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The Journal of Clinical Endocrinology... Nov 2023Acromegaly is a rare, chronic, debilitating disorder caused by prolonged hypersecretion of growth hormone (GH) and overproduction of insulin-like growth factor I...
CONTEXT
Acromegaly is a rare, chronic, debilitating disorder caused by prolonged hypersecretion of growth hormone (GH) and overproduction of insulin-like growth factor I (IGF-I). Medical therapies, including the somatostatin receptor ligand (SRL) pasireotide, are frequently used to restore biochemical control.
OBJECTIVE
As patients often receive therapy over prolonged periods, long-term data from real-life settings are needed.
METHODS
A retrospective analysis was performed using a prospectively maintained database of all patients with acromegaly from our primary care center who were enrolled in clinical studies with pasireotide (first visit November 2008). The main outcome measures were safety and biochemical control (age-adjusted IGF-I ≤ upper limit of normal).
RESULTS
Patients (n = 50) entered 4 parental studies and 30 continued in the rollover; at data cutoff (June 2022), 27 were still receiving pasireotide. Overall, median (range) exposure was 58 (3-137) months. Normal IGF-I was achieved in 54%, and acromegaly symptoms and quality of life were improved with treatment. No predictors of pasireotide response were identified; however, controlled patients had smaller tumors and lower GH at baseline. Tumor volume reduction occurred in 63% of evaluable patients (n = 10/16). Most patients presented hyperglycemic events, including 63.2% of patients with normal glucose before treatment. Older patients and those with higher IGF-I, glucose, and HbA1c at baseline had higher glucose and HbA1c during pasireotide treatment.
CONCLUSION
Pasireotide provided clinical benefit and was well tolerated for more than 11 years of treatment in acromegaly patients, most of whom were resistant to first-generation SRLs.
Topics: Humans; Acromegaly; Insulin-Like Growth Factor I; Glycated Hemoglobin; Retrospective Studies; Quality of Life; Treatment Outcome; Human Growth Hormone; Growth Hormone; Glucose; Adenoma
PubMed: 37357993
DOI: 10.1210/clinem/dgad378 -
Nature Communications Feb 2023Somatostatin receptor 2 (SSTR2) is highly expressed in neuroendocrine tumors and represents as a therapeutic target. Several peptide analogs mimicking the endogenous...
Somatostatin receptor 2 (SSTR2) is highly expressed in neuroendocrine tumors and represents as a therapeutic target. Several peptide analogs mimicking the endogenous ligand somatostatin are available for clinical use, but poor therapeutic effects occur in a subset of patients, which may be correlated with subtype selectivity or cell surface expression. Here, we clarify the signal bias profiles of the first-generation peptide drug octreotide and a new-generation small molecule paltusotine by evaluating their pharmacological characteristics. We then perform cryo-electron microscopy analysis of SSTR2-Gi complexes to determine how the drugs activate SSTR2 in a selective manner. In this work, we decipher the mechanism of ligand recognition, subtype selectivity and signal bias property of SSTR2 sensing octreotide and paltusotine, which may aid in designing therapeutic drugs with specific pharmacological profiles against neuroendocrine tumors.
Topics: Humans; Octreotide; Acromegaly; Ligands; Cryoelectron Microscopy; Neuroendocrine Tumors
PubMed: 36810324
DOI: 10.1038/s41467-023-36673-z -
Frontiers in Endocrinology 2023Cushing's syndrome, acromegaly and neuroendocrine disorders are characterized by an excess of counterregulatory hormones, able to induce insulin resistance and glucose... (Review)
Review
Cushing's syndrome, acromegaly and neuroendocrine disorders are characterized by an excess of counterregulatory hormones, able to induce insulin resistance and glucose metabolism disorders at variable degrees and requiring immediate treatment, until patients are ready to undergo surgery. This review focuses on the management of diabetes mellitus in endocrine disorders related to an excess of counterregulatory hormones. Currently, the landscape of approved agents for treatment of diabetes is dynamic and is mainly patient-centred and not glycaemia-centred. In addition, personalized medicine is more and more required to provide a precise approach to the patient's disease. For this reason, we aimed to define a practical therapeutic algorithm for management of diabetes mellitus in patients with glucagonoma, pheochromocytoma, Cushing's syndrome and acromegaly, based on our practical experience and on the physiopathology of the specific endocrine disease taken into account. This document is addressed to all specialists who approach patients with diabetes mellitus secondary to endocrine disorders characterized by an excess of counterregulatory hormones, in order to take better care of these patients. Care and control of diabetes mellitus should be one of the primary goals in patients with an excess of counterregulatory hormones requiring immediate and aggressive treatment.
Topics: Humans; Cushing Syndrome; Acromegaly; Neuroendocrine Tumors; Diabetes Mellitus; Hormones
PubMed: 37842314
DOI: 10.3389/fendo.2023.1248985 -
Journal of Patient-reported Outcomes Feb 2023Patient-reported outcome (PRO) measures are important to consider when evaluating treatments, yet there are no PRO measures for patients with acromegaly that have been...
BACKGROUND
Patient-reported outcome (PRO) measures are important to consider when evaluating treatments, yet there are no PRO measures for patients with acromegaly that have been developed in accordance with US Food and Drug Administration guidance. Acromegaly is a rare, chronic condition caused by hypersecretion of growth hormone. Disease activity is monitored by measurement in serum of growth hormone and insulin-like growth factor-I. The objectives of this research were to develop the Acromegaly Symptom Diary (ASD), establish a scoring algorithm, and evaluate the psychometric measurement properties of the ASD.
METHODS
Semistructured interviews consisting of concept elicitation and cognitive debriefing components were conducted with 16 adult participants with acromegaly. The concept elicitation component identified symptoms important to individuals with acromegaly. The cognitive debriefing component gathered information about the participants' experience with each proposed item of the ASD, their thought process for answering each question, and their interpretation of the items. The psychometric properties of the draft ASD were then evaluated using data from the ACROBAT Evolve (NCT03792555; n = 13) and ACROBAT Edge (NCT03789656; n = 47) clinical trials.
RESULTS
The 16 participants from the interviews described ongoing symptoms, with the most frequently reported being joint pain (n = 13) and fatigue (n = 12), followed by swelling (n = 8), headache (n = 7), and mood swings (n = 6), and were able to interpret and understand the ASD items and had no issues with the 24-hour recall period. From data collected in the clinical studies, the psychometric properties of internal consistency (0.91 - 0.80), test-retest reliability with item-level and total ASD scores (> 0.70), baseline construct validity (r ≥ |0.38|) across scales, and responsiveness to change (r = 0.52-0.56) were supported for the ASD. The proposed preliminary threshold range to characterize a meaningful change from the patients' perspective for the ASD total is a 4- to 6-point change for improvement or worsening out of a total score of 70.
CONCLUSION
These findings provide qualitative and quantitative evidence to support the ASD as fit for the purpose of evaluating the symptom experience of patients with acromegaly in clinical trials.
Topics: Adult; Humans; Acromegaly; Reproducibility of Results; Surveys and Questionnaires; Mental Recall; Growth Hormone
PubMed: 36792844
DOI: 10.1186/s41687-023-00541-7 -
BMC Endocrine Disorders May 2023Pregnancy in acromegaly is uncommon and still in debate for fear of tumor progression or potential threat to both mother and fetus's health. Besides, the data for... (Review)
Review
BACKGROUND
Pregnancy in acromegaly is uncommon and still in debate for fear of tumor progression or potential threat to both mother and fetus's health. Besides, the data for pregnancy complications in uncontrolled acromegaly is limited. Thus, the objective of this study was to summarize pregnancy safety and disease courses after pregnancy in acromegalic patients and review their clinical characteristics based on disease activity in the literature.
METHODS
An evaluation of eight acromegalic women from Peking Union Medical College Hospital (PUMCH) with 11 pregnancies was conducted. We also summarized a literature review of 82 disease-active pregnancies and 63 disease-controlled pregnancies with acromegaly. A second analysis was conducted to compare pregnancy courses and outcomes in different disease activities.
RESULTS
Before pregnancy, all patients had macroadenomas and underwent pituitary surgery. Pregnancy occurred at a median of 6 years (4-10) after the diagnosis of acromegaly. Assisted reproductive therapy was needed in 42.9% of participants. No cases had a premature birth or congenital malformations. Biochemical control was achieved in 50% of females before pregnancy and 75% at the last follow-up after delivery. Data analysis showed no differences in the prevalence of gestational diabetes mellitus (GDM) or pregnancy-induced hypertension (PIH) between acromegaly-active or acromegaly-controlled groups. The GDM prevalence in patients diagnosed during pregnancy (33.3%) was higher than that in patients diagnosed before pregnancy (4.8%) (p = 0.001).
CONCLUSION
Pregnancy without biochemical control in acromegaly and receiving medical treatment during pregnancy are not rare and generally safe for the fetus. There could be a higher prevalence of PIH in acromegalic pregnancies. The treatment of acromegaly and related complications can be managed with regular follow-up after pregnancy.
Topics: Pregnancy; Humans; Female; Infant; Acromegaly; China; Family; Data Analysis; Diabetes, Gestational
PubMed: 37161564
DOI: 10.1186/s12902-023-01341-2 -
European Journal of Endocrinology Oct 2020The literature on an association between acromegaly and cancer is particularly abundant on either colorectal cancer or thyroid cancer, and an endless debate is ongoing... (Review)
Review
The literature on an association between acromegaly and cancer is particularly abundant on either colorectal cancer or thyroid cancer, and an endless debate is ongoing whether patients with acromegaly should be submitted to specific oncology screening and surveillance protocols. The aim of the present work is to review the most recent data on the risk of either colorectal cancer or thyroid cancer in acromegaly and discuss the opportunity for specific screening in relation to the accepted procedures in the general population.
Topics: Acromegaly; Adenoma; Colorectal Neoplasms; Early Detection of Cancer; Endocrinology; Growth Hormone-Secreting Pituitary Adenoma; Humans; Mass Screening; Medical Oncology; Monitoring, Physiologic; Population Surveillance; Practice Guidelines as Topic; Thyroid Neoplasms
PubMed: 32698136
DOI: 10.1530/EJE-19-1009 -
Acromegaly and non-parathyroid hormone-dependent hypercalcemia: a case report and literature review.BMC Endocrine Disorders May 2021Hypercalcemia associated with acromegaly is mostly parathyroid hormone (PTH)-dependent, being caused by parathyroid hyperplasia or adenoma, which are common in... (Review)
Review
BACKGROUND
Hypercalcemia associated with acromegaly is mostly parathyroid hormone (PTH)-dependent, being caused by parathyroid hyperplasia or adenoma, which are common in individuals with multiple endocrine adenomatosis-1 (MEN-1). The rare occurrence of non-PTH-dependent hypercalcemia associated with acromegaly is attributable to complex factors involving increased intestinal calcium absorption, enhanced bone calcium release, and reduced urinary calcium elimination. Although patients with acromegaly often have mild hyperphosphatemia and hypercalciuria, clinically significant hypercalcemia is extremely rare.
CASE PRESENTATION
Here we present a case of non-PTH-dependent hypercalcemia associated with a growth hormone- (GH) and prolactin- (PRL) co-secreting pituitary macroadenoma. A 37-year-old Chinese man presented with a 6-year history of increasing ring and shoe sizes and was referred to the West China Hospital of Sichuan University for treatment of acromegaly. Pituitary magnetic resonance imaging (MRI) showed a 2.0 × 1.7 × 1.9 cm macroadenoma. Laboratory examinations revealed high serum concentrations of GH and PRL with mild hypercalcemia, hyperphosphatemia, hypercalciuria, inhibited PTH concentration, and increased bone turnover markers. Administration of cabergoline together with somatostatin resulted in sharp decreases in his GH, PRL, and serum and urinary calcium concentrations. These values were further reduced 5 months later and his PTH and bone turnover markers gradually returned to within the normal range.
CONCLUSIONS
Mild hyperphosphatemia and hypercalciuria are common in individuals with acromegaly and deserve attention because they may contribute to osteoporosis and urolithiasis. However, overt hypercalcemia is rare in such individuals. It is usually attributable to a coexisting parathyroid hyperplasia or adenoma, rarely being non-PTH-dependent. In such cases, the hypercalcemia is attributable to excessive PRL and hypogonadism and reverses with remission of acromegaly.
Topics: Acromegaly; Adenoma; Adult; China; Growth Hormone-Secreting Pituitary Adenoma; Humans; Hypercalcemia; Male; Parathyroid Hormone; Pituitary Neoplasms; Prolactinoma
PubMed: 33933067
DOI: 10.1186/s12902-021-00756-z -
Endocrine Practice : Official Journal... Oct 2021Acromegaly is associated with increased morbidity and mortality. Limited data are available on these patients' utilization and costs of health care. This study assessed...
OBJECTIVE
Acromegaly is associated with increased morbidity and mortality. Limited data are available on these patients' utilization and costs of health care. This study assessed the impact of acromegaly on employees' health benefit (direct and indirect) costs and absenteeism.
METHODS
A retrospective analysis was conducted of drug and medical claims and employer data (from January 2010 to April 2019) of patients with an acromegaly diagnosis and matched controls from a U.S. employee database. Patient claims were tracked for 12 months postdiagnosis (or matched) date. Outcomes were analyzed using separate 2-part regression models, controlling for clinical, demographic, and job-related variables.
RESULTS
Forty-seven patients with acromegaly and 940 controls were identified. Cohorts were similar in most demographic and job-related variables. Patients with acromegaly had a significantly higher Charlson comorbidity index score and higher incidence of claims for several comorbidities. Acromegaly drugs represented 16.3% of the acromegaly cohort's total costs. Total health benefit costs were $54 821 higher (P < .05) for patients compared with controls, with direct costs representing 79.8% of the difference. Total indirect costs were higher for patients with acromegaly, with short-term and long-term disability comprising most of the difference between the acromegaly and control groups. Patients with acromegaly had significantly more short-term disability days than controls, but total sick days were similar for the 2 groups.
CONCLUSION
The presence of acromegaly was associated with increased direct and indirect employee health benefit costs and increased work absenteeism.
Topics: Absenteeism; Acromegaly; Cost of Illness; Health Care Costs; Humans; Retrospective Studies; Sick Leave; United States
PubMed: 33940182
DOI: 10.1016/j.eprac.2021.04.412 -
Drug Design, Development and Therapy 2016Morbidity and mortality rates in patients with active acromegaly are higher than the general population. Adequate biochemical control restores mortality to normal rates.... (Comparative Study)
Comparative Study Review
Morbidity and mortality rates in patients with active acromegaly are higher than the general population. Adequate biochemical control restores mortality to normal rates. Now, medical therapy has an increasingly important role in the treatment of patients with acromegaly. Somatostatin receptor ligands (SRLs) are considered the standard medical therapy, either after surgery or as a first-line therapy when surgery is deemed ineffective or is contraindicated. Overall, octreotide and lanreotide are first-generation SRLs and are effective in ~20%-70% of patients. Pegvisomant, a growth hormone receptor antagonist, controls insulin-like growth factor 1 in 65%-90% of cases. Consequently, a subset of patients (nonresponders) requires other treatment options. Drug combination therapy offers the potential for more efficacious disease control. However, the development of new medical therapies remains essential. Here, emphasis is placed on new medical therapies to control acromegaly. There is a focus on pasireotide long-acting release (LAR) (Signifor LAR®), which was approved in 2014 by the US Food and Drug Administration and the European Medicine Agency for the treatment of acromegaly. Pasireotide LAR is a long-acting somatostatin multireceptor ligand. In a Phase III clinical trial in patients with acromegaly (naïve to medical therapy or uncontrolled on a maximum dose of first-generation SRLs), 40 and 60 mg of intramuscular pasireotide LAR achieved better biochemical disease control than octreotide LAR, and tumor shrinkage was noted in both pasireotide groups. Pasireotide LAR tolerability was similar to other SRLs, except for a greater frequency and degree of hyperglycemia and diabetes mellitus. Baseline glucose may predict hyperglycemia occurrence after treatment, and careful monitoring of glycemic status and appropriate treatment is required. A precise definition of patients with acromegaly who will derive the greatest therapeutic benefit from pasireotide LAR remains to be established. Lastly, novel therapies and new potential delivery modalities (oral octreotide) are summarized.
Topics: Acromegaly; Animals; Delayed-Action Preparations; Drug Delivery Systems; Drug Design; Humans; Octreotide; Somatostatin
PubMed: 26811671
DOI: 10.2147/DDDT.S77999 -
Journal of Clinical Neuroscience :... May 2022Acromegaly is a chronic progressive endocrine disease that is often accompanied by joint and bone symptoms. The correlation between bone metabolism and acromegaly is...
Acromegaly is a chronic progressive endocrine disease that is often accompanied by joint and bone symptoms. The correlation between bone metabolism and acromegaly is still unclear. In this study, 31 patients with acromegaly at Peking Union Medical College Hospital were included. Bone metabolism indices, such as β-CTX, TP1NP, T-25OHD, 1,25(OH)2D3, and SAGIT score, which represent the severity of acromegaly, were examined before operation, and the patients were followed up for at least 3 months after operation. The results showed that β-CTX and TP1NP were significantly lower than those before surgery in the remission group (p < 0.001). In the nonremission group, CTX (p = 0.226) and TP1NP (p = 0.326) did not show significant differences from those before operation. In Pearson correlation analysis, β-CTX was significantly correlated with SAGIT score (r = 0.356, p = 0.049). By multivariate linear regression analysis, it was found that β-CTX was an independent risk factor of SAGIT score (p = 0.001). In conclusion, indicators of bone metabolism are closely related to changes in acromegaly, and the β-CTX value can be used as an effective predictor for assessing acromegaly.
Topics: Acromegaly; Bone and Bones; Humans
PubMed: 35298943
DOI: 10.1016/j.jocn.2022.03.020