Outcomes of Patients with Nelson's Syndrome after Primary Treatment: A Multicenter Study from 13 UK Pituitary Centers.

CONTEXT: Long-term outcomes of patients with Nelson's syndrome (NS) have been poorly explored, especially in the modern era. OBJECTIVE: To elucidate tumor control rates, effectiveness of various treatments, and markers of prognostic relevance in patients with NS. PATIENTS, DESIGN, AND SETTING: Retrospective cohort study of 68 patients from 13 UK pituitary centers with median imaging follow-up of 13 years (range 1-45) since NS diagnosis. RESULTS: Management of Cushing's disease (CD) prior to NS diagnosis included surgery+adrenalectomy (n = 30; eight patients had 2 and one had 3 pituitary operations), surgery+radiotherapy+adrenalectomy (n = 17; two received >1 courses of irradiation, two had ≥2 pituitary surgeries), radiotherapy+adrenalectomy (n = 2), and adrenalectomy (n = 19). Primary management of NS mainly included surgery, radiotherapy, surgery+radiotherapy, and observation; 10-year tumor progression-free survival was 62% (surgery 80%, radiotherapy 52%, surgery+radiotherapy 81%, observation 51%). Sex, age at CD or NS diagnosis, size of adenoma (micro-/macroadenoma) at CD diagnosis, presence of pituitary tumor on imaging prior adrenalectomy, and mode of NS primary management were not predictors of tumor progression. Mode of management of CD before NS diagnosis was a significant factor predicting progression, with the group treated by surgery+radiotherapy+adrenalectomy for their CD showing the highest risk (hazard ratio 4.6; 95% confidence interval, 1.6-13.5). During follow-up, 3% of patients had malignant transformation with spinal metastases and 4% died of aggressively enlarging tumor. CONCLUSIONS: At 10 years follow-up, 38% of the patients diagnosed with NS showed progression of their corticotroph tumor. Complexity of treatments for the CD prior to NS diagnosis, possibly reflecting corticotroph adenoma aggressiveness, predicts long-term tumor prognosis

Explicit glycated haemoglobin goals improve subsequent HbA1c levels with no impact on health-related quality of life.

Background: National guidelines recognise the importance of individualising HbA1c targets. Many people with diabetes agree to have their targets re-evaluated in consultations in response to specific characteristics.Aims: We aimed to evaluate the impact of relaxed or stretch HbA1c goals on subsequent HbA1c levels and health-related quality of life (HR-QoL) in adults with diabetes.Methods: We randomised 50 adults with diabetes to receive HbA1c targets either 5mmol/mol above (relaxed target) or 5mmol/mol below (stretch target) current HbA1c readings for 3 months. Participants' HbA1c levels and HR-QoL according to the Euro-QoL-5D-5L (EQ-5D-5L) validated questionnaire were measured at baseline and endpoint. EQ-5D-5L outputs HR-QoL scores (EQ-5D index, range − 0.594–1.000, higher is better) and numerical values from a visual analogue scale (EQ-VAS, range 0–100, higher is better).Results: Thirty-three individuals completed endpoint evaluation. Sulphonylurea and metformin usage increased 3%. Thiazolidinedione, DPP-4 inhibitor, SGLT-2 inhibitor, GLP-1 receptor agonist, and insulin usage remained unchanged. Mean HbA1c improved by 2.9mmol/mol (95% CI -0.4–6.2,p = 0.084) in those with relaxed targets and 2.8mmol/mol (95% CI -0.2–5.7,p = 0.065) with stretch targets. There was no change in median EQ-5D index or EQ-VAS in those with relaxed targets. Median EQ-5D index worsened by 0.005 and EQ-VAS improved by 5 with stretch targets.Conclusions: Our findings suggest goal-setting using specific HbA1c targets is associated with improved HbA1c levels irrespective of the target. Median change in EQ-5D-5L scores were below the threshold of minimum clinically important difference. This may indicate the target-setting process, rather than the goal itself, is beneficial for patient HbA1c levels. Further studies are needed to evaluate these findings in greater detail