Urinary Cortisol Research Articles

DISCREPANCIES BETWEEN DIETARY AND URINE NA/K RATIO CAN BE EXPLAINED BY ALDOSTERONE, CORTISOL AND URINE VOLUME

Objective: Increased urine sodium-to-potassium (Na/K) ratio is associated with hypertension and cardiovascular disease. However, we demonstrated that urine Na/K ratio does not accurately reflect dietary Na/K ratio. As rhythmic patterns of sodium storage and release are associated with aldosterone and cortisol levels and previous studies linked tissue sodium accumulation to water conservation, we investigated whether the discrepancy between urine and dietary Na/K ratio could be explained by these factors. Design and method: We performed a post-hoc analysis of the long-term sodium balance studies Mars105 and Mars520. Ten healthy participants consumed a diet with known sodium and potassium content. For 105 or 205 days 24-hour urine samples were collected. We calculated the difference between urine and dietary Na/K ratio. A linear mixed-effect model was used to determine whether this difference varied across salt intake levels. Furthermore, we fitted two linear mixed-effect models to explain discrepancies between urine and dietary Na/K ratio. In the first, sodium intake, potassium intake, urine aldosterone and urine cortisol were fixed effects and for each factor random slopes per participant were allowed. In the second, sodium intake, potassium intake and urine volume were fixed effects and for each factor random slopes per participant were allowed. We analysed the salt intake levels 6, 9 and 12 grams separately. Results: Urine Na/K ratio underestimated dietary Na/K ratio (median difference -0.21, IQR -0.47 to 0.09). The discrepancy was significantly larger at higher salt intake levels (mean difference -0.11, -0.22 and -0.36 for 6, 9 and 12 grams salt intake, respectively, P < 0.001). At all salt intake levels, higher aldosterone levels were associated with underestimation of the dietary Na/K ratio (Figure 1A). In contrast, higher urine cortisol and higher urine volume were associated with overestimation of the dietary Na/K ratio (Figure 1B and C respectively). Conclusions: Sodium intake, aldosterone, cortisol and urine volume can explain the discrepancy between dietary and urine Na/K ratio. These data suggest that tissue sodium accumulation contributes to the inability to estimate dietary intake using the Na/K ratio in a single 24-hour urine collection.

AMBULATORY BLOOD PRESSURE MONITORING BEFORE AND AFTER TREATMENT IN SECONDARY FORMS OF HYPERTENSION

Objective: Studies using ambulatory blood pressure (BP) monitoring (ABPM) have reported that in some secondary forms of hypertension the normal nocturnal BP decrease is blunted. Design and method: The aim of our study was to compare the nocturnal BP decrease in patients with secondary hypertension before and after treatment. ABPM was performed using the validated Meditech ABPM-06. ABPM readings were obtained at 30-minute intervals for 24-hour in patients with secondary hypertension before and after treatment. The diagnosis of secondary hypertension was based on the history and laboratory data: plasma and urinary electrolytes, renal function, calcium-phosphorus system, the renin-angiotensin-aldosterone system, urinary free cortisol, suppressibility of cortisol after 1 mg dexamethasone, plasma adrenocorticotropic hormone, plasma D4 androstenedione, plasma dehydroepiandrosterone sulphate, plasma 17-alpha hydroxyprogesterone, plasma testosterone, and urinary metanephrine. BP decrease were studied in the following groups: 42 patients with primary aldosteronism (19 men and 23 women; mean age, 44±12 years), 25 patients with adrenal pheochromocytoma (11 men and 14 women; mean age, 42±13 years), and 55 patients with Cushing's syndrome (18 men and 37 women, mean age, 43±13 years). Results: Average systolic/diastolic BP decrease was: before 2/1 mmHg and after 8/6 mmHg treatment in patients with primary aldosteronism. Average systolic/diastolic BP decrease was: before 4/5 mmHg and after 9/12 mmHg treatment in patients with adrenal pheochromocytoma. Average systolic/diastolic BP decrease was: before 3/2 mmHg and after 11/9 mmHg treatment in patients with Cushing's syndrome. All differences in systolic/diastolic BP decrease were statistically significant, with a P value <.001 Conclusions: The results of our study confirm that secondary causes of hypertension lead to a reduced decrease in blood pressure during sleep. After proper treatment reduction in nighttime BP normalizes. A detailed analysis of ABPM can lead us to find the accurate etiology of hypertension.

An unusual cause of adrenal insufficiency with elevation of 17-hydroxyprogesterone: case report

BackgroundWe present an intriguing case of primary adrenal lymphoma, with associated primary adrenal insufficiency (PAI), in a patient presenting a transitory partial 21-hydroxylase deficiency during the active phase of the adrenal disease.Case presentationAn 85-years old woman was referred because of worsening asthenia, lumbar pain, generalized myalgia and arthralgia. During investigations a computed tomography (CT) scan evidenced two large bilateral adrenal masses, highly suspicious for primary adrenal tumor. The hormonal assessment revealed very low levels of morning plasma cortisol and 24-h urinary cortisol, elevated ACTH levels with low plasma concentration of aldosterone, pointing to the diagnosis of PAI. After diagnosis of PAI our patient started glucocorticoid and mineralcorticoid replacement therapy with clinical benefit. In order to further characterize the adrenal lesions, adrenal biopsy, was performed. The histology revealed a high grade non-Hodgkin lymphoma with an immunophenotype consistent with intermediate aspects between diffuse large B-cell and Burkitt lymphoma, with a high proliferation index (KI-67 > 90%). The patient received chemotherapy with epirubicin, vincristine, cyclophosphamide, and rituximab, associated with methylprednisolone that resulted in a complete clinical and radiological remission within one year. After 2 years from the diagnosis and a total of 6 cycles of rituximab, the patient was in good clinical condition and was taking only the replacement therapy for PAI. The patient initially presented also a slight increase of 17-hydroxyprogesterone (17-OHP) for age that normalize after resolution of lymphoproliferative disease.ConclusionsIn the presence of bilateral adrenal disease and/or in the presence of signs and symptoms of PAI clinicians must exclude the presence of PAL. The evidence of elevated ACTH-stimulated 17-OHP levels also in patients with other adrenal masses, together with the detection of elevated basal 17-OHP levels in our patient make it more plausible, in our view, an effect of the lesion on the “healthy” adrenal tissue residue than a direct secretory activity by the adrenal tumor.

Comprehensive evaluation of adrenal cortical cancer: Single-center 22-year experience

BackgroundAdrenocortical carcinoma (ACC) is a rare malignancy with a reported incidence of 0.5–2 cases per million population per year. Literature is scarce on this malignancy with poor prognosis and limited treatment options. The objective of this report was to report a single-center experience of this rare malignancy. MethodsA retrospective chart review (1997–2019) was performed on patients diagnosed with ACC via surgical pathology. Data were subsequently split into two time periods defined by the date of initial presentation: 1996–2007 and 2008–2019. Results52 patients were identified, 55.8 % were female, and the mean age at the time of surgery was 53 years. Most common presentations (25 % each) were: incidentalomas, abdominal pain, or hormonal hypersecretion. Laboratory evidence of hormonal hypersecretion was identified in 40.4 %. Among those patients, elevated 24-hour urinary free cortisol was the most common finding in both time periods.The overall 5-year survival rate was 53.1 % and showed significant improvement in recent years when compared between the two time periods, 85.7 % vs 40.0 %. P = 0.004. ConclusionOverall, the most common presentation of ACC was found to be equally distributed among incidentaloma, hormonal hypersecretion, and abdominal pain. Hypercortisolism, a recognized poor prognosticator, was the most frequent form of hormonal hypersecretion. The 5-year survival rate for ACC was noted to be poor in general; however, it was observed to be substantially higher in more recent years. More research is necessary to further understand this malignancy in order to optimize management and improve outcomes. Clinical relevanceThis report provides a valuable contribution and expands the knowledge base for this important yet rare malignancy. The objective of this study was to report a single-center experience of ACC by characterizing patients diagnosed with this rare disease and managed at our institution and assessing their outcomes.

Did nocturia, in hypertension, correlate with dipping status?

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The association between nocturia and hypertension has been widely reported yet remains poorly characterized, precluding a more refined understanding of blood pressure as it relates to the cardiovascular setting. Nocturia is associated with significant morbidity and mortality (1,2,3) which is thought to be mediated in large part by the fact that nocturia is a potential manifestation of systemic disease (4). Previous studies have reported that heart failure and uncontrolled hypertension were responsible for clinically significant nocturia (5,6). However, it remains unclear the relationship with any hypertension mechanism and the effect on circadian blood pressure rhythm. Purpose To investigate characteristics of hypertensive patients in who complain for nocturia. Methods We prospectively recruit 49 patients among outpatients attending the Hypertension Centre of Hospital San Luca, Istituto Auxologico Italiano. Physical examination, standard routine blood tests, urine analysis for microalbuminuria, 24-hour sodium excretion, 24-hour urinary cortisol levels, 24-hour urinary metanephrine/normetanephrine and a standard 24h ABPM has been performed. We asses in every patients the presence of nocturia (≥2 nightly voids) then we compare sub mentioned features between patients with nocturia or not. Results The population recruited demonstrate a mean age of 62 years old, it is made by a majority of men (M 61%, F 39%). We found nocturia in 13 patients on the 49 recruited. Demographic, anthropometrical and hematochemical features of the population recruited is described in Table 1. We compare patients who complain nocturia with patients with a normal number of nocturnal voids. Only height and hemoglobin demonstrate significative difference in the population. In a second analysis we compare ABPM results of patients with nocturia with patients who don’t have this symptom. The results are described in Table 2. Differently to what we expect no difference is demonstrated between the two group in dipping status, we found a significative difference in overall heart rate, this difference is evident only the day period but not in the night period. Conclusion These preliminary data suggest that patients with nocturia than patient with normal number of nocturnal voids i) have lower height and hemoglobin level, this in support to nocturia is a potential manifestation of systemic disease (4);) have both a lower overall and diurnal cardiac frequency. No dipping correlation have been found in our study, more study are needed to clarify a potential relationship with sleep disorder.

Prevalence and incidence of type 2 diabetes mellitus in patients with adrenal incidentalomas: a study of 709 cases.

To evaluate the prevalence and incidence of type 2 diabetes in patients with nonfunctioning adrenal incidentalomas (NFAI) or adrenal incidentalomas (AI) with autonomous cortisol secretion (ACS). In this single-center retrospective study, all patients with adrenal incidentalomas ≥1 cm and ACS or NFAI studied between 2013 and 2020 were included. ACS was defined by a post-dexamethasone suppression test (DST) serum cortisol concentration ≥1.8 μg/dl, in the absence of signs of hypercortisolism, and NFAI was defined as a DST < 1.8 μg/dl without biochemical evidence of hypersecretion of other hormones. Inclusion criteria were met by 231 patients with ACS and 478 with NFAI. At diagnosis, type 2 diabetes was present in 24.3% of patients. No differences were found in the prevalence of type 2 diabetes (27.7 vs. 22.6%, P = 0.137) between patients with ACS and NFAI. However, fasting plasma glucose values and glycated hemoglobin levels were significantly higher in patients with ACS than with NFAI (112 ± 35.6 vs. 105 ± 29 mg/dl, P = 0.004; and 6.5 ± 1.4 vs. 6.1 ± 0.9%, P = 0.005, respectively). Furthermore, patients with type 2 diabetes had higher urinary free cortisol (P = 0.039) and late-night salivary cortisol levels (P = 0.010) than those without type 2 diabetes. After a median follow-up of 28 months, no differences were found in the incidence of type 2 diabetes between the groups (HR 1.17, 95% 0.52-2.64). Type 2 diabetes was present in one fourth of our cohort. We found no differences in its prevalence or incidence between the groups. However, glycemic control might be worse among diabetic patients with ACS. Higher concentrations of urinary and salivary cortisol were found in patients with than without type 2 diabetes.

Diagnostic cut-off values for the urinary corticoid:creatinine ratio for the diagnosis of canine Cushing's syndrome using an automated chemiluminescent assay.

Cushing's syndrome is one of the most common endocrinopathies in dogs. The preferred screening test for spontaneous Cushing's syndrome is the low-dose dexamethasone suppression test (LDDST). The diagnostic value of urinary cortisol:creatinine ratios (UCCR) is questionable. The aim of this study was to determine diagnostic cut-off values for UCCR testing in comparison with LDDST as a clinical reference standard and to calculate the sensitivity and specificity. Data from 2018 to 2020 were obtained retrospectively from a commercial laboratory. Both LDDST and UCCR were measured by automated chemiluminescent immunoassay (CLIA). The maximum interval between both tests was 14 days. The optimal cut-off value for UCCR testing was calculated by the Youden index. The sensitivity and specificity of these cut-off values for the UCCR test and LDDST were assessed by Bayesian latent class models (BLCMs). This study included 324 dogs with both UCCR test and LDDST results. The optimal UCCR cut-off value, calculated by the Youden index, was 47.4 × 10-6 . Any UCCR <40 × 10-6 was interpreted as a negative result, 40-60 × 10-6 as values in a gray zone, and >60 × 10-6 as positive. Using the cut-off of 60 × 10-6 , BLCM showed 91% (LDDST) and 86% (UCCR test) sensitivity and a specificity of 54% (LDDST) and 63% (UCCR test). Considering an 86% sensitivity and a 63% specificity, UCCR testing may be considered a first-line investigation to rule out Cushing's syndrome using CLIA analysis. Urine samples can be collected noninvasively at home by the owner, reducing the potential impact of stress.

LC-MS/MS in clinical chemistry: Did it live up to its promise?: Consideration from the Dutch EQAS organisation

BackgroundOver the past decade the use of LC-MS/MS has increased significantly in the hospital laboratories. Clinical laboratories have switched from immunoassays to LC-MS/MS methods due to the promise of improvements in sensitivity and specificity, better standardization with often non-commutable international standards, and better between-laboratory comparison. However, it remains unclear whether routine performance of the LC-MS/MS methods have met these expectations. MethodThis study examined the EQAS results, from the Dutch SKML, of serum cortisol, testosterone, 25OH-vitaminD and cortisol in urine and saliva over 9 surveys (2020 to first half of 2021). ResultsThe study found a significant increase in the number of compounds and in the number of results measured in the different matrices, with LC-MS/MS over a period of eleven years. In 2021, approximately 4000 LC-MS/MS results were submitted (serum: urine: saliva = 58:31:11%) compared to only 34 in 2010.When compared to the individual immunoassays, the LC-MS/MS based methods for serum cortisol, testosterone and 25OH-vitaminD showed comparable but also higher between-laboratory CVs in different samples of the surveys. For cortisol, testosterone and 25OH-vitaminD the median CV was 6.8%, 6.1% and 4.7% respectively for the LC-MS/MS compared to 3.9–8.0%,4.5–6.7%, and 7.5–18.3% for immunoassays. However, the bias and imprecision of the LC-MS/MS was better than that of the immunoassays. ConclusionDespite the expectation that LC-MS/MS methods would result in smaller between-laboratory differences, as they are relatively matrix independent and better to standardize, the results of the SKML round robins do not reflect this for some analytes and may be in part explained by the fact that in most cases laboratory developed tests were used.

Maternal cortisol in 3rd trimester is associated with traits of neurodevelopmental disorder in offspring. Odense Child Cohort.

BackgroundPrenatal cortisol exposure is essential for neurodevelopment. Maternal cortisol levels could be associated with offspring autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). AimTo investigate associations between maternal 3rd trimester cortisol and offspring traits of ASD and ADHD. Material and methodsMother-child pairs were included from the prospective study Odense Child Cohort. Morning serum cortisol and 24-hour urine cortisol/cortisone were collected at gestational week 27–30. Offspring ASD and ADHD traits were assessed at age three and five years using the Child Behavior Checklist. Maternal cortisol measurements and offspring ASD and ADHD traits assessment were available in (n = 1131; 52% boys) mother-child pairs at age three and (n = 717; 54% boys) at five years of age. Maternal 24-hour urine measurement was available in a subset, at offspring three years of age (n = 300) and at five years of age (n = 217). Associations between maternal cortisol (continuous and tertiles) and offspring ASD or ADHD traits were examined in regression models adjusted for offspring sex, maternal age, pre-pregnancy BMI, parity, maternal education level, parental psychiatric disorders, and maternal smoking and stratified for offspring sex. ResultsMaternal mean age ( ± SD) was 30 years ( ± 4.4) and median BMI (25%; 75% percentiles) 23.5 kg/m2 (21.3; 26.6). Higher maternal serum cortisol levels were associated with higher prevalence of offspring ASD traits at three years of age in the total study cohort and in boys after stratifying for offspring sex. In the total population, tertiles of serum cortisol showed a significant dose-response relationship to ASD traits in unadjusted and adjusted models (p-values for linear trend, p < 0.01 and p = 0.02, respectively). In offspring at five years, associations between maternal cortisol and offspring ASD traits were non-significant (all p-values > 0.2). Maternal cortisol was not associated with offspring ADHD traits (all p-values > 0.07) in offspring at three and five years. Maternal 24-hour urine cortisol, cortisone, or cortisol/cortisone ratio were not associated with offspring ASD or ADHD traits. ConclusionHigher maternal serum cortisol in 3rd trimester was associated with offspring ASD traits at three years of age in the whole study cohort and in boys, but not in girls. This association was non-significant at five years of age.

Ketoconazole as second-line treatment for Cushing's disease after transsphenoidal surgery: systematic review and meta-analysis.

The first-line treatment for Cushing's disease is transsphenoidal surgery for pituitary tumor resection. Ketoconazole has been used as a second-line drug despite limited data on its safety and efficacy for this purpose. The objective of this meta-analysis was to analyze hypercortisolism control in patients who used ketoconazole as a second-line treatment after transsphenoidal surgery, in addition to other clinical and laboratory criteria that could be related to therapeutic response. We searched for articles that evaluated ketoconazole use in Cushing's disease after transsphenoidal surgery. The search strategies were applied to MEDLINE, EMBASE, and SciELO. Independent reviewers assessed study eligibility and quality and extracted data on hypercortisolism control and related variables such as therapeutic dose, time, and urinary cortisol levels. After applying the exclusion criteria, 10 articles (one prospective and nine retrospective studies, totaling 270 patients) were included for complete data analysis. We found no publication bias regarding reported biochemical control or no biochemical control (p = 0.06 and p = 0.42 respectively). Of 270 patients, biochemical control of hypercortisolism occurred in 151 (63%, 95% CI 50-74%) and no biochemical control occurred in 61 (20%, 95% CI 10-35%). According to the meta-regression, neither the final dose, treatment duration, nor initial serum cortisol levels were associated with biochemical control of hypercortisolism. Ketoconazole can be considered a safe and efficacious option for Cushing's disease treatment after pituitary surgery. https://www.crd.york.ac.uk/prospero/#searchadvanced, (CRD42022308041).

Evidence of persistent mild hypercortisolism in patients medically treated for Cushing's disease: the Haircush study.

Cortisol-lowering drugs may not restore a normal cortisol secretion in Cushing's disease (CD). Assess the long-term cortisol exposure in medically treated CD patients using hair-cortisol (HF) and -cortisone (HE) measurement. Multicenter prospective study. Three groups of female patients: CushMed=16 treated with a stable cortisol-lowering drug dosage and normal UFCs; CushSurg=13 cured by pituitary surgery; CushBla=15 receiving stable recommended doses of hydrocortisone following bilateral adrenalectomy. Patients were evaluated during 3 months with their usual treatments. Two late-night saliva and 24h urine samples were monthly collected in CushMed, and at study end in CushSurg and CushBla patients. A 3-cm hair sample was collected at study end in all patients. Clinical score and centralized measurement of UFC, late-night salivary cortisol (LNSF) and -cortisone (LNSE), HE, HF. Despite having almost all UFCs normalized, CushMed patients exhibited increased HE as compared to CushSurg controls (p=0.003). CushMed patients also had increased clinical score (p=0.001), UFC (p=0.03), LNSF, LNSE (p=0.0001) and variability in the latter parameters (p=0.004). CushBla patients had increased HF and HE contrasting with similar LNSE to CushSurg patients. Six of 15 CushMed patients exhibited increased HE concentrations and had increased antihypertensive drug dosage compared to CushMed patients with normal HE (p=0.05). Despite normalized UFCs, a subset of medically-treated CD patients displays an altered circadian rhythm of serum cortisol. A single HE measurement identifies chronic mild persistent hypercortisolism and could replace multiple saliva analyzes to monitor medical treatments in CD patients once UFC is normalized.

Urinary free cortisol is an independent predictive factor for early distinction between ectopic ACTH secretion and pituitary Cushing's disease

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

Pooled analysis from two osilodrostat Phase III studies in Cushing's disease (LINC 3 and LINC 4): Clinical improvements according to urinary and late-night salivary cortisol levels

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

Abstract #1413755: Subclinical Cushing’s Syndrome in an ACTH-secreting Pituitary Macroadenoma

Subclinical Cushing’s syndrome (SCS) is characterized by subtle cortisol hypersecretion, which does not result in the typical signs and symptoms of Cushing’s syndrome (CS). While many of the signs and symptoms of CS are common in the general population, there are some that are discriminatory and specific for CS: supraclavicular fat pads, proximal muscle weakness, facial plethora, and violaceous striae. SCS manifests mostly as obesity, type 2 diabetes, and hypertension. Diagnosing SCS is challenging; however, the best screening test to uncover the subtle hypercortisolism is the dexamethasone suppression test (DST). We report a case of SCS in a 62 years old Caucasian postmenopausal patient with a medical history of total thyroidectomy for Graves’ disease, post-surgical hypothyroidism, 7.4cm right pheochromocytoma status post partial right adrenalectomy, incidentally discovered pituitary macroadenoma (during imaging to look for subarachnoid hemorrhage), untreated type 2 diabetes mellitus (A1c 6.6% and stable for 1 year before treatment), hypertension, atrial fibrillation, cerebrovascular accident, and worsening migraines. Patient’s physical exam was mostly unremarkable; she had central obesity and bilateral lower extremity swelling. Pituitary work-up showed evidence of secondary hypogonadism and secondary hypothyroidism with elevated adrenocorticotropic hormone (ACTH) of 130 (AM range: 7.2-63) and cortisol of 12.6, at 11:52AM. Further work-up for hypercortisolism revealed non-suppressed cortisol (5.83mcg/dL) on the low dose DST and 49% suppression of cortisol and ACTH on the high dose DST. 24-hour urinary cortisol was normal. Patient did not perform the midnight salivary cortisol. Patient subsequently underwent trans-sphenoidal resection of the pituitary macroadenoma. Pathology analysis of the pituitary mass showed weak to moderate immunoreactivity for ACTH. Our patient had abnormal DST but normal 24hour urine cortisol. We may have missed her SCS if we screened her only with a 24hour urine cortisol. This confirms the fact that dexamethasone suppression test should be the first test in the evaluation of subclinical Cushing’s syndrome.

Abstract #1405095: PCOS Diagnosis Leading to a Delayed Diagnosis of Cushing's Disease

Polycystic ovarian syndrome (PCOS) is a common disorder affecting pre-menopausal women. Diagnostic criteria for PCOS include menstrual irregularities, biochemical or clinical hyperandrogenism and/or evidence of polycystic ovaries on ultrasound. Any 2 of the above is sufficient for a diagnosis of PCOS. However, PCOS is a diagnosis of exclusion so other pathologies should be investigated including hypercortisolemia. We present a case of Cushing's Disease in which the patient’s clinical features were previously attributed to a diagnosis of PCOS delaying appropriate intervention. A 22-year-old nulligravida woman with no significant past medical history presented to the Ob/Gyn clinic with complaints of amenorrhea and infertility. Patient noted irregular menstrual cycles since attaining menarche, she denies any headaches, galactorrhea but reported facial hirsutism and weight gain. She was initially diagnosed with PCOS but had continued amenorrhea despite treatment with medroxyprogesterone acetate. Additional work up was ordered by Gyn which noted mildly elevated Prolactin at 30.84 ng/ml. MRI head/brain subsequently ordered noted a large T2 weighted hyperintense lesion measuring 2.2 x 1.65 x 2.0 cm involving the sella with extension suggesting a pituitary macro-adenoma. Patient was referred to endocrinology for additional work up. Further evaluation showed normal repeat prolactin level with dilution study normal at 11.9 ng/ml. She was found to have secondary hypogonadism with FSH - 5.32 mIU/ml, LH- 2.1IU/L and estradiol level at < 20 pg/ml. She also had secondary hypothyroidism with TSH 0.88 mIU/ml and free T4 at 0.64 ng/dl. Morning Cortisol was at 19.13 ug/uL with baseline ACTH elevated at 127 pg/ml. This showed adequate adrenal function but concern for ACTH dependent hypercortisolemia. She had 2 failed 1 mg dexamethasone suppression test with cortisol level at 10.92 ug/uL and 20.91 ug/uL with adequate dexamethasone levels. She had 2 elevated 24-hour urine cortisol at 72ug/24hr and 81ug/24hr. She also had 2 elevated midnight salivary cortisol level at 0.338ug/dl and 0.349ug/dl. Other labs showed normal IGF-1 and normal DHEA-S. Patient was diagnosed with Cushing Disease and underwent successful transsphenoidal resection of the pituitary macroadenoma. Post operative cortisol was <2 ug/ul, she was initiated on hydrocortisone 20mg am and 10mg pm. Patient had continued monitoring for recovery of hypothalamic-pituitary-axis. A month after the surgery, patient got pregnant and was continued on her hydrocortisone and levothyroxine replacement. In our case the diagnosis and treatment of Cushing's disease was delayed due to clinical features mimicking PCOS. PCOS is a diagnosis of exclusion, and our case illustrates the importance of excluding the other endocrine pathologies, such as Cushing's disease, to prevent delaying the appropriate treatment and to mitigate the risk of increased morbidity and mortality that may be associated with them.

Abstract #1375771: A Fluke or No? Fluconazole Treatment in a Case of Ectopic Cushing Syndrome

Cushing syndrome is characterized by elevated cortisol levels due to iatrogenic causes, pituitary tumors or from an ectopic focus. Ketoconazole has been shown to effectively decrease cortisol levels without a high risk of toxicities. Here we show a case report of a patient with ectopic Cushing syndrome treated with an alternative steroidogenesis inhibitor, fluconazole. We reported a 75-year-old male with a past medical history significant for atrial fibrillation, hypertension and obstructive sleep apnea. He was admitted to the hospital due to severe hypokalemia of 2.6 mmol/L (reference range 3.6-5.2 mmol/L), a blood sugar of 498 mg/dL (reference range 7-99 mg/dL), elevated PM cortisol levels of 66.1 mcg/dL (reference range 3-13 mcg/dL) and AM Cortisol Levels of 112 (reference range 5-25mcg/dL), thus prompting an endocrinology consult. Further examination of 24-hour urine cortisol displayed elevated levels at 11,656 mcg/24hrs (reference range 4-40 mcg/24hrs). The patient failed an 8mg dexamethasone suppression test with AM cortisol levels of 57.8 mcg/dL (5-25 mcg/dL) with a dexamethasone drug level of 2713 ng/dL (reference range >200 ng/dL), excluding elevated metabolism as cause of failed suppression. Pituitary magnetic resonance imaging showed a normal pituitary gland. Patient was started on 400mg of fluconazole daily with plans to switch to 400 mg ketoconazole in outpatient care. Outpatient positron emission tomography failed to identify the source of ACTH. Additionally, petrosal sinus sampling failed to detect altered levels of ACTH secretion. Patient was readmitted to hospital one month after original diagnosis with continued hypokalemia of 2.7 mmol/L (reference range 3.6-5.2 mmol/L) and worsening diabetic symptoms. Patient was taken off ketoconazole two weeks after prior discharge, not knowing it was temporary treatment for his Cushing’s syndrome. He was restarted on 400mg fluconazole and on day three of admission, fluconazole dose was increased to 600 mg daily (Endocrinology Metabolism case reports 2019, July 3) with cortisol levels to be monitored. On day one of admission, his AM cortisol levels were 91.5 mcg/dL (reference range 5-25 mcg/dL) and declined to 76.8 mcg/dL, 72.9 mcg/dL, 69.2 mcg/dL, 66.4 mcg/dL, and 60 mcg/dL the following days with fluconazole treatment. The patient was then discharged to outpatient follow-up with continuation of 600mg fluconazole. Within a week of the latest discharge, the patient presented to the hospital again due to an episode of atrial fibrillation. AM cortisol levels were measured to be 37.2 mcg/dL (reference range 5-25 mcg/dL), showing a 59.3% decrease since his last admission. Patient was then discharged from our care to an outpatient endocrinologist. This case shows that cortisol levels in ectopic Cushing Syndrome can be effectively lowered through fluconazole treatment. This medication has a more favorable side effect profile than other steroidogenesis inhibitors such as metyrapone and mitotane. Fluconazole monotherapy or dual therapy should be investigated further as a viable option for ectopic Cushing Syndrome therapy prior to bilateral adrenalectomy.

RECOGNITION AND CLASSIFICATION OF DEPRESSION UNDER DEEP NEURAL NETWORK AND REHABILITATION EFFECT OF MUSIC THERAPY

This study was aimed at the application of a deep graph convolutional neural network (GCNN) in cerebral magnetic resonance imaging (MRI) analysis of patients with depression and the effect of Western medicine combined with music therapy in the treatment of depression. A total of 120 patients with different degrees of depression were divided into the test group with 60 cases (western medicine+music therapy) and the control group with the other 60 cases (western medicine only). All these patients underwent MRI scanning. On the basis of the deep GCNN, an optimized algorithm (O-GCNN) for depression recognition was proposed. It was found that the accuracy, sensitivity, and specificity for classification of the O-GCNN algorithm were significantly higher than those of the convolutional neural network (CNN) model, the back propagation (BP) algorithm, and the forward propagation (FP) algorithm ([Formula: see text]). The scores of somatization, interpersonal sensitivity, depression, psychoticism, and anxiety of the test group were significantly lower than those of the control group during and after treatment ([Formula: see text]). The scores of the Self-rating Depression Scale (SDS) and Hamilton depression scale (HAMD) of patients in the test group were also significantly lower than those in the control group during and after treatment; the differences were statistically significant ([Formula: see text]). The values of left hippocampal regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuation (fALFF) of patients in the test group were significantly lower than those in the control group during and after treatment ([Formula: see text]). The 24-h urinary free cortisol (UFC) content in the test group was remarkably lower during and after treatment, and the difference was statistically significant ([Formula: see text]). The results showed that the improved depression recognition algorithm O-GCNN proposed in this work had a high application value in the auxiliary diagnosis of depression. Music therapy combined with Western medicine treatment can more effectively improve the anxiety and negative mental state of patients with depression and promote the improvement of patients’ conditions.

Cushing’s Syndrome Presenting as Nonconvulsive Status Epilepticus: A Case Report and Literature Review (P9-1.011)

<h3>Objective:</h3> NA <h3>Background:</h3> Cushing’s Syndrome (CS) may present with neuropsychiatric manifestations that can mimic autoimmune encephalitis, potentially delaying diagnosis and treatment. We present a case of CS presenting with personality changes and status epilepticus and performed a literature review describing neurological manifestations of CS. <h3>Design/Methods:</h3> A male in his 50s presented with episodic word-finding difficulties, inappropriate smiling, fatigue, cognitive decline and one episode of generalized tonic clonic seizure on levetiracetam from an outside hospital. Workup revealed thrombocytopenia, hypokalemia, hypertension, normal MRI brain and sella. Continuous electroencephalogram revealed nonconvulsive status epilepticus. Lumbar puncture demonstrated elevated protein with normal white blood cell count. He was started on high-dose IV methylprednisolone followed by IVIg for presumed autoimmune encephalitis. Autoimmune encephalitis antibodies including anti-NMDA receptor were negative. CT PET scan showed bilateral adrenal enlargement, which in the context of hypokalemia, hyperglycemia, hypertension, and thrombocytopenia was concerning for severe Cushing’s Syndrome. Methylprednisolone and anti-seizure medications were stopped. Inferior petrosal sinus sampling and cerebral angiogram were unremarkable. The diagnosis was supported by elevated random and urine cortisol levels and managed with etomidate and ketoconazole. He underwent bilateral open adrenalectomy following which he was started on oral glucocorticoids. Repeat EEG showed no ictal activity and the patient remained seizure-free. <h3>Results:</h3> Literature review utilizing PubMed identified 17 articles describing CS presenting with neuropsychiatric symptoms. The most common symptoms cited were cognitive decline (23%), psychosis (18%) and seizure (6%). Additional isolated cases cited posterior reversible encephalopathy syndrome, hypogeusia and hyposmia. Most patients had significant improvement or full recovery once CS was treated. <h3>Conclusions:</h3> Cushing’s Syndrome can present with neuropsychiatric symptoms and status epilepticus. It can be an emergency requiring prompt endocrine and surgical evaluation. Serum cortisol levels should be checked in patients presenting with acute personality changes and seizures. <b>Disclosure:</b> Dr. Cameron has nothing to disclose. Dr. Venegas has nothing to disclose. Dr. Fahad has nothing to disclose. Dr. Mathew has nothing to disclose.

Association Between Parameters of Cortisol Metabolism, Biomarkers of Minerals (Zinc, Selenium, and Magnesium), and Insulin Resistance and Oxidative Stress in Women with Obesity.

This is a cross-sectional study with women divided into a group of those with obesity (n = 80) and a control group (n = 94). Statistical analysis was conducted using the SPSS program. There were high values of GPx and TBARS and reduced values of SOD in women with obesity compared to the control group. Obese women showed increased concentrations of cortisol in serum and urine as well as hypozincemia, hyposelenemia, and hypomagnesemia and increased urinary excretion of these minerals. There was a negative correlation between the cortisol/cortisone ratio and erythrocyte zinc and selenium concentrations and a significant positive correlation between GPx and SOD activity and erythrocyte and plasma concentrations of zinc and selenium. The results of the study suggest the influence of adiposity on the increase in cortisol concentrations and the role of this hormone in the compartmentalization of the minerals zinc, selenium, and magnesium. However, the association study does not allow identifying the impact of such action on the antioxidant defense system and insulin sensitivity.

Clinical Utility of Osilodrostat in Cushing's Disease: Review of Currently Available Literature.

Cushing's disease (CD) is caused by endogenous hypercortisolism as a result of adrenocorticotropin (ACTH) secretion from a pituitary tumor. The condition is associated with multiple comorbidities and increased mortality. First-line therapy for CD is pituitary surgery, performed by an experienced pituitary neurosurgeon. Hypercortisolism may often persist or recur after initial surgery. Patients with persistent or recurrent CD will generally benefit from medical therapy, often administered to patients who underwent radiation therapy to the sella and are awaiting its salutary effects. There are three groups of medications directed against CD, including pituitary-targeted medications that inhibit ACTH secretion from tumorous corticotroph cells, adrenally-directed medications that inhibit adrenal steroidogenesis and a glucocorticoid receptor (GR) antagonist. The focus of this review is osilodrostat, a steroidogenesis inhibitor. Osilodrostat (LCI699) was initially developed to lower serum aldosterone levels and control hypertension. However, it was soon realized that osilodrostat also inhibits 11-beta hydroxylase (CYP11B1), leading to a reduction in serum cortisol levels. The focus of drug development then shifted from treatment of hypertension to treatment of hypercortisolism in CD. In a series of studies (LINC 1 through 4), osilodrostat was shown to be effective in normalizing 24-h urinary free cortisol (UFC) in the majority of treated patients and was approved for patients with CD who have failed surgery or are not surgical candidates. Further study is needed to examine the role of combination therapy as well as long-term outcomes of treated patients. Osilodrostat was shown to have an overall good safety profile. Most common adverse effects include nausea, headache, fatigue, arthralgias, dizziness, prolonged QTc interval, hypokalemia. In females, the drug can cause hirsutism and acne. Osilodrostat is administered twice daily, making it a good choice for patients with difficulty adhering to more complex regimens. Osilodrostat has an important, albeit adjunctive, role in the management of patients with CD.