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El Síndrome de Nelson es una enfermedad endocrina que

consiste en la aparición de un tumor productor de ACTH en

la hipófisis tras practicar una adrenectomía bilateral.

Contenido

[ocultar] 

1 Etiología 

2 Clínica 

3 Tratamiento 

4 Referencias 

[editar]Etiología

Al extirpar las glándulas suprarrenales1 (a causa de un síndrome de

Cushing2 u otras causas) se crea una importante depleción

decortisol en sangre, por lo que se elimina el mecanismo que inhibe

las células productoras de ACTH de la hipófisis, que a su vez

proliferan y crecen, llegando a formar un verdadero tumor productorde ACTH. Aunque son tumores benignos, su crecimiento es rápido

y pueden alcanzar un gran tamaño.

[editar]Clínica

La gran hipersecreción de ACTH puede ocasionar intensa

hiperpigmentación cutánea y mucosa. La clínica por compresión

puede incluir cefalea, defectos campimétricos y, en ocasionesafectación, de pares craneales (en especial el II, III, IV y VI).

3 4 

[editar]Tratamiento

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La primera opción terapéutica es la cirugía seguida de radioterapia. 

Si no es efectiva puede ofrecerse tratamiento médico paliativo con

distintos fármacos.5 

Nelson's syndromeFrom Wikipedia, the free encyclopedia

Nelson's syndrome

Classification and external resources 

ICD-10  E24.1 

DiseasesDB   8863 

eMedicine   ped/1558

Nelson's syndrome is the rapid enlargement of a pituitary adenoma that occurs after the removal of

both adrenal glands.[1]

 

Contents

[hide] 

1 Pathophysiology 

2 Presentation 

3 Treatment 

4 History 

5 References 

[edit]Pathophysiology

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Removal of both adrenal glands, or bilateral adrenalectomy, is an operation for Cushing's syndrome. Removal

of both adrenals eliminates production of cortisol, and the lack of cortisol's negative feedback can allow any

preexisting pituitary adenoma to grow unchecked. Continued growth can cause mass effects due to physical

compression of brain tissue, along with increased production ofadrenocorticotrophic hormone (ACTH)

and melanocyte stimulating hormone (MSH). The accompanying increase in MSH is due to ACTH and MSH

being derived from a common precursor peptide, known as proopiomelanocortin (POMC).

[edit]Presentation

The common signs and symptoms include muscle weakness and skin hyperpigmentation due to excess MSH.

Nelson's syndrome is now rare because bilateral adrenalectomy is now only used in extreme circumstances.[2]

 

[edit]Treatment

Pituitary surgery is performed in some cases. The risk can also be minimized by pituitary irradiation.

[edit]History

The condition is named for the American endocrinologist Dr Don Nelson, who first reported on the phenomenon

in 1960.[3]

 

HISTORY AND DEFINITION 

NELSON AND COLLEAGUES made the original description of a pituitary macroadenoma and

high plasma ACTH, in a patient with Cushing's syndrome who had undergone bilateraladrenalectomy, in 1958 (1). Since that time there have been numerous similar case reports

and series (2-8). Nelson's syndrome remains one of the major worries facing clinicians when

considering managing patients with Cushing's disease by bilateral adrenalectomy. Of all of the features of Nelson's syndrome, the one that causes most concern is the development of 

a locally aggressive pituitary tumour, which, unusually for pituitary disease, mayoccasionally cause death from the tumour itself. This feature is especially pertinent given

the increasing use in Cushing's disease of laparoscopic bilateral adrenal surgery as a highlyeffective treatment modality to control cortisol-excess (9,10). 

Despite numerous studies and reports, there is no formal consensus of what defines

Nelson's syndrome. This is especially true in recent years since imaging with MRI allows

precise documentation of any tumour progression, whereas historically patients presentedwith masses large enough to be found with CT, simple sella tomography, or with neuro-opthalmic complications (11). Moreover, widespread access to reliable plasma ACTH assays

has greatly facilitated monitoring of patients. Thus, some will define Nelson's syndrome

according to the classical description with an evolving pituitary mass, whereas others willrely on increasing plasma ACTH levels, even in the absence of a clear pituitary mass lesion

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on MRI (12). These factors need to be borne in mind when considering the reports of 

Nelson's syndrome, as there is great heterogeneity, and it is likely that overall the modern'Nelson's syndrome' represents a different disease entity from that of the last century. 

INCIDENCE AND NATURAL HISTORY 

The reported incidence of Nelson's syndrome after bilateral adrenalectomy for Cushing's

disease is 8–38% (11). This wide variation in incidence is as likely to be due to differencesin definition as much as bias of case mix in different centres. There is also great variation inthe latency of onset from adrenalectomy to the diagnosis of Nelson's syndrome, ranging

from a few months to 24 years, or more, emphasising the need for careful life-long follow-up (10,11). 

PATHOPHYSIOLOGY 

Despite increased knowledge of the pathophysiology of corticotroph tumours, little is knownof the pathology of the corticotroph tumours that progress to Nelson's syndrome (13). It isunclear whether the adrenalectomy and the lowering of the cortisol feedback at the pituitary

itself stimulates tumour growth, or whether Nelson's syndrome develops in tumours that

were programmed to behave in an aggressive fashion from the outset. Given that not allpatients with Cushing's disease develop Nelson's syndrome following bilateraladrenalectomy, the reduced feedback from adrenal cortisol secretion cannot be the only

factor, and indeed it is likely that the tumours that show progression with clinicalconsequence are a sub-set with an aggressive phenotype. 

CLINICAL FEATURES 

Patients may present with the physical and hormonal consequences of an expandingpituitary mass and, or, the effects of ACTH hyper-secretion. Mass effects includecompression of the optic apparatus and visual field defects, headache, external

ophthalmoplegias, and hypopituitarism (11). Deep cutaneous pigmentation is frequently

present, and is due to ACTH stimulation of the melanocortin 1 receptors on melanocytes inthe skin. Pigmentation is generalised, but may also occur in cutaneous scars and sites of abrasion, and in the buccal mucosa and tongue. 

PREDICTIVE FEATURES 

Given the concern over the onset of Nelson's syndrome after adrenalectomy, numerous

studies have attempted to identify factors that predict its onset. The presence of tumour

either at surgery or on imaging has been shown to predict onset, especially if there are

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aggressive characteristics or macroadenoma (7,12). Young age at the time of 

adrenalectomy has been suggested to be predictive in some studies (14-17), but this is not

a uniform finding in all (11). The duration of Cushing's disease is predictive in some series(18), but again not in all. One area that has attracted considerable interest is whether

pituitary radiotherapy either diminishes the chance of developing Nelson's syndrome, or atleast delays its onset: it has not been found to be of benefit in several series (6,7,16),

whereas other data suggest that prophylactic pituitary radiotherapy at the time of adrenalectomy reduces the risk of progression to Nelson's syndrome (12). Some of the

difficulty in establishing the influence of these various factors is the heterogeneity of theseries in question, not least of which because of the wide time-frame over which they havebeen variously reported, and the improvements in recent years in pituitary imaging. 

More recently, some of these areas of controversy have been addressed by a modern, largeand carefully reported series from Cochin Hospital, Paris, France (19). In this single centre

series 53 patients treated by bilateral adrenalectomy for Cushing's disease were followed.

All patients were assessed on follow up after adrenalectomy by clinical assessment, pituitaryMRI and plasma ACTH. In contrast to other reports, any corticotroph tumour progression, as

determined by pituitary MRI, was reported. The independent factors that predictedprogression of corticotroph tumours included short duration of Cushing's disease and a high

plasma ACTH, measured at 0800h, 20h after the last dose of glucocorticoid. In the yearfollowing adrenalectomy an absolute increment of 100 pg/ml (22 pmol/l) was predictive of 

progression of the corticotroph tumour. Pituitary tumour on MRI at the time of adrenalectomy was also a factor predicting progression, but this was not an independent

variable when these other two variables are taken into account. Interestingly, with a median

follow up of 4.6 years (maximum follow up of 13.5 years) there was evidence of tumourprogression on MRI in 50% of the patients followed, but in only one patient was there a

complication related to the pituitary tumour itself: a short-lived oculomotor nerve palsy.These are important data as they indicate that whilst corticotroph tumour progression on

MRI is common, the clinical consequence of this appears to be less worrisome than in someolder series, at least with this duration of follow-up. An even longer-term follow up of these

data are needed to give further reassurance. 

MONITORING 

Whilst the latency of onset from the time of bilateral adrenalectomy to pituitary tumourprogression is usually within 3 years (19), progression may occur much later, and it is

crucial to continue to carefully assess for tumour progression life-long. Whilst no formalguidelines can be set out, it is reasonable to perform pituitary MRI scans before

adrenalectomy and then 6–12 months after adrenalectomy, and then yearly. As indicated

above measurement of plasma ACTH is essential in monitoring. As indicated above this maybe done by measurement of the 0800h plasma ACTH, 20h after the last dose of glucocorticoid and before the morning dose of glucocorticoid, with an increment in the value

compared to a previous value of 100 pg/ml being significant (19). A potential drawback of this type of monitoring is that high plasma ACTH levels are found in patients with primaryadrenal insufficiency without pituitary pathology. In patients with Addison's disease plasma

ACTH measured before morning glucocorticoid is frequently very elevated, but this

suppresses rapidly 120 minutes after morning glucocorticoid (20,21). In contrast, thosewith Nelson's syndrome fail to show incomplete suppression, and a cut-point of 200 pg/mlappears to be useful to define Nelson's syndrome (12). Thus, since the patient is attending

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for assessment anyway, measurement of plasma ACTH at 0800h, 20h after the last dose of 

glucocorticoid and before that morning's dose and then 120 minutes after the morning

glucocorticoid may give more consistent results when monitoring for Nelson's syndrome: anincrement in the pre-morning glucocorticoid plasma ACTH of 100 pg/ml compared to a

previous measurement, or failure to suppress plasma ACTH to less than 200 pg/ml 2 hoursafter morning glucocorticoid should prompt further assessment with imaging. Such an

assessment can be performed, if needed, on a more frequent basis than pituitary MRI. Treatment 

Observation 

If there is MRI evidence of limited tumour progression but with no anatomical compromise,observation and repeat imaging (3–6 months) is an acceptable strategy. 

Surgical  

Pituitary surgery may be performed for corticotroph tumour progression if the anatomy is

favourable for such an approach (22,23). Given that the risk is of further tumour expansionan attempt at complete hypophysectomy has been recommended, and is associated with agood long-term control of local tumour growth and lowering of plasma ACTH levels, but at a

cost of increased hypopituitarism, including diabetes insipidus (22). Despite pituitarysurgery some patients will have further progression alternative or adjuvant therapy isindicated (22,23). 

Radiotherapy  

The use of fractionated external radiotherapy is well documented in the treatment of established Nelson's syndrome (24). Over time radiotherapy lowers plasma ACTH levels, but

is associated with increases in long-term hypopituitarism. Whilst radiotherapy may control

tumour growth in many instances, some tumours may continue to expand. More recently,large series treated by stereotactic radiotherapy, delivered by the gamma knife have been

reported (25-27). In cases of a clear anatomical target this too is an effective modality of 

therapy, and may also be used after fractionated radiotherapy, as long as the dose to theoptic apparatus can be kept within safe limits. 

Medical  

There has been a long interest in medical therapy to attempt to control plasma ACTH andtumour growth. Unfortunately, apart from isolated case reports there is no medical therapy

that has been shown to consistently achieve these goals. Disappointing or variable results

have been seen with sodium valproate (28-33), and currently licensed somatostatin

analogues (34-37), although the multi-ligand analogue SOM230 (pasireotide) may prove of benefit (38). There are only occasional responses found with dopamine agonists such as

cabergoline (39-42). Recent interest has focused on the use of PPAR gamma agonists in

Nelson's syndrome. One report showed that two out of three patients responded torosiglitazone with lowering of plasma ACTH levels, but one of these subsequently escaped

(43). Rosiglitazone at maximum licensed doses has not been found to be effective (44). We

have shown recently that even higher than licensed doses of rosiglitazone (12 mg/day) arenot effective in reducing plasma ACTH levels, and by inference tumour growth (45) (figure1). The orally active alkylating agent temozolomide has been shown to be highly effective in

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a few aggressive pituitary tumours and in lowering prolactin and controlling tumour growth

in highly aggressive prolactinomas (46-48). Although there are no reports of its use in

Nelson's syndrome, temozolomide could be considered in patients with Nelson's syndromenot responding to other modalities of therapy. One major drawback of this agent is highcost. 

CONCLUSIONS 

Progression of corticotroph tumours, as detected by MRI, can be expected in up to half of 

patients undergoing bilateral adrenalectomy for Cushing's disease. Whilst this is a worrying

statistic, and Nelson's syndrome should not be underestimated, with modern follow-upincluding careful pituitary MRI and plasma ACTH, the actual numbers of patients that come

to harm appears to be low. Thus, the risks associated with Nelson's syndrome need to bebalanced against the risk of uncontrolled Cushing's disease, and in many cases may be

acceptable. This is likely to be especially true if the duration of Cushing's syndrome isrelatively long and no tumour is visible on pituitary MRI before adrenalectomy. 

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Nelson’s syndrome is the name given to theenlargement of a pituitary gland tumour associated

with excess secretion of adrenocorticotropic hormonefollowing the surgical removal of both adrenal glands,usually to treat Cushing’s disease. 

What is Nelson’s syndrome? 

Nelson’s syndrome is the term used to describe anenlargement of an adrenocorticotropic hormone -producingtumour in the pituitary gland, following surgical removal of both adrenal glands in a patient with Cushing’s disease. Thesyndrome is the name given to the effects of the enlargingtumour in the pituitary gland. The tumour produces an excessof a hormone called adrenocorticotropic hormone which isinvolved in the production of other steroid hormones (suchas cortisol). Large tumours can sometimes also invade areasaround the pituitary gland which may cause a reduction inlevels of other hormones, visual problems or it may affectnerves and blood vessels. It can also cause an increase in skinpigmentation, so patients may look as if they have a suntan.

What causes Nelson’s syndrome? 

Nelson’s syndrome results from a reduction in feedback of steroid hormones and is a consequence of removal of theadrenal glands (an adrenalectomy). In healthy individuals, thepituitary gland stimulates the adrenal glands to producesteroid hormones (such as cortisol) through production of thehormone called adrenocorticotropic hormone. These steroidhormones then act on the pituitary gland to stop it producingmore adrenocorticotropic hormone. This feedback system

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means that levels of the hormones are kept within the normalrange. In patients who have had an adrenalectomy, thisnegative feedback system does not work and the pituitarytumour may expand and produce more adrenocorticotropic

hormone.

What are the signs and symptoms of Nelson’s syndrome? 

The signs and symptoms of Nelson’s syndrome result from theenlarged tumour and the increased adrenocorticotropichormone production. The enlarged tumour compresses therest of the pituitary gland and therefore reduces the amountof other hormones produced. This can result in poorfunctioning of thethyroid gland (hypothyroidism), a lackof  growth hormone (growth hormone deficiency) anddeficiencies of the gonadotrophic hormones, luteinisinghormone and follicle stimulating hormone. The tumour canalso grow upwards from the pituitary gland and compress vitalnerves involved in vision. This may result in blind spots in thevision or, occasionally, complete blindness. The tumour maygrow to each side of the pituitary gland and affect importantnerves that are found in this area. This can result in difficultymoving the eyes, double vision or numbness on the face.Occasionally patients will also experience a headache as aresult of the enlarging tumour.

The raised levels of adrenocorticotropic hormone act on cells

in the skin to increase pigmentation. This results in darkenedor tanned skin, especially in skin creases. The tannedcomplexion is not confined to areas exposed to the sun andfrequently affects the inside of the mouth and old scars.

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How common is Nelson’s syndrome? 

Surgical removal of both adrenal glands to treat Cushing’sdisease is rarely performed nowadays due to improvements inother treatment options for this condition. However, inpatients who do require this operation, Nelson’s syndromedevelops in 20% to 40% of cases.

Is Nelson’s syndrome inherited? 

Nelson's syndrome only occurs in patients with Cushing’sdisease if they have had both adrenal glands removed. Most

cases of Cushing’s disease are not inherited, but, rarely, thesetumours can be part of a genetic condition such as multipleendocrine neoplasia.

How is Nelson’s syndrome diagnosed? 

Nelson’s syndrome is suspected in patients who havepreviously undergone surgical removal of the adrenal glands

when they develop symptoms suggestive of pituitaryenlargement such as headache, visual disturbance, skinpigmentation or other symptoms resulting from pituitaryhormone deficiencies. The doctor will request blood tests tolook for a high adrenocorticotropic hormone level along withpossible low levels of other pituitary hormones. A scan of thepituitary gland will be organised to assess the growth of thetumour and to look for effects on other areas in the brain

around the pituitary gland. Often a visual field test will beorganised to check for loss of vision. Frequently these testswill be performed as an outpatient, but occasionally thedoctor may advise an admission to hospital if treatment isrequired urgently.

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How is Nelson’s syndrome treated? 

Nelson’s syndrome is most frequently treated by surgicalremoval of the pituitary tumour, and this is usually the case if there is visual impairment or other evidence of significantgrowth of the tumour outside the pituitary gland.Occasionally, medical treatment aimed at shrinking thetumour may be suggested and radiotherapy may also be used,especially if surgery is not felt to be safe.

Hormone deficiencies may resolve after removal of thetumour, but these will be treated if symptoms persist. This

may involve thyroid hormone replacement, growth hormonereplacement and testosterone oroestrogen replacement. Mostpatients with Nelson’s syndrome will already be taking steroidreplacement therapy.

Are there any side-effects to thetreatment?

Surgery is generally safe and well tolerated, although asurgeon will go through the particular risks of the operationwith a patient. Medications that are currently used to inducetumour shrinkage include dopamine agonists and these can beassociated with headaches, dizziness and gastrointestinalsymptoms such as constipation.

Radiotherapy can be associated with damage to areas around

the pituitary gland. The risks and benefits of this treatmentwill need to be discussed with a specialist in radiationtreatment.

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What are the longer-term implications of Nelson’s syndrome? 

The successful treatment of Nelson’s syndrome depends onthe involvement of specialists including an endocrinologist, aspecialist pituitary surgeon and occasionally, a radiotherapist.The outcome is good if the condition is detected early, andthis is one of the reasons for long-term follow-up of patientswho have had surgical removal of their adrenal glands.

It is very important that any hormone deficiencies arediagnosed and treated properly so as to avoid long-termcomplications such as osteoporosis, heart diseaseand depression 

Nelson's Syndrome

General Information 

  Nelson’s syndrome is an iatrogenic condition (caused by a physician)

that occurs as a result of treating Cushing's diseasepatients by

removal of both adrenal glands.

  In Cushing’s disease, blood cortisol is elevated due to excessive

secretion of the hormone ACTH by a pituitary adenoma. ACTH

signals the adrenal gland to produce cortisol. In the past, the

identification of a pituitary adenoma was more difficult, and therefore

patients underwent removal of the adrenal glands in order to lower

the blood levels of cortisol. Because the pituitary tumor was not

removed, the tumor enlarged and excessive production of ACTH

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continued. The hormone ACTH, in excessive amounts, can stimulate

pigment production in the skin. Nelson’ syndrome develops within

one to four years of surgery in about 15 percent to 25 percent of

patients.

Symptoms 

  A key finding is darkening of skin color and increased pigmentation of

nevi.

  Because ACTH-secreting tumors are typically aggressive and

invasive, patients may develop large tumors resulting in visual loss,

pituitary failure and headache.

Diagnosis 

  The clinical history and skin pigmentation findings are usually

obvious.

  Hormonal tests generally show elevated ACTH levels in the blood but

low or normal levels of cortisol.

  Magnetic Resonance Imaging (MRI) or computed tomography (CT)

scan is important for the identification of a pituitary adenoma.

Treatment 

  Transsphenoidal surgery is the primary option but not always

effective. Radiotherapy, preferably with stereotactic radiation, controls

tumor growth in the majority of patients with residual tumor growth

after surgery.

The Neuro-ICU cares for patients with all types of neurosurgical and

neurological injuries, including stroke, brain hemorrhage, trauma and

tumors. We work in close cooperation with your surgeon or medical doctor

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with whom you have had initial contact. Together with the surgeon or

medical doctor, the NeuroICU attending physician and team members

direct your family member's care while in the ICU. The NeuroICU team

consists of the bedside nurses, nurse practioners, physicians in specialtytraining (Fellows) and attending physicians.

Fisiopatología [ 1 ] Esto puede considerarse como la enfermedad iatrogénica. La mayoría

de los casos ocurren en pacientes con síndrome de Cushing que tienen

una hormona adrenocorticotropa (ACTH) macroadenoma hipofisario

secretor. Tales pacientes tienen niveles elevados de cortisol , que

suprimen la producción de hormona liberadora de corticotropina

(CRH) de la glándula pituitaria. El mecanismo de retroalimentación

cortisol normal del hipotálamo-pituitario-adrenal (HPA) El eje está

perturbado por lo tanto, con pérdida del ritmo circadiano y la

producción excesiva de cortisol. [ 2 ] Una vez que el paciente ha tenido

una bilateral adrenalectomía , los niveles de cortisol bajan a la

normalidad y la aumenta la producción de CRH. Esto a su vez da

lugar a veces en el crecimiento descontrolado de la adenoma

pituitario , que causa el síndrome de Nelson. Mutaciones reguladoras

de genes y las mutaciones en el receptor de glucocorticoides también

pueden desempeñar un papel. compresión por el tumor puede inhibir

la liberación de otras hormonas pituitarias. El nivel alfa de hormonaestimulante de melanocitos (a-MSH) es también muy alto. Este es un

derivado del péptido precursor de ACTH que es derived.The signos y

síntomas se derivan de la presión del tumor en las estructuras

circundantes y la pérdida secundaria de otras hormonas pituitarias. 

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Epidemiología [ 1 ] 

El síndrome de Nelson es una enfermedad rara que parece estardisminuyendo aún más.Esto puede estar relacionado con una mejor

gestión de síndrome de Cushing y adenomas pituitarios. Cirugía de la

hipófisis se utiliza más a menudo, pero todavía hay un lugar definido

para suprarrenalectomía. Incluso en las primeras series, sólo el 20-

40% de los pacientes con un adenoma hipofisario que tenía

adrenalectomía bilateral desarrollado el síndrome de Nelson. Las tasas

de los estudios posteriores varían desde 8 hasta 44%. tumores

productores de ACTH son más comunes en mujeres jóvenes o demediana edad y por lo tanto son el grupo con mayor riesgo de

síndrome de Nelson. 

Los factores de riesgo 

El embarazo es un factor predisponente. 

Presentación[ 1 ] 

Historia 

  En por lo menos 99% de los casos existe una historia de la

adrenalectomía.

  Los dolores de cabeza son comunes con los tumores hipofisarios y

son probablemente el resultado del estiramiento de la sellae

diaphragma. Características del aumento de la presión

intracraneal ocurren de forma tardía y son poco frecuentes, ya que

requieren un tumor lo suficientemente grande como para obstruir

el flujo del líquido cefalorraquídeo (LCR).

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  Hipopituitarismo se produce cuando el sistema portal hipotálamo-

pituitaria es interrumpido o tejido pituitario normal es destruido

por el tumor:

o  Puede ser parcial en lugar de total. La hipófisis anterior es más

complicado que a menudo la hipófisis posterior.

o  A menudo deficiencia de la hormona es incompleta.

o  En niños y adolescentes, el crecimiento de la nota y la edad de la

pubertad.

o  En todos los pacientes, preguntar por los síntomas

de hipotiroidismo , la presencia degalactorrea y poliuria ypolidipsia. Los dos últimos se deben a la diabetes insípida .

o  El síndrome de Cushing con frecuencia retrasa el crecimiento en

los niños, pero la operación debe devolverlo. Si no, se requiere una

investigación.

o  En las mujeres la amenorrea puede ser el primer signo de la

enfermedad de la hipófisis. Galactorrea es poco común en los

hombres, pero la hiperprolactinemia suele causar disfunción

eréctil .

  Defectos del campo visual debe ser consultado acerca. Pueden ser

demasiado insidioso que se ha dado cuenta y la prueba formal

puede ser requerida. El tumor también puede causar diplopía y

lesiones craneales con la participación de la oculomotor, troclear y

abducens nervios y también la rama oftálmica del trigémino.Examen 

  En niños y adolescentes, tenga en cuenta la altura y el peso.

  La hiperpigmentación suele ser evidente. Una linea nigra es a

menudo aparente. Esta es una línea oscura desde el pubis hasta el

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ombligo. Las cicatrices y areolas se pigmentan y, como en la

enfermedad de Addison , la pigmentación es más marcada en los

pliegues de las manos. Algunos pacientes desarrollan

hiperpigmentación después de adrenalectomía bilateral, pero no

desarrollan síndrome completo de Nelson. [ 3 ] 

  En los adolescentes puede haber características de retraso de la

pubertad . En las mujeres adultas puede haber alguna regresión de

los senos o galactorrea.

  El hipotiroidismo puede causar bradicardia , pero, si el reemplazo

suprarrenal es insuficiente, el examen del pulso puede mostrar paraser rápido pero filiforme. La presión arterial es baja con

insuficiencia esteroides, pero la hipertensión es común si los

niveles son elevados.

  Compruebe los movimientos oculares como los músculos oculares

externos se verán afectados si los nervios III, IV y VI pares

craneales están implicados. El daño a la rama oftálmica del nervio

trigémino perjudicará sensación sobre la frente y tal vez reflejo

corneal. 

  Compruebe el fondo de ojo, incluyendo la búsqueda de edema de

papila .

Investigaciones [ 1 ] 

  ACTH serán muy marcadamente elevados. Un estudio encontró

que una concentración de ACTH en plasma por encima de 154pmol / L se produjo sólo en los sujetos con síndrome de

Nelson. [ 4 ] La respuesta de la ACTH a la CRH también se ha

mejorado pero esto no es necesario para el diagnóstico.

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  Thyroxine niveles puede ser baja y hormona estimulante del

tiroides (TSH) también será baja.

  Las gonadotropinas y hormonas sexuales puede ser baja. En los

niños, la hormona del crecimiento se debe medir.

  Prolactina bien puede ser elevado pero no tan alta como en un

tumor productor de prolactina.

  Orina de la mañana temprana puede hacerse la prueba de la

gravedad específica y, si es menor que 1010, entonces las pruebas

para la diabetes insípida deben llevarse a cabo.

  MRI es útil para la detección y para controlar la progresión de unmicroadenoma. Una resonancia magnética con gadolinio de la

región pituitaria y produce imágenes excelentes paraselar. La

experiencia es, sin embargo, se requiere en la interpretación. [ 5 ] 

  Perimetría formal es necesaria para los campos visuales.

Diagnóstico diferencial [ 1 ] 

  Hipoplasia suprarrenal.

  La insuficiencia suprarrenal .

  Congénita hiperplasia suprarrenal .

  Craneofaringioma .

  Terapia con glucocorticoides y el síndrome de Cushing.

  El hipopituitarismo.

  Otras causas de la pigmentación de la piel - por ejemplo ictericia

(también afecta a la esclerótica) y hemocromatosis (más de uncolor de bronce, puede estar asociada con hepatomegalia y

esplenomegalia posiblemente).

Gestión [ 1 ] 

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El uso de la resonancia magnética ha permitido la detección de

tumores, mientras que todavía están en la etapa de

microadenoma. Esto ha facilitado el tratamiento médico temprano y

evita el uso de la cirugía en algunos casos. cabergolina (un antagonista

del receptor de la dopamina) ha sido utilizado con éxito para inducir laremisión en el síndrome de Nelson con disminución de los niveles de

ACTH y resolución de los microadenomas o

macroadenomas. Octreotide (a análogo de la somatostatina

administrada parenteralmente),ciproheptadina con y

sin bromocriptina y valproato de sodio también se han utilizado con

diversos grados de éxito, a pesar de que son más eficaces para

controlar los niveles de ACTH que reducir el tamaño del tumor. Un

estudio informó el uso exitoso de la temozolomidadespués de elfracaso del tratamiento con cirugía y radioterapia. [ 6 ] La radioterapia

puede ser la opción preferida para un adenoma invasivo que muestra

la progresión. Radioterapia fraccionada de haz externo o radiocirugía

estereotáctica puede ser utilizado dependiendo del tamaño y ubicación

del tumor. Las técnicas modernas con aceleradores lineales de alta

energía producen menos dispersión de radiación y el daño por lo

menos garantía. La radioterapia se asocia con graves problemas a

largo plazo, incluidas las dificultades de aprendizaje y memoria, dañovisual y el riesgo de tumores secundarios. Cirugía aún ofrece la mejor

probabilidad de cura para los tumores que son grandes, sobre todo si

se presiona sobre las estructuras circundantes, como la óptica

aparato. Transesfenoidal cirugía da el menor riesgo de lesión

del hipotálamo . Si el retiro es incompleta o cuando hay invasión, la

irradiación adyuvante reduce la tasa de recurrencia y mejora el

pronóstico. radiocirugía estereotáctica parece muy prometedor. El

tratamiento con protones en vez de fotones (rayos X) ha mejorado laeficacia y se ha efectuado una cura en algunos pacientes en los que la

cirugía no ha tenido éxito. [ 7 ] El uso de un bisturí de rayos gamma

para enfocar el haz de radioterapia ofrece un mayor

refinamiento. [ 8 ] evaluación a largo plazo de la función pituitaria es

necesario con la terapia de reemplazo hormonal como sea

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necesario. La presión arterial también deben ser monitoreados. 

Complicaciones [ 1 ] 

  Hipopituitarismo es muy común después del tratamiento,

especialmente si el tumor era grande.

  Cambio maligno en tumores productores de ACTH es raro.

  La extensión lateral del tumor puede invadir los senos cavernosos

con atrapamiento o compresión de los nervios craneales que lo

atraviesan. Estos incluyen el oculomotor, troclear y abducens

nervios y la división oftálmica del trigémino. Superior extensión

del tumor puede comprimir o invadir el aparato óptico o el

hipotálamo. Los síntomas visuales o signos dependen de donde el

tumor presiona.  Durante la embriogénesis, las células corticales suprarrenales

pueden migrar a lo largo de la línea de descendencia gonadal e

incluso puede ser secuestrado en el hilo de los testículos,

produciendo tejido adrenal resto. En el síndrome de Nelson, este

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tejido adrenal resto puede llegar a ser estimulado y, si en los

testículos, que puede causar el agrandamiento doloroso testicular y

oligospermia. En raras ocasiones, el tejido resto suprarrenal puede

producir suficiente cortisol para producir niveles normales o

incluso causar la recurrencia del síndrome de Cushing.

El pronóstico [ 1 ] El pronóstico es bueno, siempre y cuando haya un reconocimiento

temprano. La coordinación entre los cirujanos y radioterapeutas es

importante. Postoperatorio postratamiento, con un adecuado

monitoreo y reemplazo de hormonas, es vital. La información

epidemiológica es escasa, pero los datos disponibles sugieren que laincidencia está cayendo y que los tratamientos modernos están

ayudando a reducir la morbilidad y la mortalidad. [ 1 ] [ 9 ] 

Prevención 

  Adrenalectomía bilateral se dice que tienen un riesgo aceptable,

pero el seguimiento debe incluir la conciencia del síndrome de

Nelson. [ 10 ] [ 11 ] Control de nivel de ACTH pituitaria y la RM se

recomienda 3-6 meses después de la cirugía y después con

regularidad. A nivel de ACTH alta un año después de la

adrenalectomía se piensa que es predictivo de la progresión

tumoral corticotropos. [ 2 ] 

  Irradiación de la hipófisis de rutina después de la adrenalectomía

bilateral ya no se recomienda. [ 2 ] 

  Un estudio realizado en Italia encontró que la incidencia desíndrome de Nelson se relacionó significativamente con el nivel de

cortisol en orina pretratamiento y la presencia de adenoma

hipofisario en la cirugía pituitaria anterior. Cirugía pituitaria

anterior, incluso si no tiene éxito, parece proteger contra la

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recaída. Los resultados indican que las recaídas después de un

curado por cirugía pituitaria o irradiación es un problema clínico

considerable que aumenta con el tiempo. Los hallazgos sugieren la

importancia de la presentación clínica de los pacientes y subgrupos

indican que están en alto riesgo de recaída después de la cirugía

pituitaria o la irradiación y para el desarrollo de síndrome de

Nelson después de una adrenalectomía bilateral. [ 12 ] 

Historia Aunque el síndrome de Cushing se remonta al papel Harvey Cushing

en 1932, [ 13 ] el síndrome de Nelson se remonta sólo a 1960 [ 14 ] y el

autor no ha logrado llegar a las páginas de la web de la

'whonamedit.com'.