Download - Sindrome Nelson
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 1/22
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
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 2/22
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
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 3/22
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
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 4/22
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
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 5/22
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
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 6/22
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
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 7/22
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.
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 8/22
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
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 9/22
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.
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 10/22
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.
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 11/22
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.
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 12/22
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
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 13/22
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
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 14/22
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.
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 15/22
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).
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 16/22
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
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 17/22
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.
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 18/22
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 ]
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 19/22
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
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 20/22
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
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 21/22
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
7/29/2019 Sindrome Nelson
http://slidepdf.com/reader/full/sindrome-nelson 22/22
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'.