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CUSHING’S AWARENESS DAY CUSHING’S AWARENESS DAY Cushing’s syndrome is a disorder characterized by physical and mental changes resulting from having too much cortisol (hypercortisolism) in the blood for a long period of time. There are two types of Cushing’s syndrome: Endogenous and exogenous (caused by factors outside the body) CUSHING’S OVERVIEW ENDOGENOUS CUSHING’S CLINICAL FEATURES ACTH Dependent 66 - 85% Pituitary Cushing’s disease A pituitary tumor makes excess ACTH, causing cortisol overproduction via adrenal glands Moon face Easy bruising ACTH Independent 15 - 35% Acne Hypertension Adrenal Cushing’s Syndrome Tumor on either one or both adrenal glands, enabling cortisol overproduction Thin skin Cardiac hypertrophy Weight gain High blood sugar Ectopic Cushing’s syndrome A tumor outside the pituitary or adrenal glands releases ACTH, causing the adrenals to overproduce cortisol Stretch marks Adrenal tumor Pendulous abdomen Menstrual irregularities Muscle weakness Osteoporosis Poor wound healing Skin ulcers EXOGENOUS CUSHING’S Cushing’s triggered due to excess cortisol from a source outside the body, often from a medication containing steroids INCIDENCE, PREVALENCE & IMPACT Annual Incidence Prevalence Gender Predilection Onset Cushing’s Syndrome 3.2 cases /million 57 cases/million 3-4X more common in women 30 - 60 age group Cushing’s Disease 2.4 cases/million 22 cases/million 3X more common in women 20 - 50 age group EMERGING EVIDENCE DIAGNOSIS Circulation The terms "Cushing’s" and "hypercortisolism" are often used interchangeably Urinary Free Cortisol Recent industrial research suggests that hypercortisolism may be prevalent in resistant diabetes and resistant hypertension (Corcept) Free Cortisol(5%) A study called the “The CATALYST trial“ found ~24% of difficult-to-control T2D patients had endogenous hypercortisolism Salivary free cortisol The MOMENTUM study (March 2026) found 27% of resistant hypertension patients had hypercortisolism CBG and other protein bound cortisol (95%) Total Cortisol TREATMENT GUIDELINES (ENDOCRINE SOCIETY 2026) TREATMENT Patient Scenario Recommended Action / Drug Choice 1L of Treatment : Surgery ( Tumor resection) PHARMACOLOGICAL TREATMENT Use rapid-acting inhibitors: Metyrapone, Osilodrostat or IV Etomidate Severe / Life-Threatening Pituitary-directed drugs Somatostatin analog: Pasireotide Dopamine agonist: Cabergoline Pregnancy / Breastfeeding No approved drugs; Metyrapone or Cabergoline are typically used Females w/ High Androgens Consider Ketoconazole (helps lower androgen levels) Adrenal-directed drugs Steroidogenesis inhibitors: Osilodrostat, Ketoconazole, Metyrapone, Levoketoconazole Adrenolytic drug: Mitotane Males w/ Hypogonadism Avoid Ketoconazole (can worsen the condition) Liver Injury / High Enzymes Avoid Ketoconazole due to hepatotoxicity risks Concern for Tumor Size Glucocorticoid receptor-directed drugs Mifepristone Relacorilant (under review) Consider Pasireotide or Cabergoline Ineffective Monotherapy Use Combination Therapy (e.g., Metyrapone + Ketoconazole) RESOURCES Vyuhpharma® All Rights Reserved Note: This report is generated based on publicly available data

On 𝐂𝐮𝐬𝐡𝐢𝐧𝐠’𝐬 𝐀𝐰𝐚𝐫𝐞𝐧𝐞𝐬𝐬 𝐃𝐚𝐲 2026, we join the global community in raising awareness and supporting those affected by Cushing’s syndrome/disease. Beyond raising awareness, we are also advocating for the undiagnosed. The road to a Cushing’s diagnosis is often too long and too difficult. Together, we advocate for better research and care. Our commitment to innovation and compassion drives us to stand alongside those affected today and every day.

April 8, 2026

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