Can mid-regional pro-adrenomedullin (MR-proADM) increase the prognostic accuracy of NEWS in predicting deterioration in patients admitted to hospital with mild to moderately severe illness? A prospective single-centre observational study.

OBJECTIVE: To assess the value added to the National Early Warning Score (NEWS) by mid-regional pro-adrenomedullin (MR-proADM) blood level in predicting deterioration in mild to moderately ill people. DESIGN: Prospective observational study. SETTING: The Medical Admissions Suite of the Royal Victoria Infirmary, Newcastle. PARTICIPANTS: 300 adults with NEWS between 2 and 5 on admission. Exclusion criteria included receiving palliative care, or admitted for social reasons or self-harming. Patients were enrolled between September and December 2015, and followed up for 30 days after discharge. OUTCOME MEASURE: The primary outcome measure was the proportion of patients who, within 72 hours, had an acuity increase, defined as any combination of an increase of at least 2 in the NEWS; transfer to a higher-dependency bed or monitored area; death; or for those discharged from hospital, readmission for medical reasons. RESULTS: NEWS and MR-proADM together predicted acuity increase more accurately than NEWS alone, increasing the area under the curve (AUC) to 0.61 (95% CI 0.54 to 0.69) from 0.55 (95% CI 0.48 to 0.62). When the confounding effects of presence of chronic obstructive pulmonary disease or heart failure and interaction with MR-proADM were included, the prognostic accuracy further increased the AUC to 0.69 (95% CI 0.63 to 0.76). CONCLUSIONS: MR-proADM is potentially a clinically useful biomarker for deterioration in patients admitted to hospital with a mild to moderately severe acute illness, that is, with NEWS between 2 and 5. As a growing number of National Health Service hospitals are routinely recording the NEWS on their clinical information systems, further research should assess the practicality and use of developing a decision aid based on admission NEWS, MR-proADM level, and possibly other clinical data and other biomarkers that could further improve prognostic accuracy.

An unusual cause of adrenal insufficiency and bilateral adrenal masses.

Primary adrenal insufficiency secondary to syphilis is extremely rare, with only five cases being reported in the literature. We report a case of adrenal insufficiency as a manifestation of Treponema pallidum infection (tertiary syphilis). A 69-year-old, previously fit and well Caucasian male was found to have adrenal insufficiency after being admitted with weight loss, anorexia and postural dizziness resulting in a fall. Biochemical testing showed hyponatraemia, hyperkalaemia, and an inadequate response to Synacthen testing, with a peak cortisol level of 302 nmol/L after administration of 250 µg Synacthen. Abdominal imaging revealed bilateral adrenal hyperplasia with inguinal and retroperitoneal lymphadenopathy. He was started on hydrocortisone replacement; however, it was not until he re-attended ophthalmology with a red eye and visual loss 1 month later, that further work-up revealed the diagnosis of tertiary syphilis. Following a course of penicillin, repeat imaging 5 months later showed resolution of the abnormal radiological appearances. However, adrenal function has not recovered and 3 years following initial presentation, the patient remains on both glucocorticoid and mineralocorticoid replacement. In conclusion, this case highlights the importance of considering syphilis as a potential differential diagnosis in patients presenting with adrenal insufficiency and bilateral adrenal masses, given the recent re-emergence of this condition. The relative ease of treating infectious causes of adrenal lesions makes accurate and timely diagnosis crucial. LEARNING POINTS: Infectious causes, including syphilis, should be excluded before considering adrenalectomy or biopsy for any patient presenting with an adrenal mass.It is important to perform a full infection screen including tests for human immunodeficiency virus, other blood-borne viruses and concurrent sexually transmitted diseases in patients presenting with bilateral adrenal hyperplasia with primary adrenal insufficiency.Awareness of syphilis as a potential differential diagnosis is important, as it not only has a wide range of clinical presentations, but its prevalence has been increasing in recent times.

Elevated serum fibroblast growth factor 21 levels correlate with immune recovery but not mitochondrial dysfunction in HIV infection.

BACKGROUND: Anti-retroviral treated HIV-infected patients are at risk of mitochondrial toxicity, but non-invasive markers are lacking. Serum FGF-21 (fibroblast growth factor 21) levels correlate strongly with muscle biopsy findings in inherited mitochondrial disorders. We therefore aimed to determine whether serum FGF-21 levels correlate with muscle mitochondrial dysfunction in HIV-infected patients. FINDINGS: We performed a cross-sectional study of anti-retroviral treated HIV-infected subjects (aged 29 - 71 years, n = 32). Serum FGF-21 levels were determined by quantitative ELISA. Cellular mitochondrial dysfunction was assessed by COX (cytochrome c oxidase) histochemistry of lower limb skeletal muscle biopsy. Serum FGF-21 levels were elevated in 66% of subjects. Levels correlated significantly with current CD4 lymphocyte count (p = 0.042) and with total CD4 count gain since initiation of anti-retroviral therapy (p = 0.016), but not with the nature or duration of past or current anti-retroviral treatment. There was no correlation between serum FGF-21 levels and severity of the muscle mitochondrial (COX) defect. CONCLUSIONS: Serum FGF-21 levels are a poor predictor of muscle mitochondrial dysfunction in contemporary anti-retroviral treated patients. Serum FGF-21 levels are nevertheless commonly elevated, in association with the degree of immune recovery, suggesting a non-mitochondrial metabolic disturbance with potential implications for future comorbidity.