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].

• 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]

  gain, sleep disturbance, and/or depression. [amboss.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]

• Cushingoid

  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]

  […] 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]

  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]

  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]

• Leg Swelling

  […] become skinny Increased body hair – especially on the arms, face, and around the belly button Thinning skin Acne Easy bruising Leg swelling Purple stretch marks on the abdomen and legs Constantly rosy cheeks Symptoms: Diabetes – high blood sugar levels [columbiasurgery.org]

• 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]

• Hyperpigmentation

  Nelson syndrome - hyperpigmentation, third nerve damage, and enlarging sella turcica caused by pituitary adenomas that become symptomatic following adrenalectomy. [medical-dictionary.thefreedictionary.com]

  Abstract Nelson syndrome is a rare cause of generalized mucocutaneous hyperpigmentation. [ncbi.nlm.nih.gov]

  Furthermore, hyperpigmentation of scars, the buccal mucosa, and even tongue might be observed. [symptoma.com]

  However, after adrenalectomy, the presence of hyperpigmentation and ACTH levels above 154 pmol/l had positive predictive value for the development of Nelson's syndrome. [onlinelibrary.wiley.com]

• Headache

  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. [yourhormones.info]

  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]

• Paresis

  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 [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].

As the radiation level was below 1Gy to this area, it is unlikely that the GKR treatment itself induced the malignant tumor. CONCLUSION: In patients with NS, GKR is an effective adjuvant treatment, carrying relatively few adverse effects. [ncbi.nlm.nih.gov]

Treatment options include: Surgery Radiation therapy Surgery for Nelson's Syndrome Surgical removal of the pituitary adenoma is the ideal treatment; however, it is not always possible. [pituitary.ucla.edu]

Major treatment options for Cushing's disease and Nelson's syndrome (not all of the possible treatments for Cushing's disease are included). [doi.org]

Early detection and intervention contributes to a more positive prognosis. Prognosis, however, is not good for enlarged, invasive macroadenomas where diagnosis and treatment were delayed. [visualdx.com]

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]

Prognosis The prognosis is good, providing there is early recognition. Co-ordination between surgeons and radiotherapists is important. Postoperative aftercare, with adequate long-term monitoring and replacement of hormones, is vital. [patient.info]

NELSON'S SYNDROME: INCIDENCE AND PROGNOSIS Corresponding Author Department of Endocrinology, Centre of Postgraduate Medical Education, Department of Surgery and Department of Neurosurgery, Academy of Medicine, Warsaw, Poland A. A. [onlinelibrary.wiley.com]

Treatment and prognosis Surgical resection of the pituitary adenoma is the gold-standard treatment for Nelson syndrome. If neurosurgery cannot be performed, radiation therapy is the next best management option. [radiopaedia.org]

Treatment and prognosis Management depends on the specific etiology 6. [radiopaedia.org]

Etiology Exogenous (iatrogenic) Cushing's syndrome Hypercortisolism as a result of prolonged glucocorticoid therapy Most common cause of hypercortisolism Endogenous Cushing's syndrome Types Primary hypercortisolism (ACTH-independent Cushing's syndrome [amboss.com]

Cushing syndrome Hypercortisolism A condition characterized by excess corticosteroids, due either to an hypersecretion of cortisol by a hyperfunctioning or neoplastic adrenal cortex, or due to exogenous corticosteroids Etiology Exogenous coticosteroid [medical-dictionary.thefreedictionary.com]

Najavits Developmental Perspective of Substance Use Disorder Etiology Ralph E. Tarter, Michelle Horner, and Ty Ridenour III. [apa.org]

Epidemiology Prevalence 5–6/100.000 Most often women in the 3rd and 4th decade of life Causes (Etiology) of Cushing's Syndrome ACTH-dependent Cushing's Syndrome (Overproduction of ACTH): Pituitary adenoma (Cushing's disease) Paraneoplastic ACTH production [urology-textbook.com]

In the present paper, clinical and epidemiological features of Nelson's syndrome, as well as its treatment modalities, are reviewed. Keywords : Nelson's syndrome; Cushing's syndrome; Cortisol; ACTH; Dexamethasone; Adrenal; Pituitary; Tumour. [scielo.br]

Epidemiology [ 1 ] Nelson's syndrome is rare. [patient.info]

Causes Differentiating Nelson's syndrome from Other Diseases Epidemiology and Demographics Nelson's syndrome is rare because bilateral adrenalectomy is now only used in extreme circumstances. [wikidoc.org]

An epidemiologic and clinical evaluation of Guillain- Barre syndrome reported in association with the administration of swine influenza vaccines. Am J Epidemiol. 1984;119:841–879 Langmuir AD. [vaccinarsinsardegna.org]

Epidemiology Frequency Nelson syndrome is a rare disorder, making accurately determining its incidence difficult. [emedicine.com]

In this article, the authors review the clinical manifestations, pathophysiology, diagnostic criteria, and efficacy of multimodal treatment strategies for Nelson's syndrome. [ncbi.nlm.nih.gov]

Malek, Nelson syndrome: comprehensive review of pathophysiology, diagnosis, and management, Neurosurgical Focus, 23, 3, (1), (2007). Daniel F. [doi.org]

Retrieved 2015-11-05. ^ a b c d e f g h i j k l "Nelson Syndrome: Background, Pathophysiology, Epidemiology". 2017-05-03. ^ "the definition of nelson syndrome". Dictionary.com. [en.wikipedia.org]

His research focuses on the pathophysiology of endocrine and metabolic regulation, with a special focus on clinical neuroendocrinology. [books.google.com]

Prophylactic radiotherapy at the time of bilateral adrenalectomy can prevent Nelson's syndrome (protective effect). [ncbi.nlm.nih.gov]

External radiation immediately after surgery is thought to prevent Nelson's syndrome. [endocrinesurgeon.co.uk]

Some experts believe that this compression may be prevented, at least in some people, by radiation therapy to the pituitary gland. If necessary, Nelson syndrome can be treated with radiation therapy or surgical removal of the pituitary gland. [msdmanuals.com]

Finally, contrary to previous reports, pituitary irradiation before adrenalectomy did not prevent Nelson's syndrome. [annals.org]

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.