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Purpose: This systematic literature review investigated whether extended dosing intervals (EDIs) of pharmacological acromegaly treatments reduce patient burden and costs compared with standard dosing, while maintaining effectiveness., Methods: MEDLINE/Embase/the Cochrane Library (2001-June 2021) and key congresses (2018-2021) were searched and identified systematic literature review bibliographies reviewed. Included publications reported on efficacy/effectiveness, safety and tolerability, health-related quality of life (HRQoL), and patient-reported and economic outcomes in longitudinal/cross-sectional studies in adults with acromegaly. Interventions included EDIs of pegvisomant, cabergoline, and somatostatin receptor ligands (SRLs): lanreotide autogel/depot (LAN), octreotide long-acting release (OCT), pasireotide long-acting release (PAS), and oral octreotide; no comparator was required., Results: In total, 35 publications reported on 27 studies: 3 pegvisomant monotherapy, 11 pegvisomant combination therapy with SRLs, 9 LAN, and 4 OCT; no studies reported on cabergoline, PAS, or oral octreotide at EDIs. Maintenance of normal insulin-like growth factor I (IGF-I) was observed in ≥ 70% of patients with LAN (1 study), OCT (1 study), and pegvisomant monotherapy (1 study). Achievement of normal IGF-I was observed in ≥ 70% of patients with LAN (3 studies) and pegvisomant in combination with SRLs (4 studies). Safety profiles were similar across EDI and standard regimens. Patients preferred and were satisfied with EDIs. HRQoL was maintained and cost savings were provided with EDIs versus standard regimens., Conclusions: Clinical efficacy/effectiveness, safety, and HRQoL outcomes in adults with acromegaly were similar and costs lower with EDIs versus standard regimens. Physicians may consider acromegaly treatment at EDIs, especially for patients with good disease control., (© 2022. The Author(s).)

Purpose: Patients receiving treatment for acromegaly often experience significant associated comorbidities for which they are prescribed additional medications. We aimed to determine the real-world prevalence of comorbidities and concomitant medications in patients with acromegaly, and to investigate the association between frequency of comorbidities and number of concomitantly prescribed medications., Methods: Administrative claims data were obtained from the IBM® MarketScan® database for a cohort of patients with acromegaly, identified by relevant diagnosis codes and acromegaly treatments, and a matched control cohort of patients without acromegaly from January 2010 through April 2020. Comorbidities were identified based on relevant claims and assessed for both cohorts., Results: Overall, 1175 patients with acromegaly and 5875 matched patients without acromegaly were included. Patients with acromegaly had significantly more comorbidities and were prescribed concomitant medications more so than patients without acromegaly. In the acromegaly and control cohorts, respectively, 67.6% and 48.4% of patients had cardiovascular disorders, the most prevalent comorbidities, and 89.0% and 68.3% were prescribed > 3 concomitant medications (p < 0.0001). Hypopituitarism and hypothalamic disorders, sleep apnea, malignant neoplasms and cancer, and arthritis and musculoskeletal disorders were also highly prevalent in the acromegaly cohort. A moderate, positive correlation (Spearman correlation coefficient 0.60) was found between number of comorbidities and number of concomitant medications in the acromegaly cohort., Conclusion: Compared with patients without acromegaly, patients with acromegaly have significantly more comorbidities and are prescribed significantly more concomitant medications. Physicians should consider the number and type of ongoing medications for individual patients before prescribing additional acromegaly treatments., (© 2021. The Author(s).)

Purpose: The physiological role of arginine vasopressin (AVP) in the acute stress response in humans and especially in children is unclear. The aim of this study was to explore the interaction between copeptin, a well-established surrogate marker of AVP release, and anterior pituitary hormone activation in response to acute hypoglycemic stress in children and adolescents., Methods: We conducted an exploratory single center study involving 77 children and adolescents undergoing insulin-induced hypoglycemia. Blood levels of copeptin, ACTH, cortisol, GH, prolactin, interleukin-6 (IL-6), adrenaline and noradrenaline were determined at baseline and after insulin-induced hypoglycemia., Results: Basal plasma levels of copeptin (median: 5.2 pmol/L) increased significantly after hypoglycemia (median 9.7 pmol/L; P < 0.0001). Subjects with insufficient HPA axis response or severe GH deficiency had lower hypoglycemia-induced copeptin increase (median: 2.3 pmol/L) compared with individuals with intact pituitary response (median: 5.2 pmol/L, P = 0.02). Copeptin increase correlated significantly with the maximal increase of ACTH (r s  = 0.30; P = 0.010), cortisol (r s  = 0.33; P = 0.003), prolactin (r s  = 0.25; P = 0.03), IL-6 (r s  = 0.35; P = 0.008) and with BMI-SDS (r s  = - 0.28, P = 0.01). In multivariate regression analysis, prolactin increase was the only independent variable associated with copeptin increase (P = 0.0004)., Conclusion: Our data indicate that: (1) hypoglycemic stress elicits a marked copeptin response in children and adolescents, pointing out its role as an acute stress marker in this population; (2) stress-induced AVP/copeptin release is associated with anterior pituitary activation, mainly a prolactin response.

Objective: To evaluate the maternal-fetal outcomes of CAB-induced pregnancies in patients with prolactinoma in a large cohort., Methods: The prevalence of tumor growth, miscarriage, preterm, low birth weight, congenital malformations and impairment in neuropsychological development in children among women treated with CAB were assessed in a Brazilian multicentre retrospective observational study, RESULTS: We included 194 women with a mean age of 31 (17-45) years, 43.6% presenting microadenomas and 56.4% macroadenomas, at prolactinoma diagnosis. In 233 pregnancies, CAB was withdrawn in 89%, after pregnancy confirmation. Symptoms related to tumor growth occurred in 25 cases, more frequently in macroadenomas. The overall miscarriage rate was 11%, although higher in the subgroup of patients with CAB maintainance after pregnancy confirmation (38% vs. 7.5%). Amongst the live-birth deliveries, preterm occurred in 12%, low birth weight in 6% and congenital malformations in 4.3%. Neuropsychological development impairment was reported in 7% of cases., Conclusions: Our findings confirm previous results of safety in maternal and fetal outcomes in CAB-induced pregnancies; nevertheless, CAB maintenance after pregnancy confirmation was associated with higher miscarriage rate; result that must be further confirmed.

Introduction: Acromegaly is a rare, insidious disease resulting from the overproduction of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), and is associated with a range of comorbidities. The extent of associated complications and mortality risk is related to length of exposure to the excess GH and IGF-1, thus early diagnosis and treatment is imperative. Unfortunately, acromegaly is often diagnosed late, when patients already have a wide range of comorbidities. The presence of comorbid conditions contributes significantly to patient morbidity/mortality and impaired quality of life., Methods: We conducted a retrospective literature review for information relating to the diagnosis of acromegaly, and its associated comorbidities using PubMed. The main aim of this review is to highlight the issues of comorbidities in acromegaly, and to reinforce the importance of early diagnosis and treatment., Findings and Conclusions: Successful management of acromegaly goes beyond treating the disease itself, since many patients are diagnosed late in disease evolution, they present with a range of comorbid conditions, such as cardiovascular disease, diabetes, hypertension, and sleep apnea. It is important that patients are screened carefully at diagnosis (and thereafter), for common associated complications, and that biochemical control does not become the only treatment goal. Mortality and morbidities in acromegaly can be reduced successfully if patients are treated using a multimodal approach with comprehensive comorbidity management.

Aims: The current article provides a brief overview of the criteria for defining disease control in acromegaly., Methods: This was a retrospective, narrative review of previously published evidence chosen at the author's discretion along with an illustrative case study from Latin America., Findings and Conclusions: In the strictest sense, "cure" in acromegaly is defined as complete restoration of normal pulsatile growth hormone secretion, although this is rarely achieved. Rather than "cure", as such, it is more appropriate to refer to disease control and remission, which is defined mainly in terms of specific biochemical targets (for growth hormone and insulin-like growth factor-1) that predict or correlate with symptoms, comorbidities and mortality. However, optimal management of acromegaly goes beyond biochemical control to include control of tumour growth (which may be independent of biochemical control) and comprehensive management of the symptoms and comorbidities typically associated with the disease, as these may not be adequately managed with acromegaly-specific therapy alone.