Potential pitfalls in diagnosis of immunotherapy-induced hypothalamic-pituitary-adrenal axis abnormalities: a clinical case.

Summary: Short synacthen tests (SST) are frequently used for assessing adrenocorticotropin hormone (ACTH) deficiency. In this study, we present the case of a 53-year-old man receiving immunotherapy for metastatic melanoma, who subsequently developed immune checkpoint inhibitor (ICI)-induced hypothyroidism and was investigated for the presence of ICI-induced hypocortisolaemia on different occasions. Despite two reassuring SSTs, he subsequently developed clinical and biochemical evidence of ACTH deficiency. The ACTH on local measurement was not conclusive in keeping with ICI-related ACTH deficiency but when repeated using an alternative assay confirmed the diagnosis. The case illustrates the evolution of ACTH deficiency and exposes the potential pitfalls of screening strategies. Two important lessons may be gleaned from this case: (i) SSTs can be normal in early cases of secondary adrenal insufficiency, for example, hypophysitis due to adrenal reserve and (ii) when there is mismatch between the clinical and biochemical presentation, the ACTH should be repeated using a different assay. Learning points: Short synacthen tests, useful for ruling out adrenalitis and primary adrenal failure, may be normal in early adrenocorticotrophic hormone deficiency and secondary adrenal failure due to residual adrenal reserve.If clinical suspicion of adrenal insufficiency persists despite an initial satisfactory SST, it is important to recognise the need for re-assessment of cortisol levels.Insulin tolerance test remains a useful tool in the investigation of secondary adrenal insufficiency.Levothyroxine replacement may accelerate the metabolism of cortisol in cases of concurrent hypothyroidism and hypoadrenalism, and therefore, glucocorticoid replacement must precede levothyroxine treatment, to avoid adrenal crisis.The prevalence of immunotherapy-related endocrinopathies is likely to increase with increasing use of ICI and it is crucial that clinicians are alert to their subtle symptoms.

Retrograde Radiological Gastrostomy Technique and Retrograde Stent Placement in a Completely Occluded Cervical Esophagus.

Malignant obstruction of the cervical esophagus presents some anatomical and technical challenges when considering radiologic or endoscopic intervention. This case report describes the failure of antegrade access to place a gastrostomy tube and stent due to complete luminal occlusion from an esophageal tumor. The ultrasound-guided percutaneous gastric puncture was performed to achieve retrograde pneumodistension to allow radiologic gastrostomy insertion. Subsequently, the cervical esophagus was retrogradely cannulated via insertion of a guidewire from the gastrostomy site. A distal release esophageal stent was then inserted over the wire and deployed from the mouth in an antegrade manner. However, due to the unpredictable proximal shortening of distal release stents, this stent was eventually shortened and displaced so that it no longer covered the top of the tumor stricture, and further antegrade access failed. Once more, a retrograde access approach was adopted via the gastrostomy stoma, a guidewire and catheter were passed retrogradely through the original stent and out through the mouth. A distal release stent system was then inserted in a retrograde manner via the gastrostomy stoma, effectively making it a proximal release stent which enabled more precise positioning of the stent above the tumor. Palliation was achieved until death, and beyond expected mean survival.

Dynamics in insulin requirements and treatment safety.

AIMS: The majority of insulin users have elevated HbA1c. There is growing recognition that the low success rates are due to variations in insulin requirements. Thus, frequent dosage adjustments are needed. In practice, adjustments occur sporadically due to limited provider availability. We investigated intra-individual dynamics of insulin requirements using data from a service evaluation of the d-Nav® Insulin Guidance Service. This service facilitates automated insulin dosage adjustments, as often as needed, to achieve and maintain optimal glycemic balance. METHODS: Data were collected from subjects who have been using the service for more than a year. Events of considerable and persistent decrease in insulin requirements were identified by drops in total daily insulin ≥25%. RESULTS: Overall, 62 patients were studied over an average period of 2.1±0.5 (mean±standard deviation) years. Stability in HbA1c was attained after ~3 quarters at 7.4%±0.2% (57.4mmol/mol±1mmol/mol). Events were identified in 56.5% of the patients. On average, each affected patient had 0.8±0.4 events per year, lasting 9.7±6.6weeks, while total daily insulin dosage decreased by 41.4±13.4%. CONCLUSIONS: Our findings may call attention to a major contributing factor to hypoglycemia among insulin users. In reality, insulin dosage is seldom adjusted and thus transient periods of decrease in insulin requirements and overtreatment are usually overlooked.

A novel approach to optimise glycaemic control in insulin users.

Insulin therapy has been available for almost a century. However, its success rate is still disappointing where the majority of users sustain harmfully elevated glycated haemoglobin (HbA1c) levels. The key element essential for effective and safe insulin therapy is frequent dosage titration to overcome constant variations in insulin requirements. In reality, dosage titration is done sporadically during clinic visits. A scalable solution to this problem is being reviewed. A diabetes nurses service improves glycaemic control without overburdening the health system. The service relies on a handheld device, which provides patients with an insulin dose recommendation for each injection while using the device to monitor glucose. Similar to the approach providers use during clinical encounters, the device analyses stored glucose trends and constantly titrates insulin dosage without care providers' supervision. In this report, we describe the logic behind the technology by providing examples from users.