Cushing's Patients Research Articles

7385 Prevalence of Central Hypothyroidism in Cushing Syndrome and Thyroid Function Tests After Cushing Treatment

Abstract Disclosure: T. Kunavisarut: None. A. Sriwijitkamol: None. Cushing syndrome can be associated with thyroid dysfunction. We investigated the association between Cushing syndrome and thyroid dysfunction. We conducted a retrospective study at Siriraj Hospital in Thailand and analyzed thyroid function tests in 80 Cushing's patients. The inclusion criteria were patients diagnosed with Cushing syndrome with thyroid function tests recorded at diagnosis of Cushing syndrome. Patients who had an abnormal thyroid function test at diagnosis of Cushing syndrome must have a thyroid function test after treatment of Cushing syndrome. Of the 80 patients, sixty-five patients (81.2%) had normal thyroid function at diagnosis, 12 patients (15%) had central hypothyroidism and three patients (3.8%) had subclinical hyperthyroidism.Interestingly, among 12 patients who had central hypothyroidism, eight patients (66.7%) were diagnosed with Cushing disease. Three patients (25%) were diagnosed with adrenal Cushing syndrome and one patient (8.3%) was diagnosed with ectopic Cushing syndrome. This finding suggested that central hypothyroidism may not be exclusively due to the mass effect of the pituitary tumor on the normal pituitary because adrenal Cushing syndrome and ectopic Cushing syndrome can also cause central hypothyroidism. Among 12 patients with central hypothyroidism at diagnosis of Cushing syndrome, nine patients (75%) normalized their thyroid function after remission of Cushing syndrome without Levothyroxine replacement. Moreover, patients with central hypothyroidism had significantly higher median 24-hour urine-free cortisol levels than euthyroid patients (1030.5 ug/day vs. 404.5 ug/day, p=0.017), indicating a potential correlation between cortisol excess and low FT4 levels. These findings suggest that hypercortisolism in Cushing syndrome can suppress the hypothalamic-pituitary-thyroid axis, but this suppression is often reversible with successful Cushing's treatment. This study highlights the importance of central hypothyroidism, which can occur in all types of Cushing syndrome. If the patients did not have hypothyroid symptoms, Levothyroxine replacement may not be necessary. For patients who already received Levothyroxine and had normal thyroid function tests, Levothyroxine can be carefully tapered and potentially discontinued because successful Cushing syndrome treatment can ultimately normalize thyroid function tests. Presentation: 6/1/2024

8475 Automated Insulin Delivery System with Concentrated Regular U500 Insulin in Cushing Syndrome

Abstract Disclosure: F. Erenler: None. J. Aurora: None. Background: Concentrated regular U-500 (U-500R) insulin is commonly used in patients with T2DM, who are highly insulin-resistant, requiring more than 200 units of insulin per day. Utilizing U-500R reduces the number of daily injections, decreases injection volume, and improves cost effectiveness. There has been a case report with U-500R in an automated insulin delivery (AID) system with successful results (1). To our knowledge there is no data on AID system use in Cushing patients with T2DM using U-500R. We present a case of a patient with Cushing Syndrome (CS) with poor BG control using >250 units/day of SC U-500R with improved BG control after switching to Omnipod 5 AID system. Clinical Case: A 57 y.o. male initially presented with hypogonadotropic hypogonadism and subsequently diagnosed with ACTH-dependent CS, which is complicated by obesity, uncontrolled T2DM, lower extremity wounds, and DVTs. He was diagnosed with CS with multiple abnormal 1 mg dexamethasone suppression tests (DST) (max AM cortisol 5.9 mcg/dL; RR <1.8 mcg/dL, dexamethasone level 300), elevated urine free cortisol (UFC) (max UFC/Cr 77.6 mcg/mg/L; RR: 5-64 mcg/24-hr) and elevated salivary cortisol (max cortisol 0.2 mcg/dL; RR: <0.09 mcg/dL). He had suppressed cortisol with 8 mg DST. An MRI sella showed left-sided hypoechoic 0.9 cm mass. Desmopressin (DDAVP) stimulation test and Ga-68 DOTATATE-PET scan were negative. As a result of his abnormal MRI sella and elevated cortisol, he underwent transsphenoidal surgery of the left pituitary. Pathology was non-diagnostic for a pituitary adenoma. Post-op 24-hr UFC and 1 mg DST levels remained high. DDAVP stimulation test and Ga-68 DOTATATE-PET were repeated post-op and were negative. Due to complications of CS, he was initially treated with cabergoline, but switched to osilodrostat due to intolerances. He is currently on 2 mg BID dose and 24-hr UFC has been normal since then (UFC 20 mcg/L, Cr 0.67 mg, UFC/Cr 12 mcg/mg/L). He continued to have uncontrolled hyperglycemia despite normalization of UFC. On his CGM data, he was in target range (70-180 mg/dL) 5% of the time despite using U-500R 95 units SC TID. Given his severe hyperglycemia and insulin resistance, he was switched to an AID system with U-500R and his time in target range improved over 60% after a month of use and his total daily dose of insulin decreased to less than 200 units. Conclusion: U-500R proved to be safe and effective with Omnipod 5 AID. To our knowledge, this is the first reported patient with CS using U-500R with Omnipod 5 AID. In patients without CS, the AID algorithm continuously kept BG well below the set target, especially overnight. Notably, our patient did not have this overnight hypoglycemia trend, which should be expected with his disease. We are hoping to increase the awareness of U-500R with AID systems, especially for patients with incurable CS. Reference:1.Aurora J Jr, Saraswat A. J Endocr Soc. 2023;7(Suppl 1):bvad114.873. Presentation: 6/3/2024

Atypical presentation of Cushing's disease with weight loss and hypokalemia.

ACTH-secreting pituitary adenomas causing Cushing's disease (CD) typically present with weight gain, whereas weight loss and hypokalemia in endogenous Cushing's patients are suggestive of ectopic ACTH production. We report a case of CD presenting with atypical features of marked weight loss and hypokalemia. A 75-year-old female was admitted to the hospital with a history of profound weight loss, associated with uncontrolled hypertension, hyperglycemia, severe proximal muscle weakness, and hypokalemia. Subsequent investigations, including 24-h urinary free cortisol, 48-h low-dose dexamethasone suppression test, MRI of the sella, and bilateral inferior petrosal sinus sampling, confirmed CD without any evidence of ectopic ACTH production. She became eucortisolemic with medical therapy of ketoconazole and cabergoline, subsequently regained her weight, and became normokalemic. This case illustrates that patients with CD may present with symptoms and biochemical findings that would otherwise suggest ectopic ACTH production. Patients with CD do not always present with classical clinical features and may present with symptoms and biochemical findings that would otherwise suggest ectopic ACTH production. While most patients with CD typically lose weight after biochemical remission, some patients gain weight after the normalization of cortisol levels. This case highlights the need to entertain a broad differential in patients presenting with hypokalemia and weight loss and the need to exclude hypercortisolemia.

Adipocyte Glucocorticoid Receptor Activation With High Glucocorticoid Doses Impairs Healthy Adipose Tissue Expansion by Repressing Angiogenesis.

In Human, glucocorticoids (GC) are commonly prescribed because of their anti-inflammatory and immunosuppressive properties. However, high doses of GC often lead to adverse side effects including diabetes and lipodystrophy. We recently reported that adipocyte glucocorticoid receptor (GR)-deficient (AdipoGR-KO) mice under corticosterone (CORT) treatment exhibited a massive adipose tissue (AT) expansion associated with a paradoxical improvement of metabolic health compared to control mice. However, whether GR may control adipose development remains unclear. Here, we show a specific induction of the hypoxiainducible factor HIF-1α and the pro-angiogenic Vascular Endothelial Growth Factor-A expression in GR-deficient adipocytes of AdipoGR-KO mice as compared to control mice, together with an increased adipose vascular network, as assessed by 3D-analysis imaging. GR activation reduced HIF-1α recruitment on Vegfa promoter resulting from Hif-1α downregulation at the transcriptional and post-translational levels. Importantly, in CORT-treated AdipoGR-KO mice, the blockade of VEGFA by a soluble decoy receptor prevented AT expansion and the healthy metabolic phenotype. Finally, in subcutaneous AT from Cushing patients, higher VEGFA expression was associated with a better metabolic profile. Collectively, these results highlight that adipocyte GR negatively controls AT expansion and metabolic health through the down-regulation of the major angiogenic effector VEGFA and inhibiting vascular network development. (LIPOCUSH, NCT01688349).

ODP143 Cushing Syndrome - A Potential Risk Factor For Atrial Fibrillation

Abstract Introduction Cushing syndrome (CS) is a systemic disorder characterized by prolonged exposure to high cortisol hormones. Our study analyses the association of Cushing syndrome as a risk factor for atrial fibrillation (A-fib), its effect on associated complications and mortality. Methods We conducted a retrospective analysis of 3 years of the National Inpatient Sample (NIS) data base from 2016 to 2018. Patients with Cushing syndrome, in association with/without A-fib were selected using ICD-10 diagnosis code. Discharge-level weight analysis was used to produce a national estimate. We conducted multivariate regression analysis to calculate odds ratio. RESULTS: During the study period 107,024,275 patient met inclusion criteria. 35,309 patient was diagnosed with CS. Mean age of Cushing patients was 52 and non-Cushing patients was 49. History of hypertension, congestive heart failure (CHF) and obstructive sleep apnea (OSA) were more prevalent in CS population (42. 03% v 29.34%, 20.99% vs 14.18, 17.29% v 5.86). Cushing patients had less prevalence of ischemic heart disease (5.10% v 5.91%). After adjusting with age, hypertension, CHF, ischemic heart disease, race and OSA, CS is related with higher prevalence of A-fib (OR 1.13, 1. 03-1.24, p = 0. 014). However it doesn't increase the complications of A-fib. While 3.70% patients with both CS and A-fib developed ischemic stroke, 3.81% patients without Cushing had the ischemic strokes. No arterial embolic events were detected in CS patients with A-fib, but 0.41% of patients without CS had arterial embolism. Univariate regressions demonstrated no significant association between CS and ischemic stroke associated with A-fib (p = 0.898). Our study also demonstrated that CS is related with high in-hospital mortality. When it was adjusted to age, sex, congestive heart failure, ischemic stroke and chronic kidney disease, CS with concomitant A-fib is associated 1.8 times higher mortality (OR 1.8, 1.27- 2.60, p = 0. 001). Discussion Several studies have demonstrated a possible association between serum cortisol level and the risk of A-fib. To our knowledge, this is the first study to demonstrate CS's clinical significance on A-fib. In our analysis, a statistically significant association was found between A-fib and CS with higher in-hospital mortality reported in patients with CS and concomitant A-fib. Patients with CS tend to have higher CHA2DS2-VASc Score but there is no association with higher risk of complications from A-fib. Our study prompts the need for further research to establish CS as an important risk factor for atrial fibrillation. Presentation: No date and time listed

Evaluation of autoantibody signatures in pituitary adenoma patients using human proteome arrays.

To identify the specific diagnostic biomarkers related to pituitary adenomas (PAs), we performed serological antibody profiles for three types of PAs, namely Acromegaly, Cushing's and Nonfunctional Pituitary Adenomas (NFPAs), using the human proteome (HuProt) microarray. This is the first study describing the serum autoantibody profile of PAs. We performed serological autoantibody profiling of four healthy controls, four Acromegaly, three Cushing's and three NFPAs patient samples to obtain their autoantibody profiles, which were used for studying expression, interaction and altered biological pathways. Further, significant autoantibodies of PAs were compared with data available for glioma, meningioma and AAgAtlas for their specificity. Autoantibody profile of PAs led to the identification of differentially expressed significant proteins such as AKNAD1 (AT-Hook Transcription Factor [AKNA] Domain Containing 1), NINJ1 (Nerve injury-induced protein 1), L3HYPDH (Trans-3-hydroxy-L-proline dehydratase), RHOG (Rho-related GTP-binding protein) and PTP4A1 (Protein Tyrosine Phosphatase Type IVA 1) in Acromegaly. Protein ABR (Active breakpoint cluster region-related protein), ST6GALNAC6 (ST6 N-acetylgalactosaminide alpha-2, 6-sialyltransferase 6), NOL3 (Nucleolar protein 3), ANXA8 (Annexin A8) and POLR2H (RNA polymerase II, I and III subunit H) showed an antigenic response in Cushing's patient's serum samples. Protein dipeptidyl peptidase 3 (DPP3) and reticulon-4 (RTN4) exhibited a very high antigenic response in NFPA patients. These proteins hold promise as potential autoantibody biomarkers in PAs.

Cardiovascular complications of Cushings syndrome: Impact on morbidity and mortality.

Cardiovascular complications of Cushings syndrome: Impact on morbidity and mortality.

Hypocortisolemia following unilateral adrenalectomy

Abstract Objective Unilateral adrenalectomy (UA) is the best option for unilateral functioning and non-functioning adrenal adenomas, localized primary or metastatic carcinomas. Post-operative hypocortisolemia (HC) in Cushing Syndrome is well known, but several studies reported HC after UA for other indications. A systematic full endocrine investigation for all adrenal mass is not systematic and dexamethasone suppression test (DST) is not recommended in non-Cushing functioning tumours. Double secretion (autonomous cortisol co-secretion) is a rare phenomenon. The purpose of the study was to review incidence of postoperative HC in a tertiary centre. Methods Retrospective study (2012–2020) looking for hypocortisolemia after UA in patients operated for Cushing Syndrome and other endocrine tumours. Pre- and postoperative laboratory findings were reviewed in a total of 115 patients with UA. Patients receiving perioperative dexamethasone (DEX) for nausea and vomiting prophylaxis were included as well. Results UA (51 right and 64 left) were performed in 47 women and 68 men (mean age 53.5 y.), laparoscopically in 97 (84.3%, 3 converted). UA indications included: Cushing (8), autonomous cortisol secretion (10, in 2 with combined Conn), Conn syndrome (37), pheochromocytoma (24), non-functioning adenoma (10, adrenal carcinoma (3), adrenal metastasis (19) and other diagnosis (4). 18 patients had a preoperative DST (15.7%). Anaesthesia reports revealed that 53/115 patients received DEX. 51/115 patients had a control of postoperative cortisol level. Hypocortisolemia was observed overall in 28/51 patients, by excluding Cushing patients in 24/45, in 19/53 patients who received DEX and in 7/48 in those without DEX. Confusion comes when patients receiving DEX had normal postoperative cortisolemia. Conclusion The fact that some patients received DEX (ERAS pathway), complicated the interpretation of cortisol levels at postoperative day one (D1). DEX is known to supress the hypothalamic-pituitary-adrenal axis (HPA axis) at D1. Thus, claiming that hypocortisolemia is the result of cortisol co-secretion (adenoma with double secretion), also able to supress the HPA axis, is not possible in patients who received DEX. These results suggests 1) to fully investigate all hormone functions in case of adrenal mass and 2) not administrating DEX in patients undergoing UA, for adequately assessing the HPA axis function postoperatively.

Gene expression changes in the brain of a Cushing's syndrome mouse model.

Excess glucocorticoid exposure affects emotional and cognitive brain functions. The extreme form, Cushing's syndrome, is adequately modelled in the AdKO2.0 mouse, consequential to adrenocortical hypertrophy and hypercorticosteronemia. We previously reported that the AdKO2.0 mouse brain undergoes volumetric changes that resemble closely those of Cushing's syndrome human patients, as well as changes in expression of glial related marker proteins. In the present work, the expression of genes related to glial and neuronal cell populations and functions was assessed in regions of the anterior brain, hippocampus, amygdala and hypothalamus. Glucocorticoid target genes were consistently regulated, including CRH mRNA suppression in the hypothalamus and induction in amygdala and hippocampus, even if glucocorticoid receptor protein was downregulated. Expression of glial genes was also affected in the AdKO2.0 mouse brain, indicating a different activation status in glial cells. Generic markers for neuronal cell populations, and cellular integrity were only slightly affected. Our findings highlight the vulnerability of glial cell populations to chronic high levels of circulating glucocorticoids.

The Glucocorticoid Receptor-Dependent Stress Response in Human Erythropoiesis Is BCL11A-Dependent

Extrapolations from data in mouse models and from human erythroid cells expanded ex vivo with the glucocorticoid receptor (GR) agonist Dexamethasone (Dex), suggest that GR plays an important role in the regulation of stress erythropoiesis 1. However, the mechanistic details of stress erythropoiesis are still poorly understood.By exploring the effects of Dex on erythroid expansion of CD34+ cells from a large number of healthy adult donors (n=25), we documented that Dex expands a population of immature erythroid cells which express high levels of BCL11A. In addition, in these cells BCL11A is mostly in the nuclei, compared to cells grown without Dex. These results suggest that GR regulates the transcriptional activity of BCL11A.To validate the role of BCL11A in the Dex response, we made observations in cells from patients with BCL11A deficiencies 2. We found that BCL11A-deficient CD34+ cells generate lower numbers of maturing erythroid cells compared to controls with Dex addition, suggesting that they respond poorly to Dex (Fig 1). Of note, RNAseq analyses indicate that erythroid cells expanded from the patients express levels of BCL11A lower than that of their parent cells while the levels of expression of other genes known to mediate the response to Dex of erythroid cells (ZFP36L2, CDKNIC and PPARA 3-5) expressed by these cells is normal.Further we extended our observations to Cushing's patients with highier cortisol levels, before(V1) and after their treatment(V2) using concurrent age and weight matched healthy controls (MC). There is no significant difference in frequency of CD34+ cells among V1, V2 and MC (range 0.3-2% in all cases). CD34 pos cells from all groups express similar levels of cKIT, IL-3Rβ, CXCR4 and CALR. However, a greater proportion of CD34+ cells from V1 express CD36 and CD110 (the thrombospondin and thrombopoietin receptor) and CD133 (the hematopoietic stem cell marker prominin) than those from V2 and MC (60-80% vs 10-20%), suggesting that the circulating progenitor cells from active Cushing's patients are a unique population likely generated in response to their high cortisol levels given that the phenotype of CD34+ cells from the blood of V2 patients is similar to that found in MC. The phenotype of CD34+ cells from Cushing's patients in vivo is similar to that of CD34+ cells generated in vitro after 2-4 days of culture with Dex 3,6,7. V1 progenitor cells generate similarly large number of immature erythroid cells in culture with and without Dex. By contrast with normal cells, these active cells also express lower levels of the cytoplasm-restricted form of GRα (GRS203) and greater levels of GILZ and BCL11A than normal or V2 cells.In conclusion, the data presented here indicate that GR activation switches the erythroid differentiation program from the steady-state to the stress mode and that activation of BCL11A is part of the response of erythroid cells to Dex.References1) Varricchio et al Am J Blood Res. 2014;4:53; 2) Funnell et al Blood 2015; 126:89; 3) Ashley et al JCI 2020;130:2097; 4) Zhang L et al Nature 2013;499:92; 5) Lee et al Nature 2015;522:474; 6) Heideveld et al Haematologica 2015; 100:1396; 7) Xiang et al Blood 2015;125:1803. [Display omitted] DisclosuresMigliaccio: Dompe farmaceutici Spa R&D: Other: received funding for reserach .

Pituitary surgery for Cushing's disease.

Surgery is currently the first-line treatment of Cushing's disease. Surgery for Cushing's patients requires technical specificity, especially if no adenoma is identified on dedicated preoperative pituitary MRI. From 2006 to 2020, 683 patients with Cushing's disease were operated on with a mononostril endoscopic endonasal approach by the same two senior neurosurgeons. Here, we report the particularities of this challenging surgery. A rigorous and planned surgical strategy avoids the pitfalls of Cushing's disease surgery and leads to a high rate of endocrine remission.

Thrombin Generation Assay and Hemostatic Profile for Elucidating Hypercoagulability in Endogenous Canine Hyperadrenocorticism

Canine hyperadrenocorticism is a common endocrine disorder caused by chronic secretion of glucocorticoid, often associated with hypercoagulability and secondary thrombosis. The thrombin generation assay (TGA) evaluates hemostasis globally by measuring endogenous thrombin potential. We aimed to determine whether TGA is suitable for assessing hypercoagulability in dogs with endogenous hyperadrenocorticism (HAC), and to correlate TGA with coagulation markers including fibrinogen, antithrombin (AT), D-dimer, prothrombin time (PT) and activated partial thromboplastin time (aPTT), and with routine laboratory tests for elucidating prothrombotic mechanisms and evaluating their utility as hypercoagulability screening tests. Thrombin generation performed with high activator concentration showed significantly higher endogenous thrombin potential (ETP) (P = .0239) and peak thrombin (P = .0281) in Cushing patients. Fibrinogen (P = <.0001) and AT (P = .0444) activities were significantly higher in the HAC group, while those of PT (P = .0046) and aPTT (P = .0002) were lower. Basal cortisol levels correlated positively with fibrinogen (r = 0.4503; P = .0355) and negatively with AT activity (r = -0.4580; P = .0280). Fibrinogen and hematocrit values were inversely correlated (r = -0.4853; P = .0076). Our study confirmed the presence of higher thrombin generation in dogs with HAC. However, TGA performed with lower activator concentrations was unsuitable for detecting hypercoagulability. Higher AT and fibrinogen levels and lower aPTT activity were identified in dogs with HAC relative to controls suggesting a potential role for the combined use of these assays when assessing hypercoagulability in canine hyperadrenocorticism.

Lateral one-third gland resection in Cushing patients with failed adenoma identification leads to low remission rates: long-term observations from a small, single-center cohort

BackgroundCurrently, there are no guidelines for neurosurgeons treating patients with Cushing’s disease (CD) when intraoperative adenoma identification is negative. Under these circumstances, a total hypophysectomy or hemi-hypophysectomy on the side indicated by inferior petrosal sinus sampling (IPSS) is the approach being used, although there is a subsequent risk of hypopituitarism. Data on whether one-third lateral pituitary gland resection results in cure of hypercortisolism and low rates of hypopituitarism remain inconclusive.MethodsRetrospective single-center study of CD patients with failed intraoperative adenoma identification and subsequent resection of the lateral one-third of the pituitary gland as predicted by IPSS. We assessed (i) histopathological findings, (ii) early and long-term remission rates, and (iii) rates of additional pituitary hormone insufficiency.ResultsTen women and three men met the inclusion criteria. At 3 months, remission was noted in six (46%) patients: three (23%) had histologically confirmed adenomas, two (15%) had ACTH hyperplasia, and one patient (8%) was positive for Crooke’s hyaline degeneration. New pituitary hormone deficits were noted in two patients (15%). After a median (±SD) follow-up of 14±4 years, recurrence was noted in two (15%) patients. Long-term control of hypercortisolism was attained by 10 patients (77%), with additional therapies required in nine (69%) of them.ConclusionsIn CD patients with failed intraoperative adenoma visualization, lateral one-third gland resection resulted in low morbidity and long-term remission in 31% of patients without the need for additional therapies. Bearing in mind the sample size of this audit, the indication for lateral one-third-gland resection has to be critically appraised and discussed with the patients before surgery.

Clinical, hormonal, radiological and morphological comparison of patients with clinically evident Cushing's disease and patients with silent corticotroph cell adenoma

Purpose: The aim of the study was to review our clinical 7 years experiences with silent corticotroph adenoma (SCA) and Cushing disease (CD) with regard to clinical, radiological features, immunohistochemical and surgical outcomes and compare the results between two groups.&#x0D; Material and Methods: We retrospectively reviewed a series of patients (n=17; SCA 10, CD 7) with corticotroph adenomas and collected biochemical, neuroradiological and pathological data of those during follow-up time. &#x0D; Results: Mean pre-operative ACTH values of the patients with CD and SCA were 60.4±29.5, 45.5±34.6 pg/mL, respectively. Mean preoperative cortisol of the patient with CD (21.2±4.4 vs 11.5±4.0 mcg/dL) was increased than the patients with SCA measurements’. Patients with SCA had larger pituitary mass (20.4±4.5 vs 8.8±4.0 mm) than the patients with CD. And cavernous sinus invasion also was determined in all patients with SCA. Sparsely granulation staining was more common in all patients with SCA (7/10) or CD (4/7).&#x0D; Conclusion: SCAs are totally different from functional CD adenomas related with clinical characteristics and postoperative outcomes. SCA can be thought of as a diverse group of pituitary adenomas.

Choroidal imaging in patients with Cushing syndrome.

Glucocorticoid intake is a well-established risk factor for central serous chorioretinopathy that belongs to the pachychoroid spectrum disease (PSD). The study aimed to assess the prevalence of PSD and analyse the choroidal phenotype in patients with Cushing syndrome. A cross-sectional study was performed in Ophtalmopôle hôpital Cochin, Paris, France, with a systematic evaluation of hospitalized patients with Cushing syndrome, between November 2017 and July 2018. 56 eyes from 28 Cushing syndrome patients and 56 eyes of 28 age and gender-matched, and close spherical equivalent healthy participants were included. All patients underwent a complete ophthalmic examination including Enhanced-Depth Imaging (EDI)-Optical Coherence Tomography (OCT). Measures of subfoveal, 1000µm nasal and 1000µm temporal choroidal thicknesses were realized, and the presence of choroidal pachyvessels was evaluated. Hormonal tests evaluated the corticotropic axis. The number of eyes with PSD was significantly higher in Cushing syndrome patients as compared to controls (21.4% versus 3.6%, p=0.004). In Cushing patients' eyes, 17.9% had a pachychoroid pigment epitheliopathy (PPE) and 3.6% had a polypoidal choroidal vasculopathy. Pachyvessels were more common in Cushing syndrome patients than in healthy subjects (71.4% versus 42.9%, p=0.002). Mean subfoveal choroidal thickness was 331±110µm in Cushing patients, with no statistical difference between the two groups. There was no correlation between choroidal thickness and urinary and salivary cortisol levels. Patients with Cushing syndrome have a higher prevalence of PDS. An ophthalmologic specialized follow-up of these patients with EDI-OCT could detect chorioretinal abnormalities and adapt the surveillance of these patients.

Neuropsychological Functioning in Patients with Cushing's Disease and Cushing's Syndrome.

To present a systematic review of the presence and severity of neuropsychological impairment in the six main neuropsychological domains (attention, executive function, language, visuospatial processing, intelligence, and memory) in patients with Cushing's disease (CD) and/or Cushing's Syndrome (CS) at various stages of the illness. The work aims to identify neuropsychological leverage points for focused diagnosis and rehabilitation in CS/CD patients. A pubmed literature search was performed and augmented by searching the reference lists of review articles identified by this search strategy. After excluding irrelevant hits, we systematically extracted data from 27 studies for each main neuropsychological domain, differentiating between active disease, short- and long-term remission. The literature gives evidence for neuropsychological impairment in all domains in Cushing patients with active disease. The most consistent impairments concerned memory and visuo-spatial processing, whereas the data are discordant for all other domains. Significant improvement of neuropsychological function - although not returning to normal in all domains - is shown in short-term and long-term remission of the disease. However, the published literature is thin, suffering from repetitive subsample analyses publishing, methodological concerns as lack of control for confounders such as depression. Memory is the most extensively investigated domain in CS/CD patients and impairment is most prominent in active disease. Patients should be counseled that neuropsychological function will improve with normalization of hypercortisolism and over time. More studies with more stringent methodological criteria, larger patient samples and controlling for confounders are required to enhance our understanding of neuropsychological function in patients with CS/CD.

Not all laparoscopic adrenalectomies are equal: analysis of postoperative outcomes based on tumor functionality.

Laparoscopic adrenalectomy is known to have a low complication rate; however, the influence of functional tumor subtype on postoperative outcomes is not well defined. Patients undergoing laparoscopic adrenalectomy for benign adrenal tumors between 2009 and 2017 were selected from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. Patient demographics, postoperative outcomes, and length of stay were compared between tumor subtypes. A total of 3946 patients underwent a laparoscopic adrenalectomy during the study period; 3214 (81.5%) were performed for non-functional adenomas, and 732 (18.6%) for functional tumors-467 (64%) aldosteronomas, 184 (25%) cortisol-producing adenomas, and 81 (11%) pheochromocytomas. The risk of any complication was highest for patients with Cushing's (6.5%) and lowest with Conn's syndrome (1.1%) compared to other lesions (3.7% pheochromocytoma, 5.3% adenoma, p < 0.001). Among the patients with functional tumors, those with cortisol-producing adenomas had the highest rates of both deep surgical site infection (1.6%, p = 0.026) and urinary tract infection (2.2%, p = 0.029), whereas myocardial infarction was most prevalent in patients with pheochromocytoma (2.5%, p = 0.012). When adjusted for demographic differences, BMI, and comorbidity scores, no tumor type was associated with increased complication rate; instead aldosteronoma (vs. benign adenoma) was independently predictive of fewer adverse events [0.3 (95% CI 0.1-0.7), p = 0.004] and a shorter length of hospital stay [0.6 (95% CI 0.4-0.8), p = 0.001]. The overall mortality rate was low at 0.4%, although significantly higher in Cushing's patients (2.2%, p = 0.015). Laparoscopic adrenalectomy is a safe operation with low mortality and complication rates. However, postoperative risks differ between tumor subtype, so patients should be counseled accordingly.

Comparative analysis of rhinologic outcomes in Cushing disease and non-functioning pituitary adenoma in patients submitted to endoscopic endonasal transsphenoidal surgery.

Adrenocorticotropic hormone (ACTH) secreted by pituitary tumors lead to changes in nasal cavity anatomy and physiology. As a consequence of hormonal alteration, there is an abnormal soft tissue and an increased capillary fragility, inducting to a thinner mucosa that acts in the healing process. We compared post-operative nasal alterations in patients with Cushing's disease versus patients with non-functioning macroadenomas who underwent endoscopic endonasal transsphenoidal surgery. A retrospective study with 14 patients with Cushing's disease who underwent initial transsphenoidal endonasal surgery for an ACTH-secreting adenoma was conducted. Forty-two patients who underwent the same surgery for non-functioning adenomas were selected as controls. The following data were collected: operative technique, endoscopic alterations in late post-operative period and post-operative nasal complaints. There were 13/14 (92.9%) females with Cushing disease versus 23/42 (54.8%) in the non-functioning adenoma group. Surgical approach was similar in both groups, with no differences in flap usage, turbinectomies or ethmoidectomies. No difference occurred concerning endoscopic alterations or nasal complaints in post-operative period. Post-operative results are similar, and healing could be expected to be equal.

Differences in skin lesions of endogenous and exogenous Cushing's patients.

IntroductionCushing’s syndrome is a rare condition characterized by increased glucocorticoid levels. Dermatologically, it causes a variety of skin conditions such as atrophy, striae, acne, plethora, hypertrichosis, hirsutism, acanthosis nigricans, hyperpigmentation, alopecia, purpura and fragile skin. Although skin lesions of Cushing’s syndrome have been described, exogenous and endogenous types have not been studied in detail.AimTo determine differences in possible skin lesions depending on the cause of Cushing’s syndrome.Material and methodsA total of 35 patients – 16 iatrogenic Cushing’s syndrome patients and 19 endogenous Cushing’s syndrome patients – who were diagnosed in Erciyes University and 15 healthy individuals were included in this study.ResultsThere was at least one skin finding in 34 (97.1%) of the patients with Cushing’s syndrome and 9 (60%) in the control group (p = 0.001). Comparison regarding skin findings in patient and control groups revealed that hypertrichosis, hyperpigmentation, and fungal infections were significantly more frequent in the patient group than the control group. Hirsutism was found more frequently in the endogenous group whereas stria, hypertrichosis and fungal infections were more frequent in the exogenous group.ConclusionsSince Cushing’s syndrome is a rare disease and it is often diagnosed later in life, data on the frequency of skin findings are limited and sparse in the literature. In the comparison of endogenous Cushing’s and exogenous Cushing’s groups, acne, hypertrichosis, and fungal infections were found more frequently in the exogenous Cushing’s group and hirsutism more frequently in the endogenous Cushing’s group.

Glucocorticoid Regulation of Food-Choice Behavior in Humans: Evidence from Cushing's Syndrome.

The mechanisms by which glucocorticoids regulate food intake and resulting body mass in humans are not well-understood. One potential mechanism could involve modulation of reward processing, but human stress models examining effects of glucocorticoids on behavior contain important confounds. Here, we studied individuals with Cushing's syndrome, a rare endocrine disorder characterized by chronic excess endogenous glucocorticoids. Twenty-three patients with Cushing's syndrome (13 with active disease; 10 with disease in remission) and 15 controls with a comparably high body mass index (BMI) completed two simulated food-choice tasks (one with “explicit” task contingencies and one with “probabilistic” task contingencies), during which they indicated their objective preference for viewing high calorie food images vs. standardized pleasant, unpleasant, and neutral images. All participants also completed measures of food craving, and approximately half of the participants provided 24-h urine samples for assessment of cortisol and cortisone concentrations. Results showed that on the explicit task (but not the probabilistic task), participants with active Cushing's syndrome made fewer food-related choices than participants with Cushing's syndrome in remission, who in turn made fewer food-related choices than overweight controls. Corroborating this group effect, higher urine cortisone was negatively correlated with food-related choice in the subsample of all participants for whom these data were available. On the probabilistic task, despite a lack of group differences, higher food-related choice correlated with higher state and trait food craving in active Cushing's patients. Taken together, relative to overweight controls, Cushing's patients, particularly those with active disease, displayed a reduced vigor of responding for food rewards that was presumably attributable to glucocorticoid abnormalities. Beyond Cushing's, these results may have relevance for elucidating glucocorticoid contributions to food-seeking behavior, enhancing mechanistic understanding of weight fluctuations associated with oral glucocorticoid therapy and/or chronic stress, and informing the neurobiology of neuropsychiatric conditions marked by abnormal cortisol dynamics (e.g., major depression, Alzheimer's disease).