Denosumab-associated hypocalcemia: Does gender play a role?

OBJECTIVE: It is well recognized that the presentation, treatment, and outcomes of various diseases may differ between men and women. We recently reported a 7.4% rate of denosumab-associated hypocalcemia in community-dwelling osteoporotic patients. This study sought to investigate the role of gender in this complication. STUDY DESIGN: Retrospective community-dwelling cohort. METHOD: The databases of a large health maintenance organization were searched for adult patients treated with denosumab for osteoporosis in 2010-2018. Rates and predictors of denosumab-associated hypocalcemia (serum calcium ≤8.5 mg/mL) were analyzed by gender. RESULTS: The cohort included 1871 women and 134 men. Compared with the women, the men were characterized by older median age (81 vs. 77 years, p = 0.005), higher likelihood to receive denosumab as a first-line treatment (22% vs. 6%, p < 0.001), less treatment with calcium supplements (42% vs. 53%, p = 0.012), and lower median eGFR level (66.1 vs. 79.8 mL/min/1.73m2, p < 0.001). Denosumab-associated hypocalcemia developed in 133 women (7.1%) and 16 men (11.9%) (p = 0.04); the drug was discontinued in 75% and 61%, respectively. The strongest predictors of hypocalcemia in women were levels of pretreatment albumin-adjusted serum calcium (OR 0.08, 95% CI (0.04, 0.14)) and creatinine (OR 2.43, 95% CI (1.45, 4.05)). There were no predictors in men. On propensity matching of 126 men and 126 women, gender was not a predictor of hypocalcemia. CONCLUSION: Denosumab-treated men were significantly older than treated women and had a lower eGFR and more advanced osteoporosis. These findings suggest that selection bias rather than male genderper se underlies the higher rate of denosumab-associated hypocalcemia in men.

Bone-Marrow Suppression in Elderly Patients Following Empiric Radioiodine Therapy: Real-Life Data.

Background: Elderly patients with differentiated thyroid cancer (DTC) tend to have more advanced disease at presentation, for which high activities of radioiodine (RAI) are often recommended. However, the 2015 American Thyroid Association guidelines recommend that empirically administered activities of RAI >150 mCi should be avoided in patients >70 years of age, based on calculated bone-marrow exposure according to two dosimetry-based studies. This study aimed to evaluate the effect of RAI treatment on bone-marrow function in elderly DTC patients. Methods: DTC patients ≥70 years of age who received RAI treatment and on whom a complete blood count was performed before and after treatment were included. Blood counts within one year before RAI and one year following treatment were compared in order to assess for marrow suppression. The impact of demographic, clinical, and laboratory variables on complete blood count were assessed. Results: One hundred fifty-three treatments in 122 patients met inclusion criteria, with a mean patient age of 76 ± 4.3 years, and 75% were women. High-risk features at presentation included T4 disease in 17%, lymph node metastases in 34%, and distant metastases in 14%. Mean RAI activity was 136.8 ± 48 mCi (82% ≥ 100 mCi, 66% ≥ 150 mCi). Of 153 RAI treatments analyzed, 114 (74%) were first treatments, 28 (18%) second treatments, seven (5%) third treatments, and four (3%) fourth treatments. At 0-3 months after RAI treatment, there was a statistically significant decrease in platelets (238 ± 66 vs. 216 ± 69 × 109/L, 10% decrease; p < 0.001), white blood cells (WBC; 6.9 ± 2 vs. 6.1 ± 1.9 × 109/L, 13% decrease; p < 0.001), and hemoglobin (Hb) in women (12.8 ± 1.1 vs. 12.4 ± 1.1 g/dL, 3% decrease; p = 0.01). Mean platelets, WBC, Hb in women, and lymphocytes remained decreased (but within the reference range) one year after treatment. Subgroup analysis demonstrated platelet suppression only with activities ≥100 mCi, and WBC and Hb suppression only with activities ≥150 mCi, with mean values within the reference ranges. There were no clinically significant cytopenia events during follow-up. Conclusions: Empiric RAI treatment in elderly patients causes mild bone-marrow suppression, with little clinical significance. Activities of 150-200 mCi can be safely used when indicated.

Cushing's syndrome: comparison between Cushing's disease and adrenal Cushing's.

PURPOSE: The most common etiology of Cushing's syndrome (CS) is an ACTH-producing pituitary adenoma (pitCS), reported as 2-3 times more frequent than primary adrenal CS (adrCS). We aimed to analyze and compare features of patients with pitCS and adrCS. METHODS: A retrospective file review of 196 consecutive patients (age 46.8 ± 15.6 years, 76% female) diagnosed with CS in 2000-2017 and followed for 5.2 ± 4.2 years; 109 (55.6%) had pitCS and 76 (38.8%) adrCS. Epidemiologic, clinical and biochemical factors were compared between and within the pitCS and adrCS groups. RESULTS: The relative proportion of pitCS to adrCS (1.4) was lower than previously reported and gradually decreased during the study years to only 1.2 in 2012-2017. The most common reason for CS screening was weight-gain in the pitCS group (48.6%) and adrenal incidentaloma in the adrCS group (39.5%). The pitCS patients were diagnosed at younger age (42.5 ± 15.1 vs. 51.6 ± 15.1 years, p < 0.001) and had lower prevalence of hypertension (51.4 vs. 74%, p = 0.005). There was no between-group difference in severity of hypercortisoluria. Within the adrCS group, patients diagnosed after detection of an adrenal incidentaloma had milder hypercortisoluria than the remaining patients, presented with smaller adrenal lesions (35.9 ± 16.3 vs. 49.1 ± 33.7 cm, p = 0.04), and received post-adrenalectomy glucocorticoid treatment for shorter periods (13 ± 11.6 vs. 31 ± 40 months, p = 0.04). CONCLUSIONS: The relative proportion of adrCS to pitCS is rising, probably because of an increasing detection of cortisol-secreting adrenal incidentalomas associated with milder hypercortisolism. There is no difference between pitCS and adrCS in the severity of hypercortisoluria, although significant clinical differences were found.

Predictors of hypoglycemia in hospitalized patients with diabetes mellitus.

Hypoglycemia is common among hospitalized patients with diabetes mellitus (DM), and is associated with increased morbidity and mortality. Identify pre-admission risk factors associated with in-hospital hypoglycemia. Historical prospectively collected data of adult DM patients hospitalized to medical wards between 2011 and 2013. Hypoglycemia and serious hypoglycemia were defined as at least one blood glucose measurement ≤ 70 and < 54 mg/dl, respectively, during hospitalization. The primary outcome was in-hospital hypoglycemia. The cohort included 5301 patients (mean age 73 ± 13 years, 51% male), including 792 patients (15%) with hypoglycemia, among them 392 patients (7%) with serious hypoglycemia. Patients with hypoglycemia or serious hypoglycemia during hospitalization were older, compared to patients without hypoglycemia and more likely to have chronic renal failure and cerebrovascular disease. Malignancy and female gender were risk factors for hypoglycemia, but not for serious hypoglycemia, while congestive heart failure was associated with increased risk only for serious hypoglycemia. Diabetes mellitus' duration over 10 years was associated with an almost threefold increased risk for hypoglycemia, compared to DM duration less than a year. Insulin treatment and glycated hemoglobin > 9% were also more common in patients with hypoglycemia. Insulin treatment was associated with a fourfold increase in the risk for hypoglycemia among all glycated hemoglobin categories. Our results identified several risk factors for in-hospital hypoglycemia in patients with DM. These findings may lead to appropriate monitoring and early intervention to prevent hypoglycemia and to reduce morbidity and mortality associated with in-hospital hypoglycemia.

Long-term outcomes in older patients with hyperglycemia on admission for ischemic stroke.

AIMS: Evaluate the association between admission blood glucose (ABG) and mortality in older patients with or without diabetes mellitus (DM) hospitalized for acute ischemic stroke (AIS). METHODS: Observational data of patients ≥65years, admitted for AIS between January 2011 and December 2013. ABG levels were classified to categories: ≤70 (low), 70-110 (normal), 111-140 (mildly elevated), 141-180mg/dl (moderately elevated) and >180mg/dl (markedly elevated). Main outcome was all-cause mortality at the end-of-follow-up. RESULTS: Cohort included 854 patients, 347 with (mean±SD age 80±8, 44% male), and 507 without DM (mean±SD age 78±8, 53% male). There was a significant interaction between DM, ABG and mortality at end-of-follow-up (p≤0.05). In patients without DM there was a dose-dependent association between ABG category and mortality: adjusted hazard ratios (95% CI) compared to normal ABG were 1.8 (1.2-2.8), 2.9 (1.6-5.2) and 4.5 (2.1-9.7), respectively, for mildly, moderately and markedly elevated ABG. In patients with DM there was no association between ABG and mortality. There was no interaction between DM, ABG and in-hospital mortality or length of stay (LOS). Irrespective of DM status, compared to normal ABG levels, increased ABG category was associated with increased in-hospital mortality: adjusted odds ratios were 3.9 (1.1-13.4), 7.0 (1.8-28.1), and 20.3 (4.6-89.6) with mildly, moderately and markedly elevated ABG, respectively. Mean LOS was 6±5, 7±8, 8±7, and 8±8days, respectively. CONCLUSION: In older patients without DM hospitalized for AIS, elevated ABG is associated with increased long-term mortality. Irrespective of DM status, elevated ABG was associated with increased in-hospital mortality and LOS.

Sodium levels on admission are associated with mortality risk in hospitalized patients.

AIMS: Abnormal sodium values are common among hospitalized patients. We aimed to investigate the association of admission sodium values and mortality. METHODS: Historical prospectively data of adult patients hospitalized to medical wards between January 2011 and December 2013. Admission sodium values were classified to five categories: severe hyponatremia (<125mEq/L), mild hyponatremia (125-135mEq/L), normal sodium values (135-145mEq/L), mild hypernatremia (145-150mEq/L) and severe hypernatremia (>150mEq/L). Main outcomes were length of hospitalization, in-hospital mortality and mortality at the end-of-follow-up. RESULTS: The cohort included 27,889 patients (mean age 67±18years, 52% males). The total follow-up was 1065days. Most patients had normal sodium values (76%), 22% had hyponatremia, 3% had hypernatremia. Mean age increased with increase in severity of hyponatremia or hypernatremia. Median length of hospitalization was longer with mild and severe hypernatremia (7 and 5days, respectively) or with mild and severe hyponatremia (4 and 4days, respectively), compared to normal sodium levels (3days). Compared to in-hospital mortality with normal sodium levels (5%), mortality was higher with mild and severe hyponatremia (9% and 14%, respectively) and was highest with mild (28%), and severe hypernatremia (52%). Mortality rate at the end of follow-up was 28% with normal sodium levels, 44% and 48% with mild and severe hyponatremia, 66% and 90% with mild and severe hypernatremia, respectively. CONCLUSIONS: Abnormal sodium values on admission were associated with longer hospitalization and increased short- and long-term mortality. Mortality risk was higher with hypernatremia, compared to hyponatremia.

Effect of dietary fatty acid composition on fatty acid profiles of polar and neutral lipid tissue fractions in zebra finches, Taeniopygia guttata.

The growing awareness that the fatty acid (FA) composition of the diets of birds, and ultimately their tissues, influence physiological performance variables, such as aerobic capacity, thermosensitivity, digestive efficiency, etc., underscores the need to understand how differences in dietary fatty acid composition actually translate into differences in the fatty acid composition of specific tissues. We quantified the fatty acid profiles of polar and neutral lipid fractions of several tissues in zebra finches (Taeniopygia guttata) and compared these profiles among birds fed either a control diet of only hulled millet, or one of two experimental diets of hulled millet supplemented with either 8% (by mass) sunflower seed oil (omega6-enriched diet) or linseed oil (omega3-enriched diet). We found that different lipid fractions vary widely in their diversity and complexity of FA composition, with neutral lipids being much less structurally diverse than those of polar lipids, for example, and that the fatty acid compositions of different organs exhibited different propensities to be altered by the diet, with brain and cardiac tissues having lower levels of flexibility than skeletal muscle and liver. We also present evidence suggesting that adipose tissue may be used to sequester essential FAs when they occur in the diet at levels that exceed immediate requirements. We conclude that the fatty acid composition of adipose tissue may not be a particularly useful indicator of the dietary FA composition of birds, and suggest that future studies investigating the relationships between the FA profiles of bird tissues and bird diets and/or physiological performance variables examine multiple tissues and distinguish between neutral and polar lipid fractions.