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There are several
trails of evidence that suggest that the hypothalamic-pituitary
axis (HPA) is involved in the development of nausea. Many
of the adverse effects commonly associated with chemotherapy,
such as nausea, vomiting and fatigue, are clinical characteristics
of adrenal insufficiency (e.g. Addison's syndrome) (Burke,
1992).
It appears that the activity of the hypothalamic-pituitary-adrenal
(HPA) axis in general, and cortisol in particular, are
involved in the genesis or expression of nausea and perhaps vomiting.
- Cortisol (hydrocortisone),
the principal glucocorticoid in humans, is secreted by the adrenal
cortex. It is regulated by a feedback mechanism that involves
levels of adrenocorticotropic hormone (ACTH), produced in the
anterior pituitary, which in turn is regulated by corticotropin-releasing
hormone (CRH) from the hypothalamus.
- Cortisol production
follows a circadian rhythm with blood levels being highest from
5 a.m. to 9 a.m. and reaching a nadir in late evening. This
has been linked to the observation that emesis after platinum
is lower when the platinum is given at 6 p.m. than when it is
given at 6 a.m. Similarly, Fredrikson (Fredrikson
et al., 1993) and Hursti (Hursti
et al., 1993) showed that patients with low nocturnal urinary
cortisol levels had a higher level of nausea on treatment and
on two posttreatment days than patients with a higher level
of urinary cortisol.
- Studies of endocrine
factors in nausea development have primarily focused on cortisol
because of the known efficacy of the steroid dexamethasone for
control of chemotherapy-induced nausea (Tavorath
et al., 1996; Roila et al., 1998).
ACTH and the steroid methylprednisolone have also been shown
to have anti-emetic effects in chemotherapy (Seymour,
1993).
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