Morbidities and mortality among hospitalized patients with hypopituitarism: Prevalence, causes and management.

Hypopituitarism is a highly heterogeneous multisystem disorder that can have a major impact on long-term morbidity and mortality, but even more so during acute medical conditions requiring hospitalization. Recent studies suggest a significant in-hospital burden with prolonged length of stay, increased rate of intensive care unit (ICU) admission, and initiation of mechanical ventilation - all of which may lead to an increased risk of in-hospital mortality. On the one hand, patients with hypopituitarism are often burdened by metabolic complications, including obesity, hypertension, dyslipidemia, and hyperglycemia, which alone, or in combination, are known to significantly alter relevant physiological mechanisms, including metabolism, innate and adaptive immune responses, coagulation, and wound healing, thereby contributing to adverse in-hospital outcomes. On the other hand, depending on the extent and the number of pituitary hormone deficiencies, early recognition of hormone deficiencies and appropriate management and replacement strategy within a well-organized multidisciplinary team are even stronger determinants of short-term outcomes during acute hospitalization in this vulnerable patient population. This review aims to provide an up-to-date summary of recent advances in pathophysiologic understanding, clinical implications, and recommendations for optimized multidisciplinary management of hospitalized patients with hypopituitarism.

Risk of heart failure in inflammatory bowel disease: a Swedish population-based study.

BACKGROUND AND AIMS: Dysregulation of inflammatory and immune responses has been implicated in the pathogenesis of heart failure (HF). But even if inflammation is a prerequisite for inflammatory bowel disease (IBD), little is known about HF risk in IBD. METHODS: In this Swedish nationwide cohort, patients with biopsy-confirmed IBD were identified between 1969 and 2017 [n = 81,749, Crohn's disease (CD, n = 24,303), ulcerative colitis (UC, n = 45,709), and IBD-unclassified (IBD-U, n = 11,737)]. Each patient was matched with up to five general population reference individuals (n = 382,190) and IBD-free full siblings (n = 95,239) and followed until 31 December 2019. Flexible parametric survival models estimated the adjusted hazard ratio (aHR) and standardized cumulative incidence for HF, with 95% confidence intervals (CI). RESULTS: There were 5,582 incident HF identified in IBD patients (incidence rate [IR]: 50.3/10,000 person-years) and 20,343 in reference individuals (IR: 37.9) during a median follow-up of 12.4 years. IBD patients had a higher risk of HF than reference individuals (aHR 1.19, 95% CI 1.15 to 1.23). This increased risk remained significant ≥20 years after IBD diagnosis, leading to one extra HF case per 130 IBD patients until then. The increased risk was also observed across IBD subtypes: CD (IR: 46.9 vs. 34.4; aHR 1.28 [1.20 to 1.36]), UC (IR: 50.1 vs. 39.7; aHR 1.14 [1.09 to 1.19]), and IBD-U (IR: 60.9 vs. 39.0; aHR 1.28 [1.16 to 1.42]). Sibling-controlled analyses showed slightly attenuated association (IBD: aHR 1.10 [1.03 to 1.19]). CONCLUSIONS: Patients with IBD had a moderately higher risk of developing HF for ≥20 years after IBD diagnosis than the general population.

Eosinophilic esophagitis and risk of incident major adverse cardiovascular events: a nationwide matched cohort study.

BACKGROUND: Inflammatory diseases have been associated with an increased cardiovascular risk. However, data on incident major adverse cardiovascular events (MACE) from large population-based cohorts of patients with eosinophilic esophagitis (EoE) is lacking. METHODS: This study included all Swedish adults with EoE without a record of previous cardiovascular disease (CVD) (1990-2017, N = 1546) with follow-up until 2019. Individuals with EoE were identified from prospectively recorded histopathology reports from all Swedish pathology departments (n = 28). EoE patients were matched at index date for age, sex, calendar year and county with up to five general population reference individuals (N = 7281) without EoE or CVD. Multivariable-adjusted hazard ratios (aHRs) for MACE (ischemic heart disease, congestive heart failure, stroke and cardiovascular mortality) were calculated using Cox proportional hazards models. Full sibling comparisons and adjustment for cardiovascular medication were performed. RESULTS: During a median follow-up of 6.0 years, we observed 65 incident MACE in patients with EoE (6.4/1000 person-years (PY)) and 225 in reference individuals (4.7/1000 PY). EoE was not associated with a higher risk of MACE (aHR = 1.14, 95% CI = 0.86-1.51) or any of its components. No differences between age, sex and follow-up time were observed. The results remained stable in sensitivity analyses, including when adjusting for relevant cardiovascular medications and a full sibling comparison. CONCLUSIONS: In this large population-based cohort study, patients with EoE had no increased risk of MACE compared to reference individuals and full siblings. The results are reassuring for patients with EoE.

Microscopic Colitis and Risk of Incident Psoriasis: A Nationwide Population-Based Matched Cohort Study.

Background: Microscopic colitis (MC) has been associated with several immune-mediated diseases including psoriasis, but earlier research has been limited to psoriasis occurring before MC. Data from large-scale cohort studies investigating MC and risk of future psoriasis are lacking. Objective: To examine the association between MC and psoriasis. Methods: In a nationwide, population-based, matched cohort study in Sweden from 2007 to 2021, we identified 8404 patients with biopsy-verified MC (diagnosed in 2007-2017), 37,033 matched reference individuals, and 8381 siblings without MC. Information on MC was obtained through the ESPRESSO cohort (a Swedish histopathology database with nationwide coverage). Using Cox regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for psoriasis up until 2021. Results: During a median follow-up of 9.2 years (interquartile range = 6.7-11.7), 179 MC patients and 440 reference individuals were diagnosed with psoriasis (241.1 vs 131.8 events per 100,000 person-years), corresponding to one extra case of psoriasis in 91 patients with MC over 10 years. After adjustment for the matching variables (birth year, sex, county of residence, and calendar period) and level of education, we computed an adjusted hazard ratio (aHR) of 1.82 (95% CI = 1.53-2.17). Stratified by sex, estimates were similar and when examining the aHR across different lengths of follow-up, we found significantly elevated estimates up to 10 years after MC diagnosis. Compared to MC-free siblings, the aHR was 1.85 (95% CI = 1.36-2.51). Conclusion: Patients with MC are at an almost doubled risk of psoriasis compared to the general population. Clinicians need to consider psoriasis in MC patients with skin lesions.

Long-term risk of myocarditis in patients with inflammatory bowel disease: a nationwide cohort study in Sweden.

OBJECTIVES: Despite a suggested link between inflammatory bowel disease (IBD) and myocarditis, the association has not been well-established. This study aimed to investigate the long-term risk of myocarditis in patients with IBD. METHODS: This nationwide cohort involved all patients with biopsy-confirmed IBD in Sweden (1969-2017) (n=83,264, Crohn's disease [CD, n=24,738], ulcerative colitis [UC, n=46,409], and IBD-unclassified [IBD-U, n=12,117]), general population reference individuals (n=391,344), and IBD-free full siblings (n=96,149), and followed until 2019. Primary outcome was incident myocarditis and secondary outcome was severe myocarditis (complicated with heart failure, death, or readmission). Flexible parametric survival models were used to estimate adjusted hazard ratios (aHR) and cumulative incidence of outcomes, along with 95% confidence intervals (CIs). RESULTS: During a median follow-up of 12 years, there were 256 myocarditis cases in IBD patients (incidence rate [IR]=22.6/100,000 person-years) and 710 in reference individuals (IR=12.9), with an aHR of 1.55 (95%CI: 1.33 to 1.81). The increased risk persisted through 20 years after IBD diagnosis, corresponding to one extra myocarditis case in 735 IBD patients until then. This increased risk was observed in CD (aHR=1.48 [1.11 to 1.97]) and UC (aHR=1.58 [1.30 to 1.93]). IBD was also associated with severe myocarditis (IR: 10.1 vs. 3.5; aHR=2.44 [1.89 to 3.15]), irrespective of IBD subtypes (CD: aHR=2.39 [1.43 to 4.01], UC: aHR=2.82 [1.99 to 4.00], and IBD-U: aHR=3.14 [1.55 to 6.33]). Sibling comparison analyses yielded similar results. CONCLUSIONS: Patients with IBD had an increased risk of myocarditis, especially severe myocarditis, for ≥20 years after diagnosis, but absolute risks were low.

Incident cardiac arrhythmias associated with metabolic dysfunction-associated steatotic liver disease: a nationwide histology cohort study.

BACKGROUND: Prior studies suggest a link between metabolic dysfunction-associated steatotic liver disease (MASLD) and incident arrhythmias, including atrial fibrillation (AF). However, robust data are lacking from cohorts with liver histology, which remains the gold standard for staging MASLD severity. METHODS: This population-based cohort included all Swedish adults with histologically-confirmed MASLD and without prior cardiac arrhythmias (1966-2016; n = 11,206). MASLD was defined from prospectively-recorded histopathology, and characterized as simple steatosis, non-fibrotic steatohepatitis (MASH), non-cirrhotic fibrosis, or cirrhosis. MASLD patients were matched to ≤ 5 controls without MASLD or arrhythmias, by age, sex, calendar year and county (n = 51,856). Using Cox proportional hazards modeling, we calculated multivariable-adjusted hazard ratios (aHRs) for incident arrhythmias (including AF, bradyarrhythmias, other supraventricular arrhythmias, ventricular arrhythmias/cardiac arrest). RESULTS: Over a median follow-up of 10.8 years, incident arrhythmias were confirmed in 1351 MASLD patients (10.3/1000 person-years [PY]) and 6493 controls (8.7/1000PY; difference = 1.7/1000PY; aHR = 1.30, 95%CI 1.22-1.38), and MASLD patients had significantly higher rates of incident AF (difference = 0.9/1000PY; aHR = 1.26, 95%CI 1.18-1.35). Rates of both overall arrhythmias and AF were significantly elevated across all MASLD histological groups, particularly cirrhosis (differences, 8.5/1000PY and 5.3/1000PY, respectively). In secondary analyses, MASLD patients also had significantly higher rates of incident ventricular arrhythmias/cardiac arrest (aHR = 1.53, 95%CI 1.30-1.80), bradyarrhythmias (aHR = 1.26, 95%CI 1.06-1.48), and other supraventricular arrhythmias (aHR = 1.27, 95%CI 1.00-1.62), compared to controls. CONCLUSIONS: Compared to matched controls, patients with biopsy-confirmed MASLD had modest but significantly higher incidence of cardiac arrhythmias, including AF, bradyarrhythmias, other supraventricular arrhythmias and ventricular arrhythmias/cardiac arrest. Excess risk was observed across all stages of MASLD and was highest with cirrhosis.

Dyslipidaemia and growth hormone deficiency - A comprehensive review.

Growth hormone deficiency (GHD) is a common complication of several pituitary and hypothalamic disorders and dependent on the onset of disease. It may have severe clinical implications ranging from growth retardation in childhood-onset, to impaired lipid metabolism and increased cardiovascular risk and mortality in adults. GH effectively modulates lipid metabolism at multiple levels and GHD has been associated with an atherogenic lipid profile, that can be reversed by GH replacement therapy. Despite increasing knowledge on the effects of GH on several key enzymes regulating lipid metabolism and recent breakthroughs in the development and wider availability of recombinant GH preparations, several questions remain regarding the replacement therapy in adults with GHD. This review aims to comprehensively summarize the current knowledge on (i) lipid profile abnormalities in individuals with GHD, (ii) proposed mechanisms of action of GH on lipid and lipoprotein metabolism, and (iii) clinical implications of GH replacement therapy in individuals diagnosed with GHD.

Microscopic colitis and risk of incident rheumatoid arthritis: A nationwide population-based matched cohort study.

BACKGROUND: Microscopic colitis (MC) has been linked to several autoimmune conditions. Results from previous studies on the association with rheumatoid arthritis (RA) have been inconsistent. AIM: To assess the risk of future RA in MC. METHODS: We conducted a nationwide matched cohort study in Sweden of 8179 patients with biopsy-verified MC (diagnosed in 2007-2017), 36,400 matched reference individuals and 8202 siblings without MC, with follow-up until 2021. Information on MC was obtained from all of Sweden's regional pathology registers (n = 28) through the ESPRESSO cohort. Data on incident RA were collected from the National Patient Register. Using Cox regression, we calculated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 9.1 years (interquartile range = 6.7-11.7), 73 MC patients and 183 reference individuals from the general population were diagnosed with RA (99 vs. 55 events per 100,000 person-years), equivalent to one extra case of RA in 226 patients with MC followed for 10 years. These rates corresponded to an aHR of 1.83 (95% CI = 1.39-2.41). The aHR was highest during the first year of follow-up (2.31 [95% CI = 1.08-4.97]) and remained significantly elevated up to 5 years after MC diagnosis (aHR 2.16; 95% CI = 1.42-3.30). Compared to siblings, without MC, the aHR was 2.04 (95% CI = 1.18-3.56). CONCLUSION: Patients with MC are at a nearly two-fold risk of developing RA compared to the general population. Knowledge of this increased risk may expedite evaluation for RA in patients with MC presenting with joint symptoms and/or arthralgia, thus preventing delay until RA diagnosis.

Statin use and risk of colorectal cancer in patients with inflammatory bowel disease.

Background: Statin use has been linked to a reduced risk of advanced colorectal adenomas, but its association with colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) - a high risk population for CRC - remains inconclusive. Methods: From a nationwide IBD cohort in Sweden, we identified 5273 statin users and 5273 non-statin users (1:1 propensity score matching) from July 2006 to December 2018. Statin use was defined as the first filled prescription for ≥30 cumulative defined daily doses and followed until December 2019. Primary outcome was incident CRC. Secondary outcomes were CRC-related mortality and all-cause mortality. Cox regression estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Findings: During a median follow-up of 5.6 years, 70 statin users (incidence rate (IR): 21.2 per 10,000 person-years) versus 90 non-statin users (IR: 29.2) were diagnosed with incident CRC (rate difference (RD), -8.0 (95% CIs: -15.8 to -0.2 per 10,000 person-years); aHR = 0.76 (95% CIs: 0.61 to 0.96)). The benefit for incident CRC was duration-dependent in a nested case-control design: as compared to short-term use (30 days to <1 year), the adjusted odd ratios were 0.59 (0.25 to 1.43) for 1 to <2 years of use, 0.46 (0.21 to 0.98) for 2 to <5 years of use, and 0.38 (0.16 to 0.86) for ≥5 years of use (Pfor tread = 0.016). Compared with non-statin users, statin users also had a decreased risk for CRC-related mortality (IR: 6.0 vs. 11.9; RD, -5.9 (-10.5 to -1.2); aHR, 0.56 (0.37 to 0.83)) and all-cause mortality (IR: 156.4 vs. 231.4; RD, -75.0 (-96.6 to -53.4); aHR, 0.63 (0.57 to 0.69)). Interpretation: Statin use was associated with a lower risk of incident CRC, CRC-related mortality, and all-cause mortality. The benefit for incident CRC was duration-dependent, with a significantly lower risk after ≥2 years of statin use. Funding: This research was supported by Forte (i.e., the Swedish Research Council for Health, Working Life and Welfare).

Familial coaggregation of MASLD with hepatocellular carcinoma and adverse liver outcomes: Nationwide multigenerational cohort study.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD) is the fastest growing cause of hepatocellular carcinoma (HCC) worldwide. However, whether family members of individuals with MASLD also share an increased risk of developing HCC is unknown. METHODS: This nationwide multigenerational cohort study involved family members of all Swedish adults diagnosed with biopsy-proven MASLD (1969-2017), and matched general population comparators. Using the Swedish Multi-generation Register, we identified 38,018 first-degree relatives (FDRs: parents, siblings, offspring) and 9,381 spouses of patients with MASLD, as well as 197,303 comparator FDRs and 47,572 comparator spouses. We used Cox proportional hazards models to calculate adjusted hazard ratios (aHRs) for HCC, major adverse liver outcomes (cirrhosis, decompensated liver disease or liver transplantation), liver-related mortality, extrahepatic cancer, and non-liver-related mortality. RESULTS: Over a median of 17.6 years, the rate of the primary outcome HCC was higher in MASLD FDRs vs. comparator FDRs (13 vs. 8/100,000 person-years [PY]; aHR 1.80, 95% CI 1.36-2.37). The HCC risk was further increased in FDRs of individuals with liver fibrosis/cirrhosis (aHR 2.14, 95% CI 1.07-4.27; PHeterogeneity = 0.03). MASLD FDRs also had higher rates of major adverse liver outcomes (73 vs. 51/100,000 PY; aHR 1.52, 95% CI 1.36-1.69) and liver-related mortality (20 vs. 11/100,000 PY; aHR 2.14, 95% CI 1.67-2.74). MASLD FDRs with any concomitant chronic liver condition experienced accelerated progression of liver disease (aHR 1.47, 95% CI 1.29-1.67). MASLD spouses were at higher risks of major adverse liver outcomes (86 vs. 74/100,000 PY; aHR 1.23, 95% CI 1.01-1.51) and liver-related mortality (25 vs. 19/100,000 PY; aHR 1.93, 95% CI 1.15-3.23), but not of HCC (aHR 1.43, 95% CI 0.87-2.35). CONCLUSIONS: There is distinct familial clustering of adverse liver-related outcomes in families of individuals with biopsy-proven MASLD, with higher relative risks of HCC, progressive liver disease, and liver-related mortality, but absolute risks are low. IMPACT AND IMPLICATIONS: Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly termed NAFLD) clusters in families with high genetic susceptibility and shared environmental risk factors, but the risks of developing hepatocellular carcinoma and other major liver-related outcomes in family members of individuals with MASLD are largely unknown. This large nationwide multigenerational cohort study involving family members (first-degree relatives and spouses) of individuals with biopsy-proven MASLD and of matched general population comparators found slightly increased risks of hepatocellular carcinoma in first-degree relatives, and of developing cirrhosis and liver-related mortality in all family members of individuals with biopsy-proven MASLD. The findings of this study provide large-scale evidence to inform clinical practice guidelines for recommendations on the early identification of individuals at higher risk of liver-related morbidity and mortality.

Long-term Risk of Stroke in Patients With Inflammatory Bowel Disease: A Population-Based, Sibling-Controlled Cohort Study, 1969-2019.

BACKGROUND AND OBJECTIVES: Patients with inflammatory bowel disease (IBD) are at an increased risk of thromboembolic events, but evidence on the long-term risk of stroke remains scarce. We aimed to explore whether patients with a biopsy-confirmed IBD had an increased long-term risk of stroke. METHODS: This cohort included all patients with biopsy-confirmed IBD in Sweden between 1969 and 2019 and up to 5 matched reference individuals per patient who were randomly selected from the general population and IBD-free full siblings. The primary outcome was incident overall stroke; secondary outcomes were ischemic and hemorrhagic strokes. Stroke was identified from the Swedish National Patient Register by using both primary and secondary diagnoses. Adjusted hazard ratios (aHRs) for stroke were estimated by flexible parametric survival models. RESULTS: A total of 85,006 patients with IBD (including Crohn disease [CD, n = 25,257], ulcerative colitis [UC, n = 47,354], and IBD-unclassified [IBD-U, n = 12,395]), 406,987 matched reference individuals, and 101,082 IBD-free full siblings were included in the analysis. We observed 3,720 incident strokes in patients with IBD (incidence rate [IR] 32.6 per 10,000 person-years) and 15,599 in reference individuals (IR 27.7; aHR 1.13, 95% CI 1.08-1.17). The elevated aHR remained increased even 25 years after diagnosis, corresponding to 1 additional stroke case per 93 patients with IBD until then. The excess aHR was mainly driven by ischemic stroke (aHR 1.14; 1.09-1.18) rather than hemorrhagic stroke (aHR 1.06; 0.97-1.15). The risk of ischemic stroke was significantly increased across IBD subtypes (CD [IR 23.3 vs 19.2; aHR 1.19; 1.10-1.29], UC [IR 25.7 vs 22.6; aHR 1.09; 1.04-1.16], and IBD-U [IR 30.5 vs 22.8; aHR 1.22; 1.08-1.37]). Similar results were found when patients with IBD were compared with their siblings. DISCUSSION: Patients with IBD were at an increased risk of stroke, especially of ischemic events, irrespective of the IBD subtype. The excess risk persisted even 25 years after diagnosis. These findings highlight the need for clinical vigilance about the long-term excess risk of cerebrovascular events in patients with IBD.

Risk of Severe Infection in Patients With Biopsy-proven Nonalcoholic Fatty Liver Disease - A Population-based Cohort Study.

BACKGROUND & AIMS: It has been suggested that patients with nonalcoholic fatty liver disease (NAFLD) might be at increased risk of severe infections, but large-scale data from cohorts with biopsy-proven NAFLD are lacking. METHODS: Population-based cohort study including all Swedish adults with histologically confirmed NAFLD (n = 12,133) from 1969 to 2017. NAFLD was defined as simple steatosis (n = 8232), nonfibrotic steatohepatitis (n = 1378), noncirrhotic fibrosis (n = 1845), and cirrhosis (n = 678). Patients were matched to ≤5 population comparators (n = 57,516) by age, sex, calendar year, and county. Swedish national registers were used to ascertain incident severe infections requiring hospital admission. Multivariable adjusted Cox regression was used to estimate hazard ratios in NAFLD and histopathological subgroups. RESULTS: Over a median of 14.1 years, 4517 (37.2%) patients with NAFLD vs 15,075 (26.2%) comparators were hospitalized for severe infections. Patients with NAFLD had higher incidence of severe infections than comparators (32.3 vs. 17.0/1000 person-years; adjusted hazard ratio [aHR], 1.71; 95% confidence interval, 1.63-1.79). The most frequent infections were respiratory (13.8/1000 person-years) and urinary tract infections (11.4/1000 person-years). The absolute risk difference at 20 years after NAFLD diagnosis was 17.3%, equal to one extra severe infection in every 6 patients with NAFLD. Risk of infection increased with worsening histological severity of NAFLD (simple steatosis [aHR, 1.64], nonfibrotic steatohepatitis [aHR, 1.84], noncirrhotic fibrosis [aHR, 1.77], and cirrhosis [aHR, 2.32]. Also compared with their full siblings, patients with NAFLD were at increased risk of severe infections (aHR, 1.54; 95% confidence interval, 1.40-1.70). CONCLUSIONS: Patients with biopsy-proven NAFLD were at significantly higher risk of incident severe infection requiring hospitalization both compared with the general population and compared with siblings. Excess risk was evident across all stages of NAFLD and increased with worsening disease severity.

Why do patients with hypopituitarism still present an increased mortality?

Hypopituitarism is defined as a lack or decreased secretion of one or several pituitary hormones. It can result from diseases of the pituitary gland or from pathologies of the superior regulatory center, i.e. the hypothalamus, thereby decreasing hypothalamic releasing hormones and consequently the pituitary hormones. It is still a rare disease with an estimated prevalence of 30-45 patients/100,000 and an incidence of 4-5/100,000/year. This review summarizes the currently available data with a focus on etiologies of hypopituitarism, evidence on mortality rates in patients with hypopituitarism, temporal trends in mortality , and associated diseases, pathophysiological mechanisms and risk factors that affect mortality risk in these patients.

Effects of Rapid On-Site Evaluation on Diagnostic Accuracy of Thyroid Fine-Needle Aspiration.

INTRODUCTION: Fine-needle aspiration (FNA) is well-established for the evaluation of suspicious thyroid nodules. However, a significant proportion is nondiagnostic. Rapid on-site evaluation (ROSE) has been proposed to improve the overall adequacy of FNA. METHODS: Retrospective cohort study comparing adequacy of thyroid FNA findings pre- and postimplementation of ROSE at a tertiary center in Switzerland. Patients undergoing thyroid FNA from January 2016 to December 2019 were included. The primary outcome was the rate of nondiagnostic findings (Bethesda System for Reporting Thyroid Cytopathology category I). RESULTS: In total, 410 thyroid nodule FNAs were performed. Of those, 309 with standard FNA and 101 with ROSE. The majority of patients were female (71%), with a median age of 56 years (IQR 46-68) and a nodule diameter of 1.9 cm (IQR 1.2-2.9). Implementation of ROSE led to a decrease in nondiagnostic findings from 41.1% to 23.8%, with an odds ratio of 0.42 (95% CI: 0.24-0.72; p = 0.002). Implementation of ROSE was associated with significantly higher rates of Bethesda category III (27.7% vs. 19.1%), category IV (15.8% vs. 5.5%), and Bethesda category VI (6.9% vs. 2.3%). Repeated FNA was performed in 29.1% before and 20.8% after implementation of ROSE (p = 0.18). The mean number of FNA per nodule was reduced from 1.4 (0.6) to 1.2 (0.4) with ROSE (p = 0.04). CONCLUSIONS: Implementation of ROSE of thyroid nodule specimen improved diagnostic adequacy of FNA, reducing nondiagnostic findings. However, due to increased equivocal findings (Bethesda category III), there was no significant reduction of repeat FNA.

Sex-Specific Differences in Outcomes Following Thyroidectomy: A Population-Based Cohort Study.

INTRODUCTION: Numbers of thyroidectomies and awareness of postoperative quality measures have both increased. Potential sex-specific variations in clinical outcomes of patients undergoing thyroidectomy are controversial. OBJECTIVE: The aim of this study was to investigate sex-specific differences in outcomes following thyroidectomy. METHODS: This is a population-based cohort study of all adult patients undergoing either hemi- or total thyroidectomy in Switzerland from 2011 to 2015. The primary outcome was all-cause 30-day readmission rate. The main secondary outcomes were intensive care unit (ICU) admission, surgical re-intervention, in-hospital mortality, length of hospital stay (LOS), postoperative calcium disorder, vocal cord paresis, and hematoma. RESULTS: Of 16,776 patients undergoing thyroidectomy, the majority of patients undergoing thyroidectomy were female (79%), with a median age of 52 (IQR 42-64) years. Within 30 days after the surgery, male patients had significantly higher rates of hospital readmission (adjusted risk ratio [RR] 1.38; 95% confidence interval [95% CI] 1.11-1.72, p = 0.008) and higher risks for postoperative ICU admission (RR 1.25; 95% CI, 1.09-1.44, p = 0.003) than female patients. There were no significant differences among sexes in the LOS, rates of surgical re-interventions, or in-hospital mortality. While postoperative calcium disorders due to hypoparathyroidism were less prevalent among male patients (RR 0.63; 95% CI, 0.54-0.72, p < 0.001), a 2-fold higher incidence rate of postoperative hematoma was observed (RR 1.93, 95% CI, 1.51-2.46, p < 0.001). CONCLUSIONS: Male patients undergoing thyroidectomy have higher 30-day hospital readmission and ICU admission rates. Following surgery, male patients revealed higher rates of neck hematoma, while hypocalcemia was more frequent among female patients.

Safety of parathyroidectomy in older vs. younger patients with primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism is a prevalent endocrinopathy for which surgery is the only curative option. Parathyroidectomy is primarily recommended in younger and symptomatic patients, while there are still concerns regarding surgical complications in older patients. We therefore assessed the association of age with surgical outcomes in patients undergoing parathyroidectomy in a large population in Switzerland. METHODS: Population-based cohort study of adult patients with primary hyperparathyroidism undergoing parathyroidectomy in Switzerland between 2012 and 2018. The cohort was divided into four age groups (<50 years, 50-64 years, 65-74 years, ≥75 years). The primary outcome was a composite of in-hospital postoperative complications. Secondary outcomes were intensive care unit (ICU) admission, unplanned 30-day-readmission, and prolonged length of hospital stay. RESULTS: We studied 2642 patients with a median (IQR) age of 62 (53-71) years. Overall, 111 patients had complications including surgical re-intervention, hypocalcemia, and vocal cord paresis. As compared to <50 year-old patients, older patients had no increased risk for in-hospital complications after surgery (50-64 years: odds ratio (OR): 0.51 (95% CI, 0.28 to 0.92); 65-74 years: OR: 0.72 (95% CI, 0.39 to 1.33); ≥75 years: OR: 1.03 (95% CI, 0.54 to 1.95), respectively. There was also no association of age and rates of ICU-admission and unplanned 30-day-readmission, but oldest patients had longer hospital stays (OR: 2.38 (95% CI, 1.57 to 3.60)). CONCLUSION: ≥50 year-old patients undergoing parathyroidectomy had comparable risk of in-hospital complications as compared with younger ones. These data support parathyroidectomy in even older patients with primary hyperparathyroidism as performed in clinical routine.

Excess Mortality Among Hospitalized Patients With Hypopituitarism-A Population-Based, Matched-Cohort Study.

CONTEXT: Patients with hypopituitarism face excess mortality in the long-term outpatient setting. However, associations of pituitary dysfunction with outcomes in acutely hospitalized patients are lacking. OBJECTIVE: The objective of this work is to assess clinical outcomes of hospitalized patients with hypopituitarism with or without diabetes insipidus (DI). DESIGN, SETTING, AND PATIENTS: In this population-based, matched-cohort study from 2012 to 2017, hospitalized adult patients with a history of hypopituitarism were 1:1 propensity score-matched with a general medical inpatient cohort. MAIN OUTCOME MEASURES: The primary outcome was in-hospital mortality. Secondary outcomes included all-cause readmission rates within 30 days and 1 year, intensive care unit (ICU) admission rates, and length of hospital stay. RESULTS: After matching, 6764 cases were included in the study. In total, 3382 patients had hypopituitarism and of those 807 (24%) suffered from DI. All-cause in-hospital mortality occurred in 198 (5.9%) of patients with hypopituitarism and in 164 (4.9%) of matched controls (odds ratio [OR] 1.32, [95% CI, 1.06-1.65], P = .013). Increased mortality was primarily observed in patients with DI (OR 3.69 [95% CI, 2.44-5.58], P < .001). Patients with hypopituitarism had higher ICU admissions (OR 1.50 [95% CI, 1.30-1.74], P < .001), and faced a 2.4-day prolonged length of hospitalization (95% CI, 1.94-2.95, P < .001) compared to matched controls. Risk of 30-day (OR 1.31 [95% CI, 1.13-1.51], P < .001) and 1-year readmission (OR 1.29 [95% CI, 1.17-1.42], P < .001) was higher among patients with hypopituitarism as compared with medical controls. CONCLUSIONS: Patients with hypopituitarism are highly vulnerable once hospitalized for acute medical conditions with increased risk of mortality and adverse clinical outcomes. This was most pronounced among those with DI.

Interleukin-1 Antagonism Decreases Cortisol Levels in Obese Individuals.

Context: Increased cortisol levels in obesity may contribute to the associated metabolic syndrome. In obesity, the activated innate immune system leads to increased interleukin (IL)-1ß, which is known to stimulate the release of adrenocorticotropin hormone (ACTH). Objectives: We hypothesized that in obesity IL-1 antagonism would result in downregulation of the hypothalamo-pituitary-adrenal axis, leading to decreased cortisol levels. Design and Participants: In this prospective intervention study, we included 73 patients with obesity (body mass index [BMI] ≥30 kg/m2) and at least one additional feature of the metabolic syndrome. Outcome Measures: The primary end point was change in morning cortisol from baseline to after the administration of the IL-1 receptor antagonist (anakinra/Kineret®, total dose 3 × 100 mg). Secondary end points were effects on salivary cortisol and ACTH. Results: Median age was 56 years, 50.7% of patients were female, and median BMI was 36.3 kg/m2. Median morning serum cortisol levels (nmol/L) decreased significantly after IL-1 antagonism [from baseline, 452 to 423; absolute difference, -38.7; 95% confidence interval (CI), -64 to -13.4; P = 0.0019]. Similar effects were found for salivary cortisol levels (-2.8; 95% CI, -4.4 to -1.3; P = 0.0007), ACTH levels (-2.2; 95% CI; -4.2 to -0.1; P = 0.038), systolic blood pressure (-5.2, 95% CI, -8.5 to -1.8; P = 0.0006), and heart rate (-2.9; 95% CI, -4.7 to -1.0; P = 0.0029). Conclusion: IL-1 antagonism in obese individuals with features of the metabolic syndrome leads to a decrease in serum cortisol, salivary cortisol, and ACTH levels along with a reduction in systolic blood pressure and heart rate.