Nelson syndrome

Disease Description (Causes and Symptoms)

• Definition/Cause: This condition occurs after bilateral adrenalectomy. With the loss of the negative feedback normally exerted by cortisol produced by the adrenal glands, anterior pituitary cells that secrete adrenocorticotropic hormone (ACTH) undergo hyperplasia or grow into an adenoma, resulting in excessive ACTH secretion.
• Pathophysiology: When cortisol levels fall following adrenal removal, negative feedback in the hypothalamic-pituitary axis is lost, leading to proliferation and hyperfunction of corticotroph cells. In some cases, this progresses to a giant pituitary mass that compresses surrounding structures.
• Major symptoms: Hyperpigmentation of the skin and mucous membranes (brown discoloration), headache, visual impairment (mainly bitemporal hemianopic visual-field defects), anterior pituitary hypofunction (including growth delay, cessation of menstruation, and hypothyroidism), and sometimes diabetes insipidus (due to posterior pituitary involvement in severe cases) and generalized weakness.
• Onset/Epidemiology: It can develop within several months to several years after bilateral adrenalectomy. Although the incidence varies by study, it has been reported to be approximately within the range of several percent (e.g., from a few percent to several tens of percent).

Treatment Methods and Precautions

• Standard treatment
  • Surgical treatment: If the mass is large or compresses the optic nerve or brain, transsphenoidal pituitary resection (microsurgery) is considered first.
  • Radiation therapy: Local radiation therapy or gamma knife/stereotactic radiosurgery (SRS) is effective in suppressing tumor growth and may be used before or after surgery or alone when surgery is not possible.
  • Drug treatment: In some patients, dopamine agonists (e.g., cabergoline) may reduce ACTH levels and tumor size, while anticancer drugs (e.g., temozolomide) may be considered for refractory, invasive, or recurrent tumors. The effects of somatostatin analogs and other endocrine drugs are limited.
  • Hormone replacement: Patients who have undergone bilateral adrenalectomy require lifelong glucocorticoid (and, if necessary, mineralocorticoid) supplementation. If anterior pituitary hypofunction develops, necessary hormone replacement, including thyroid hormone, sex hormones, and growth hormone, is administered concurrently.
• Lifestyle management
  • Take medications regularly (especially steroid replacement) and receive education on increasing the dose during infection or stress
  • Seek medical attention immediately if visual changes occur or headaches worsen
• Precautions and risk of complications
  • Pituitary hypofunction (permanent hormone deficiencies) may occur after radiation therapy or surgery
  • Surgical complications: cerebrospinal fluid leakage, infection, optic nerve injury, and others
  • Neurological compression symptoms may worsen with long-term excessive ACTH levels or tumor progression

Checklist Before an Outpatient Visit (Items to Prepare and Points to Confirm)

• Items to prepare/bring
  • List of currently taken medications (including steroids), and medical records documenting allergies, previous surgeries, and diagnoses
  • Previous blood test results (especially ACTH, cortisol, thyroid hormones, etc.) and recent MRI/CT reports and images (CD/USB if possible)
  • Symptom record: time of onset, patterns of worsening/improvement, visual changes (photographs or a description of symptoms), changes in skin color, menstrual changes, and presence of polyuria/nocturia
• Key points to confirm with the doctor during the outpatient visit
  • Current steroid replacement dose and dosing schedule
  • Timing and results of recent ACTH/cortisol tests
  • Whether there have been any changes on previous pituitary imaging

(Including example questions)

• "What are my recent ACTH and cortisol levels?"
• "How has the tumor size changed on the recent MRI?"

Examples of General Questions to Ask the Doctor

• What are the expected effects and side effects of this medication (or radiation therapy)?
• How will hormone replacement change after surgery or radiation therapy? Will lifelong supplementation be necessary?
• What is the risk of recurrence, and how often should follow-up tests (blood tests and MRI) be performed?
• What should I be careful about if I am planning a pregnancy?

Examples of Disease-Specific Questions

• If radiation therapy (stereotactic radiosurgery or gamma knife) is chosen instead of surgery, what are the expected tumor suppression rate and the long-term risk of pituitary dysfunction?
• What is the target ACTH level, and what are the next treatment options if the level does not remain stable?