Hypothalamic-Pituitary Endocrine Functions
No criteria used to establish brain death attempt to determine
whether functions of the hypothalamus are preserved. Clinical studies have indicated
that hypothalamic and anterior pituitary functions are preserved to a certain degree
for a certain period after the onset of brain death. Hall and colleagues[46]
and Schrader and coworkers[47]
reported normal levels
of anterior pituitary hormones, the half-lives of which are less than 1 hour, such
as thyroid-stimulating hormone, prolactin, growth hormone (GH), and luteinizing hormone,
as well as positive test results for the hypothalamic hormone luteinizing hormone-releasing
hormone and thyrotropin-releasing hormone for 2 to 24 hours after determination of
brain death. Sugimoto and associates[48]
confirmed
that concentrations of these hormones were normal for more than 1 week.
In contrast, the level of vasopressin, a hormone produced in the
hypothalamus and stored in the posterior pituitary, decreased sharply after brain
death.[49]
However, the occurrence of diabetes
insipidus is variable. In one study, many patients did not have diabetes insipidus
after brain death.[49]
Another study found that
24 (77%) of 31 patients with brain death had clinical diabetes insipidus.[50]
When arginine vasopressin is added to the infusion in cases of brain death with
diabetes insipidus, the heart beat can be maintained for several months.[11]
[12]
It was reported that plasma levels of the
thyroid
hormones triiodothyronine (T3
) and thyroxin (T4
) were decreased
markedly after brain death.[51]
[52]
T3
supplement in the brain-dead organ donor to treat the metabolic defect
improved organ function before and after transplantation,[51]
[53]
although Goarin and colleagues[54]
denied the effectiveness of T3
administration for the improvement of hemodynamic
status and myocardial function in brain-dead patients.
The diaphragma sellae protects the pituitary gland from compression
caused by swelling of the brain. Blood supply to the pituitary gland comes mostly
from the superior, middle, and inferior hypophyseal arteries and the capsular arteries.
The portal venous system is another source of blood supply to the anterior lobe.
In brain death, blood supply through the superior hypophyseal artery and the portal
vein can easily be blocked. However, blood supply through the cavernous portion
of the internal carotid artery and its branches, such as the inferior hypophyseal
artery and the capsular artery, may be spared.[55]
[56]
Morphologic studies of brain death indicate
that damage to the anterior lobe is incomplete but severe, whereas the posterior
lobe is relatively preserved.[48]
However, because
antidiuretic hormone is synthesized in the hypothalamus and transferred to the posterior
lobe of the pituitary through axoplasmic flow along the long axon, depletion of antidiuretic
hormone may be greater than would be expected from the slight morphologic damage
seen in the posterior lobe.
In studies on brain death, the hypothalamic hormones, such as
GH-releasing hormone, corticotropin-releasing hormone (CRH), thyroxine-releasing
hormone, and luteinizing hormone-releasing hormone were found in trace to subnormal
levels.[48]
[57]
Schrader and coworkers[47]
reported a normal GH
response to hypoglycemic stimulation. Arita and associates[58]
also demonstrated that insulin and arginine increased GH levels in brain-dead patients.
Hypoglycemia affects glucoreceptors in the ventromedial nucleus to stimulate GH-releasing
hormone and CRH release and stimulates GH or ACTH release, indicating that some hypothalamic
function is preserved. The origin of the hypothalamic hormones released in brain
death cannot be identified. Results from morphologic studies of the hypothalamus
are controversial. Walker and colleagues[17]
reported
that the neurons with lytic changes were intermingled with relatively normal cells,
a result that may account for the sustained secretion of hypothalamic hormones.
Sugimoto and coworkers[48]
observed extensive necrosis
of the hypothalamus after the sixth day of brain death and postulated a nonbrain
supply of these hormones, such as the pancreas, intestine, or adrenal gland. The
hypothalamus receives its blood supply through the branches of the superior hypophyseal
and posterior communicating arteries. Blood flow to the hypothalamus, at least its
basal part, may be preserved in relatively mild instances of intracranial hypertension.
The survival of the hypothalamus after brain death is an issue for future study.
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