Przemysław Witek, Grzegorz Zieliński, Katarzyna Szamotulska, Maria Maksymowicz and Grzegorz Kamiński
Corticotroph macroadenomas are a rare cause of Cushing's disease (CD), but their properties are not well-recognised. The aim of this study was to evaluate the clinical and pathological aspects of corticotroph macroadenomas with particular emphasis on proliferation markers and their associations with the efficacy of surgical treatment.
A prospective cohort study was conducted in a tertiary referral centre in Poland.
In total, 59 patients with CD (20 macroadenomas and 39 microadenomas) were included in this study. Hormonal and imaging parameters, histopathological and ultrastructural features of the corticotroph tumours and the early surgical outcomes were evaluated.
ACTH and ACTH/cortisol ratios were higher in macroadenomas (P<0.001 and P=0.002 respectively). Greater tumour volumes were associated with higher Ki-67 and p53 expression (P
trend=0.009 and P
trend=0.024 respectively) and the rates of sparsely granulated adenomas (P
trend=0.036). Immediate postoperative remission and early biochemical remission rates were lower in macroadenomas compared to microadenomas (P<0.001). A logistic regression model showed that the immediate postoperative remission or early biochemical remission depended on tumour volume (P=0.005 and P=0.006 respectively) and invasiveness based on Knosp grades 3 and 4 for macroadenomas and a lack of surgical pseudocapsule for microadenomas (P=0.004 and P=0.007 respectively).
Corticotroph macroadenomas differ from the more common microadenomas not only in terms of hormonal and imaging characteristics but also in terms of immunohistochemical and ultrastructural features and proliferation markers. The early effectiveness of surgery depends primarily on tumour volume and invasiveness.
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.