Adrenal Venous Sampling Helps Surgical Decisions in Type of Cushing’s

Cushing’s syndrome patients with tumors on both adrenal glands — which sit on top of the kidneys — could undergo adrenal venous sampling, a procedure where blood samples are taken from both adrenal glands to determine which tumors to remove, researchers suggest.

Their study, “Outcomes of Adrenal Venous Sampling in Patients with Bilateral Adrenal Masses and ACTH-Independent Cushing’s Syndrome,” was published in the World Journal of Surgery. The work was a collaboration between SUNY Upstate Medical University in Syracuse and the University of Pittsburgh.

Cushing’s syndrome, a condition characterized by excess cortisol, can be divided into two main subtypes. In some patients, the disease is dependent on tumors secreting the adrenocorticotropic hormone (ACTH), which stimulates the release of cortisol from the adrenal glands. In others, adrenal tumors are solely responsible for excess cortisol and do not require ACTH for functioning.

ACTH-independent Cushing’s syndrome (AICS), the latter subtype, constitutes about 10% to 15% of endogenous — an overproduction of cortisol within the body — Cushing’s syndrome cases, with cortisol-secreting adenomas in just one gland (unilateral) being the most common cause.

Compared to unilateral adenomas, adrenal tumors in both glands (bilateral) in patients with AICS are difficult to diagnose. Disease management in these rare cases depends on the challenging determination of the lesion’s exact location and of the functional status of the benign tumors (if they are actively secreting cortisol).

Surgical removal of both adrenal glands, also known as bilateral adrenalectomy, “ensures cure of AICS, but leads to permanent corticosteroid dependence and a lifelong risk of adrenal crisis,” investigators explained. Therefore, screening for the presence of unilateral or bilateral adenomas is essential to avoid unnecessary surgery.

“Adrenal venous sampling (AVS) has been reported in a single institutional series … to aid in successful localization of cortisol-secreting adrenal adenomas in patients with bilateral adrenal masses and AICS,” researchers wrote.

Researchers retrospectively assessed the usefulness of AVS in guiding management of patients with bilateral adrenal masses plus AICS.

Nine women (age 51-73) with bilateral adrenal masses and AICS were included in the study. All subjects had undergone AVS at the University of Pittsburgh Medical Center from 2008 to 2016. None of the patients had apparent symptoms of Cushing’s syndrome.

“Samples were obtained for testing of epinephrine [also called adrenaline] and cortisol from both [adrenal veins] and the external iliac vein. Multiple samples were obtained to ensure adequate sampling,” they wrote.

Adrenal glands produce cortisol and epinephrine, among other hormones, which are critical for maintaining good health. In AICS, there’s an overproduction of both hormones that’s independent on the release of ACTH, which is produced by the brain’s pituitary gland.

Successful adrenal venous sampling was achieved in eight women. “One patient with unsuccessful catheterization had [other additional diseases] and passed away from unrelated reasons,” researchers reported.

AVS results indicated that all patients had bilateral cortisol-secreting adenomas.

“Surgical management was strongly influenced by adrenal mass size. However, AVS may have influenced surgical decision-making in some cases, particularly when minimal difference in size was noted in adrenal mass sizes,” they reported.

Six women underwent adrenalectomy: three had the gland with larger size mass removed (unilateral type of surgery); two had both glands removed; and one had the right gland removed followed by the left one, five months later, due to continuous hormonal overproduction without experiencing symptoms of Cushing’s syndrome.

Evidence suggests that removal of the larger adrenal mass in patients with bilateral cortisol-secreting adenomas improves Cushing’s syndrome presentation.

In theory, unilateral adrenalectomy reduces cortisol production through the removal of the oversecreting mass. Because of this, unilateral adrenalectomy of the larger adrenal mass was chosen in half of this study’s surgical cases, instead of bilateral adrenalectomy.

Tissue analysis revealed multiple-lump masses, also known as macronodular adrenal hyperplasia (MAH), in all six surgical cases.

In addition, computed tomography (CT) scan findings were predictive of bilateral MAH, with scans showing evidence of one or multiple nodules on one or both adrenal glands.

“To the best of our knowledge, this is the second study to evaluate the utility of AVS in guiding management of patients with bilateral adrenal masses and AICS,” investigators said.

The first study was by Young and included 10 patients with a more severe presentation of Cushing’s syndrome and other individual characteristics, which contributed to the differences in results, compared to the current study. In Young’s study, half the subjects had unilateral adrenal masses.

Patients with bilateral cortisol-secreting masses frequently have a milder form of Cushing’s syndrome, which corroborates researchers’ findings.

Despite suggesting that adrenal venous sampling is useful in excluding a unilateral adenoma as the cause of AICS, this study’s sample size is small.

“More data are needed before AVS can be advocated as essential for management of patients with bilateral adrenal masses and AICS,” researchers concluded.

From https://cushingsdiseasenews.com/2018/10/02/adrenal-venous-sampling-helps-surgical-decisions-type-cushings-syndrome/?utm_source=Cushing%27s+Disease+News&utm_campaign=a990429aad-RSS_WEEKLY_EMAIL_CAMPAIGN&utm_medium=email&utm_term=0_ad0d802c5b-a990429aad-72451321

Pregnancy Could Be Linked to Onset of Cushing’s Symptoms

More than 25 percent of women with Cushing’s disease experienced their first symptoms within one year of giving birth, a small study by the Pacific Neuroscience Institute found.

The findings suggest a possible causal relationship between the biological stress of pregnancy and Cushing’s disease (CD), with more than a two-fold risk of women developing the disease within one year of pregnancy.

The study, “Pregnancy-associated Cushing’s disease? An exploratory retrospective study,” was published in the journal Pituitary.

Eighty percent of Cushing’s disease cases are women, and most are of reproductive age.

Levels of the body’s main stress hormone, cortisol, normally increase during pregnancy. In the last weeks before birth, cortisol levels are two to three times higher than normal, similar to Cushing’s disease.

Because cortisol levels gradually increase during pregnancy, a diagnosis of Cushing’s disease within the gestation period is problematic.

Circumstantial “evidence suggests a higher incidence of CD immediately following pregnancy, in the peripartum period [a few weeks after childbirth],” the study’s authors wrote.

To shed additional light on the matter, researchers retrospectively investigated the frequency of Cushing’s disease onset related to pregnancy.

A total of 64 women with biochemically-diagnosed Cushing’s disease and treated at Providence Saint John’s Health Center in Santa Monica, California, from July 2007 to December 2017 were included in this study.

For the analysis, patients were divided into three groups:

  1. Women with pregnancy-associated CD: “defined as symptom-onset within 1 year of pregnancy that was explicitly linked to the pregnancy by the patient’s own recollection of her pregnancy and subsequent symptoms related to CD”;
  2. Women of reproductive age: “defined as age 15–45 years, in whom CD onset was not associated temporally with pregnancy within the past year”;
  3. Women not of reproductive age at the time of CD onset.

Results showed that 64 percent of the patients were of childbearing age at the time of diagnosis. Of these, 27 percent (11 women) had pregnancy-associated Cushing’s disease. This might be due to small, slow-growing or dormant corticotroph pituitary adenomas that were stimulated by pregnancy-related hormonal changes; however, this hypothesis was not confirmed by the researchers.

On average, patients in group 1 had two pregnancies prior to Cushing’s disease onset, compared to zero for 30 other women with disease onset during reproductive age. This suggests that undergoing the biological stress of pregnancy more than once could play a role in Cushing’s development.

“Another possible explanation of the association between CD and pregnancy is simply that patients are more likely to remember the onset of their CD symptoms in relation to a landmark life event such as pregnancy and childbirth, which leads to long-term physical changes in most women, irrespective of Cushing’s status,” the researchers noted.

In contrast, 19 of the 30 patients at reproductive age without pregnancy-associated disease had no pregnancies before being diagnosed, which weakens the association between pregnancy and Cushing’s and draws attention to various other factors that may also be involved in disease onset, apart from gestation-related hormonal changes.

The time from the onset of symptoms to diagnosis for women with pregnancy-related disease varied from two to six years.

“It was in fact weight gain or failure to lose weight post-pregnancy, which was the most frequent complaint and presentation in our patients with pregnancy-associated CD, and which often lead to an eventual diagnosis of CD,” the researchers stated.

“As such, appropriate biochemical testing may be indicated in women who 6–18 months after pregnancy, are still unable to lose the weight of pregnancy, continue to gain weight, have new, persistent or more [treatment-resistant] hypertension and diabetes mellitus, and/or other classical stigmata of CD,” they suggested.

All patients with biochemically-confirmed Cushing’s disease underwent surgery to remove pituitary adenoma. Sustained surgical remission rates for groups 1, 2, and 3 were 91%, 80%, and 83%, respectively.

“This possible association suggests a heightened degree of clinical suspicion and biochemical testing for CD may be warranted after childbirth. Further study of this possible link between pregnancy and CD is warranted,” the team concluded.

From https://cushingsdiseasenews.com/2018/09/21/cushings-disease-symptoms-onset-pregnancy-could-be-linked-study-suggests/

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