Improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and Subclinical Cushing Syndrome

Eur J Endocrinol. 2016 Jul 22. pii: EJE-16-0465. [Epub ahead of print]

Abstract

OBJECTIVE:

Beneficial effects of adrenalectomy on cardiovascular risk factors in patients with Subclinical Cushing Syndrome (SCS) are uncertain. We sought to conduct a systematic review and meta-analysis with the following objectives: 1) determine the effect of adrenalectomy compared to conservative management on cardiovascular risk factors in patients with SCS and 2) compare the effect of adrenalectomy on cardiovascular risk factors in patients with SCS versus those with a non-functioning (NF) adrenal tumor.

METHODS:

Medline In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial were searched on November 17th, 2015. Reviewers extracted data and assessed methodological quality in duplicate.

RESULTS:

We included 26 studies reporting on 584 patients with SCS and 457 patients with NF adrenal tumors. Studies used different definitions of SCS. Patients with SCS undergoing adrenalectomy demonstrated an overall improvement in cardiovascular risk factors (61% for hypertension, 52% for diabetes mellitus, 45% for obesity and 24% for dyslipidemia). When compared to conservative management, patients with SCS undergoing adrenalectomy experienced improvement in hypertension (RR 11, 95% CI 4.3 – 27.8) and diabetes mellitus (RR 3.9, 95%CI 1.5- 9.9), but not dyslipidemia (RR 2.6, 95%CI 0.97 -7.2) or obesity (RR 3.4 (95%CI 0.95-12)). Patients with NF adrenal tumors experienced improvement in hypertension (21/54 patients), however, insufficient data exist for comparison to patients with SCS.

CONCLUSIONS:

Available low to moderate quality evidence from heterogeneous studies suggests a beneficial effect of adrenalectomy on cardiovascular risk factors in patients with SCS overall and as compared to conservative management.

[PubMed – as supplied by publisher]

From http://www.ncbi.nlm.nih.gov/pubmed/27450696

Video: Adrenalectomy for Cushing’s Syndrome Surgical Management

Adrenalectomy for Cushing Syndrome Surgical Management by Dr Anup Gulati

History of Patient
A 35 yrs old female with complaint of…
Weight Gain over last 2 years (weighing 115 kg at present)
Pulse 70, BP 124/76. No history of episodes of hypertension.
CECT whole abdomen suggestive of left adrenal 5×5 cm cystic mass
Dexamethasone suppression test positive for Cushing’s disease.
Rest all hormone profile normal.

Adrenal glands are attached with kidneys sometimes release excess hormones which cause cushing’s disease. Urologists do Adrenalectomy procedure which can cure Cushing’s disease.

 

Masked renal dysfunction in patients with adrenal Cushing’s syndrome manifested by adrenalectomy

INTRODUCTION AND OBJECTIVES

Many patients with primary aldosteronism (PA) exhibit a decline in renal function after adrenalectomy. Excessive aldosterone secretion causes glomerular hyperfiltration, and cancellation of this excessive secretion manifests the masked renal dysfunction. Considering the mineralocorticoid effect of cortisol as with aldosterone, excessive cortisol secretion may also mask the renal dysfunction of patients with adrenal Cushing’s syndrome (CS). However, postoperative changes in renal function in patients with CS have not been evaluated. We evaluated changes in renal function after adrenalectomy in patients with functional adrenal tumor.

METHODS

A total of 164 consecutive patients underwent adrenalectomy for unilateral functional adrenal tumor at our institution between January 2004 and October 2014. Of the 164 patients, we retrospectively analyzed 118 patients (PA/CS/subclinical Cushing’s syndrome [SCS]/pheochromocytoma [PCC]: n = 51/21/13/33, respectively) who were followed up for over 6 months and whose change in renal function was evaluable. Laboratory data, including baseline hormone levels before medical treatment, were collected from medical records. Estimated glomerular filtration rate (eGFR) values were obtained using the 3-variable Japanese equation. Renal dysfunction was defined as a 20% reduction in eGFR from baseline to within 3 times average during the 6 months post-operation. The change in eGFR before and after the operation was analyzed in each adrenal tumor.

RESULTS

The mean change in eGFR before and after the operation was -14% (range, -55%-18%) in patients with PA, -9% (-48%-23%) in patients with CS, -2% in patients with SCS, and -2% in patients with PCC. The eGFR decline in patients with PA and CS was significant (p < 0.0001 and p = 0.0171, respectively), while there was no significant change in patients with SCS and PCC. After the operation, 39% (20/51) and 24% (5/21) of patients with PA and CS manifested renal dysfunction, respectively, while none of the patients with SCS and PCC manifested renal dysfunction. Preoperative renal function was not correlated with manifested renal dysfunction. Multivariate analysis identified older age and higher levels of plasma aldosterone concentration as independent predictors of renal dysfunction manifestation in patients with PA, while no clinical predictor was identified in patients with CS.

CONCLUSIONS

This is the first report that has shown a decline in eGFR after adrenalectomy in patients with CS. Possible masked renal damage should be considered in patients with CS as well as PA.

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Patients with ARMC5 mutations: The NIH clinical experience

Screenshot 2016-05-27 13.12.55

 

Adrenal Disorders

R Correa, M Zilbermint, A Demidowich, F Faucz, A Berthon, J Bertherat, M Lodish, C Stratakis

Summary: Researchers conducted this study to describe the different phenotypical characteristics of patients with armadillo repeat containing 5 (ARMC5) mutations, located in 16p11.2 and a likely tumor-suppressor gene. They determined that patients with bilateral adrenal enlargement, found on imaging tests, should be screened for ARMC5 mutations, which are associated with subclinical Cushing’s syndrome (CS) and primary hyperaldosteronism (PA).

Methods:

  • Researchers identified 20 patients with ARMC5 mutations (germline and/or somatic) who were enrolled in a National Institutes of Health (NIH) protocol.
  • They obtained sociodemographic, clinical, laboratory, and radiological data for all participants.

Results:

  • Three families (with a total of 8 patients) were identified with ARMC5 germline mutations; the rest of the patients (13/20) had sporadic mutations.
  • The male to female ratio was 1.2:1; mean age was 48 years and 60% of patients were African American.
  • Forty percent of patients were diagnosed with CS, 20% with subclinical CS, 30% with hyperaldosteronism, and 10% had no diagnosis.
  • The mean serum cortisol (8 am) and Urinary Free Cortisol were 13.1 mcg/dl and 77 mcg/24 hours, respectively.
  • Nearly all patients (95%) had bilateral adrenal enlargement found on CT or MRI.
  • Patients underwent the following treatments: Bilateral adrenalectomy (45%), unilateral adrenalectomy (25%), medical treatment (20%), and no treatment (10%).
  • ARMC5 mutations are associated with primary macronodular adrenal hyperplasia (PMAH) and are also seen in patients with PA, especially among African Americans.

From http://www.mdlinx.com/endocrinology/conference-abstract.cfm/ZZ37C4C5D3BF1A4FAE9C479A696660535B/57884/?utm_source=confcoveragenl&utm_medium=newsletter&utm_content=abstract-list&utm_campaign=abstract-AACE2016&nonus=0

Unilateral andrenalectomy may be valid first-line treatment for Cushing’s syndrome

Debillon E, et al. J Clin Endocrinol Metab. 2015;doi:10.1210/jc.2015-2662.

In patients with evident Cushing’s syndrome related to primary bilateral macronodular adrenal hyperplasia, unilateral adrenalectomy of the large gland appears to be a suitable alternative to bilateral adrenalectomy as a first-line treatment, according to recent findings.

Unilateral adrenalectomy yielded normalized urinary free cortisol and improved Cushing’s syndrome, according to the researchers.

Olivier Chabre , MD, PhD, of the Service d’Endocrinologie-Diabétologie-Nutrition in France, and colleagues evaluated all patients (n = 15) with overt Cushing’s syndrome related to primary bilateral macronodular adrenal hyperplasia who underwent unilateral laparoscopic adrenalectomy of the larger gland between 2001 and 2015. Patients were seen for clinical and biological follow-up assessments at 1, 3 and 6 months postoperatively, 5 years after surgery and at the time of the last available urinary free cortisol measurement.

The study’s primary outcome measures were pre- and postoperative levels of urinary free cortisol, plasma cortisol, adrenocorticotropic hormone (ACTH), BMI, blood pressure, plasma glucose and lipids and measurements of these values on follow-up assessments. Patients were followed for a median of 60 months.

The researchers found that in early postoperative measurements, all 15 patients who underwent unilateral adrenalectomy achieved normal or low urinary free cortisol. Between 7 days and 1 month, there was a decrease in median urinary free cortisol from 2.19 times the upper limit of normal (ULN) at baseline to 0.27 ULN (P = .001). At 1 month, only one patient had elevated urinary free cortisol, and this patient went into remission by month 3 and continued to be in remission after 12 years of follow-up.

Forty percent of the patients developed adrenal insufficiency after unilateral adrenalectomy and latent adrenal insufficiency could not be excluded in two of the other patients. No predictors of postoperative adrenal insufficiency were identified.

Six of the patients had diabetes before unilateral adrenalectomy surgery; four of those were treated with antidiabetes drugs. At 12 months, only two of these patients had a continued need for antidiabetes drugs and had reductions in HbA1c despite decreases in their treatment. Recurrence occurred in two patients, demonstrating urinary free cortisol above the ULN at 7 years postoperatively and 8 years postoperatively. Both cases required treatment with mitotane, and in one of the patients, adrenalectomy of the second gland was required 9 years after the initial adrenalectomy.

According to the researchers, postoperative management and vigilant follow-up is needed in order to monitor patients for the risk for adrenal insufficiency.

“Further prospective studies are needed to better evaluate the long-term benefits of [unilateral adrenalectomy], which has one major benefit over [bilateral adrenalectomy]: if needed, [unilateral adrenalectomy] can be transformed in [bilateral adrenalectomy], while the opposite is obviously not true,” the researchers wrote. “One could propose that in further prospective studies [bilateral adrenalectomy] could be performed only if [unilateral adrenalectomy] fails to normalize [urinary free cortisol] at 1 month postoperatively.” – by Jennifer Byrne

Disclosure: The researchers report no relevant financial disclosures.

From Healio