Use of late-night salivary cortisol to monitor response to medical treatment in Cushing’s disease

Abstract

Objective 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. Design Exploratory analysis evaluating LNSC during a Phase III study of long-acting pasireotide in Cushing’s disease (clinicaltrials.gov: NCT01374906). Methods 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. Results 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. Conclusion 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.

Sexual Dimorphism in Cellular and Molecular Features in Human ACTH-Secreting Pituitary Adenomas

“…Interest in SSTR5 rests on the fact that that pasireotide, a somatostatin analogue with affinity for several somatostatin receptor subtypes including SSTR5, is being used to contain tumoural corticotrope secretion. Clinical efficacy of subcutaneous pasireotide is possibly superior in women [89], but gender-skewed sample collection-the vast majority of samples were from female donors-might have influenced this result. Overexpression of SSTR5 has recently been reported among USP8-mutated corticotrope adenomas compared to wild-type adenomas [49]; however, USP8 mutations were found in adenomas from female patients only, thus this finding could be gender-rather than USP8-variant specific.…”

Versatile Functions of Somatostatin and Somatostatin Receptors in the Gastrointestinal System

“…Octreotide, lanreotide, and pasireotide are applied to acromegaly, Cushing’s syndrome, and carcinoid syndrome, respectively ( 69 , 70 , 74 ). SST (Pasireotide 10-30mg/4ws/year) decreased urinary free cortisol and late-night salivary cortisol to normal levels in patients with Cushing’s disease ( 19 ). NETs are heterogeneous malignancies in different neuroendocrine systems and higher incidents in the GI and Non-GI tract of SST analogs have been confirmed in antisecretory and antitumor efficacy ( 19 , 68 – 70 , 74 , 78 , 79 , 83 ).…”

“…SST (Pasireotide 10-30mg/4ws/year) decreased urinary free cortisol and late-night salivary cortisol to normal levels in patients with Cushing’s disease ( 19 ). NETs are heterogeneous malignancies in different neuroendocrine systems and higher incidents in the GI and Non-GI tract of SST analogs have been confirmed in antisecretory and antitumor efficacy ( 19 , 68 – 70 , 74 , 78 , 79 , 83 ). The FDA approved peptide-receptor radionuclide therapy (Lutathera ® ) for gastroenteropancreatic NETs; the treatment can improve patient survival ( 71 , 79 ).…”

Levoketoconazole: a novel treatment for endogenous Cushing's syndrome

“…Measuring late-night salivary cortisol (LNSC) levels can help assess loss in the diurnal physiological rhythm of cortisol secretion [53,54]. Restoring the diurnal cortisol rhythm is of clinical importance in patients with CS, as the disruption of this rhythm is thought to result in comorbidities such as hypertension and impaired glucose metabolism [55,56].…”