Cardiometabolic Disease Burden and Steroid Excretion in Benign Adrenal Tumors : A Cross-Sectional Multicenter Study.

BACKGROUND: Benign adrenal tumors are commonly discovered on cross-sectional imaging. Mild autonomous cortisol secretion (MACS) is regularly diagnosed, but its effect on cardiometabolic disease in affected persons is ill defined. OBJECTIVE: To determine cardiometabolic disease burden and steroid excretion in persons with benign adrenal tumors with and without MACS. DESIGN: Cross-sectional study. SETTING: 14 endocrine secondary and tertiary care centers (recruitment from 2011 to 2016). PARTICIPANTS: 1305 prospectively recruited persons with benign adrenal tumors. MEASUREMENTS: Cortisol excess was defined by clinical assessment and the 1-mg overnight dexamethasone-suppression test (serum cortisol: <50 nmol/L, nonfunctioning adrenal tumor [NFAT]; 50 to 138 nmol/L, possible MACS [MACS-1]; >138 nmol/L and absence of typical clinical Cushing syndrome [CS] features, definitive MACS [MACS-2]). Net steroid production was assessed by multisteroid profiling of 24-hour urine by tandem mass spectrometry. RESULTS: Of the 1305 participants, 49.7% had NFAT (n = 649; 64.1% women), 34.6% had MACS-1 (n = 451; 67.2% women), 10.7% had MACS-2 (n = 140; 73.6% women), and 5.0% had CS (n = 65; 86.2% women). Prevalence and severity of hypertension were higher in MACS-2 and CS than NFAT (adjusted prevalence ratios [aPRs] for hypertension: MACS-2, 1.15 [95% CI, 1.04 to 1.27], and CS, 1.37 [CI, 1.16 to 1.62]; aPRs for use of ≥3 antihypertensives: MACS-2, 1.31 [CI, 1.02 to 1.68], and CS, 2.22 [CI, 1.62 to 3.05]). Type 2 diabetes was more prevalent in CS than NFAT (aPR, 1.62 [CI, 1.08 to 2.42]) and more likely to require insulin therapy for MACS-2 (aPR, 1.89 [CI, 1.01 to 3.52]) and CS (aPR, 3.06 [CI, 1.60 to 5.85]). Urinary multisteroid profiling revealed an increase in glucocorticoid excretion from NFAT over MACS-1 and MACS-2 to CS, whereas androgen excretion decreased. LIMITATIONS: Cross-sectional design; possible selection bias. CONCLUSION: A cardiometabolic risk condition, MACS predominantly affects women and warrants regular assessment for hypertension and type 2 diabetes. PRIMARY FUNDING SOURCE: Diabetes UK, the European Commission, U.K. Medical Research Council, the U.K. Academy of Medical Sciences, the Wellcome Trust, the U.K. National Institute for Health Research, the U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.

Intrarenal hemodynamics and kidney function in pheochromocytoma and paraganglioma before and after surgical treatment.

PURPOSE: Current evidence regarding renal involvement in pheochromocytoma and paraganglioma (PPGL) is scant. More accurate diagnostic methods, such as renal Doppler ultrasound for intrarenal hemodynamic studies, may provide more detailed information on renal function. It might be postulated that renal function in PPGL patients might be altered by high blood pressure and excess secretion of catecholamines. The aim of this prospective study was to assess intrarenal blood flow parameters in PPGL patients included in the prospective monoamine-producing tumour (PMT) study and to evaluate the effects of normalisation of catecholamine production after surgical treatment on long-term renal function. MATERIALS AND METHODS: Seventy consecutive patients (aged 46.5 ± 14.0 years) with PPGL were included. Forty-eight patients from the PMT study cohort, matched for age, gender, blood pressure level and presence of hypertension, served as a control group. Renal artery doppler ultrasound spectral analysis included mean resistance index (RRI) and pulsatility index (PI). Forty-seven patients completed 12 months follow-up. RESULTS: There were no differences in renal parameters such as RRI, PI and kidney function between PPGL and non-PPGL patients as assessed by renal ultrasound, serum creatinine, eGFR and albumin excretion rate. No correlations between kidney function parameters, intrarenal doppler flow parameters and plasma catecholamines were observed in PPGL patients. At 12 months after surgery, no differences in creatinine level, eGFR, albumin excretion rate, RI and PI were found as compared to baseline results. CONCLUSIONS: In contrast to patients with other forms of secondary hypertension, our study did not show differences in intrarenal blood flow parameters and renal function between PPGL and non-PPGL subjects. Intrarenal hemodynamics and renal function did not change after normalisation of catecholamine levels by surgical treatment.

A very rare origin of a tumor in the right atrium.

Primary cardiac tumors are extremely uncommon but metastases can result from direct invasion from the mediastinum, hematogenous spread or extension of the tumor into the vena cava and the right atrium. A CASE REPORT: A 37-year-old male with no previous history of chronic diseases was admitted to the hospital due to non-specific chest discomfort, non-productive cough and weakness lasting for several weeks. Physical examination was unremarkable except for tachycardia and bibasal rales. Chest radiogram revealed multiple pulmonary lesions suggesting metastases. A mass in the right adrenal gland was found on abdominal ultrasound and CT scan. In addition, a pathological lesion in the inferior vena cava extending to the right atrium was detected. Echocardiography revealed a pedunculated mass measuring 2.3x1.5 cm, located in the right atrium, which originated from the inferior vena cava. During the diastole, it prolapsed to the right ventricle but did not significantly affect blood flow through the tricuspid valve. Adrenal tumor biopsy revealed adrenocortical cancer and treatment with mitotane was started. After a seizure episode, brain MRI was performed and showed metastases surrounded by edema. Due to the patient's poor general condition and progression of the disease during mitotane treatment was later withdrawn and the patient was referred for the hospice care where he died 2 months later. CONCLUSIONS: Adrenocortical cancer is a rare malignant neoplasm with an estimated annual incidence of 4-12 cases per 1,000,000. It is characterized by a tendency for local invasion and multiple metastases to the lungs, liver and bones. In the literature, there are only a few cases of adrenocortical cancer directly extending from the inferior vena cava to the right atrium.

Primary pigmented nodular adrenocortical disease (PPNAD) as an underlying cause of symptoms in a patient presenting with hirsutism and secondary amenorrhea: case report and literature review.

Hypercortisolemia in females may lead to menstrual cycle disturbances, infertility, hirsutism and acne. Herewith, we present a 18-year-old patient, who was diagnosed due to weight gain, secondary amenorrhea, slowly progressing hirsutism, acne and hot flashes. Thorough diagnostics lead to a conclusion, that the symptoms was the first manifestation of primary pigmented nodular adrenocortical disease (PPNAD). All symptoms of Cushing syndrome including hirsutism and menstrual disturbances resolved after bilateral adrenalectomy. Our report indicates that oligo- or amenorrhea, hirsutism, acne in combination with weight gain, growth failure, hypertension and slightly expressed cushingoid features in a young woman requires diagnostics towards hypercortisolemia. Despite PPNAD is a very rare cause of ACTH-independent Cushing syndrome, it has to be taken into consideration, especially when adrenal glands appear to be normal on imaging and paradoxical rise in cortisol level in high-dose dexamethasone test is observed. Unlike in our patient, in vast majority of patients, PPNAD is associated with Carney complex (CC). Therefore, these patients and their first-degree relatives should be always carefully screened for symptoms of PPNAD, CC and genetic mutations of PRKAR1A, PDE11A, and PDE8B genes.

Salivary testosterone may not serve as a screening test in the diagnosis of biochemical hyperandrogenism.

AIM: The diagnosis of biochemical hyperandrogenism is still challenging because a set of appropriate, recommended diagnostic tests has not been established. In our study, we aimed to answer the question of whether salivary testosterone is a reliable test to establish the diagnosis of biochemical hyperandrogenism as compared to serum total testosterone (TT) measured either by liquid chromatography-tandem mass spectrometry (LC-MS/MS) or immunoassay and to assess which set of biochemical tests would be the most appropriate for the identification of biochemical hyperandrogenism. METHODS: A total of 39 women, aged 18-45 years, with clinical or biochemical hyperandrogenism and 41 healthy individuals, aged 19-45 years, were enrolled in the study. Salivary testosterone was measured using the Salimetrics test. Serum TT was measured either using the LC-MS/MS method or immunoassay, and dehydroepiandrosterone sulphate (DHEA-S) and androstenedione were measured using LC-MS/MS. RESULTS: In 15 of 17 (88%) patients with elevated serum TT measured by LC-MS/MS and in 14 of 16 (87%) measured with immunoassay, salivary testosterone showed normal levels. In 11 of 39 women (28%) with normal serum testosterone levels, DHEA-S was elevated. All patients with elevated androstenedione presented with an elevated concentration of either serum testosterone or DHEA-S. CONCLUSION: Salivary testosterone measurement may lead to the underdiagnosis of biochemical hyperandrogenism. Both serum testosterone and DHEA-S should be measured in the endocrine work-up toward biochemical hyperandrogenism.

Total testosterone to dihydrotestosterone ratio assessed by LC-MS/MS predicts a worse metabolic profile not only in PCOS patients.

OBJECTIVES: Total testosterone/dihydrotestosterone ratio (TT/DHT) was found to determine metabolic risk in polycystic ovary syndrome (PCOS). The aim of this study was to analyze whether (TT/DHT) may be helpful in predicting metabolic risk not only in PCOS patients but also in healthy women. MATERIAL AND METHODS: Total testosterone (TT), dihydrotestosterone (DHT), androstendione and dehydroepiandrosterone sulphate (DHEA-S) were measured by LC-MS/MS in 36 women with PCOS and in 29 age-matched controls without clinical hyperandrogenism. In all participants, anthropometric data, lipids, adipose tissue percent (%fat), HOMA-IR were also assessed. RESULTS: The studied groups were not different in terms of age, BMI, waist circumference, %fat and HOMA-IR. In the patients group, mean TT and androstendione levels were significantly higher as compared to controls (1.4 nmol/L vs. 1.0 nmol/L, P < 0.001) and (6.6 nmol/L vs. 4.9 nmol/L, P < 0.01), respectively. In the patients group, mean TT/DHT ratio was significantly higher compared to controls (3.6 vs. 2.7, P < 0.01) and correlated with BMI (r = 0.37, P < 0.05), waist circumference (r = 0.44, P < 0.01), %fat (r = 0.30, P < 0.05), as well as with insulin levels (r = 0.38, P < 0.05) and HOMA-IR (r = 0.44, P < 0.05). The association between TT/DHT ratio and unfavorable metabolic parameters was also seen in controls. CONCLUSION: Total testosterone/dihydrotestosterone ratio assessed by LC-MS/MS correlates with a worse metabolic profile not only in PCOS patients, but also in healthy women.

[IgG4-related disease - a case report]. / Choroba IgG4-zalezna ­ opis przypadku.

Immunoglobulin G4-related disease (IgG4-RD) is a comparatively new condition that may involve more than one organ. The lack of characteristic, pathognomonic clinical symptoms may delay the diagnosis of this disease. The diagnosis is based upon clinical manifestation, elevated serum levels of IgG4 and histopathologic examination with immunohistochemical staining to reveal infiltration of IgG4-positive plasma cells. The first line treatment is oral glucocorticoids. A CASE REPORT: 38-year-old woman with Hashimoto disease, chronic sinusitis and chronic hepatitis of unknown etiology was admitted to the Department of Endocrinology because of moderate eyelids swelling accompanied by redness for 3 years. Graves' orbitopathy and systemic vasculitis were suspected, however both were excluded (negative antibodies results: anty-TSHR, ANCA, ANA). Serologic investigation of Sjögren's syndrome was also negative. In Magnetic Resonance Imaging (MRI) of orbits there were described bilateral mild extension of lateral rectus muscles, normal signal of adipose tissue and bilateral lacrimal glands enlargement. Moreover, increased IgG4 serum levels were detected. The material derived from perinasal sinuses surgery was analyzed in histopathology examination with immunohistochemical staining, which revealed characteristic features of chronic inflammatory process and increased numbers of IgG4 - positive plasma cells (>50 in a large field of view). The diagnosis of IgG4-RD was established. Because of non-effective oral methylprednisolone therapy in the past, the patient was referred to Clinic of Rheumatology for further treatment. After the therapy with methylprednisolone and azathioprine there were observed the significant reduction of symptoms. CONCLUSIONS: Because of lack of characteristic symptoms of IgG4- RD, it should be always considered in differential diagnosis of chronic inflammatory diseases of various organs.

The diagnosis of nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, based on serum basal or post-ACTH stimulation 17-hydroxyprogesterone, can lead to false-positive diagnosis.

OBJECTIVE: As nonclassic congenital adrenal hyperplasia (NCCAH) needs to be taken into account in women with hyperandrogenism, we aimed to assess whether the recommended level of poststimulated 17OHP ≥30 nmol/l confirms NCCAH. PATIENTS AND METHODS: Forty, consecutive women with biochemical and/or clinical hyperandrogenism (aged 25·4, 18-38) suspected of having NCCAH were recruited to the study. In patients with 17OHP level between 5·1 and 29·9 nmol/l an ACTH stimulation test was performed. In patients with basal or poststimulated 17OHP ≥30 nmol/l, twenty-four-hour urinary steroid profile (USP) analysis was performed and CYP21A2 mutation was assessed. In selected patients with poststimulated 17OHP <30 nmol/l USP was also performed. RESULTS: The group was divided into two subgroups with basal or poststimulated 17OHP ≥30 nmol/l (group A) and with poststimulated 17OHP <30 nmol/l (group B). Among 40 patients, basal or poststimulated 17OHP ≥30 nmol/l was found in 21, but NCCAH was confirmed by USP followed by genetic testing only in 5 (24%). Four patients were diagnosed as heterozygotes, and in twelve, no CYP21A2 mutation was detected. CONCLUSION: The diagnosis of NCCAH based only on serum 17OHP measurements (basal or poststimulated) may lead to false-positive diagnosis when performed by immunoassay with a cut-off value of ≥30 nmol/l. The definitive diagnosis can be established based on USP and/or genetic testing.

The morning and late-night salivary cortisol ranges for healthy women may be used in pregnancy.

OBJECTIVES: The diagnosis of adrenal dysfunction in pregnancy and in women taking oral contraceptives remains a diagnostic challenge. Salivary cortisol seems to be a useful tool for the diagnosis of Cushing's syndrome and adrenal insufficiency. However, the changes in salivary cortisol concentration in healthy pregnancy are not clearly defined. DESIGN: The aim of our study was to compare diurnal changes in salivary cortisol in healthy pregnant women, healthy controls and women on oral contraceptives. PATIENTS: The study groups consisted of (i) 41 healthy pregnant women, (ii) 42 healthy women and (iii) 12 healthy women on oral contraceptives. MEASUREMENTS: Serum and salivary cortisol in the morning and salivary late-night cortisol were measured with Roche ECLIA cortisol test (Elecsys 2010) in each trimester and postpartum. RESULTS: Despite the elevation of morning serum cortisol in the second and third trimesters of pregnancy, the morning salivary values as well as late-night salivary cortisol throughout all trimesters were not significantly different from control values (P > 0·5). In the postpartum period, the morning and late-night salivary cortisol values were significantly lower than in late pregnancy. The morning and late-night salivary cortisol values in women on contraceptives were also not different from those in the healthy women group. CONCLUSION: The results of our study suggest that reference values for salivary cortisol established for a healthy adult population can be used for pregnant women and women on oral contraceptives in the initial diagnostic testing for Cushing's syndrome and adrenal insufficiency.

LC-MS/MS improves screening towards 21-hydroxylase deficiency.

Basal serum 17OHP measurement remains the first screening step for nonclassic congenital adrenal hyperplasia (NCCAH) and the accuracy of the test is of high value. The aim of this study was to compare the accuracy of immunoassays to LC-MS/MS in the assessment of serum 17OHP and androgens concentration in women with hyperandrogenism and controls. 17OHP, total testosterone, androstendione and DHEA-S were measured in 39 women with clinically and/or biochemically evident hyperandrogenism and in 29 age-matched controls without clinical hyperandrogenism. 17OHP and androgens were measured by immunoassays and by LC-MS/MS. In patients group median 17OHP level measured by immunoassays was significantly higher compared to LC-MS/MS (5.49 nmol/l-ELISA NovaTec® and 3.57 nmol/l-ELISA DRG® versus 1.56 nmol/l-LC-MS/MS p < 0.0001) as well as in the control group (2.58 nmol/l-ELISA DRG® versus 1.14 nmol/l-LC-MS/MS p < 0.0001). Additional, unnecessary diagnostic procedures explaining elevated 17OHP level were undertaken in 85% of patients when NovaTec® test was used, in 50% when ELISA DRG® and in none when LC-MS/MS method was applied. Total testosterone, androstendione and DHEA-S concentrations in the patients and the controls assessed by the immunoassays were also significantly higher compared to LC-MS/MS. LC-MS/MS is more reliable diagnostic tool in the measurement of serum 17OHP and androgens concentrations compared to immunoassays in women with hyperandrogenism.

Increased concentration of T-cell receptor rearrangement excision circles (TREC) in peripheral blood in Graves' disease.

BACKGROUND: T-cell receptor rearrangement excision circles (TREC) are circular DNA molecules generated during T-cell maturation in the thymus. Recent studies suggested that a decreased TREC concentration in peripheral blood may be a general feature of autoimmunity. Our purpose was to assess the TREC concentration in Graves' disease (GD). METHODS: TREC concentration was assessed by real time PCR in DNA samples isolated from peripheral blood leucocytes among younger (n = 94, age range 6-29 years) and older patients with GD (n = 93, age range 57-80 years) and age-matched controls (n = 206). RESULTS: TREC concentration decreased with age in all subjects, but it was significantly higher in GD compared with controls (P = 9·4 × 10(-10) ). TREC concentration was higher (P = 0·0038) in hyperthyroid (n = 78) than euthyroid (n = 82) patients with GD, but in both groups, it remained increased relative to controls (P = 2·2 × 10(-11) and P = 4·4 ×10(-7) , respectively). CONCLUSIONS: Patients with GD, particularly those with hyperthyroidism, have increased concentration of TREC which may suggest increased rather than decreased thymic activity. Thus, GD does not follow the paradigm suggested for other autoimmune disorders which links autoimmunity with thymic senescence.

[68Ga]Ga-DOTA-TATE in diagnosis of MEN syndrome.

Not required for Clinical Vignette.

Vitamin D insufficiency in healthy pregnant women living in Warsaw.

BACKGROUND/OBJECTIVES: Ensuring the optimal level of 25-hydroxy-vitamin D (250HD) in serum (concentration above 30 ng/ml) is essential for protecting the health of the mother and the developing fetus. Vitamin D plays an important role in maintaining proper bone structure, preventing infections, reducing the risk of premature birth and gestational diabetes. The aim of the study was to verify whether healthy pregnant residents of Warsaw were deficient in vitamin D. MATERIAL AND METHODS: The material consisted of 150 serum samples of 50 healthy women in 1st, 2nd and 3rd trimester of pregnancy 72.7% of the sera were from women who reported taking multivitamin supplements containing vitamin D3 (71% out of that group was taking 400 IU daily). The concentration of 250HD was measured using the vitamin D total assay on Elecsys 2010 automatic analyzer (Roche Diagnostics). RESULTS: The average serum 250HD concentrations of 50 women in 1st, 2nd and 3rd trimester of pregnancy were respectively: 23.1 ng/ml, 24.8 ng/ml, and 25.1 ng/ml, with no statistically significant differences. The optimal levels of 250HD (30-80 ng/ml) were found in 30.0% of samples, hypovitaminosis (20-30 ng/ml) occurred in 38.7%, deficiency (10-20 ng/ml) in 24.0% and severe deficiency (less than 10 ng/ml) in 7.3% of cases. Mean concentration of 250HD in winter season (October 1 - March 31) was 23.6 ng/ml and in summer season (April 1 - September 30) was 25.5 ng/ml, with no statistically significant difference. On the basis of the BMI in 1st trimester two subgroups were distinguished from the studied subjects: BMI <21 (13 patients, 39 samples) and BMI >25 (14 patients, 42 samples). Mean 250HD concentration in these groups were 27.3 and 23.5 ng/ml respectively (p<0.05). High statistical significance (p<0.001) was found among the total number of samples with 250HD deficiency and severe deficiency (<20 ng/ml) and samples with hypovitaminosis and optimal 250HD level (>20 ng/ml) in these groups. CONCLUSIONS: Regardless of trimester and season, vitamin D below the optimal level is a common occurrence during pregnancy and the current level of supplementation among Polish pregnant women appears to be insufficient. Our data suggest that special attention should be paid to the problem of vitamin D insufficiency in overweight pregnant women.

Characteristics of Congenital Adrenal Hyperplasia Diagnosed in Adulthood: A Literature Review and Case Series.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol synthesis. CAH, depending on its clinical form, is usually diagnosed in the neonatal period, later in childhood, in adolescence, or in young adults. Herein, we report a case series of eight individuals in whom CAH was diagnosed between the ages of 18 and 81 years. METHODS: We report on clinical presentations, hormonal tests, adrenal/gonadal imaging, and genetic findings. The clinical data of eight people with CAH, including four women (46, XX) and four men (46, XY), were reviewed. A genetic analysis of the cytochrome P450 family 21 subfamily A member 2 (CYP21A2) gene was performed in six patients. A comprehensive literature review was also conducted. CASE SERIES: Partial cortisol deficiency was found in all patients. The most frequent genotype was the homozygotic I173N mutation in CYP21A2. Adrenal masses were detected in seven patients, except for the youngest. Most of the patients were of short stature. Hypogonadotropic hypogonadism was detected in two males, and three females presented with primary amenorrhea. Hirsutism was noticeable in three females. All of the patients developed insulin resistance, and half of them were obese. CONCLUSIONS: The clinical presentations of different forms of CAH overlapped. Genotype-phenotype correlations were strong but not absolute. The management of CAH should be individualized and based on clinical and laboratory findings. Furthermore, the assessment of the cortisol response to adrenocorticotrophic hormone stimulation should be mandatory in all adults with CAH. Additionally, the regular long-term screening of cardiometabolic status is required in the CAH population.

Huge Hematoma as First Manifestation of Adrenocortical Carcinoma: A Case Report.

BACKGROUND Adrenocortical carcinoma (ACC) is a rare malignancy associated with unfavorable prognosis. It is mainly diagnosed in the fifth or sixth decade of life. Symptoms of ACC are associated with hormonal activity, presence of metastases, and size of the tumor. The treatment and prognosis depend on the stage of the disease assessed with the ENSAT staging system. CASE REPORT A 38-year-old White man was admitted to our department from the city hospital due to a huge hematoma of the right adrenal gland (130×100 mm). On admission, the patient's condition was stable, and no active bleeding or other complications were present. Therefore, initially, conservative treatment was performed. The control CT scan showed reduction of the hematoma (90×80 mm). Due to the unknown character of the tumor and the sudden onset of bleeding, the patient was prepared for elective surgery according to the phaeochromocytoma surgery protocol. Following preparation, the patient underwent right-sided adrenalectomy. In the postoperative histopathological examination, adrenocortical carcinoma was diagnosed, which allowed the patient to receive appropriate oncological treatment. CONCLUSIONS There is currently no clear algorithm for the management of adrenal hemorrhage. A hemodynamically unstable patient requires urgent surgical treatment. Patients in good general condition should be prepared for early elective surgery.

High prevalence of frailty in patients with adrenal adenomas and adrenocortical hormone excess: a cross-sectional multi-centre study with prospective enrolment.

OBJECTIVE: Frailty, characterized by multi-system decline, increases vulnerability to adverse health outcomes and can be measured using Frailty Index (FI). We aimed to assess the prevalence of frailty in patients with adrenal disorders (based on hormonal sub-type) and examine association between FI and performance-based measures of physical function. DESIGN: Multi-centre, cross-sectional study (March 2019-August 2022). METHODS: Adult patients with adrenal disorders (non-functioning adrenal adenomas [NFA], mild autonomous cortisol secretion [MACS], Cushing syndrome [CS], primary aldosteronism [PA]) and referent subjects without adrenal disorders completed a questionnaire encompassing 47 health variables (comorbidities, symptoms, daily living activities). FI was calculated as the average score of all variables and frailty defined as FI ≥ 0.25. Physical function was assessed with hand grip, timed up-and-go test, chair rising test, 6-minute walk test, and gait speed. RESULTS: Compared to referent subjects (n = 89), patients with adrenal disorders (n = 520) showed increased age, sex, and body mass index-adjusted prevalence of frailty (CS [odds ratio-OR 19.2, 95% confidence interval-CI 6.7-70], MACS [OR 12.5, 95% CI 4.8-42.9], PA [OR 8.4, 95% CI 2.9-30.4], NFA [OR 4.5, 95% CI 1.7-15.9]). Prevalence of frailty was similar to referent subjects when post-dexamethasone cortisol was <28 nmol/L and was higher when post-dexamethasone cortisol was 28-50 nmol/L (OR 4.6, 95% CI 1.7-16.5). FI correlated with all measures of physical function (P < .001). CONCLUSIONS: Whilst frailty prevalence was highest in patients with adrenocortical hormone excess, even patients with NFA demonstrated an increased prevalence compared to the referent population. Future longitudinal studies are needed to evaluate the impact of various management strategies on frailty.

Sarcoid-like Lung Disease as a Reaction to Silica from Exposure to Bentonite Cat Litter Complicated by End-Stage Renal Failure-A Case Report.

A 44-year-old woman was admitted to hospital with end-stage renal failure, productive cough, and decreased exercise tolerance. She had owned nine cats, which resulted in long-term exposure (18 years) to silica-containing bentonite cat litter. High-resolution computed tomography of the chest showed micronodular lesions in the lungs, and mild mediastinal lymphadenopathy. A lung biopsy revealed multinucleated giant cells, some of which had birefringent material and Schaumann bodies. X-ray photoelectron spectroscopy revealed the presence of silicon in the lung biopsy specimen, as well as in the patient's cat litter. The pulmonary condition was suggestive of sarcoid-like lung disease, rather than silicosis, sarcoidosis, or hypersensitivity pneumonitis, according to the clinicopathological findings. Renal failure appeared to be a result of chronic hypercalcemia due to extrarenal calcitriol overproduction in activated alveolar macrophages. Ultimately, the patient was diagnosed with sarcoid-like lung disease complicated by end-stage renal failure from exposure to bentonite cat litter. Therapy with steroids, in addition to elimination of the bentonite cat litter exposure, resulted in a significant improvement in the health condition. At a follow-up visit after 4 months, an almost complete resolution of the lung lesions and a significant improvement in renal function were observed.

The Influence of Time of Day of Vaccination with BNT162b2 on the Adverse Drug Reactions and Efficacy of Humoral Response against SARS-CoV-2 in an Observational Study of Young Adults.

An increasing body of evidence from both academic and clinical studies shows that time-of-day exposure to antigens might significantly alter and modulate the development of adaptive immune responses. Considering the immense impact of the COVID-19 pandemic on global health and the diminished efficacy of vaccination in selected populations, such as older and immunocompromised patients, it is critical to search for the most optimal conditions for mounting immune responses against SARS-CoV-2. Hence, we conducted an observational study on 435 healthy young adults vaccinated with two doses of BNT162b2 (Pfizer-BioNTech) vaccine to determine whether time-of-day of vaccination influences either the magnitude of humoral response or number of adverse drug reactions (ADR) being reported. We found no significant differences between morning and afternoon vaccination in terms of both titers of anti-Spike antibodies and frequency of ADR in the studied population. In addition, our analysis of data on the occurrence of ADR in 1324 subjects demonstrated that the second administration of vaccine in those with previous SARS-CoV-2 infection was associated with lower incidence of ADR. In aggregate, vaccination against COVID-19 with two doses of BNT162b2 mRNA vaccine is presumed to generate an equally efficient anti-Spike humoral response.

Age-dependent and sex-dependent disparity in mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: an international, retrospective, cohort study.

BACKGROUND: The association between cortisol secretion and mortality in patients with adrenal incidentalomas is controversial. We aimed to assess all-cause mortality, prevalence of comorbidities, and occurrence of cardiovascular events in uniformly stratified patients with adrenal incidentalomas and cortisol autonomy (defined as non-suppressible serum cortisol on dexamethasone suppression testing). METHODS: We conducted an international, retrospective, cohort study (NAPACA Outcome) at 30 centres in 16 countries. Eligible patients were aged 18 years or older with an adrenal incidentaloma (diameter ≥1 cm) detected between Jan 1, 1996, and Dec 31, 2015, and availability of a 1 mg dexamethasone suppression test result from the time of the initial diagnosis. Patients with clinically apparent hormone excess, active malignancy, or follow-up of less than 36 months were excluded. Patients were stratified according to the 0800-0900 h serum cortisol values after an overnight 1 mg dexamethasone suppression test; less than 50 nmol/L was classed as non-functioning adenoma, 50-138 nmol/L as possible autonomous cortisol secretion, and greater than 138 nmol/L as autonomous cortisol secretion. The primary endpoint was all-cause mortality. Secondary endpoints were the prevalence of cardiometabolic comorbidities, cardiovascular events, and cause-specific mortality. The primary and secondary endpoints were assessed in all study participants. FINDINGS: Of 4374 potentially eligible patients, 3656 (2089 [57·1%] with non-functioning adenoma, 1320 [36·1%] with possible autonomous cortisol secretion, and 247 [6·8%] with autonomous cortisol secretion) were included in the study cohort for mortality analysis (2350 [64·3%] women and 1306 [35·7%] men; median age 61 years [IQR 53-68]; median follow-up 7·0 years [IQR 4·7-10·2]). During follow-up, 352 (9·6%) patients died. All-cause mortality (adjusted for age, sex, comorbidities, and previous cardiovascular events) was significantly increased in patients with possible autonomous cortisol secretion (HR 1·52, 95% CI 1·19-1·94) and autonomous cortisol secretion (1·77, 1·20-2·62) compared with patients with non-functioning adenoma. In women younger than 65 years, autonomous cortisol secretion was associated with higher all-cause mortality than non-functioning adenoma (HR 4·39, 95% CI 1·93-9·96), although this was not observed in men. Cardiometabolic comorbidities were significantly less frequent with non-functioning adenoma than with possible autonomous cortisol secretion and autonomous cortisol secretion (hypertension occurred in 1186 [58·6%] of 2024 patients with non-functioning adenoma, 944 [74·0%] of 1275 with possible autonomous cortisol secretion, and 179 [75·2%] of 238 with autonomous cortisol secretion; dyslipidaemia occurred in 724 [36·2%] of 1999 patients, 547 [43·8%] of 1250, and 123 [51·9%] of 237; and any diabetes occurred in 365 [18·2%] of 2002, 288 [23·0%] of 1250, and 62 [26·7%] of 232; all p values <0·001). INTERPRETATION: Cortisol autonomy is associated with increased all-cause mortality, particularly in women younger than 65 years. However, until results from randomised interventional trials are available, a conservative therapeutic approach seems to be justified in most patients with adrenal incidentaloma. FUNDING: Deutsche Forschungsgemeinschaft, Associazione Italiana per la Ricerca sul Cancro, Università di Torino.