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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 -
Endocrine Jul 2023Secondary diabetes mellitus (DM) is a common complication of acromegaly, encountered in up to 55% of cases. Vice versa, the prevalence of acromegaly is markedly higher... (Review)
Review
Secondary diabetes mellitus (DM) is a common complication of acromegaly, encountered in up to 55% of cases. Vice versa, the prevalence of acromegaly is markedly higher in cohorts of patients with type 2 DM (T2DM). The presence of secondary DM depends primarily on acromegaly status and is associated with increased cardiovascular morbidity, malignancy rate and overall mortality. The principal pathophysiologic mechanism is increased insulin resistance due to excessive lipolysis and altered fat distribution, reflected at the presence of intermuscular fat and attenuated, dysfunctional adipose tissue. Insulin resistance is ascribed to the direct, diabetogenic effects of growth hormone (GH), which prevail over the insulin-sensitizing effects of insulin-like growth factor 1 (IGF-1), probably due to higher glucometabolic potency of GH, IGF-1 resistance, or both. Inversely, GH and IGF-1 act synergistically in increasing insulin secretion. Hyperinsulinemia in portal vein leads to enhanced responsiveness of liver GH receptors and IGF-1 production, pointing towards a mutually amplifying loop between GH-IGF-1 axis and insulin. Secondary DM occurs upon beta cell exhaustion, principally due to gluco-lipo-toxicity. Somatostatin analogues inhibit insulin secretion; especially pasireotide (PASI) impairs glycaemic profile in up to 75% of cases, establishing a separate pathophysiologic entity, PASI-induced DM. In contrast, pegvisomant and dopamine agonizts improve insulin sensitivity. In turn, metformin, pioglitazone and sodium-glucose transporters 2 inhibitors might be disease-modifying by counteracting hyperinsulinemia or acting pleiotropically. Large, prospective cohort studies are needed to validate the above notions and define optimal DM management in acromegaly.
Topics: Humans; Acromegaly; Insulin-Like Growth Factor I; Insulin Resistance; Prospective Studies; Human Growth Hormone; Growth Hormone; Insulin; Diabetes Mellitus
PubMed: 36882643
DOI: 10.1007/s12020-023-03339-1 -
Endocrinology and Metabolism Clinics of... Sep 2019Pituitary adenomas are common. The impact of pituitary tumors on fertility are mainly caused by oversecretion and/or undersecretion of pituitary hormones or compression... (Review)
Review
Pituitary adenomas are common. The impact of pituitary tumors on fertility are mainly caused by oversecretion and/or undersecretion of pituitary hormones or compression of pituitary stalk and normal pituitary tissue by the tumor. Diagnosing and managing pituitary tumors during pregnancy involve many challenges, including the effect of hormone excess or deficiency on pregnancy outcome, changes in the pituitary or pituitary-related hormones, changes in tumor size, and the impact of various treatments of pituitary tumors on maternal and fetal outcomes. This article discusses the diagnosis and treatment of patients with prolactinomas, acromegaly, Cushing disease, and other pituitary tumors during pregnancy.
Topics: Acromegaly; Female; Humans; Pituitary Neoplasms; Pregnancy; Prolactinoma
PubMed: 31345524
DOI: 10.1016/j.ecl.2019.05.004 -
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 -
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... Apr 2023Paltusotine is a once-daily, oral, nonpeptide small-molecule somatostatin receptor type 2 (SST2) agonist in clinical development for treatment of acromegaly. (Clinical Trial)
Clinical Trial
CONTEXT
Paltusotine is a once-daily, oral, nonpeptide small-molecule somatostatin receptor type 2 (SST2) agonist in clinical development for treatment of acromegaly.
OBJECTIVE
This work aimed to evaluate change in insulin-like growth factor I (IGF-I) levels in patients switched from octreotide long-acting release or lanreotide depot monotherapy to paltusotine.
METHODS
A phase 2, open-label, prospective, multicenter, multinational, nonrandomized, single-arm exploratory study was conducted in which dosage uptitrations were performed in a double-blinded manner. At 26 global sites, patients with acromegaly switched to paltusotine from injected somatostatin receptor ligand (SRL)-based therapy. Patients received 13-week treatment with once-daily oral paltusotine (10-40 mg/d). The primary end point was change from baseline to week 13 in IGF-I for patients who switched from long-acting octreotide or lanreotide depot monotherapy to paltusotine (group 1). All patients underwent a 4-week paltusotine washout at end of treatment period (wk 13-17). IGF-I, growth hormone (GH), patient-reported outcome, and safety data were collected.
RESULTS
Forty-seven patients enrolled. In group 1 (n = 25), IGF-I and GH showed no significant change between SRL baseline and end of paltusotine treatment at week 13 (median change in IGF-I = -0.03×upper limit of normal [ULN]; P = .6285; GH = -0.05 ng/mL; P = .6285). IGF-I and GH rose significantly in the 4 weeks after withdrawing paltusotine (median change in IGF-I = 0.55×ULN; P < .0001 [median increase 39%]; GH = 0.72 ng/mL; P < .0001 [109.1% increase]). No patients discontinued because of adverse events (AE); no treatment-related serious AEs were reported.
CONCLUSION
These results suggest once-daily oral paltusotine was effective in maintaining IGF-I values in patients with acromegaly who switched from injected SRLs. Paltusotine was well tolerated with a safety profile consistent with other SRLs.
Topics: Humans; Acromegaly; Octreotide; Insulin-Like Growth Factor I; Prospective Studies; Peptides, Cyclic; Human Growth Hormone; Treatment Outcome
PubMed: 36353760
DOI: 10.1210/clinem/dgac643 -
Trends in Endocrinology and Metabolism:... Apr 2020Here I review vertebral fractures (VFs) as an emerging complication of acromegaly through a pathway of key questions in order to help clinicians manage the disease.... (Review)
Review
Here I review vertebral fractures (VFs) as an emerging complication of acromegaly through a pathway of key questions in order to help clinicians manage the disease. Peculiarities of acromegalic osteopathy are that VFs are common but not explained by low bone mineral density (BMD) being related to disease duration and activity, and occurring even after remission.
Topics: Acromegaly; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Spinal Fractures
PubMed: 32187523
DOI: 10.1016/j.tem.2020.01.011 -
Annales D'endocrinologie Jun 2021Acromegaly is a chronic disease due to growth hormone (GH) and insulin-like growth factor 1 (IGF-1) excess. It is associated with various systemic complications... (Review)
Review
Acromegaly is a chronic disease due to growth hormone (GH) and insulin-like growth factor 1 (IGF-1) excess. It is associated with various systemic complications including cardiovascular disease. Arterial hypertension occurs in about 20% to 30% of patients. Its pathogenesis is mainly related to the increase in plasma volume secondary to a sodium retaining actions of GH and IGF-1 in the kidney, but abnormalities in vessel architecture and reactivity participate. Left ventricular hypertrophy and diastolic dysfunctions were frequently reported in echo-based studies and are mostly mild and without clinical consequences. Recent cardiac MRI studies described a much lower frequency of myocardial hypertrophy than echo-based assessments. Progression to systolic dysfunction with congestive heart failure is nowadays very rare. Risk of coronary heart disease and of clinically significant arrythmias does not seem to be increased. Acromegaly-related cardiac valve abnormalities may be related to fibrotic changes and seem to persist after effective treatment of acromegaly. Advances in acromegaly treatment over the last decades significantly diminished the cardiovascular burden of the disease, with the cardiovascular disease anymore being the leading cause of death.
Topics: Acromegaly; Cardiovascular Diseases; Cardiovascular System; Heart Disease Risk Factors; Heart Failure; Human Growth Hormone; Humans; Hypertrophy, Left Ventricular
PubMed: 33168155
DOI: 10.1016/j.ando.2020.03.010 -
Archives of Medical Research Dec 2023Pegvisomant, the first and currently only clinically available growth hormone receptor antagonist, is an effective therapeutic option for the medical treatment of... (Review)
Review
Pegvisomant, the first and currently only clinically available growth hormone receptor antagonist, is an effective therapeutic option for the medical treatment of acromegaly, a rare disorder characterized by excessive growth hormone secretion. With now over 20 years of real world experience, its safety and efficacy is well-established. However, several aspects of its clinical use are still controversially discussed. The high cost of pegvisomant has limited its use in several countries, and recent studies have reported a lower efficacy than the initial clinical trials. A reported increase in tumor volume under therapy varies between studies and has been attributed to either actual growth or re-expansion after cessation of somatostatin receptor ligand therapy. Furthermore, different combinations of pegvisomant and other therapeutic agents aiming at reduction of acromegaly disease activity have been proposed to increase or retain effectiveness while lowering side effects and cost. This review aims to assess current clinical data on the safety and efficacy of pegvisomant while also addressing controversies surrounding its use.
Topics: Humans; Acromegaly; Receptors, Somatotropin; Human Growth Hormone; Hormone Antagonists; Insulin-Like Growth Factor I
PubMed: 37659952
DOI: 10.1016/j.arcmed.2023.102884 -
The Journal of Clinical Endocrinology... Sep 2023Acromegaly is a chronic condition caused by the excessive production of growth hormone and is characterized by progressive morphological and systemic complications, as...
Acromegaly is a chronic condition caused by the excessive production of growth hormone and is characterized by progressive morphological and systemic complications, as well as increased prevalence of psychopathologies, which markedly affect patients' quality of life. The advancing multimodal therapies, while significantly improving the morbidity and mortality, have limited impact on psychopathologies, which often persist despite disease remission. The most common psychopathologies in acromegaly include depression, anxiety and affective disorders, together with sexual dysfunction, which may be considered as either a consequence or potentially even a contributory factor to these psychopathologies. Approximately one-third of patients with acromegaly manifest depression, whereas two-thirds of patients display anxiety, with both conditions tending to be more prevalent and severe in younger patients with shorter duration of disease. Apparently, a major impact of psychological discomfort in women compared with men appears to be the fact that women tend to internalize whereas men tend to externalize their distress. Personality disorders also commonly associated with acromegaly, especially due to body image suffering, are linked to sexual dysfunction, which seems to affect women more than men. In summary, psychopathology in acromegaly is a major determinant of the quality of life and a complex array of psychological abnormalities are associated with acromegaly.
Topics: Male; Humans; Female; Acromegaly; Quality of Life; Human Growth Hormone; Anxiety; Sexual Dysfunction, Physiological; Mental Disorders
PubMed: 37139644
DOI: 10.1210/clinem/dgad237