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Nelson Syndrome

Cushing's Syndrome

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.


Presentation

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]
  • 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]
  • 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]
  • One of the main signs is weight gain and more body fat, such as: increased fat on your chest and tummy, but slim arms and legs a build-up of fat on the back of your neck and shoulders – known as a "buffalo hump" a red, puffy, rounded face Other symptoms[nhs.uk]
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]
  • The most common cause of cushingoid features is iatrogenic corticosteroid use, while some herbal preparations can also increase circulating corticosteroid levels leading to Cushing syndrome.[ncbi.nlm.nih.gov]
  • Most children and adolescents with CD have a typical cushingoid appearance. Subtle, subclinical or cyclical features are uncommon. In our patient series, all 33 CD patients experienced facial changes and weight gain.[scielo.br]
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]
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]
  • 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]
  • weakness, muscle atrophy Menstrual disorders Striae rubrae, acne, edema Mental changes, headache Hyperpigmentation of the skin is a sign for ACTH-production (via POMC).[urology-textbook.com]
  • weakness Depression, anxiety and irritability Loss of emotional control Cognitive difficulties New or worsened high blood pressure Headache Increased pigmentation of the skin Bone loss, leading to fractures over time In children, impaired growth When[mayoclinic.org]
Hyperpigmentation
  • Furthermore, hyperpigmentation of scars, the buccal mucosa, and even tongue might be observed.[symptoma.com]
  • 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]
  • The syndrome that now bears his name was characterized by hyperpigmentation, a sellar mass, and increased plasma ACTH levels. The treatment of Cushing disease has changed drastically since the 1950s, when the choice was adrenalectomy.[ncbi.nlm.nih.gov]
  • It is characterized by excess adreno-corticotropin secretion and hyperpigmentation of the skin and mucus membranes. The authors present a comprehensive review of the pathophysiology, diagnosis, and management of NS.[ncbi.nlm.nih.gov]
Hyperpigmentation
  • Furthermore, hyperpigmentation of scars, the buccal mucosa, and even tongue might be observed.[symptoma.com]
  • 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]
  • The syndrome that now bears his name was characterized by hyperpigmentation, a sellar mass, and increased plasma ACTH levels. The treatment of Cushing disease has changed drastically since the 1950s, when the choice was adrenalectomy.[ncbi.nlm.nih.gov]
  • It is characterized by excess adreno-corticotropin secretion and hyperpigmentation of the skin and mucus membranes. The authors present a comprehensive review of the pathophysiology, diagnosis, and management of NS.[ncbi.nlm.nih.gov]
Linea Nigra
  • The degree of pigmentation varies depending on the racial origin of the child and the serum concentrations of adrenocorticotropin (ACTH). [8] 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. [1] [2] [3] [4] [7] Assessment of the pubertal stage [1] [2] [3] [4] [6] 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]
Skin Atrophy
  • atrophy, neuropsychiatric dysfunction, osteoporosis, truncal–central obesity, weight gain–water retention, moon face, weakness, fatigue, backache, headache, thirst, urination, DM, osteoporosis Lab Hypersecretion of cortisol, loss of the usual circadian[medical-dictionary.thefreedictionary.com]
  • She had become hypertensive (140/110 mm Hg) with the development of moon face, truncal obesity (weight gain of 4 kg in a 2-year period), reddish striae on her abdomen and skin atrophy when admitted in December 2007.[nature.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]
  • 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]
  • 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[symptoma.com]
  • Signs & Symptoms Symptoms of Nelson syndrome include intense skin pigmentation, headaches, visual field disturbances and the cessation of menstrual periods in females.[rarediseases.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]

Workup

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].

Small Liver
  • Liver disease is suggested if hepatomegaly, small liver, splenomegaly, or peripheral signs of liver disease are present.[emedicine.medscape.com]

Treatment

  • 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]
  • Currently available treatments include surgical, radiation, and medical therapy.[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]
  • The treatment of Cushing disease has changed drastically since the 1950s, when the choice was adrenalectomy. Thus, the occurrence, diagnosis, and treatment of Nelson syndrome have changed as well.[ncbi.nlm.nih.gov]
  • The primary treatment for Nelson's syndrome is transsphenoidal surgery. Other stand-alone therapies, which in many cases have been used as adjuvant treatments with surgery, include radiotherapy, radiosurgery, and pharmacotherapy.[ncbi.nlm.nih.gov]

Prognosis

  • 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]
  • 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]
  • 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]
  • , prevention, prognosis, and additional useful information HERE .[dovemed.com]
  • 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]

Etiology

  • Treatment and prognosis Management depends on the specific etiology 6.[radiopaedia.org]
  • 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]
  • 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]
  • ACTH-dependent cortisol excess due to a pituitary adenoma is called Cushing disease, and it is responsible for 80% of endogenous Cushing syndrome. [1] [2] [3] Etiology There are two main etiologies of Cushing syndrome: endogenous hypercortisolism and[ncbi.nlm.nih.gov]
  • Lacroix, Classic and Recent Etiologies of Cushing??s Syndrome, Treatments in Endocrinology, 10.2165/00024677-200201020-00002, 1, 2, (79-94), (2002). Jeffrey A. Norton, Michelle Li, Jennifer Gillary and Hop N.[doi.org]

Epidemiology

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

Pathophysiology

  • OBJECTIVE: To review the pathophysiology and therapeutic modalities availble for Nelson syndrome. METHODS: We reviewed the current literature including managment for Nelson syndrome.[ncbi.nlm.nih.gov]
  • The authors present a comprehensive review of the pathophysiology, diagnosis, and management of NS. Corticotroph adenomas in NS remain challenging tumors that can lead to significant rates of morbidity and mortality.[ncbi.nlm.nih.gov]
  • 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]
  • His research focuses on the pathophysiology of endocrine and metabolic regulation, with a special focus on clinical neuroendocrinology.[books.google.com]

Prevention

  • Prophylactic radiotherapy at the time of bilateral adrenalectomy can prevent Nelson's syndrome (protective effect).[ncbi.nlm.nih.gov]
  • Taking medicines to prevent bone loss. This can help reduce the risk of fractures if you develop osteoporosis. Taking medicine to decrease the amount of glucocorticoid medicine that you need.[medlineplus.gov]
  • External radiation immediately after surgery is thought to prevent Nelson's syndrome.[endocrinesurgeon.co.uk]
  • At the time of discharge, the patient should have a dietary consult and how to prevent osteoporosis. The pharmacist should educate the patient on the prevention of peptic ulcer disease, diabetes, and weight gain.[ncbi.nlm.nih.gov]
  • Getting treated early can help prevent any long-term effects of Cushing syndrome. If you use inhaled steroids, you can decrease your exposure to the steroids by using a spacer and by rinsing your mouth after breathing in the steroids.[medlineplus.gov]

References

Article

  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.

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Last updated: 2019-06-28 12:19