Nelson's syndrome

Overview

Nelson's syndrome is a rare but serious condition that occurs in some individuals after surgical removal of both adrenal glands (bilateral adrenalectomy), typically done to treat Cushing’s disease when other treatments fail. The syndrome is characterized by the rapid growth of a pituitary adenoma (a benign tumor in the pituitary gland), leading to excessive production of adrenocorticotropic hormone (ACTH). This increase in ACTH can cause hyperpigmentation of the skin, visual disturbances due to tumor expansion, and other complications related to pituitary dysfunction.

The condition was first described in 1958 by Dr. Don Nelson, and though it is less common today due to advances in Cushing’s disease treatment, it remains a significant postoperative risk. Close monitoring of patients after adrenalectomy is crucial to detect Nelson’s syndrome early and intervene appropriately.

Causes

Nelson's syndrome develops as a result of a feedback imbalance following bilateral adrenalectomy. In patients with Cushing’s disease, a pituitary adenoma produces excess ACTH, which in turn stimulates the adrenal glands to produce cortisol. When both adrenal glands are removed to control cortisol overproduction, the normal feedback inhibition on the pituitary gland is lost.

This lack of negative feedback leads to unregulated growth of the existing pituitary adenoma, resulting in significantly elevated ACTH levels and tumor expansion. The precise risk factors that determine who will develop Nelson’s syndrome after adrenalectomy are not fully understood, but larger or more aggressive pituitary adenomas and lack of radiation therapy are considered contributing factors.

Symptoms

The symptoms of Nelson’s syndrome vary depending on the size and growth rate of the pituitary tumor and the level of ACTH being produced. Common signs and symptoms include:

Hormonal and Systemic Effects

• Hyperpigmentation: Darkening of the skin, especially in areas exposed to friction (e.g., knuckles, elbows, skin creases)

• Elevated ACTH levels: Often significantly higher than before adrenalectomy

Neurological and Visual Symptoms

• Headaches: Due to expanding pituitary mass

• Visual field defects: Especially bitemporal hemianopia (loss of peripheral vision in both eyes) due to optic chiasm compression

• Cranial nerve palsies: In rare cases where tumor invades surrounding structures

Other Symptoms

• Fatigue

• Weight loss (in contrast to weight gain seen in Cushing’s disease)

• Possible pituitary hormone deficiencies (hypopituitarism)

Diagnosis

Diagnosis of Nelson’s syndrome relies on a combination of clinical evaluation, laboratory tests, and imaging studies, particularly in patients with a history of bilateral adrenalectomy for Cushing’s disease.

• Clinical history: A history of adrenal gland removal and Cushing’s disease is key to suspecting Nelson’s syndrome

• Blood tests: Markedly elevated plasma ACTH levels, typically higher than 200 pg/mL

• Skin examination: Documentation of hyperpigmentation changes

• Magnetic Resonance Imaging (MRI): Used to detect pituitary tumor growth or new tumor development

• Visual field testing: Performed to assess potential optic nerve involvement

Treatment

The treatment of Nelson’s syndrome involves reducing ACTH production, managing pituitary tumor growth, and addressing any pituitary hormone deficiencies. Management is typically done through a multidisciplinary approach involving endocrinologists, neurosurgeons, and radiation oncologists.

Medical Therapy

• Somatostatin analogs: Such as pasireotide or octreotide to suppress ACTH secretion in some patients

• Dopamine agonists: Including cabergoline, used in select cases to reduce tumor activity

• Steroid replacement: Lifelong glucocorticoid and mineralocorticoid therapy is required due to lack of adrenal glands

Surgical Treatment

• Transsphenoidal surgery: To remove the pituitary tumor, especially if the tumor is causing visual impairment or compressive symptoms

Radiation Therapy

• Stereotactic radiosurgery or conventional radiotherapy: May be used postoperatively or as an alternative to surgery for controlling tumor growth

• Prophylactic pituitary irradiation at the time of adrenalectomy may reduce the risk of developing Nelson's syndrome

Hormonal Replacement

• Monitoring and replacement of other pituitary hormones (e.g., thyroid hormone, growth hormone, sex hormones) if deficiencies develop

Prognosis

The prognosis for Nelson’s syndrome depends on early diagnosis and effective management of the pituitary tumor. While the condition can be serious and potentially life-threatening if untreated, outcomes have improved significantly with modern surgical and radiological techniques.

Patients require lifelong monitoring of ACTH levels, pituitary imaging, and hormone replacement therapy. Visual outcomes are generally favorable if intervention occurs before significant optic nerve damage. Preventive strategies, such as prophylactic pituitary irradiation during adrenalectomy, may reduce the incidence of Nelson’s syndrome in high-risk individuals.

With appropriate care, many patients can manage Nelson’s syndrome effectively and maintain a good quality of life.