Subclinical Cushing's Syndrome Research Articles

PS-C21-4: EPIGENETIC ALTERATION OF 11B;-HYDROXYSTEROID DEHYDROGENASE 1 IN THE ADIPOSE TISSUE OF PATIENTS WITH ENDOCRINE HYPERTENSION

Objective: 11Beta-hydroxysteroid dehydrogenase 1 (11β;-HSD1) is a key enzyme involved in metabolic syndrome. The epigenetic control of 11β;-HSD1 is unclear. We examined the 11β;-HSD1 mRNA level and methylation status of the promoter region of the 11β;-HSD1 gene in the adipose tissue of patients with endocrine hypertension. Methods: We evaluated 8 adipose tissue specimens from patients with subclinical Cushing syndrome (SCS) due to cortisol-producing adenomas, 10 tissue specimens from patients with primary aldosteronism due to aldosterone-producing adenoma (APA) and 7 tissue specimens from patients with non-functioning adrenal adenoma (NFA). SCS and primary aldosteronism were diagnosed according to the guideline of the Japanese Endocrine Society. The mRNA level of 11β;-HSD1 was quantified using a real-time PCR. Isolated DNA was treated with bisulfite and amplified using primers specific for the human 11β;-HSD1 promoter region. Results: The glycohemoglobin level was significantly higher in patients with SCS or APA compared with those with NFA (p < 0.05). Blood pressure was significantly elevated in patients with APA compared with those with SCS or NFA (p < 0.01). The 11β;-HSD1 mRNA level was significantly increased in the adipose tissues of SCS and APA compared with NFA patients (p < 0.05). The methylation ratio was significantly lower in SCS compared with APA or NFA patients (p < 0.05). Conclusion: 11β;-HSD1 gene expression is partly controlled by an epigenetic mechanism in human tissues. The pathophysiological roles of epigenetic control of 11β;-HSD1 gene expression in adipose tissue requires further study.

PS-R03-3: INTERMITTENTLY SCANNED CONTINUOUS GLUCOSE MONITORING IN A DIFFICULT PATIENT WITH GESTATIONAL DIABETES MELLITUS AND SUBCLINICAL CUSHING'S SYNDROME: A CASE REPORT

A 41-year-old woman was admitted to the obstetrics department because of epigastric pain, nausea, and fatigue at 31 weeks of gestation. She was suspected of subclinical Cushing's syndrome based on high plasma cortisol and low ACTH levels along with an incidentally discovered tumor in the left adrenal gland 4 years prior to conception. 3 months before admission, 75 g oral glucose tolerance test yielded one point positive (81–169–174 mg/dL) and diagnosis of gestational diabetes mellitus was made. Diet and exercise therapy was started on an outpatient basis. While blood glucose control had been favorable, she discontinued visits to outpatient clinics due to difficulty in physical activity. At the time of admission, blood glucose level was running more than 200 mg/dl, and self-monitoring of blood glucose (SMBG) and insulin self-injection therapy were proposed for immediate blood glucose control accordingly. However, the patient had psychiatric symptoms that were presumably associated with delusional disorder and subclinical Cushing's syndrome. As such, she refused to implement both procedures on account of a strong fear against puncture, which caused blood glucose management difficult. Despite understanding the necessity of SMBG and potential risks to the fetus, the patient frequently expressed anxiety and could not perform SMBG. Given the difficult circumstance, intermittently scanned continuous glucose monitoring was installed to reduce invasive procedures. As a result, blood glucose levels were under good control with 0.43 U/kg of insulin per day until the delivery by cesarean section at 34 weeks of gestation. A healthy infant weighing 2442 g was delivered without complications. Here we highlight utility and efficacy of intermittently scanned continuous glucose monitoring in a difficult patient with gestational diabetes mellitus and subclinical Cushing's syndrome.

The Role of Serum Inflammation-Based Scores in Diagnosis and Assessing Remission in Cushing's Disease.

Chronic hypercortisolism causes diverse alterations in the immune system and inflammatory disruptions. Serum inflammation-based scores (SIBS) are indicators of systemic inflammatory status. This study aims to determine the role of SIBS in the diagnosis and evaluation of remission in patients with Cushing's disease (CD). This retrospective cross-sectional study was conducted on 195 participants; 52 patients diagnosed and followed up after treatment with CD, 65 patients with subclinical Cushing's syndrome (SCS), and 78 healthy individuals whose complete blood counts (CBC) were obtained for analysis. Participants with additional diseases or drug use that could affect CBC were excluded from the study. SIBS of the three groups were compared. Scores considered were neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). The correlations between SIBS and initial diagnostic tests for hypercortisolism were analyzed. The SIBS of patients with CD at the diagnosis were compared with those after remission. In addition, receiver operator characteristic curve analyses were used to determine the diagnostic accuracy, specificity, and sensitivity of the scores significantly high in the CD group. MLR and SII values were significantly higher in CD patients than in the healthy group (p<0.01). NLR and SII were significantly higher in patients with CD than those with SCS (p<0.05). There were no significant differences between the SCS and the control groups in all SIBS. We determine significant, positive, and moderately correlated findings between SIBS and initial diagnostic tests for hypercortisolism in the CD group (0.30<r<0.70; p<0.05). All of the scores evaluated were significantly lower in the remission of the disease compared to the active period (p<0.001). An optimal cut-off MLR value of 0.20 showed the best diagnostic value (p=0.003; sensitivity, 78.4%; specificity, 51.4%), and an optimal cut-off SII value of 776.20 showed the best diagnostic value (p=0.017; sensitivity, 54.9%; specificity, 70.0%). The SIBS, which can be easily calculated with the data obtained from CBC and do not have additional costs, can contribute to the diagnosis and assessment of remission in patients with CD.

Carney complex presenting as subclinical Cushing syndrome in a child due to a novel Phosphodiesterase 11A mutation

BackgroundSeveral disease-causing genes have been implicated in Carney complex (CNC), including PRKAR1A, PDE8B(Phosphodiesterase 8B),and PDE11A (Phosphodiesterase 11A). The purpose of this study was to describe the clinical features of CNC in a Chinese patient and identify potential pathogenic mutations. MethodsGenomic DNA was extracted from the peripheral venous blood obtained from one Chinese CNC family from Shandong province. Subsequently, targeted region sequencing (TRS) and Sanger sequencing validation were performed to identify and validate likely pathogenic mutations. ResultsGenetic analyses revealed a novel PDE11A variant that was predicted to lead to CNC. The patient's mother presented with the same genetic mutation. ConclusionThis study identifies new genetic mutation in CNC（PDE11A: NM_016953: exon11: c1921A>G (p./p.Lys641Glu). CNC patients presenting with subclinical Cushing's syndrome should be treated.

The Entity of Connshing Syndrome: Primary Aldosteronism with Autonomous Cortisol Secretion.

Connshing syndrome (CoSh) (adrenal-related synchronous aldosterone (A) and cortisol (C) excess) represents a distinct entity among PA (primary hyperaldosteronisms) named by W. Arlt et al. in 2017, but the condition has been studied for more than 4 decades. Within the last few years, this is one of the most dynamic topics in hormonally active adrenal lesions due to massive advances in steroids metabolomics, molecular genetics from CYP11B1/B2 immunostaining to genes constellations, as well as newly designated pathological categories according to the 2022 WHO classification. In gross, PA causes 4-10% of all high blood pressure (HBP) cases, and 20% of resistant HBP; subclinical Cushing syndrome (SCS) is identified in one-third of adrenal incidentalomas (AI), while CoSh accounts for 20-30% to 77% of PA subjects, depending on the tests used to confirm autonomous C secretion (ACS). The clinical picture overlaps with PA, hypercortisolemia being mild. ACS is suspected in PA if a more severe glucose and cardiovascular profile is identified, or there are larger tumours, ACS being an independent factor risk for kidney damage, and probably also for depression/anxiety and osteoporotic fractures. It seems that one-third of the PA-ACS group harbours mutations of C-related lines like PRKACA and GNAS. A novel approach means we should perform CYP11B2/CYP11B1 immunostaining; sometimes negative aldosteronoma for CYP11B1 is surrounded by micronodules or cell clusters with positive CYP11B1 to sustain the C excess. Pitfalls of hormonal assessments in CoSh include the index of suspicion (check for ACS in PA patients) and the interpretation of A/C ratio during adrenal venous sample. Laparoscopic adrenalectomy is the treatment of choice. Post-operative clinical remission rate is lower in CoSh than PA. The risk of clinically manifested adrenal insufficiency is low, but a synthetic ACTH stimulating testing might help to avoid unnecessary exposure to glucocorticoids therapy. Finally, postponing the choice of surgery may impair the outcome, having noted that long-term therapy with mineralocorticoids receptors antagonists might not act against excessive amounts of C. Awareness of CoSh improves management and overall prognosis.

ODP639 The Occurrence and Predictors of Postoperative Adrenal Insufficiency for Patients With Subclinical Cushing's Syndrome

Abstract Objective To identify the occurrence and predictive factors of postoperative adrenal insufficiency in patients with subclinical Cushing's syndrome (SCS), and try to provide evidence for decision-making in SCS management. Methods The present retrospective analysis included 77 patients who underwent unilateral laparoscopic adrenalectomy for SCS between December 2011 and April 2021. Among them, 59 patients with complete follow-up data were included. We compared clinical characteristics of patients with and without postoperative adrenal insufficiency. The logistic regression model was used to find the potential risk factors in predicting the occurrence of postoperative adrenal insufficiency. The receiver operating characteristic (ROC) curve was used to evaluate the predictive values. Results We included 59 patients, of whom the incidence of postoperative adrenal insufficiency is 42.37%. The circadian rhythms of adrenocorticotropic hormone (ACTH) and cortisol disappeared in both two groups. Compared patients without postoperative adrenal insufficiency, patients with postoperative adrenal insufficiency were characterized by suppressed plasma ACTH level [1.11(1.11, 1.83) pmol/L vs 2.56(1.16, 4.63) pmol/L], elevated midnight cortisol level [268. 00(164. 00, 347.50) nmol/L vs 181.50(156.32, 227. 00) nmol/L] and increased cortisol level after 1 mg overnight dexamethasone suppression test (DST) [281. 00(241. 00, 396.64) nmol/L vs 172.50(144. 05, 215.25) nmol/L] (all P &amp;lt; 0. 05). Multivariate logistic regression analysis showed that the serum cortisol after a 1 mg-DST was the only independent predictive factor for the occurrence of postoperative adrenal insufficiency. The ROC curve showed that the best cut-off value of the serum cortisol after a 1 mg-DST was 233 nmol/L, with a sensitivity of 80. 00% and a specificity of 82.35%. The combination of the serum cortisol after a 1 mg-DST, plasma ACTH and midnight cortisol had the highest predictive accuracy (83. 05%). Conclusion Patients who underwent unilateral laparoscopic adrenalectomy for SCS had a risk of postoperative adrenal insufficiency. The pre-surgical assessment of the serum cortisol after a 1 mg-DST plus elevated midnight cortisol and suppressed plasma ACTH had predictive value for the occurrence of postoperative adrenal insufficiency. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:00 p.m. - 1:05 p.m.

ODP621 Hypertension with Hypokalemia in Pregnancy? Think "Cushing's Syndrome"

Abstract Introduction Pregnancy is uncommon in women with Cushing's syndrome (CS) as hypercortisolism and hyperandrogenism suppress gonadotropins leading to anovulatory cycles. Such pregnancies carry a higher rate of fetal morbidity and mortality. Therefore, it is of paramount importance to diagnose and treat CS in pregnancy. The diagnosis of CS in pregnancy is challenging due to the physiologic changes of the hypothalamic-pituitary-adrenal axis during pregnancy. We describe a case of CS in pregnancy that was a successfully treated with surgery. Case description An asymptomatic 39-year-old pregnant female patient with gestational hypertension was admitted to the hospital after she was found to have uncontrolled hypertension (while on 3 anti-hypertensive medications) and severe hypokalemia with potassium level of 2.8 mEq/L. She was 14 weeks pregnant at the time. She has a family history of primary aldosteronism in her father successfully treated with adrenalectomy at the age of 60. Her work up included blood work (done at 13: 42) which showed sodium level of 146 mEq/L, plasma aldosterone concentration of &amp;lt;1 ng/dL, plasma renin activity of 1.0 ng/mL/hr, total testosterone of 46 ng/dL, DHEA-S of 31 mcg/dL, plasma metanephrines &amp;lt;50 pg/mL, 24-hour urine metanephrines 70 ug, 24-hour urine normetanephrines 164 ug/24 hrs, ACTH 5 pg/mL, and cortisol 28.2 mcg/dl. MRI abdomen without contrast showed a 3.5×3.0×4.2 cm left adrenal nodule consistent with adenoma. Patient was diagnosed with non-ACTH dependent subclinical CS based on her elevated cortisol and low ACTH levels. She underwent left laparoscopic adrenalectomy and was discharged on oral hydrocortisone. Pathology showed adrenal cortical adenoma. Her blood pressure normalized shortly after surgery and her anti-hypertensive medications were stopped. Discussion Pregnancy is associated with multiple changes in the hypothalamic-pituitary-adrenal axis making diagnosis of CS in pregnancy challenging. Those changes include increased Cortisol binding globulin production leading to increased serum cortisol level and lack of suppression with Dexamethasone beside placental production of CRH and ACTH, all leading to increased salivary and urinary free cortisol levels, as well. This case of hypertension and hypokalemia in pregnancy presented a diagnostic dilemma. Furthermore, the clinical presentation was confounded by a family history of primary aldosteronism. However, the low serum ACTH level highly suggested the diagnosis of CS. Unfortunately, there are no pregnancy-specific guidelines for the diagnosis of CS. The dexamethasone suppression test is not recommended as it often yields false-positive results. The use of urinary free cortisol and late-night salivary cortisol is recommended, and the diagnosis is established when results are three to four times the upper limit of normal. ACTH levels &amp;lt;10 pg/ml are suggestive of adrenal CS. MRI without contrast can be used for imaging. To date, there have been over 260 reported cases of CS in pregnancy with more than half of them being. Presentation: No date and time listed

Usefulness of cortisol/ACTH ratio (CAR) for diagnosis of cushing's syndrome: comparison of CAR with findings in dexamethasone suppression test

Cushing's syndrome and subclinical Cushing's syndrome (SCS) are conditions of increased cortisol secretion from the adrenal glands. Cushing's syndrome includes adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (Cushing's disease) and ACTH-independent Cushing's syndrome (AICS). The purpose of this study was to investigate the diagnostic potential of the cortisol / adrenocorticotropic hormone (ACTH) ratio (CAR) for diagnosis of Cushing's syndrome or SCS in adult subjects. This was a single-center, retrospective, observational study. This study enrolled 44 subjects with SCS, 14 AICS, 10 CD, and 248 non-Cushing's syndrome subjects who had undergone a 1 mg dexamethasone suppression test (1 mg DST). Definition of SCS was as follows: no physical signs characteristic of Cushing syndrome and cortisol was ≥ 83 nmol/L in 1 mg DST. The diagnostic potential of CAR for diagnosis of Cushing's syndrome was evaluated by comparing the correlation between CAR and after-load cortisol level in 1 mg DST. As the results, there was a strong positive correlation between CAR and after-load cortisol level in subjects with AICS (r = 0.800, p < 0.005). CAR was 10,040 ± 4170 nmol/pmol in subjects with NCS, 17,535 ± 10,246 nmol/pmol in SCS, 101,221 ± 18,009 nmol/pmol in AICS, and 4324 ± 2051 nmol/pmol in CD, all of which were significantly higher compared to those with AICS (p < 0.0005). The cutoff values of CAR for screening at our institution were 11,849.6 nmol/pmol for AICS (AUC 0.935, p < 0.005, sensitivity 92.3%, specificity 83.5%) and 7006.1 nmol/pmol for CD (AUC 0.714, p < 0.05, sensitivity 100.0%, specificity 46.8%). There was a positive correlation between CAR and adrenal adenoma diameter in subjects with AICS (r = 0.508, p < 0.05), but there was no correlation between tumor diameter and CAR in subjects with SCS and CD. In conclusion, high CAR indicates increased cortisol secretion from the adrenal glands. Since CAR is a simple indicator that can be easily evaluated by general practitioners as well as endocrinologists, we think CAR would be useful for the early detection of Cushing's syndrome.

Mixed corticomedullary tumor of the adrenal gland.

Mixed corticomedullary tumor (MCMT) of the adrenal gland is an extremely rare tumor characterized by an admixture of steroidogenic cells and chromaffin cells in a single tumor mass simultaneously producing adrenocortical hormones and catecholamines; it is associated with ectopic adrenocorticotropic hormone (ACTH) in some cases. We reviewed and summarized clinicopathological data of 28 MCMTs, including four metastatic tumors in 26 previous reports. These reports included 21 females and 7 males, and the average tumor sizes were 4.8 ± 2.5 cm and 12.6 ± 6.4 cm in the non-metastatic and metastatic groups, respectively (P<0.001). The clinical manifestations and laboratory data were as follows: Cushing or subclinical Cushing syndrome, 58% (14/24); hypertension, 71% (17/24); elevated adrenocortical hormones, 75% (18/24); elevated catecholamines, 75% (18/24); and ectopic ACTH, 71% (10/14). All four patients with metastatic MCMTs had poor prognoses and elevated adrenocortical hormone levels; however, only two patients had elevated catecholamine levels. Immunohistochemistry was essential for the pathologic diagnosis of MCMTs. In this study, using an improved technique, we detected ectopic ACTH-producing cells in the same paraffin-embedded sections reported to be negative in our previous reports. As MCMT is composed of cells with embryologically different origins, its pathogenesis has been explained by various hypotheses. We compared MCMT to the adrenal gland of birds and the early stage of human fetuses, in which nests of chromaffin cells and steroidogenic cells admix without the formation of cortex and medulla. MCMT is characterized by the immaturity of organogenesis and might be classified as an adrenal embryonal tumor.

Clinical, biochemical and radiological retrospective analysis in patients with adrenal incidentaloma

Giriş: Bu çalışmada, adrenal insidentaloma nedeniyle takip edilen hastaların epidemiyolojik, demografik, klinik özellikleri, tedavi yaklaşımları ve yaşam sürelerinin değerlendirilmesi amaçlanmıştır. Yöntem: 2010–2014 yılları arasında Mersin Üniversitesi Araştırma ve Uygulama Hastanesi Endokrinoloji Bölümünde adrenal insidentaloma nedeniyle tedavi ve takipleri yapılan 46 hastanın verileri retrospektif olarak incelendi. Bulgular: Çalışmaya alınan olguların 13’ü erkek, 33’ü kadın ve yaş ortalaması 54.09±10.7 idi. En sık başvuru nedeni %34.78 hastada karın ağrısı, en sık tanı konulan radyolojik yöntem % 60.87 dinamik sürrenal BT, en sık yerleşim yeri sol surrenal bezdi. Kitle çapı ortalama 26.8±16.5 mm arasında idi. Hipertansiyon sıklığı %50, obezite sıklığı %47.8, tip 2 diyabet sıklığı %21.7, osteoporoz sıklığı ise %42.8 ve metabolik sendrom sıklığı %41.3 olarak saptandı. Hormonal değerlendirme sonuçlarına göre %82.61’inde fonksiyonsuz adrenal adenom (FAA), %15.21’inde subklinik Cushing sendromu (SCS), %2.1’inde aldesteronoma görüldü. Adrenalektomiye giden 8 olguda myelolipom, feokromasitoma ve adrenokortikal adenom tanısı konuldu. Bir hasta karaciğer yetmezliğinden exitus oldu. Hastaların takiplerinde hormonal aktivasyon ve lezyon boyutunda büyüme saptanmadı. Sonuç: AI’ların çok farklı patolojik ve radyolojik görünümler ile karşımıza çıkmasından dolayı demografik, etiyolojik, klinik, laboratuar ve radyolojik verilerin bir bütün olarak değerlendirilmesi tedavi ve takibinde önemlidir.

Predictors of renal function after adrenalectomy in patients with Cushing or subclinical Cushing syndrome.

The postoperative course of renal function remains unclear in Cushing syndrome. We examined changes in renal function after adrenalectomy in patients with Cushing syndrome and attempted to identify predictors of renal impairment. The study population comprised 76 patients who underwent adrenalectomy for Cushing and subclinical Cushing syndrome between 2001 and 2018. Renal function and other factors were evaluated pre-operation, at 1 postoperative month, and 1 postoperative year. We defined a ≥10% decrease in the estimated glomerular filtration rate at 1 postoperative year as renal impairment, and predictors associated with this reduction were investigated. The relationship between renal function and steroid replacement after surgery was also examined. Mean pre-operative estimated glomerular filtration rate was 82.2 ml/min/1.73 m2 . While mean estimated glomerular filtration rate was significantly lower at 1 postoperative month than the pre-operative value (71.7 ml/min/1.73 m2 [89.1%], p < 0.001), no significant differences were observed between 1 postoperative year and pre-operation (79.5 ml/min/1.73 m2 [97.6%], p = 0.108). Twenty-six patients (34.2%) developed renal impairment. A multivariate analysis identified a low pre-operative adrenocorticotropic hormone level as an independent predictor of renal impairment (odds ratio 6.30, p = 0.031). Among 43 patients with available records of steroid replacement history, 18 (41.9%) developed renal impairment. The ratio of patients with a reduced steroid replacement dose at 1 postoperative month was significantly lower among patients with renal impairment than those without (22.2% vs. 56.0%, p = 0.027). The pre-operative adrenocorticotropic hormone level was a predictor of renal function after adrenalectomy in patients with Cushing or subclinical Cushing syndrome.

Coexistence of bone and vascular disturbances in patients with endogenous glucocorticoid excess

PurposeBone and vascular diseases are considered to share pathogenic mechanisms. Excess glucocorticoids, key regulators of cardiovascular and metabolic homeostasis, may promote both diseases simultaneously. We used endogenous Cushing's syndrome (CS) to investigate whether glucocorticoid excess underlies coexisting bone and vascular diseases. MethodsWe included 194 patients with adrenal tumors (ATs): autonomous cortisol secretion (ACS, n = 97) and non-functional AT (n = 97). ACS was further classified into overt CS (n = 17) and subclinical CS (SCS, n = 80). Arterial stiffness was defined as a brachial-ankle pulse wave velocity (baPWV) ≥ 1800 cm/s. ResultsPatients with ACS had higher coexistence rates of vertebral fracture and arterial stiffness (23 % vs. 2 %; p < 0.001) and vertebral fracture and abdominal aortic calcification (22 % vs. 1 %; p < 0.001) than those with non-functional AT. In patients with ACS, baPWV was negatively correlated with trabecular bone score (TBS, r = −0.33; p = 0.002), but not with bone mineral density, and vertebral fracture was associated with arterial stiffness in the logistic regression analysis. In the multivariate analysis of variance, the degree of cortisol excess (defined as CS, SCS, and non-functional AT) determined the correlation between TBS and baPWV (partial η2 = 0.07; p < 0.001). In the analysis of covariance, patients with coexisting vertebral fracture and arterial stiffness had higher levels of serum cortisol after the 1-mg dexamethasone suppression test than those without. ConclusionIn endogenous glucocorticoid excess, bone and vascular diseases frequently coexisted, and deteriorated bone quality, not bone loss, was related to arterial stiffness. Thus, glucocorticoid excess may perturb the bone-vascular axis.

Differences in Regulation of Cortisol Secretion Contribute to Left Ventricular Abnormalities in Patients With Essential Hypertension.

Left ventricular (LV) abnormalities were reported in patients with overt and subclinical Cushing syndrome. The aim of this study was to investigate the relationships of daily plasma cortisol profile and cortisol response to an overnight suppression test with cardiac changes in patients with hypertension. In a cross-sectional study, we included 136 nondiabetic, patients with essential hypertension who were free of cardiovascular and renal complications. Plasma cortisol was measured at 8 am, 3 pm, and 12 am and at 8 am after overnight suppression with 1 mg dexamethasone (dexamethasone suppression test [DST]). Echocardiography was performed with standard B-mode and tissue-Doppler imaging. LV hypertrophy was present in 30% and LV diastolic dysfunction in 51% of patients who were older and had significantly higher body mass index, systolic blood pressure, duration of hypertension, and 12 am and DST cortisol. LV mass index and relative wall thickness increased progressively across tertiles of DST cortisol, together with progressive worsening of diastolic function. LV mass index was directly related to age, systolic blood pressure, duration of hypertension, and 12 am and DST cortisol, and inversely to creatinine clearance. Multivariate regression analysis showed independent correlation of LV mass index with body mass index, systolic blood pressure, and 12 am and DST cortisol. Logistic regression showed that DST cortisol independently predicted LV hypertrophy. Midnight and DST plasma cortisol levels are independent determinants of LV mass and geometry in patients with essential hypertension suggesting that even minor changes in regulation of cortisol secretion could contribute to cardiac abnormalities in these patients.

Bilateral adrenal uptake of 123I MIBG scintigraphy with mild catecholamine elevation, the diagnostic dilemma, and its characteristics

Cases in which bilateral adrenal 123I-Metaiodobenzylguanidine (123I-MIBG) scintigraphy accumulation is sometimes shown, with mildly elevated catecholamine (CA) or metanephrine (MN) levels (within 3 times the upper reference limit) are diagnostic dilemmas. We experienced 3 cases of adrenal incidentalomas with this dilemma in the differential diagnosis. The clinical diagnosis was subclinical Cushing's syndrome in 2 cases, and primary aldosteronism in 1. Despite suspected CA excess in clinical symptoms and imaging findings, the pathological findings of all these tumors were revealed to be cytochrome P450 family 11 subfamily B member 1 (CYP11B1) positive adrenocortical adenomas. Interestingly, adrenal medullary hyperplasia (AMH) was detected in the adrenal parenchyma of all those backgrounds. To clarify the clinical features of such cases, a cross-sectional study was conducted at the Kobe University Hospital from 2014 to 2020. One-hundred sixty-four patients who had undergone 123I-MIBG scintigraphy were recruited. Among them, 10 patients (6.1%) met the above criteria, including the presented 3 cases. Plasma adrenaline, noradrenaline, urinary metanephrine, and normetanephrine had values of 0.05 ± 0.05 ng/mL, 0.63 ± 0.32 ng/mL, 0.22 ± 0.05 mg/day, and 0.35 ± 0.16 mg/day, respectively. Nine cases were complicated with hypertension, and symptoms related to CA excess were observed. Half of them (5 cases) including presented 3 cases had unilateral adrenal tumors. These suggest that in cases of bilateral adrenal uptake on 123I-MIBG, AMH needs to be considered. Adrenocortical adenomas may be associated with AMH and further larger investigation is needed for this pathology.

Adrenal hemangioma with subclinical cushing's syndrome

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Monitoring for the long-term metabolic complications in patients with subclinical cushing's syndrome: service evaluation

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

A 30-Year, Single-Center Experience of Unilateral Adrenalectomy for Primary Bilateral Macronodular Adrenal Hyperplasia

ObjectiveThe aim was to assess the short- and long-term outcomes of unilateral adrenalectomy (UA) in patients with primary bilateral macronodular adrenal hyperplasia (PBMAH). MethodsWe conducted a retrospective study of 124 patients with PBMAH who underwent UA. ResultsOne hundred sixteen patients were available for follow-up (median, 28.5 months). Cushingoid features remitted in 43 of 65 patients (70.8%) with overt Cushing syndrome (CS). Hypertension and diabetes mellitus improved in 79 of 96 (82.3%) and 29 of 42 patients (69.0%), respectively. Glucocorticoid insufficiency developed in 7 of 116 patients (6.0%) after the surgery, and it resolved in all the patients during follow-up. The mean 24-hour urinary free cortisol level decreased gradually from 456.02 ± 422.33 mg/24 h at baseline to 84.47 ± 70.06 mg/24 h within 3 months and then increased progressively in some patients. Sixty-four of the 116 patients (55.2%) had biochemical recurrence and 43 patients (67.2%) underwent contralateral adrenalectomy. The median time interval between the second operation and the first UA was 24 months. Patients with overt CS had a larger surgical-side or contralateral adrenal volume than patients without overt CS. Patients with a contralateral adrenal volume of >33.54 mL or with a preoperative urinary free cortisol level of >216.08 mg/24 h were more likely to have recurrence. ConclusionThe efficiency of UA is transient for the majority of patients, and the indications should be strictly limited to those with subclinical or milder CS. Patients who undergo successful UA still require close life-time follow-up for the recurrence of hypercortisolism.

Incidentally discovered myelolipomatous adrenal adenomas, including six cases presenting with hypercortisolism

Most adrenal incidentalomas are non-functioning adenomas that require no treatment. The presence of a myelolipomatous component of adrenal incidentalomas is a rare, but well-known occurrence in both hyperplastic and neoplastic lesions of the adrenal cortex. Although the improvements in abdominal imaging have increased identification of myelolipomatous adrenal cortical adenomas radiologically, due to the rarity of this lesion, the clinical pathological features of these lesions are unclear and can sometimes cause diagnostic difficulty. Eleven patients had surgeries at The University of Texas MD Anderson Cancer Center. Four additional cases were provided from an external collaborator. Of the 15 cases, there were 5 male and 10 female patients, with a median age of 52 years (mean 54 years, range 28–84 years). Clinical presentation included adrenal incidentaloma (n = 9), Cushing syndrome (n = 4, including 1 as a part of Carney complex), and subclinical Cushing syndrome (n = 2, including 1 with bilateral macronodular adrenal hyperplasia). In this study, we present the clinicopathologic features of fifteen myelolipomatous adrenal adenomas, the largest series published thus far.

Abstract #1004351: Subclinical Cushing's Syndrome, a Commonly Missed Phenomenon in Diabetic Patients

Abstract #1004351: Subclinical Cushing's Syndrome, a Commonly Missed Phenomenon in Diabetic Patients

Abstract No. 191 Adrenal venous sampling for lateralization of cortisol hypersecretion in patients with adrenocorticotropic hormone–independent Cushing syndrome and bilateral adrenal masses

To evaluate adrenal venous sampling (AVS) in guiding surgical management of patients with adrenocorticotropic hormone (ACTH) independent Cushing syndrome (CS) and bilateral adrenal masses 28 patients with bilateral adrenal masses and ACTH independent autonomous cortisol secretion who underwent AVS from January 1, 2008, to August 1, 2020, were identified. Methodology and data interpretation were performed as previously described. Cortisol and epinephrine levels were measured from each adrenal vein (AV) and the inferior vena cava (IVC). AVS was technically successful if plasma epinephrine concentration in AV-IVC was > 100 pg/mL. AV/IVC cortisol ratio for each adrenal gland and cortisol lateralization ratio (CLR) were calculated. Previously described parameters were utilized for interpretation: AV/IVC cortisol ratio of > 6.5 on one side and ≤3.3 on the contralateral side with CLR ≥ 2.3 was consistent with a unilateral cortisol-secreting adenoma whereas bilateral AV/IVC cortisol ≥ 4.1 with CLR < 2 was consistent with bilateral cortisol hypersecretion. Clinical, imaging, laboratory, pathology and follow-up data were collected. Primary outcome measure was hypercortisolism recurrence. 28 patients underwent AVS. Patients underwent subsequent right (n = 12) or left (n = 9) total, right total and left partial (n = 1) or bilateral total (n = 3) adrenalectomy. 3 patients were recommended adrenalectomy but were lost to follow up and not included in outcome analysis. Initial presentation included incidental adrenal masses (12%), subclinical CS (64%), overt CS (24%). Sequela included hypertension (88%), osteoporosis/osteopenia (38%), diabetes mellitus (36%), hyperlipidemia (56%), weight gain (76%), depression (52%). AVS was successful in all 28 patients. Data were interpreted as described above to guide laterality of adrenalectomy. Mean AV/IVC cortisol for unilateral adrenalectomies was 12 with mean CLR 3.7. Mean AV/IVC for bilateral adrenalectomies was 8.67 right and 6.33 left with CLR 0.76. Among 29 resected adrenal glands, pathology demonstrated benign adrenocortical adenomas (52%) and macronodular hyperplasia (48%) and mean dominant nodule maximum diameter of 2.7cm and mean weight of 18.2g. At a mean follow-up of 21.8 months, there was no clinical or biochemical recurrence of ACTH-independent hypercortisolism with most recent cortisol of 12.8 ± 7.5 mcg/dL and ACTH of 19.7 ± 13.1 pg/mL. AVS can be used to guide surgical management in patients with ACTH independent Cushing syndrome and bilateral adrenal masses, with favorable midterm outcomes.