Transsphenoidal surgery (TSS) is the treatment of choice in Cushing’s disease. However, recurrence rates are substantial and currently there are no robust predictors of late prognosis. As accumulating evidence challenge the accuracy of the traditionally used early postoperative cortisol values, alternative tests are required. The study of Cambos et al., published in a recent issue of the European Journal of Endocrinology, adds to the existing data that support a role of the desmopressin test as an early and reliable predictive marker in successfully TSS-treated patients. However, despite these promising data, the use of this test is hampered by the fact that it can be applied only in patients with a documented preoperative positive test. Moreover, the lack of robust criteria to define positive postoperative responses represents another major limitation.
D A Vassiliadi and S Tsagarakis
I Perogamvros, D A Vassiliadi, O Karapanou, E Botoula, M Tzanela and S Tsagarakis
The treatment of subclinical hypercortisolism in patients with bilateral adrenal incidentalomas (AI) is debatable. We aimed to compare the biochemical and clinical outcome of unilateral adrenalectomy vs a conservative approach in these patients.
The study included 33 patients with bilateral AI; 14 patients underwent unilateral adrenalectomy of the largest lesion (surgical group), whereas 19 patients were followed up (follow-up group). At baseline and at each follow-up visit, we measured 0800 h plasma ACTH, midnight serum cortisol (MSF), 24-h urinary-free cortisol (UFC) and serum cortisol following a standard 2-day low-dose-dexamethasone-suppression test (LDDST). We evaluated the following comorbidities: arterial hypertension, impaired glucose tolerance or diabetes mellitus, dyslipidemia and osteoporosis.
Baseline demographic, clinical characteristics and the duration of follow-up (53.9±21.3 vs 51.8±20.1 months, for the surgical vs the follow-up group) were similar between groups. At the last follow-up visit the surgical group had a significant reduction in post-LDDST cortisol (2.4±1.6 vs 6.7±3.9 μg/dl, P=0.002), MSF (4.3±2 vs 8.8±4.6 μg/dl, P=0.006) and 24-h UFC (50.1±21.1 vs 117.9±42.4 μg/24 h, P=0.0007) and a significant rise in mean±s.d. morning plasma ACTH levels (22.2±9.6 vs 6.9±4.8 pg/ml, P=0.002). Improvement in co-morbidities was seen only in the surgical group, whereas no changes were noted in the follow-up group.
Our early results show that removal of the largest lesion offers significant improvement both to cortisol excess and its metabolic consequences, without the debilitating effects of bilateral adrenalectomy. A larger number of patients, as well as a longer follow-up, are required before drawing solid conclusions.
E Vassilatou, D A Vassiliadi, K Salambasis, H Lazaridou, N Koutsomitopoulos, N Kelekis, D Kassanos, D Hadjidakis and G Dimitriadis
Limited data exist concerning the presence of polycystic ovary syndrome (PCOS) in premenopausal women with nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the prevalence of PCOS in overweight and obese premenopausal women with NAFLD.
Prospective, observational, and cross-sectional study.
We studied 110 apparently healthy, overweight, and obese (BMI: 25.1–49.1 kg/m2) premenopausal women (age: 18–45 years) reporting no or minimal alcohol consumption for NAFLD with abdominal ultrasonography after excluding causes of secondary liver disease and for PCOS (Rotterdam criteria) with clinical examination, biochemical evaluation, and pelvic ultrasonography. Insulin resistance (IR) was assessed by homeostasis model assessment of IR (HOMA-IR), and free androgen index was calculated.
NAFLD was detected in 71/110 women (64.5%). Women with NAFLD compared to women without NAFLD were more commonly diagnosed with PCOS (43.7% vs 23.1%, respectively, P=0.04), metabolic syndrome (30.2% vs 5.3%, respectively, P=0.003), and abnormal lipid profile (81.1% vs 51.3%, P=0.002). All women with abnormal glucose metabolism had NAFLD (P=0.01). Although PCOS was associated with NAFLD (OR 2.6, 95% CI: 1.1–6.2, P=0.04), in a multivariate analysis higher HOMA-IR values (OR 2.2, 95% CI: 1.1–4.4, P=0.02) and triglyceride levels (OR 1.01, 95% CI: 1.00–1.02, P=0.04) independently predicted NAFLD, after adjusting for age, BMI, and waist-to-hip ratio.
These findings indicate an increased prevalence of PCOS in overweight and obese premenopausal women with NAFLD, although it is not supported that the syndrome is primarily involved in NAFLD. Evaluation for PCOS may be considered in these women.
G Ntali, A Asimakopoulou, T Siamatras, J Komninos, D Vassiliadi, M Tzanela, S Tsagarakis, A B Grossman, J A H Wass and N Karavitaki
In this study, we aim to assess the long-term survival and causes of death in a retrospective cohort study on patients with all aetiologies of endogenous Cushing's syndrome (CS) (except adrenal cancer), presenting to two large tertiary endocrine referral centres, and to identify variables predicting mortality.
Subjects and methods
The records of all patients presenting with endogenous CS in the Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK and the Department of Endocrinology, ‘Evangelismos’ General Hospital, Athens, Greece between 1967–2009 (Oxford series) and 1962–2009 (Athens series) were reviewed. The standardised mortality ratio (SMR) was calculated for the Oxford series.
In total, 418 subjects were identified (311 with Cushing's disease (CD), 74 with adrenal Cushing's (AC) and 33 with ectopic Cushing's (EC)). In CD, the probability of 10-year survival was 95.3% with 71.4% of the deaths attributed to cardiovascular causes or infection/sepsis. SMRs were significantly high overall (SMR 9.3; 95% CI, 6.2–13.4, P<0.001), as well as in all subgroups of patients irrespective of their remission status. In AC, the probability of 10-year survival was 95.5% and the SMR was 5.3 (95% CI, 0.3–26.0) with P=0.2. Patients with EC had the worst outcome with 77.6% probability of 5-year survival.
In this large series of patients with CS and long-term follow-up, we report that in CD the mortality is significantly affected, even after apparently successful treatment. The SMR of patients with AC was high, but this was not statistically significant. The implicated pathophysiological mechanisms for these findings need to be further elucidated aiming to improve the long-term outcome.