CRH test may replace invasive method in diagnosing Cushing’s disease: Study
Its accuracy is comparable to that of BIPSS, the current gold standard
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The corticotropin-releasing hormone (CRH) stimulation test is a reliable tool for diagnosing Cushing’s disease, according to a recent study.
Results show that its accuracy is comparable to that of bilateral inferior petrosal sinus sampling (BIPSS), the gold standard but invasive method, in distinguishing Cushing’s disease from ectopic Cushing’s syndrome.
The “CRH test … may obviate the need for an invasive test, such as BIPSS, to confirm the diagnosis of [Cushing’s disease],” researchers wrote.
The study, “A positive corticotropin-releasing hormone test may obviate the need for petrosal sinus sampling in patients with cushing’s disease,” was published in the Journal of Endocrinological Investigation.
BIPSS is costly, carries risk of complications
In Cushing’s disease, a tumor in the brain’s pituitary gland secretes excessive amounts of adrenocorticotropic hormone (ACTH), which signals the adrenal glands sitting atop the kidneys to overproduce cortisol. Over time, excess cortisol in the bloodstream can drive disease symptoms. High blood cortisol can also be caused by ACTH-secreting tumors outside the pituitary gland, a condition known as ectopic Cushing’s syndrome.
BIPSS is considered the gold standard for diagnosing Cushing’s disease. It involves measuring ACTH levels in the inferior petrosal sinuses, the veins that drain blood and fluids from the pituitary gland. However, the procedure is costly and must be performed in specialized centers. And because it’s invasive, it carries a low but definite risk of complications.
CRH is a signaling molecule that triggers the pituitary gland to release more ACTH, which, in turn, boosts cortisol production. In the CRH test, administration of CRH increases ACTH and cortisol levels in people with pituitary-related Cushing’s disease, but not in those with high cortisol due to other non-pituitary causes.
In this report, researchers in Italy investigated whether the CRH test can distinguish between individuals with and without a pituitary tumor when compared with BIPSS.
All patients in study had surgery to remove tumor
The team examined medical data from 502 people with Cushing’s disease and 21 with ectopic Cushing’s syndrome. Of the Cushing’s disease patients who underwent BIPSS, nearly all (94.0%) tested positive for elevated ACTH, compared with none of those with ectopic Cushing’s. All patients had undergone a CRH test and surgery to remove the ACTH-secreting tumor.
The researchers determined that the optimal cutoff for an increase in ACTH after the CRH test to confirm Cushing’s disease was 47%, yielding an area under the curve (AUC) of 0.94. AUC is a value between zero and one that indicates how well a test distinguishes between two states (with or without Cushing’s disease), with values closer to one indicating greater accuracy.
Our study shows that a positive CRH test reliably differentiates [Cushing’s disease] from [ectopic Cushing’s syndrome] and obviates the need for BIPSS.
When the researchers used a 50% increase in ACTH as a diagnostic cutoff, the CRH test correctly identified most (87%) cases of Cushing’s disease and nearly all (95%) of ectopic Cushing’s syndrome. In comparison, BIPSS correctly diagnosed almost all (94%) cases of Cushing’s disease and all (100%) cases of ectopic Cushing’s.
Among Cushing’s disease patients, the diagnostic accuracy of CRH was higher in those with small pituitary tumors — up to 9 mm (0.35 inches) in diameter — than in those with larger tumors (greater than 9 mm), as assessed by MRI (89% vs. 76%). When even smaller tumors were examined, including those smaller than 6 mm (0.24 inches) and those larger than 6 mm, the correct classification was similar (85% vs. 89%).
The CRH test correctly classified more Cushing’s disease patients without a pituitary tumor visible on MRI than those with a positive MRI examination (91% vs. 85%). Lastly, sex did not affect CRH test performance in terms of diagnostic accuracy.
“Our study shows that a positive CRH test reliably differentiates [Cushing’s disease] from [ectopic Cushing’s syndrome] and obviates the need for BIPSS,” the team concluded.
