Pseudo-Cushing’s Syndrome- An Overview

Introduction

Pseudo-Cushing's syndrome is a condition in which the symptoms are typically similar to that of Cushing's syndrome. Even for experienced endocrinologists, distinguishing between pseudo-Cushing's and Cushing's syndrome presents a substantial clinical problem. The symptoms overlap in clinical and laboratory results, making it difficult to form a conclusive diagnosis. However, a patient's clinical history occasionally aids in differentiating them, as in the case of alcoholics. Pseudo-Cushing's syndrome occurs due to the activation of the hypothalamic-pituitary-adrenal axis. However, once the underlying cause of deranged cortisol levels is managed, the pseudo-Cushing's syndrome can be effectively treated.

What Is Cushing's Syndrome?

• Cushing's syndrome, or hypercortisolism, is an endocrine disorder. The condition is characterized by an excess amount of cortisol in the body. Cortisol is an important steroid hormone produced by the adrenal glands.

• Individuals affected by Cushing's syndrome present with a variety of physical signs and symptoms: rounded or moon face appearance, redness of the face, weight gain in the upper body, weight gain on the upper back, acne, baldness in women, facial hair growth, increased blood pressure, increase blood sugar levels, skin becomes thin and easily bruisable, purple colored striations on the skin, weak bones, infertility in both men and women, hyperpigmentation of the skin, etc.

• The causes of Cushing's syndrome are overuse of cortisol medications (corticosteroids), an adrenal tumor, a tumor in the pituitary gland, etc.

What Is Pseudo-Cushing's Syndrome?

Pseudo-Cushing's syndrome includes several medical conditions associated with mild to moderate physical and biochemical symptoms of Cushing's syndrome. However, the increased cortisol level is secondary to other factors. Furthermore, unlike Cushing's syndrome, pseudo-syndrome Cushing's is not caused by a problem with the hypothalamic-pituitary-adrenal axis. Some symptoms and mildly elevated hormone levels observed in pseudo-Cushing's syndrome overlap with those seen in Cushing's syndrome. However, the tumors associated with Cushing's syndrome are absent in people affected by pseudo-Cushing's syndrome. Neuropsychiatric disorders, alcoholism, insulin-resistant obesity, polycystic ovary syndrome, and end-stage renal disease are the main disorders associated with pseudo-Cushing's syndrome.

What Are the Other Names for Pseudo-Cushing's Syndrome?

The alternative name for pseudo-Cushing's syndrome is non-neoplastic hypercortisolism.

Is Pseudo-Cushing Syndrome a Common Condition?

• The exact incidence of pseudo-Cushing's syndrome is unknown because of the lack of enough reported cases and case studies.

• About 50 % of depression disorder patients show signs of hypercortisolemia, which is especially common in the melancholic subtype.

• In a study including 190 people with type 2 diabetes, about 33 % of the patients had increased cortisol levels.

• Even infants exposed to alcohol through breast milk (alcoholic mothers) can develop pseudo-Cushing's syndrome.

• 18 % of the men in a facility for alcohol detoxification had elevated serum cortisol levels.

What Causes Pseudo-Cushing's Syndrome?

The exact mechanism that leads to the development of the pseudo-Cushing's syndrome. However, the majority of the research suggests central activation of corticotropin-releasing hormone. Some frequently occurring conditions that present with symptoms overlapping with symptoms of Cushing's syndrome and associated hypercortisolism are:

• Chronic Alcoholism or Alcohol Abuse - Alcohol may directly stimulate the release of cortisol, according to certain research. It is unknown why some alcoholic patients get pseudo-Cushing's syndrome while others do not.

• Depression - Hyperactivity of the hypothalamic-pituitary axis is thought to be associated with obesity which leads to the development of pseudo-Cushing's syndrome.

• Obesity - The causes of hyperactivation of the Hypothalamic-pituitary-adrenal axis in obesity, which include hyperresponsiveness to various neuropeptides, stressors, nutritional variables, stimulation from increased peripheral metabolism, decreased cortisone to cortisol conversion, etc.

• Physical and mental stress.

• Eating disorders.

• Uncontrolled diabetes.

• Polycystic ovarian syndrome or PCOS (a hormonal disorder that results in enlarged ovaries with tiny cysts on the margins).

• Malnutrition.

• Obstructive sleep apnea (a condition in which the muscles supporting the soft tissues in the throat become temporarily relaxed and breathing gets cut off for some time).

What Are the Symptoms of Pseudo-Cushing's Syndrome?

Symptoms of pseudo-Cushing's syndrome are generally similar to Cushing's syndrome. These symptoms include:

• Some patients are asymptomatic, while others may exhibit full-blown Cushing's syndrome symptoms.

• Accumulation of fat around the stomach and abdomen (truncal obesity).

• Moon face or roundness of the face.

• Upper body weight gain, giving the appearance of a hump known as the buffalo hump.

• Fat pads above the clavicular region.

• Facial hair growth in women.

• Thin and easily bruisable skin.

• Purple striations on the skin.

• Increased blood pressure.

• Reduced bone density.

• Muscle weakness occurs due to muscle fiber dysfunction.

How Is Pseudo-Cushing's Syndrome Diagnosed?

The diagnosis of pseudo-Cushing's syndrome involves:

• Blood Examinations: Blood samples are collected, and cortisol and adrenocorticotropic hormone levels are evaluated. The levels of these hormones are elevated in the case of pseudo-Cushing's syndrome.

• 24-Hour Urinary Cortisol: This test measures the amount of cortisol present in the urine for 24 hours. The levels are moderately increased in the case of a pseudo-Cushing's syndrome, typically not exceeding two to three times the reference range.

• Low Dose Dexamethasone Suppression Test: A small dose of cortisol-like-drugs, for example, Dexamethasone, is taken followed by blood sample collection the following morning.

• Late Night Salivary Cortisol: Two samples are collected around 11:00 pm and midnight, ideally throughout two consecutive nights. The patients are not supposed to smoke or drink twelve hours before the test; the patients should not brush one hour before the test and not eat or drink anything thirty minutes before the test.

How Is Pseudo-Cushing's Syndrome Treated?

The treatment of pseudo-Cushing's syndrome is done by treating the condition's underlying cause.

• An endocrinologist should be consulted for patients who exhibit symptoms of Cushing's syndrome. For the therapy of depression or alcohol misuse, a psychiatrist should be consulted.

• Depressed patients with suicidal thoughts should be assessed and treated accordingly.

• Alcohol withdrawal syndrome is likely to develop and should be expected and avoided because it may contribute to pseudo-Cushing's syndrome. In a patient with persistent alcoholism, acute alcohol withdrawal can result in delirium tremens (visual and auditory hallucinations, whole-body tremors, and vomiting), which can harm both the patient and others.

• People with obesity or malnutrition should consult a dietician or nutritionist.

• No specific medicinal treatment is required except for those affected by depressive disorders and alcoholism.

• Tests should be done to check and treat uncontrolled diabetes mellitus and polycystic ovarian syndrome.

Conclusion

Pseudo-Cushing's syndrome is an endocrine disorder characterized by symptoms similar to that of Cushing's syndrome. However, the hormone levels are mildly or moderately deranged. The condition is also known as non-neoplastic hypercortisolism. Conditions associated with pseudo-Cushing's syndrome include chronic alcoholism, depression, malnutrition, obesity, uncontrolled diabetes, etc. The hormone level returns to the range, and symptoms subside once the underlying condition is treated. For example- when alcohol consumption is stopped, the associated symptoms of pseudo-Cushing's syndrome also get better.