Voriconazole-Associated Periostitis: New Insights into Pathophysiology and Management.

Voriconazole-associated periostitis (VAP) is an underrecognized and unpredictable side effect of long-term voriconazole therapy. We report two cases of VAP occurring in the post-transplant setting: a 68-year-old lung transplant recipient who required ongoing voriconazole therapy, in whom urinary alkalinization was used to promote fluoride excretion and minimize voriconazole-related skeletal toxicity, and a 68-year-old stem-cell transplant recipient with a high voriconazole dose requirement, identified on pharmacogenomic testing to be a CYP2C19 ultrarapid metabolizer, the dominant enzyme in voriconazole metabolism. This is the first reported case of pharmacogenomic profiling in VAP and may explain the variability in individual susceptibility to this uncommon adverse effect. Our findings provide new insights into both the management and underlying pathophysiology of VAP. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Copeptin is increased by nausea and vomiting during hypertonic saline infusion in healthy individuals.

OBJECTIVE: Measurement of hypertonic saline-stimulated copeptin has recently been described for the differentiation of polyuria-polydipsia syndrome. This study aims to determine the copeptin response to intravenous 3% hypertonic saline, including evaluation of adverse effects, in a local cohort of healthy adults >18 years in Australia. DESIGN: Prospective clinical study. METHODS: Twenty healthy volunteers (10 males and 10 females) were recruited. Participants underwent infusion of 3% hypertonic saline via a previously described standardized protocol, until the plasma sodium was ≥150 mmol/L, with measurement of plasma copeptin. RESULTS: Mean peak sodium was 152 mmol/L ± SD 1.4 with osmolality 315 mmol/kg ± SD 3.9. Median volume of hypertonic saline infused to reach target sodium ≥ 150 mmol/L was 1536 mL (IQR 1362, 1992). Mean rate of plasma sodium rise was 5.9 mmol/L/hour ± SD 1.5. Hypertonic saline-stimulated copeptin had non-parametrical distribution with median of 33.8 pmol/L (IQR 27.6, 63.6). Overall median symptom burden was 6/10 (range 3/10-9/10). Copeptin was significantly higher for those who experienced nausea and/or vomiting (n = 13) (median 39.0 pmol/L; IQR 32.5, 90), compared to those participants who did not experience either (median 20.0 pmol/L; IQR 13.0, 31.0) (P = 0.003). There were no serious adverse events. CONCLUSION: Hypertonic saline-stimulated copeptin measurements were similar in our population compared with previously reported reference intervals in healthy volunteers. There is a wide range of stimulated copeptin measurements in the healthy population. Nausea and vomiting are common adverse effects which enhance the copeptin response.

Antimicrobial stewardship in diabetic ketoacidosis: a single-centre experience.

BACKGROUND: Diabetic ketoacidosis (DKA) is a common and serious complication arising predominantly in patients with type 1 diabetes mellitus. International data demonstrate that infection is one of the most common precipitating causes of DKA. Currently there are limited data regarding the role of antimicrobial stewardship (AMS) in this setting. AIM: To provide epidemiologic data regarding infections precipitating DKA, microbiological aetiology and antimicrobial prescribing practices in order to inform AMS interventions. METHODS: Retrospective chart review of all type 1 diabetes mellitus DKA presentations from May 2015 to June 2018. RESULTS: In total, 249 DKA presentations occurred in 111 patients. Suspected infection accounted for 100/249 (40%) presentations, and only 36/249 (14.5%) were proven or probable infections. Skin and soft tissue infection was the most common (9/36, 25%), followed by urinary tract infection (8/36, 22%) and respiratory tract infection (7/36, 19%). A pathogen was identified in 24/100 presumed infections and included Staphylococcus aureus (24, 46%), Klebsiella pneumoniae (4/24, 17%) and Escherichia coli (3/24, 13%). No viral pathogens were identified. Of 80 empirical antimicrobial prescriptions, 75% were inappropriate based on guideline management of the documented suspected infection. Single agent ceftriaxone was appropriately prescribed in 7/23 (30%) cases, and was most frequently prescribed overall 23/80 (29%). CONCLUSION: This study demonstrates a lower incidence of infection compared to most previous publications, and suggests that infection-precipitated DKA may be over reported. Furthermore, our findings provide support for the role of AMS in the management of DKA.

Diabetes care: addressing psychosocial well-being in young adults with a newly developed assessment tool.

BACKGROUND: Psychosocial assessment should be part of clinic visits for people with diabetes mellitus (DM). AIMS: To assess the usage and acceptance of a diabetes psychosocial assessment tool (DPAT) and to profile the clinical and psychosocial characteristics of young people with diabetes. METHODS: Over a 12-month period, young adults (18-25 years) attending diabetes clinic were offered DPAT. The tool embeds validated screening tools including the Problem Areas in Diabetes 20 (PAID-20) questionnaire, the Patient Health Questionnaire-4 (PHQ-4) and the World Health Organization Well-Being Index-5 (WHO-5). Baseline clinical data were collected and questions regarding social support, body image, eating concerns, hypoglycaemia and finances were included. RESULTS: Over the 12 month, the form was offered to 155 participants (64.6% of eligible attendees). The majority (96.1%) had type 1 DM with a mean duration of 10.5 (±5.3 SD) years. Average glycated haemoglobin (HbA1c) was 8.7% (±1.5 SD) (or 71.2 mmol/mol ±16.5 SD). Severe diabetes-related distress (PAID-20 ≥ 40) was found in 19.4%. Low WHO-5 scores (28-50 points) were seen in 14.8%. PHQ-4 identified 25.8% with anxiety and 16.1% with depression. Significant weight, shape and eating concerns were identified in 27.1, 26.6 and 28.4%, respectively. Serious hypoglycaemia concerns were raised by 4.5%. CONCLUSION: DPAT revealed a high prevalence of psychosocial stress among young adults with DM. The tool was easy to use and accepted by patients and may aid streamlining referrals to relevant members of a multidisciplinary team.

Visual loss in pregnancy.

Visual loss in pregnancy may be caused by a variety of reasons including pituitary adenomas. Prolactinomas (PRLs) are the most common hormone-secreting tumours in pregnant women. As most PRLs present with menstrual abnormalities, infertility or galactorrhoea, they are most commonly diagnosed before pregnancy. We present the case of a 30-year-old primigravida who presented at 36+5 weeks gestation with headaches and left-sided visual loss. MRI of the pituitary gland confirmed a 10×11 mm left suprasellar mass. Results of her anterior pituitary function were unremarkable for her gestational age. Postpartum, she underwent an endoscopic endonasal resection of the pituitary tumour. The histology was consistent with a PRL. Literature review reveals only one possible case of a new diagnosis of a PRL during pregnancy. It highlights the importance to consider a wide range of differential diagnoses when assessing visual loss in pregnancy.

Man with epigastric pain and persistently elevated serum lipase.

Serum lipase and amylase are commonly requested in individuals presenting with abdominal pain for investigation of acute pancreatitis. Pancreatic hyperenzymaemia is not specific for acute pancreatitis, occurring in many other pancreatic and non-pancreatic conditions. Where persistent elevation of serum lipase and amylase occurs in the absence of a diagnosed cause or evidence of laboratory assay interference, ongoing radiological assessment for pancreatic disease is required for 24 months before a diagnosis of benign pancreatic hyperenzymaemia can be made. We report a case of a 71-year-old man with epigastric pain and elevated serum lipase levels. He was extensively investigated, but no pancreatic disease was detected. He is asymptomatic, but serum lipase levels remain elevated 18 months after his initial presentation.

Rare case of meningococcal sepsis-induced testicular failure, primary hypothyroidism and hypoadrenalism: Is there a link?

Severe illness can lead to multiple transient endocrinopathies. In adult patients, neuroendocrine alterations include sick euthyroid syndrome, an increase in corticosteroid levels, increase in prolactin levels, decreased insulin growth factor 1 levels and hypogonadism. We report the case of a 24-year-old man with meningococcal sepsis with multiple end-organ complications who developed persistent non-autoimmune hypothyroidism, adrenal insufficiency and primary hypogonadism all requiring hormone replacement. While adrenal insufficiency as part of the Waterhouse-Friderichsen syndrome is well described, reports of primary hypothyroidism and persistent primary hypogonadism in severe illness are exceedingly rare. Multiple combined endocrinopathies as in this case have not been reported previously. This case highlights the necessity of screening for endocrine abnormalities in severe illness and the need for treatment if persistent. It also raises a novel concept of meningococcal sepsis causing multiple endocrinopathies possibly via disseminated intravascular coagulopathy-related ischaemic damage.

Should all patients with hyperparathyroidism be screened for a CDC73 mutation?

Primary hyperparathyroidism (PH) is a common endocrine abnormality and may occur as part of a genetic syndrome. Inactivating mutations of the tumour suppressor gene CDC73 have been identified as accounting for a large percentage of hyperparathyroidism-jaw tumour syndrome (HPT-JT) cases and to a lesser degree account for familial isolated hyperparathyroidism (FIHP) cases. Reports of CDC73 whole gene deletions are exceedingly rare. We report the case of a 39 year-old woman with PH secondary to a parathyroid adenoma associated with a large chromosomal deletion (2.5 Mb) encompassing the entire CDC73 gene detected years after parathyroidectomy. This case highlights the necessity to screen young patients with hyperparathyroidism for an underlying genetic aetiology. It also demonstrates that molecular testing for this disorder should contain techniques that can detect large deletions. LEARNING POINTS: Necessity of genetic screening for young people with hyperparathyroidism.Importance of screening for large, including whole gene CDC73 deletions.Surveillance for patients with CDC73 gene mutations includes regular calcium and parathyroid hormone levels, dental assessments and imaging for uterine and renal tumours.