Cushing Syndrome – A Review

Posted on July 18, 2023 by MaryO
Abstract

Importance  Cushing syndrome is defined as a prolonged increase in plasma cortisol levels that is not due to a physiological etiology. Although the most frequent cause of Cushing syndrome is exogenous steroid use, the estimated incidence of Cushing syndrome due to endogenous overproduction of cortisol ranges from 2 to 8 per million people annually. Cushing syndrome is associated with hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders.

Observations  Cushing syndrome characteristically presents with skin changes such as facial plethora, easy bruising, and purple striae and with metabolic manifestations such as hyperglycemia, hypertension, and excess fat deposition in the face, back of the neck, and visceral organs. Cushing disease, in which corticotropin excess is produced by a benign pituitary tumor, occurs in approximately 60% to 70% of patients with Cushing syndrome due to endogenous cortisol production. Evaluation of patients with possible Cushing syndrome begins with ruling out exogenous steroid use. Screening for elevated cortisol is performed with a 24-hour urinary free cortisol test or late-night salivary cortisol test or by evaluating whether cortisol is suppressed the morning after an evening dexamethasone dose. Plasma corticotropin levels can help distinguish between adrenal causes of hypercortisolism (suppressed corticotropin) and corticotropin-dependent forms of hypercortisolism (midnormal to elevated corticotropin levels). Pituitary magnetic resonance imaging, bilateral inferior petrosal sinus sampling, and adrenal or whole-body imaging can help identify tumor sources of hypercortisolism. Management of Cushing syndrome begins with surgery to remove the source of excess endogenous cortisol production followed by medication that includes adrenal steroidogenesis inhibitors, pituitary-targeted drugs, or glucocorticoid receptor blockers. For patients not responsive to surgery and medication, radiation therapy and bilateral adrenalectomy may be appropriate.

Conclusions and Relevance  The incidence of Cushing syndrome due to endogenous overproduction of cortisol is 2 to 8 people per million annually. First-line therapy for Cushing syndrome due to endogenous overproduction of cortisol is surgery to remove the causative tumor. Many patients will require additional treatment with medications, radiation, or bilateral adrenalectomy.

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Thyroid cancer: Cushing syndrome is a lesser-known warning sign – what is it?

Posted on February 1, 2021 by MaryO

Thyroid cancer survival rates are 84 percent for 10 years or more if diagnosed early. Early diagnosis is crucial therefore and spotting the unusual signs could be a matter of life and death. A sign your thyroid cancer has advanced includes Cushing syndrome.

What is it?

What is Cushing syndrome?

 

Cushing syndrome occurs when your body is exposed to high levels of the hormone cortisol for a long time, said the Mayo Clinic.

The health site continued: “Cushing syndrome, sometimes called hypercortisolism, may be caused by the use of oral corticosteroid medication.

“The condition can also occur when your body makes too much cortisol on its own.

“Too much cortisol can produce some of the hallmark signs of Cushing syndrome — a fatty hump between your shoulders, a rounded face, and pink or purple stretch marks on your skin.”

In a study published in the US National Library of Medicine National Institutes of Health, thyroid carcinoma and Cushing’s syndrome was further investigated.

The study noted: “Two cases of thyroid carcinoma and Cushing’s syndrome are reported.

“Both of our own cases were medullary carcinomas of the thyroid, and on reviewing the histology of five of the other cases all proved to be medullary carcinoma with identifiable amyloid in the stroma.

“A consideration of the temporal relationships of the development of the carcinoma and of Cushing’s syndrome suggested that in the two cases with papillary carcinoma these conditions could have been unrelated, but that in eight of the nine cases with medullary carcinoma there was evidence that thyroid carcinoma was present at the time of diagnosis of Cushing’s syndrome.

“Medullary carcinoma of the thyroid is also probably related to this group of tumours. It is suggested that the great majority of the tumours associated with Cushing’s syndrome are derived from cells of foregut origin which are endocrine in nature.”

In rare cases, adrenal tumours can cause Cushing syndrome a condition arising when a tumour secretes hormones the thyroid wouldn’t normally create.

Cushing syndrome associated with medullary thyroid cancer is uncommon.

The syndrome is more commonly caused by the pituitary gland overproducing adrenocorticotropic hormone (ACTH), or by taking oral corticosteroid medication.

See a GP if you have symptoms of thyroid cancer, warns the NHS.

The national health body added: “The symptoms may be caused by less serious conditions, such as an enlarged thyroid, so it’s important to get them checked.

“A GP will examine your neck and can organise a blood test to check how well your thyroid is working.

“If they think you could have cancer or they’re not sure what’s causing your symptoms, you’ll be referred to a hospital specialist for more tests.”

 

Adapted from https://www.express.co.uk/life-style/health/1351753/thyroid-cancer-signs-symptoms-cushing-syndrome

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Cushing Syndrome Results in Poor Quality of Life Even After Remission

Posted on August 18, 2018 by MaryO

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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Reasons You Have Flab Around Your Abdomen

Posted on April 24, 2017 by MaryO

Some diseases and conditions could be responsible for your abdominal fat.
Mita Majumdar | Updated: April 24, 2017 6:15 pm

Visceral fat or unhealthy belly fat that surrounds the liver and other organs in the abdomen puts you at risk for serious health problems, such as, metabolic syndrome, heart disease, and type 2 diabetes. But, what causes your pot belly or beer fat in the first place? The most obvious answers you will get is – ‘You are not exercising enough’, or, ‘you are eating too much of fatty foods or sugary foods’, or ‘you are not eating the right foods’, or ultimately, ‘It’s genetics! You got it from your parents’. All of these reasons are true, of course. However, some diseases/ disorders and conditions, too, could be responsible for your abdominal fat and these have nothing to do with not exercising or not eating right. Following are some of these disorders.

Cushing’s Syndrome

Cushing’s syndrome, also called hypercortisolism, is an endocrine disorder that occurs when your body is exposed to high cortisol levels over a long period of time. It is a treatable disorder, however, if it is chronic, the symptoms can last lifelong.

Symptoms: Symptoms vary according to the severity of the disorder. The characteristic symptoms include –

  • Fatty tissue deposits in the midsection
  • Fatty deposits in the upper back, especially between the shoulders, so that it resembles a hump
  • Puffy face
  • Violaceous stretch marks (pink or purple) on the arms, breast, stomach, and thighs that are more than 1 cm wide. [1]
  • Easy bruising
  • Fatigue
  • Hirsutism and irregularity in menstruation in women
  • Loss of libido and erectile dysfunction in men
  • Cognitive dysfunction, depression, unpredictable emotional outbursts, irritability is present in 70-85 percent of people with Cushing’s syndrome.[1]

Causes:

  • Overuse of corticosteroids
  • Overproduction of cortisol by the adrenal glands

Management:

  • Surgery is the first line of treatment for Cushing’s syndrome.
  • Medication include: [2]

a.Pituitary gland directed therapy

b.Adrenal-blocking drugs

c.Glucocorticoid receptor-antagonizing drugs

  • Pituitary radiotherapy

Addison’s disease

Addison’s disease, also called adrenal insufficiency, is a disorder where your adrenal glands produce insufficient hormones, especially, glucocorticoids including cortisol and aldosterone. It is a life-threatening disease that can affect anyone irrespective of their gender or age.

How do glucocorticoids influence abdominal fats? Glucocorticoids including cortisol convert the fats into energy in the liver. They also help your body respond to stress. When sufficient amount of glucocorticoids are not produced by the adrenal glands, the fats accumulate in the abdominal area, and you see it as flab around your middle.

Symptoms:

  • Hyperpigmentation
  • Extreme fatigue
  • Low blood sugar and low blood pressure
  • Salt craving as one of the functions of adrenal glands is to maintain the sodium-potassium balance in the body
  • Nausea, vomiting, abdominal pain
  • Weight loss but gain in abdominal fat

Causes:

  • Insufficient production of adrenal cortex hormones
  • Stopping of prescribed corticosteroids
  • Tuberculosis and other infections of adrenal glands
  • Spread of cancer to the adrenal glands

Management:

  • Oral corticosteroids or corticosteroid injections
  • Intravenous injections of hydrocortisone, saline solution, and dextrose in case of Addisonian crisis

Stress

Chronic stress is a very big cause of belly fat. When you are exposed to stress, a chain reaction starts in the body because of the dysregulation of HPA axis of the neuroendocrine system. HPA axis is a complex interaction between the hypothalamus, pituitary gland, and adrenal glands. The hypothalamus produces a corticotropin releasing hormone (CRH) and vasopressin. These together stimulate the secretion of adrenocorticotropic hormone (ACTH). ACTH is transported by the blood to the adrenal glands, which then produces corticosteroids, mainly, cortisol from cholesterol. One of the functions of cortisol is to signal the body to store fat, and specifically, the fat storage occurs in the abdominal area, where the cortisol receptors are greater. Researchers have found that stress causes hyperactivation of HPA axis, leading to accumulation of fat tissue, especially in the abdomen region.

So, the more and longer you are stressed (or if you are chronically stressed), chances are that you will be carrying more belly fat!

Ascites

Ascites is the buildup of fluid in the abdominal space. Ascites usually occurs in people with cancer, and it is then called malignant ascites. Onset of ascites is generally the terminal phase in cancer. Ascites also occurs in patients with liver cirrhosis, kidney failure, or heart disease.

Symptoms:

The first sign of ascites is an increase in abdominal girth accompanied by weight gain. [4] Although it looks like it is belly fat, it is actually the fluid that causes the bulging.

Other symptoms include:

  • Shortness of breath
  • Nausea and vomiting
  • Swelling in the feet and ankle
  • Decreased appetite, sense of fullness, bloating
  • Fatigue
  • Haemorrhoids

Management:

If the ascites is not causing any discomfort, it may not require any treatment. Treatment of ascites can have many side effects. Talk to your doctor before you go in for management/ treatment.

Abdominal hernia

Abdominal hernia is a swelling or a bulge in the abdominal area where an organ or fatty tissue pushes through a weak spot in the abdominal wall. The abdominal wall is made up of tough connective tissue and tendons that stretch from the ribs to the groin. Depending on the position of the weakness in your abdominal wall, the hernia can be inguinal (groin), femoral (upper thigh), umbilical (belly button), hiatal (upper stomach), or even incisional. Incisional hernia can occur when the intestine pushes through a weak spot at the site of abdominal surgery.

Symptoms:

  • Visible bulge that may or may not cause discomfort
  • Feeling of heaviness in the abdomen
  • Sharp pain when you strain or lift objects

Causes:

  • Constipation and diarrhoea
  • Persistent coughing and sneezing
  • Straining or suddenly lifting a heavy object

Management:

  • Umbilical hernia, common in young children, mostly resolves by itself as the abdominal muscles get stronger.
  • Other abdominal hernia normally do not resolve by themselves. Doctors suggest waiting and watching.
  • If treatment is required, surgery is the only option. Surgery involves pushing the hernia back into the abdomen and repairing the abdominal wall.

Menopause

Menopause is certainly not a disease or a disorder. It is the time in a woman’s life when she stops menstruating and cannot become pregnant because her ovaries stop producing the required amounts of hormones oestrogen and progesterone. A woman reaches menopause when she has not had her periods for 12 months.

Symptoms:

  • Hot flashes and/ or night sweats
  • Vaginal dryness
  • Mood swings
  • Sleep disturbances

It is very common to gain belly fat during menopause. This is because of the low oestrogen levels. Oestrogen seems to influence the distribution of fat in the body, in a way that the fat is redistributed from the hips, buttocks, and thighs to the belly. However, a study published in the journal Metabolism reported that though women did significantly gain belly fat, especially deep inside the belly, relative fat distribution is not significantly different after menopause. [5] But the fact remains that women do gain flab in the abdomen after menopause.

Belly fat can be seriously harmful. If your belly fat is not because of the above-mentioned conditions, you can lose it by adopting a healthy lifestyle that includes sleeping enough, exercising regularly, eating right, and reducing stress.

Reference

  1. Sharma ST, Nieman LK, Feelders RA. Cushing’s syndrome: epidemiology and developments in disease management. Clinical Epidemiology. 2015;7:281-293. doi:10.2147/CLEP.S44336.
  1. Feelders RA, Hofland LJ. Medical treatment of Cushing’s disease. J Clin Endocrinol Metab. 2013;98:425–438.
  1. Kyrou I, Chrousos GP, Tsigos C. Stress, visceral obesity, and metabolic complications. Ann N Y Acad Sci. 2006 Nov;1083:77-110.
  1. Sinicrope FA. Ascites. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003.
  2. Franklin RM, Ploutz-Snyder L, Kanaley JA. Longitudinal changes in abdominal fat distribution with menopause. Metabolism. 2009 Mar;58(3):311-5. doi: 10.1016/j.metabol.2008.09.030.

Adapted from http://www.thehealthsite.com/diseases-conditions/reasons-you-have-flab-around-your-abdomen-f0417/

 

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Young people with Cushing syndrome may be at higher risk for suicide, depression

Posted on March 30, 2016 by MaryO

Children with Cushing syndrome may be at higher risk for suicide as well as for depression, anxiety and other mental health conditions long after their disease has been successfully treated, according to a study by researchers at the National Institutes of Health.

Cushing syndrome results from high levels of the hormone cortisol. Long-term complications of the syndrome include obesity, diabetes, bone fractures, high blood pressure, kidney stones and serious infections. Cushing’s syndrome may be caused by tumors of the adrenal glands or other parts of the body that produce excess cortisol. It also may be caused by a pituitary tumor that stimulates the adrenal glands to produce high cortisol levels. Treatment usually involves stopping excess cortisol production by removing the tumor.

“Our results indicate that physicians who care for young people with Cushing syndrome should screen their patients for depression-related mental illness after the underlying disease has been successfully treated,” said the study’s senior author, Constantine Stratakis, D(med)Sci, director of the Division of Intramural Research at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. “Patients may not tell their doctors that they’re feeling depressed, so it’s a good idea for physicians to screen their patients proactively for depression and related conditions.”

Cushing syndrome may affect both adults and children. A recent study estimated that in the United States, there are 8 cases of Cushing syndrome per 1 million people per year.

The researchers published their findings in the journal Pediatrics. They reviewed the case histories of all children and youth treated for Cushing syndrome at NIH from 2003 to 2014, a total of 149 patients. The researchers found that, months after treatment, 9 children (roughly 6 percent) had thoughts of suicide and experienced outbursts of anger and rage, depression, irritability and anxiety. Of these, 7 experienced symptoms within 7 months of their treatment.

Two others began experiencing symptoms at least 48 months after treatment.

The authors noted that children with Cushing syndrome often develop compulsive behaviors and tend to become over-achievers in school. After treatment, however, they then become depressed and anxious. This is in direct contrast to adults with Cushing syndrome, who tend to become depressed and anxious before treatment and gradually overcome these symptoms after treatment.

The authors stated that health care providers might try to prepare children with Cushing syndrome before they undergo treatment, letting them know that their mood may change after surgery and may not improve for months or years. Similarly, providers should consider screening their patients periodically for suicide risk in the years following their treatment.

Source: NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development

From http://www.news-medical.net/news/20160329/Young-people-with-Cushing-syndrome-may-be-at-higher-risk-for-suicide-depression.aspx

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