The diagnostic value of prolactin adjustment in bilateral inferior petrosal sinus sampling for differentiating Cushing's disease from the ectopic ACTH syndrome: a systematic review and meta-analysis

Background Adrenocorticotropin (ACTH)-dependent Cushing's syndrome can arise from a pituitary tumour (Cushing's disease) or an ectopic ACTH-secreting tumour, making precise differentiation essential for effective treatment. Bilateral inferior petrosal sinus sampling (BIPSS) is the gold standard for this differentiation, but false-negative results can limit its accuracy. Adding prolactin (PRL) measurement to BIPSS has been proposed to improve diagnostic precision. This meta-analysis evaluates how correction for prolactin levels ('prolactin adjustment') affects the diagnostic value of BIPSS in distinguishing Cushing's disease from ectopic ACTH syndrome. Methods A systematic literature search was conducted in PubMed, Scopus, EMBASE, Web of Science, and Google Scholar up to July 2024. Studies were included if they provided data on BIPSS with and without PRL adjustment for ACTH-dependent Cushing's syndrome. Data extraction and quality assessment were performed, and diagnostic accuracy metrics were analysed using bivariate generalised linear mixed modelling. Results A total of 10 studies with 310 participants were included. The pooled sensitivity and specificity of BIPSS with PRL adjustment were 0.96 (95 CI: 0.93-0.98) and 0.68 (95 CI: 0.52-0.81), respectively. The diagnostic odds ratio (DOR) was 48.0 (95 CI: 19.0-123.0), with a positive likelihood ratio (LR) of 3.00 (95 CI: 1.9-4.7) and a negative LR of 0.06 (95 CI: 0.03-0.12). The area under the summary receiver operating characteristic (SROC) curve was 0.95 (95 CI: 0.93-0.97). For BIPSS without PRL adjustment, the pooled sensitivity was 0.90 (95 CI: 0.86-0.93) and specificity was 0.74 (95 CI: 0.59-0.85), with a DOR of 27.0 (95 CI: 13.0-59.0). The SROC curve area was 0.92 (95 CI: 0.89-0.94). Prolactin adjustment improved sensitivity (P < 0.01) without a significant change in specificity (P = 0.13). Conclusions Prolactin adjustment in BIPSS slightly improves sensitivity for diagnosing Cushing's disease but does not enhance specificity for ectopic ACTH syndrome. This highlights the value of PRL measurement in improving diagnostic accuracy and reducing false negatives, while BIPSS remains crucial for ruling out EAS in clinical practice

Seroepidemiological Study of Visceral Leishmaniasis (Kala-azar) in Ardabil Province, Iran, 1986 – 2009

Introduction & Objective: Visceral Leishmaniasis (kala-azar) is the most important endemic disease in Northwestern Iran, particularly in Ardabil province. This study aimed to review the seroepidemiological studies which have been performed in Ardabil province during 1986-2009. Materials & Methods: In this descriptive analytical study, studies which have been carried out from 1986 through 2009 in Northwestern Iran about clinical, diagnostic and epidemiological features of Kala azar, using DAT, were reviewed. Collected data were analyzed using the SPSS software. Results: in total, 2703 of human visceral leishmaniasis were detected by direct agglutination test (DAT) in Ardabil province, 1787 (66.1%) of them were from Meshkin-shahr district, 837 (31%) cases were from Moghan district, and 79 (2.9%) cases were from Ardabil district. Ninety eight percent of the cases were under 10 years old while only 0.5% of the VL cases were ≥20 years old and 17% of them were under 1 year of age. Conclusion: Currently Kala-Azar is the most important endemic disease in Northwestern Iran, particularly in Ardabil province. Anti-Leishmania antibodies at the titers of ≥1:3200 using DAT along with clinical signs including fever, anemia and hepatosplenomegaly are considered as active visceral leishmaniasis. DAT antibody titer of 1/800 and lower and absent of clinical signs is considered as negative VL