Cargando…

Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing’s Disease: Does Size Matter?

Background: Reports on clinical and biochemical differences between adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas and macroadenomas are limited and inconsistent. Objective: Compare clinical and biochemical characteristics of patients with corticotroph microadenomas and macroad...

Descripción completa

Detalles Bibliográficos
Autores principales: Akirov, Amit, Shimon, Ilan, Fleseriu, Maria, Dotan, Idit, Manisterski, Yossi, Aviran-Barak, Nirit, Nadler, Varda, Alboim, Sandra, Shochat, Tzipora, Tsvetov, Gloria, Hirsch, Dania
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8953359/
https://www.ncbi.nlm.nih.gov/pubmed/35329884
http://dx.doi.org/10.3390/jcm11061558
_version_ 1784675831462756352
author Akirov, Amit
Shimon, Ilan
Fleseriu, Maria
Dotan, Idit
Manisterski, Yossi
Aviran-Barak, Nirit
Nadler, Varda
Alboim, Sandra
Shochat, Tzipora
Tsvetov, Gloria
Hirsch, Dania
author_facet Akirov, Amit
Shimon, Ilan
Fleseriu, Maria
Dotan, Idit
Manisterski, Yossi
Aviran-Barak, Nirit
Nadler, Varda
Alboim, Sandra
Shochat, Tzipora
Tsvetov, Gloria
Hirsch, Dania
author_sort Akirov, Amit
collection PubMed
description Background: Reports on clinical and biochemical differences between adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas and macroadenomas are limited and inconsistent. Objective: Compare clinical and biochemical characteristics of patients with corticotroph microadenomas and macroadenomas and assess predictive factors for biochemical response to dynamic testing for Cushing’s disease (CD) in a clinical trial and a systematic review. A second aim was to evaluate differences between macroadenomas with and without cavernous and sphenoid sinus invasion. Methods: Retrospective charts review of patients with CD, treated at Rabin Medical Center between 2000 and 2020 or at Maccabi Healthcare Services in Israel between 2005 and 2017. Clinical and biochemical factors were compared between patients with corticotroph microadenomas and macroadenomas. We have also performed a systematic review of all studies (PRISMA guidelines) comparing corticotroph microadenomas with macroadenomas up to 31 November 2021. Results: The cohort included 105 patients (82 women, 78%; mean age, 41.5 ± 14.5 years), including 80 microadenomas (mean size, 5.2 ± 2.2 mm) and 25 macroadenomas (mean size, 18.0 ± 7.7 mm). Other baseline characteristics were similar between groups. Most common presentation suggestive for hypercortisolemia among patients with both micro- and macroadenomas were weight gain (46.3% vs. 48.0%, p = NS) and Cushingoid features (27.5% vs. 20.0%, p = NS). Mean 24 h urinary free cortisol (5.2 ± 5.4 × ULN vs. 7.8 ± 8.7 × ULN) and serum cortisol following low-dose dexamethasone (372.0 ± 324.5 vs. 487.6 ± 329.8 nmol/L), though higher for macroadenomas, were not significant. Levels of ACTH were greater for macroadenomas (1.9 ± 1.2 × ULN vs. 1.3 ± 0.8 × ULN, respectively, p = 0.01). Rates of recurrent/persistent disease were similar, as were rates of post-operative adrenal insufficiency and duration of post-operative glucocorticoid replacement. Macroadenomas with sphenoid or cavernous sinus invasion were associated with higher ACTH, 24 h free urinary cortisol, and serum cortisol following low-dose dexamethasone, compared with suprasellar or intrasellar macroadenomas. Conclusions: While ACTH-secreting macroadenomas exhibit higher plasma ACTH than microadenomas, there was no association between tumor size with cortisol hypersecretion or clinical features of hypercortisolemia. Though overall rare, increased awareness is needed for patients with CD with tumor extension in the cavernous or sphenoid sinus, which displays increased biochemical burden, highlighting that extent/location of the adenoma may be more important than size per se. Our systematic review, the first on this topic, highlights differences and similarities with our study.
format Online
Article
Text
id pubmed-8953359
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-89533592022-03-26 Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing’s Disease: Does Size Matter? Akirov, Amit Shimon, Ilan Fleseriu, Maria Dotan, Idit Manisterski, Yossi Aviran-Barak, Nirit Nadler, Varda Alboim, Sandra Shochat, Tzipora Tsvetov, Gloria Hirsch, Dania J Clin Med Article Background: Reports on clinical and biochemical differences between adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas and macroadenomas are limited and inconsistent. Objective: Compare clinical and biochemical characteristics of patients with corticotroph microadenomas and macroadenomas and assess predictive factors for biochemical response to dynamic testing for Cushing’s disease (CD) in a clinical trial and a systematic review. A second aim was to evaluate differences between macroadenomas with and without cavernous and sphenoid sinus invasion. Methods: Retrospective charts review of patients with CD, treated at Rabin Medical Center between 2000 and 2020 or at Maccabi Healthcare Services in Israel between 2005 and 2017. Clinical and biochemical factors were compared between patients with corticotroph microadenomas and macroadenomas. We have also performed a systematic review of all studies (PRISMA guidelines) comparing corticotroph microadenomas with macroadenomas up to 31 November 2021. Results: The cohort included 105 patients (82 women, 78%; mean age, 41.5 ± 14.5 years), including 80 microadenomas (mean size, 5.2 ± 2.2 mm) and 25 macroadenomas (mean size, 18.0 ± 7.7 mm). Other baseline characteristics were similar between groups. Most common presentation suggestive for hypercortisolemia among patients with both micro- and macroadenomas were weight gain (46.3% vs. 48.0%, p = NS) and Cushingoid features (27.5% vs. 20.0%, p = NS). Mean 24 h urinary free cortisol (5.2 ± 5.4 × ULN vs. 7.8 ± 8.7 × ULN) and serum cortisol following low-dose dexamethasone (372.0 ± 324.5 vs. 487.6 ± 329.8 nmol/L), though higher for macroadenomas, were not significant. Levels of ACTH were greater for macroadenomas (1.9 ± 1.2 × ULN vs. 1.3 ± 0.8 × ULN, respectively, p = 0.01). Rates of recurrent/persistent disease were similar, as were rates of post-operative adrenal insufficiency and duration of post-operative glucocorticoid replacement. Macroadenomas with sphenoid or cavernous sinus invasion were associated with higher ACTH, 24 h free urinary cortisol, and serum cortisol following low-dose dexamethasone, compared with suprasellar or intrasellar macroadenomas. Conclusions: While ACTH-secreting macroadenomas exhibit higher plasma ACTH than microadenomas, there was no association between tumor size with cortisol hypersecretion or clinical features of hypercortisolemia. Though overall rare, increased awareness is needed for patients with CD with tumor extension in the cavernous or sphenoid sinus, which displays increased biochemical burden, highlighting that extent/location of the adenoma may be more important than size per se. Our systematic review, the first on this topic, highlights differences and similarities with our study. MDPI 2022-03-11 /pmc/articles/PMC8953359/ /pubmed/35329884 http://dx.doi.org/10.3390/jcm11061558 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Akirov, Amit
Shimon, Ilan
Fleseriu, Maria
Dotan, Idit
Manisterski, Yossi
Aviran-Barak, Nirit
Nadler, Varda
Alboim, Sandra
Shochat, Tzipora
Tsvetov, Gloria
Hirsch, Dania
Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing’s Disease: Does Size Matter?
title Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing’s Disease: Does Size Matter?
title_full Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing’s Disease: Does Size Matter?
title_fullStr Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing’s Disease: Does Size Matter?
title_full_unstemmed Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing’s Disease: Does Size Matter?
title_short Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing’s Disease: Does Size Matter?
title_sort clinical study and systematic review of pituitary microadenomas vs. macroadenomas in cushing’s disease: does size matter?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8953359/
https://www.ncbi.nlm.nih.gov/pubmed/35329884
http://dx.doi.org/10.3390/jcm11061558
work_keys_str_mv AT akirovamit clinicalstudyandsystematicreviewofpituitarymicroadenomasvsmacroadenomasincushingsdiseasedoessizematter
AT shimonilan clinicalstudyandsystematicreviewofpituitarymicroadenomasvsmacroadenomasincushingsdiseasedoessizematter
AT fleseriumaria clinicalstudyandsystematicreviewofpituitarymicroadenomasvsmacroadenomasincushingsdiseasedoessizematter
AT dotanidit clinicalstudyandsystematicreviewofpituitarymicroadenomasvsmacroadenomasincushingsdiseasedoessizematter
AT manisterskiyossi clinicalstudyandsystematicreviewofpituitarymicroadenomasvsmacroadenomasincushingsdiseasedoessizematter
AT aviranbaraknirit clinicalstudyandsystematicreviewofpituitarymicroadenomasvsmacroadenomasincushingsdiseasedoessizematter
AT nadlervarda clinicalstudyandsystematicreviewofpituitarymicroadenomasvsmacroadenomasincushingsdiseasedoessizematter
AT alboimsandra clinicalstudyandsystematicreviewofpituitarymicroadenomasvsmacroadenomasincushingsdiseasedoessizematter
AT shochattzipora clinicalstudyandsystematicreviewofpituitarymicroadenomasvsmacroadenomasincushingsdiseasedoessizematter
AT tsvetovgloria clinicalstudyandsystematicreviewofpituitarymicroadenomasvsmacroadenomasincushingsdiseasedoessizematter
AT hirschdania clinicalstudyandsystematicreviewofpituitarymicroadenomasvsmacroadenomasincushingsdiseasedoessizematter