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Alvarez M, Donato A, Rincon J, Rincon O, Lancheros N, Mancera P, Guzman I. Evaluation of pituitary tumor volume as a prognostic factor in acromegaly: A cross-sectional study in two centers. World J Radiol 2025; 17:100168. [DOI: 10.4329/wjr.v17.i3.100168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 01/14/2025] [Accepted: 02/14/2025] [Indexed: 03/27/2025] Open
Abstract
BACKGROUND Acromegaly is caused by a pituitary neuroendocrine tumor (PitNET) with excessive production of growth hormone (GH), leading to multisystem complications. Previous studies have identified predictors of disease persistence following surgery and poor response to medical treatment, including tumor size, vertical and horizontal extensions of the adenoma, hyperintensity in T2-weighted magnetic resonance imaging, granulation density, and pre- and postoperative GH and insulin-like growth factor 1 (IGF-1) levels.
AIM To evaluate PitNET volume as a complementary prognostic factor in patients with acromegaly.
METHODS This is a retrospective descriptive study with an analytical component evaluating the correlation between the volumetric analysis of GH-producing PitNETs, IGF-1 levels before and after surgery, disease control during follow-up, and the line of therapy required for disease control in a cohort of patients treated at two centers: Endocrinology Department of the Central Military Hospital and Centros Médicos Colsanitas, Bogotá, Colombia.
RESULTS A total of 77 patients with acromegaly (42 men, 35 women) were included in this study. The mean age at diagnosis was 42 years (SD: 12), with a mean disease duration of 9.9 years (SD: 7.2). The mean pituitary tumor volume was 4358 mm³ (SD: 6291, interquartile range [IQR]: 13602). Patients with controlled acromegaly had a mean PitNET volume of 3202 mm³ (SD: 4845, 95%CI: 621-5784) compared to 5513 mm³ (SD: 7447, 95%CI: 1545-9482) in the uncontrolled group (P = 0.15). A PitNET volume exceeding 3697 mm³ was associated with a higher likelihood of requiring third or fourth-line therapy (50% vs 36%; P = 0.03).
CONCLUSION PitNET volume was associated with the need for higher-line therapy to manage acromegaly but did not correlate with long-term disease control or with pre- or postsurgical IGF-1 levels. Nevertheless, a trend towards an inverse relationship between tumor volume and future disease control was observed. While macroadenoma classification remains crucial, among patients with macroadenomas, those with a volume exceeding 3697 mm³ could have worse prognosis.
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Affiliation(s)
- Mauricio Alvarez
- Department of Endocrinology, Hospital Militar Central, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Angel Donato
- Department of Neuroradiology, Hospital Militar Central, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Juliana Rincon
- Department of Epidemiology, Fundación Universitaria Sanitas, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Oswaldo Rincon
- Department of Endocrinology, Hospital Militar Central, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Natalia Lancheros
- Department of Clinical Medicine, Centros Médicos Colsanitas, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Pedro Mancera
- Department of Endocrinology, Universidad Militar Nueva Granada, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Isaac Guzman
- Department of Endocrinology, Hospital Militar Central, Bogota 110221, Distrito Capital de Bogotá, Colombia
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Biagetti B, Araujo-Castro M, Tebe C, Marazuela M, Puig-Domingo M. Real-world evidence of effectiveness and safety of pasireotide in the treatment of acromegaly: a systematic review and meta-analysis. Rev Endocr Metab Disord 2025; 26:97-111. [PMID: 39527181 PMCID: PMC11790789 DOI: 10.1007/s11154-024-09928-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/04/2024] [Indexed: 11/16/2024]
Abstract
Pasireotide long-acting release (PAS-LAR) is a second-generation somatostatin receptor ligand (SRL) approved for acromegaly treatment. This meta-analysis aimed to evaluate the real-world effectiveness and safety of PAS-LAR in patients with acromegaly resistant to first-generation somatostatin receptor ligands (fgSRL). A systematic literature search was conducted in PubMed and Web of Science for real-world studies on PAS-LAR in acromegaly published between 2014 and 2023. Random-effects meta-analyses were performed on biochemical control rates, tumor shrinkage, and metabolic parameters. Twelve studies comprising 409 patients were included. The pooled rate of insulin-like growth factor 1 (IGF-1) control was 57.9% [95% CI: 48.4-66.8] and the percentage of patients with tumor shrinkage was 33.3% [95%CI: 19.7-50.4]. Significant reductions were observed in growth hormone standardized mean difference (SMD) 0.6 ng/mL [95% CI: 0.3 to 1.0] and IGF-1 levels SMD 0.9 ULN [95% CI: 0.4 to 1.4]. However, as expected, a worsening in glucose metabolism was noted as an increase in fasting glucose SMD - 0.8 mg/dL [95% CI: -1.0 to -0.5, p < 0.01], glycated hemoglobin SMD - 0.5% [95% CI: -0.7 to -0.2]. and type 2 diabetes mellitus prevalence SMD - 11.5% (95% CI: -17.5 to -5.5). PAS-LAR demonstrated higher effectiveness in real-world settings, with over 60% of patients achieving IGF-1 control compared to the around 30% efficacy observed in clinical trials. These findings suggest that PAS-LAR is an effective option for acromegaly patients resistant to fgSRL, but careful monitoring of glucose levels is essential. The high heterogeneity observed across studies emphasizes the need for identifying PAS-LAR response biomarkers to set-up individualized treatment approaches for optimizing patient outcomes.
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Affiliation(s)
- Betina Biagetti
- Endocrinology & Nutrition Department, Hospital Universitario Vall de Hebrón, CIBERER U747 (ISCIII), ENDO-ERN, Barcelona, Spain.
| | - Marta Araujo-Castro
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain & Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Madrid, Spain
| | - Cristian Tebe
- Biostatistics Support and Research Unit Germans Trias i Pujol Research Institute and Hospital (IGTP), Badalona, Spain
| | - Mónica Marazuela
- Endocrinology & Nutrition Department, Hospital Universitario La Princesa Madrid, Madrid, Spain
| | - Manel Puig-Domingo
- Endocrinology & Nutrition Department, Hospital Universitario Germans Trias i Pujol, CIBERER U747 (ISCIII), Universitat Autònoma de Barcelona, Badalona, Spain.
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3
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Occhi G, Voltan G, Chiloiro S, Bianchi A, Maffei P, Dassie F, Mantovani G, Del Sindaco G, Ferone D, Gatto F, Losa M, Cannavò S, Scaroni C, Ceccato F. The paradoxical GH response at OGTT does not predict Pasireotide efficacy but matters for glucose metabolism. J Endocrinol Invest 2025:10.1007/s40618-025-02534-3. [PMID: 39841390 DOI: 10.1007/s40618-025-02534-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 01/10/2025] [Indexed: 01/23/2025]
Abstract
PURPOSE A paradoxical increase in GH after oral glucose load (GH-Par) characterizes about one-third of acromegaly patients and is associated with a better response to first-generation somatostatin receptor ligands (fg-SRLs). Pasireotide is typically considered as a second-/third-line treatment. Here, we investigated the predictive role of GH-Par in pasireotide response and adverse event development. METHODS we collected a multicenter Italian retrospective cohort of 59 patients treated with pasireotide for at least 3 months, all having GH profile from OGTT. IGF-1 normalization or at least 30% reduction at the last follow-up visit defined a responder patient. RESULTS Considering the entire cohort, median IGF-1 levels before pasireotide (available in 57 patients) were 1.38 times the upper limit of normal (ULN) in patients with large (median size 18 mm) and invasive (82%) adenomas after failure of fg-SRL treatment. After a 40-month median treatment, pasireotide effectively reduced IGF-1 ULN levels in 41 patients, 37 of whom achieving normalization, and 4 with a ≥ 30% reduction. Thirteen patients were classified as GH-Par. The median pasireotide duration, dosage, and efficacy (9/12 responder in the GH-Par group and 32/45 in the GH-NPar) were similar between groups. However, the occurrence of new-onset or worsening glucose metabolism alterations (GMAs) after pasireotide was more frequent in GH-NPar (from 37 to 80%; p < 0.001) compared to GH-Par patients (from 69 to 76%), likely due to the higher prevalence of pre-existing GMAs in the GH-Par group before starting pasireotide (p = 0.038). CONCLUSIONS The GH-Par does not predict the response to pasireotide in acromegaly but can predict a worse metabolic profile.
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Affiliation(s)
- G Occhi
- Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35128, Padua, Italy.
| | - G Voltan
- Department of Medicine (DIMED), University of Padova, Padua, Italy
- Endocrine Disease Unit, University-Hospital of Padova, Padua, Italy
| | - S Chiloiro
- Pituitary Unit, Division of Endocrinology and Metabolism, IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy
- Department of Translational Medicine and Surgery, University Cattolica del Sacro Cuore, Rome, Italy
| | - A Bianchi
- Pituitary Unit, Division of Endocrinology and Metabolism, IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy
- Department of Translational Medicine and Surgery, University Cattolica del Sacro Cuore, Rome, Italy
| | - P Maffei
- Department of Medicine (DIMED), University of Padova, Padua, Italy
| | - F Dassie
- Department of Medicine (DIMED), University of Padova, Padua, Italy
| | - G Mantovani
- Department of Clinical Sciences and Community Health, University of Milan, 20122, Milan, Italy
- Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
| | - G Del Sindaco
- Department of Clinical Sciences and Community Health, University of Milan, 20122, Milan, Italy
- Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
| | - D Ferone
- Endocrinology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - F Gatto
- Endocrinology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - M Losa
- Department of Neurosurgery, IRCCS San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy
| | - S Cannavò
- Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
| | - C Scaroni
- Department of Medicine (DIMED), University of Padova, Padua, Italy
- Endocrine Disease Unit, University-Hospital of Padova, Padua, Italy
| | - F Ceccato
- Department of Medicine (DIMED), University of Padova, Padua, Italy
- Endocrine Disease Unit, University-Hospital of Padova, Padua, Italy
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Freda PU. Acromegaly: diagnostic challenges and individualized treatment. Expert Rev Endocrinol Metab 2025; 20:63-85. [PMID: 39757391 PMCID: PMC11832332 DOI: 10.1080/17446651.2024.2448784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 12/05/2024] [Indexed: 01/07/2025]
Abstract
INTRODUCTION Acromegaly is due in almost all cases to a GH-secreting pituitary tumor. GH and IGF-1 excesses lead to its multi-system clinical manifestations and comorbidities. Acromegaly is under-diagnosed and typically presents with advanced disease. When early or mild, clinical recognition and biochemical confirmation are especially challenging. Individualized treatment may optimize patient outcome. AREAS COVERED This review covers challenges to diagnosing acromegaly and reviews therapies for acromegaly with a focus on those aspects that can be individualized. EXPERT OPINION The first step in diagnosing acromegaly is recognizing it clinically. To improve this, increase awareness and education of the general population and healthcare professionals about the acromegaly phenotype is needed. Once suspected clinically, IGF-1 measurement is the initial step in making the biochemical diagnosis. GH may be < 1.0 µg/L after oral glucose suppression in early/mild cases. GH and IGF-1 should be considered in concert. Providers should be aware of conditions that can alter GH and IGF-1 levels and each assay's performance. An individualized treatment approach is best employed. Surgery is preferred as initial treatment and medical therapy as initial adjuvant therapy. In individualizing therapy, the advantages and disadvantages of each option and predictors of response to them should be considered.
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Affiliation(s)
- Pamela U Freda
- Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA
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Marques-Pamies M, Gil J, Sampedro-Nuñez M, Valassi E, Biagetti B, Giménez-Palop O, Hernández M, Martínez S, Carrato C, Villar-Taibo R, Araujo-Castro M, Blanco C, Simón-Muela I, Simó-Servat A, Xifra G, Vázquez F, Pavón I, Rosado JA, García-Centeno R, Zavala R, Hanzu FA, Mora M, Aulinas A, Vilarrasa N, Librizzi S, Calatayud M, de Miguel P, Alvarez-Escola C, Picó A, Salinas I, Fajardo-Montañana C, Cámara R, Bernabéu I, Jordà M, Webb SM, Marazuela M, Puig-Domingo M. Personalized Medicine in Acromegaly: The ACROFAST Study. J Clin Endocrinol Metab 2024; 110:30-40. [PMID: 38943661 PMCID: PMC11651705 DOI: 10.1210/clinem/dgae444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 03/25/2024] [Accepted: 06/26/2024] [Indexed: 07/01/2024]
Abstract
CONTEXT Medical treatment of acromegaly is currently performed through a trial-and-error approach using first-generation somatostatin receptor ligands (fgSRLs) as first-line drugs, with an effectiveness of about 50%, and subsequent drugs are indicated through clinical judgment. Some biomarkers can predict fgSRLs response. OBJECTIVE Here we report the results of the ACROFAST study, a clinical trial in which a protocol based on predictive biomarkers of fgSRLs was evaluated. METHODS This was a prospective trial (21 university hospitals) comparing the effectiveness and time-to-control of 2 treatment protocols during 12 months: (A) a personalized protocol in which the first options were fgSRLs as monotherapy or in combination with pegvisomant, or pegvisomant as monotherapy depending on the short acute octreotide test (sAOT) results, tumor T2 magnetic resonance (MRI) signal or immunostaining for E-cadherin; and (B) a control group with treatment always started by fgSRLs and the other drugs included after demonstrating inadequate control. RESULTS Eighty-five patients participated; 45 in the personalized and 40 in the control group. More patients in the personalized protocol achieved hormonal control compared to those in the control group (78% vs 53%, P < .05). Survival analysis revealed a hazard ratio for achieving hormonal control adjusted by age and sex of 2.53 (CI, 1.30-4.80). Patients from the personalized arm were controlled in a shorter period of time (P = .01). CONCLUSION Personalized medicine is feasible using a relatively simple protocol, and it allows a higher number of patients to achieve control in a shorter period of time.
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Affiliation(s)
| | - Joan Gil
- Endocrine Research Unit, Germans Trias i Pujol Research Institute
(IGTP), Badalona 08916, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER,
Unidad 747), Instituto de Salud Carlos III (ISCIII),
Barcelona 28029, Spain
| | - Miguel Sampedro-Nuñez
- Department of Endocrinology and Nutrition, La Princesa University
Hospital, Madrid 28006, Spain
| | - Elena Valassi
- Endocrine Research Unit, Germans Trias i Pujol Research Institute
(IGTP), Badalona 08916, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER,
Unidad 747), Instituto de Salud Carlos III (ISCIII),
Barcelona 28029, Spain
- Department of Endocrinology and Nutrition, Germans Trias i Pujol University
Hospital, Badalona 08916, Spain
| | - Betina Biagetti
- Department of Endocrinology and Nutrition, Vall Hebron University
Hospital, Barcelona 08035, Spain
| | - Olga Giménez-Palop
- Department of Endocrinology and Nutrition, Parc Taulí University
Hospital, Sabadell 08208, Spain
| | - Marta Hernández
- Department of Endocrinology and Nutrition, Arnau de Vilanova University
Hospital, Lleida 25198, Spain
- Endocrine Research Unit, Lleida Institute for Biomedical Research Dr.
Pifarré Foundation (IRBLleida), Lleida 25198,
Spain
| | - Silvia Martínez
- Department Hormonal Laboratory, Germans Trias i Pujol University
Hospital, Badalona 08916, Spain
| | - Cristina Carrato
- Department of Pathology, Germans Trias i Pujol University
Hospital, Badalona 08916, Spain
| | - Rocío Villar-Taibo
- Department of Endocrinology and Nutrition, Clínico de Santiago University
Hospital, Santiago de Compostela 15706, Spain
| | - Marta Araujo-Castro
- Department of Endocrinology and Nutrition, Ramón y Cajal University
Hospital, Madrid 28034, Spain
- Instituto de Investigación Ramón y Cajal (IRYCIS),
Madrid 28034, Spain
| | - Concepción Blanco
- Department of Endocrinology and Nutrition, Príncipe de Asturias University
Hospital, Madrid 28805, Spain
| | - Inmaculada Simón-Muela
- Department of Endocrinology and Nutrition, Joan XXIII University
Hospital, Tarragona 43005, Spain
- Endocrine Research Unit, Institut d´Investigació Sanitària Pere Virgili
(IISPV), Tarragona 43005, Spain
- Rovira i Virgili University (URV), Tarragona
43003, Spain
- Endocrine Research Unit, Institut d'Investigació Biomèdica de Bellvitge
(IDIBELL), Hospitalet de LLobregat 08907,
Spain
| | - Andreu Simó-Servat
- Department of Endocrinology and Nutrition, Mutua de Terrassa University
Hospital, Terrassa 08221, Spain
| | - Gemma Xifra
- Department of Endocrinology and Nutrition, Josep Trueta University
Hospital, Girona 17007, Spain
| | - Federico Vázquez
- Department of Endocrinology and Nutrition, Germans Trias i Pujol University
Hospital, Badalona 08916, Spain
| | - Isabel Pavón
- Department of Endocrinology and Nutrition, Getafe University
Hospital, Madrid 28905, Spain
| | - José Antonio Rosado
- Department of Endocrinology and Nutrition, Getafe University
Hospital, Madrid 28905, Spain
| | - Rogelio García-Centeno
- Department of Endocrinology and Nutrition, Gregorio Marañón University
Hospital, Madrid 28007, Spain
| | - Roxana Zavala
- Department of Endocrinology and Nutrition, Joan XXIII University
Hospital, Tarragona 43005, Spain
| | - Felicia Alexandra Hanzu
- Department of Endocrinology and Nutrition, Hospital Clinic University
Hospital, Barcelona 08036, Spain
- Endocrine Research Unit, Institut d’Investigacions Biomèdiques August Pi I
Sunyer (IDIBAPS), Barcelona 08036, Spain
| | - Mireia Mora
- Department of Endocrinology and Nutrition, Hospital Clinic University
Hospital, Barcelona 08036, Spain
- Endocrine Research Unit, Institut d’Investigacions Biomèdiques August Pi I
Sunyer (IDIBAPS), Barcelona 08036, Spain
| | - Anna Aulinas
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER,
Unidad 747), Instituto de Salud Carlos III (ISCIII),
Barcelona 28029, Spain
- Department of Endocrinology and Nutrition, Research Center for Pituitary
Diseases, Institut de Recerca Sant Pau (IIB-Sant Pau), Hospital Sant
Pau, Barcelona 08041, Spain
| | - Nuria Vilarrasa
- Endocrine Research Unit, Institut d'Investigació Biomèdica de Bellvitge
(IDIBELL), Hospitalet de LLobregat 08907,
Spain
- Department of Endocrinology and Nutrition, Bellvitge University
Hospital, Hospitalet de Llobregat 08907, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades
Metabólicas (CIBERDEM), Instituto de Salud Carlos III (ISCIII),
Madrid 28029, Spain
| | - Soledad Librizzi
- Department of Endocrinology and Nutrition, 12 de Octubre University
Hospital, Madrid 28041, Spain
| | - María Calatayud
- Department of Endocrinology and Nutrition, 12 de Octubre University
Hospital, Madrid 28041, Spain
| | - Paz de Miguel
- Department of Endocrinology and Nutrition, Clínico San Carlos University
Hospital, Madrid 2546, Spain
| | | | - Antonio Picó
- Department of Endocrinology and Nutrition, General University Hospital Dr
Balmis, Miguel Hernández University, Alicante
03010, Spain
- Endocrine Research Unit, Instituto de Investigación Sanitaria y Biomédica
de Alicante (ISABIAL), Alicante 03010, Spain
| | - Isabel Salinas
- Department of Endocrinology and Nutrition, Germans Trias i Pujol University
Hospital, Badalona 08916, Spain
| | | | - Rosa Cámara
- Department of Endocrinology and Nutrition, La Fe University
Hospital, Valencia 46026, Spain
| | - Ignacio Bernabéu
- Department of Endocrinology and Nutrition, Clínico de Santiago University
Hospital, Santiago de Compostela 15706, Spain
| | - Mireia Jordà
- Endocrine Research Unit, Germans Trias i Pujol Research Institute
(IGTP), Badalona 08916, Spain
| | - Susan M Webb
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER,
Unidad 747), Instituto de Salud Carlos III (ISCIII),
Barcelona 28029, Spain
- Department of Endocrinology and Nutrition, Research Center for Pituitary
Diseases, Institut de Recerca Sant Pau (IIB-Sant Pau), Hospital Sant
Pau, Barcelona 08041, Spain
- Departament de Medicina, Universitat Autònoma de Barcelona
(UAB), Bellaterra 08193, Spain
| | - Mónica Marazuela
- Department of Endocrinology and Nutrition, La Princesa University
Hospital, Madrid 28006, Spain
| | - Manel Puig-Domingo
- Endocrine Research Unit, Germans Trias i Pujol Research Institute
(IGTP), Badalona 08916, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER,
Unidad 747), Instituto de Salud Carlos III (ISCIII),
Barcelona 28029, Spain
- Department of Endocrinology and Nutrition, Germans Trias i Pujol University
Hospital, Badalona 08916, Spain
- Departament de Medicina, Universitat Autònoma de Barcelona
(UAB), Bellaterra 08193, Spain
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Schilbach K, Raverot G. Does size really matter? A closer look at the absolute size of growth hormone-secreting pituitary adenomas. Pituitary 2024; 27:440-443. [PMID: 39212829 DOI: 10.1007/s11102-024-01449-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/15/2024] [Indexed: 09/04/2024]
Affiliation(s)
- Katharina Schilbach
- Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany.
- Deggendorf Institute of Technology, Deggendorf, Germany.
| | - Gérald Raverot
- Department of Endocrinology, Reference Centre for Rare Pituitary Diseases HYPO, "Groupement Hospitalier Est" Hospices Civils de Lyon, Bron, France
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Marazuela M, Martínez-Hernandez R, Marques-Pamies M, Biagetti B, Araujo-Castro M, Puig-Domingo M. Predictors of biochemical response to somatostatin receptor ligands in acromegaly. Best Pract Res Clin Endocrinol Metab 2024; 38:101893. [PMID: 38575404 DOI: 10.1016/j.beem.2024.101893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/06/2024]
Abstract
Although predictors of response to first-generation somatostatin receptor ligands (fg-SRLs), and to a lesser extent to pasireotide, have been studied in acromegaly for many years, their use is still not recommended in clinical guidelines. Is there insufficient evidence to use them? Numerous biomarkers including various clinical, functional, radiological and molecular markers have been identified. The first ones are applicable pre-surgery, while the molecular predictors are utilized for patients not cured after surgery. In this regard, factors predicting a good response to fg-SRLs are specifically: low basal GH, a low GH nadir in the acute octreotide test, T2 MRI hypointensity, a densely granulated pattern, high immunohistochemistry staining for somatostatin receptor 2 (SSTR2), and E-cadherin. However, there is still a lack of consensus regarding which of these biomarkers is more useful or how to integrate them into clinical practice. With classical statistical methods, it is complex to define reliable and generalizable cut-off values for a single biomarker. The potential solution to the limitations of traditional methods involves combining systems biology with artificial intelligence, which is currently providing answers to such long-standing questions that may eventually be finally included into the clinical guidelines and make personalized medicine a reality. The aim of this review is to describe the current knowledge of the main fg-SRLs and pasireotide response predictors, discuss their current usefulness, and point to future directions in the research of this field.
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Affiliation(s)
- Mónica Marazuela
- Department of Endocrinology and Nutrition Hospital Universitario La Princesa, Universidad Autónoma de Madrid,Instituto de Investigación Princesa, and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER GCV14/ER/12), Madrid, Spain.
| | | | | | - Betina Biagetti
- Endocrinology & Nutrition Service, Vall d'Hebron University Hospital and Vall d'Hebron Research Institute (VHIR), Department of Medicine, Autonomous University of Barcelona, Reference Networks (ERN), 08035 Barcelona, Spain
| | - Marta Araujo-Castro
- Endocrinology & Nutrition Department. Hospital Universitario Ramón y Cajal, Spain & Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Madrid, Spain
| | - Manel Puig-Domingo
- Department of Endocrinology and Nutrition, Department of Medicine, Germans Trias i Pujol Research Institute and Hospital, Universitat Autònoma de Barcelona, Spain and Centro de Investigación Biomédica en Red de Enfermedades Raras CIBERER G747, Badalona, Spain
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8
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Kasuki L, Lamback E, Antunes X, Gadelha MR. Biomarkers of response to treatment in acromegaly. Expert Rev Endocrinol Metab 2024; 19:71-80. [PMID: 38078447 DOI: 10.1080/17446651.2023.2293107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Accepted: 12/06/2023] [Indexed: 01/03/2024]
Abstract
INTRODUCTION Medical treatment of acromegaly is based in a `trial and error` approach. First-generation somatostatin receptor ligands (fg-SRL) are prescribed as first-line medical therapy to the vast majority of patients, despite lack of disease control in approximately 60% of patients. However, other drugs used in acromegaly treatment are available (cabergoline, pasireotide and pegvisomant). AREAS COVERED In this article, we review and discuss the biomarkers of response to medical treatment in acromegaly. EXPERT OPINION Biomarkers for fg-SRL that can already be applied in clinical practice are: gender, age, pretreatment GH and IGF-I levels, cytokeratin granulation pattern, and the expression of somatostatin receptor type 2. Using biomarkers of response could guide treatment towards precision medicine with greater efficacy and lower costs.
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Affiliation(s)
- Leandro Kasuki
- Neuroendocrinology Research Center/Endocrinology Division, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Neuroendocrinology Division, Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde, Rio de Janeiro, Brazil
- Endocrinology Division, Hospital Federal de Bonsucesso, Rio de Janeiro, Brazil
| | - Elisa Lamback
- Neuroendocrinology Research Center/Endocrinology Division, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Neuroendocrinology Division, Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde, Rio de Janeiro, Brazil
- Neuropathology and Molecular Genetics Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde, Rio de Janeiro, Brazil
| | - Ximene Antunes
- Neuroendocrinology Research Center/Endocrinology Division, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Mônica R Gadelha
- Neuroendocrinology Research Center/Endocrinology Division, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Neuroendocrinology Division, Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde, Rio de Janeiro, Brazil
- Neuropathology and Molecular Genetics Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde, Rio de Janeiro, Brazil
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