Outcomes of pituitary surgery for Cushing’s disease: a systematic review and meta-analysis

Stroud, Anna; Dhaliwal, Pearl; Alvarado, Raquel; Winder, Mark J.; Jonker, Benjamin; Grayson, Jessica W.; Hamizan, Aneeza Khairiyah Wan; Harvey, Richard J.; McCormack, Ann

doi:10.1007/s11102-020-01066-8

Cited by 52 publications

(54 citation statements)

References 74 publications

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“…Since a higher rate of morbidity, including poorly controlled diabetes mellitus, hypokalemia, venous thromboembolism, gastrointestinal hemorrhage, and osteoporosis, has been complicated in patients with refractory Cushing’s disease, several pharmaceutical treatments such as insulin, mineral corticoid antagonists, anticoagulants, proton pump inhibitors, and anti-osteoporotic agents are required during the perioperative period ( 91 , 93 ). In a recent systematic review, the complete surgical remission and recurrence rates of macro-tumors in primary surgery were 68% (95% confidence interval [CI]; 60–76) and 30% (95% CI; 18–43), and those in revision surgery are 49% (95% CI; 23–75) and 45% (95% CI; 0–98), respectively ( 94 ). If the tumor extends into the suprasellar region, a transcranial approach may be needed ( 88 ).…”

Section: Treatmentmentioning

confidence: 99%

Aggressive Cushing’s Disease: Molecular Pathology and Its Therapeutic Approach

et al. 2021

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Cushing’s disease is a syndromic pathological condition caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (ACTHomas) mediated by hypercortisolemia. It may have a severe clinical course, including infection, psychiatric disorders, hypercoagulability, and metabolic abnormalities, despite the generally small, nonaggressive nature of the tumors. Up to 20% of ACTHomas show aggressive behavior, which is related to poor surgical outcomes, postsurgical recurrence, serious clinical course, and high mortality. Although several gene variants have been identified in both germline and somatic changes in Cushing’s disease, the pathophysiology of aggressive ACTHomas is poorly understood. In this review, we focused on the aggressiveness of ACTHomas, its pathology, the current status of medical therapy, and future prospects. Crooke’s cell adenoma (CCA), Nelson syndrome, and corticotroph pituitary carcinoma are representative refractory pituitary tumors that secrete superphysiological ACTH. Although clinically asymptomatic, silent corticotroph adenoma is an aggressive ACTH-producing pituitary adenoma. In this review, we summarize the current understanding of the pathophysiology of aggressive ACTHomas, including these tumors, from a molecular point of view based on genetic, pathological, and experimental evidence. The treatment of aggressive ACTHomas is clinically challenging and usually resistant to standard treatment, including surgery, radiotherapy, and established medical therapy (e.g., pasireotide and cabergoline). Temozolomide is the most prescribed pharmaceutical treatment for these tumors. Reports have shown that several treatments for patients with refractory ACTHomas include chemotherapy, such as cyclohexyl-chloroethyl-nitrosourea combined with 5-fluorouracil, or targeted therapies against several molecules including vascular endothelial growth factor receptor, cytotoxic T lymphocyte antigen 4, programmed cell death protein 1 (PD-1), and ligand for PD-1. Genetic and experimental evidence indicates that some possible therapeutic candidates are expected, such as epidermal growth factor receptor tyrosine kinase inhibitor, cyclin-dependent kinase inhibitor, and BRAF inhibitor. The development of novel treatment options for aggressive ACTHomas is an emerging task.

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Section: Treatmentmentioning

confidence: 99%

Aggressive Cushing’s Disease: Molecular Pathology and Its Therapeutic Approach

et al. 2021

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“…After initial remission, around 18% recur with a wide heterogeneity and variability between studies (reported recurrence rates between 1 and 38%). Macroadenomas are more likely to recur than microadenomas, 30 vs 17% (94).…”

Section: Treatment and Outcomementioning

confidence: 99%

“…The goals of treatment in patients with CD are to normalise cortisol excess, maintain normal pituitary function and achieve tumour control. The mainstay of treatment is removal of the tumour by transsphenoidal surgical (TSS) resection (12), which results in initial biochemical remission in about 80 percent of patients (94). A dedicated and experienced surgeon, a visible microadenoma at preoperative MRI, and a low postoperative morning cortisol are factors that predict higher rates of remission (94).…”

Section: Treatment and Outcomementioning

confidence: 99%

“…The mainstay of treatment is removal of the tumour by transsphenoidal surgical (TSS) resection (12), which results in initial biochemical remission in about 80 percent of patients (94). A dedicated and experienced surgeon, a visible microadenoma at preoperative MRI, and a low postoperative morning cortisol are factors that predict higher rates of remission (94). After initial remission, around 18% recur with a wide heterogeneity and variability between studies (reported recurrence rates between 1 and 38%).…”

Section: Treatment and Outcomementioning

confidence: 99%

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Cushing’s disease and aggressive pituitary tumours : Aspects on epidemiology, treatment, and long-term follow-up

Bengtsson

2021

Linköping University Medical Dissertations

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This thesis focuses on clinical and epidemiological aspects of aggressive pituitary tumours/carcinomas and Cushing's disease. Pituitary carcinomas account for only 0.1-0.2% of the tumours originating from the anterior pituitary gland and are defined solely by the event of distant metastases, whereas aggressive pituitary tumours are defined by their clinical behaviour of rapid/progressive growth despite optimal treatment with surgery, radiotherapy and medical agents. The prognosis for individuals with aggressive tumours/carcinomas has been poor with few treatment options. However, case reports indicated better outcomes after treatment with the alkylating agent temozolomide. In study I and III, we investigated 24 patients (16 aggressive tumours and 8 carcinomas) given treatment with temozolomide. We found an initial response rate (tumour regression ≥30%) in 10/21 evaluable patients, with complete regression in two carcinomas. Favourable response was associated with low tumour expression of the DNA repair protein MGMT; in responders median 9% (range 5-20%) vs non-responders median 93% (50-100%). Our results also indicated a longer survival in patients with low MGMT. Out of 11 patients with MGMT >10%, nine died with an estimated median survival of 26 months (95% CI 14-38), whereas only 1/6 patients with lower MGMT died from tumour progression during a follow-up of median 83 months (range 12-161).

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“…Hypercortisolism is associated with higher risks of metabolic, musculoskeletal, immunological, and neuropsychiatric complications, which result in significant morbidity and mortality. Therefore, CD requires early diagnosis and treatment, and transsphenoidal surgery (TSS) is currently the treatment of choice (2,3). The reported remission rates are between 68% and 98% (4).…”

Section: Introductionmentioning

confidence: 99%

Management of thyrotoxicosis occurring after surgery for Cushing’s disease: a case series

Jiang¹,

Yang²,

Feng³

et al. 2021

Gland Surg

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Background: Thyrotoxicosis is a rare complication of surgery for Cushing's disease (CD). In clinical practice, given the rarity of this condition, patients may be misdiagnosed, and thus not treated appropriately.This study describes the clinical features and management of thyrotoxicosis in this context. Methods:We retrospectively screened a pituitary database for CD patients who underwent surgery at Peking Union Medical College Hospital between 2010 and 2017. The electronic medical records and documentation of 732 patients were searched in order to identify instances of thyrotoxicosis.Results: Fourteen patients developed postoperative thyrotoxicosis after CD remission, representing 1.9% of all the CD patients who underwent surgery and 2.5% of the CD patients who were in remission after surgery. The onset of thyrotoxicosis occurred at a median of 3.5 months after surgery. At the onset, 13 patients (92.9%) were on a maintenance dose of hydrocortisone and were managed using a higher dose of hydrocortisone. One patient had normal adrenal function and was managed by observation first, then using anti-thyroid drugs. Thyrotoxicosis was transient in all but one patient, and lasted 1.9±0.7 months (range, 1- months).Conclusions: Thyrotoxicosis is a rare complication that develops during the recovery period following surgery for CD. It occurs only after the surgical resolution of hypercortisolism, and in particular alongside adrenal insufficiency during the 4 months following CD remission. Awareness of this situation should be promoted among physicians, and patients should be managed on the basis of the clinical setting and manifestation.

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Outcomes of pituitary surgery for Cushing’s disease: a systematic review and meta-analysis

Cited by 52 publications

References 74 publications

Aggressive Cushing’s Disease: Molecular Pathology and Its Therapeutic Approach

Aggressive Cushing’s Disease: Molecular Pathology and Its Therapeutic Approach

Cushing’s disease and aggressive pituitary tumours : Aspects on epidemiology, treatment, and long-term follow-up

Management of thyrotoxicosis occurring after surgery for Cushing’s disease: a case series

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