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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 -
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 -
Reviews in Endocrine & Metabolic... Dec 2020The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and... (Review)
Review
The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.
Topics: Acromegaly; Consensus; Dopamine Agonists; Humans; Neurosurgical Procedures; Patient Care Team; Practice Guidelines as Topic; Radiotherapy; Receptors, Somatotropin; Somatostatin
PubMed: 32914330
DOI: 10.1007/s11154-020-09588-z -
Pituitary Feb 2024The 14th Acromegaly Consensus Conference was convened to consider biochemical criteria for acromegaly diagnosis and evaluation of therapeutic efficacy.
PURPOSE
The 14th Acromegaly Consensus Conference was convened to consider biochemical criteria for acromegaly diagnosis and evaluation of therapeutic efficacy.
METHODS
Fifty-six acromegaly experts from 16 countries reviewed and discussed current evidence focused on biochemical assays; criteria for diagnosis and the role of imaging, pathology, and clinical assessments; consequences of diagnostic delay; criteria for remission and recommendations for follow up; and the value of assessment and monitoring in defining disease progression, selecting appropriate treatments, and maximizing patient outcomes.
RESULTS
In a patient with typical acromegaly features, insulin-like growth factor (IGF)-I > 1.3 times the upper limit of normal for age confirms the diagnosis. Random growth hormone (GH) measured after overnight fasting may be useful for informing prognosis, but is not required for diagnosis. For patients with equivocal results, IGF-I measurements using the same validated assay can be repeated, and oral glucose tolerance testing might also be useful. Although biochemical remission is the primary assessment of treatment outcome, biochemical findings should be interpreted within the clinical context of acromegaly. Follow up assessments should consider biochemical evaluation of treatment effectiveness, imaging studies evaluating residual/recurrent adenoma mass, and clinical signs and symptoms of acromegaly, its complications, and comorbidities. Referral to a multidisciplinary pituitary center should be considered for patients with equivocal biochemical, pathology, or imaging findings at diagnosis, and for patients insufficiently responsive to standard treatment approaches.
CONCLUSION
Consensus recommendations highlight new understandings of disordered GH and IGF-I in patients with acromegaly and the importance of expert management for this rare disease.
Topics: Humans; Acromegaly; Insulin-Like Growth Factor I; Delayed Diagnosis; Human Growth Hormone; Growth Hormone
PubMed: 37923946
DOI: 10.1007/s11102-023-01360-1 -
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 -
Endocrinology and Metabolism Clinics of... Dec 2019Hypertension is one of the most frequent complications in acromegaly, with a median frequency of 33.6% (range, 11%-54.7%). Although the pathogenesis has not been fully... (Review)
Review
Hypertension is one of the most frequent complications in acromegaly, with a median frequency of 33.6% (range, 11%-54.7%). Although the pathogenesis has not been fully elucidated, it probably results from concomitant factors leading to expansion of extracellular fluid volume, increase of peripheral vascular resistance, and development of sleep apnea syndrome. Because the effect of normalization of growth hormone and insulinlike growth factor 1 excess on blood pressure levels is unclear, an early diagnosis of hypertension and prompt antihypertensive treatment are eagerly recommended, regardless of the specific treatment of the acromegalic disease and the level of biochemical control attained.
Topics: Acromegaly; Antihypertensive Agents; Humans; Hypertension
PubMed: 31655776
DOI: 10.1016/j.ecl.2019.08.008 -
Frontiers in Endocrinology 2022Molecular therapeutic targets in growth hormone (GH)-secreting adenomas range from well-characterized surface receptors that recognize approved drugs, to surface and... (Review)
Review
Molecular therapeutic targets in growth hormone (GH)-secreting adenomas range from well-characterized surface receptors that recognize approved drugs, to surface and intracellular markers that are potential candidates for new drug development. Currently available medical therapies for patients with acromegaly bind to somatostatin receptors, GH receptor, or dopamine receptors, and lead to attainment of disease control in most patients. The degree of control is variable: however, correlates with both disease aggressiveness and tumor factors that predict treatment response including somatostatin receptor subtype expression, granulation pattern, kinases and their receptors, and other markers of proliferation. A better understanding of the mechanisms underlying these molecular markers and their relationship to outcomes holds promise for expanding treatment options as well as a more personalized approach to treating patients with acromegaly.
Topics: Humans; Acromegaly; Adenoma; Receptors, Somatostatin; Growth Hormone-Secreting Pituitary Adenoma; Pituitary Neoplasms
PubMed: 36545335
DOI: 10.3389/fendo.2022.1068061 -
Best Practice & Research. Clinical... Dec 2022Acromegaly is a systemic disease associated with increased morbidity and mortality that can be prevented with adequate disease control. Three modalities of treatment... (Review)
Review
Acromegaly is a systemic disease associated with increased morbidity and mortality that can be prevented with adequate disease control. Three modalities of treatment (surgery, medical treatment, and radiotherapy) are available; however, a significant proportion of patients still maintain disease activity despite treatment. Therefore, there is a need for innovations in the treatment of acromegaly that include changes in the current trial and error approach and the development of new drugs. In this review, we summarize the recent innovations in the treatment of acromegaly and address the future perspectives in this field.
Topics: Humans; Somatostatin; Acromegaly; Human Growth Hormone
PubMed: 35688725
DOI: 10.1016/j.beem.2022.101679 -
Neurology India 2020Growth hormone (GH) hypersecretion from a pituitary adenoma results in acromegaly, an endocrinological disorder with multiple systemic manifestations that presents... (Review)
Review
Growth hormone (GH) hypersecretion from a pituitary adenoma results in acromegaly, an endocrinological disorder with multiple systemic manifestations that presents several unique challenges in terms of perioperative management and long term outcomes. Current guidelines provide stringent criteria for determining biochemical remission, necessitating an aggressive approach to management. Despite the development of several non-surgical therapies, transsphenoidal surgery, the endoscopic approach in particular, remains the primary line of treatment for rapid normalization of GH and Insulin-like growth factor with a low incidence of perioperative morbidity. Tumor size and invasiveness are important factors predicting surgical outcomes with better rates of postoperative remission seen in smaller and non-invasive tumors. Postoperative remission rates reported in literature with the 2020 consensus criteria vary from 30 to 85% probably reflecting varying prevalence rates of invasive tumors. Thus, a significant proportion of patients fail to achieve remission after surgery for whom treatment options for residual disease must be carefully considered. This review article discusses the surgical management of acromegaly and provides a summary of contemporary outcomes and current treatment controversies.
Topics: Acromegaly; Adenoma; Humans; Neurosurgical Procedures; Pituitary Gland; Pituitary Neoplasms; Treatment Outcome
PubMed: 32611892
DOI: 10.4103/0028-3886.287664 -
Endocrinology and Metabolism (Seoul,... Dec 2023Since our discovery in 2006 that acromegaly is associated with an increased risk of vertebral fractures, many authors have confirmed this finding in both cross-sectional... (Review)
Review
Since our discovery in 2006 that acromegaly is associated with an increased risk of vertebral fractures, many authors have confirmed this finding in both cross-sectional and prospective studies. Due to the high epidemiological and clinical impact of this newly discovered comorbidity of acromegaly, this topic has progressively become more important and prominent over the years, and the pertinent literature has been enriched by new findings on the pathophysiology and treatment. The aim of this narrative review was to discuss these novel findings, integrating them with the seminal observations, in order to give the reader an updated view of how the field of acromegaly and bone is developing, from strong clinical observations to a mechanistic understanding and possible prevention and treatment.
Topics: Humans; Acromegaly; Bone Density; Cross-Sectional Studies; Prospective Studies; Spinal Fractures
PubMed: 38164073
DOI: 10.3803/EnM.2023.601