Time to Recovery of Adrenal Function After Curative Surgery for Cushing's Syndrome Depends on Etiology

Berr, Christina M.; Dalmazi, Guido Di; Oßwald, Andrea; Ritzel, Katrin; Bidlingmaier, Martin; Geyer, Lucas L.; Treitl, Marcus; Hallfeldt, Klaus; Rachinger, Walter; Reisch, Nicole; Blaser, Rainer; Schopohl, Jochen; Beuschlein, Felix; Reincke, Martín

doi:10.1210/jc.2014-3632

Cited by 71 publications

(57 citation statements)

References 28 publications

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“…The recovery of adrenal function in patients persistently remitted during follow-up was associated with younger age at surgical intervention, in agreement with other studies [7, 8, 22], while there is only one paper showing the contrary [11]. The presence of other pituitary insufficiencies, which represent one of the most common complications of pituitary surgery, had also a negative impact on the recovery of adrenal function, probably as a result of more aggressive and radical surgical intervention, as previously suggested [16].…”

Section: Discussionsupporting

confidence: 91%

“…This observation confirms the results by Alexandraki et al [8], who showed that recovery within 2 years had an NPV of 98.1% and a PPV of 59.3%, with a slightly higher PPV probably as a consequence of a longer follow-up. In a similar way, Berr et al [7] showed that in 54 patients with CD, the recovery of adrenal function occurred within 3 years in case of subsequent disease recurrence.…”

Section: Discussionmentioning

confidence: 82%

“…In this context, normalization of basal and stimulated plasmatic cortisol that occurs during follow-up of surgically cured patients may represent the recovery of the HPA axis or the onset of CD recurrence. It was demonstrated that patients who recurred during follow-up recovered their adrenal function earlier than patients with persistent remission [7], but previous studies assessing the duration of AI after successful pituitary surgery always included the relapsed cases [7-11]. This may lead to an underestimation of the overall duration of AI.…”

Section: Introductionmentioning

confidence: 99%

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Recovery of Adrenal Function after Pituitary Surgery in Patients with Cushing Disease: Persistent Remission or Recurrence?

et al. 2019

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Background: Cushing disease (CD) represents the principal cause of endogenous hypercortisolism. The first-line therapy of CD is surgical removal of the ACTH-secreting pituitary adenoma, which is generally followed by adrenal insufficiency (AI). Objective: To analyze the recovery of AI in patients with CD after pituitary surgery in relation with recurrence and persistent remission of CD. Patients and Methods: We performed a retrospective analysis of patients with CD who met the following inclusion criteria: adult age, presence of AI 2 months after the surgical intervention, and a minimum follow-up of 3 years after the surgical intervention. Results: Sixty-one patients were followed for a median of 6 years. Ten (16.4%) patients recurred during follow-up. The patients who restored adrenal function did so after a median time of 19 months, with a significantly shorter time in the recurrence group (12.5 vs. 25 months, p = 0.008). All 10 patients who recurred recovered their adrenal function within 22 months. The recovery rate of AI in the persistent remission group was 37.3% (19/51) at 3 years and 55.8% (24/43) at 5 years. In all patients the duration of AI was negatively associated with disease recurrence. Conclusion: The duration of postsurgical AI in patients with recurrent CD is significantly shorter than that in patients with persistently remitted CD, and this parameter may be a useful predictor of recurrence. Patients showing a normal pituitary-adrenal axis within 2 years after surgery should be strictly monitored as they are at higher risk of disease relapse.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

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Recovery of Adrenal Function after Pituitary Surgery in Patients with Cushing Disease: Persistent Remission or Recurrence?

et al. 2019

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“…They also reported that the mean recovery time was 6.5 months (range, 1 to 50) in SC patients and 11.2 months (range, 1 to 60) in those with OC, and they observed a tight relationship between the degree of hypercortisolism and the time to recovery, similar to our data. Some studies reported that old age at surgery is a critical factor influencing recovery time in patients with adrenal CS [2122], but the clinical features were only explained as a factor influencing recovery time in patients with adrenal CS independently of age in our study by multivariate analysis. These results support that SC patients have a lower degree of cortisol excess that is not sufficient to fully suppress the HPA axis.…”

Section: Discussionmentioning

confidence: 56%

The Recovery of Hypothalamic-Pituitary-Adrenal Axis Is Rapid in Subclinical Cushing Syndrome

et al. 2016

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BackgroundIn subclinical Cushing syndrome (SC), it is assumed that glucocorticoid production is insufficient to cause a clinically recognizable syndrome. Differences in hormonal levels or recovery time of the hypothalamic-pituitary-adrenocortical (HPA) axis after adrenalectomy between patients with overt Cushing syndrome (OC) and SC remain unknown.MethodsThirty-six patients (10 with OC and 26 with SC) with adrenal Cushing syndrome who underwent adrenalectomy from 2004 to 2014 were reviewed retrospectively. Patients were treated with glucocorticoid after adrenalectomy and were reevaluated every 1 to 6 months using a rapid adrenocorticotropic hormone (ACTH) stimulation test.ResultsLevels of basal 24-hour urine free cortisol (UFC), serum cortisol after an overnight dexamethasone suppression test (DST), and serum cortisol and 24-hour UFC after low-dose DST and high-dose DST were all significantly lower in patients with SC compared with OC. Basal ACTH levels showed significantly higher in patients with SC compared with OC. The probability of recovering adrenal function during follow-up differed significantly between patients with OC and SC (P=0.001), with significant correlations with the degree of preoperative cortisol excess. Patients with OC required a longer duration of glucocorticoid replacement to recover a normal ACTH stimulation test compared with patients with SC (median 17.0 months vs. 4.0 months, P<0.001).ConclusionThe HPA axis recovery time after adrenalectomy in patients with SC is rapid and is dependent on the degree of cortisol excess. More precise definition of SC is necessary to achieve a better management of patients and to avoid the risk of under- or over-treatment of SC patients.

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“…Plasma cortisol, ACTH and midnight salivary cortisol were measured as described previously (11). Post-DST cortisol was measured during the morning, 8-10 h after oral administration of 1-mg of dexamethasone, and levels <50 nmol/L were considered adequately suppressed.…”

Section: Clinical and Hormonal Evaluationmentioning

confidence: 99%

Cortisol-related metabolic alterations assessed by mass spectrometry assay in patients with Cushing's syndrome

Dalmazi

Quinkler²,

Deutschbein

et al. 2017

European Journal of Endocrinology

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OBJECTIVE: Endogenous hypercortisolism is a chronic condition associated with severe metabolic disturbances and cardiovascular sequela. The aim of this study was to characterize metabolic alterations in patients with different degrees of hypercortisolism by mass-spectrometry-based targeted plasma metabolomic profiling and correlate the metabolomic profile with clinical and hormonal data. DESIGN: Cross-sectional study. METHODS: Subjects (n = 149) were classified according to clinical and hormonal characteristics: Cushing's syndrome (n = 46), adrenocortical adenomas with autonomous cortisol secretion (n = 31) or without hypercortisolism (n = 27). Subjects with suspicion of hypercortisolism, but normal hormonal/imaging testing, served as controls (n = 42). Clinical and hormonal data were retrieved for all patients and targeted metabolomic profiling was performed. RESULTS: Patients with hypercortisolism showed lower levels of short-/medium-chain acylcarnitines and branched-chain and aromatic amino acids, but higher polyamines levels, in comparison to controls. These alterations were confirmed after excluding diabetic patients. Regression models showed significant correlation between cortisol after dexamethasone suppression test (DST) and 31 metabolites, independently of confounding/contributing factors. Among those, histidine and spermidine were also significantly associated with catabolic signs and symptoms of hypercortisolism. According to an discriminant analysis, the panel of metabolites was able to correctly classify subjects into the main diagnostic categories and to distinguish between subjects with/without altered post-DST cortisol and with/without diabetes in >80% of the cases. CONCLUSIONS: Metabolomic profiling revealed alterations of intermediate metabolism independently associated with the severity of hypercortisolism, consistent with disturbed protein synthesis/catabolism and incomplete -oxidation, providing evidence for the occurrence of metabolic inflexibility in hypercortisolism. AbstractObjective: Endogenous hypercortisolism is a chronic condition associated with severe metabolic disturbances and cardiovascular sequela. The aim of this study was to characterize metabolic alterations in patients with different degrees of hypercortisolism by mass-spectrometry-based targeted plasma metabolomic profiling and correlate the metabolomic profile with clinical and hormonal data. Design: Cross-sectional study. Methods: Subjects (n = 149) were classified according to clinical and hormonal characteristics: Cushing's syndrome (n = 46), adrenocortical adenomas with autonomous cortisol secretion (n = 31) or without hypercortisolism (n = 27). Subjects with suspicion of hypercortisolism, but normal hormonal/imaging testing, served as controls (n = 42). Clinical and hormonal data were retrieved for all patients and targeted metabolomic profiling was performed. Results: Patients with hypercortisolism showed lower levels of short-/medium-chain acylcarnitines and branchedchain and aromatic amino acids, but hi...

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Time to Recovery of Adrenal Function After Curative Surgery for Cushing's Syndrome Depends on Etiology

Abstract: Time to recovery of adrenal function is dependent on the underlying etiology of CS.

Cited by 71 publications

References 28 publications

Recovery of Adrenal Function after Pituitary Surgery in Patients with Cushing Disease: Persistent Remission or Recurrence?

Recovery of Adrenal Function after Pituitary Surgery in Patients with Cushing Disease: Persistent Remission or Recurrence?

The Recovery of Hypothalamic-Pituitary-Adrenal Axis Is Rapid in Subclinical Cushing Syndrome

Cortisol-related metabolic alterations assessed by mass spectrometry assay in patients with Cushing's syndrome

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