Cushing Syndrome Results in Poor Quality of Life Even After Remission

Functional remission did not occur in most patients with Cushing syndrome who were considered to be in biochemical and clinical remission, according to a study published in Endocrine. This was evidenced by their quality of life, which remained impaired in all domains.

The term “functional remission” is a psychiatric concept that is defined as an “association of clinical remission and a recovery of social, professional, and personal levels of functioning.” In this observational study, investigators sought to determine the specific weight of psychological (anxiety and mood, coping, self-esteem) determinants of quality of life in patients with Cushing syndrome who were considered to be in clinical remission.

The cohort included 63 patients with hypercortisolism currently in remission who completed self-administered questionnaires that included quality of life (WHOQoL-BREF and Cushing QoL), depression, anxiety, self-esteem, body image, and coping scales. At a median of 3 years since remission, participants had a significantly lower quality of life and body satisfaction score compared with the general population and patients with chronic diseases. Of the cohort, 39 patients (61.9%) reported having low or very low self-esteem, while 16 (25.4%) had high or very high self-esteem. Depression and anxiety were seen in nearly half of the patients and they were more depressed than the general population. In addition, 42.9% of patients still needed working arrangements, while 19% had a disability or cessation of work.

Investigators wrote, “This impaired quality of life is strongly correlated to neurocognitive damage, and especially depression, a condition that is frequently confounded with the poor general condition owing to the decreased levels of cortisol. A psychiatric consultation should thus be systematically advised, and [selective serotonin reuptake inhibitor] therapy should be discussed.”

Reference

Vermalle M, Alessandrini M, Graillon T, et al.  Lack of functional remission in Cushing’s Syndrome [published online July 17, 2018]. Endocrine. doi:10.1007/s12020-018-1664-7

From https://www.endocrinologyadvisor.com/general-endocrinology/functional-remission-quality-of-life-cushings-syndrome/article/788501/

Metyrapone Reduced Urinary-Free Cortisol Levels in Cushing Syndrome

Metyrapone treatments helped patients with Cushing syndrome reach normal, urinary-free cortisol levels in the short-term and also had long-term benefits, according to a study published in Endocrine.

This observational, longitudinal study evaluated the effects of the 11β -hydroxylase inhibitor metyrapone on adult patients with Cushing syndrome. Urinary-free cortisol and late-night salivary cortisol levels were evaluated in 31 patients who were already treated with metyrapone to monitor cortisol normalization and rhythm.

The average length of metyrapone treatment was 9 months, and 6 patients had 24 months of treatment. After 1 month of treatment, the mean urinary-free cortisol was reduced from baseline by 67% and mean late-night salivary cortisol level decreased by 57%.

Analyzing only patients with severe hypercortisolism, after 1 month of treatment, the mean urinary-free cortisol decreased by 86% and the mean late-night salivary cortisol level decreased 80%. After 3 months, normalization of the mean urinary-free cortisol was established in 68% of patients. Mean late-night salivary cortisol levels took longer to decrease, especially in severe and very severe hypercortisolism, which could take 6 months to drop. Treatment was more successful at normalizing cortisol excretion (70%) than cortisol rhythm (37%). Nausea, abdominal pain, and dizziness were the most common adverse events, but no severe adverse event was reported.

Future research is needed to evaluate a larger cohort with randomized dosages and stricter inclusion criteria to evaluate metyrapone’s effects on cortisol further.

Study researchers conclude that metyrapone was successful and safe in lowering urinary-free cortisol after just 1 month of treatment and controlling long-term levels in patients with Cushing syndrome.

This study was supported by Novartis.

Reference

Ceccato F, Zilio M, Barbot M, et al. Metyrapone treatment in Cushing’s syndrome: a real-life study [published online July 16, 2018]. Endocrine. doi: 10.1007/s12020-018-1675-4

From https://www.endocrinologyadvisor.com/general-endocrinology/metyrapone-cushing-syndrome/article/786716/

Benefits of Medication Before Surgery for Cushing’s Syndrome Still Unclear

In Europe, nearly 20 percent of patients with Cushing’s syndrome receive some sort of medication for the disease before undergoing surgery, a new study shows.

Six months after surgery, these patients had remission and mortality rates similar to those who received surgery as a first-line treatment, despite having worse disease manifestations when the study began. However, preoperative medication may limit doctors’ ability to determine the immediate success of surgery, researchers said.

A randomized clinical trial is needed to conclusively address if preoperative medication is a good option for Cushing’s patients waiting for surgery, they stated.

The study, “Preoperative medical treatment in Cushing’s syndrome. Frequency of use and its impact on postoperative assessment. Data from ERCUSYN,” was published in the European Journal of Endocrinology. 

Surgery usually is the first-line treatment in patients with Cushing’s syndrome. But patients also may receive preoperative medication to improve cortisol excess and correct severe diseases occurring simultaneously with Cushing’s.

Multiple studies have hypothesized that preoperative medication can have a beneficial effect on patients who undergo surgery. However, data on the beneficial impact of medication on morbidity, and the immediate surgical and long-term outcomes in patients with Cushing’s syndrome, are limited and inconclusive.

So, researchers made use of the European Registry on Cushing’s Syndrome (ERCUSYN), the largest database that collects information on diagnosis, management, and long-term follow-up in Cushing’s patients.

The team set out to collect information of the prevalence of preoperative medication in Cushing’s patients throughout Europe, and whether it influences patients’ outcomes after surgery. It also aimed to determine the differences between patients who receive preoperative medication versus those who undergo surgery directly.

Researchers analyzed 1,143 patients in the ERCUSYN database from 57 centers in 26 countries. Depending on what was causing the disease, patients were included in four major groups: pituitary-dependent Cushing’s syndrome (68%), adrenal-dependent Cushing’s syndrome (25%), Cushing’s syndrome from an ectopic source (5%), and Cushing’s syndrome from other causes (1%).

Overall, 20 percent of patients received medication – ketoconazole, metyrapone, or a combination of both – before surgery. Patients with ectopic and pituitary disease were more likely to receive medication compared to patients whose disease stemmed from the adrenal glands. Preoperative treatment lasted for a median of 109 days.

Patients in the pituitary group who were prescribed preoperative medication had more severe clinical features at diagnosis and poorer quality of life compared to those who received surgery as first-line treatment. No differences were found in the other groups.

But patients with pituitary-dependent disease receiving medication were more likely to have normal cortisol within seven days of surgery, or the immediate postoperative period, compared to patients who had surgery without prior medication. These patients also had a lower remission rate.

Within six months of surgery, however, there were no differences in morbidity or remission rates observed between each group. Also, no differences were seen in perioperative mortality rates – within one month of surgery.

Interestingly, researchers noted that patients who took medication prior to surgery were less likely to be in remission immediately after surgery. The reason, they suggest, might be because the medication already had begun to improve the clinical and biochemical signs of the disease, “so changes that take place in the first week after surgery may be less dramatic.”

“A randomized trial assessing simple endpoints, such as length of hospital stay, surgical impression and adverse effects of surgery, is needed to conclusively demonstrate that [preoperative medication] is a valid option in patients waiting for surgical correction of hypercortisolism,” the team concluded.

From https://cushingsdiseasenews.com/2018/02/22/benefits-cushings-syndrome-pre-surgery-medication-unclear-study/

Pregnant Women with Hypertension and Hypercortisolism May Have Cushing’s

Pregnant woman with hypertension and significant signs of hypercortisolism (high cortisol levels) may have Cushing’s disease, according to a new case report.

The report, titled “A Case of Cushing’s Syndrome in Pregnancy,” was published in the Iranian Journal of Medical Sciences.

While Cushing’s rarely occurs in women during pregnancy, high cortisol levels can lead to major complications for both the mother and the fetus, such as premature birth and high fetal mortality.

However, it can be difficult to diagnose pathological hypercortisolism in these women as the symptoms might resemble other diseases that commonly occur during pregnancy, such as preeclampsia (high blood pressure during pregnancy) and gestational diabetes.

Unfortunately, there are no effective long-term medical therapies for Cushing’s. The most definitive therapy is the surgical removal of the pituitary or adrenal adenoma, if that is the case of hypercortisolism.

The case report details that a 29-year old women in the 27th week of pregnancy presented to the Ghaem Hospital clinic in Mashhad, Iran, with edema, weakness, and hypertension. Her symptoms also included truncal obesity, moon face (her face had a rounded appearance), purple steria on her upper and lower limbs and abdomen, excessive edema, and wet skin.

At first, she was hospitalized for suspected preeclampsia, but the diagnosis was later excluded.

The patient’s hormonal profile showed high levels of 24-hour urine cortisol. There were also low levels of adrenocorticotropic hormone (ACTH), which results from a negative feedback due to excessive cortisol. However, plasma cortisol is generally elevated during pregnancy, and therefore may not be the best method for diagnosis.

An abdominal ultrasonography revealed a well-defined mass in the right adrenal gland.

While hospitalized, the patient experienced two crises of blood pressure, and while preeclampsia was ruled out, the physicians could find no more plausible explanation than eclampsia (the onset of seizures in a women with preeclampsia).

Since eclampsia was suspected, the physicians terminated the pregnancy at 28th week of gestation using misoprostol. The woman delivered a male infant weighing 1.94 pounds.

Two days after birth, the physicians conducted a computed tomography (CT) scan and again found a mass in the right adrenal gland.

As a result, the patient underwent a laparoscopic right adrenalectomy to remove the mass one week after giving birth. The patient’s blood pressure normalized and cortisol levels declined. Her condition remained stable after surgery.

“Cushing’s syndrome should be considered in hypertensive pregnant patients with remarkable signs of hypercortisolism,” the researchers concluded. “The best results would be achieved through a collaboration between obstetricians, endocrinologists, and surgeons.”

From https://cushingsdiseasenews.com/2017/12/19/pregnant-women-hypertension-hypercortisolism-may-have-cushings-disease/

Patients Undergoing Adrenalectomy Should Receive Steroid Substitutive Therapy

All patients who undergo removal of one adrenal gland due to Cushing’s syndrome (CS) or adrenal incidentaloma (AI, adrenal tumors discovered incidentally) should receive a steroid substitutive therapy, a new study shows.

The study, “Predictability of hypoadrenalism occurrence and duration after adrenalectomy for ACTH‐independent hypercortisolism,” was published in the Journal of Endocrinological Investigation.

CS is a rare disease, but subclinical hypercortisolism, an asymptomatic condition characterized by mild cortisol excess, has a much higher prevalence. In fact, subclinical hypercortisolism, is present in up to 20 percent of patients with AI.

The hypothalamic-pituitary-adrenal axis (HPA axis) is composed of the hypothalamus, which releases corticotropin-releasing hormone (CRH) that acts on the pituitary to release adrenocorticotropic hormone (ACTH), that in turn acts on the adrenal gland to release cortisol.

To avoid excess cortisol production, high cortisol levels tell the hypothalamus and the pituitary to stop producing CRH and ACTH, respectively. Therefore, as CS and AI are characterized by high levels of cortisol, there is suppression of the HPA axis.

As the adrenal gland is responsible for the production of cortisol, patients might need steroid substitutive therapy after surgical removal of AI. Indeed, because of HPA axis suppression, some patients have low cortisol levels after such surgeries – clinically known as post-surgical hypocortisolism (PSH), which can be damaging to the patient.

While some researchers suggest that steroid replacement therapy should be given only to some patients, others recommend it should be given to all who undergo adrenalectomy (surgical removal of the adrenal gland).

Some studies have shown that the severity of hypercortisolism, as well as the degree of HPA axis suppression and treatment with ketoconazole pre-surgery in CS patients, are associated with a longer duration of PSH.

Until now, however, there have been only a few studies to guide in predicting the occurrence and duration of PSH. Therefore, researchers conducted a study to determine whether HPA axis activity, determined by levels of ACTH and cortisol, could predict the occurrence and duration of PSH in patients who undergo an adrenalectomy.

Researchers studied 80 patients who underwent adrenalectomy for either CS or AI. Prior to the surgery, researchers measured levels of ACTH, urinary free cortisol (UFC), and serum cortisol after 1 mg dexamethasone suppression test (1 mg-DST).

After the surgery, all patients were placed on steroid replacement therapy and PSH was determined after two months. For those with PSH, levels of cortisol were determined every six months for at least four years.

Results showed that PSH occurred in 82.4 percent of CS patients and 46 percent of AI patients. PSH lasted for longer than 18 months in 50 percent of CS and 30 percent of AI patients. Furthermore, it lasted longer than 36 months for 35.7 percent of CS patients.

In all patients, PSH was predicted by pre-surgery cortisol levels after the 1 mg-DST, but with less than 70 percent accuracy.

In AI patients, a shorter-than-12-month duration of PSH was not predicted by any HPA parameter, but was significantly predicted by an absence of pre-surgery diagnosis of subclinical hypercortisolism.

So, this study did not find any parameters that could significantly predict with high sensitivity and specificity the development or duration of PSH in all patients undergoing adrenalectomy.

Consequently, the authors concluded that “the PSH occurrence and its duration are hardly predictable before surgery. All patients undergoing unilateral adrenalectomy should receive a steroid substitutive therapy.”

From https://cushingsdiseasenews.com/2017/12/08/therapy-cushings-patients-adrenalectomy/

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