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Targeting Aggressive Pituitary Adenomas at the Molecular Level—A Review
 
 
Article

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

1
Institute of Endocrinology, Rabin Medical Center Beilinson Hospital, Petach Tikva 4941492, Israel
2
Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
3
Pituitary Center and Departments of Medicine (Endocrinology) and Neurological Surgery, Oregon Health & Science University, Portland, OR 97239, USA
4
Maccabi Health Care Services, Tel Aviv 6473925, Israel
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Maccabi Health Care Services-Central Laboratory, Rehovot 7644620, Israel
6
Statistical Consulting Unit, Rabin Medical Center, Beilinson Hospital, Petach Tikva 4941492, Israel
*
Author to whom correspondence should be addressed.
Academic Editor: Fernando Cordido
J. Clin. Med. 2022, 11(6), 1558; https://doi.org/10.3390/jcm11061558
Received: 7 February 2022 / Revised: 28 February 2022 / Accepted: 9 March 2022 / Published: 11 March 2022
(This article belongs to the Special Issue Management of Pituitary Tumors: Current and Future Treatment Options)
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. View Full-Text
Keywords: corticotroph adenoma; Cushing’s disease; pituitary corticotroph adenoma; Cushing’s disease; pituitary
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MDPI and ACS Style

Akirov, A.; Shimon, I.; Fleseriu, M.; Dotan, I.; Manisterski, Y.; Aviran-Barak, N.; Nadler, V.; Alboim, S.; Shochat, T.; Tsvetov, G.; Hirsch, D. Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing’s Disease: Does Size Matter? J. Clin. Med. 2022, 11, 1558. https://doi.org/10.3390/jcm11061558

AMA Style

Akirov A, Shimon I, Fleseriu M, Dotan I, Manisterski Y, Aviran-Barak N, Nadler V, Alboim S, Shochat T, Tsvetov G, Hirsch D. Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing’s Disease: Does Size Matter? Journal of Clinical Medicine. 2022; 11(6):1558. https://doi.org/10.3390/jcm11061558

Chicago/Turabian Style

Akirov, Amit, Ilan Shimon, Maria Fleseriu, Idit Dotan, Yossi Manisterski, Nirit Aviran-Barak, Varda Nadler, Sandra Alboim, Tzipora Shochat, Gloria Tsvetov, and Dania Hirsch. 2022. "Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing’s Disease: Does Size Matter?" Journal of Clinical Medicine 11, no. 6: 1558. https://doi.org/10.3390/jcm11061558

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