Most Subclinical Cushing’s Patients Don’t Require Glucocorticoids After Adrenalectomy

Patients with subclinical hypercortisolism, i.e., without symptoms of cortisol overproduction, and adrenal incidentalomas recover their hypothalamic-pituitary-adrenal (HPA) axis function after surgery faster than those with Cushing’s syndrome (CS), according to a study.

Moreover, the researchers found that an HPA function analysis conducted immediately after the surgical removal of adrenal incidentalomas — adrenal tumors discovered by chance in imaging tests — could identify patients in need of glucocorticoid replacement before discharge.

Using this approach, they found that most subclinical patients did not require treatment with hydrocortisone, a glucocorticoid taken to compensate for low levels of cortisol in the body, after surgery.

The study, “Alterations in hypothalamic-pituitary-adrenal function immediately after resection of adrenal adenomas in patients with Cushing’s syndrome and others with incidentalomas and subclinical hypercortisolism,” was published in Endocrine.

The HPA axis is the body’s central stress response system. The hypothalamus releases corticotropin-releasing hormone (CRH) that acts on the pituitary gland to release adrenocorticotropic hormone (ACTH), leading the adrenal gland to produce cortisol.

As the body’s defense mechanism to avoid excessive cortisol secretion, high cortisol levels alert the hypothalamus to stop producing CRH and the pituitary gland to stop making ACTH.

Therefore, in diseases associated with chronically elevated cortisol levels, such as Cushing’s syndrome and adrenal incidentalomas, there’s suppression of the HPA axis.

After an adrenalectomy, which is the surgical removal of one or both adrenal glands, patients often have low cortisol levels (hypocortisolism) and require glucocorticoid replacement therapy.

“Most studies addressing the peri-operative management of patients with adrenal hypercortisolism have reported that irrespective of how mild the hypercortisolism was, such patients were given glucocorticoids before, during and after adrenalectomy,” the researchers wrote.

Evidence also shows that, after surgery, glucocorticoid therapy is administered for months before attempting to test for recovery of HPA function.

For the past 30 years, researchers at the University Hospitals Cleveland Medical Center have withheld glucocorticoid therapy in the postoperative management of patients with ACTH-secreting pituitary adenomas until there’s proof of hypocortisolism.

“The approach offered us the opportunity to examine peri-operative hormonal alterations and demonstrate their importance in predicting need for replacement therapy, as well as future recurrences,” they said.

In this prospective observational study, the investigators extended their approach to patients with subclinical hypercortisolism.

“The primary goal of the study was to examine rapid alteration in HPA function in patients with presumably suppressed axis and appreciate the modulating impact of surgical stress in that setting,” they wrote. Collected data was used to decide whether to start glucocorticoid therapy.

The analysis included 14 patients with Cushing’s syndrome and 19 individuals with subclinical hypercortisolism and an adrenal incidentaloma. All participants had undergone surgical removal of a cortisol-secreting adrenal tumor.

“None of the patients received exogenous glucocorticoids during the year preceding their evaluation nor were they taking medications or had other illnesses that could influence HPA function or serum cortisol measurements,” the researchers noted.

Glucocorticoid therapy was not administered before or during surgery.

To evaluate HPA function, the clinical team took blood samples before and at one, two, four, six, and eight hours after the adrenalectomy to determine levels of plasma ACTH, serum cortisol, and dehydroepiandrosterone sulfate (DHEA-S) — a hormone produced by the adrenal glands.

Pre-surgery assessment of both groups showed that patients with an incidentaloma plus subclinical hypercortisolism had larger adrenal masses, higher ACTH, and DHEA-S levels, but less serum cortisol after adrenal function suppression testing with dexamethasone.

Dexamethasone is a man-made version of cortisol that, in a normal setting, makes the body produce less cortisol. But in patients with a suppressed HPA axis, cortisol levels remain high.

After the adrenalectomy, the ACTH concentrations in both groups of patients increased. This was found to be negatively correlated with pre-operative dexamethasone-suppressed cortisol levels.

Investigators reported that “serum DHEA-S levels in patients with Cushing’s syndrome declined further after adrenalectomy and were undetectable by the 8th postoperative hour,” while incidentaloma patients’ DHEA-S concentrations remained unchanged for the eight-hour postoperative period.

Eight hours after surgery, all Cushing’s syndrome patients had serum cortisol levels of less than 2 ug/dL, indicating suppressed HPA function. As a result, all of these patients required glucocorticoid therapy for several months to make up for HPA axis suppression.

“The decline in serum cortisol levels was slower and less steep [in the incidentaloma group] when compared to that observed in patients with Cushing’s syndrome. At the 6th–8th postoperative hours only 5/19 patients [26%] with subclinical hypercortisolism had serum cortisol levels at ≤3ug/dL and these 5 were started on hydrocortisone therapy,” the researchers wrote.

Replacement therapy in the subclinical hypercortisolism group was continued for up to four weeks.

Results suggest that patients with an incidentaloma plus subclinical hypercortisolism did not have an entirely suppressed HPA axis, as they were able to recover its function much faster than the CS group after surgical stress.

From https://cushingsdiseasenews.com/2018/10/11/most-subclinical-cushings-patients-dont-need-glucocorticoids-post-surgery-study/?utm_source=Cushing%27s+Disease+News&utm_campaign=a881a1593b-RSS_WEEKLY_EMAIL_CAMPAIGN&utm_medium=email&utm_term=0_ad0d802c5b-a881a1593b-72451321

Finding Ways to Deal with Post-surgery Anxieties

Post-traumatic stress disorder (PTSD) following Cushing’s disease is a real issue many of us face. However, we don’t have to let it control our lives — there are ways to cope.

Cushing’s changes us both mentally and physically. We become forgetful. We lose strength. We become someone we don’t recognize in the mirror. We lose hair on our heads and gain it everywhere else. We’re always in pain, and we’re always sick, with no end in sight (or at least it feels that way).

Some days will be trying and seem as if nothing seems to work, no matter what you do. I promise that you’re not alone, and you will make it through those days.

Following are a list of ways to deal with post-surgery scares:

  • Therapy/counseling: If you can afford it, talk with a professional about your health worries and how your anxiety affects you. It takes the burden off your caregivers who don’t like to see you suffer because they care so much.
  • Journaling: Journaling is a therapeutic and inexpensive way to let out your worries. Documenting your anxieties can help you keep track of how your thought processes are changing. Writing out your stresses is cathartic. Give it a try — if you haven’t already.
  • Yoga or any light exercise: If you’re in the early stages of recovery, you shouldn’t go straight back to the gym — working out is a stressor on the body. Light yoga, such as restorative yoga, in which you practice stretching, deep breathing, and relaxation, will help your mind and body to recover. Light walks are amazing for the brain and body post-surgery.
  • Delve into things you enjoy: Read, cook, go for walks, sit outside, etc. Do whatever feeds your soul and keeps your mind free from negative thoughts. Feeding your soul is one sure way to keep your mind and body happy and healthy.
  • Other ideas from the CushieWiki
  • Please share your ideas in the comments on this post or on the message boards

Adapted from https://cushingsdiseasenews.com/2018/10/19/cushings-post-surgery-anxieties-ptsd-post-traumatic-stress-disorder-journaling-yoga-therapy/

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

8 medical conditions that could cause sudden weight gain

Weight gain can be associated with hormonal conditions, mood disorders, or other physiological factors. A sudden and unexplained weight gain could be your body’s way of signalling an underlying medical issue that needs to be addressed. For the sake of health and long-term well-being, it is important to differentiate between a few harmless extra kilos and a fluctuation that could be hiding a bigger problem. You can only be certain after consulting a healthcare practitioner.

If the weighing scale says your numbers are up but you haven’t changed your eating and exercise habits, you might consider any of the 8 medical conditions:

1.     Hypothyroidism The American Thyroid Association reveals that one in eight women will develop a thyroid disorder during her lifetime. Hypothyroidism refers to an underactive thyroid. The thyroid controls several body functions and your metabolism is one of them. If you’re not producing enough thyroid hormone your body can’t burn as much energy. Symptoms appear throughout your system. They include: weight gain, exhaustion, drier skin, thinner hair, bloating, muscle weakness, constantly feeling cold, and constipation. Once diagnosis is confirmed a doctor can prescribe an oral replacement for thyroid hormone that can relieve symptoms within weeks.

2.     Polycystic ovary syndrome (PCOS) One in 10 women of childbearing age undergoes PCOS. It is an endocrine disorder characterised by an imbalance in the sex hormones oestrogen and testosterone.  This results in irregular periods, acne and even facial hair growth. The disorder also disrupts the way the body uses insulin — which is the hormone responsible for converting carbohydrates into energy. As a result the sugars and starches you consume are stored as fat instead of energy, thus, weight gain. PCOS has no cure but women who have it can manage their symptoms with lifestyle changes and medication. A doctor’s consultation will help you find an appropriate method.

3. Insomnia Avoid fake news! Subscribe to the Standard SMS service and receive factual, verified breaking news as it happens. Text the word ‘NEWS’ to 22840 Sleep deprivation can negatively impact both your metabolism and your hunger hormones. Sleeping too little increases ghrelin, the hormone that signals the body that it’s time to eat, while lowering leptin, the hormone that says you are full. The result: increased cravings and snacking to get more energy through the day. Insomnia increases impulsive eating. A 2018 study published in the American Journal of Clinical Nutrition found that the right amount of sleep could mean consuming up to 10 fewer grams of sugar throughout the day.

4.     Tumours Weight gain around your belly as opposed to your lower body or other areas can be more dangerous to your health. Large pelvic area tumours like uterine or ovarian tumours can inflate the abdomen the way excess fat does. In some cases they can also be cancerous. In addition to weight gain, symptoms of ovarian or uterine tumours include vaginal bleeding, lower back pain, constipation and painful intercourse. But these signs are common for other conditions as well so it‘s worth confirming with a doctor to rule out any possible complications.

5. Peri menopause and menopause Perimenopause -the transition period to menopause can start as early as a woman’s mid-thirties, but usually starts in their forties. This period triggers hormones like oestrogen to rise and fall unevenly, which can cue weight gain in some women. Genetics are a good starting point on how your body experiences these changes, so it would be helpful to look into how it affected your mother and other older women in your family. Other signs of perimenopause are mood swings, irregular periods, hot flashes, and changes in libido. Age also contributes to loss of muscle mass and increase in body fat. An Ob-Gyn should be able to talk you through these changes and recommend management options.

6.     Mood disorders Depression and anxiety can result in fatigue, lack of focus and irritability. Some people cope with anxious or sad feelings by mindlessly munching on food they don’t really need. Additionally chronic stress throws your body into fight-or-flight mode, leading to a surge of adrenaline, as well as a heavy dose of the hormone cortisol –responsible for restoring energy reserves and storing fat.

7. Cushing syndrome Sometimes tumours on the pituitary or adrenal glands can contribute to a condition known as Cushing’s disease which is characterised by high levels of cortisol in the blood. Taking long term steroids could also result in this disease. Patients with Cushing syndrome will experience rapid weight gain in the face, abdomen and chest. They also display slender arms and legs compared to the heavy weight in the core of the body. Other symptoms include: high blood pressure, mood swings, osteoporosis, discoloured stretch marks, acne, and fragile skin. Depending on the cause, Cushing‘s disease can be treated in a different ways.

8. New medication Before starting on any new prescription medication, ask your doctor if weight gain is a possible side effect. Birth control pills may lead to weight gain depending on the brand, dosage, and the person’s hormonal levels. Psychiatric medications, especially for depression and bipolar disorder, have been known to cause weight gain, as they target the brain. Similarly, taking insulin to manage diabetes or medications that treat high blood pressure can also lead to extra kilos, so staying active and sticking to a strict meal plan can help you take insulin without unnecessarily weight gain.

Adapted from https://www.standardmedia.co.ke/lifestyle/article/2001297348/8-medical-conditions-that-could-cause-sudden-weight-gain

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/

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