Williams syndrome

Disease Description (Causes and Symptoms)

• Definition summary: Cushing syndrome is a syndrome caused by abnormally excessive exposure to glucocorticoids in the body. It is classified as exogenous (medication-related) or endogenous (excess hormone secretion).
• Main causes
  • Exogenous: Long-term use of high doses of synthetic corticosteroids (steroids) is the most common cause.
  • Endogenous:
    • ACTH-secreting tumor of the pituitary gland (Cushing disease, ACTH-dependent)
    • Cortisol-secreting tumor of the adrenal gland (adrenal tumor, ACTH-independent)
    • Excess ACTH secretion from ectopic sources (e.g., small-cell lung cancer)
• Pathophysiology (briefly): Excess cortisol affects carbohydrate, lipid, and protein metabolism as well as immune and blood pressure regulation, causing central obesity, muscle weakness, osteoporosis, hyperglycemia and hypertension, and skin changes.
• Main symptoms
  • Body shape and skin: Moon face, fat accumulation at the back of the neck (buffalo hump), central obesity, wasting of the limbs, thin skin that bruises easily, purple striae
  • Systemic symptoms: Muscle weakness, increased risk of osteoporosis/fractures, hypertension, hyperglycemia (or diabetes), frequent infections, acne, hirsutism, menstrual irregularities and sexual dysfunction
  • Mental and neurological symptoms: Depression, anxiety, reduced concentration, sleep disturbances

Treatment Methods and Precautions

• General principles: Remove the cause (if possible) → correct the excess cortisol state → manage complications
• Treatment by cause
  • Exogenous (excess steroid use): Gradually reduce the dose (taper) and then discontinue it according to the doctor's instructions. Sudden discontinuation can cause adrenal insufficiency (including hypotension and shock), so medical instructions must be followed.
  • Pituitary (Cushing disease): Transsphenoidal tumor resection is the first-line treatment. If surgery is not possible or residual tumor remains, radiation therapy or drug treatment (e.g., pasireotide) may be considered.
  • Adrenal tumor: Partial or total adrenalectomy (laparoscopic or open surgery). Adjuvant treatment may be necessary depending on the pathology results.
  • Ectopic ACTH-secreting tumor: Identification and treatment of the primary lesion (surgery, chemotherapy, etc.).
  • Drug treatment (before or after surgery, or when surgery is not possible): Cortisol synthesis inhibitors (e.g., mitotane, metyrapone, ketoconazole, osilodrostat, etc.) or drugs that suppress ACTH secretion.
• Complication and symptom management
  • Hypertension and diabetes: Treatment according to standard guidelines (antihypertensive drugs and glucose control)
  • Osteoporosis: After a bone mineral density test, treatment with calcium, vitamin D, bisphosphonates, etc. may be considered.
  • Infections and impaired wound healing: Monitor infection risk and provide necessary vaccinations and wound care.
  • Increased risk of venous thromboembolism: Assess the risk and provide prevention (exercise, compression, and anticoagulation if necessary).
• Precautions
  • Do not stop steroids on your own (especially if taken long term).
  • Stress-dose steroid management is needed before and after surgery (to prevent adrenal insufficiency).
  • Even with long-term treatment, some metabolic and skeletal complications may persist, so follow-up care is essential.

Checklist Before an Outpatient Visit (Including Items to Bring, Records, and Sample Questions)

• Items to bring (documents/information)
  • List of all medications and supplements currently being taken (especially steroid preparations, doses, and duration of use)
  • Copies of previous test results (blood tests, 24-hour urine tests, blood glucose and lipid tests, bone mineral density tests, etc.)
  • Copies of previous imaging studies (abdominal CT, pituitary MRI, etc.), if available
  • Record of when symptoms began and how they have progressed (weight changes, skin changes, menstrual or sexual changes, etc.)
  • Recently measured values at home, such as blood pressure and midnight blood glucose, if possible
• Symptom checklist to present to the doctor during the outpatient visit
  • Weight changes (where the weight was gained), muscle weakness, history of fractures, fatigue, depressive symptoms, acne, hirsutism, etc.
• Simple measurements that can be taken during the outpatient visit (if possible)
  • Blood pressure measurement, checking weight and waist circumference, and a simple muscle strength assessment (walking and ability to perform daily activities)
• Includes sample questions to ask during the outpatient visit (general sample questions are also provided in the section below)

General Sample Questions to Ask the Doctor

• What are the main benefits and possible side effects of this medication (or surgery)?
• Among the treatment options expected in my case (surgery, medication, or radiation), which is recommended and why?
• What is the recurrence rate after treatment? What is the follow-up testing plan if it recurs?
• Are there any lifestyle habits or dietary measures that require special attention before or after surgery?
• How should blood glucose, blood pressure, and osteoporosis be managed during or after treatment?

Examples of Disease-Specific Questions

• What do my test results (e.g., 24-hour urinary cortisol, late-night salivary cortisol, low-dose dexamethasone suppression test, and blood ACTH level) mean? (Related to determining the cause, such as whether it is ACTH-dependent or ACTH-independent.)
• A small lesion (microadenoma) was found on my pituitary MRI. How do you determine whether it is large enough to require surgery or whether monitoring alone is possible?

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