Inflammation-based scores in a large cohort of adrenocortical carcinoma and adrenocortical adenoma: role of the hormonal secretion pattern.

BACKGROUND: Serum inflammation-based scores can predict clinical outcome in several cancer types, including adrenocortical carcinoma (ACC). It is unclear whether the extent of inflammation-based scores alterations in ACC reflects malignancy, steroid excess, or both. METHODS: We investigated a large retrospective cohort of adrenocortical adenomas (ACA, n = 429) and ACC (n = 61) with available baseline full blood count and hormonal evaluation. We examined the relationship between different inflammation-based scores [neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), and prognostic nutrition index (PNI)] and both malignancy and steroid secretion patterns. RESULTS: All inflammation-based scores differed between ACC and ACA: patients with ACC had higher NLR, PLR, SII and lower LMR and PNI levels compared to ACA (all p values < 0.001). NLR showed a positive correlation with cortisol levels after overnight 1 mg-dexamethasone suppression test (1 mg-DST), both in ACC and ACA (p < 0.01). The ROC curve analysis determined NLR > 2.6 as the best cut-off to discriminate ACC from ACA [AUC = 0.846, p < 0.01]. At multivariable analysis, NLR > 2.6 was independently associated with ACC, 1 mg-DST cortisol levels and age, but not with tumour size. Considering the ACC, NLR and SII were higher and PNI was lower in patients with cortisol excess compared to those without cortisol excess (p = 0.002, p = 0.007, and p = 0.044 respectively). Finally, LMR and NLR differed between inactive-ACC (n = 10) and inactive-ACA (n = 215) (p = 0.040 and p = 0.031, respectively). CONCLUSION: Inflammation-based scores are related to steroid secretion both in ACC and ACA. ACCs present a higher grade of inflammation regardless of their hormonal secretion, likely as a feature of malignancy itself.

Whole blood transcriptomic signature of Cushing's syndrome.

OBJECTIVE: Cushing's syndrome is characterized by high morbidity and mortality with high interindividual variability. Easily measurable biomarkers, in addition to the hormone assays currently used for diagnosis, could reflect the individual biological impact of glucocorticoids. The aim of this study is to identify such biomarkers through the analysis of whole blood transcriptome. DESIGN: Whole blood transcriptome was evaluated in 57 samples from patients with overt Cushing's syndrome, mild Cushing's syndrome, eucortisolism, and adrenal insufficiency. Samples were randomly split into a training cohort to set up a Cushing's transcriptomic signature and a validation cohort to assess this signature. METHODS: Total RNA was obtained from whole blood samples and sequenced on a NovaSeq 6000 System (Illumina). Both unsupervised (principal component analysis) and supervised (Limma) methods were used to explore the transcriptome profile. Ridge regression was used to build a Cushing's transcriptome predictor. RESULTS: The transcriptomic profile discriminated samples with overt Cushing's syndrome. Genes mostly associated with overt Cushing's syndrome were enriched in pathways related to immunity, particularly neutrophil activation. A prediction model of 1500 genes built on the training cohort demonstrated its discriminating value in the validation cohort (accuracy .82) and remained significant in a multivariate model including the neutrophil proportion (P = .002). Expression of FKBP5, a single gene both overexpressed in Cushing's syndrome and implied in the glucocorticoid receptor signaling, could also predict Cushing's syndrome (accuracy .76). CONCLUSIONS: Whole blood transcriptome reflects the circulating levels of glucocorticoids. FKBP5 expression could be a nonhormonal marker of Cushing's syndrome.

68Ga-pentixafor PET/CT in the localization diagnosis of primary aldosteronism concurrent subclinical cushing's syndrsome: two case reports.

PURPOSE: Adrenal venous sampling (AVS) is recommended for subtyping primary aldosteronism (PA). However, in cases of PA, concurrent subclinical Cushing's syndrome (SCS) has the potential to confound AVS results. Pentixafor, a CXC chemokine receptor type 4-specific ligand, has been reported as a promising marker to evaluate functional nature of adrenal adenomas. This study aims to investigate the clinical value of Gallium-68 Pentixafor Positron Emission Tomography-Computed Tomography (68Ga-Pentixafor PET/CT) in the localization diagnosis of patients with PA plus SCS. METHODS: Two patients with a confirmed diagnosis of PA plus SCS underwent AVS and 68Ga-Pentixafor PET/CT. RESULTS: AVS results revealed no lateralization for both patients while 68Ga-Pentixafor PET/CT showed a unilateral adrenal nodule with increased uptake of 68Ga-Pentixafor. Unilateral adrenalectomy was performed based on the results of 68Ga-Pentixafor PET/CT. Subsequently, complete biochemical remission of autonomous aldosterone and cortisol secretion were achieved in both cases. CONCLUSIONS: 68Ga-Pentixafor PET/CT shows promising potential for the localization of aldosterone and cortisol co-secreting adrenal adenoma in patients with PA plus SCS.

Beyond symptomatology: A comparative analysis of unilateral and bilateral macronodular mild autonomous cortisol secretion.

OBJECTIVE: To investigate the clinical, laboratory findings and signal intensity index (SII) on magnetic resonance imaging (MRI) of patients with bilateral and unilateral macronodular mild autonomous cortisol secretion (MACS). PATIENTS AND MEASUREMENTS: Clinical and laboratory findings of 81 patients with MACS were examined from retrospective records. SII of adenomas and internodular areas were evaluated by MRI. The unilateral group included patients with an adrenal macronodule (≥1 cm) in a single adrenal gland, while the bilateral group included patients with at least one macronodule in both adrenal glands. RESULTS: In total, 46 patients were in the unilateral (57%), while 35 (43%) patients were in the bilateral groups. The dehydroepiandrosterone sulphate (DHEA-S) level was lower in the unilateral than in the bilateral group (p < .001). The presence of type 2 diabetes mellitus (T2DM), glycosylated haemoglobin (HbA1c) and low-density lipoprotein (LDL) concentrations were higher in the bilateral group (p < .05). However, no significant difference was detected in terms of adrenocorticotropic hormone (ACTH) and overnight 1 mg dexamethasone suppression test (DST) between the two groups (p > .05). There was no difference in SII between adenomas within the same patient, as well as between the unilateral and bilateral groups (p > .05). Logistic regression analysis based on the differentiation between unilateral and bilateral macronodular MACS demonstrated that DHEA-S, HbA1c and LDL concentrations were associated factors. CONCLUSION: DHEA-S levels may not be as suppressed in patients with bilateral macronodular MACS as compared to those with unilateral adenoma. T2DM and hypercholesterolaemia have a higher frequency in bilateral patients. However, ACTH, overnight 1 mg DST and SII may not provide additional information for differentiation of bilaterality and unilaterality.

Thyroid function spectrum in Cushing's syndrome.

PURPOSE: Thyroid disorders have been reported in hypercortisolism patients. Endogenous Cushing's syndrome (CS) potentially complicates its metabolic sequelae. We investigated thyroid function in CS patients to determine this relationship. METHODS: In this cross-sectional study, we screened CS patients from 2016 to 2019 at our hospital. Patient demographic, medical history, and laboratory data were collected. Additionally, we performed a meta-analysis to demonstrate the prevalence of thyroid dysfunction in patients with CS. RESULTS: Among 129 CS patients, 48.6% had triiodothyronine (TT3), 27.9% had thyroxine (TT4), 24.6% had free T3 (FT3), 27.7% had free T4 (FT4), and 6.2% had thyroid-stimulating hormone (TSH) levels below the reference values. Those with clinical CS showed more pronounced thyroid suppression than did those with subclinical CS. Cortisol levels were markedly greater in patients with pituitary hypothyroidism (P < 0.001). Serum cortisol levels throughout the day and post low-dose dexamethasone-suppression test (LDDST) results correlated with thyroid hormone levels, particularly in ACTH-independent CS. Correlations varied by thyroid status; FT3 and TSH were linked to cortisol in euthyroid individuals but not in those with low T3 or central hypothyroidism. TSH levels notably halved from the lowest to highest cortisol tertile post-LDDST. Finally, meta-analysis showed 22.7% (95% CI 12.6%-32.9%) central hypothyroidism in 528 CS patients of nine studies. CONCLUSION: Thyroid hormone levels are significantly correlated with cortisol levels and are impaired in patients with CS. However, the physiological adaptation and pathological conditions need further study.

Clinical and imaging presentations are associated with function in incidental adrenocortical adenomas: a retrospective cohort study.

OBJECTIVE: The aim of this study is to assess whether clinical and imaging characteristics are associated with the hormonal subtype, growth, and adrenalectomy for incidental adrenal cortical adenomas (ACAs). DESIGN: This is a single-center cohort study. METHODS: Consecutive adult patients with incidental ACA were diagnosed between 2000 and 2016. RESULTS: Of the 1516 patients with incidental ACA (median age 59 years, 62% women), 699 (46%) had nonfunctioning adenomas (NFAs), 482 (31%) had mild autonomous cortisol secretion (MACS), 62 (4%) had primary aldosteronism (PA), 39 (3%) had Cushing syndrome, 18 (1%) had PA and MACS, and 226 (15%) had incomplete work-up. Age, sex, tumor size, and tumor laterality, but not unenhanced computed tomography Hounsfield units (HU), were associated with hormonal subtypes. In a multivariable analysis, ≥1 cm growth was associated with younger age (odds ratio [OR] = 0.8 per 5-year increase, P = .0047) and longer imaging follow-up (OR = 1.2 per year, P < .0001). Adrenalectomy was performed in 355 (23%) patients, including 38% of MACS and 15% of NFA. Adrenalectomy for NFA and MACS was more common in younger patients (OR = 0.79 per 5-year increase, P = .002), larger initial tumor size (OR = 2.3 per 1 cm increase, P < .0001), ≥1 cm growth (OR = 15.3, P < .0001), and higher postdexamethasone cortisol (OR = 6.6 for >5 vs <1.8 µg/dL, P = .002). CONCLUSIONS: Age, sex, tumor size, and laterality were associated with ACA hormonal subtype and can guide diagnosis and management. Tumor growth was more common with younger age and longer follow-up. Unenhanced HU did not predict hormonal subtype or growth. Adrenalectomy for MACS and NFA was mainly performed in younger patients with larger tumor size, growth, and elevated postdexamethasone cortisol.

Emergencia hipertensiva como debut de síndrome de Cushing paraneoplásico / Hypertensive Emergency as the Debut of Paraneoplastic Cushing Syndrome

Presentamos el caso de un paciente con antecedentes de hipertensión arterial vasculorrenal tratada un año antes, que acude a urgencias por emergencia hipertensiva (HTA) y disnea. Descartada primera sospecha de reestenosis de arteria renal con angiografía por tomografía computarizada (angioTC), se completa el estudio confirmándose diagnóstico de cáncer de pulmón mediante prueba de imagen y anatomía patológica. En el estudio de hipertensión se detecta elevación de hormona adrenocorticótropa (ACTH), hipercortisolismo y datos analíticos de hiperaldosteronismo. Con el diagnóstico final de síndrome de Cushing secundario a producción ectópica de ACTH se inicia tratamiento médico, sin llegar a recibir nada más por fallecimiento del paciente a los pocos días.(AU)

We present the case of a patient with a history of renal-vascular hypertension treated with stent one year previously, who attended the emergency room due to hypertensive emergency and dyspnea. Once the first suspicion of renal artery restenosis was ruled out with CT angiography, the study was completed, confirming the diagnosis of lung cancer through imaging and pathological anatomy. In the hormonal study, elevation of ACTH, hypercortisolism and analytical data of hyperaldosteronism were detected. With the final diagnosis of Cushing's syndrome secondary to ectopic production of ACTH, medical treatment was started, without being able to receive anything else due to the death of the patient after a few days.(AU)

Bilateral Adrenocortical Nodular Disease and Cushing's Syndrome.

Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and Bilateral Macronodular Adrenocortical Disease (BMAD) are two forms of Adrenocortical Nodular Diseases causing Cushing's syndrome, but are two very distinct conditions. PPNAD, affecting mostly young patients with an almost constant severe Cushing's syndrome, is characterized by pigmented micronodules, usually less than 1 cm, not always visible on imaging. On the contrary, BMAD is predominantly diagnosed in the fifth and sixth decades, with highly variable degrees of cortisol excess, from mild autonomous cortisol secretion to overt Cushing's syndrome. BMAD presents as large bilateral adrenal macronodules, easily observed on imaging. Both diseases are often genetically determined: frequently PPNAD is observed in a multiple neoplasia syndrome, Carney complex (CNC), and a germline genetic defect is identified in around 80% of index cases, always affecting key actors of the cAMP/PKA pathway: mostly PRKAR1A, encoding the PKA 1-alpha regulatory subunit. On the other hand, BMAD appears mostly isolated, and two predisposing genes are known at present: ARMC5, accounting for around 20% of index cases, and the recently identified KDM1A, causing the rare presentation with food-dependent Cushing's syndrome, mediated by the ectopic expression of the Glucose-dependent Insulinotropic Polypeptide receptor (GIPR) in adrenal nodules. GIPR was the first demonstrated receptor to illegitimately regulate cortisol secretion in nodular adrenocortical diseases, and a myriad of other receptors and paracrine signals were discovered afterward. The last 30 years were pivotal in the understanding of the genetics and pathophysiology of Bilateral Adrenocortical Nodular Diseases, leading to a personalized approach of these fascinating conditions.

The conundrum of differentiating Cushing's syndrome from non-neoplastic hypercortisolism: a systematic review and meta-analysis.

CONTEXT: Once hypercortisolemia is confirmed, differential diagnosis between Cushing's syndrome (CS) due to neoplastic endogenous hypercortisolism and non-neoplastic hypercortisolism (NNH, pseudo-Cushing's syndrome) is crucial. Due to worldwide corticotropin-releasing hormone (CRH) unavailability, accuracy of alternative tests to dexamethasone (Dex)-CRH, is clearly needed. OBJECTIVE: Assess the diagnostic accuracy of Dex-CRH test, desmopressin stimulation test, midnight serum cortisol (MSC), and late-night salivary cortisol (LNSC) levels to distinguish CS from NNH. METHODS: Articles through March 2022 were identified from Scopus, Web of Science, MEDLINE, EMBASE, and PubMed. All steps through the systematic review were performed independently and in duplicate and strictly adhered to the updated PRISMA-DTA checklist. DATA SYNTHESIS: A total of 24 articles (1900 patients) were included. Dex-CRH had a pooled sensitivity and specificity of 91% (95%CI 87-94%; I2 0%) and 82% (73-88%; I2 50%), desmopressin test 86% (81-90%; I2 28%) and 90% (84-94%; I2 15%), MSC 91% (85-94%; I2 66%) and 81% (70-89%; I2 71%), and LNSC 80% (67-89%; I2 57%) and 90% (84-93%; I2 21%), respectively. Summary receiver operating characteristics areas under the curve were Dex-CRH 0.949, desmopressin test 0.936, MSC 0.942, and LNSC 0.950 without visual or statistical significance. The overall risk of studies bias was moderate. CONCLUSION: Dex-CRH, the desmopressin stimulation test, and MSC have similar diagnostic accuracy, with Dex-CRH and MSC having slightly higher sensitivity, and the desmopressin test being more specific. LNSC was the least accurate, probably due to high heterogeneity, intrinsic variability, different assays, and lack of consistent reported cutoffs. When facing this challenging differential diagnosis, the results presented here should increase clinicians' confidence when deciding which test to perform.

Effects of glucocorticoids on adipose tissue plasticity.

Glucocorticoids (GCs) play an important role in metabolic adaptation, regulating carbohydrate-lipid homeostasis and the immune system. Because they also have anti-inflammatory and immunosuppressive properties, synthetic analogues of GCs have been developed and are widely used in the treatment of chronic inflammatory conditions and in organ transplantation. GCs are among the most commonly prescribed drugs in the world. However, long term and high GC doses can cause side effects such as GC-induced diabetes and lipodystrophy. In recent years, a large number of independent studies have reported the effects of constitutive and adipocyte-specific deletion of the GC receptor (GR) in mice under different diets and treatments, resulting in contrasting phenotypes. To avoid potential compensatory mechanisms associated with the constitutive adipocyte GR silencing during adipose tissue development, our team has generated an inducible mouse model of GR deletion specifically in the adipocyte (AdipoGR-KO). Using this mouse model, we were able to demonstrate the critical role of the adipocyte GR in GC-induced metabolic changes. Indeed, under conditions of hypercorticism, AdipoGR-KO mice showed an improvement in glucose tolerance and insulin sensitivity, as well as in lipid profile, despite a massive increase in adiposity. This result is explained by a densification of adipose tissue vascularization, highlighting the repressive role of adipocyte GR in the healthy expansion of this tissue. Our work has largely contributed to the demonstration of the important role of the adipocyte GR in the physiology and pathophysiology of the adipose tissue and its impact on energy homeostasis.

Frequency of low-dose dexamethasone suppression test (LDDST) response patterns and their correlation with clinicopathologic signs in dogs suspected of having Cushing's syndrome: A retrospective study.

A retrospective cross-sectional study was conducted to assess the frequency of low-dose dexamethasone suppression test (LDDST) patterns in canine patients that had clinicopathologic signs consistent with Cushing's syndrome (CS). Medical records for patients of interest (N = 128) were reviewed between January 2014 and December 2020 to analyse and classify LDDST results based upon the following patterns: lack of suppression, partial suppression, complete suppression, escape, or inverse. Complete suppression, lack of suppression, partial suppression, escape, and inverse patterns were identified in 39.1%, 31.2%, 14.1%, 10.1% and 5.5% of cases respectively. LDDST results were also evaluated with respect to clinical signs, serum alkaline phosphatase (ALP) activity, urine specific gravity (USG) and adrenal ultrasonographic findings. There was no association between LDDST patterns and clinical signs (p = 0.11), increased ALP (p = 0.32), USG (p = 0.33) or adrenal ultrasonographic findings (p = 0.19). In all dogs that demonstrated complete suppression or an inverse pattern, CS was excluded by the attending clinician. The diagnosis of CS was also excluded without further exploration in 23.1%, 7.5% and 5.6% of dogs that demonstrated an escape pattern, lack of suppression and partial suppression pattern, respectively. These results suggest that the clinical significance of LDDST patterns, particularly escape and inverse patterns, are misunderstood by some clinicians, leading them to prematurely exclude the diagnosis of CS.

Evaluation of Adrenal Incidentaloma.

Adrenal incidentalomas have increased due to advanced and more sensitive imaging modalities, their increased utilization, and the aging population. Most adrenal incidentalomas are nonfunctional and benign, but a subset of patients has functional and/or malignant tumors. The evaluation of patients with an adrenal incidentaloma involves addressing 2 clinical questions: (1) Is the tumor functional? (2) Is the tumor malignant? A careful history and physical examination focused on signs and symptoms of adrenal functional tumors, biochemical testing, and imaging features are the cornerstone in the evaluation of patients with an adrenal incidentaloma.

A Rare Cyclic Cushing Syndrome Mystery Illustrates Diagnostic Principles.

Pheochromocytomas predominantly produce catecholamines, and rarely also produce ACTH, causing Cushing syndrome (CS). Cyclic CS, an uncommon presentation of hypercortisolism, poses a diagnostic challenge. We report a 71-year-old woman who developed cyclic ectopic ACTH secretion from a pheochromocytoma. Previous evaluations showed intermittent elevations in cortisol and ACTH levels, normal pituitary magnetic resonance imaging, and an adrenal nodule. On admission, she was hypertensive and had cushingoid features. Bilateral inferior petrosal sinus sampling with desmopressin stimulation and an 8-mg dexamethasone suppression test suggested ectopic ACTH secretion, but ACTH increased during the peripheral desmopressin stimulation test. Plasma normetanephrines were about 2-fold above the upper reference limit. 18F-fluoro-dopa and 68Gallium-DOTATATE positron emission tomography/computed tomography scans, computed tomography, and magnetic resonance imaging identified an adrenal mass. After doxazosin adrenoceptor blockade, she underwent right adrenalectomy; histopathology and immunohistochemistry confirmed an ACTH-secreting pheochromocytoma. Postoperative blood pressure normalized and serum cortisol and plasma ACTH levels were suppressed, requiring physiologic hydrocortisone replacement. This case underscores the importance of considering pheochromocytoma in ACTH-dependent hypercortisolism with elevated metanephrines and an adrenal mass. Timely diagnosis and treatment can reduce morbidity and improve quality of life.

Evaluating the usefulness of plasma chromogranin A measurement in cyclic ACTH-dependent Cushing's syndrome.

Cushing's syndrome, a clinical condition characterized by hypercortisolemia, exhibits distinct clinical signs and is associated with cyclic cortisol secretion in some patients. The clinical presentation of cyclic Cushing's syndrome can be ambiguous and its diagnosis is often challenging. We experienced a 72-year-old woman with cyclic ACTH-dependent Cushing's syndrome caused by a pulmonary carcinoid tumor. Diagnosis was challenging because of the extended trough periods, and the responsible lesion was initially unidentified. A subsequent follow-up computed tomography revealed a pulmonary lesion, and ectopic ACTH secretion from this lesion was confirmed by pulmonary artery sampling. Despite the short peak secretion period of ACTH (approximately one week), immunostaining of the surgically removed tumor confirmed ACTH positivity. Interestingly, stored plasma chromogranin A levels were elevated during both peak and trough periods. The experience in evaluating this patient prompted us to investigate the potential use of plasma chromogranin A as a diagnostic marker of ACTH-dependent Cushing's syndrome. A retrospective study was conducted to determine the efficacy of plasma chromogranin A in three patients with ectopic ACTH syndrome (EAS), including the present case, and six patients with Cushing's disease (CD) who visited our hospital between 2018 and 2021. Notably, plasma chromogranin A levels were higher in patients with EAS than in those with CD. Additionally, a chromogranin A level in the present case during the trough phase was lower than that in the peak phase, and was similar to those in CD patients. The measurement of plasma chromogranin A levels could aid in differentiating EAS from CD.

Ectopic adrenocortical adenoma characterized by hypogonadism: a case report and review of the literature.

BACKGROUND: Currently, there is a scarcity of cases and diagnostic data regarding ectopic adrenocortical adenomas, particularly in relation to their impact on gonadal function and localization diagnostic techniques. We report a typical case of ectopic adrenocortical adenomas and the data of treatment follow-up, and review the literature of 31 available cases of ectopic adrenocortical adenomas. CASE PRESENTATION: A 27-year-old Chinese female patient was admitted to our hospital for hypertension, hyperglycaemia and primary amenorrhea. The patient was functionally diagnosed with ACTH-independent CS and hypogonadotropic hypogonadism. Radiological evaluations, including Computed Tomography (CT) and functional imaging, identified a mass at the left renal hilum. Histological assessments post-surgical excision confirmed the mass to be an ectopic adrenocortical adenoma. A subsequent 3-month follow-up showed no signs of disease recurrence, a swift recovery of the cortisol axis was observed, with a partial recuperation of the gonadal axis. REVIEW: Our literature review shows that the most common ectopic areas of cortisol adenomas are renal hilum and hepatic region. The most positive biomarker is Melan A, and only a few cases have been diagnosed with functional localization. CONCLUSION: Ectopic adrenocortical adenomas may be asymptomatic in the early stage and can impact gonadal function. Physicians who treat hypogonadism must be aware of the need to test cortisol levels and perform functional localization in patients with lumps present.

High LDL Particle and APOB Concentrations in Patients With Adrenal Cortical Adenomas: A Cross Sectional Study.

CONTEXT: Patients with nonfunctioning adenomas (NFA), adenomas with mild autonomous cortisol secretion (MACS) and Cushing syndrome (CS) demonstrate an increased cardiovascular risk. OBJECTIVE: To determine the extent of lipoprotein abnormalities in NFA, MACS, and CS. METHODS: We conducted a single-center cross-sectional study of patients with NFA (n = 167), MACS (n = 213), CS (n = 142) and referent subjects (n = 202) between January 2015 and July 2022. Triglyceride-rich lipoprotein particles (TRLP), low density lipoprotein particles (LDLP), high density lipoprotein particles (HDLP), their subclasses and sizes were measured using nuclear magnetic resonance spectroscopy. Multivariable logistic analyses were adjusted for age, sex, BMI, smoking, hypertension, diabetes and lipid lowering drug therapy. RESULTS: In age- and sex-adjusted analysis, all patients categories demonstrated increased very large TRLP, large TRLP and greater TRL size (odds ratio (OR) ranging from 1.22 to 2.08) and total LDLP (OR ranging from 1.22 to 1.75) and decreased LDL and HDL size compared to referent subjects. In fully adjusted analysis, LDLP concentrations remained elevated in all patient categories (odds ratios ranging from 1.31 to 1.84). Total cholesterol, LDL cholesterol, triglycerides and apolipoprotein B were also higher in all patient categories in age- and sex-adjusted analysis with apoB remaining elevated in all patient categories in fully adjusted analysis. Similar LDLP and apoB elevations were observed in all patient categories after excluding subjects on lipid lowering therapy. CONCLUSION: Patients with overt, mild, and even absent cortisol excess demonstrate lipoprotein profile abnormalities, in particular, high LDLP and apoB concentrations, which conceivably contribute to high cardiometabolic risk.

Cushing's Syndrome is Associated with a Higher Risk of Cancer - A Nationwide Cohort Study.

CONTEXT: Patients with Cushing's syndrome (CS) have higher risk of obesity and diabetes, which are important risk factors of cancers. However, if patients with CS have a higher incidence of cancer remains unknown. OBJECTIVE: To investigate if endogenous CS is associated with increased cancer incidence. DESIGN: A nationwide cohort study. SETTING: Analysis of the data retrieved from Taiwan's National Health Insurance program in 2006-2017. PARTICIPANTS: Between 2006-2017, 1278 patients with newly diagnosed endogenous CS were identified. Among them, 1246 patients without a history of malignancy were enrolled in this study. EXPOSURES: Endogenous CS. MAIN OUTCOMES MEASURES: The age- and sex-standardized incidence rate of all-cause cancer and age-sex-calendar year standardized incidence ratio (SIR) of cancer in association with endogenous CS. RESULTS: The age- and sex-standardized incidences of CS decreased from 4.84 to 3.77 per million person-years between 2006-2017. The age at diagnosis of CS was 45.3 ± 14.8 years, and 80.0% of the patients were female. Cushing's disease and adrenal CS accounted for 35.4% and 64.6% of patients with CS, respectively. The incidence rate of cancer in patients with CS was 7.77 (95% Confidence Interval [CI] = 5.84-10.14) per 1000 person-years, with an SIR of 2.08 (95% CI = 1.54-2.75). The three most common cancer types were liver (27.7%), kidney (16.7%), and lung (13.0%). CONCLUSIONS: Patients with endogenous CS have a higher incidence of cancer.

Cognitive functions and the brain-derived neurotrophic factor in patients with mild autonomous cortisol secretion.

CONTEXT: The impact of abnormal cortisol secretion on cognitive functions in patients with mild autonomous cortisol secretion (MACS) remains uncertain. OBJECTIVE: To assess cognitive functions, determine serum brain-derived neurotrophic factor (BDNF) concentration in patients with MACS, and investigate the association between cognitive subdomains and BDNF. METHODS: We prospectively recruited 84 participants-28 patients with MACS, 28 patients with nonfunctional adrenal adenoma (NFAA), and 28 control subjects matched for age, gender, body mass index (BMI), visceral adiposity, and educational level. The serum BDNF concentration of participants was measured. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-focused interviews and Montreal Cognitive Assessments (MoCA) were carried out by an experienced psychiatrist. RESULTS: Patients with MACS had a higher serum BDNF concentration than the NFAA (P = .001), while that of patients with NFAA was lower than the controls (P = .044). Linear regression analysis revealed BMI and morning cortisol after overnight 1 mg dexamethasone (DST) were mostly associated with BDNF (P < .05). No significant difference was found in MoCA scores between MACS and NFAA groups (P = .967), whereas those were lower than the control group (P = .004). When the cognitive subdomains were examined separately, MACS group performed higher memory score than NFAA (P = .045), but lower language scores than both the NFAA (P = .024) and control groups (P < .001). In the whole group, BDNF concentration was positively correlated with memory score (r = 0.337, P = .002), whereas DST was negatively correlated with language score (r = -0.355, P = .008). CONCLUSION: Low-grade hypercortisolism is associated with elevated BDNF concentrations, which may be a protective factor for memory function in patients with MACS relative to those with NFAA.

Unveiling the Uncommon: Cushing's Syndrome (CS) Masquerading as Severe Hypokalemia.

Cushing's syndrome (CS) arises from an excess of endogenous or exogenous cortisol, with Cushing's disease specifically implicating a pituitary adenoma and exaggerated adrenocorticotropic hormone (ACTH) production. Typically, Cushing's disease presents with characteristic symptoms such as weight gain, central obesity, moon face, and buffalo hump. This case report presents an unusual manifestation of CS in a 48-year-old male with a history of hypertension, where severe hypokalemia was the primary presentation. Initial complaints included bilateral leg swelling, muscle weakness, occasional shortness of breath, and a general feeling of not feeling well. Subsequent investigations revealed hypokalemia, metabolic alkalosis, and an abnormal response to dexamethasone suppression, raising concerns about hypercortisolism. Further tests, including 24-hour urinary free cortisol and ACTH testing, confirmed significant elevations. Brain magnetic resonance imaging (MRI) identified a pituitary macroadenoma, necessitating neurosurgical intervention. This case underscores the rarity of CS presenting with severe hypokalemia, highlighting the diagnostic challenges and the crucial role of a collaborative approach in managing such intricate cases.