Background Long-term glucocorticoid therapy is a key component of immunosuppression for kidney transplant recipients (KTR), leading to significant cumulative glucocorticoid exposure. The aims of this study are to investigate the prevalence of adrenal insufficiency (AI) in KTR taking prednisolone and to develop a screening algorithm to identify patients at highest risk of AI. Methods In this cross-sectional cohort study, 67 KTR receiving prednisolone underwent a short synacthen test (SST) and measurement of cumulative glucocorticoid exposure. Results 72% (n = 48) of participants failed the SST. Participants with AI had a higher daily prednisolone dose (4.9 vs 4.2mg/day,  p = 0.002) and greater cumulative glucocorticoid exposure (289 vs 111mg/kg,  p = 0.03) than those with intact adrenal function. Participants with AI had a lower baseline cortisol than participants with intact adrenal function (143 vs 303nmol/l,  p < 0.001). Morning cortisol of > 288nmol/l predicted a normal SST with 100% specificity (95% CI 92–100%) and 70% sensitivity (95% CI 56–78%), therefore excluding AI. Conclusions Our results suggest KTR are at higher risk for AI than previously reported. A morning serum cortisol measurement is a useful screening tool in this cohort, reducing the need for stimulatory testing by 44%. KTR with AI need education regarding glucocorticoid sick rules similar to patients with other forms of AI.

Summary Acute respiratory distress syndrome (ARDS) is a rare but life-threatening complication of diabetic ketoacidosis (DKA). We present the case of a young female, with no previous diagnosis of diabetes, presenting in DKA complicated by ARDS requiring extra corporeal membrane oxygenation (ECMO) ventilator support. This case report highlights the importance of early recognition of respiratory complications of severe DKA and their appropriate management. Learning points ARDS is a very rare but life-threatening complication in DKA. The incidence of ARDS remains unknown but less frequent than cerebral oedema in DKA. The mechanism of ARDS in DKA has multifactorial aetiology, including genetic predisposition. Early recognition and consideration of rare pulmonary complication of DKA can increase survival rate and provide very satisfactory outcomes. DKA patients who present with refractory ARDS can be successfully rescued by ECMO support.

Background Immune checkpoint inhibitors (ICIs) are a novel class of oncological agents which are used to treat a number of malignancies. To date seven agents have been approved by the Food and Drug Administration (FDA) to treat both solid and haematological malignancies. Despite their efficacy they have been associated with a number of endocrinopathies. We report a unique case of hypophysitis, thyroiditis, severe hypercalcaemia and pancreatitis following combined ICI therapy. Case presentation A 46-year old Caucasian female with a background history of malignant melanoma and lung metastases presented to the emergency department with lethargy, nausea, palpitations and tremors. She had been started on a combination of nivolumab and ipilimumab 24 weeks earlier. Initial investigations revealed thyrotoxicosis with a thyroid stimulating hormone (TSH) of < 0.01 (0.38–5.33) mIU/L, free T4 of 66.9 (7–16) pmol/.L. TSH receptor and thyroperoxidase antibodies were negative. She was diagnosed with thyroiditis and treated with a beta blocker. Six weeks later she represented with polyuria and polydipsia. A corrected calcium of 3.54 (2.2–2.5) mmol/l and parathyroid hormone (PTH) of 9 (10–65) pg/ml confirmed a diagnosis of non-PTH mediated hypercalcaemia. PTH-related peptide and 1, 25-dihydroxycholecalciferol levels were within the normal range. Cross-sectional imaging and a bone scan out ruled bone metastases but did reveal an incidental finding of acute pancreatitis – both glucose and amylase levels were normal. The patient was treated with intravenous hydration and zoledronic acid. Assessment of the hypothalamic-pituitary-adrenal (HPA) axis uncovered adrenocorticotrophic hormone (ACTH) deficiency with a morning cortisol of 17 nmol/L. A pituitary Magnetic Resonance Image (MRI) was unremarkable. Given her excellent response to ICI therapy she remained on ipilimumab and nivolumab. On follow-up this patient’s thyrotoxicosis had resolved without anti-thyroid mediations – consistent with a diagnosis of thyroiditis secondary to nivolumab use. Calcium levels normalised rapidly and remained normal. ACTH deficiency persisted, and she is maintained on oral prednisolone. Conclusion This is a remarkable case in which ACTH deficiency due to hypophysitis; thyroiditis; hypercalcaemia and pancreatitis developed in the same patient on ipilimumab and nivolumab combination therapy. We postulate that hypercalcaemia in this case was secondary to a combination of hyperthyroidism and secondary adrenal insufficiency.

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Background  Fine needle aspiration (FNA) cytology is the preferred method for assessing thyroid nodules for malignancy. Concern remains about the rate of false negative results. The primary aim of this study is to investigate the malignancy rate of thyroid nodules initially classified as benign (Thy 2). Methods We retrospectively examined 658 nodules in 653 (429 female) patients between January 2013 to December 2017. All FNA biopsies (FNABs) were performed under ultrasound (US) guidance by a radiologist with expertise in thyroid pathology. Nodules were cytologically classified according to the UK Royal College of Pathologists guidelines. Decisions about further management were made at a regular thyroid multidisciplinary meeting. Follow up of the Thy 2 nodules was determined based on clinical and radiological criteria. Results The mean age (± SD) was 53.2 (14.6) years. Five hundred out of 658 (76.0%) nodules were classified as Thy 2 (benign) after the first FNAB. Of these thyroid nodules initially classified as benign, 208 (41.6%) underwent repeat FNAB and 9 (1.8%) were surgically removed without repeat FNAB. The remainder were followed up clinically and/or radiologically. Seven (1.4%) of nodules initially classified as Thy 2 were later shown to be or to harbor malignancy after a follow-up of 74.5 (± 19.7) months. Papillary thyroid microcarcinomas were found co-incidentally in two thyroid glands of benign nodules, giving a true prevalence of 5/500 (1.0%). Conclusions With a well targeted FNAB, the false negative rate of an initial benign thyroid FNA is very low thus routine second FNAB is not required in patients with a thyroid nodule initially deemed benign. Multidisciplinary input is imperative in informing decision making.

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The co-existence of a corticotroph adenoma and a pituitary cyst is very unusual. We present the case of a 50-year-old female who presented with a Cushingoid phenotype, severe hypokalaemia, hyperglycaemia and hypertension. Urinary free cortisol was markedly elevated at 50 fold. ACTH levels were elevated at 121.4 pg/ml. She failed both the low and high dose dexamethasone suppression tests. The CRF test did not show a satisfactory rise in ACTH levels but the Inferior petrosal sinus sampling revealed a central to peripheral ACTH gradient highly suggestive of Pituitary dependant Cushing’s. MRI pituitary revealed a large cystic lesion with a small solid component. Computed Tomography (CT) of thorax abdomen and pelvis was normal. A trans-sphenoidal hypophysectomy was performed, during which a fine needle aspiration of the intra-cystic fluid was obtained. This showed markedly elevated pituitary hormone levels of ACTH (1399pg/ml), prolactin (353,084mIU/L), TSH (217IU/L) FSH (205mIU/ml) and GH (519 ng/ml) consistent with a multifunctional pituitary cyst. Neuropathology of the solid component confirmed a corticotroph adenoma. Post-operative am cortisol levels were persistently suppressed to less than 50 nmol/l with marked improvement in clinical features. This case highlights the challenges in the work up of Cushing’s syndrome and the limitations of diagnostic tests. The coexistence of a corticotroph adenoma and a multifunctional pituitary cyst is very unusual and to our knowledge has not been reported before.