Cushing’s Syndrome Eludes Treatment Paradigm or Standard Approach to Care

Results of two systematic reviews indicate that while surgery is the preferred treatment, many patients present with contraindications without an accepted management paradigm leaving clinicians to follow a patient-centric approach to care.

With commentary by Eliza B. Geer, MD

Cushing’s syndrome may arise from an endogenous glucocorticoid excess is either adrenocorticotropic hormone (ACTH)-dependent or ACTH-independent; each variation has numerous underlying causes, including pituitary tumor, adrenal tumor, or other unknown causes.

Although rare, ectopic Cushing’s syndrome results from a non-pituitary ACTH-producing source. Cushing’s disease, a type of Cushing’s syndrome, affects an estimated 1.2 to 2.4 million people each year, and is caused by an ACTH-secreting pituitary adenoma.1

While surgery is preferred for treatment of Cushing's syndrome many patients need a medical approach instead.

Gaining insights into treatment preferences and efficacy for Cushing’s syndrome were the focus of two separate systematic reviews and meta-analyses, both published in the journal, Pituitary: one regarding medical treatments for Cushing’s syndrome,2 and the other comparing endoscopic versus microscopic transsphenoidal surgery for Cushing’s disease.3

Assessing Medical Management of Cushing’s Syndrome

The meta-analysis examining medical care of individuals with Cushing’s syndrome encompassed 1520 total patients across 35 studies, most of whom had Cushing’s disease.2 However, only 2 of the 35 studies were randomized trials, highlighting the lack of and clear need for controlled clinical trials on medical therapies for Cushing’s syndrome.

Surgery is typically first-line treatment—whether transsphenoidal pituitary adenomectomy for Cushing’s disease,4 removal of the ACTH-producing tumor in ectopic Cushing’s syndrome or adrenalectomy in ACTH-independent Cushing’s syndrome.5

However, many patients require medical therapy owing to contraindications for surgery, for recurrent disease, or to control cortisol secretion prior to surgery or radiotherapy. Results of the meta-analysis reflected wide-ranging normalization of cortisol levels depending upon the agent used– from 35.7% for cabergoline to nearly 82% for mitotane in Cushing’s disease.2 Combination therapy (medications used either together or sequentially) was shown to increase effectiveness in normalizing cortisol levels.2

In an interview with EndocrineWeb, Eliza B. Geer, MD, medical director of the Multidisciplinary Pituitary and Skull Base Tumor Center at Memorial Sloan Kettering Cancer Center in New York City, noted that most medical therapies for Cushing’s syndrome are used off-label (in the US), and thus may lack clinical trial efficacy and safety data; consequently, this review provides useful information for treatment selection. However, Dr. Geer said there was substantial diversity of treatments reviewed in this paper – including tumor-directed therapies, cortisol synthesis inhibitors, an adrenolytic therapy, and a receptor blocker, used alone or in combination.

Further, treatments used in the studies addressed a range of Cushing’s etiologies and reflected heterogeneous study designs (for example follow-up ranged from 2 weeks to 11.5 years).2  As such, she said, “findings provided by this review should be viewed in the context of a broader clinical understanding of Cushing’s treatment.”

Specifically, Dr. Geer said, “Dr. Broersen’s analysis found that efficacy of medical therapy was improved by prior radiotherapy. But we know that radiotherapy is recommended on an individualized basis in only a fraction of Cushing’s patients, depending on tumor behavior and treatment history. Also, the fact that mitotane was shown here to have the highest efficacy of all therapies does not make this the appropriate treatment for all, or even most, Cushing’s patients; mitotane is adrenolytic and has a high rate of significant adverse effects.”

Too Many Questions Persist, Necessitating Focus on Attaining Management Paradigm

Dr. Geer also highlighted the need for answers to basic questions when investigating Cushing’s treatments: How do we define ‘successful’ treatment? What goals of care can patients expect? Which cortisol measurements and cut-offs can be used? How do we define clinical remission—resolution of which symptoms and comorbidities? She said Cushing’s syndrome is one of the most challenging endocrine diseases to treat because of the lack of an accepted, universal treatment or management paradigm.

Treatment is often multimodal and always multidisciplinary, with patient-specific decision trees that must consider many factors, including goals of care, treatment history, disease etiology and severity, tumor behavior, and individual responses to medical therapies, she told EndocrineWeb.

She concluded, “While Broersen et al’s study provides a useful review of available medical therapies, it reinforces something we already know about the treatment of Cushing’s: Expertise is required.”

Pituitary surgery is first-line treatment for Cushing’s disease. Currently, there are two main techniques for transsphenoidal pituitary surgery: microscopic and endoscopic. The operating microscope provides three-dimensional vision and may be advantageous in identifying small tumors; the broader field of vision afforded by the endoscope may be advantageous for complete resection of large tumors.3  Generally, despite an absence of studies directly comparing relative remission and complication rates between microscopic versus endoscopic approaches, most surgical centers choose to use one or the other; few have both.3

Examining the Surgical Options to Manage Cushing’s Disease

The second systematic review is the first to compare remission and recurrence rates, and mortality after microscopic versus endoscopic transsphenoidal pituitary surgery for Cushing’s disease.3 The review included 97 studies of 6695 patients: 5711 individuals having the microscopic procedure and 984 undergoing endoscopic surgery.

Results of the meta-analysis found no clear difference between the two techniques in overall remission (80%) or recurrence (10%).3 Short-term mortality for both techniques was < 0.5%. However, endoscopic surgery was associated with a greater occurrence of cerebrospinal fluid leak (12.9 vs 4.0%) but a lesser occurrence of transient diabetes insipidus (11.3 vs 21.7%).3

The authors reported a higher percentage of patients in remission (76.3 vs. 59.9%) and lower percentage recurrence rates (1.5 vs 17.0%) among patients undergoing endoscopic surgery for macroadenomas.3

When interviewed regarding the second meta-analysis,3 Dr. Geer said that the potential benefit of endoscopy over microscopy has been questioned for ACTH-secreting tumors specifically since most are microadenomas.

“With the caveat that few studies (four of the 97 reviewed) compared techniques directly, Broersen et al3 found that endoscopic surgery was associated with higher remission rates compared to microscopic surgery for large tumors, but the two techniques were comparable for small tumors,” said Dr. Geer, however, “one limitation of these data is the lack of standardized criteria to define diagnosis and remission of Cushing’s among the studies reviewed.”

Need for Consistency in Clinical Trials and Surgical Expertise

The study investigators concluded, “endoscopic surgery for patients with Cushing’s disease reaches comparable results for microadenomas, and probably better results for macroadenomas than microscopic surgery,” despite the greater learning curve associated with endoscopic surgery.3 As such, based on their findings, the authors concluded that “endoscopic surgery may thus be considered the current standard of care. Microscopic surgery can be used based on neurosurgeon’s preference.” They did not respond to EndocrineWeb for a request for comment.

As more neurosurgeons receiving training with the endoscope, the preferred technique for pituitary surgery is changing. Dr. Geer said, “Broersen’s review provides reassurance that the newer endoscopic technique is at least equal to the microscope for microadenomas and may be preferred for macroadenomas.”

“However, [conclusions based on the systematic review] do not change our role as endocrinologists treating Cushing’s disease, which is to refer, when indicated, to the available neurosurgeon with the most favorable outcomes and lowest rate of complications, both of which depend directly on level of experience with the procedure and the instrument being used, whether endoscope or microscope,” she said.

The authors had no financial conflicts to declare.

From https://www.endocrineweb.com/professional/cushings/cushings-syndrome-eludes-treatment-paradigm-standard-approach-care

Mild Cases of Cushing’s Syndrome Present Diagnostic Challenges

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.

References

  1. Loriaux DL. Diagnosis and differential diagnosis of Cushing’s syndromeN 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 studyJ 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 managementClin 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/

Drug trial begins for Cushing’s syndrome therapy

Participant enrollment has concluded for a phase 3 trial investigating the safety and efficacy of levoketoconazole, a cortisol synthesis inhibitor, for the treatment of endogenous Cushing’s syndrome, according to a press release from Strongbridge Biopharma, the drug’s developer.

The single-arm, open-label SONICS study will include the 90 enrolled participants and may allow a small number of other patients to enroll also, according to the release.

After titration to a therapeutic dose of levoketoconazole (Recorlev), participants will maintain treatment for 6 months, the primary efficacy endpoint. Longer-term evaluation for safety will extend to 1 year. A planned 6-month double blind, placebo-controlled, randomized withdrawal extension, dubbed LOGICS, will include approximately half of the participants from SONICS.

“The need for a safe and effective, next-generation cortisol synthesis inhibitor, such as Recorlev, in the treatment of Cushing’s syndrome is substantial. Through achieving target enrollment in the SONICS study, we are one step closer to better understanding the clinical value of Recorlev and potentially bringing a new therapeutic treatment option to this community,” said Matthew Pauls, president and chief executive officer of Strongbridge Biopharma.

The company expects to announce results of SONICS in the second quarter of 2018 and of LOGICS in the third quarter, according to the release.

For more information:

Clinicaltrials.gov/ct2/show/NCT01838551

From https://www.healio.com/endocrinology/adrenal/news/online/%7Bdddb8b5b-e4c8-412f-b4b8-82acde8f21a2%7D/drug-trial-begins-for-cushings-syndrome-therapy

Phase 3 SONICS Study Evaluating RECORLEV™ (levoketoconazole) in Endogenous Cushing’s Syndrome

DUBLIN, Ireland and TREVOSE, Pa., June 27, 2017 (GLOBE NEWSWIRE) — Strongbridge Biopharma plc, (Nasdaq:SBBP), a global commercial-stage biopharmaceutical company focused on the development and commercialization of therapies for rare diseases with significant unmet needs, today announced that it has met its enrollment target of 90 patients in the Phase 3 SONICS study evaluating the safety and efficacy of RECORLEV(levoketoconazole), a next-generation cortisol synthesis inhibitor, for the treatment of endogenous Cushing’s syndrome. Based upon strong interest in the SONICS study at the end of screening, a small number of additional potential study participants remain in screening and will be allowed to enroll, if qualified.

“We would like to sincerely thank our investigators, their clinical teams, and, most importantly, all of the patients from many countries around the globe for their continued dedication and participation in the SONICS study,” said Fredric Cohen, M.D., chief medical officer of Strongbridge Biopharma. “We currently still have patients in screening for SONICS due to the high level of interest and demand in the study.  Although we have reached target enrollment, we are pleased to extend the study for a brief period to accommodate those in screening who qualify. This will enable us to report top-line results in the second quarter of 2018,” Dr. Cohen added.

“The need for a safe and effective, next-generation cortisol synthesis inhibitor, such as RECORLEV, in the treatment of Cushing’s syndrome is substantial. Through achieving target enrollment in the SONICS study, we are one step closer to better understanding the clinical value of RECORLEV and potentially bringing a new therapeutic treatment option to this community,” said Matthew Pauls, president and chief executive officer of Strongbridge Biopharma. “Because we strongly believe in the potential of RECORLEV to become a best-in-class therapy, and as previously announced, we have strengthened our Phase 3 development plan to include LOGICS, a nine-week, placebo-controlled study, which will complement the long-term SONICS study. We anticipate availability of top-line data from the LOGICS study in the third quarter of 2018,” Pauls added.

SONICS and LOGICS are multinational Phase 3 studies designed to evaluate the safety and efficacy of RECORLEV when used to treat endogenous Cushing’s syndrome. SONICS is a single-arm, open-label study conducted in three treatment phases. Patients titrate to a therapeutic dose in the first phase and are maintained at the therapeutic dose for six months in the second phase, the end of which marks the primary efficacy time point. A six-month extended evaluation is included for long-term safety evaluations. LOGICS uses a placebo-controlled, double-blind, randomized-withdrawal design. Approximately 35 patients with Cushing’s syndrome will be randomized in LOGICS, of which approximately one-half will have previously completed SONICS. Together, the SONICS and LOGICS studies will include the participation of approximately 100 clinical research sites in over 20 countries in North America, Europe and the Middle East.

For more information on the SONICS study, please visit ClinicalTrials.gov and reference identifier: NCT01838551.

About Endogenous Cushing’s Syndrome
Endogenous Cushing’s syndrome (CS) is a rare but serious and potentially lethal endocrine disease caused by chronic elevated cortisol exposure. Most people with CS have a variety of signs and symptoms – many of which, when they occur by themselves, are common and do not necessarily point to an underlying disease; this makes recognition of CS difficult. Common presenting symptoms include weight gain or obesity, fatigue, muscle weakness, headaches, mood or sleep disturbances, facial rounding or redness, excess body hair growth in women or baldness in men, thinned skin with stretch marks, easy bruising and other skin changes including acne, mood or sleep disturbances and irregular periods or loss of libido.  Patients are often found by their doctors to have new-onset or worsening of high blood pressure, abnormal levels of blood lipids, such as cholesterol, polycystic ovaries and abnormal blood glucose or diabetes. People with uncontrolled disease are seriously ill and have a 2- to 4-fold higher mortality rate than age- and gender-matched controls, mainly due to metabolic and cardiovascular complications. Treatment options for CS include surgery, radiation therapy, and medical treatment. Cushing’s syndrome most commonly affects adults ages 20-50 and is more prevalent in females, accounting for about 70 percent of all cases.

About Strongbridge Biopharma
Strongbridge Biopharma is a global commercial-stage biopharmaceutical company focused on the development and commercialization of therapies for rare diseases with significant unmet needs. Strongbridge’s first commercial product is KEVEYIS® (dichlorphenamide), the first and only FDA-approved treatment for hyperkalemic, hypokalemic, and related variants of Primary Periodic Paralysis. KEVEYIS has orphan drug exclusivity status in the U.S. through August 7, 2022. In addition to establishing this neuromuscular disease franchise, the Company has a clinical-stage pipeline of therapies for rare endocrine diseases. Strongbridge’s lead compounds include RECORLEV (levoketoconazole), a cortisol synthesis inhibitor currently being studied for the treatment of endogenous Cushing’s syndrome, and veldoreotide, a next-generation somatostatin analog being investigated for the treatment of acromegaly, with potential additional applications in Cushing’s syndrome and neuroendocrine tumors. Both RECORLEV and veldoreotide have received orphan designation from the U.S. Food and Drug Administration and the European Medicines Agency. For more information, visit www.strongbridgebio.com.

Forward-Looking Statements
This press release contains forward-looking statements that involve substantial risks and uncertainties.  All statements, other than statements of historical facts, contained in this press release, are forward-looking statements. These statements relate to future events and involve known and unknown risks, including, without limitation, uncertainties regarding Strongbridge’s strategy, plans, anticipated investment, status and results of clinical trials and objectives of management for future operations. The words “anticipate,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “project,” “target,” “will,” “would,” or the negative of these terms or other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are based on current expectations, estimates, forecasts and projections and are not guarantees of future performance or development and involve known and unknown risks, uncertainties and other factors. The forward-looking statements contained in this press release are made as of the date of this press release, and Strongbridge Biopharma does not assume any obligation to update any forward-looking statements except as required by applicable law.

Contacts:

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Elixir Health Public Relations
Lindsay Rocco
+1 862-596-1304
lrocco@elixirhealthpr.com

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From http://www.globenewswire.com/news-release/2017/06/27/1029452/0/en/Strongbridge-Biopharma-plc-Completes-Target-Enrollment-of-90-Patients-in-the-Phase-3-SONICS-Study-Evaluating-RECORLEV-levoketoconazole-in-Endogenous-Cushing-s-Syndrome.html

Cushing’s Syndrome and Skin Problems

By Afsaneh Khetrapal, BSc (Hons)

Cushing’s Syndrome (sometimes called hypercortisolism) is a hormonal disease caused by an abnormally high level of the hormone cortisol in the body. This may arise because of an endogenous or exogenous source of cortisol. Endogenous causes include the elevated production of cortisol by the adrenal glands, while exogenous causes include the excessive use of cortisol or other similar steroid (glucocorticoid) hormones over a prolonged period of time.

The adrenal glands are situated just above each kidney, and form part of the endocrine system. They have numerous functions such as the production of hormones called catecholamines, which includes epinephrine and norepinephrine. Interestingly, the outer layer (cortex) of the adrenal glands has the distinct responsibility of producing cortisol. This hormone is best known for its crucial role in the bodily response to stress.

At physiologically appropriate levels, cortisol is vital in maintaining normal sleep-wake cycles, and acts to increase blood sugar levels. It suppresses the immune system, regulates the effect of insulin on the metabolism of fats, proteins, and carbohydrates, and help with the homeostasis of water in the body.

Exogenous corticosteroids can also lead to Cushing’s syndrome, when they are used as a form of long-term treatment for various medical conditions. In fact, the long-term use of steroid medication is the most common reason for the development of Cushing’s syndrome.

Prednisolone is the most commonly prescribed steroid medicine. It belongs to a class of medicine that is sometimes used to treat conditions such as certain forms of arthritis and cancer. Other uses include the rapid and effective reduction of inflammation in conditions such as asthma and multiple sclerosis (MS), as well as the treatment of autoimmune conditions such as lupus erythematosus, and rheumatoid arthritis.

Overall, Cushing’s syndrome is quite uncommon and affects approximately 1 in 50,000 people. Most of them are adults between the ages of 20 and 50.  Women are 3 times more commonly affected than men. Additionally, patients who are obese, or those who have type 2 diabetes with poorly controlled blood sugar and blood pressure show a greater predisposition to the disorder.

Symptoms of Cushing’s syndrome

There are numerous symptoms associated with Cushing’s syndrome, which range from muscle weakness, hypertension, curvature of the spine (kyphosis), osteoporosis, and depression, to fatigue Specific symptoms which pertain to the skin are as follows:

  • Thinning of the skin and other mucous membranes: the skin becomes dry and bruises easily. Cortisol causes the breakdown of some dermal proteins along with the weakening of small blood vessels. In fact, the skin may become so weak as to develop a shiny, paper-thin quality which allows it to be torn easily.
  • Increased susceptibility of skin to infections
  • Poor wound healing  of bruises, cuts, and scratches
  • Spots appear on the upper body, that is, on the face, chest or shoulders
  • Darkened skin which is seen on the neck
  • Wide, red-purple streaks (at least half an inch wide) called striae which are most common on the sides of the torso, the lower abdomen, thighs, buttocks, arms, and breasts, or in areas of weight gain. The accumulation of fat caused by Cushing’s syndrome stretches the skin which is already thin and weakened due to cortisol action, causing it to hemorrhage and stretch permanently, healing by fibrosis.
  • Acne: this can develop in patients of all ages.
  • Swollen ankles: this is caused by the accumulation of fluid, called edema.
  • Hyperhidrosis (excessive sweating)

Reviewed by Dr Liji Thomas, MD

From http://www.news-medical.net/health/Cushings-Syndrome-and-Skin-Problems.aspx

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