Cushing’s Syndrome Subtype Affects Postoperative Time to Adrenal Recovery

Berr CM. J Clin Endocrinol Metab. 2014;doi:10.1210/jc.2014-3632.

January 16, 2015

In patients undergoing curative surgical tumor resection for Cushing’s syndrome, the time to recovery of adrenal function is contingent upon the underlying etiology of the disease, according to recent findings.

In the retrospective study, researchers reviewed case records of 230 patients with Cushing’s syndrome. All patients were seen at a tertiary care center in Munich between 1983 and 2014, whose cases were documented in the German Cushing’s Registry. Patients were divided into three subgroups of Cushing’s syndrome: Cushing’s disease, adrenal Cushing’s syndrome and ectopic Cushing’s syndrome.

After applying various exclusion criteria, the researchers identified 91 patients of the three subgroups who were undergoing curative surgery at the hospital. The patients were followed for a median of 6 years. The researchers defined adrenal insufficiency as the need for hydrocortisone replacement therapy, and collected this information from patient records and laboratory results.

The duration of adrenal insufficiency was calculated as the interval between successful surgery and the completion of hydrocortisone replacement therapy. Cushing’s syndrome recurrence was defined as biochemical and clinical signs of hypercortisolism.

The researchers found a significant difference between Cushing’s syndrome subtypes in the likelihood of regaining adrenal function within 5 years of follow-up: The probability was 82% in ectopic Cushing’s syndrome, 58% in Cushing’s disease and 38% in adrenal Cushing’s syndrome (P=.001). Among the 52 participants who recovered adrenal function, the median type to recovery also differed between subtypes and was 0.6 years in ectopic Cushing’s syndrome, 1.4 years in Cushing’s disease and 2.5 years in adrenal Cushing’s syndrome (P=.002).

An association also was found between younger age and adrenal recovery in the Cushing’s disease participants (P=.012).

This association was independent of sex, BMI, symptom duration, basal adrenocorticotropic hormone and cortisol levels. No association was seen between adrenal recovery and length of hypercortisolism or postoperative glucocorticoid replacement dosage.

“It is the main finding of this series that the median duration of tertiary adrenal insufficiency was dependent on the etiology of [Cushing’s syndrome]: It was shortest in the ectopic [Cushing’s syndrome], intermediate in [Cushing’s disease] and longest in adrenal [Cushing’s syndrome] caused by unilateral cortisol producing adenoma,” the researchers wrote. “The significant difference to [Cushing’s disease] is an unexpected finding since by biochemical means cortisol excess is generally less severe in adrenal [Cushing’s syndrome]. If confirmed by others, our data have clinical impact for the follow-up of patients after curative surgery: Patients should be informed that adrenocortical function may remain impaired in benign conditions such as cortisol-producing adenoma.”

Disclosure: The study was funded in part by the Else Kröner-Fresenius Stiftung.

The original article is here: Healio

Cushing’s Syndrome Etiology Affects Adrenal Function Recovery

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

Design:

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

The probability of recovering adrenal function within a 5 years follow-up differed significantly between subtypes (p=0.001). It was 82 % in ectopic CS, 58 % in Cushing’s disease 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 (IQR 0.03–1.1) years in ectopic CS, 1.4 (IQR 0.9–3.4) years in CD, and 2.5 (IQR 1.6–5.4) years in adrenal CS (p=0.002). In CD the Cox proportional-hazards model showed that the probability of recovery was associated with younger age (hazard ratio 0.896, 95% CI 0.822–0.976, p=0.012), independently of sex, BMI, duration of symptoms, and basal ACTH and cortisol levels. There was no correlation with length and extend of hypercortisolism or postoperative glucocorticoid replacement doses.

Conclusions:

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

Myth: “Each Person Requires the Same Dose of Steroid in Order to Survive…

Myth: “Each person requires the same dose of steroid in order to survive with Secondary or Primary Adrenal Insufficiency”

myth-busted

Fact: In simple terms, Adrenal Insufficiency occurs when the body does not have enough cortisol in it. You see, cortisol is life sustaining and we actually do need cortisol to survive. You have probably seen the commercials about “getting rid of extra belly fat” by lowering your cortisol. These advertisements make it hard for people to actually understand the importance of the function of cortisol.

After a Cushing’s patient has surgery, he/she goes from having very high levels of cortisol to no cortisol at all. For pituitary patients, the pituitary, in theory, should start working eventually again and cause the adrenal glands to produce enough cortisol. However, in many cases; the pituitary gland does not resume normal functioning and leaves a person adrenally insufficient. The first year after pit surgery is spent trying to get that hormone to regulate on its own normally again. For a patient who has had a Bilateral Adrenalectomy (BLA), where both adrenal glands are removed as a last resort to “cure” Cushing’s; his/her body will not produce cortisol at all for his/her life. This causes Primary Adrenal Insufficiency.

All Cushing’s patients spend time after surgery adjusting medications and weaning slowly from steroid (cortisol) to get the body to a maintenance dose, which is the dose that a “normal” body produces. This process can be a very long one. Once on maintenance, a patient’s job is not over. He/She has to learn what situations require even more cortisol. You see, cortisol is the stress hormone and also known as the Fight or Flight hormone. Its function is to help a person respond effectively to stress and cortisol helps the body compensate for both physical and emotional stress. So, when faced with a stressor, the body will produce 10X the baseline levels in order to compensate. When a person can not produce adequate amounts of cortisol to compensate, we call that Adrenal Insufficiency. If it gets to the point of an “Adrenal Crisis”, this means that the body can no longer deal and will go into shock unless introduced to extremely high levels of cortisol, usually administered through an emergency shot of steroid.

There are ways to help prevent a crisis, by taking more steroid than the maintenance dose during times of stress. This can be anything from going to a family function (good stress counts too) to fighting an infection or illness. Acute stressors such as getting into a car accident or sometimes even having a really bad fight require more cortisol as well.

It was once believed that everyone responded to every stressor in the exact same way. So, there are general guidelines about how much more cortisol to introduce to the body during certain stressors. For instance, during infection, a patient should take 2-3X the maintenance dose of steroid (cortisol). Also, even the maintenance dose was considered the same for everyone. Now a days, most doctors will say that 20 mg of Hydrocortisone (Steroid/Cortisol) is the appropriate maintenance dose for EVERYONE. Now, we know that neither is necessarily true. Although the required maintenance dose is about the same for everyone; some patients require less and some require more. I have friends who will go into an adrenal crisis if they take LESS than 30 mg of daily steroid. On the other hand, 30 mg may be way too much for some and those folks may even require LESS daily steroid, like 15 mg. Also, I want to stress (no pun intended) that different stressors affect different people differently. For some, for instance, an acute scare may not affect them. However, for others, receiving bad news or being in shock WILL put their bodies into crisis. That person must then figure out how much additional steroid is needed.

Each situation is different and each time may be different. Depending on the stressor, a person may need just a little more cortisol or a lot. Every person must, therefore, learn their own bodies when dealing with Adrenal Insufficiency. This is VERY important! I learned this the hard way. As a Clinical Psychologist; I assumed that my “coping skills” would be enough to prevent a stressor from putting me into crisis. That was FAR from the truth! I have learned that I can not necessarily prevent my body’s physiological response to stress. People often ask me, “BUT you are a psychologist! Shouldn’t you be able to deal with stress?!!!!” What they don’t realize is that my BODY is the one that has to do the job of compensating. Since my body can not produce cortisol at all, my job is to pay close attention to it so that I can take enough steroid to respond to any given situation. We all have to do that. We all have to learn our own bodies. This is vitally important and will save our lives!

To those we have lost in our community to Adrenal Insufficiency after treatment of Cushing’s, Rest in Peace my friends! Your legacies live on forever!

~ By Karen Ternier Thames

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/