How Do Steroidogenesis Inhibitors Work?

Steroidogenesis inhibitors are a class of drugs used to treat Cushing’s disease in adult patients ineligible for or who had a failed pituitary surgery.

Cushing’s disease is a metabolic disorder caused by the overproduction of corticosteroid (cortisol-a stress hormone) hormones by the adrenal cortex (a small organ on top of each kidney) and often involves obesity and high blood pressure. Cortisol helps maintain blood sugar levels, protects the body from physical stress, and suppresses inflammation. Many a time, Cushing’s disease is the result of adrenocorticotropic hormone hypersecretion secondary to a pituitary tumor. Patients with Cushing’s disease suffer from various comorbidities that increase the risk of mortality, and the disease is characterized by signs and symptoms such as:

• Acne
• Fatigue
• Weight gain and fatty tissue deposits, particularly around the midsection and upper back, in the face (moon face), and between the shoulders (buffalo hump)
• Pink or purple stretch marks (striae) on the skin of the abdomen, thighs, breasts, and arms.
• Thinning, fragile skin that bruises/bleeds easily
• Muscle weakness
• Increased thirst/urination
• Hypertension (high blood pressure)
• Hyperglycemia (high blood sugar) 
• Headache
• Mood swings
• Irritability/depression
• Slow wound healing
• Bone pain

Steroidogenesis inhibitors possess anti-adrenal activity, which works by binding to and inhibiting the activity of 11-beta-hydroxylase, the enzyme that catalyzes the final step of cortisol synthesis. The inhibition of 11-beta-hydroxylase prevents the production of excess cortisol, thereby decreasing and normalizing the levels of cortisol.

Steroidogenesis inhibitors are administered via oral route, typically twice daily with or without food.

Steroidogenesis inhibitors work by decreasing the cortisol overproduction in the body by blocking the enzyme known as "11-beta-hydroxylase" (enzyme that catalyzes the final step in the biosynthesis of endogenous cortisol) and thus maintaining a normal cortisol level.

Steroidogenesis inhibitors are indicated for Cushing’s disease in adults for whom pituitary surgery is not an option or has not been a curative treatment.

Some of the common side effects include:

• Nausea
• Vomiting
• Diarrhea
• Headache
• Abdominal pain
• Tiredness/weakness
• Decreased appetite
• Acne
• Dyspepsia (a persistent or recurrent pain or discomfort in the upper abdomen)
• Adrenal insufficiency 
• Muscle/back pain

Other rare side effects include:

• Dizziness 
• Fatigue 
• Rash/itching
• Increased blood corticotrophin
• Hypokalemia (low blood potassium level)
• Anemia (low red blood cell count)
• Hypotension (low blood pressure)
• Urinary tract infection 
• Pyrexia (fever)
• Hirsutism (a condition in women which results in excessive growth of dark or coarse hair in a male-like pattern)
• Alopecia (unpredictable, patchy hair loss)
• Insomnia (trouble falling and/or staying asleep)
• Edema (swelling caused by excess fluid trapped in the body tissues)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of steroidogenesis inhibitors include:

• Isturisa
• Osilodrostat