Usefulness of Time-Point Serum Cortisol and ACTH Measurements for the Adjustment of Glucocorticoid Replacement in Adrenal Insufficiency.

BACKGROUND: Adjustment of daily hydrocortisone dose on clinical criteria lacks sensitivity for fine tuning. Long term hydrocortisone (HC) over-replacement may lead to increased morbidity and mortality in patients with adrenal insufficiency (AI). Biochemical criteria may help detecting over- or under-replacement but have been poorly evaluated. METHODS: Multicenter, institutional, pharmacokinetic study on ACTH and cortisol plasma profiles during HC replacement in 27 AI patients compared to 29 matched controls. All AI patients were administered HC thrice daily at doses of 6, 10 and 14 mg/m2/d. Blood samples were drawn hourly from 0800h to 1900h. The main outcome measures were: i) plasma peak cortisol and cortisol area under the curve (AUC) in AI patients compared to controls, ii) correlations between cortisol AUC vs single-point cortisol or ACTH decrease from baseline (ΔACTH) and iii) the predictive value of the two latters for obtaining AI patients' cortisol AUC in the control range. RESULTS: Cortisol peaks were observed 1h after each HC intake and a dose response was demonstrated for cortisol peak and cortisol AUC. The comparison of AI patients' cortisol AUC to controls showed that 81.5% AI patients receiving 6mg/m2/d were adequately replaced, whereas most patients receiving higher doses were over-replaced. The correlation coefficient between 1000h/1400h cortisol concentrations and 0800-1900h cortisol AUC were 0.93/0.88 respectively, whereas the 0800-1200h ΔACTH fairly correlated with 0800-1900h cortisol AUC (R = 0.57). ROC curve analysis indicated that the 1000h and 1400h cortisol concentrations best predicted over-replacement. CONCLUSIONS: Patients receiving a 6mg/m2 hydrocortisone daily dose exhibited the most physiological daytime cortisol profile. Single point plasma cortisol correlated with daytime cortisol AUC in AI patients. Although hydrocortisone dose should be currently determined on clinical grounds, our data suggest that single point plasma cortisol may be an adjunct for further hydrocortisone dose adjustment in AI patients.

Sorafenib increases 18-FDG colic uptake: demonstration in patients with differentiated thyroid cancer.

BACKGROUND: To assess 18-fluorodeoxyglucose (FDG) bowel uptake in patients with differentiated thyroid cancer (DTC) treated with sorafenib. FINDINGS: Visual (5-point scale) and high maximum standard uptake value (SUVmax) semi-quantitative analyses were conducted in 63 positron emission tomography (PET) studies performed in patients on sorafenib (group 1, n = 20), in a control group (group 2, n = 28) and in patients on sunitinib or vandetanib (group 3, n = 15).Moderate or high and diffuse bowel uptake (grade 4 or 5) was observed in 90% of the PET scans of group 1 versus none in group 2. Only 20% of PET scans in group 3 were scored grade 4. SUVmax values were significantly higher for all colic segments in group 1 than in group 2 (P < 0.0001) or 3 (P < 0.0004). This uptake pattern appeared rapidly (one month) and disappeared after sorafenib withdrawal. CONCLUSIONS: FDG uptake is increased in the colon of DTC patients treated by sorafenib.

Postablation (131)I scintigraphy with neck and thorax SPECT-CT and stimulated serum thyroglobulin level predict the outcome of patients with differentiated thyroid cancer.

OBJECTIVE: Neck and thorax single photon emission computed tomography with computed tomography (SPECT-CT) improves the reliability of postablation (131)I whole-body scan (WBS) for differentiated thyroid cancer (DTC). The aim of this study was to assess the prognostic value for persistent or recurrent disease of postablation (131)I scintigraphy combining WBS and neck and thorax SPECT-CT with that of the previously known predictive factors. METHODS: This is a single referral center prospective study with a median follow-up of 29 months. Postablation (131)I WBS and neck and thorax SPECT-CT were performed in 170 consecutive patients treated between 2006 and 2008. Stimulated serum thyroglobulin (Tg) and anti-thyroglobulin antibodies (TgAb) levels were measured. The impact on disease-free survival of age; gender; postablation (131)I scintigraphy; stimulated serum Tg level; T, N, and M status; and macroscopic lymph node involvement was assessed by univariate and multivariate analyses. RESULTS: Persistent or recurrent disease was observed in 32 (19%) patients. In the whole group of patients, only positive WBS with SPECT-CT was related to an increased risk of persistent or recurrent disease (hazards ratio (HR)=65.21, 95% confidence interval (CI)=26.03-163.39, P<0.0001). In patients without TgAb (n=146), both positive WBS with SPECT-CT (HR=18.86, 95% CI=5.02-70.85, P<0.0001) and serum Tg level ≥58 ng/ml (HR=4.42, 95% CI=1.18-16.53, P=0.0271) were associated with an increased risk. CONCLUSION: In patients with DTC, the cross analysis of postablation (131)I scintigraphy with neck and thorax SPECT-CT and stimulated serum Tg level enables early assessment of the risk of persistent or recurrent disease.