Study Examines Therapy Options for Post-adrenalectomy Low Glucocorticoid Levels

Hydrocortisone and prednisone have comparable safety and effectiveness when used as glucocorticoid replacement therapy in patients with adrenal adenoma or Cushing’s disease who underwent adrenalectomy, a new study shows.

The study, “Comparison of hydrocortisone and prednisone in the glucocorticoid replacement therapy post-adrenalectomy of Cushing’s Syndrome,” was published in the journal Oncotarget.

The symptoms of Cushing’s syndrome are related to excessive levels of glucocorticoids in our body. Glucocorticoids are a type of steroid hormones produced by the adrenal gland. Consequently, a procedure called adrenalectomy – removal of the adrenal glands – is usually conducted in patients with Cushing’s syndrome.

Unfortunately, adrenalectomy leads to a sharp drop in hormones that are necessary for our bodies. So, post-adrenalectomy glucocorticoid replacement therapy is required for patients.

Hydrocortisone and prednisone are synthetic glucocorticoids that most often are used for glucocorticoid replacement therapy.

Treatment with either hydrocortisone or prednisone has proven effective in patients with Cushing’s syndrome. However, few studies have compared the two treatments directly to determine if there are significant advantages of one therapy over another.

Chinese researchers set out to compare the effectiveness and safety of hydrocortisone and prednisone treatments in patients with Cushing’s syndrome, up to six months after undergoing adrenalectomy.

Patients were treated with either hydrocortisone or prednisone starting at day two post-adrenalectomy. The withdrawal schedule varied by individual patients.

At baseline, both groups had similar responses to the adrenalectomy, including the correction of hypertension (high blood pressure), hyperglycemia (high blood glucose levels), and hypokalemia (low potassium levels). Furthermore, most patients in both groups lost weight and showed significant improvement, as judged by a subjective evaluation questionnaire.

Hydrocortisone did show a significant advantage over prednisone in the improvement of liver function, but its use also was associated with significant swelling of the lower extremities, as compared to prednisone.

Patients in both groups went on to develop adrenal insufficiency (AI) during glucocorticoid withdrawal. However, there were no significant differences in the AI incidence rate – 35 percent in the hydrocortisone group versus 45 percent in the prednisone group. The severity of A also was not significantly different between the groups.

Furthermore, most of the AI symptoms were relieved by going back to the initial doses of the glucocorticoid replacement.

As there were no significant differences between the two treatments, the findings support “the use of both hydrocortisone and prednisone in the glucocorticoid replacement therapy post-adrenalectomy for patients of adrenal adenoma or Cushing’s disease,” researchers concluded.

From https://cushingsdiseasenews.com/2018/01/11/post-adrenalectomy-glucocorticoid-replacement-therapy/

Six controversial issues on subclinical Cushing’s syndrome

Abstract

Subclinical Cushing’s syndrome is a condition of hypercortisolism in the absence of signs specific of overt cortisol excess, and it is associated with an increased risk of diabetes, hypertension, fragility fractures, cardiovascular events and mortality.

The subclinical Cushing’s syndrome is not rare, being estimated to be between 0.2–2 % in the adult population. Despite the huge number of studies that have been published in the recent years, several issues remain controversial for the subclinical Cushing’s syndrome screening, diagnosis and treatment.

The Altogether to Beat Cushing’s syndrome Group was founded in 2012 for bringing together the leading Italian experts in the hypercortisolism-related diseases. This document represents the Altogether to Beat Cushing’s syndrome viewpoint regarding the following controversial issues on Subclinical Cushing’s syndrome (SCS):

(1) Who has to be screened for subclinical Cushing’s syndrome?
(2) How to screen the populations at risk?
(3) How to diagnose subclinical Cushing’s syndrome in patients with an adrenal incidentaloma?
(4) Which consequence of subclinical Cushing’s syndrome has to be searched for?
(5) How to address the therapy of choice in AI patients with subclinical Cushing’s syndrome?
(6) How to follow-up adrenal incidentaloma patients with subclinical Cushing’s syndrome surgically or conservatively treated?

Notwithstanding the fact that most studies that faced these points may have several biases (e.g., retrospective design, small sample size, different criteria for the subclinical Cushing’s syndrome diagnosis), we believe that the literature evidence is sufficient to affirm that the subclinical Cushing’s syndrome condition is not harmless and that the currently available diagnostic tools are reliable for identifying the majority of individuals with subclinical Cushing’s syndrome.

Keywords

Subclinical hypercortisolism, Adrenal incidentalomas, Hypertension, Diabetes, Osteoporosis

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

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

Address all correspondence and requests for reprints to: Martin Reincke, MD, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstr. 1, D-80336 Munich, Germany. E-mail: .

Successful tumor resection in endogenous Cushing’s syndrome (CS) results in tertiary adrenal insufficiency requiring hydrocortisone replacement therapy.

The aim was to analyze the postsurgical duration of adrenal insufficiency of patients with Cushing’s disease (CD), adrenal CS, and ectopic CS.

We performed a retrospective analysis based on the case records of 230 patients with CS in our tertiary referral center treated from 1983–2014. The mean follow-up time was 8 years.

We included 91 patients of the three subtypes of CS undergoing curative intended surgery and documented followup after excluding cases with persistent disease, pituitary radiation, concurrent adrenostatic or somatostatin analog treatment, and malignant adrenal disease.

The probability of recovering adrenal function within a 5 years followup differed significantly between subtypes (P = .001). It was 82% in ectopic CS, 58% in CD and 38% in adrenal CS. In the total cohort with restored adrenal function (n = 52) the median time to recovery differed between subtypes: 0.6 years (interquartile range [IQR], 0.03–1.1 y) in ectopic CS, 1.4 years (IQR, 0.9–3.4 y) in CD, and 2.5 years (IQR, 1.6–5.4 y) in adrenal CS (P = .002). In CD the Cox proportional-hazards model showed that the probability of recovery was associated with younger age (hazard ratio, 0.896; 95% confidence interval, 0.822–0.976; P = .012), independently of sex, body mass index, duration of symptoms, and basal ACTH and cortisol levels. There was no correlation with length and extend of hypercortisolism or postoperative glucocorticoid replacement doses.

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

Safety of DR-HC for adrenal insufficiency

Conventional treatment of adrenal insufficiency involves cortisol replacement therapy with twice- or thrice-daily oral hydrocortisone. Recently dual-release hydrocortisone (DR-HC) administered once daily to provide high levels of cortisol during the morning, followed by a gradual decrease throughout the day is being used. This results in considerably lower cortisol exposure during the afternoon and evening compared with immediate-release thrice-daily hydrocortisone, thereby mimicking normal cortisol secretion more closely than conventional therapy.

Nilsson et al. conducted a study to evaluate the long-term safety of DR-HC and whether the difference in the incidence of adverse events persisted over time and if it was related to different levels of exposure to cortisol. They conducted a randomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden. The results of the study of the newly developed DR-HC showed that long-term maintenance treatment and rescue therapy was well tolerated up to 27 months of continuous treatment.

Read full article titled ‘Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency’ by Nilsson et al., European Journal of Endocrinology 171 pp 369 – 377, DOI: 10.1530/EJE-14-0327

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