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

Not required for Clinical Vignette.

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.

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.

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.

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.

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.

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.

Approach to large adrenal tumors.

PURPOSE OF REVIEW: To summarize the data concerning approach to large adrenal tumors (LAT's), since recent guidelines published in 2016 recommend individual approach rather than clear size cut-off of a tumor that should be removed. RECENT FINDINGS: Although the risk of malignancy clearly correlates with the size of a lesion, tumor size of more than 4 cm in diameter represents only 31-61% specificity for the diagnosis of malignant tumor. Therefore, the risk of malignancy and decision about surgery should not be based only on the size of a tumor but assessed in terms of imaging studies, growth pattern during follow-up and new tool that is urine/serum steroid metabolomics. SUMMARY: Approach to patients with LAT's should be individualized. Patients with LAT's should be managed by an expert multidisciplinary team, that includes an endocrinologist, a radiologist, a pathologist, and an adrenal surgeon.

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.

The regulation of cyclin D promoters - review.

Cyclins are key regulators of cell cycle progression and survival. Particularly cyclins D (cyclin D1, D2, and D3) act in response to the mitogenic stimulation and are pivotal mediators between proliferative pathways and the nuclear cell cycle machinery. Dysregulation of cyclins expression results in impaired development, abnormal cell growth or tumorigenesis. In this review we summarize current knowledge about regulatory role of the cyclin D promoters, transcriptional factors: regulators, co-activators and adaptor proteins necessary to their activation. We focused on the intracellular signaling pathways vital to cell growth, differentiation and apoptosis including transcription factor families: activator protein 1 (AP1), nuclear factor (NFκB), signal transducer and activator of transcription (STAT), cAMP response element-binding protein (CREB) and Sp/NF-Y, with a special insight into the tissue specific cyclin representation.

Primary aldosteronism is highly prevalent in patients with hypertension and moderate to severe obstructive sleep apnea.

STUDY OBJECTIVES: It has been suggested that there might be a pathophysiological link and overlap between primary aldosteronism (PA) and obstructive sleep apnea (OSA). Therefore, in a prospective study, we evaluated the frequency of PA in hypertensive patients suspected of having OSA. METHODS: We included 207 consecutive hypertensive patients (mean age 53.2 ± 12.1 years, 133 M, 74 F) referred for polysomnography on the basis of one or more of the following clinical features: typical OSA symptoms, resistant or difficult-to-treat hypertension, diabetes, or cardiovascular disease. PA was diagnosed based on thew saline infusion test. RESULTS: Moderate-to-severe OSA was diagnosed in 94 patients (45.4% of the whole group). PA was diagnosed in 20 patients with OSA (21.3%) compared with 9 patients in the group without OSA (8.0%; P = .006). PA was also frequent in patients in whom symptoms of OSA were a sole indication for PA screening (15.4%) and in patients with and without resistant hypertension (24.5% and 17.8%, respectively). Most patients with PA and OSA were diagnosed with bilateral adrenal hyperplasia (18 patients, 90%). There were no major differences in clinical characteristics between patients with OSA with PA and those without PA. In multivariate models, moderate-to-severe OSA predicted the presence of PA (odds ratio 2.89, P = .018). CONCLUSIONS: Patients with clinically important moderate-to-severe OSA are characterized by a relatively high frequency of PA. Our results support the recommendations to screen patients with moderate-to-severe OSA for PA, regardless of the presence of other indications for PA screening.

Left Ventricular Structural and Functional Alterations in Patients With Pheochromocytoma/Paraganglioma Before and After Surgery.

OBJECTIVES: This study sought to evaluate left ventricular (LV) structure and function in pheochromocytoma and paraganglioma (PPGL) patients before and after curative surgery. BACKGROUND: Data on catecholamine-induced effects on LV structure and function in patients with PPGL are limited and conflicting. METHODS: The study evaluated 81 consecutive patients with a PPGL, among whom 66 were evaluated 12 months after tumor removal. Fifty patients matched for age, sex, hypertension presence, and blood pressure (BP) levels served as a control group (non-PPGL group). Echocardiography was employed to assess the LV mass index (LVMI), systolic function including speckle tracking echocardiography, and diastolic function. RESULTS: Patients with PPGL were characterized by higher LVMI (median 103 [interquartile range (IQR): 88 to 132] g/m2 vs. median 94 [IQR: 74 to 106] g/m2; p = 0.006) and frequency of LV hypertrophy (44.4% vs. 24.0%; p = 0.018) compared with the non-PPGL group. Patients with PPGLs were characterized by lower global longitudinal strain (GLS) and early diastolic mitral annular velocity compared with patients in the non-PPGL group (median -17.2% [IQR: 15.6% to 18.9%] vs. median -19.3% [IQR: 17.7% to 20.6%]; p < 0.001; and median 11.1 [IQR: 8.3 to 13.0] cm/s vs. median 12.3 [IQR: 10.6 to 14.6] cm/s; p = 0.018, respectively). Presence of LV hypertrophy and GLS were independently associated with plasma free metanephrine concentrations. In operated patients, there were lower frequencies of LV hypertrophy (39.4% vs. 22.7%; p = 0.003), LVMI (median 98 [IQR: 85 to 115] g/m2 vs. median 90 [IQR: 76 to 109] g/m2; p < 0.001), and the ratio of transmitral early diastolic velocity to early diastolic mitral annular velocity (median 6.8 [IQR: 5.5 to 8.6] vs. median 6.0 [IQR: 5.0 to 7.6]; p = 0.005) but higher values for GLS (median -17.4 [IQR: -15.8 to 19.1] vs. median -18.5 [IQR: -17.1 to 20.1] p < 0.001) after compared with before surgery. CONCLUSIONS: Catecholamine excess in patients with PPGLs can lead not only to LV hypertrophy, but also to impairment of systolic LV function and subclinical alterations of diastolic LV function, independently of BP levels. These structural and functional changes are reversible after surgical intervention.

SEMA3A and IGSF10 Are Novel Contributors to Combined Pituitary Hormone Deficiency (CPHD).

Background: The mutation frequencies of pituitary transcription factors genes in patients with combined pituitary hormone deficiencies (CPHD) vary substantially between populations. However, apart from PROP1 the mutation rate of other genes is low and for almost half of the patients with CPHD the routine sequencing of known genes is unsuccessful in the identification of genetic causes. Methods: A cohort of 66 sporadic and nine familial CPHD cases (80 patients in total) were subjected to initial testing of the genes PROP1, POU1F1, LHX3, LHX4, and HESX1 using a targeted gene panel and MLPA. In patients who tested negative, a whole exome sequencing approach was employed. Results: In nine of the familial cases and 32 of the sporadic patients mutations in the PROP1 gene were found (the common pathogenic variants included c.301_302delAG and c.150delA). Mutations were also found in genes so far not related directly to CPHD. A unique homozygous and clinically relevant variant was identified in the SEMA3A gene, which may contribute to neural development and his phenotypic spectrum including short stature and isolated hypogonadotropic hypogonadism (IHH). Another pathogenic variant p.A1672T was found in the IGSF10 gene reported to be responsible for delayed puberty and neuronal migration during embryogenesis. Several suspected novel but predicted benign variants were also identified for the CHD7, WDR11 and FGF17 genes. Conclusion: Although PROP1 defects account for a majority of CPHD patients, identification of rare, less frequent variants constitutes a big challenge. Multiple genetic factors responsible for CPHD are still awaiting discovery and therefore the usage of efficient genomic tools (i.e., whole exome sequencing) will further broaden our knowledge regarding pituitary development and function.

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.

Urine Steroid Metabolomics as a Novel Tool for Detection of Recurrent Adrenocortical Carcinoma.

CONTEXT: Urine steroid metabolomics, combining mass spectrometry-based steroid profiling and machine learning, has been described as a novel diagnostic tool for detection of adrenocortical carcinoma (ACC). OBJECTIVE, DESIGN, SETTING: This proof-of-concept study evaluated the performance of urine steroid metabolomics as a tool for postoperative recurrence detection after microscopically complete (R0) resection of ACC. PATIENTS AND METHODS: 135 patients from 14 clinical centers provided postoperative urine samples, which were analyzed by gas chromatography-mass spectrometry. We assessed the utility of these urine steroid profiles in detecting ACC recurrence, either when interpreted by expert clinicians or when analyzed by random forest, a machine learning-based classifier. Radiological recurrence detection served as the reference standard. RESULTS: Imaging detected recurrent disease in 42 of 135 patients; 32 had provided pre- and post-recurrence urine samples. 39 patients remained disease-free for ≥3 years. The urine "steroid fingerprint" at recurrence resembled that observed before R0 resection in the majority of cases. Review of longitudinally collected urine steroid profiles by 3 blinded experts detected recurrence by the time of radiological diagnosis in 50% to 72% of cases, improving to 69% to 92%, if a preoperative urine steroid result was available. Recurrence detection by steroid profiling preceded detection by imaging by more than 2 months in 22% to 39% of patients. Specificities varied considerably, ranging from 61% to 97%. The computational classifier detected ACC recurrence with superior accuracy (sensitivity = specificity = 81%). CONCLUSION: Urine steroid metabolomics is a promising tool for postoperative recurrence detection in ACC; availability of a preoperative urine considerably improves the ability to detect ACC recurrence.

Detecting adrenal insufficiency in patients with immunoglobulin A nephropathy, lupus nephritis, and transplant recipients qualified for glucocorticoid withdrawal.

INTRODUCTION: Long­term glucocorticoid (GC) therapy is the most common cause of secondary adrenal insufficiency (AI), which undiagnosed may lead to life­threatening adrenal crisis. OBJECTIVES: The aim of the study was to evaluate AI in patients treated long­term with GCs, receiving a low maintenance dose (≤5 mg of prednisone or equivalent), namely, its prevalence and persistence, risk factors, and diagnostic accuracy of morning cortisol and dehydroepiandrosterone sulfate (DHEA­S) levels. PATIENTS AND METHODS: Adrenal function was evaluated in 40 patients before and after GC withdrawal and at least 1 year later. Based on morning cortisol levels and short Synacthen test, patients were divided into 3 groups: AI, intermediate (partial AI), and AS (adrenal sufficiency). Receiver operator characteristic curves were calculated to assess the diagnostic value of morning cortisol and DHEA­S levels before GC withdrawal. RESULTS: Before GC withdrawal, 42.5% of patients had AI or partial AI, which together persisted in 64.3% of those patients after withdrawal. After more than a year, the adrenal function returned to normal only in 14% of patients. Cushingoid feature occurred more often in the AI group compared with the AS group (60% vs 13%; P = 0.03). Morning cortisol levels of 14.91 µg/dl or higher (411 nmol/l) gave 100% negative predictive value to rule out AI. Morning cortisol of 6.51 µg/dl or less (179.6 nmol/l) gave 100% positive predictive value to rule in AI. DHEA­S proved to be a worse parameter for AI diagnosis. CONCLUSIONS: AI is common in patients treated with GCs and may persist for years after GC withdrawal. Cushingoid features are associated with a higher risk of AI. Morning cortisol levels may facilitate AI diagnosis.

Surgical treatment of abdominal paragangliomas.

INTRODUCTION: Extraperitoneal, abdominal paragangliomas most commonly originate from the sympathetic nervous system. Typical features include catecholamine overproduction and the potential for malignancy. Lesions are usually located paravertebrally, but when growing in a more expansive manner they may also appear between the inferior vena cava and aorta. In the authors' opinion this site excludes laparoscopic tumourectomy. MATERIAL AND METHODS: Twenty-eight patients were selected for surgical management of abdominal paragangliomas in the past eight years at our endocrine surgical centre. This group consisted of 21 (75%) women and seven (25%) men, aged 14 to 84 years (mean 47.9). In 13 (46.4%) cases paroxysmal hypertension was observed. Type 2 diabetes was noted in another 10 (35.7%) patients, and Takotsubo acute coronary syndrome in two (7.1%). Patients were preoperatively qualified for either open surgery or laparoscopic tumourectomy based on visualisation and location of the tumours in imaging studies. RESULTS: All patients were successfully operated. Eleven (39.3%) patients qualified for laparoscopy, while the remaining 17 (60.7%) were treated with an open surgical approach due to difficult access to the lesion. The mean operative time was 130 minutes for laparoscopy and 120 minutes for laparotomy (p = 0.2). There were no local or general complications after either type of procedure. CONCLUSIONS: The use of laparoscopic access is practically excluded in the treatment of paragangliomas located between the inferior vena cava and aorta, especially at the level of the renal vessels and extending superiorly to the diaphragm.