Nelson’s Syndrome

What Is Nelson’s Syndrome?

Nelson’s syndrome is a serious clinical condition in patients who have undergone surgery of adrenal glands to treat Cushing's disease or Cushing’s syndrome. This "post adrenalectomy" syndrome was first reported through case studies of patients in 1959 by Dr. Fon H Nelson, an endocrinologist, and physician who first elaborated on this pituitary tumor.

Nelson's syndrome is a clinical challenge to both physicians and patients due to its features’ complexity. This article elaborates the features of this pituitary tumor, the disorders of the adrenal gland that are indicated for surgery, and the management of Nelson’s syndrome.

What Are the Clinical Features of Nelson Syndrome?

In this pituitary tumor, multiple clinical symptoms arise, all of which start with hyperpigmentation of the skin, hyperpigmentation of the scrotum, the areolae, and of the gingiva. Gingival hyperpigmentation or the oral mucosal membrane hyperpigmentation that may be accompanied or preceded by gingival hypertrophy (enlargement or overgrowth of gingival tissue causing variations in its contour) is a very obvious oral characteristic feature of this disease, just like the hyperpigmented skin surface of the individual.

The serious clinical feature of this disease or tumor is hemianopia, wherein there may be partial loss of the visual field in one eye. Hemianopias can be temporary or permanent, usually depending on the extent of the pituitary tumor. Complete visual loss is not uncommon in very large pituitary tumors of this disease which can be progressive and also a hindrance to the patient other than accessory clinical symptoms like headaches, severe fatigue (malaise or weakness), the underlying reason mainly being the pituitary gland dysfunctionality.

The characteristic feature that distinguishes this syndrome is that it is seldom found in patients suffering from an adrenal disease and is instead found in those patients who have undergone surgical adrenalectomy or removal of one or both of the adrenal glands. In the past decades, the surgical procedure to avoid long-term complications as a result of Cushing's disease has led to the physician's and surgeon’s recommendation of it, that is, the bilateral adrenalectomy procedure. However, in the recent decade, this surgical modality is not preferred anymore as it can make the patients more prone to the risk of developing Nelson's syndrome.

What Adrenal Gland Disorders Necessitate Adrenalectomy?

The adrenal glands situated bilaterally above the kidneys are major endocrine hormonal organs that secrete for the purpose of growth and development, sexual function, and metabolism in the human body.

Though in normal individuals not suffering from any systemic disease, the problems of adrenal glands should be definitely rare, still, the conditions that impact the adrenal glands are varied, ranging from cancerous tumors to hypercortisolism (increased production of cortisol or stress hormone - Cushing’s syndrome or disease), hyperaldosteronism (excess production of aldosterone - the pituitary hormone that regulates salt metabolism as well as blood pressure), and pheochromocytoma (a condition characterized by overproduction or over secretion of hormones like catecholamines and metanephrines that severely causes an imbalance or an unregulated mechanism of blood pressure control).

Overproduction of steroid hormones or cancers of the adrenal gland themselves though less common, definitely is indicative for the patient to undergo adrenalectomy.

Why Is Adrenalectomy Done?

Adrenalectomy is a procedure done through an open incision and open surgery for large cancers of the adrenal glands. For mild to moderate-sized cancers, the adrenalectomy can be performed in smaller incisions by robotic surgery or through a laparoscopy that is minimally invasive in comparison (laparoscopic adrenalectomy).

Unilateral adrenalectomy usually allows the other existing adrenal gland in the body to cope. It allows the patient a better long-term prognosis from either cancer or Cushing’s syndrome or the above-enlisted conditions that interfere with the adrenal gland metabolism.

However, it is bilateral adrenalectomy that is of the most risk to the patient as both glands are bilaterally eliminated atop the kidneys, and medications replace the normal metabolic function of the glands. Hence it makes the patient more prone to Nelson's syndrome.

What Investigations Help Diagnose Nelson’s Syndrome?

Primarily tests for evaluation are conducted by the physician for assessing the plasma ACTH (adrenocorticotropic hormone) levels. An ACTH increase greater than 30 % and with a positive history of adrenalectomy is confirmative of diagnosis of the syndrome.

An MRI (magnetic resonance imaging) may show either a new tumor or enlargement of a long-standing or previously recurrent tumor. MRI and plasma ACTH levels with patients' medical history along with certain severe clinical features limited exclusively to pituitary tumor enlargements like sudden or progressive visual loss and hemianopias are very confirmative and hence gold standard diagnosis for detection and confirmation prior to surgical intervention.

Mainly diagnosis proves useful only in the long-term prognosis of these cases after surgery of the tumor as early diagnosis can help prevent the postoperative complications. This tumor, though slow, can often be clinically asymptomatic for a limited duration (also early detection can help the physician manage endocrine complications like diabetes insipidus or hypopituitarism in these individuals prior to surgery).

How Can Nelson’s Syndrome Be Treated?

1. The mainline treatment is usually surgical resection of the tumor and is performed mainly by either craniotomy surgery or endoscopic or transsphenoidal route surgeries.

2. Radiosurgery that usually directs the radiation specifically (using a gamma source and knife) to the enlarged or the cancerous tissue in the pituitary gland proves an effective option both as an alternative to surgery and if post-operative outcomes fail after surgery in these individuals. Radiosurgery is thus proven very effective as per current research and an effective alternate modality for improving long-term recovery outcomes in these cases. Radiotherapy, on the other hand, can be prophylactically used post-surgery in bilateral adrenalectomy cases.

3. This would be a contraindication in patients who have already received radiation therapy (though previously). Also, as these individuals cannot produce cortisol anymore, the Glucocorticoids and Mineralocorticoids are administered permanently to compensate for the loss of natural cortisol production. Somatostatin analogs and Dopamine agonists are other drugs that have proved effective as per recent research alongside Hydrocortisone or Glucocorticoid/Mineralocorticoid administration every day.

Conclusion:

Nelson’s syndrome is a complex clinical entity and challenge. With current treatment modalities, though the prognosis is improved for these cases, early detection and recognition of symptoms are essential in adrenalectomy patients to combat this tumor.