John Newell-Price, Rosario Pivonello, Antoine Tabarin, Maria Fleseriu, Przemysław Witek, Mônica R Gadelha, Stephan Petersenn, Libuse Tauchmanova, Shoba Ravichandran, Pritam Gupta, André Lacroix and Beverly M K Biller
Monitoring of patients with Cushing’s disease on cortisol-lowering drugs is usually performed with urinary free cortisol (UFC). Late-night salivary cortisol (LNSC) has an established role in screening for hypercortisolism and can help to detect the loss of cortisol circadian rhythm. Less evidence exists regarding the usefulness of LNSC in monitoring pharmacological response in Cushing’s disease.
Exploratory analysis evaluating LNSC during a Phase III study of long-acting pasireotide in Cushing’s disease (clinicaltrials.gov: NCT01374906).
Mean LNSC (mLNSC) was calculated from two samples, collected on the same days as the first two of three 24-h urine samples (used to calculate mean UFC [mUFC]). Clinical signs of hypercortisolism were evaluated over time.
At baseline, 137 patients had evaluable mLNSC measurements; 91.2% had mLNSC exceeding the upper limit of normal (ULN; 3.2 nmol/L). Of patients with evaluable assessments at month 12 (n = 92), 17.4% had both mLNSC ≤ULN and mUFC ≤ULN; 22.8% had mLNSC ≤ULN, and 45.7% had mUFC ≤ULN. There was high variability in LNSC (intra-patient coefficient of variation (CV): 49.4%) and UFC (intra-patient CV: 39.2%). mLNSC levels decreased over 12 months of treatment and paralleled changes in mUFC. Moderate correlation was seen between mLNSC and mUFC (Spearman’s correlation: ρ = 0.50 [all time points pooled]). Greater improvements in systolic/diastolic blood pressure and weight were seen in patients with both mLNSC ≤ULN and mUFC ≤ULN.
mUFC and mLNSC are complementary measurements for monitoring treatment response in Cushing’s disease, with better clinical outcomes seen for patients in whom both mUFC and mLNSC are controlled.
Fabrice Bonneville, Louis-David Rivière, Stephan Petersenn, John S Bevan, Aude Houchard, Caroline Sert, Philippe J Caron and the PRIMARYS Study Group
Pituitary adenoma MRI T2 signal intensity associates with tumor characteristics including responsiveness to somatostatin analogs (SSAs). These analyses determined whether baseline T2 signal intensity predicts response to primary medical treatment with long-acting SSA.
Post hoc analyses of the prospective multicenter, open-label, single-arm PRIMARYS study in which patients with treatment-naïve GH-secreting pituitary macroadenomas received fixed-dose lanreotide autogel (120 mg) every 4 weeks for 48 weeks.
Associations were investigated between adenoma T2-signal hypo/iso/hyperintensity and treatment responses at week 48/last visit: hormonal control (GH ≤2.5 μg/L and IGF-1 normalization); tumor response (tumor volume reduction (TVR) ≥20%); separate GH/IGF-1 control and change from baseline in GH/IGF-1 and tumor volume.
Adenomas were hypointense at baseline in 50/85 (59%) patients using visual assessment. Of these, 40% achieved hormonal control and 76% achieved a tumor response. Significant univariate associations arose for hypo- vs isointensity with tumor response and achievement of GH ≤2.5 μg/L, but not IGF-1 normalization or overall hormonal control. In multivariate analysis, tumor response was six times more likely for hypo- vs iso-intense tumors (= 6.15; 95% CI: 1.36–27.88). In univariate change-from-baseline analyses, hypo- vs isointensity was associated with greater TVR and IGF-1 reduction but not change in GH. In multivariate analysis, IGF-1 decreased by an estimated additional 65 μg/L (P = 0.0026)) for hypo- vs isointense.
Patients with hypointense vs isointense GH-secreting macroadenomas had greater reductions in IGF-1 following primary treatment with lanreotide autogel and were more likely to achieve tumor response. Assessment of T2 signal intensity at baseline may help to predict long-term responses to primary treatment with SSAs.