Remission in Cushing's disease is predicted by cortisol burden and its withdrawal following pituitary surgery

doi:10.1007/s40618-020-01495-z

. 2021 Sep;44(9):1869-1878.

doi: 10.1007/s40618-020-01495-z. Epub 2021 Jan 16.

Remission in Cushing's disease is predicted by cortisol burden and its withdrawal following pituitary surgery

A Dutta^#¹, N Gupta^#¹, R Walia², A Bhansali¹, P Dutta¹, S K Bhadada¹, R Pivonello³, C K Ahuja⁴, S Dhandapani⁵, A Hajela¹, C Simeoli³, N Sachdeva¹, U N Saikia⁶

Affiliations

¹ Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Nehru Extension block, Chandigarh, 160012, India.
² Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Nehru Extension block, Chandigarh, 160012, India. ramawalia@rediffmail.com.
³ Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Naples, Italy.
⁴ Department of Radiology, PGIMER, Chandigarh, India.
⁵ Department of Neurosurgery, PGIMER, Chandigarh, India.
⁶ Department of Histopathology, PGIMER, Chandigarh, India.

^# Contributed equally.

PMID: 33453019
DOI: 10.1007/s40618-020-01495-z

Remission in Cushing's disease is predicted by cortisol burden and its withdrawal following pituitary surgery

A Dutta et al. J Endocrinol Invest. 2021 Sep.

. 2021 Sep;44(9):1869-1878.

doi: 10.1007/s40618-020-01495-z. Epub 2021 Jan 16.

Authors

A Dutta^#¹, N Gupta^#¹, R Walia², A Bhansali¹, P Dutta¹, S K Bhadada¹, R Pivonello³, C K Ahuja⁴, S Dhandapani⁵, A Hajela¹, C Simeoli³, N Sachdeva¹, U N Saikia⁶

Affiliations

¹ Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Nehru Extension block, Chandigarh, 160012, India.
² Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Nehru Extension block, Chandigarh, 160012, India. ramawalia@rediffmail.com.
³ Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Naples, Italy.
⁴ Department of Radiology, PGIMER, Chandigarh, India.
⁵ Department of Neurosurgery, PGIMER, Chandigarh, India.
⁶ Department of Histopathology, PGIMER, Chandigarh, India.

^# Contributed equally.

PMID: 33453019
DOI: 10.1007/s40618-020-01495-z

Abstract

Aim: To ascertain the predictors of remission and relapse in patients of Cushing's disease (CD) undergoing pituitary transsphenoidal surgery (TSS).

Methods: Patients with CD subjected to TSS over 35 years at a tertiary care center were included. Patients were grouped into remission and persistent disease at 1 year after surgery, and were further followed up for relapse. Demographic, clinical, biochemical, histological, radiological and post-operative follow-up parameters were analyzed.

Results: Of the 152 patients of CD, 145 underwent TSS. Remission was achieved in 95 (65.5%) patients at 1 year. Patients in remission had shorter duration of symptoms prior to presentation (p = 0.009), more frequent presence of proximal myopathy (p = 0.038) and a tumor size of < 2.05 cm (p = 0.016) in comparison to those with persistent disease. Post-TSS, immediate post-operative 0800-h cortisol (< 159.85 nmol/L; p = 0.001), histological confirmation of tumor (p = 0.045), duration of glucocorticoid replacement (median 90 days; p = 0.001), non-visualization of tumor on MRI (p = 0.003), new-onset hypogonadism (p = 0.001), 3-month 0800-h cortisol (< 384.9 nmol/L; p = 0.001), resolution of diabetes (p = 0.001) and hypertension (p = 0.001), and recovery of hypothalamic-pituitary-adrenal axis (p = 0.018) favored remission. In logistic regression model, requirement of glucocorticoid replacement (p = 0.033), and resolution of hypertension post-TSS (p = 0.003) predicted remission. None of the parameters could predict relapse.

Conclusion: The study could ascertain the predictors of remission in CD. Apart from the tumor characteristics, surgical aspects and low post-operative 0800-h cortisol, the results suggest that baseline clinical parameters, longer glucocorticoid replacement, and resolution of metabolic complications post-TSS predict remission in CD. Long-term follow-up is essential to look for relapse.

Keywords: Cushing’s disease; Predictors; Relapse; Remission; Transsphenoidal surgery.

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References

1. Newell-Price J, Bertagna X, Grossman AB, Nieman LK (2006) Cushing’s syndrome. Lancet 367:1605–1617. https://doi.org/10.1016/S0140-6736(06)68699-6 - DOI - PubMed
1. Lacroix A, Feelders RA, Stratakis CA, Nieman LK (2015) Cushing’s syndrome. Lancet Lond Engl 386:913–927. https://doi.org/10.1016/S0140-6736(14)61375-1 - DOI
1. Pivonello R, Isidori AM, De Martino MC et al (2016) Complications of Cushing’s syndrome: state of the art. Lancet Diabetes Endocrinol 4:611–629. https://doi.org/10.1016/S2213-8587(16)00086-3 - DOI - PubMed
1. Pivonello R, De Martino MC, De Leo M et al (2008) Cushing’s Syndrome. Endocrinol Metab Clin North Am 37(135–149):ix. https://doi.org/10.1016/j.ecl.2007.10.010 - DOI
1. Pivonello R, De Leo M, Cozzolino A, Colao A (2015) The treatment of Cushing’s disease. Endocr Rev 36:385–486. https://doi.org/10.1210/er.2013-1048 - DOI - PubMed - PMC

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[1] Newell-Price J, Bertagna X, Grossman AB, Nieman LK (2006) Cushing’s syndrome. Lancet 367:1605–1617. https://doi.org/10.1016/S0140-6736(06)68699-6 - DOI - PubMed

[2] Newell-Price J, Bertagna X, Grossman AB, Nieman LK (2006) Cushing’s syndrome. Lancet 367:1605–1617. https://doi.org/10.1016/S0140-6736(06)68699-6 - DOI - PubMed

[3] Lacroix A, Feelders RA, Stratakis CA, Nieman LK (2015) Cushing’s syndrome. Lancet Lond Engl 386:913–927. https://doi.org/10.1016/S0140-6736(14)61375-1 - DOI

[4] Lacroix A, Feelders RA, Stratakis CA, Nieman LK (2015) Cushing’s syndrome. Lancet Lond Engl 386:913–927. https://doi.org/10.1016/S0140-6736(14)61375-1 - DOI

[5] Pivonello R, Isidori AM, De Martino MC et al (2016) Complications of Cushing’s syndrome: state of the art. Lancet Diabetes Endocrinol 4:611–629. https://doi.org/10.1016/S2213-8587(16)00086-3 - DOI - PubMed

[6] Pivonello R, Isidori AM, De Martino MC et al (2016) Complications of Cushing’s syndrome: state of the art. Lancet Diabetes Endocrinol 4:611–629. https://doi.org/10.1016/S2213-8587(16)00086-3 - DOI - PubMed

[7] Pivonello R, De Martino MC, De Leo M et al (2008) Cushing’s Syndrome. Endocrinol Metab Clin North Am 37(135–149):ix. https://doi.org/10.1016/j.ecl.2007.10.010 - DOI

[8] Pivonello R, De Martino MC, De Leo M et al (2008) Cushing’s Syndrome. Endocrinol Metab Clin North Am 37(135–149):ix. https://doi.org/10.1016/j.ecl.2007.10.010 - DOI

[9] Pivonello R, De Leo M, Cozzolino A, Colao A (2015) The treatment of Cushing’s disease. Endocr Rev 36:385–486. https://doi.org/10.1210/er.2013-1048 - DOI - PubMed - PMC

[10] Pivonello R, De Leo M, Cozzolino A, Colao A (2015) The treatment of Cushing’s disease. Endocr Rev 36:385–486. https://doi.org/10.1210/er.2013-1048 - DOI - PubMed - PMC

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Remission in Cushing's disease is predicted by cortisol burden and its withdrawal following pituitary surgery

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Remission in Cushing's disease is predicted by cortisol burden and its withdrawal following pituitary surgery

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