The SONICS study met its primary and secondary endpoints, demonstrating a statistically significant normalization rate of urinary free cortisol
at six months.
Methods used to evaluate adrenal fatigue included salivary cortisol rhythm, direct awakening cortisol, cortisol awakening response, morning serum cortisol, night salivary cortisol, area under curve measurement, dexamethasone suppression test, dehydroepiandosterone sulfate or DHEA-S, adrenocorticotropic hormone or ACTH, mental stress test, 24-hour urinary free cortisol
, cosyntrophin stimulation test, morning area under curve, corticotrophin releasing hormone, total urinary cortisol metabolites and oral glucose tolerance test.
The open-label, single-arm SONICS study achieved statistical significance of its pre-specified primary endpoint, with 30% of patients achieving normalization of mean urinary free cortisol
following six months of maintenance treatment with RECORLEV without a dose increase.
In short, initial screening was based on the presence of relevant clinical features and biochemical confirmation through the following screening tests: increased 24-h urinary free cortisol
according to the upper cutoffs of reference intervals; loss of diurnal circadian rhythm in salivary cortisol with midnight salivary cortisol concentrations exceeding 1.5 ng/mL; and lack of suppression of serum cortisol (fasting serum cortisol >1.8 [micro]g/dL) with use of the low-dose DST with 1 mg overnight or 2 mg over 2 days.
While its use has been shown to effectively reduce urinary free cortisol
in patients with Cushing's syndrome, adrenal insufficiency is a known side effect of therapy [4, 5].
There was no clinical evidence of cortisol excess, and screening 24-hour urinary free cortisol
Relationships between 24-hour urinary free cortisol
concentrations and metabolic syndrome in obese children.
According to the company, the primary efficacy endpoint will assess the impact of ATR-101 on urinary free cortisol
concentration, and secondary endpoints will evaluate the impact of ATR-101 on adrenal steroids/steroid intermediates and adrenocorticotropic hormone.
They were considered in remission after surgery if morning cortisol suppression (<50nmol/l) was observed after 1 mg dexamethasone overnight ; if adrenal insufficiency was demonstrated and if repeated 24 h urinary free cortisol
measures were within normal parameters (<280nmol/24h).
Biochemical diagnostic examinations--including 24-hour urinary free cortisol
, low-dose dexamethasone suppression test, and assessment of midnight plasma cortisol or late-night salivary cortisol --should be done when there is clinical suspicion.
Then one of three biochemical screening tests is recommended: (a) the 24-hour Urinary Free Cortisol
(UFC) test, (b) the latenight salivary cortisol test, or (c) the 1 mg overnight dexamethasone suppression test (DST).
High-dose dexamethasone caused 50% suppression of serum cortisol, but not of 24 h urinary free cortisol
. A diagnosis of Cushing's syndrome was made.