Late-night salivary cortisol often fluctuates widely in Cushing’s disease

Among patients with new, persistent or recurrent Cushing’s disease, researchers observed cortisol levels that fluctuated widely over 6 months, with measurements falling into the normal range more than 50% of the time for a few patients, according to findings from a prospective study.

“Cortisol levels, as represented by late-night salivary cortisol, in Cushing’s disease patients without variable symptoms fluctuate much more widely than many endocrinologists may realize,” Laurence Kennedy, MD, FRCP, chairman of the department of endocrinology, diabetes and metabolism at the Cleveland Clinic, told Endocrine Today. “In patients with recurrent or persistent Cushing’s disease, the late-night salivary cortisol can be normal much more frequently than has been appreciated.”

Kennedy and colleagues analyzed late-night salivary samples (between 11 p.m. and midnight) from 16 patients with confirmed Cushing’s disease for up to 42 consecutive nights between January and June 2014 (age range, 27-62 years). Researchers defined normal late-night salivary cortisol as between 29 ng/dL and 101 ng/dL.

Within the cohort, eight patients had a new diagnosis of Cushing’s disease and underwent transsphenoidal surgery; eight patients had recurrent or persistent Cushing’s disease.

Researchers observed at least three peaks and two troughs in 12 of the 16 patients, and late-night salivary cortisol levels were in the normal range on at least one occasion in 14 patients (all patients with recurrent/persistent disease and six of eight patients with new disease). Only two of the 16 patients exhibited fluctuations that were deemed cyclical, according to researchers, with the interval between peaks approximately 4 days, they noted.

In five of the eight patients with recurrent or persistent disease, the lowest late-night salivary cortisol measurement was at or below the limit of detection on the assay and approximately 1 in 3 measurements were in the normal range, researchers found. Four patients had normal measurements more than 50% of the time.

Additionally, six of the patients with recurrent or persistent disease had measurements in the normal range on two consecutive nights on at least one occasion, two patients had six such measurements in a row, and one had 31 consecutive normal levels, according to researchers.

In six patients with newly diagnosed Cushing’s disease with at least one normal late-night salivary cortisol measurement, the maximum levels ranged from 1.55 to 15.5 times the upper limit of normal.

“First, widely fluctuant cortisol levels in patients with Cushing disease do not appear to be associated with fluctuating symptoms, at least in our patient population,” Kennedy said. “Second, you need to be careful drawing conclusions on the efficacy of potential medical treatments for Cushing’s disease based on only one or two late-night salivary cortisol levels, given the extreme variation that occurs in the untreated patient. Third, diagnosing recurrent or persistent Cushing’s disease can be challenging at the best of times, and, though it is felt that late-night salivary cortisol may be the best test for early diagnosis, it may require more than the suggested two, three or four tests on successive nights to make the diagnosis.”

Kennedy said better tests for diagnosing Cushing’s disease are needed, adding that investigating the potential utility of salivary cortisone could be useful. – by Regina Schaffer

For more information:

Lawrence Kennedy, MD, can be reached at Cleveland Clinic, Department of Endocrinology, Diabetes and Metabolism, 9500 Euclid Ave., Cleveland, OH 44195; email: kennedl4@ccf.org.

Disclosures: The authors report no relevant financial disclosures.

From https://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7Bf9721377-6a2a-401c-a16d-2d4624233b63%7D/late-night-salivary-cortisol-often-fluctuates-widely-in-cushings-disease

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/

Cushing Patients Could Be Diagnosed, Subtyped Using Plasma Steroid Levels

Patients with different subtypes of Cushing’s syndrome (CS) have distinct plasma steroid profiles. This could be used as a test for diagnosis and classification, a German study says.

The study, “Plasma Steroid Metabolome for Diagnosis and Subtyping Patients with Cushing Syndrome,” appeared in the journal Clinical Chemistry.

A quick diagnosis of CS is crucial so that doctors can promptly give therapy. However, diagnosing CS is often complicated by the multiple tests necessary not just to diagnose the disease but also to determine its particular subtype.

Cortisol, which leads to CS when produced at high levels, is a steroid hormone. But while earlier studies were conducted to determine whether patients with different subtypes of CS had distinct steroid profiles, the methods researchers used were cumbersome and have been discontinued for routine use.

Recently, a technique called LC-MS/MS has emerged for multi-steroid profiling in patients with adrenocortical dysfunction such as congenital adrenal hyperplasia, adrenal insufficiency and primary aldosteronism.

Researchers at Germany’s Technische Universität in Dresden used that method to determine whether patients with the three main subtypes of CS (pituitary, ectopic and adrenal) showed differences in plasma steroid profiles. They measured levels of 15 steroids produced by the adrenal glands in single plasma samples collected from 84 patients with confirmed CS and 227 age-matched controls.

They found that CS patients saw huge increases in the plasma steroid levels of 11-deoxycortisol (289%), 21-deoxycortisol (150%), 11-deoxycorticosterone (133%), corticosterone (124%) and cortisol (122%), compared to patients without the disease.

Patients with the ectopic subtype had the biggest jumps in levels of these steroids. However, plasma 18-oxocortisol levels were particularly low in ectopic disease. Other steroids demonstrated considerable variation.

Patients with the adrenal subtype had the lowest concentration of dehydroepiandrosterone (DHEA) and DHEA-SO4, which are androgens. Patients with the ectopic and pituitary subtype had the lowest concentration of aldosterone.

Through the use of 10 selected steroids, patients with different subtypes of CS could be identified almost as closely as with other tests, including the salivary and urinary free cortisol test, the dexamethasone-suppressed cortisol test, and plasma adrenocorticotropin levels. The misclassification rate using steroid levels was 9.5 percent, compared to 5.8 percent in other tests.

“This study using simultaneous LC-MS/MS measurements of 15 adrenal steroids in plasma establishes distinct steroid metabolome profiles that might be useful as a test for CS,” the team concluded, adding that using LC-MS/MS is advantageous, as specimen preparation is simple and the entire panel takes 12 minutes to run. This means it could be offered as a single test for both identification and subtype classification.

From https://cushingsdiseasenews.com/2018/01/02/plasma-steroid-levels-used-screen-diagnosis-subtyping-patients-cushing-syndrome/

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