Hypocalcemia and Hypophosphatemia following Concurrent Denosumab Injection and Ferric Carboxymaltose Infusion in a Patient with Normal Renal Function.

Hypocalcemia following denosumab administration is well described. Hypophosphatemia following an intravenous iron infusion is an increasingly recognized adverse effect. Intravenous iron preparations increase fibroblast growth factor 23 (FGF23) levels. This both stimulates renal phosphate excretion and reduces 1,25-dihydroxyvitamin D (1,25(OH)2D) levels, resulting in reduced calcium absorption. Both osteoporosis and iron deficiency are common and frequently co-occur. The convenience and efficacy of both denosumab, a subcutaneous injection, and ferric carboxymaltose (Ferinject®), a 15-minute intravenous infusion, both of which can be given in the primary care setting, make these preferred treatment options. However, prescribers are often unaware of potential adverse outcomes, especially when these medications are given in tandem. We present a case of symptomatic hypocalcemia and hypophosphatemia in a 29-year-old woman with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and normal renal function, in the setting of concurrent denosumab and ferric carboxymaltose administration for treatment of glucocorticoid-induced osteoporosis and iron deficiency anemia.

Adrenal gland haemorrhages following motor vehicle accident with resultant adrenal insufficiency.

Summary: Adrenal gland haemorrhage is an uncommon, yet likely under-diagnosed complication of high-impact trauma, such as motor vehicle accidents (MVA). It usually occurs with multi-trauma and is associated with additional injuries to the ribs, liver, kidney, spleen and vertebrae. Trauma cases with resultant adrenal gland injury have higher mortality rates. Primary adrenal insufficiency as a result of bilateral adrenal haemorrhage is potentially fatal. We report three cases of life-threatening adrenal insufficiency following adrenal injuries sustained in MVA's. Case 1 was a 60-year-old-male who presented with acute haemodynamic instability on admission. Case 2 was an 88-year-old female on anticoagulation for atrial fibrillation, who developed haemodynamic instability 10 days into her admission. Case 3 was a 46-year-old male who developed hyponatraemia 2 weeks post-MVA. All were commenced on stress dose hydrocortisone replacement with improvement in clinical status. Only case 1 has had complete adrenal axis recovery, whereas the other patients remain on maintenance hydrocortisone replacement. Our cases demonstrate acute and subacute presentations of adrenal insufficiency following traumatic bilateral adrenal haemorrhages and highlight the importance of assessing adrenal morphology and function in any trauma patient with haemodynamic instability or hyponatraemia. Learning points: Adrenal gland haemorrhage is an under-diagnosed consequence of high-impact trauma. Trauma patients with adrenal haemorrhage have a significantly increased mortality risk. Bilateral adrenal gland haemorrhage can result in life-threatening adrenal insufficiency requiring urgent glucocorticoid replacement. Biochemical assessment of the adrenocortical axis should be considered in all patients presenting with high-impact trauma following motor vehicle accidents. Given the potential for delayed presentation, any patients with new haemodynamic instability should have repeat biochemistry and/or imaging performed, even if initial adrenal imaging and investigations were normal.

Poor Glycemic Control Is Associated With Decreased Survival in Lung Transplant Recipients.

BACKGROUND: Diabetes mellitus (DM) is associated with increased mortality after transplantation, but the effect of glycemic control on survival is unknown.We sought to determine the relationship between glycemic control (random blood glucose [RBG], fasting blood glucose [FBG], and glycated hemoglobin [HbA1c]) and survival in all lung transplant (LTx) recipients and those with either persistent or no DM. METHODS: All 210 LTx recipients from August 1, 2010 to November 1, 2013, were included (median observation 3.0 years). All underwent oral glucose tolerance tests pre-LTx and serially post-LTx. All glucose and HbA1c results from LTx until study end were included, and hazard ratios were calculated. RESULTS: Of 210 patients, 90 had persistent DM, and 84 had no DM. Overall mortality/repeat LTx was 31%. In the whole cohort, each 1 mM (18 mg/dL) increase in mean FBG and RBG and each 1% increase in mean HbA1c were associated with mortality increases of 18% (95% confidence interval [CI], 5-32%, P = 0.006), 38% (95% CI, 15-65%; P < 0.001), and 46% (95% CI, 15-85%; P = 0.002), respectively. RBG correlated with mortality in the persistent DM and no DM groups, 37% (95% CI, 7-75%; P = 0.012) and 109% (95% CI, 3-323%; P = 0.041) increases/1 mM, respectively). CONCLUSIONS: Glycemic control strongly correlates with survival after LTx. RBG predicted mortality overall and in patients with and without DM. We propose hyperglycemia be managed promptly after LTx.

Prevalence and predictors of diabetes after lung transplantation: a prospective, longitudinal study.

OBJECTIVE: To determine incidence and prevalence of diabetes mellitus (DM) after lung transplantation (LTx), identify risk factors for persistent DM after LTx, and determine its effect on survival. RESEARCH DESIGN AND METHODS: This was a prospective, longitudinal study comparing DM status before and after LTx using oral glucose tolerance tests (OGTTs). DM prevalence and changes in metabolic control over time were determined. Risk factors for persistent DM and survival differences by DM status were assessed. RESULTS: Between August 2010 and December 2012, 156 patients underwent LTx. DM prevalence after 3, 12, and 24 months was 47%, 44%, and 40%, respectively. A further 20%, 11%, and 7% had impaired glucose tolerance and/or impaired fasting glucose. Incidence of new-onset DM after transplant (NODAT) was 32%, 30%, and 24% after 3, 12, and 24 months. Nonfasting insulin levels and second phase insulin release fell 3 months after transplant (Tx) but returned to baseline by 2 years. The only risk factors for NODAT were 1- and 2-h glucose levels on pre-Tx OGTT (OR 1.73 [95% CI 1.19-2.50], P = 0.004, and 1.84 [1.22-2.77], P = 0.004, respectively). Survival was reduced in patients with DM at study end versus those without (estimated mean 979 days [95% CI 888-1,071] vs. 1,140 days [1,070-1,210], P = 0.023). CONCLUSIONS: Most patients had dysglycemia during the first year after LTx, and 32% developed NODAT. Hyperglycemia was caused both by ß-cell dysfunction and by insulin resistance. Only pre-Tx OGTT glucose levels predicted persistent NODAT. As DM was common and associated with reduced survival, early detection and management of DM in LTx recipients are warranted.

An unexpectedly high prevalence of undiagnosed diabetes in patients awaiting lung transplantation.

BACKGROUND: Diabetes mellitus (DM) is a common complication after lung transplantation but its prevalence prior to transplantation has not been determined. We sought to determine the prevalence of and risk factors for DM in adults awaiting lung transplantation and to determine whether pre-transplant DM could be diagnosed by hemoglobin A1c (HbA1c) alone. METHODS: All patients wait-listed for lung transplantation over a 2-year period had HbA1c measured. Those not known to have DM also underwent an oral glucose tolerance test (OGTT) with insulin levels. RESULTS: Of 190 patients listed for lung transplantation, 30 (16%) had been diagnosed previously with DM. Twelve patients received transplants and 1 came off the waiting list before having an OGTT. The remaining patients underwent OGTT: 14 were newly diagnosed with DM and 29 with pre-diabetes. One patient vomited during the test and was excluded from analyses. Thus, 41% of all screened waiting list patients had DM (known or newly diagnosed) or pre-diabetes. Neither age, BMI, prednisolone dose nor family history correlated with dysglycemia. Patients with newly diagnosed DM and pre-diabetes were more insulin-resistant than those with normoglycemia. HbA(1c) correlated poorly with OGTT. CONCLUSIONS: Patients awaiting lung transplantation have unexpectedly high rates of DM and pre-diabetes despite close medical follow-up. Screening for DM with an OGTT will allow early intervention, which may improve outcomes after transplantation.

Efficacy and safety of oral continuous low-dose versus short-term high-dose vitamin D: a prospective randomised trial conducted in a clinical setting.

OBJECTIVE: To compare the efficacy and safety of a 10-day, high-dose v a 3-month, continuous low-dose oral cholecalciferol course in a vitamin D deficient population. The primary end points were the change in serum 25-hydroxyvitamin D (25(OH)D) concentrations at 3 months and the development of hypercalcaemia and hypercalciuria. DESIGN, SETTING AND PARTICIPANTS: Fifty-nine vitamin D deficient inpatients (serum 25(OH)D < or = 50 nmol/L) were enrolled in a prospective, randomised, open-label trial. Participants were randomly assigned to a high-dose regimen of cholecalciferol 50 000 IU daily for 10 days or a 3-month, continuous low-dose cholecalciferol regimen of 3000 IU daily for 30 days, followed by 1000 IU daily for 60 days. Both groups received calcium citrate 500 mg daily. RESULTS: Twenty-six patients completed the study within 3 - or + 1 months. The mean increases in serum 25(OH)D were similar in both the high- and low-dose groups (to 55 v 51 nmol/L, respectively; P = 0.9). There was no significant difference in the proportion of subjects who attained serum 25(OH)D concentrations > 50 nmol/L between the high- and low-dose groups (9/10 v 13/14, respectively; P = 1.0). Hypercalciuria (urine calcium > 7.5 mmol/day) occurred in three patients (two low-dose, one high-dose), while renal impairment worsened in one patient. No patient developed hypercalcaemia (corrected calcium > 2.6 mmol/L), vitamin D toxicity (25(OH)D > 200 nmol/L) or nephrolithiasis during the study. CONCLUSION: Both the 10-day, high-dose and the 3-month, low-dose cholecalciferol regimens effectively increased serum 25(OH)D to within the normal range. The high-dose regimen may be an effective and cheap alternative for patients with vitamin D deficiency. TRIAL REGISTRATION: Australian Clinical Trials Registry ACTRN 12607000338460.

Cushing syndrome in a young woman due to primary pigmented nodular adrenal disease.

OBJECTIVE: To report a case of Cushing syndrome due to apparently sporadic primary pigmented nodular adrenal disease in a young woman. METHODS: We describe the clinical, biochemical, radiologic, and histologic findings of Cushing syndrome due to the rare condition of primary pigmented nodular adrenal disease. RESULTS: A 30-year-old woman presented with a 2-year history of worsening itch without rash over her shoulders and arms and weight gain, particularly around the abdomen and face. Careful questioning did not elicit any history of exogenous glucocorticoid use (systemic or topical), including hydrocortisone. On examination, the patient had a slightly rounded and plethoric face, a small buffalo hump, central adiposity, and thin skin with a few small striae on her inner thighs. No features of the Carney complex were observed. Investigations showed hypercortisolism with suppressed corticotropin and normal adrenal imaging despite documentation of enlarged adrenal glands at removal. High-dose dexamethasone administration was followed by a decrease in urinary free cortisol excretion rather than a paradoxical rise as previously reported in primary pigmented nodular adrenal disease. No mutations were detected in the PRKAR1A gene. CONCLUSIONS: Primary pigmented nodular adrenal disease should be suspected in patients with corticotropin-independent Cushing syndrome who have normal adrenal imaging. The role of genetic testing in apparently sporadic cases is not established, but cumulative experience may be helpful in defining the frequency of PRKAR1A mutations.