Nelson syndrome is a phenomenon described in patients who undergo total bilateral adrenalectomy (TBA), mainly in the attempt to treat Cushing's disease [1] [2] [3] [4]. Studies report a variable incidence rate of this potentially life-threatening syndrome, ranging from 8-38% in most of the reports [1], but some authors have established that Nelson syndrome appears in up to 47% of patients in whom TBA was performed [4] [5]. The exact pathogenesis of Nelson syndrome remains unknown, as well as why initial signs and symptoms may appear within months or after a few decades [1]. One of the main characteristics of Nelson syndrome is a rapidly expanding mass in the sellar region (sometimes termed corticotrophinoma) that directly compresses the optic chiasm or optic tract, resulting in visual field deficits, palsies of different cranial nerves, ophthalmoplegia, and headaches [1] [3] [6]. Hypersecretion of adrenocorticotropic hormone (ACTH) that persists despite TBA is the second cardinal feature and excessive stimulation of melanocyte production is the reason why hyperpigmentation of the skin (often appearing in a generalized fashion) is a constitutive feature of Nelson syndrome [1] [2] [6]. Furthermore, hyperpigmentation of scars, the buccal mucosa, and even tongue might be observed [1]. In rare cases, paraovarian or paratesticular tumors can develop due to stimulation of gonadal tissues by ACTH, whereas hypopituitarism, oligospermia accompanied by testicular pain, and diabetes insipidus have also been reported [1].

Many reports have stressed the role of close monitoring of patients who undergo TBA because of the life-threatening nature of Nelson syndrome [1]. For this reason, the first piece of information that points to Nelson syndrome is a positive history for this surgical procedure. During the physical examination, physicians must conduct a meticulous neurological and ophthalmological assessment, which will unequivocally show visual field deficits, and together with pigmentation of the skin, help to make a presumptive diagnosis. Laboratory studies must include ACTH testing with reference to the last glucocorticoid dose that patients take for Cushing's disease - One sample should be obtained at 8 AM (values of > 500 ng/L are considered to be high), 20 hours after the last dose, and in the early morning before the next glucocorticoid dose [1] [3]. An increase in > 30% of physiological values on three separate occasions has been proposed as a diagnostic criterion for Nelson syndrome, but in addition to laboratory criteria, and imaging procedures must be used to confirm clinical suspicion [1]. MRI of the endocranium is a highly useful study that identifies a sellar mass [1] [3]. In fact, some authors advocate the regular use of MRI every 6-12 months after TBA in order to detect the hypophyseal tumor as early as possible [3].

The treatment of Nelson Syndrome aims to manage the symptoms and control the growth of the pituitary tumor:

• Surgery: Transsphenoidal surgery may be performed to remove the tumor.
• Radiation Therapy: Used to shrink the tumor or prevent further growth.
• Medications: Drugs that suppress ACTH production or block its effects may be prescribed.
• Hormone Replacement: Patients may require hormone replacement therapy to address deficiencies caused by the removal of the adrenal glands.

The prognosis for Nelson Syndrome varies depending on the size and growth rate of the pituitary tumor and the effectiveness of treatment. Early detection and intervention can improve outcomes. Regular follow-up is essential to monitor for tumor recurrence and manage any complications.

Nelson Syndrome typically develops after bilateral adrenalectomy, a surgical procedure to remove both adrenal glands. This surgery is often performed to treat Cushing's disease, a condition characterized by excessive cortisol production. The removal of the adrenal glands eliminates cortisol feedback inhibition, leading to increased production of ACTH by the pituitary gland and potential tumor growth.

Nelson Syndrome is a rare condition, with its incidence decreasing due to advancements in the treatment of Cushing's disease. It is more commonly observed in patients who have undergone adrenalectomy without subsequent radiation therapy to the pituitary gland. The syndrome can occur at any age but is most frequently diagnosed in adults.

The pathophysiology of Nelson Syndrome involves the loss of cortisol feedback inhibition on the pituitary gland following adrenalectomy. This results in increased production of ACTH, which stimulates the growth of pituitary corticotroph cells, leading to tumor formation. The excess ACTH also causes hyperpigmentation by stimulating melanocytes, the cells responsible for skin pigmentation.

Preventing Nelson Syndrome primarily involves careful management of Cushing's disease. This includes considering alternative treatments to adrenalectomy, such as pituitary surgery or medical therapy, and using radiation therapy to prevent pituitary tumor growth if adrenalectomy is necessary. Regular monitoring of ACTH levels and pituitary imaging can help detect early signs of tumor development.

Nelson Syndrome is a rare but serious condition that can develop after the surgical removal of the adrenal glands. It is characterized by the growth of a pituitary tumor and excessive production of ACTH, leading to symptoms such as skin darkening and headaches. Diagnosis involves clinical evaluation, laboratory tests, and imaging studies. Treatment options include surgery, radiation, and medication. Early detection and intervention are crucial for improving patient outcomes.

If you or someone you know has undergone adrenalectomy and is experiencing symptoms like skin darkening, headaches, or vision problems, it is important to seek medical evaluation. Nelson Syndrome is a rare condition that requires careful monitoring and management. Treatment options are available to control symptoms and prevent complications. Regular follow-up with healthcare providers is essential to ensure the best possible outcomes.

1. Barber TM, Adams E, Ansorge O, Byrne JV, Karavitaki N, Wass JA. Nelson's syndrome. Eur J Endocrinol. 2010;163(4):495-507.
2. van Aken MO, Pereira AM, van den Berg G, Romijn JA, Veldhuis JD, Roelfsema F. Profound amplification of secretory-burst mass and anomalous regularity of ACTH secretory process in patients with Nelson's syndrome compared with Cushing's disease. Clin Endocrinol (Oxf). 2004;60(6):765-772.
3. Munir A, Newell-Price J. Nelson's Syndrome. Arq Bras Endocrinol Metabol. 2007;51(8):1392-1396.
4. Pereira MA, Halpern A, Salgado LR, et al. A study of patients with Nelson's syndrome. Clin Endocrinol (Oxf). 1998;49(4):533-539.
5. Patel J, Eloy JA, Liu JK. Nelson's syndrome: a review of the clinical manifestations, pathophysiology, and treatment strategies. Neurosurg Focus. 2015;38(2):E14.
6. Assié G, Bahurel H, Coste J, et al. Corticotroph tumor progression after adrenalectomy in Cushing's disease: a reappraisal of Nelson's syndrome. Journal of Clinical Endocrinology and Metabolism. 2007;92:172–170.