Hypothalamic serotonin transporters in subjects suspect for hypothalamic damage

Pituitary insufficiency is associated with sleep disturbances, metabolic
abnormalities and a decreased quality of life despite proper hormonal
substitution. The pituitary is both anatomically and functionally closely
related to the hypothalamus, a highly organized part of the brain that plays a
crucial role in many homeostatic processes including sleep-wake rhythm, energy
metabolism, body temperature regulation and activity of the autonomic nervous
system. Because the disorders associated with pituitary insufficiency show many
similarities with the diverse functions of the hypothalamus, hypothalamic
dysfunction may be involved in the pathophysiology of these disorders. Until
recently, no diagnostic tools have been available to confirm hypothalamic
dysfunction in these patients.
Recent developments in radionucleotide imaging of brain have enabled
visualisation of serotonine transport in the human hypothalamus in vivo.
Serotonin plays a very important role in the regulation of the hypothalamic
functions. We hypothesize that patients suffering from hypothalamic dysfunction
may also have a hyposerotonergic neurotransmission.
Therefore, we will investigate if there are differences in serotonin
transporters in the hypothalamus between subjects with hypopituitarism and
clinical suspicion of hypothalamic dysfunction, subjects with hypopituitarism
but without suspicion of hypothalamic dysfunction and healthy age- and
gender-matched controls.

To investigate if there are differences in serotonin transporters in the
hypothalamus between subjects with hypopituitarism suspect for hypothalamic
damage, subjects with hypopituitarism and no suspicion of hypothalamic damage
and healthy age- and gender-matched controls.

Cross-sectional case-control study

Subjects will visit the research unit twice. During the first visit every
potential participant will be screened for in- and exclusion criteria and
instructed to fill out four validated neuropsychiatric questionnaires. The day
before the SPECT scan all subjects will take 2 x 100 mg potassium iodide
tablets p.o.
In the morning of the second visit, all subjects receive 100 mg potassium
iodide tablets p.o. and a urine pregnancy test will be performed in all
premenopausal females. Thereafter a catheter will be placed in an antecubital
vein for respectively blood sampling (maximum volume will not exceed 75mL) and
administration of the radioligand [123I]FP-CIT. At 1, 2 and 3 hours after
administering, a SPECT brain scan will be performed which takes about 40
minutes each, during which the participant lies down on his back on the gamma
camera bed. The radioligand [123I]FP-CIT has a European (CPMP) registration. In
the trials preceding the marketing authorization it has been shown that no
serious side effects occur after administration of this radioligand.
As the dose equivalent per [123I]FP-CIT injection amounts to 2.7 mSv, the total
dose equivalent of the participant subjects will amount less than 10.0 mSv (WHO
category IIb). For careful analyses of the SPECT scan, a MRI of the brain will
be performed on the same day, requiring lying as still as possible for 20
minutes.