Time to Recovery of Adrenal Function After Curative Surgery for Cushing’s Syndrome Depends on Etiology

Address all correspondence and requests for reprints to: Martin Reincke, MD, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstr. 1, D-80336 Munich, Germany. E-mail: .

Successful tumor resection in endogenous Cushing’s syndrome (CS) results in tertiary adrenal insufficiency requiring hydrocortisone replacement therapy.

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

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

We included 91 patients of the three subtypes of CS undergoing curative intended surgery and documented followup after excluding cases with persistent disease, pituitary radiation, concurrent adrenostatic or somatostatin analog treatment, and malignant adrenal disease.

The probability of recovering adrenal function within a 5 years followup differed significantly between subtypes (P = .001). It was 82% in ectopic CS, 58% in CD 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 years (interquartile range [IQR], 0.03–1.1 y) in ectopic CS, 1.4 years (IQR, 0.9–3.4 y) in CD, and 2.5 years (IQR, 1.6–5.4 y) in adrenal CS (P = .002). In CD the Cox proportional-hazards model showed that the probability of recovery was associated with younger age (hazard ratio, 0.896; 95% confidence interval, 0.822–0.976; P = .012), independently of sex, body mass index, duration of symptoms, and basal ACTH and cortisol levels. There was no correlation with length and extend of hypercortisolism or postoperative glucocorticoid replacement doses.

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

Cushing’s Awareness Challenge 17

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Another of Robin’s wonderful images.

A similar image from the CushieWiki

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No wonder Cushing’s is so hard to diagnose!

maryo colorful zebra

Remaining calm = Reducing illness

Have you ever noticed that when you are “stressed” you can feel either emotionally/physically depleted or energized?  When our body is under stress the brain responds by producing epheniphrine or adrenaline, sending signals to our adrenal glands, increasing the rate at which our heart beats while releasing oxygen to our muscles.  The long term response to this process produces cortisol (aka the stress hormone) facilitating the release of energy throughout our body.  However, when our body isn’t properly balanced these hormones can wreak havoc on our wellness possibly resulting in one of three conditions:  Cushing’s syndrome, Cushing’s disease or Addison’s disease.

adrenal-glandsThe actual Adrenal glands sit physically atop both kidneys, taking on a triangular shape and a roundish rectangular type shape.  These glands are responsible for our sex hormones and cortisol, helping us respond to stress amongst other functions.  When our body is under stress, physically and/or nutritionally, it responds one of two ways:  Produces too much or too little of the cortisol hormone.  Our Adrenal glands also contribute to regulating our blood sugar, blood pressure, salt and water.

Adrenal disorders can cause our body to make too much or not enough of these hormones, bringing about adrenal gland related syndromes and disease.  Cushing’s syndrome results from our body making too much versus Addison’s disease produces too little.

Cushing’s syndrome vs. Cushing’s disease

Glucocorticoids (naturally produced in our body or received through medicine) are groups of corticosteroids (cortisol or dexamethasone) involved in metabolizing our carbohydrate and protein.  When taken synthetically (i.e. treatment of allergies, skin problems, and respiratory problems) or over-produced naturally, the side effects can result in “Cushing’s syndrome”.

Cushing’s syndrome can occur one of two ways:  Endogenous or Exogenous.  Endogenous is caused by the body (usually through tumors).  Exogenous is caused by medication.  In both cases, the body produces too much cortisol.

Symptoms: Severe fatigue/muscle weakness, high blood sugar and high blood pressure, upper body obesity, thin arms/legs, bruising easily

Treatment:  The cure and treatment for Cushing’s disease can come through medicine, surgery, or by lowering the dosage of your current synthetic hormone treatment.  Cushing’s syndrome can be cured.

Cushing’s disease is the most common form of endogenous Cushing’s syndrome and is likely treatable.  Caused by a tumor in the pituitary gland secreting too much Adrenocorticotropic hormone (ACTH), this type of tumor does not spread and can be removed through surgery.

Nutrition:  See a nutritionist or dietician for your condition.  Mostly, avoid excess sodium.  High blood sugar (hyperglycemia) and high blood pressure can easily occur with this condition.  Bone loss density is common with this condition, so be extra aware of your calcium (800 – 1200 mg per day, based upon age) and Vitamin D intake (5mcg from age 0-50, increasing up to 10 mcg 50-71, and 15 mcg after 71).  Eating healthy, balanced and whole food (versus processed) is extremely important.

(Resource:  http://www.aboutcushings.com/understanding-cushings-disease/causes-and-differences.jsp)

Addison’s disease

Opposite from Cushing’s syndrome, Addison’s disease doesn’t make “enough” of the sex hormones and cortisol.  The result of this disease causes our immune system to attack our tissue, damaging our adrenal glands.

Symptoms:  Weight loss, muscle weakness, increasingly worse fatigue, low blood pressure and patchy or dark skin.

Treatment:  If left untreated, the condition can be fatal.  Lifetime hormone treatment is usually required. Addison disease patients should always carry medical/emergency ID on them, listing their medication, dosage and disease

Lab tests can confirm that you have Addison’s disease. If you don’t treat it, it can be fatal. You will need to take hormone pills for the rest of your life. If you have Addison’s disease, you should carry an emergency ID. It should say that you have the disease, list your medicines and say how much you need in an emergency.”

(Ref: http://www.nlm.nih.gov/medlineplus/cushingssyndrome.html, NIH: National Institute of Neurological Disorders and Stroke)                                                                                                                                                                                                                                        Learning how to balance our stress-filled lives is extremely important to our overall health.  Healthy nutrition always contributes benefits to our overall wellness.  We can overwhelm our endocrine system by simply not eating nutritionally.  Understanding that “Food is a drug” is vitally important to how we help our body naturally heal itself.  The above two conditions are the result of our body not handling the stress we are putting it through, causing our body to producing too much or too little of the sex hormones and cortisol.

Unless we first address what we can do naturally through nutrition, the medicine we consume will only do so much in helping our body heal completely.  You simply cannot continue doing the same thing over and over again, expecting the medicine to do all the work.  Some diseases are brought upon us through our environment (emotionally as well as physically) as well as our diet/nutrition.  Reviewing our entire wellness is always wisdom whenever we’re diagnosed with anything.

Certainly listen to your doctor and their advice.  But also ask your doctor to refer you to a nutritionist or clinical/registered dietician for a complete evaluation that includes a review of your nutritional diet/wellness.  Too often we reach for a pill or a procedure to “fix” our health problems, ignoring what we should be doing on our own to help our body heal.  Medical intervention is the result of providing our body with what it cannot produce on its own.  Nutrition should always be the “natural” medicine we take, as well as what we might need through prescribed medication.

Adapted from (Spelling errors corrected) http://hamptonroads.com/2013/10/remaining-calm-reducing-illness

Differences Between Cushing’s Syndrome and Cushing’s Disease

What’s the difference between Cushing’s Disease and Cushing’s Syndrome?

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Cushing’s syndrome is a hormonal disorder

Cortisol is a normal hormone produced in the outer portion of the adrenal glands. When functioning normally, cortisol helps the body respond to stress and change. It mobilizes nutrients, modifies the body’s response to inflammation, stimulates the liver to raise blood sugar, and helps control the amount of water in the body. Cortisol production is regulated by the adrenocorticotrophic hormone (ACTH), produced in the pituitary gland. Spontaneous overproduction of cortisol in the adrenals is divided into two groups – those attributed to an excess of ACTH and those that are independent of ACTH.

Cushing’s syndrome is the term used to describe a group of symptoms that occur when a persons’ cortisol levels are too high (known as hypercortisolism) for too long. The majority of people have Cushing’s syndrome because they are regularly taking certain medicine(s) that continually add too much cortisol to the body. Doctors call this an “exogenous” (outside the body) cause of Cushing’s syndrome. Other people have Cushing’s syndrome because something is causing the adrenal gland(s) to overproduce cortisol. Doctors call this an “endogenous” (inside the body) cause of Cushing’s syndrome.

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Cushing’s disease is a form of Cushing’s syndrome

Cushing’s disease is the most common form of endogenous Cushing’s syndrome. It is caused by a tumor in the pituitary gland that secretes excessive amounts of a hormone called Adrenocorticotropic hormone, or ACTH. Fortunately, this type of tumor is typically benign. Unlike a cancerous (malignant) tumor, a benign tumor stays in its original location and will not spread. After you are diagnosed with Cushing’s syndrome, it is important that your doctor continues the diagnostic process to determine the cause of hypercortisolism.

From the message boards It is not only a tumor that causes Cushings Disease—many of us have the rarer form of this rare disease which is Pituitary Hyperplasia. It also causes CD and may be nodular (shown on MRI s a tumor) or dispersed (meaning spread throughout the gland).

How a pituitary tumor causes Cushing’s disease

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ACTH is a hormone produced in your pituitary gland. ACTH travels to your adrenal glands and signals them to produce cortisol.

Pituitary adenomas are benign tumors of the pituitary gland which secrete increased amounts of ACTH, causing excessive cortisol production. Most patients have a single adenoma. First described in 1912 by neurosurgeon Harvey Cushing in his book The Pituitary Body and its Disorders, Cushing’s disease is the most common cause of spontaneous Cushing’s syndrome, accounting for 60 to 70 percent of cases.

If a person has Cushing’s disease, it means that a group of abnormal cells has built up in the pituitary gland to form an ACTH-producing pituitary tumor. These abnormal cells produce ACTH, just as normal pituitary gland cells do—only far too much. The excess ACTH travels to adrenal glands. The adrenal glands are then bombarded with signals to produce more and more cortisol. As a result, the adrenal glands continuously secrete too much cortisol.

Ectopic ACTH Syndrome

Some benign or malignant (cancerous) tumors that arise outside the pituitary can produce ACTH. This condition is known as ectopic ACTH syndrome. Lung tumors cause more than 50 percent of these cases. Other less common types of tumors that can produce ACTH are thymomas, pancreatic islet cell tumors, and medullary carcinomas of the thyroid.

Adrenal Tumors

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An abnormality of the adrenal glands such as an adrenal tumor may cause Cushing’s syndrome. Most of these cases involve non-cancerous tumors called adrenal adenomas, which release excess cortisol into the blood.

Adrenocortical carcinomas, or adrenal cancers, are the least common cause of Cushing’s syndrome. Cancer cells secrete excess levels of several adrenal cortical hormones, including cortisol and adrenal androgens. Adrenocortical carcinomas often cause very high hormone levels and rapid onset of symptoms.

Familial Cushing’s syndrome

Most cases of Cushing’s syndrome are not genetic. However, some individuals may develop Cushing’s syndrome due to an inherited tendency to develop tumors of one or more endocrine glands. In Primary Pigmented Micronodular Adrenal Disease, children or young adults develop small cortisol-producing tumors of the adrenal glands. In Multiple Endocrine Neoplasia Type I (MEN I), hormone secreting tumors of the parathyroid glands, pancreas and pituitary occur. Cushing’s syndrome in MEN I may be due to pituitary, ectopic or adrenal tumors.

Risk factors

Obesity, type 2 diabetes, poorly controlled blood glucose (blood sugar levels), and high blood pressure may increase the risk of developing this disorder.

Adapted from http://www.cushiewiki.com/index.php?title=Cushing%27s_Disease_or_Syndrome