An Ectopic Cushing’s Syndrome with Severe Psychiatric Presentation

Posted on January 12, 2024 by MaryO

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We report a case of severe EAS in a young Tunisian man resulting from a well differentiated Neuroendocrine Tumor (NET) of the lung. Besides catabolic signs and profound hypokalemia orienting towards Cushing’s Syndrome (CS), psychiatric symptoms were particularly severe, dominant and atypical including persecutory delusions, depression and anxiety.

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Post-traumatic Stress Symptoms Common in Cushing’s Patients Before Surgery

Posted on June 29, 2019 by MaryO

Patients with Cushing’s disease may develop post-traumatic stress symptoms, which are generally resolved once they undergo surgery to remove the tumor, but can persist in some cases, a study shows.

The study, “Posttraumatic stress symptoms (PTSS) in patients with Cushing’s disease before and after surgery: A prospective study,” was published in the Journal of Clinical Neuroscience.

Cushing’s disease is an endocrine disorder characterized by excess secretion of the adrenocorticotropic hormone (ACTH) by a pituitary adenoma (tumor of the pituitary gland). This leads to high levels of cortisol, a condition known as hypercortisolism.

Chronic hypercortisolism is associated with symptoms such as central obesity, buffalo hump, body bruising, muscle weakness, high blood pressure, high blood sugar, and weak bones.

Additionally, patients can develop psychiatric disorders including depression, anxiety, and cognitive dysfunction, all of which contribute considerably to a lower health-related quality of life.

Depression and anxiety rates are particularly high in Cushing’s disease patients, with 54% of them experiencing major depression and 79% having anxiety.

Due to the significant impact of psychological factors in these patients, they may be susceptible to post-traumatic stress symptoms (PTSS). But more information on this phenomenon in these patients is still needed.

To address this lack of data, a group of Chinese researchers conducted a prospective study to investigate the occurrence, correlated factors, and prognosis of PTSS in patients with Cushing’s disease.

A total of 49 patients newly diagnosed with Cushing’s disease who underwent transsphenoidal removal of the tumor as their first-line treatment were asked to participate in this study. Another group of 49 age- and sex-matched healthy individuals were included as controls.

PTSS was measured using the Impact of Event Scale-Revised (IES-R), depression/anxiety were measured using the Hospital Anxiety and Depression scale (HADS), and quality of life was measured using the 36-item short-form (SF-36). These parameters were measured before surgery, and then at six and 12 months after the procedure.

Before surgery, 15 patients (30.6%) had PTSS. These patients also had higher cortisol levels, worse levels of depression/anxiety, and worse quality of life scores than those without PTSS.

While most of the patients recovered after the operation, there were five (33.3%) for whom PTSS persisted for more than a year.

Additionally, one patient who had a recurrence of Cushing’s disease developed PTSS between six and 12 months after the first surgery.

PTSS severity showed consistent improvement after surgery, which was correlated with better depression/anxiety scores and psychological aspects of the SF-36. However, Cushing’s disease patients in remission still performed worse than healthy individuals concerning their physical and mental health.

Therefore, “patients with [Cushing’s disease] can develop PTSS, and they may persist for over a year even after successful surgery. Combined psychological intervention is advised for these patients,” the researchers concluded.

From https://cushingsdiseasenews.com/2019/06/25/cushings-patients-often-have-post-traumatic-stress-symptoms

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Mild Cases of Cushing’s Syndrome Present Diagnostic Challenges

Posted on August 16, 2017 by MaryO

By Tori Rodriguez, MA, LPC

 

In the early 20th century, the term “pluriglandular syndrome” was coined by Harvey Cushing to describe the disorder that results from chronic tissue exposure to excessive levels of glucocorticoids.1 Now called Cushing’s syndrome, the condition affects an estimated 10-15 million people annually, most often women and individuals between the ages of 20 and 50 years.2 Risk factors and common comorbidities include hypertension, obesity, osteoporosis, uncontrolled diabetes, depression, and anxiety.3

Presentation

The clinical presentation of the disorder is heterogenous and varies by sex, age, and disease severity. Common signs and symptoms include central adiposity, roundness of the face or extra fat around the neck, thin skin, impaired short-term memory and concentration, irritability, hirsutism in women, fatigue, and menstrual irregularity.4 Because each of these features may be observed in a wide range of other conditions, it may be difficult to diagnose cases that are not severe.

“It can be challenging to differentiate the milder forms from pseudo-Cushing’s states,” which are characterized by altered cortisol production and many of the same clinical features as Cushing’s syndrome, according to Roberto Salvatori, MD, the medical director of the Johns Hopkins Pituitary Center, Baltimore, Maryland. These may include alcoholism, obesity, eating disorders, and depression. “Because Cushing’s can cause depression, for example, it is sometimes difficult to determine which came first,” he says. In these states, however, hypercortisolism is believed to be driven by increased secretion of hypothalamic corticotropin-releasing hormone, which is suppressed in Cushing’s syndrome.5

Causes and Diagnosis

If Cushing’s syndrome is suspected on the basis of the patient’s physical appearance, the diagnostic workup should include a thorough medical history, physical exam, and 1 or more of the following tests to establish hypercortisolism: the 24-hour urinary cortisol test, the low-dose dexamethasone suppression test, or the late-night salivary cortisol test. “We sometimes use 2 or 3 of these tests since 1 may not accurately reflect cortisol production in a particular patient,” Dr Salvatori notes. The next step is to determine the source of the hypercortisolism, which may involve the high-dose dexamethasone suppression test, magnetic resonance imaging, or petrosal sinus sampling.2

Medication is the most common cause of Cushing’s syndrome. These iatrogenic or exogenous cases typically result from corticosteroids administered for conditions such as asthma, allergies, and autoimmune disorders.6 More rarely, the disorder can be caused by the use of medroxyprogesterone. In these cases, corticosteroids should be reduced or discontinued under medical care, if possible.

Endogenous Cushing’s syndrome results from the presence of benign or malignant tumors on the adrenal or pituitary glands or elsewhere in the body. These tumors can interfere with the adrenal glands’ production of cortisol that is usually prompted by the adrenocorticotropic hormone (ACTH) released by the pituitary gland.6 There are 3 different mechanisms by which the process can occur.

  • Pituitary adenomas, which account for approximately 70% of endogenous cases of Cushing’s syndrome, secrete ACTH and stimulate additional cortisol production. Because of the large proportion of cases this condition represents, it is specifically referred to as Cushing’s disease. It is more common in women than men (with a ratio of 3 to 4:1), although in pediatric patients, it occurs more frequently in boys vs girls.5
  • Adrenal tumors (adenomas, malignant tumors, or micronodular hyperplasia) produce cortisol in their own tissue in addition to the amount produced by the adrenal glands. These tumors, which cause approximately 15% of endogenous Cushing’s syndrome cases, are more common in children vs adults and in women vs men.
  • Benign or malignant tumors elsewhere in the body, most often the lungs, thyroid, thymus, and pancreas, secrete ACTH and trigger the excessive release of cortisol. An estimated 15% of endogenous cases are attributed to these types of tumors.

Treatment

Surgery is the first-line treatment for Cushing’s syndrome. “We first want to try to figure out the cause of the disorder,” Dr Salvatori says. “Ideally, treatment involves surgery to remove the tumor that is causing it.”

When surgery is unsuccessful, contraindicated, or delayed, other treatment options include radiation or medications that inhibit cortisol, modulate the release of ACTH, or inhibit steroidogenesis.5 Bilateral adrenalectomy may be indicated for patients who do not respond to medication or other surgery.

If surgical resection of the tumor is successful, then “all of the comorbidities reverse, but if it is unsuccessful or must be delayed, you would treat each comorbidity” with the appropriate medication; for example, antihypertensives for high blood pressure and antidiabetic medications for diabetes, Dr Salvatori advises. In severe cases, prophylactic antibiotics may be indicated for the prevention of severe infections such as pneumonia.

It is also important to inquire about and address psychiatric symptoms related to Cushing’s syndrome, even in patients who are in remission. It has been proposed that the chronic hypercortisolism and dysfunction of the HPA axis may “lead to structural and functional changes in the central nervous system, developing brain atrophy, particularly in the hippocampus, which may determine the high prevalence of psychiatric disorders, such as affective and anxiety disorders or cognitive dysfunctions,” according to a recently published paper on the topic.7 Patients should be screened with self-report questionnaires such as the Beck Depression Inventory and the Hospital Anxiety and Depression Scale, and management of psychiatric symptoms may include patient education, psychotropic medications, and referral to a mental health professional.

Future Directions

Several trials are currently planned or underway, including a phase 2 randomized, double-blind, placebo-controlled study of an oral medication called ATR-101 by Millendo Therapeutics, Inc. (ClinicalTrials.gov identifier: NCT03053271). In addition to the need for novel medical therapies, refined imaging techniques could improve surgical success rates in patients with Cushing’s disease in particular, according to Dr Salvatori. “A significant portion of these patients have tumors too small to be detected by MRI, and the development of more sensitive MRI could improve detection and provide a surgical target” for neurosurgeons treating the patients, he says.

Summary

Milder cases of Cushing’s syndrome present diagnostic challenges are a result overlapping features with various other conditions. Diagnosis may require careful observation as well as biochemical and imaging tests.

RELATED ARTICLES

References

  1. Loriaux DL. Diagnosis and differential diagnosis of Cushing’s syndrome. N Engl J Med. 2017;376:1451-1459. doi:10.1056/NEJMra1505550
  2. American Association of Neurological Surgeons. Cushing’s syndrome/disease. http://www.aans.org/Patients/Neurosurgical-Conditions-and-Treatments/Cushings-Disease. Accessed August 1, 2017.
  3. León-Justel A, Madrazo-Atutxa A, Alvarez-Rios AI, et al. A probabilistic model for cushing’s syndrome screening in at-risk populations: a prospective multicenter study. J Clin Endocrinol Metab. 2016;101:3747-3754. doi:10.1210/jc.2016-1673
  4. The Pituitary Society. Cushing’s syndrome and disease–symptoms. https://pituitarysociety.org/patient-education/pituitary-disorders/cushings/symptoms-of-cushings-disease-and-cushings-syndrome. Accessed August 1, 2017.
  5. Sharma ST, Nieman LK, Feelders RA. Cushing’s syndrome: epidemiology and developments in disease management. Clin Epidemiol. 2015;7:281-293. doi:10.2147/CLEP.S44336
  6. National Institutes of Health: Eunice Kennedy Shriver National Institute of Child Health and Human Development. What causes Cushing’s syndrome?https://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/causes.aspx. Accessed August 1, 2017.
  7. Santos A, Resmini E, Pascual JC, Crespo I, Webb SM. Psychiatric symptoms in patients with Cushing’s syndrome: prevalence, diagnosis and management. Drugs. 2017;77:829-842. doi:10.1007/s40265-017-0735-z

From http://www.endocrinologyadvisor.com/adrenal/cushings-syndrome-diagnosis-treatment/article/682302/

Filed under: adrenal, Cushing, Cushing's, pituitary | Tagged: , , , , , , , , , , , , , , , | Leave a comment »

Study links genetic mutations, Cushing syndrome

Posted on June 6, 2017 by MaryO

Researchers have determined mutations in the gene CABLES1 may lead to Cushing syndrome, a rare disorder in which the body overproduces the stress hormone cortisol.

The National Institutes of Health study findings published in Endocrine-Related Cancer found four of the 181 children and adult patient examined had mutant forms of CABLES1 that do not respond to cortisol.

The determination proved significant because normal functioning CABLES1 protein, expressed by the CABLES1 gene, slows the division and growth of pituitary cells that produce the hormone adrenocorticotropin (ACTH).

Researchers at the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) joined scientists from other institutions in the United States, France and Canada, in the evaluation.

“The mutations we identified impair the tumor suppressor function in the pituitary gland,” Constantine A. Stratakis, the study’s senior author and director of the NICHD Division of Intramural Research, said. “This discovery could lead to the development of treatment strategies that simulate the function of the CABLES1 protein and prevent recurrence of pituitary tumors in people with Cushing syndrome.”

Cushing syndrome symptoms include obesity, muscle weakness, fatigue, high blood pressure, high blood sugar, depression and anxiety, officials said, adding excess cortisol found in the disorder can result from certain steroid medications or from tumors of the pituitary or adrenal glands.

Researchers maintain that more studies are needed to fully understand how CABLES1 suppresses tumor formation in the pituitary gland.

 

From https://lifesciencedaily.com/stories/21624-study-links-genetic-mutations-cushing-syndrome/

Filed under: Clinical trials, Cushing's, pituitary | Tagged: , , , , , , , , , , , , , , | Leave a comment »

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

Filed under: adrenal, Cushing's, pituitary, symptoms, Treatments | Tagged: , , , , , , , , , , , , , , , , , | Leave a comment »

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