a significant impairment of both cortical and cancellous bone. In this article, we summarize the pathophysiology, clinical aspects and the new diagnostic tools to better understand bone impairment in acromegaly.
Topics: Absorptiometry, Photon; Acromegaly; Bone Density; Bone Remodeling; Bone and Bones; Fractures, Bone; Humans
PubMed: 28880058
DOI: 10.23736/S0391-1977.17.02733-X