Pituitary Isolation Syndrome

Destructive lesions of the pituitary stalk, as occur with head

injury, surgical transection, tumor, or granuloma, produce a characteristic pattern of pituitary

dysfunction.593,594 Central diabetes

insipidus (DI) develops in a large percentage of patients, depending on the level at which the stalk has
been sectioned. If the cut is

close to the hypothalamus, DI is almost always produced, but if

the section is low on the stalk, the incidence is lower. The extent to

which nerve terminals in the upper stalk are preserved determines

the clinical course. The classic triphasic syndrome of initial polyuria followed by normal water control
and then by AVP deficiency

over a period of 1 week to 10 days occurs in fewer than half of the

patients. The sequence is attributed to an initial loss of neurogenic

control of the neural lobe, followed by autolysis of the neural lobe

with release of AVP into the circulation, and finally by complete

loss of AVP. However, full expression of polyuria requires adequate

cortisol levels; if cortisol is deficient, AVP deficiency may be present with only minimal polyuria. DI can
also develop after stalk

injury without an overt transitional phase. When DI occurs after

head injury or operative trauma, varying degrees of recovery can

be seen even after months or years. Sprouting of nerve terminals

in the stump of the pituitary stalk may give rise to sufficient functioning tissue to maintain water
balance. In contrast to the effects

of stalk section, nondestructive injury to the neurohypophysis or

stalk, as during surgical resection of sellar tumors, can sometimes

give rise to transient or delayed SIADH.595

Although head injury, granulomas, and tumors are the most

common causes of acquired DI, other cases develop in the absence

of a clear-cut cause.596 Autoimmune disease of the hypothalamus may be the cause in some instances,
as was suggested by the

finding of autoantibodies to neurohypophyseal cells in a third of

cases of idiopathic DI in one series.597 However, autoantibodies

were also frequently found in association with histiocytosis X.

Later reports suggested the importance of continued vigilance in

cases of idiopathic DI. A definite cause is frequently uncovered in

time, including a high proportion of occult germinomas, whose

detection by MRI may be preceded by elevated levels of hCG in

CSF.598 Congenital DI can be part of a hereditary disease. DI in

the Brattleboro rat is due to an autosomal recessive genetic defect

that impairs production of AVP but not of oxytocin. In contrast,

inherited forms of DI in humans have been attributed to mutations in the vasopressin V2 receptor gene
or less frequently in the

aquaporin or the AVP genes.599–601

Menstrual cycles cease after stalk section, although gonadotropins may still be detectable, unlike the
situation after hypophysectomy. Plasma glucocorticoid levels and urinary excretion of cortisol

decline after hypophysectomy and stalk section, but the change is

slower after stalk section. A transient increase in cortisol secretion

after stalk section is believed to be due to release of ACTH from

preformed stores. The ACTH response to the lowering of blood

cortisol is markedly reduced, but ACTH release after stress may

Reduction in thyroid function after stalk section is similar to that seen with hypophysectomy. The fall in
GH secretion is said to be the most sensitive indication of damage to the stalk, but the insidious nature
of this endocrinologic change in adults who have suffered traumatic brain injuries may cause it to be
overlooked and therefore contribute to delayed rehabilitation.602 Humans with stalk sections or with
tumors of the stalk region have widely varying levels of hyperprolactinemia and may have
galactorrhea.603 PRL responses to hypoglycemia and to TRH are blunted, in part because of loss of
neural connections with the hypothalamus. PRL responses to dopamine agonists and antagonists in
patients with pituitary isolation syndrome are similar to those in patients with prolactinomas.
Interestingly, PRL secretion continues to show a diurnal variation in patients with either hypothalamic-
pituitary disconnection or microprolactinoma.412 Both forms of hyperprolactinemia are characterized
by a similarly increased frequency of PRL pulses and a marked rise in nonpulsatile or basal PRL secretion,
although the disruption is greater in the tumoral hyperprolactinemia. An incomplete pituitary isolation
syndrome may occur with the empty sella syndrome, intrasellar cysts, or pituitary adenomas.604,605
Anterior pituitary failure after stalk section is in part due to loss of specific neural and vascular links to
the hypothalamus and in part due to pituitary infarction.