Bilateral Adrenalectomy Negatively Affects Quality of Life in Cushing’s Patients

Bilateral adrenalectomy, in which the adrenal glands are removed, has a bigger negative impact on the quality of life of patients with Cushing’s disease than other treatment options, a recent study suggests.

This may be due to the longer exposure to high levels of cortisol in these patients, which is known to greatly affect their quality of life, the authors hypothesize.

The study, “Bilateral adrenalectomy in Cushing’s disease: Altered long-term quality of life compared to other treatment options,” was published in the journal Annales d’Endocrinologie.

Cushing’s disease is caused by a tumor in the pituitary gland in the brain that secretes large amounts of adrenocorticotropic hormone, which, in turn, stimulates the adrenal glands to produce high levels of cortisol (a glucocorticoid hormone).

The gold standard for treating Cushing’s disease is the surgical removal of the pituitary gland tumor. However, 31% of these patients still require a second-line treatment — such as another surgery, radiotherapy, medical treatment, and/or bilateral adrenalectomy — due to persistent or recurrent disease.

Bilateral adrenalectomy is increasingly used to treat patients with Cushing’s disease, with high rates of success and low mortality rates. However, since the absence of adrenal glands leads to a sharp drop in cortisol, this treatment implies lifelong glucocorticoid replacement therapy and increases the risk of developing Nelson syndrome.

Nelson syndrome is characterized by the enlargement of the pituitary gland and the development of pituitary gland tumors, and is estimated to occur in 15-25% of Cushing’s patients who have a bilateral adrenalectomy.

Despite being cured with any of these treatment options, patients still seem to have a lower quality of life than healthy people. In addition, there is limited data on the impact of several of the treatment options on quality of life.

Researchers in France evaluated the long-term quality of life of Cushing’s disease patients who underwent bilateral adrenalectomy and compared it with other therapeutic options.

Quality of life was assessed through three questionnaires: one of general nature, the Short Form-36 Health Survey (SF-36); one on disease-specific symptoms, the Cushing QoL questionnaire; and the last focused on mental aspects, the Beck depression inventory (BDI).

Researchers analyzed the medical data, as well as the results of the questionnaires, of 34 patients with Cushing’s disease — 24 women and 10 men — at two French centers. The patients’ mean age was 49.3, and 17 had undergone bilateral adrenalectomy, while the remaining 17 had surgery, radiotherapy, or medical treatment.

Results showed that patients who underwent a bilateral adrenalectomy were exposed to high levels of cortisol significantly longer (6.1 years) than those on other treatment options (1.3 years). This corresponds with the fact that this surgery is conducted only in patients with severe disease that was not controlled with first-line and/or second-line treatment.

These patients also showed a lower quality of life — particularly in regards to the general health, bodily pain, vitality, and social functioning aspects of the SF-36 questionnaire, and the Cushing QoL questionnaire and BDI — compared with those who underwent other therapeutic options.

This and other studies support the hypothesis that these patients’ lower quality of life may be caused by longer exposure to high cortisol levels, and “its physical and psychological consequences, as well as the repeated treatment failures,” according to the researchers. Additionally, the presence of Nelson syndrome in these patients was associated with a significantly lower quality of life related to mental aspects.

The team also found that adrenal gland insufficiency was a major predictor of a lower quality of life in these patients, regardless of the therapeutic option, suggesting it may have a stronger negative impact than the type of treatment.

They noted, however, that additional and larger prospective studies are necessary to confirm these results.

From https://cushingsdiseasenews.com/2018/09/28/bilateral-adrenalectomy-lowers-cushing-patients-quality-life-study/

Fluconazole Found to Be Safe Alternative for Patient with Recurrent Cushing’s

Treatment with fluconazole after cabergoline eased symptoms and normalized cortisol levels in a patient with recurrent Cushing’s disease who failed to respond to ketoconazole, a case study reports.

The case report, “Fluconazole as a Safe and Effective Alternative to Ketoconazole in Controlling Hypercortisolism of Recurrent Cushing’s Disease: A Case Report,” was published in the International Journal of Endocrinology Metabolism.

Ketoconazole, (brand name Nizoral, among others) is an anti-fungal treatment used off-label for Cushing’s disease to prevent excess cortisol production, a distinct symptom of the disease. However, severe side effects associated with its use often result in treatment discontinuation and have led to its unavailability or restriction in many countries.

Consequently, there is a need for alternative medications that help manage disease activity and clinical symptoms without causing adverse reactions, and that could be given to patients who do not respond to ketoconazole treatment.

In this case report, researchers in Malaysia reported on a 50-year-old woman who fared well with fluconazole treatment after experiencing severe side effects with ketoconazole.

The woman had been in remission for 16 years after a transsphenoidal surgery — a minimally invasive brain surgery to remove a pituitary tumor — but went to the clinic with a three-year history of high blood pressure and gradual weight gain.

She also showed classic symptoms of Cushing’s disease: moon face, fragile skin that bruised easily, and purple stretch marks on her thighs.

Blood and urine analysis confirmed high cortisol levels, consistent with a relapse of the pituitary tumor. Accordingly, magnetic resonance imaging (MRI) of her brain showed the presence of a small tumor on the right side of the pituitary gland, confirming the diagnosis of recurrent Cushing’s disease.

Doctors performed another transsphenoidal surgery to remove the tumor, and a brain MRI then confirmed the success of the surgery. However, her blood and urine cortisol levels remained markedly high, indicating persistent disease activity.

The patient refused radiation therapy or adrenal gland removal surgery, and was thus prescribed ketoconazole twice daily for managing the disease. But after one month on ketoconazole, she experienced low cortisol levels.

Hydrocortisone — a synthetic cortisol hormone — was administered to maintain steady cortisol levels. However, she developed severe skin itching and peeling, which are known side effects of ketoconazole. She also suffered a brain bleeding episode, for which she had to have a craniotomy to remove the blood clot.

Since she experienced adverse effects on ketoconazole, which also hadn’t decreased her disease activity, the doctors switched her to cabergoline. Cabergoline (marketed as Dostinex, among others) is a dopamine receptor agonist that has been shown to be effective in managing Cushing’s disease.

But cabergoline treatment also did not lower the disease activity, and her symptoms persisted.

The doctors then added fluconazole (marketed as Diflucan, among others), an anti-fungal medication, based on studies that showed promising results in managing Cushing’s syndrome. Three months after the addition of fluconazole to her treatment plan, the patient’s clinical symptoms and cortisol levels had responded favorably.

At her next clinical visit 15 months later, her condition remained stable with no adverse events.

“This case demonstrates the long-term efficacy of fluconazole in tandem with cabergoline for the control of recurrent Cushing’s disease,” the researchers wrote.

The favorable outcome in this case also “supports the notion that fluconazole is a viable substitute for ketoconazole in the medical management of this rare but serious condition,” they concluded.

From https://cushingsdiseasenews.com/2018/09/27/fluconazole-safe-effective-alternative-recurrent-cushings-patient-case-report/

Minimally Invasive Approaches Lead to High Remission Rates in Children

Minimally invasive diagnostic methods and transnasal surgery may lead to remission in nearly all children with Cushing’s disease, while avoiding more aggressive approaches such as radiation or removal of the adrenal glands, a study shows.

The study, “A personal series of 100 children operated for Cushing’s disease (CD): optimizing minimally invasive diagnosis and transnasal surgery to achieve nearly 100% remission including reoperations,” was published in the Journal of Pediatric Endocrinology and Metabolism.

Normally, the pituitary produces adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands to produce cortisol. When a patient has a pituitary tumor, that indirectly leads to high levels of cortisol, leading to development of Cushing’s disease (CD).

In transnasal surgery (TNS), a surgeon goes through the nose using an endoscope to remove a pituitary tumor. The approach is the first-choice treatment for children with Cushing’s disease due to ACTH-secreting adenomas — or tumors — in the pituitary gland.

Micro-adenomas, defined as less than 4 mm, are more common in children and need surgical expertise for removal. It is necessary to determine the exact location of the tumor before conducting the surgery.

Additionally, many surgeons perform radiotherapy or bilateral adrenalectomy (removal of both adrenal glands) after the surgery. However, these options are not ideal as they can be detrimental to children who need to re-establish normal growth and development patterns.

Dieter K. Lüdecke, a surgeon from Germany’s University of Hamburg, has been able to achieve nearly 100% remission while minimizing the need for pituitary radiation or bilateral adrenalectomy. In this study, researchers looked at how these high remission rates can be achieved while minimizing radiotherapy or bilateral adrenalectomy.

Researchers analyzed 100 patients with pediatric CD who had been referred to Lüdecke for surgery from 1980-2009. Data was published in two separate series — series 1, which covers patients from 1980-1995, and series 2, which covers 1996-2009. All the surgeries employed direct TNS.

Diagnostic methods for CD have improved significantly over the past 30 years. Advanced endocrine diagnostic investigations, such as testing for levels of salivary cortisol in the late evening and cortisol-releasing hormone tests, have made a diagnosis of CD less invasive. This is particularly important for excluding children with obesity alone from children with obesity and CD. Methods to determine the precise location of micro-adenomas have also improved.

The initial methodology to localize tumors was known as inferior petrosal sinus sampling (IPSS), an invasive procedure in which ACTH levels are sampled from the veins that drain the pituitary gland.

In series 1, IPSS was performed in 24% of patients, among which 46% were found to have the wrong tumor location. Therefore, IPSS was deemed invasive, risky, and unreliable for this purpose.

All adenomas were removed with extensive pituitary exploration. Two patients in series 1 underwent early repeat surgery; all were successful.

Lüdecke introduced intraoperative cavernous sinus sampling (CSS), an improved way to predict location of adenomas. This was found to be very helpful in highly select cases and could also be done preoperatively for very small adenomas.

In series 2, CSS was used in only 15% of patients thanks to improved MRI and endocrinology tests. All patients who underwent CSS had correct localization of their tumors, indicating its superiority over IPSS.

In series 2, three patients underwent repeat TNS, which was successful. In these recurrences, TNS minimized the need for irradiation. The side effects of TNS were minimal. Recurrence rate in series 1 was 16% and 11% in series 2.

While Lüdecke’s patients achieved a remission rate of 98%, other studies show cure rates of 45-69%. Only 4% of patients in these two series received radiation therapy.

“Minimally invasive unilateral, microsurgical TNS is important functionally for both the nose and pituitary,” the researchers concluded. “Including early re-operations, a 98% remission rate could be achieved and the high risk of pituitary function loss with radiotherapy could be avoided.”

From https://cushingsdiseasenews.com/2018/09/04/minimally-invasive-methods-yield-high-remission-in-cushings-disease-children/

%d bloggers like this: