How to treat Cushing's syndrome?

Define Cushing's Syndrome.

Cushing's syndrome is a hormonal condition characterized by high cortisol levels or steroid use. Untreated, it causes physical changes, metabolic issues, and serious health problems. High cortisol levels (hypercortisolism) from long-term steroid use or tumors induce Cushing's syndrome, a dangerous hormonal condition. Rapid weight gain, especially in the face and upper back, along with thin, easily bruised skin, muscle weakness, and purple stretch marks, is common. Surgery or medicine usually cures it. This condition is rare, occurring approximately 2-3 times per million individuals annually.

Causes 

• Endogenous means inside.

• Adrenal glands overproduce cortisol. 

• Cushing's disease (pituitary adenoma) causes excess ACTH production. 

• Rare adrenal tumors or ectopic ACTH-producing tumors. 

• External (exogenous): 

• Long-term use of glucocorticoids (e.g., prednisone) for asthma, arthritis, or autoimmune illnesses.

Other signs: 

• High blood pressure. 

• Muscle weakness and bulk loss. 

• Acne, bruising, and fragile skin. 

• Bone loss (osteoporosis).

Complications 

• Metabolic: Type 2 diabetes, obesity. 

• Cardiovascular: Hypertension, a higher risk of heart disease. 

• Immune: Suppressed immunity leads to frequent infections. 

• Skeletal: Osteoporosis and fractures. 

What are three Cushing's symptoms?

Important Cushing's Syndrome Signs 

• Moon face: Fat redistribution causes a rounder, fuller face. 

• Buffalo hump: A fat pad between the shoulders and upper back. 

• Purple stretch marks (striae): Wide, colourful marks on the abdomen, thighs, or breasts.

Additional Common Symptoms 

• Increased weight in the middle and upper back, with slimmer arms and legs. 

• The skin appears fragile and is prone to easy bruising. 

• The patient exhibits high blood pressure and may be at risk for type 2 diabetes. 

• The patient experiences muscle weakness and bone loss due to osteoporosis. 

Doctors first look for moon face, buffalo hump, and purple stretch marks to suspect Cushing's syndrome.

Cushing's syndrome diagnosis

Hormone and imaging testing establish sustained cortisol excess and its source to diagnose Cushing's syndrome. The 24-hour urine free cortisol, late-night salivary cortisol, and low-dose dexamethasone suppression tests are the best first-line testing.

First Step: Screening Tests

First, doctors screen for abnormal cortisol levels: 

• 24-hour urinary free cortisol (UFC): Tracks daily urine excretion of cortisol. High amounts indicate hypercortisolism. 

• Salivary cortisol levels should be low at night; persistently high levels indicate a lack of normal rhythm. 

• Low-dose dexamethasone suppression test (DST): A synthetic steroid reduces cortisol in healthy individuals but maintains high levels in Cushing's syndrome.

Step 2: Confirmation Testing

Further testing confirms the diagnosis if screening is positive: 

• • Repeat testing is necessary to eliminate false positives, as stress, sadness, and alcohol usage can mimic Cushing's. 
• • Plasma ACTH measurement: This test helps determine if the extra cortisol is caused by too much ACTH from the pit

Third Step: Imaging Studies

Biochemical confirmation is followed by imaging to find the source. MRI of the pituitary gland can detect adenomas (Cushing's disease). 

• Adrenal CT/MRI: Detects adrenal tumors or hyperplasia. 

• Chest/abdominal scans: Check for ectopic ACTH-producing tumors, such as lung cancer.

Important Considerations 

• Repeated and thorough testing is necessary to distinguish pseudo-Cushing's syndrome from persistent drinking, depression, and obesity. 

• To diagnose, biochemical proof and clinical connection are needed, including physical signs (moon face, buffalo hump, purple striae) and abnormal cortisol testing. Early diagnosis is crucial to prevent consequences, including diabetes, hypertension, osteoporosis, and cardiovascular disease.

Which patient is most likely to have Cushing's?

Cushing's disease, which happens when a pituitary adenoma makes too much ACTH, is most often seen in women between 25 and 45 years old who gain weight in their trunk, have a round "moon" face, and purple stretch marks on

Cushing's Disease: Differentiation from Other Types 

• Cushing's disease: pituitary adenoma causes excess ACTH, leading to the adrenal glands overproducing cortisol. 

• Cushing's syndrome can also be caused by adrenal tumors, ectopic ACTH-producing tumors, or long-term steroid use.

The typical Cushing's Disease patient profile 

• The condition is more common in women between the ages of 25 and 45. 

 Symptoms:  Central obesity with thin arms/legs. 

• The condition is characterized by facial redness and a rounded "moon" face. 

• "Buffalo hump" refers to the accumulation of fat between the shoulders. 

• The abdomen and thighs are covered in purple stretch marks. 

• Women's menstrual irregularity. 

• Muscle weakness and weariness. 

Lab Results: 

• The patient's cortisol levels do not respond to dexamethasone. 

• High ACTH levels (pituitary-driven). Pituitary MRI may reveal a tiny adenoma.

An example case

Woman, 30, with:  Rapid weight gain in abdomen and face. 

• Her abdomen has purple stretch marks.

• She also exhibits hypertension and irregular menstrual cycles. 

• She also has elevated levels of cortisol and ACTH.

This profile strongly implies Cushing's illness, not adrenal or ectopic origins.

The video about managing Cushing's syndrome

Treatment for Cushing's

• Adjust medication: Reduce or stop steroid medicines if they are the cause. 

• Surgery: Removal of pituitary or adrenal tumors. 

• Radiation therapy for unremoved pituitary adenomas. 

• Drugs such as ketoconazole and metyrapone, which reduce cortisol production, are also used.

If Cushing's syndrome is caused by steroid medication, the dose is reduced or stopped under medical supervision. If it's caused by a tumor (pituitary, adrenal, or ectopic), surgery is usually the first-line treatment, followed by radiation or cortisol controls.

The main treatment methods

1. Cushing's Syndrome from Medication 

• Cause: Prolonged usage of glucocorticoids (e.g., prednisone, dexamethasone). 

• Prevent adrenal insufficiency by gradually decreasing or discontinuing the medicine under medical supervision. 

• Consider switching to non-steroid drugs as an alternative therapy.

2. Pituitary tumor (Cushing's) 

• First-line: Transsphenoidal surgery for pituitary adenoma removal. 

• For incomplete elimination, use radiation therapy or medicines (e.g., pasireotide, cabergoline) to suppress ACTH production. 

• Temporary control: Ketoconazole, metyrapone, or mitotane can reduce cortisol until permanent treatment is accessible.

3. Adrenal Tumors 

• Treatment: Adrenalectomy, surgical removal of the troubled adrenal gland. 

• Patients post-surgery may require cortisol supplementation till adrenal gland recovery.

4. ACTH-producing ectopic tumors 

• Treatment: Surgically remove the tumor, typically from the lungs or pancreas. 

• If the tumor remains unremoved, medications such as ketoconazole, mitotane, and mifepristone can impede the synthesis of cortisol.

5. Lifestyle and Supportive Measures 

• Diet and exercise: Manage weight gain, diabetes, and hypertension. 

• Ensure bone health with calcium, vitamin D, and bisphosphonates to avoid osteoporosis. 

• Psychological support: Counseling for mood swings and depression.

Risks and Considerations 

• Surgery risks: Pituitary or adrenal surgery may cause transient adrenal insufficiency, necessitating steroid replacement. 

• Medication side effects: Ketoconazole may impact liver function, requiring monitoring. 

• Cushing's illness may reappear following surgery, necessitating long-term monitoring.

What is the life expectancy for individuals with Cushing's syndrome?

The duration of Cushing's syndrome depends on your health and the ease of your treatment. The median survival time after successful therapy was 40 years in one study.

Cushing's Syndrome conclusion

Chronic cortisol exposure causes Cushing's syndrome, a dangerous but curable hormonal condition. Pituitary adenomas (Cushing's disease), adrenal tumors, ectopic ACTH-producing tumors, and long-term steroid use can cause it.

Most people can go into remission and improve their quality of life with early diagnosis and therapy.