Adrenocortical Insufficiency Clinical Trial
Official title:
Optimization of the Evaluation of the Adrenal Function After Discontinuation of a Prolonged Therapy With Corticosteroids
The study (forward-looking and opened) will concern 70 subjects having had a systemic
prolonged treatment with corticosteroids for intestinal chronic inflammatory disease,
recruited in the services of gastroenterology and endocrinology of the North Hospital of
Marseille (France). The primary objective of the study is to estimate a new test, the "long"
synacthen stimulation test, using an IM injection of 1 mg of delate synacthen, with regard
to the definitive standard. Indeed, this long test could be realized in ambulatory
conditions, and turn out more contributory than the definitive standard to estimate the
capacities of answer of the adrenal glands in front of a prolonged stress, as it is the case
during a surgical procedure for example.
The secondary objectives are: 1) to determine the relation between the value of basal
cortisol and the peak of stimulation of cortisol during short and long tests. This could
allow to clarify better the conditions in which it is absolutely necessary to realize a
dynamic test, 2) to determine the relation between cortisol assay in the plasma and in the
saliva. The sample of saliva is simple and non-invasive, and presents the advantage to be
able to be realized in ambulatory conditions and by the patient himself.
The cortisonic withdrawal syndrome is another complication which can arise when a prolonged
corticosteroid therapy is discontinued. Clinically, it looks like a chronic adrenocortical
insufficiency, but with normal ranges of plasma cortisol. It is probably in touch with a
physical dependence to the taking of above physiological doses of GC over a long period. Its
physiopathology remains badly known, but could bring in a deficit of secretion of DHEA-S
(dehydro-epiandrosterone sulphate), another hormone secreted by the adrenal glands. One of
the secondary objectives of the study will consist in informing the variations of DHEA-S
after a prolonged corticotherapy, in the basal state and after stimulation by the long
synacthen stimulation test.
Synthetic glucocorticoids (GC) are used in the treatment of numerous inflammatory or
auto-immune diseases, in particular the intestinal chronic inflammatory diseases (Crohn's
disease, chronic ulcerative colitis). In case of discontinuation of a prolonged (superior to
3-4 weeks) and systemic treatment, deleterious side effects are frequent, with in particular
a risk of adrenocortical insufficiency and withdrawal cortisonic syndrome. Our protocol of
medical research concerns these two complications, and aims at optimizing the evaluation of
the adrenal function.
The adrenocortical insufficiency after prolonged corticotherapy is the most frequent cause
of secondary adrenocortical insufficiency. It is due to the braking of the
hypothalamo-pituitary-adrenal (HPA) axis which controls the endogenous secretion of
cortisol. It is mostly transient, but can last several months, and exposes to a risk of
acute decompensation. An adapted coverage with replacement doses of hydrocortisone (natural
GC) is thus necessary during the treatment discontinuation, together with regular hormonal
revaluations to track down the recovery of the adrenal function. These evaluations are based
on biological measurements, because of the absence of specific clinical symptoms. At first,
basal plasma cortisol at 08:00 am (physiological peak of the hormone) is assayed. A value
lower than 8 µg / dl (220 nmol / l) allows to do the positive diagnosis of adrenal
insufficiency and a value superior to 20 µg / dl (550 nmol / l) to exclude it. Between these
2 values, a doubt remains on the capacities of the adrenal glands to secrete enough cortisol
in case of stress, and the realization of a dynamic test of stimulation is then necessary.
The standard test used in common practice is the "short" synacthene stimulation test
(fragment 1-24 of the ACTH, the hormone secreted by the pituitary gland and stimulating the
secretion of cortisol) using an IV injection of 250 µg of immediate synacthen. The study
(forward-looking and opened) will concern 70 subjects having had a systemic prolonged
treatment with corticosteroids for intestinal chronic inflammatory disease, recruited in the
services of gastroenterology and endocrinology of the North Hospital of Marseille (France).
The primary objective of the study is to estimate a new test, the "long" synacthen
stimulation test, using an IM injection of 1 mg of delate synacthen, with regard to the
definitive standard. Indeed, this long test could be realized in ambulatory conditions, and
turn out more contributory than the definitive standard to estimate the capacities of answer
of the adrenal glands in front of a prolonged stress, as it is the case during a surgical
procedure for example.
The secondary objectives are: 1) to determine the relation between the value of basal
cortisol and the peak of stimulation of cortisol during short and long tests. This could
allow to clarify better the conditions in which it is absolutely necessary to realize a
dynamic test, 2) to determine the relation between cortisol assay in the plasma (classically
used) and in the saliva ( which is validated for the evaluation of the other adrenal
pathology as the Cushing's syndrome, but not still in the adrenocortical insufficiency after
prolonged corticotherapy). The sample of saliva is simple and non-invasive, and presents the
advantage to be able to be realized in ambulatory conditions and by the patient himself.
The cortisonic withdrawal syndrome is another complication which can arise when a prolonged
corticosteroid therapy is discontinued. Clinically, it looks like a chronic adrenocortical
insufficiency, but with normal ranges of plasma cortisol. It is probably in touch with a
physical dependence to the taking of above physiological doses of GC over a long period. Its
physiopathology remains badly known, but could bring in a deficit of secretion of DHEA-S
(dehydro-epiandrosterone sulphate), another hormone secreted by the adrenal glands. One of
the secondary objectives of the study will consist in informing the variations of DHEA-S
after a prolonged corticotherapy, in the basal state and after stimulation by the long
synacthen stimulation test.
;
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic