Skip to content
2000
Volume 25, Issue 10
  • ISSN: 1871-5303
  • E-ISSN: 2212-3873
file format text download EPUB
file format pdf download PDF
side by side viewer icon HTML

Abstract

Background

The possibility of sustained disease remission in functioning pituitary adenomas after drug withdrawal is well-known for prolactinomas and it has also been described in a subset of acromegalic patients. On the contrary, medical treatment for Cushing’s Disease (CD) is generally considered a life-long measure except for previously radio-treated patients. Sparse evidence of spontaneous remissions in CD has been reported, mainly related to a possible pituitary tumor apoplexy. To the best of our knowledge, none of these cases has included the use of a pituitary targeting agent.

Case Presentation

Herein, we have reported the case of a radiotherapy-naïve patient with persistent CD after pituitary surgery who participated in the CSOMG230 trials, presenting sustained remission after Long-acting Release (LAR) pasireotide withdrawal. Under monthly pasireotide LAR 40 mg, the patient achieved urinary hormone control and clinical signs of cortisol excess normalization. After 8 years of treatment, the patient completed the study protocol and had to withdraw the drug as it was no longer available for CD in Italy. Before starting new therapies, we reassessed hormone levels that were surprisingly within normal ranges. At 24 months after the last dose of pasireotide, the patient was still in clinical and biochemical full remission. We have also briefly reviewed previous cases of sustained remission after somatostatin analogues withdrawal in other functioning pituitary adenomas.

Conclusion

Far from the general rule, this case suggests that prolonged treatment with pasireotide LAR might induce a durable CD remission. A dose down-titration/suspension might be considered in patients well-controlled on long-term therapy and with negative pituitary imaging. However, close monitoring is recommended given the high rate of complications in untreated patients.

© 2025 The Author(s).
Published by Bentham Science Publishers. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/emiddt/10.2174/0118715303328077240719055819
2024-07-30
2025-08-14

  • From This Site

    /content/journals/emiddt/10.2174/0118715303328077240719055819
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
The full text of this item is not currently available.

References

  1. LimumpornpetchP. MorganA.W. TiganescuA. BaxterP.D. Nyawira NyagaV. Pujades-RodriguezM. StewartP.M. The effect of endogenous cushing syndrome on all-cause and cause-specific mortality.J. Clin. Endocrinol. Metab.202210782377238810.1210/clinem/dgac26535486378
     [Google Scholar]
  2. FleseriuM. AuchusR. BancosI. Ben-ShlomoA. BertheratJ. BiermaszN.R. BoguszewskiC.L. BronsteinM.D. BuchfelderM. CarmichaelJ.D. CasanuevaF.F. CastinettiF. ChansonP. FindlingJ. GadelhaM. GeerE.B. GiustinaA. GrossmanA. GurnellM. HoK. IoachimescuA.G. KaiserU.B. KaravitakiN. KatznelsonL. KellyD.F. LacroixA. McCormackA. MelmedS. MolitchM. MortiniP. Newell-PriceJ. NiemanL. PereiraA.M. PetersennS. PivonelloR. RaffH. ReinckeM. SalvatoriR. ScaroniC. ShimonI. StratakisC.A. SwearingenB. TabarinA. TakahashiY. TheodoropoulouM. TsagarakisS. ValassiE. VarlamovE.V. VilaG. WassJ. WebbS.M. ZatelliM.C. BillerB.M.K. Consensus on diagnosis and management of Cushing’s disease: A guideline update.Lancet Diabetes Endocrinol.202191284787510.1016/S2213‑8587(21)00235‑734687601
     [Google Scholar]
  3. MelmedS. CasanuevaF.F. HoffmanA.R. KleinbergD.L. MontoriV.M. SchlechteJ.A. WassJ.A.H. Endocrine Society Diagnosis and treatment of hyperprolactinemia: An Endocrine Society clinical practice guideline.J. Clin. Endocrinol. Metab.201196227328810.1210/jc.2010‑169221296991
     [Google Scholar]
  4. SalaE. CarosiG. Del SindacoG. MungariR. CremaschiA. SerbanA.L. RonchiC.L. FerranteE. ArosioM. MantovaniG. Long-term remission of acromegaly after somatostatin analogues withdrawal: a single-centre experience.J. Endocrinol. Invest.202144122593259910.1007/s40618‑021‑01562‑z34018167
     [Google Scholar]
  5. Popa IlieI.R. HerdeanA.M. HerdeanA.I. GeorgescuC.E. Spontaneous remission of Cushing’s disease: A systematic review.Ann. Endocrinol. (Paris)202182661362110.1016/j.ando.2021.10.00234687655
     [Google Scholar]
  6. de BruinC. FeeldersR.A. WaaijersA.M. van KoetsveldP.M. Sprij-MooijD.M. LambertsS.W.J. HoflandL.J. Differential regulation of human dopamine D2 and somatostatin receptor subtype expression by glucocorticoids in vitro.J. Mol. Endocrinol.2009421475610.1677/JME‑08‑011018852217
     [Google Scholar]
  7. MondinA. ManaraR. VoltanG. TizianelI. DenaroL. FerrariM. BarbotM. ScaroniC. CeccatoF. Pasireotide-induced shrinkage in gh and acth secreting pituitary adenoma: A systematic review and meta-analysis.Front. Endocrinol. (Lausanne)20221393575910.3389/fendo.2022.93575935846311
     [Google Scholar]
  8. LacroixA. GuF. GallardoW. PivonelloR. YuY. WitekP. BoscaroM. SalvatoriR. YamadaM. TauchmanovaL. RoughtonM. RavichandranS. PetersennS. BillerB.M.K. Newell-PriceJ. ArnaldiG. AshaH.S. BandgarT. BarkanA. BieringH. BexM. BolanowskiM. BronsteinM.D. BrueT. BrueraD. CavagniniF. ComlekciA. De BlockC. DelibasiT. Fajardo-MontañanaC. FeeldersR.A. FleseriuM. GadelhaM.R. GeerE.B. HeaneyA. HoudeG. IchiharaA. ImranS.A. IoachimescuA. KadiogluP. LiY. LoliP. NishiyamaM. RozhinskayaL. RuchalaM. SaitohY. SchöflC. SchopohlJ. ShimatsuA. ShimizuC. SnabboonT. SnyderP. SuzakiN. TabarinA. TakahashiY. BrittoS.T. T’SjoenG. VantyghemM-C. VelkeniersB. WebbS. YamadaS. Efficacy and safety of once-monthly pasireotide in Cushing’s disease: A 12 month clinical trial.Lancet Diabetes Endo.201861172610.1016/S2213‑8587(17)30326‑129032078
     [Google Scholar]
  9. FleseriuM. PetersennS. BillerB.M.K. KadiogluP. De BlockC. T’SjoenG. VantyghemM.C. TauchmanovaL. WojnaJ. RoughtonM. LacroixA. Newell-PriceJ. Long-term efficacy and safety of once-monthly pasireotide in Cushing’s disease: A Phase III extension study.Clin. Endocrinol. (Oxf.)201991677678510.1111/cen.1408131465533
     [Google Scholar]
  10. CeccatoF. ArtusiC. BarbotM. LizzulL. PinelliS. CostantiniG. NieroS. AntonelliG. PlebaniM. ScaroniC. Dexamethasone measurement during low-dose suppression test for suspected hypercortisolism: Threshold development with and validation.J. Endocrinol. Invest.20204381105111310.1007/s40618‑020‑01197‑632060745
     [Google Scholar]
  11. BarbotM. AlbigerN. KoutroumpiS. CeccatoF. FrigoA.C. ManaraR. FassinaA. GardimanM.P. ScanariniM. ManteroF. ScaroniC. Predicting late recurrence in surgically treated patients with Cushing’s disease.Clin. Endocrinol. (Oxf.)201379339440110.1111/cen.1213323278711
     [Google Scholar]
  12. NiemanL.K. BillerB.M.K. FindlingJ.W. Newell-PriceJ. SavageM.O. StewartP.M. MontoriV.M. The diagnosis of cushing’s syndrome: an endocrine society clinical practice guideline.J. Clin. Endocrinol. Metab.20089351526154010.1210/jc.2008‑012518334580
     [Google Scholar]
  13. DicksteinG. SpindelA. ShechnerC. AdawiF. GutmanH. Spontaneous remission in Cushing’s disease.Arch. Intern. Med.1991151118518910.1001/archinte.1991.004000101710281985595
     [Google Scholar]
  14. DicksteinG. AradE. ShechnerC. Late complications in remission from Cushing disease. Recurrence of tumor with reinfarction or transformation into a silent adenoma.Arch. Intern. Med.1997157202377238010.1001/archinte.1997.004404101090139361580
     [Google Scholar]
  15. Le NestourE. AbécassisJ.P. BertagnaX. BonninA. LutonJ.P. Silent necrosis of a pituitary corticotroph adenoma revealed by timely magnetic resonance imaging: A cause of spontaneous remission of Cushing’s disease.Eur. J. Endocrinol.1994130546947110.1530/eje.0.13004698180674
     [Google Scholar]
  16. PignattaA.B. DíazA.G. GómezR.M. BrunoO.D. Spontaneous remission of Cushing’s disease after disappearance of a microadenoma attached to the pituitary stalk.Pituitary200471454910.1023/B:PITU.0000044626.25624.4815638298
     [Google Scholar]
  17. GuzzoM.F. CarvalhoL.R. BronsteinM.D. Ketoconazole treatment decreases the viability of immortalized pituitary cell lines associated with an increased expression of apoptosis-related genes and cell cycle inhibitors.J. Neuroendocrinol.201527761662310.1111/jne.1227725808816
     [Google Scholar]
  18. NowakE. VogelF. AlbaniA. BraunL. RubinsteinG. ZoppS. RitzelK. BeuschleinF. TheodoropoulouM. ReinckeM. Diagnostic challenges in cyclic Cushing’s syndrome: a systematic review.Lancet Diabetes Endocrinol.202311859360610.1016/S2213‑8587(23)00150‑X37429301
     [Google Scholar]
  19. BatistaD.L. ZhangX. GejmanR. AnsellP.J. ZhouY. JohnsonS.A. SwearingenB. Hedley-WhyteE.T. StratakisC.A. KlibanskiA. The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas.J. Clin. Endocrinol. Metab.200691114482448810.1210/jc.2006‑124516940446
     [Google Scholar]
  20. MurasawaS. KageyamaK. SugiyamaA. IshigameN. NiiokaK. SudaT. DaimonM. Inhibitory effects of SOM230 on adrenocorticotropic hormone production and corticotroph tumor cell proliferation in vitro and in vivo.Mol. Cell. Endocrinol.20143941-2374610.1016/j.mce.2014.07.00125011056
     [Google Scholar]
  21. ZatelliM.C. PiccinD. VignaliC. TagliatiF. AmbrosioM.R. BondanelliM. CiminoV. BianchiA. SchmidH.A. ScanariniM. PontecorviA. De MarinisL. MairaG. UbertiE.C. Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion.Endocr. Relat. Cancer20071419110210.1677/ERC‑06‑002617395978
     [Google Scholar]
  22. CoopmansE.C. van der LelyA.J. SchneidersJ.J. NeggersS.J.C.M.M. Potential antitumour activity of pasireotide on pituitary tumours in acromegaly.Lancet Diabetes Endocrinol.20197642542610.1016/S2213‑8587(19)30113‑530956093
     [Google Scholar]
  23. ChiloiroS. GiampietroA. BianchiA. TartaglioneT. BimaC. VitaM.G. SpinelloM. PontecorviA. De MarinisL. Acromegaly can be cured by first-line pasireotide treatment?Endocrine201964119619910.1007/s12020‑019‑01874‑430798431
     [Google Scholar]
  24. YuN. WangL. YangH. PanH. DuanL. ZhuH. Persistent remission of acromegaly in a patient with GH-secreting pituitary adenoma: Effect of treatment with pasireotide long-acting release and consequence of treatment withdrawal.J. Clin. Pharm. Ther.202247683584010.1111/jcpt.1361535167717
     [Google Scholar]
  25. DalyA.F. Comment on “Persistent remission of acromegaly in a patient with GH-secreting pituitary adenoma: Effect of treatment with pasireotide long-acting release and consequence of treatment withdrawal”.J. Clin. Pharm. Ther.20224791490149010.1111/jcpt.1365135313386
     [Google Scholar]
  26. LombardiM. LupiI. CosottiniM. RossiG. ManettiL. RaffaelliV. SardellaC. MartinoE. BogazziF. Lower prolactin levels during cabergoline treatment are associated to tumor shrinkage in prolactin secreting pituitary adenoma.Horm. Metab. Res.2014461393994210.1055/s‑0034‑138992525230324
     [Google Scholar]
  27. AndersenI.B. SørensenM.G.R. DogansenS.C. Cheol RyongK. VilarL. Feldt-RasmussenU. KroghJ. Withdrawal of dopamine agonist treatment in patients with hyperprolactinaemia: A systematic review and meta-analysis.Clin. Endocrinol. (Oxf.)202297551953110.1111/cen.1471435261059
     [Google Scholar]
  28. XiaM.Y. LouX.H. LinS.J. WuZ.B. Optimal timing of dopamine agonist withdrawal in patients with hyperprolactinemia: a systematic review and meta-analysis.Endocrine2018591506110.1007/s12020‑017‑1444‑929043560
     [Google Scholar]
  29. ZouY. LiD. GuJ. ChenS. WenX. DongJ. JiangX. The recurrence of prolactinoma after withdrawal of dopamine agonist: a systematic review and meta-analysis.BMC Endocr. Disord.202121122510.1186/s12902‑021‑00889‑134774043
     [Google Scholar]
  30. KatznelsonL. LawsE.R.Jr MelmedS. MolitchM.E. MuradM.H. UtzA. WassJ.A.H. Acromegaly: an endocrine society clinical practice guideline.J. Clin. Endocrinol. Metab.201499113933395110.1210/jc.2014‑270025356808
     [Google Scholar]
  31. AvramidisA. PolyzosS.A. EfstathiadouZ. KitaM. Sustained clinical inactivity and stabilization of GH/IGF-1 levels in an acromegalic patient after discontinuation of somatostatin analogue treatment.Endocr. J.200855235135710.1507/endocrj.K07E‑05518379126
     [Google Scholar]
  32. VerhelstJ.A. AbramsP.J. AbsR. Remission of acromegaly following long-term therapy with cabergoline: Report of two cases.Pituitary200811110310710.1007/s11102‑007‑0041‑y17530416
     [Google Scholar]
  33. AuriemmaR.S. GaldieroM. GrassoL.F.S. VitaleP. CozzolinoA. LombardiG. ColaoA. PivonelloR. Complete disappearance of a GH-secreting pituitary macroadenoma in a patient with acromegaly: Effect of treatment with lanreotide Autogel and consequence of treatment withdrawal.Eur. J. Endocrinol.2010162599399910.1530/EJE‑09‑076920156970
     [Google Scholar]
  34. RamírezC. VargasG. GonzálezB. GrossmanA. RábagoJ. SosaE. Espinosa-de-Los-MonterosA.L. MercadoM. Discontinuation of octreotide LAR after long term, successful treatment of patients with acromegaly: Is it worth trying?Eur. J. Endocrinol.20121661212610.1530/EJE‑11‑073821993154
     [Google Scholar]
  35. VilarL. FleseriuM. NavesL.A. AlbuquerqueJ.L. GadelhaP.S. dos Santos FariaM. NascimentoG.C. MontenegroR.M.Jr MontenegroR.M. Can we predict long-term remission after somatostatin analog withdrawal in patients with acromegaly? Results from a multicenter prospective trial.Endocrine201446357758410.1007/s12020‑013‑0094‑924272601
     [Google Scholar]
  36. HatipogluE. BozcanS. KadiogluP. Discontinuation of somatostatin analogs while acromegaly is in long-term remission.Pituitary201518455456010.1007/s11102‑014‑0608‑325301076
     [Google Scholar]
  37. Alvarez-EscolaC. Cardenas-SalasJ. Active postoperative acromegaly: Sustained remission after discontinuation of somatostatin analogues.Endocrinol. Diabetes Metab. Case Rep.20162016201610.1530/EDM‑16‑009227933171
     [Google Scholar]
  38. CasagrandeA. BronsteinM.D. JalladR.S. MoraesA.B. EliasP.C.L. CastroM. CzepielewskiM.A. BoschiA. Ribeiro-OliveiraA.Jr SchweizerJ.R.O.L. VilarL. NazatoD.M. GadelhaM.R. AbuchamJ. all other investigators of the study Long-term remission of acromegaly after octreotide withdrawal is an uncommon and frequently unsustainable event.Neuroendocrinology2017104327327910.1159/00044654227161443
     [Google Scholar]
  39. CasagrandeA. BronsteinM.D. JalladR.S. MotaJ.I. TabetA. AbuchamJ. Remission of acromegaly after treatment withdrawal in patients controlled by cabergoline alone or in combination with octreotide: Results from a multicenter study.J. Endocrinol. Invest.201740552352810.1007/s40618‑016‑0595‑528012070
     [Google Scholar]
  40. PuglisiS. SpagnoloF. RagoneseM. CannavòS. FerraùF. First report on persistent remission of acromegaly after withdrawal of long-term pegvisomant monotherapy.Growth Horm. IGF Res.201945171910.1016/j.ghir.2019.02.00130772778
     [Google Scholar]
  41. RonchiC.L. RizzoE. LaniaA.G. PivonelloR. GrottoliS. ColaoA. GhigoE. SpadaA. ArosioM. Beck-PeccozP. Preliminary data on biochemical remission of acromegaly after somatostatin analogs withdrawal.Eur. J. Endocrinol.20081581192510.1530/EJE‑07‑048818166813
     [Google Scholar]
/content/journals/emiddt/10.2174/0118715303328077240719055819
Loading
Long-term Remission in Functioning Pituitary Adenomas after Medical Therapy Withdrawal: A Chance for Cushing’s Disease
Endocr Metab Immune Disord Drug Targets 25, 824 (2025); https://doi.org/10.2174/0118715303328077240719055819
/content/journals/emiddt/10.2174/0118715303328077240719055819
/content/journals/emiddt/10.2174/0118715303328077240719055819
Loading

Data & Media loading...


  • Article Type:     Case Report
Keyword(s): CD remission; Cushing’s disease; medical therapy; pasireotide LAR; pituitary adenomas; somatostatin analogues

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test