Nelson Syndrome Follow-up
- Author: Thomas A Wilson, MD; Chief Editor: Stephen Kemp, MD, PhD more...
Further Outpatient Care
Monitor patients at 3-month to 4-month intervals with measurement of growth parameters, blood pressure, and assessment of thyroid function and pubertal development. Loss of pituitary function after pituitary radiotherapy is inevitable, although the time taken for this to occur varies and depends on the dose and number of fractions of radiation that are administered. Growth failure may precede biochemical evidence of growth hormone deficiency with pharmacologic testing. Overnight growth hormone sampling is thought to be more sensitive than pharmacologic testing because the hypothalamus is more radiosensitive than the pituitary and neurosecretory dysfunction may precede actual growth hormone (GH) deficiency. For this reason, patients who have received pituitary radiation need ongoing follow-up of their growth and thyroid function at 3-month and 6-month intervals by an endocrinologist, and patients may require pubertal induction or treatment of hypogonadism in addition to their ongoing replacement with hydrocortisone and fludrocortisone.
Thyroid function should be measured at least every 6 months or more frequently if growth velocity is declining and deficiency is evolving. Thyroxin supplementation is necessary when the free T4 levels are below the reference range. Thyroid-stimulating hormone (TSH) is not helpful in determining adequacy of thyroxin replacement in patients with central hypothyroidism.
Patients with central diabetes insipidus require treatment with desmopressin acetate (DDAVP). The dosage required varies among individuals and can range from 50-400 mcg/d administered as a single or twice daily dose orally. It may also be administered as a nasal spray, in which case the dose is 5-40 mcg/d usually in 2 divided doses. The evening dose is usually larger to reduce problems with nocturia.
Children who receive DDAVP need to have regular sodium measurements, with the frequency determined by the stability of the child. More frequent measurements are needed if the child develops increased fluid losses due to intercurrent illness, hot ambient temperatures, or GI losses.
Patients with a normal sense of thirst should be allowed to drink ad libitum because by doing so they regulate their own osmolality. Fluid management is difficult in patients with diabetes insipidus who lack normal thirst sensation. Regular weighing on accurate scales is important, and prescribed fluid intake must be administered based upon the size of the child and the environmental conditions. Greater vigilance and more frequent measurements of sodium are needed in these children.
Some physicians believe that children receiving DDAVP should be allowed to "break through" and become polyuric periodically to avoid the risk of hyponatremia. Mixed opinion exists about the frequency with which breakthrough is required.
Patients with Nelson syndrome who have undergone radiotherapy and have multiple pituitary hormone deficiencies require lifelong endocrine follow-up. Transition is ideally achieved in the late adolescent years in a clinic that has both adult and pediatric endocrinologists.
Inpatient & Outpatient Medications
Replacement of hormones depends upon those that are found to be deficient. Regular clinical and biochemical assessment identifies these deficiencies. These may include the need for pubertal induction and sex hormone replacement and growth hormone replacement in addition to adrenal hormone replacement. Patients with central diabetes insipidus also require DDAVP, available as a nasal spray or tablet.
Nelson syndrome has become increasingly uncommon because of the significant improvements in all aspects of biochemical and radiological diagnosis and surgical and medical management of Cushing syndrome.
Hyperpigmentation with adrenocorticotropin (ACTH) levels above 154 pg/mL have been shown to have a high positive predictive value of Nelson syndrome or ectopic ACTH syndrome.
These patients should have an MRI of the pituitary. If no tumor is detected, and ectopic ACTH syndrome is ruled out, MRI of the pituitary should be periodically repeated.
Appropriate workup should enable accurate early identification of nearly all cases of ACTH-secreting pituitary adenoma, enabling prevention of virtually all cases; thus, Nelson syndrome should become a disease of the past.
The following are the potential complications in patients with pituitary macroadenomas:
Related to the primary disease - Visual loss, hypopituitarism, and cranial nerve complications
Related to surgical intervention - Infection, stroke, hypothalamic damage, hypopituitarism, and visual loss
Related to radiotherapy - Hypopituitarism, damage to vision, difficulties with learning or memory, and the risk of developing second tumors
The prognosis for patients with Nelson syndrome is good with early recognition, prompt coordinated treatment with surgeons and radiotherapists, and appropriate hormone replacement. The falling incidence and lack of longitudinal studies suggest that good recent epidemiological data are lacking.
The predominant cause of morbidity from Nelson syndrome is from local tumor extension or invasion. Patients with this disorder become deeply pigmented because the action of ACTH on melanocytes. Malignant transformation of ACTH-secreting Nelson tumors has been reported, although this is very rare. Morbidity in Nelson syndrome may be due to loss of pituitary function because of compression or replacement of normal pituitary tissue or compression of structures adjacent to the pituitary fossa by the tumor. Lateral extension of the tumor may result in invasion of the cavernous sinuses and entrapment or compression of the cranial nerves that traverse it (the oculomotor, trochlear, and abducens nerves and the ophthalmic division of the trigeminal). Superior extension of the tumor can lead to compression or invasion of the optic apparatus or the hypothalamus. The visual symptoms or signs observed depend on the point at which the tumor impinges the optic apparatus.
Although headaches are common and are probably due to stretching of the dura of the diaphragma sellae by the tumor, obstruction of cerebrospinal fluid (CSF) flow is rare because this requires the tumor to be sufficiently large enough to obstruct the foramen of Monro in the third ventricle. Dural invasion with CSF leak and meningitis has been reported, although it is a rare complication.
During embryogenesis, adrenal cortical cells may migrate along the line of gonadal descent and may even be sequestered in the hilum of the testes, giving rise to adrenal rest tissue. In Nelson syndrome, this adrenal rest tissue may become stimulated. When in the testes, it can result in painful testicular enlargement and oligospermia. Rarely, the adrenal rest tissue can produce sufficient cortisol to normalize levels or even cause recurrence of Cushing syndrome.
The main educational requirements for patients with Nelson syndrome relate to their need to increase replacement glucocorticoid doses with intercurrent illness, physical stress, or anesthesia and the need for parenteral steroids before anesthesia or with vomiting or severe diarrhea.
Patients receiving other treatment also require education specific to that treatment (eg, administration of growth hormone injections or DDAVP).
All patients on steroid replacement should wear a Medic Alert bracelet or medallion.
If patients have hypogonadotropic hypogonadism, they also require counseling at an appropriate age about the availability of assisted reproduction.
For excellent patient education resources, visit eMedicineHealth's Thyroid and Metabolism Center. Also, see eMedicineHealth's patient education articles Hypopituitarism in Children and Anatomy of the Endocrine System.
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