Adrenal Function After Adrenalectomy for Subclinical Hypercortisolism and Cushing's Syndrome: A Systematic Review of the Literature

Dalmazi, Guido Di; Berr, Christina M.; Fassnacht, Martin; Beuschlein, Felix; Reincke, Martín

doi:10.1210/jc.2014-1401

Cited by 104 publications

(92 citation statements)

References 41 publications

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“…This results in the need for hydrocortisone replacement in patients with subclinical and overt adrenal Cushing’s syndrome after curative adrenalectomy (27). Therefore, 46 consecutively recruited patients underwent a cosyntropin stimulation test to assess cortisol reserve 10–14 days after removal of the aldosterone-producing adrenocortical adenoma.…”

Section: Resultsmentioning

confidence: 99%

Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism

Lang²,

et al. 2017

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BACKGROUND. Adrenal aldosterone excess is the most common cause of secondary hypertension and is associated with increased cardiovascular morbidity. However, adverse metabolic risk in primary aldosteronism extends beyond hypertension, with increased rates of insulin resistance, type 2 diabetes, and osteoporosis, which cannot be easily explained by aldosterone excess.METHODS. We performed mass spectrometry–based analysis of a 24-hour urine steroid metabolome in 174 newly diagnosed patients with primary aldosteronism (103 unilateral adenomas, 71 bilateral adrenal hyperplasias) in comparison to 162 healthy controls, 56 patients with endocrine inactive adrenal adenoma, 104 patients with mild subclinical, and 47 with clinically overt adrenal cortisol excess. We also analyzed the expression of cortisol-producing CYP11B1 and aldosterone-producing CYP11B2 enzymes in adenoma tissue from 57 patients with aldosterone-producing adenoma, employing immunohistochemistry with digital image analysis.RESULTS. Primary aldosteronism patients had significantly increased cortisol and total glucocorticoid metabolite excretion (all P < 0.001), only exceeded by glucocorticoid output in patients with clinically overt adrenal Cushing syndrome. Several surrogate parameters of metabolic risk correlated significantly with glucocorticoid but not mineralocorticoid output. Intratumoral CYP11B1 expression was significantly associated with the corresponding in vivo glucocorticoid excretion. Unilateral adrenalectomy resolved both mineralocorticoid and glucocorticoid excess. Postoperative evidence of adrenal insufficiency was found in 13 (29%) of 45 consecutively tested patients.CONCLUSION. Our data indicate that glucocorticoid cosecretion is frequently found in primary aldosteronism and contributes to associated metabolic risk. Mineralocorticoid receptor antagonist therapy alone may not be sufficient to counteract adverse metabolic risk in medically treated patients with primary aldosteronism.FUNDING. Medical Research Council UK, Wellcome Trust, European Commission.

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Section: Resultsmentioning

confidence: 99%

Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism

Lang²,

et al. 2017

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“…Few studies have compared the recovery time between patients with OC and SC. Di Dalmazi et al [20] reported that only 65% of SC patients had postsurgical adrenal insufficiency, compared with 99.7% of OC patients. 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.…”

Section: Discussionmentioning

confidence: 99%

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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“…Postoperative adrenal insufficiency is the consequence of long‐standing suppression of hypothalamic corticotropin‐releasing hormone secretion, pituitary ACTH secretion and atrophy of normal adrenal cortex. Hypothalamic‐pituitary‐adrenal (HPA) axis suppression is present in all patients undergoing adrenalectomy for overt ACTH‐independent CS and in approximately 50% of patients with MACE . Hence, following surgery most patients require glucocorticoid (GC) therapy for adrenal insufficiency replacement until the HPA axis recovers.…”

Section: Introductionmentioning

confidence: 99%

Extensive clinical experience: Hypothalamic‐pituitary‐adrenal axis recovery after adrenalectomy for corticotropin‐independent cortisol excess

Hurtado

Cortes

Natt

et al. 2018

Clinical Endocrinology

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The HPA axis recovery interval was the longest for patients with severe CS. Surprisingly, patients with moderate CS recovered their HPA axis as quickly as those with MACE. Glucocorticoid withdrawal symptoms were observed in all groups, with more events in patients with severe CS. This study emphasizes the need to counsel patients on expectations for HPA axis recovery and address intervention for GWS based on individual preoperative parameters.

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Adrenal Function After Adrenalectomy for Subclinical Hypercortisolism and Cushing's Syndrome: A Systematic Review of the Literature

Cited by 104 publications

References 41 publications

Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism

Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism

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

Extensive clinical experience: Hypothalamic‐pituitary‐adrenal axis recovery after adrenalectomy for corticotropin‐independent cortisol excess

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