Background: The diagnosis of acromegaly still poses a clinical challenge, and prolonged diagnostic delay is common. The most important assays for the biochemical diagnosis and management of acromegaly are growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Objective: Discuss the role of IGF-1, basal serum GH, and nadir GH after oral glucose tolerance test (OGTT) for the diagnosis, management, and treatment of patients with acromegaly. Methods: We performed a narrative review of the published data on the biochemical diagnosis and monitoring of acromegaly. An English-language search for relevant studies was conducted on PubMed from inception to 1 January 2021. The reference lists of relevant studies were also reviewed. Results: Serum IGF-1 levels, basal GH values, and nadir GH after OGTT play a major role in the diagnosis, management, and treatment of patients with acromegaly. Measurement of IGF-1 levels is the key factor in the diagnosis and monitoring of acromegaly, but basal and nadir GH following OGTT are also important. However, several factors may significantly influence the concentrations of these hormones, including assay methods, physiologic and pathologic factors. In some cases, discordant GH and IGF-1 levels may be challenging and usually requires additional data and monitoring. Conclusion: New GH and IGF-1 standards are much more precise and provide more accurate tools to diagnose and monitor patients with acromegaly. However, all these biochemical tools have their limitations, and these should be taken under consideration, along with the history, clinical features and imaging studies, when assessing patients for acromegaly.

Objective: Cancer incidence in patients with endogenous Cushing's syndrome (CS) has never been established. Here, we aimed to assess the cancer risk in patients with CS as compared with individually matched controls. Design: A nationwide retrospective matched cohort study of patients with endogenous CS diagnosed between 2000 and 2023 using the database of Clalit Health Services in Israel. Methods: Patients with adrenal carcinoma or ectopic CS were excluded. Patients with CS were matched in a 1:5 ratio, with controls individually matched for age, sex, socioeconomic status, and body mass index. The primary outcome was defined as the first diagnosis of any malignancy following a CS diagnosis. Risk of malignancy was calculated using the Cox proportional hazard model, with death as a competing event. Results: A total of 609 patients with CS and 3018 controls were included [mean age at diagnosis, 48.0 ± 17.2 years; 2371 (65.4%) women]. The median follow-up was 14.7 years (IQR, 9.9–20.2 years). Patients with CS had an increased cancer risk, with a hazard ratio (HR) of 1.78 (95% CI 1.44–2.20) compared with their matched controls. The risk of malignancy was elevated in patients with Cushing's disease (251 cases and 1246 controls; HR 1.65, 95% CI 1.15–2.36) and in patients with adrenal CS (200 cases and 991 controls; HR 2.36, 95% CI 1.70–3.29). The increased cancer risk in patients with CS persists after exclusion of thyroid malignancies. Conclusion: Endogenous CS is associated with increased malignancy risk. These findings underscore the need for further research to establish recommendations for cancer screening in this population.

Objective: Patients with endogenous Cushing's syndrome (CS) have elevated mortality, particularly during active disease. A recent meta-analysis reported reduced mortality rates after 2000 in adrenal CS and Cushing disease (CD), though many studies lacked population-matched controls. Methods: Nationwide retrospective study (2000-2023) in Israel using the Clalit Health Services database to assess all-cause mortality in patients with endogenous CS matched 1:5 with controls by age, sex, socioeconomic-status, and body mass index (BMI). Primary outcome was all-cause mortality. Secondary outcomes included cause-specific mortality, impact of hypercortisolism remission, disease source, and mortality risk factors. Results: The cohort included 609 cases with CS (mean age 48.1 ± 17.2 years; 65.0% women) and 3018 matched controls (47.9 ± 17.2 years; 65.4% women). Over a median follow-up of 16 years, 133 cases (21.8%) and 472 controls (15.6%) died (HR = 1.44, 95% CI, 1.19-1.75). Both patients with CD (HR = 1.73, 95% CI, 1.27-2.36) and adrenal CS (HR = 1.31, 95% CI, 1.00-1.81) had increased mortality risk. Patients without remission within 2 years had a higher mortality risk than those achieving remission (HR = 1.44, 95% CI, 1.00-2.17). Mortality was similar for CD and adrenal CS (HR = .83, 95% CI, .56-1.24). Older age, male gender, and prior malignancy were independent risk factors for mortality. Conclusion: This is the largest national cohort study on mortality risk in CS over the past 2 decades, showing a significantly higher risk compared to matched controls in a homogeneous database. While etiology had no impact, remission significantly affected mortality, highlighting the importance of disease control for long-term survival.

Objective: The management of visual field damage in patients with macroprolactinomas is a major therapeutic challenge. We aimed to study the visual morbidity associated with macroprolactinoma and its outcomes following medical and surgical treatment. We aimed to identify predictors of visual recovery. Methods: We retrospectively reviewed patient's data including clinical presentation, serial pituitary magnetic resonance imaging, laboratory tests, visual symptoms and neuro‐ophthalmologic examination, visual field tests and optical coherence tomography tests. The main outcome was complete visual field recovery. Descriptive analyses were conducted. Predictors of visual recovery were investigated. Patients: The study cohort included 150 patients with macroprolactinoma [median follow‐up, 6.0 years (interquartile range (IQR) 2.9–10.6)]. Results: At diagnosis, visual field defects were evident in 40 patients (26.7%). At the end of follow‐up, 24 out of 39 available visual field tests (61.5%) exhibited complete recovery. Patients that achieved complete visual recovery had smaller macroadenomas at diagnosis [30.5 mm (15.0–80.0) vs. 42.0 mm (30.0–85.0), p < .01], lower baseline serum prolactin levels [1414 mcg/L (489–3586) vs. 4119 mcg/L (2715–6315), p < .01], lower rates of central hypogonadism (78.3% vs. 93.3%, p = .05) and central hypothyroidism (20.8% vs. 53.3%, p = .04), lower rates of compressive optic neuropathy (35.3% vs. 87.5%, p = .02) and a better visual acuity (better than 6/8 in both eyes, 93.7% vs. 28.6%, p < .01). Conclusions: In our cohort of 150 patients with macroprolactinoma, 40 patients (26.7%) presented with visual field defects, of which 61.5% achieved complete visual recovery with treatment. Patients that achieved complete visual recovery presented with smaller macroadenomas, lower serum prolactin levels, lower rates of central hypogonadism and central hypothyroidism, lower rates of compressive optic neuropathy and better visual acuity.

Objective: Endogenous Cushing's syndrome (CS) has been linked with an increased risk of cancer. We aimed to evaluate the association between cancer risk and disease remission postsurgery in adrenal CS and Cushing's disease (CD). Design: A nationwide retrospective matched-cohort study of patients with CS diagnosed between 2000 and 2023 in Israel, using Clalit Health Services’ database. Methods: Patients with CS were matched 1:5 with controls by age, sex, socioeconomic status, and BMI. Remission status postsurgery was assessed within 2 years after the diagnosis of CS. The outcome measured was time to first diagnosis of malignancy, at least 3 years post-CS diagnosis, excluding those who died or developed cancer earlier. Malignancy risk, stratified by remission status, was evaluated using Cox proportional hazards with death as a competing event. Results: The cohort comprised 388 cases and 1862 controls [mean age at diagnosis, 47.4 ± 16.8 years; 1534 (68.2%) women]. Among patients with CD, those who did not achieve remission within 2 years postdiagnosis (n = 69) had a higher risk of malignancy compared to those who achieved remission (n = 99) (HR 3.89, 95% CI 1.41-10.75). Cancer risk in patients with CD who achieved remission was similar to that of the controls (HR 0.58, 95% CI .23-1.47). In patients with adrenal CS, the risk of cancer was comparable between those who did not achieve early remission (n = 39) and those who did (n = 113) (HR 1.68, 95% CI .83-3.40). Conclusion: Though cancer risk is higher in both CD and adrenal CS, we have shown that achieving surgical remission within 2 years may attenuate cancer risk in patients with CD, but not in those with adrenal CS.