Nelson syndrome is an infrequent clinical entity that represents the development of skin pigmentation, an expanding and often aggressive pituitary mass, and marked elevations of adrenocorticotropic hormone (ACTH) after total bilateral adrenalectomy as a therapeutic modality for Cushing's disease. Visual field deficits are also reported as a result of direct compression of the optic chiasm. Clinical criteria, magnetic resonance imaging (MRI) of the endocranium, and a positive history for adrenalectomy are crucial findings during the diagnostic workup.
Nelson syndrome is a phenomenon described in patients who undergo total bilateral adrenalectomy (TBA), mainly in the attempt to treat Cushing's disease    . Studies report a variable incidence rate of this potentially life-threatening syndrome, ranging from 8-38% in most of the reports , but some authors have established that Nelson syndrome appears in up to 47% of patients in whom TBA was performed  . 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 . 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   . 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   . Furthermore, hyperpigmentation of scars, the buccal mucosa, and even tongue might be observed . 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 .
Entire Body System
- Weight Gain
gain is commonly seen in Cushing's Syndrome, Cushing's Syndrome itself is a rare cause of weight gain. [columbiasurgery.org]
Symptoms include a round face, thin arms and legs, severe fatigue and muscle weakness, high blood pressure and high blood sugar, purple or pink stretch marks on the skin, and weight gain, especially in the abdomen. [icd10data.com]
If your Cushing's syndrome isn't curable, you'll want to look for ways to manage your weight gain, muscle weakness, and tiredness. Partner with your doctor on that, and tell your doctor how you're feeling. [webmd.com]
gain, sleep disturbance, and/or depression. [amboss.com]
Typically, patients have the following clinical features 6 : rounded face, sometimes described as 'moon-shaped' progressive centripetal obesity and weight gain prominent supraclavicular fat pad, sometimes known as a 'buffalo hump' purple skin striae easy [radiopaedia.org]
As an aside, it should be noted that doctors will sometimes describe certain patients with features identical to Cushing's syndrome as having 'Cushingoid' features. [medicinenet.com]
Medical therapy: In patients who fail to have remission of their Cushingoid state after surgery, there are several medications which can be used to help control cortisol levels. [pituitary.org]
[…] by central obesity, moon facies, and a buffalo hump : decreased libido : decreased libido, virilization, and/or irregular menstrual cycles Secondary hypertension ( 90% of cases) Increased susceptibility to infections Peptic ulcer disease Cataracts “CUSHINGOID [amboss.com]
Most people who appear to have some of the classic physical features of Cushing’s syndrome (Cushingoid appearance) do not actually have the disease. [nadf.us]
Examination revealed Cushingoid habitus, hyperpigmented TBA scar, bilateral ptosis [right more than left, [Figure 2], restriction of extra-ocular movements, bitemporal hemianopia and proximal muscle weakness. [ijem.in]
- Leg Swelling
swelling Purple stretch marks on the abdomen and legs Constantly rosy cheeks Symptoms: Diabetes – high blood sugar levels Hypertension – high blood pressure Mood changes – many patients feel "hyper" while others have sudden mood swings Muscle weakness [columbiasurgery.org]
Nelson syndrome - hyperpigmentation, third nerve damage, and enlarging sella turcica caused by pituitary adenomas that become symptomatic following adrenalectomy. [medical-dictionary.thefreedictionary.com]
The manifestations that comprise the disease known as Nelson syndrome are pituitary hyperplasia and cutaneous hyperpigmentation, which sometimes follow bilateral adrenalectomy, in patients with hypercortisolism. [ncbi.nlm.nih.gov]
Some patients develop hyperpigmentation after bilateral adrenalectomy but do not develop full-blown Nelson's syndrome. [ 5 ] In adolescents there may be features of delayed puberty. [patient.info]
- Linea Nigra
The degree of pigmentation varies depending on the racial origin of the child and the serum concentrations of adrenocorticotropin (ACTH).  Patients usually appear hyperpigmented with a linea nigra (pigmentation extending up the midline from the pubis [emedicine.medscape.com]
Patients usually appear hyperpigmented in linea nigra, scars, gingivae, palmer creases, scrotum and areolae.      Assessment of the pubertal stage      Excessive adrenal androgens in patients with previous Cushing syndrome [explainmedicine.com]
A linea nigra is often apparent. This is a dark line from the pubis to the umbilicus. Scars and areolae are pigmented and, as with Addison's disease, pigmentation is more marked in the creases of the hands. [patient.info]
- Muscle Weakness
Some symptoms are upper body obesity thin arms and legs severe fatigue and muscle weakness high blood pressure high blood sugar easy bruising lab tests can show if you have it and find the cause. [icd10data.com]
He noticed increasing abdominal girth, generalised weakness, easy fatigability, proximal muscle weakness, decreased libido, erectile dysfunction, loss of pubic and axillary hairs and worsening of proximal muscle weakness, diabetes and hypertension. [ijem.in]
weakness Causes Removal of adrenal glands for the purpose of treating Cushing's disease eliminates cortisol production. [medigest.uk]
Risk Factors Screening Natural History, Complications, and Prognosis Natural History Complications Prognosis Diagnosis Diagnostic Criteria History and Symptoms Muscle weakness Physical Examination Skin hyperpigmentation due to excess MSH. [wikidoc.org]
Typical clinical features include central obesity, thin, easily bruisable skin, abdominal striae, secondary hypertension, hyperglycemia, and proximal muscle weakness. [amboss.com]
Characterized by enlarged pituitary tumor, progressive hyperpigmentation, headache, increased plasma adrenocorticotropic hormone levels, and visual field defect in association with a history of Cushing syndrome. [visualdx.com]
A syndrome caused by rapid growth of a pituitary tumor after bilateral adrenalectomy for Cushing disease, marked by hyperpigmentation of the skin, headaches, and vision disturbances. [yourdictionary.com]
Occasionally, patients will also experience a headache as a result of the enlarging tumour. The raised levels of adrenocorticotropic hormone act on cells in the skin to increase pigmentation. [pituitary.org.uk]
This invasive tumor enlarges, often causing visual loss, pituitary failure and headaches. One key characteristic of Nelson's disease is dark skin pigmentation, resulting from the skin pigment cells responding to the release of ACTH. [uclahealth.org]
Neuropsychological outcome - behavioral/affective aspect : Many patients suffer from depression, irritability, apathy and inattention post-operatively, and onset is accompanied by new/worsening neurological signs (ataxia, paresis, oculomotor dysfunction [posteriorfossa.org]
A cranial nerve III paresis was present in three patients (23%) preoperatively (complete in two, partial in one). Anterior pituitary hormone deficiencies were present in four patients ( Table 2 ). Table 2. [doi.org]
In case No. 3 re-growth of an invasive pituitary tumour caused serious visual deterioration and paresis of both abducens and the left oculomotor nerves. [journals.viamedica.pl]
- Recurrent Headache
When the TMZ treatment started, the patient complained about recurrent headaches and blindness of the right eye (earlier, after the neurosurgery, she had light sensitivity and could see the contours of objects). [hindawi.com]
Many reports have stressed the role of close monitoring of patients who undergo TBA because of the life-threatening nature of Nelson syndrome . 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  . 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 . MRI of the endocranium is a highly useful study that identifies a sellar mass  . 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 .
- Barber TM, Adams E, Ansorge O, Byrne JV, Karavitaki N, Wass JA. Nelson's syndrome. Eur J Endocrinol. 2010;163(4):495-507.
- 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.
- Munir A, Newell-Price J. Nelson's Syndrome. Arq Bras Endocrinol Metabol. 2007;51(8):1392-1396.
- Pereira MA, Halpern A, Salgado LR, et al. A study of patients with Nelson's syndrome. Clin Endocrinol (Oxf). 1998;49(4):533-539.
- 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.
- 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.