Treatment Guidelines for Hyponatremia Stay the Course

International guidelines designed to minimize the risk of complications that can occur when correcting severe hyponatremia have been widely accepted for a decade. On the basis of the results of a recent large retrospective study of patients hospitalized with hyponatremia, it has been suggested that hyponatremia guidelines have gone too far in limiting the rate of rise of the serum sodium concentration; the need for therapeutic caution and frequent monitoring of the serum sodium concentration has been questioned. These assertions are reminiscent of a controversy that began many years ago. After reviewing the history of that controversy, the evidence supporting the guidelines, and the validity of data challenging them, we conclude that current safeguards should not be abandoned. To do so would be akin to discarding your umbrella because you remained dry in a rainstorm. The authors of this review, who represent 20 medical centers in nine countries, have all contributed significantly to the literature on the subject. We urge clinicians to continue to treat severe hyponatremia cautiously and to wait for better evidence before adopting less stringent therapeutic limits.</p

Tissue Glucocorticoid Metabolism in Adrenal Insufficiency:A Prospective Study of Dual-release Hydrocortisone Therapy

Background: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo.Study Design and Methods: Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls.Results: Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11β-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11β-HSD2 activity. Hepatic 11β-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11β-HSD1 in subcutaneous adipose tissue.Conclusion: Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC

A Systematic Approach to the Treatment of Hyponatraemia.

The work in this thesis was designed to develop an evidence base for the mainstays of treatment of acute and chronic hyponatraemia, and to contribute to our understanding of the morbidity and mortality associated with hyponatraemia. The work provides the first head to head comparison of bolus and slow infusion of 3% saline in acute syndrome of inappropriate antidiuresis (SIAD), and demonstrates bolus administration of 3% saline is associated with faster initial elevation of plasma sodium concentration and improvement in GCS, thus supporting the switch to bolus treatment of symptomatic acute SIAD. We present the first prospective randomised controlled trial data for fluid restriction in chronic SIAD, using prospective data in a well-defined cohort of patients. The results highlight the suboptimal efficacy of fluid restriction in a significant proportion of patients with chronic SIAD. The thesis also illustrates how improvements in the management approach to hyponatraemia in our hospital have led to a reduction in mortality in patients with severe hyponatraemia over time. While hyponatraemia-treatment rates are higher in elderly patients than their younger counterparts with hyponatraemia, plasma sodium is more often uncorrected at discharge. Hyponatraemia in both age groups is associated with increased mortality compared with eunatraemic controls, but the impact is greater in younger patients. The data produced from these studies emphasise the clinical need for other treatment strategies for chronic SIAD, particularly if a clinically significant reduction in morbidity is to be targeted, both in clinical practice and in future research studies.</p

How should we interrogate the hypothalamic-pituitary-adrenal axis in patients with suspected hypopituitarism?

Hypopituitarism is deficiency of one or more pituitary hormones, of which adrenocorticotrophic hormone (ACTH) deficiency is the most serious and potentially life-threatening. It may occur in isolation or, more commonly as part of more widespread pituitary failure. Diagnosis requires demonstration of subnormal cortisol rise in response to stimulation with hypoglycemia, glucagon, ACTH(1-24) or in the setting of acute illness. The choice of diagnostic test should be individualised for the patient and clinical scenario. A random cortisol and ACTH level may be adequate in making a diagnosis in an acutely ill patient with a suspected adrenal crisis e.g. pituitary apoplexy. Often however, dynamic assessment of cortisol reserve is needed. The cortisol response is both stimulus and assay- dependent and normative values should be derived locally. Results must be interpreted within clinical context and with understanding of potential pitfalls of the test used. </p

An evolving spectrum of diabetes in a woman with GCK-MODY

Coexistence of autoimmune diabetes and maturity-onset diabetes of the young (MODY) is rare. We report the first case of coexisting latent autoimmune diabetes of adulthood (LADA) and glucokinase (GCK) MODY. A 32-year-old woman was treated with insulin for gestational diabetes at age 32 years; post-partum, her fasting blood glucose was 6.0 mmol/L and 2-h glucose was 11.8 mmol/L following an oral glucose tolerance test, and she was maintained on diet alone. Five years later, a diagnosis of LADA was made when she presented with fasting blood glucose of 20.3 mmol/L and HbA1C 125 mmol/mol (13.6%). GCK-MODY was identified 14 years later when genetic testing was prompted by identification of a mutation in her cousin. Despite multiple daily insulin injections her glycaemic control remained above target and her clinical course has been complicated by multiple episodes of hypoglycaemia with unawareness. Although rare, coexistence of latent autoimmune diabetes of adulthood and monogenic diabetes should be considered if there is a strong clinical suspicion, for example, family history. Hypoglycaemic unawareness developed secondary to frequent episodes of hypoglycaemia using standard glycaemic targets for LADA. This case highlights the importance of setting fasting glucose targets within the expected range for GCK-MODY in subjects with coexisting LADA

Acute airway compromise due to parathyroid tumour apoplexy: an exceptionally rare and potentially life-threatening presentation

Abstract Background Spontaneous haemorrhage into a parathyroid adenoma is a rare and potentially life-threatening presentation. Case presentation We report the case of a 45 year old female recently diagnosed with primary hyperparathyroidism who presented with chest discomfort and acute airway compromise due to spontaneous extracapsular haemorrhage into a parathyroid adenoma. Computed tomography (CT) imaging showed a hypopharyngeal haematoma extending 10 cm into the superior mediastinum. Surgical decompression of the cyst followed by enbloc resection of the parathyroid tumour was performed after elective intubation. Calcium and parathyroid hormone (PTH) levels had fallen prior to surgery and remain normal post-operatively. Conclusion Spontaneous parathyroid haemorrhage should be considered in any patient with unexplained spontaneous cervical haemorrhage, particularly if there is a history of hyperparathyroidism. Initial evaluation of such patients should include serum calcium and PTH as well as imaging

Erratum to: Acute airway compromise due to parathyroid tumour apoplexy: an exceptionally rare and potentially life-threatening presentation

BACKGROUND: Spontaneous haemorrhage into a parathyroid adenoma is a rare and potentially life-threatening presentation. CASE PRESENTATION: We report the case of a 45 year old female recently diagnosed with primary hyperparathyroidism who presented with chest discomfort and acute airway compromise due to spontaneous extracapsular haemorrhage into a parathyroid adenoma. Computed tomography (CT) imaging showed a hypopharyngeal haematoma extending 10 cm into the superior mediastinum. Surgical decompression of the cyst followed by enbloc resection of the parathyroid tumour was performed after elective intubation. Calcium and parathyroid hormone (PTH) levels had fallen prior to surgery and remain normal post-operatively. CONCLUSION: Spontaneous parathyroid haemorrhage should be considered in any patient with unexplained spontaneous cervical haemorrhage, particularly if there is a history of hyperparathyroidism. Initial evaluation of such patients should include serum calcium and PTH as well as imaging