Maria Tomkins

Central diabetes insipidus (CDI) is a clinical syndrome which results from loss or impaired function of vasopressinergic neurons in the hypothalamus/posterior pituitary, resulting in impaired synthesis and/or secretion of arginine vasopressin (AVP). AVP deficiency leads to the inability to concentrate urine and excessive renal water losses, resulting in a clinical syndrome of hypotonic polyuria with compensatory thirst. CDI is caused by diverse etiologies, although it typically develops due to neoplastic, traumatic, or autoimmune destruction of AVP-synthesizing/secreting neurons. This review focuses on the diagnosis and management of CDI, providing insights into the physiological disturbances underpinning the syndrome. Recent developments in diagnostic techniques, particularly the development of the copeptin assay, have improved accuracy and acceptability of the diagnostic approach to the hypotonic polyuria syndrome. We discuss the management of CDI with particular emphasis on management of fluid intake and pharmacological replacement of AVP. Specific clinical syndromes such as adipsic diabetes insipidus and diabetes insipidus in pregnancy as well as management of the perioperative patient with diabetes insipidus are also discussed.

Hyponatremia is the most common electrolyte disturbance seen in clinical practice, affecting up to 30% of acute hospital admissions, and is associated with significant adverse clinical outcomes. Acute or severe symptomatic hyponatremia carries a high risk of neurological morbidity and mortality. In contrast, chronic hyponatremia is associated with significant morbidity including increased risk of falls, osteoporosis, fractures, gait instability, and cognitive decline; prolonged hospital admissions; and etiology-specific increase in mortality. In this Approach to the Patient, we review and compare the current recommendations, guidelines, and literature for diagnosis and treatment options for both acute and chronic hyponatremia, illustrated by 2 case studies. Particular focus is concentrated on the diagnosis and management of the syndrome of inappropriate antidiuresis. An understanding of the pathophysiology of hyponatremia, along with a synthesis of the duration of hyponatremia, biochemical severity, symptomatology, and blood volume status, forms the structure to guide the appropriate and timely management of hyponatremia. We present 2 illustrative cases that represent common presentations with hyponatremia and discuss the approach to management of these and other causes of hyponatremia.

INTRODUCTION: Metabolic encephalopathy is a rare but potentially devastating complication of diabetic ketoacidosis (DKA). This case highlights the dramatic cognitive decline of a young man due to metabolic encephalopathy complicating DKA. The aims of this case report are to highlight metabolic encephalopathy as a complication of DKA and to explore the current research in diabetic related brain injury. The importance of investigation and treatment of reversible causes of encephalopathy is also demonstrated. CASE PRESENTATION: A 35-year-old man with a background of type 1 diabetes mellitus (T1DM) and relapsing remitting multiple sclerosis (RRMS) presented to the emergency department (ED) in a confused and agitated state. Prior to admission he worked as a caretaker in a school, smoked ten cigarettes per day, took excess alcohol and smoked cannabis twice per week. Following initial investigations, he was found to be in DKA. Despite timely and appropriate management his neurological symptoms and behavioural disturbance persisted. Neuroimaging revealed temporal lobe abnormalities consistent with an encephalopathic process. The patient underwent extensive investigation looking for evidence of autoimmune, infective, metabolic, toxic and paraneoplastic encephalopathy, with no obvious cause demonstrated. Due to persistent radiological abnormalities a temporal lobe biopsy was performed which showed marked astrocytic gliosis without evidence of vasculitis, inflammation, infarction or neoplasia. A diagnosis of metabolic encephalopathy secondary to DKA was reached. The patient's cognitive function remained impaired up to 18 months post presentation and he ultimately required residential care. CONCLUSIONS: Metabolic encephalopathy has been associated with acute insults such as DKA, but importantly, the risk of cerebral injury is also related to chronic hyperglycaemia. Mechanisms of cerebral injury in diabetes mellitus continue to be investigated. DKA poses a serious and significant neurological risk to patients with diabetes mellitus. To our knowledge this is the second case report describing this acute complication.

BACKGROUND: Long-term glucocorticoid therapy is a key component of immunosuppression for kidney transplant recipients (KTRs), leading to significant cumulative glucocorticoid exposure. The aims of this study are to investigate the prevalence of adrenal insufficiency (AI) in KTRs taking prednisolone and to develop a screening algorithm to identify patients at the highest risk of AI. METHODS: In this cross-sectional cohort study, 67 KTRs receiving prednisolone underwent a short synacthen test (SST) and measurement of cumulative glucocorticoid exposure. RESULTS: A total of 72% (n = 48) of participants failed the SST. Participants with AI had a higher daily prednisolone dose (4.9 versus 4.2 mg/day; P = .002) and greater cumulative glucocorticoid exposure (289 versus 111 mg/kg; P = .03) than those with intact adrenal function. Participants with AI had lower baseline cortisol than participants with intact adrenal function (143 versus 303 nmol/L; P < .001). Morning cortisol of >288 nmol/L predicted a normal SST with 100% specificity [95% confidence interval (CI) 92-100] and 70% sensitivity (95% CI 56-78%), therefore excluding AI. CONCLUSIONS: Our results suggest KTRs are at a 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%. KTRs with AI need education regarding glucocorticoid sick rules, similar to patients with other forms of AI.