Steroid Excess Research Articles

9202 Characterizing The Physiological Side-Effects Of Over-The-Counter Arthritis Supplements

Abstract Disclosure: K.S. Wei: None. M.O. De La Torre: None. A. Flores: None. C.E. Chiu: None. T.E. Angell: None. Introduction: Over the counter (OTC) health supplements are commonly used by patients for a variety of ailments but may contain active ingredients that are not stated, such as glucocorticoids. Here, we present a case series of 12 patients seen by the Endocrinology Consult service at an urban safety net hospital during 2022-2023 and determined to have iatrogenic adrenal insufficiency (AI) from specific OTC supplements that surreptitiously contained glucocorticoids. Clinical Cases:12 patients using OTC arthritis supplements [Artri King (n=8), Ardosons (n=3), and Ajo Rey (n=1)] were identified. Median age was 52 years and 33.3% were female. All started using the supplements because of joint pain. Median length of use prior to cessation was 6 months. The most common presenting symptoms were nausea/vomiting (42%), fatigue (42%), abdominal pain (33%), and dizziness (17%). The most common physical exam findings of steroid excess included moon facies (66%), central adiposity (66%), abdominal striae (50%), dorsocervical fat pad (33%), and bruising (33%). 3/12 patients required ICU admission. Cortisol assessment was performed in 11/12 patients, which showed normal cortisol level in 1 patient (cortisol ≥16 mcg/dL), AI in 3 patients (cortisol ≤3 mcg/dL), and an equivocal level (cortisol 3-16 mcg/dL) in 7 patients. Cosyntropin stimulation testing in 6/7 patients with equivocal cortisol levels suggested AI in 4 (cortisol level <16 mcg/dL at 60 minutes after ACTH stimulation), whereas 2 showed lower but normal response (cortisol levels 18.2 mcg/dL and 18.4 mcg/dL). In total, 10/12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis. The most common regimens were hydrocortisone 20mg qAM/10mg qPM (33%) and hydrocortisone 5mg qAM/5mg qPM (17%). To date, 2/10 patients have successfully discontinued steroid replacement. Conclusion: These cases demonstrate possible Cushing’s syndrome and/or adrenal insufficiency after unintentional exposure to glucocorticoids in these OTC arthritis supplements, which has only previously been reported in a small number of case reports (1). This series collected over a 2-year period offers important clinical insights: Because patients may not identify or recall a supplement, possible use of OTC medications for arthritis or other anti-inflammatory purposes should be specifically assessed in patients presenting with adrenal insufficiency (especially with concomitant findings suggesting Cushing’s syndrome). For patients on such supplements, immediate discontinuation may not be possible without cortisol replacement and should be done with caution. 1)Boncompagni A.C. et al. A case of iatrogenic Cushing syndrome and subsequent adrenal insufficiency from a hidden ingredient in the supplement Artri Ajo King. J Am Coll Emerg Physicians Open. 2023;4(4):e13007. Presentation: 6/1/2024

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

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

Comprehensive Review on the Virulence Factors and Therapeutic Strategies with the Aid of Artificial Intelligence against Mucormycosis.

Mucormycosis, a rare but deadly fungal infection, was an epidemic during the COVID-19 pandemic. The rise in cases (COVID-19-associated mucormycosis, CAM) is attributed to excessive steroid and antibiotic use, poor hospital hygiene, and crowded settings. Major contributing factors include diabetes and weakened immune systems. The main manifesting forms of CAM─cutaneous, pulmonary, and the deadliest, rhinocerebral─and disseminated infections elevated mortality rates to 85%. Recent focus lies on small-molecule inhibitors due to their advantages over standard treatments like surgery and liposomal amphotericin B (which carry several long-term adverse effects), offering potential central nervous system penetration, diverse targets, and simpler dosing owing to their small size, rendering the ability to traverse the blood-brain barrier via passive diffusion facilitated by the phospholipid membrane. Adaptation and versatility in mucormycosis are facilitated by a multitude of virulence factors, enabling the pathogen to dynamically respond to various environmental stressors. A comprehensive understanding of these virulence mechanisms is imperative for devising effective therapeutic interventions against this highly opportunistic pathogen that thrives in immunocompromised individuals through its angio-invasive nature. Hence, this Review delineates the principal virulence factors of mucormycosis, the mechanisms it employs to persist in challenging host environments, and the current progress in developing small-molecule inhibitors against them.

Association of adrenal steroids with metabolomic profiles in patients with primary and endocrine hypertension.

Endocrine hypertension (EHT) due to pheochromocytoma/paraganglioma (PPGL), Cushing's syndrome (CS), or primary aldosteronism (PA) is linked to a variety of metabolic alterations and comorbidities. Accordingly, patients with EHT and primary hypertension (PHT) are characterized by distinct metabolic profiles. However, it remains unclear whether the metabolomic differences relate solely to the disease-defining hormonal parameters. Therefore, our objective was to study the association of disease defining hormonal excess and concomitant adrenal steroids with metabolomic alterations in patients with EHT. Retrospective European multicenter study of 263 patients (mean age 49 years, 50% females; 58 PHT, 69 PPGL, 37 CS, 99 PA) in whom targeted metabolomic and adrenal steroid profiling was available. The association of 13 adrenal steroids with differences in 79 metabolites between PPGL, CS, PA and PHT was examined after correction for age, sex, BMI, and presence of diabetes mellitus. After adjustment for BMI and diabetes mellitus significant association between adrenal steroids and metabolites - 18 in PPGL, 15 in CS, and 23 in PA - were revealed. In PPGL, the majority of metabolite associations were linked to catecholamine excess, whereas in PA, only one metabolite was associated with aldosterone. In contrast, cortisone (16 metabolites), cortisol (6 metabolites), and DHEA (8 metabolites) had the highest number of associated metabolites in PA. In CS, 18-hydroxycortisol significantly influenced 5 metabolites, cortisol affected 4, and cortisone, 11-deoxycortisol, and DHEA each were linked to 3 metabolites. Our study indicates cortisol, cortisone, and catecholamine excess are significantly associated with metabolomic variances in EHT versus PHT patients. Notably, catecholamine excess is key to PPGL's metabolomic changes, whereas in PA, other non-defining adrenal steroids mainly account for metabolomic differences. In CS, cortisol, alongside other non-defining adrenal hormones, contributes to these differences, suggesting that metabolic disorders and cardiovascular morbidity in these conditions could also be affected by various adrenal steroids.

Unmasking Distorted Reflections: Exploring Body Image, Alcohol, and Drug Use in Nighttime Entertainment Districts

Background: Violence within nighttime entertainment districts (NEDs) has been blamed on problematic masculinity and has predominantly been attributed to excessive alcohol intake and steroid use in men. In this report we conducted two studies to: (1) ascertain whether researchers could act as third-party raters of body weight and muscle mass in NED patrons; and (2) to examine the relationship between body self-image, inebriation, alcohol preloading behaviors and drug use in the NEDs. Methods: Study 1 employed an observational approach to establish inter-rater reliability for ratings of muscle mass and weight. In Study 2 data (n = 2,745) were collected through breathalyzing and questionnaires to examine individuals’ self-image and drinking and drug-taking behaviors. Results: Participants’ self-ratings of muscle and weight significantly differed from researchers’ ratings, with males perceiving themselves as less muscular and females perceiving themselves as heavier. Perceived weight and muscle size did not relate to alcohol levels, but an interaction was found for female steroid users who perceived themselves as less muscular. Conclusions: Findings indicated a distortion in participants’ perceived body image, with a desire for muscularity among both males and females. These results underscore the complex interplay between self-perception, societal ideals, and drug use in young NED patrons.

Molecular mechanisms of steroid-resistant asthma

Steroid-resistant asthma (SRA) is clinically significant, approximately 10–15% of individuals with asthma do not exhibit a positive response to standard treatments. While this subset represents a relatively small proportion of asthma patients, severe refractory asthma places a substantial burden on healthcare resources and contributes significantly to illness and death. Additionally, the quality of life of patients is greatly affected by the adverse effects of excessive steroid consumption, there is a need to identify individuals who do not react well to steroid medication and the ongoing difficulties of these asthma patients in controlling their diseases, which have a large socio-economic impact. The current short article reviews the common molecular mechanisms responsible for steroid resistance in asthma patients.

FRI199 Severe Hypertriglyceridemia And Acute Pancreatitis In A Patient With Adrenocortical Carcinoma (ACC) Taking Mitotane

Abstract Disclosure: B.N. Cortez: None. D.G. Varghese: None. A. Naimian: None. R. Mallorson: None. T. Magee: None. S. Kelley: None. N. Roper: None. A.T. Fojo: None. J. Del Rivero: None. Background: Adrenocortical carcinoma (ACC) is a rare tumor with an incidence of 0.7-2 per million people per year, and a poor prognosis with a five-year survival &amp;lt;35%. Many patients present with steroid hormone excess (glucocorticoids, mineralocorticoids, androgens). Treatment of choice for a localized primary or recurrence is radical surgical resection, which offers the best chance for prolonged recurrence-free survival. However, patients with recurrent or metastatic disease are infrequently curable by surgery alone. Chemotherapy options have limited benefit, though platinum-based therapies have response rates of 25-30%. Mitotane has been used for the treatment of advanced ACC since the 1960s and is generally recommended to reduce risk of future recurrence. Clinical case: A 36-year-old female of Ashkenazi Jewish ancestry presented with a prior history of well-differentiated, grade 1 pancreatic neuroendocrine tumor (NET) fully resected with no evidence of recurrence. On follow up MRI 7 months after resection, she was found to have a 3.8 x 2.5 x 3.3 cm bilobed left adrenal mass. Laparoscopic biopsy was initially reported as NET, however, a second opinion was reported as ACC. She subsequently had laparoscopic surgery with intraoperative tumor spillage and surgical pathology was consistent with high grade ACC, Ki67 of 15-25% with invasion through the adrenal capsule. Germline genetic testing showed no variants of concern. Post-adrenalectomy, the patient’s starting dose was 1g mitotane each day with replacement hydrocortisone. When on 2.5 grams daily, her symptoms were mild diarrhea, fatigue and occasional headaches. One month after starting mitotane, she developed extreme abdominal pain, nausea and vomiting and presented to the ED. Computed tomography at the time revealed no evidence of disease (5 months after resection). Laboratory results were significant for mild leukocytosis, as well as elevated lipase (510 U/L, 0-160), cholesterol (451 mg/dL, 125-200), triglycerides (&amp;gt;10,000 mg/dL, &amp;lt;150), and LDL (168 mg/dL, &amp;lt;100), with a lactic acid of 2.6 mmol/L (&amp;lt;2) consistent with acute pancreatitis likely due to hypertriglyceridemia. Microbiology positive for parainfluenza virus. Her condition worsened and she subsequently developed septic shock, acute renal failure, for which she received hemodialysis, and multiorgan failure. On her ninth day of admission, she succumbed to disease. Conclusion: While some studies show hypertriglyceridemia secondary to mitotane, others only show elevated cholesterol at 6 and 3 months, respectively. We describe an ACC patient with a history of fatty liver disease and mixed hyperlipidemia who developed severe hypertriglyceridemia and acute pancreatitis leading to multiorgan failure about one month after starting mitotane. This case highlights hypertriglyceridemia as a serious complication of mitotane in a patient with preexisting dyslipidemia. Presentation: Friday, June 16, 2023

SAT336 A Successful Ovulation Induction And Embryo Generation In A Woman With P450-oxidoreductase Deficiency From Mutation G539R, Which Preferentially Impairs 17,20-lyase Activity

Abstract Disclosure: S. Charoensri: None. M. Thakur: None. R.J. Auchus: None. Introduction: Cytochrome P450 oxidoreductase (POR) deficiency is an autosomal recessive disorder causing decreased activity of several P450 enzymes, including CYP21A2, CYP17A1, and CYP19A1 that are essential for steroidogenesis in the adrenals and gonads. Female POR deficiency patients are typically manifested with genital ambiguity, abnormal menstruation, and infertility. Very few pregnancies have been documented from these patients. Case presentation: During an evaluation for infertility, a 35-year-old woman with late menarche, irregular cycles, and unruptured ovarian follicles was diagnosed with POR deficiency due to compound heterozygous pathogenic variant c.1615G&amp;gt;C (G539R) and a large deletion c.1669+5_1669+32del in the POR gene. Because mutation G539R preferentially impairs the 17,20-lyase activity of CYP17A1, she underwent in-vitro fertilization (IVF) with the protocol that has been used successfully to achieve pregnancy in incomplete 17-hydroxylase deficiency. Oral dexamethasone of 0.5 mg/day was given to suppress the adrenal-derived progesterone. After one menstrual cycle induced with estradiol and progesterone priming, leuprolide acetate was used to down-regulate endogenous gonadotropin secretion, then the oocyte maturation was induced with recombinant follicle-stimulating hormone (rFSH) and highly purified menotrophin. In the first cycle, 6 eggs were retrieved, 2 that were mature and fertilized with intracytoplasmic sperm injection (ICSI); however, none advanced to the blastocyst stage. She underwent the same protocol in a second IVF cycle with higher rFSH dosing. Despite increasing dexamethasone to 1.5 mg/day, progesterone rose to 4.9 ng/mL, while estradiol peaked at 120 pg/mL, consistent with progesterone accumulation in the developing ovarian follicles due to POR deficiency. From 6 eggs retrieved, 5 eggs were mature and all fertilized, and 3 developed past day 3. On day 6, one embryo (grading 5BB) was biopsied for preimplantation genetic testing and frozen. The second phase of the treatment plan is to lower adrenal-derived progesterone with a combination of hydrocortisone and prednisolone, prepare the endometrium with estradiol followed by progesterone, and perform embryo transfer. Conclusions: Very few examples of pregnancy in women with POR deficiency have been reported, and we describe the first example of successful ovulation induction and embryo generation in a woman with POR deficiency caused by the G539R mutation, which preferentially impairs 17,20-lyase activity. The complex array of steroid excess and deficiencies, from both adrenal and ovarian origin, must be systematically managed during assisted reproduction treatment for these women. Presentation: Saturday, June 17, 2023

Secondary Adrenal Insufficiency in Psoriasis

A 40-year-old male with chronic plaque psoriasis developed symptoms of secondary adrenal insufficiency due to long-term use of steroids. He presented with facial puffiness, increased abdominal fat deposition, and other signs of steroid excess. Glucocorticoid replacement therapy was initiated based on body surface area, requiring careful monitoring to maintain cortisol levels and prevent excessive exposure to glucocorticoids.

The prophylactic effects of naringin on steroid-induced early-stage osteonecrosis in rats: a preliminary study.

The excessive steroid may cause dyslipidaemia and oxidative insult during femoral head osteonecrosis, inducing bone loss and impairment of the intraosseous blood system. In contrast, bio-flavanone naringin has shown antioxidant, antiresorptive and lipid-lowering bioactivities. The present research is an effort to explore the anti-ON potential of naringin in vivo and in vitro. After a 6-week treatment, the femora were dissected for histological examination following bone mineral density assay by X-ray absorptiometry. Blood samples were examined for coagulation, oxidative stress, lipid transportation and endothelial injury. Marrow samples were cultured and assayed for adipogenic and osteogenic alterations by ALP activity, mineralization, RT-qPCR and western blot analysis. The results showed that naringin exerted a dose-dependent effect on reducing ON incidence, with inhibition of osteoporosis, oxidative stress and dyslipidaemia. The mechanism included the suppression of PPARγ2 for adipogenesis of bone marrow stem cells (BMSCs) and the prevention of oxidative stress in endothelium injury. Naringin may restore steroid-impaired osteogenesis by enhancing the mRNA and protein expression of osteogenic markers in a dose-ascending manner and new bone formation can be found in naringin groups. Taken together, our findings showed that naringin may serve as a prophylactic agent and selective PPARγ modulator for the early-stage ON.

The puzzle of extensive tinea incognito with a young woman: a case report a tinea incognito with Cushing’s disease

Introduction: Tinea incognito is a rare condition commonly found in abused topical or systemic steroids. Considering their immunosuppression status, Cushing’s syndrome predisposes patients to infectious diseases. Most patients of Cushing’s syndrome are as a result of adrenocorticotropic hormone production from a pituitary adenoma, which is referred to as Cushing’s disease. Here, we reported a rare co-occurrence of tinea incognito and Cushing’s syndrome secondary to a giant pituitary tumor. Case presentation: Extensive cutaneous and nail lesions were diagnosed with the tinea incognito and tinea unguium, and endocrine or rheumatic disorders were considered as underlying disease-causing extensive tinea incognito. A series of laboratory and imaging tests were performed. We found that a giant pituitary tumor was the primary etiology of multiple cutaneous appearances and secondary disorders. There was an exceptionally unusual co-occurrence of extensive tinea incognito and pituitary adenoma in our case. Discussion: We observed a rare co-occurrence of extensive tinea incognito and pituitary adenoma, which should be taken into consideration in the urgent diagnostic criterion of tinea incognito given the potential underlying condition. Conclusion: Tinea incognito is not only associated with a history of topical or systemic steroid use, but also the association that underlying diseases related to excessive endogenous steroid production are supported to be taken into account.

165 Randel Lecture: Androgen Excess Domestic Livestock Models—What can they Tell us About the Mechanisms Underlying Anovulation?

Abstract Ovulatory disorders are a major factor in female infertility. Our laboratory has identified several populations of cows and a population of sheep that have excess androgen (High A4) in dominant follicles and ovarian cortex cultures in the US and in the Middle East with increased steroidogenic enzyme production in somatic cells. Within our research herd, the High A4 females have irregular estrous cycles where behavioral estrus and ovulation are not coupled and are often anovulatory. Follicular waves of growth, during the estrous cycle, are disrupted in High A4 cows with development of persistent follicles, and an absence of normal follicular-wave estrogen patterns in blood plasma compared with Controls. Increased ovarian cortex fibrosis, oxidative stress markers and plasma pro- inflammatory lipids were present in High A4 cows indicating increased inflammation. High A4 granulosa cells have altered gene transcripts indicating cell cycle arrest and expression of genes enriched in other somatic cell types resulting in altered cell identity. Furthermore, High A4 ovarian cortex cultures secrete increased pro-inflammatory cytokines and have reduced follicle progression to later stages supporting follicular arrest. Treatment of High A4 ovarian cortex cultures with Vascular Endothelial Growth Factor 165 suppressed excess steroids, fibrosis, pro-inflammatory cytokines and relieved follicular arrest. Concentrations of Anti-Mullerian Hormone (AMH) were greater in High A4 vs Controls in both follicular fluid and ovarian cortex culture media supporting that AMH could be a factor contributing to follicular arrest. Many of the characteristics of High A4 cows and sheep identified are similar to polycystic ovary syndrome (PCOS) in women. Thus, High A4 cow and sheep are excellent models to unravel androgen excess molecular mechanisms involved in follicular arrest and female infertility contributing to anovulation.

PD03-08 SURGICAL AND FUNCTIONAL OUTCOMES OF BILATERAL SYNCHRONOUS ADRENALECTOMY FOR FUNCTIONAL TUMORS: A COHORT STUDY

You have accessJournal of UrologyCME1 Apr 2023PD03-08 SURGICAL AND FUNCTIONAL OUTCOMES OF BILATERAL SYNCHRONOUS ADRENALECTOMY FOR FUNCTIONAL TUMORS: A COHORT STUDY Keshav Agarwal, Rashmi Ramachandran, Nikhil Tandon, and Rajeev Kumar Keshav AgarwalKeshav Agarwal More articles by this author , Rashmi RamachandranRashmi Ramachandran More articles by this author , Nikhil TandonNikhil Tandon More articles by this author , and Rajeev KumarRajeev Kumar More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003220.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bilateral synchronous adrenalectomy has the potential for significant surgical and functional morbidity. We reviewed our 15-year experience with bilateral synchronous adrenalectomy to assess safety, surgical outcomes, morbidity and impact on health-related quality of life. METHODS: In an IRB approved study, we reviewed our prospective database of patients who underwent bilateral synchronous adrenalectomy for functional tumours between April 2008 and August 2022. Demographic profile, metabolic and radiological parameters, operative details and complications were recorded. Follow-up was obtained either in-person or telephonically and analysed for resolution of symptoms, quality of life using the WHO-QoL BREF questionnaire and complications of chronic steroid intake. RESULTS: During the study period, 337 adrenalectomies were performed which were bilateral in 51 patients, 48 undergoing both surgeries synchronously. 33 of these 48 patients had bilateral pheochromocytomas and 15 had Cushing’s syndrome. Among patients with Cushing’s syndrome, three had life-threatening symptoms requiring urgent bilateral surgery. Clinical details are given in Table 1. 40 patients had transperitoneal laparoscopic surgery and 8 underwent open surgery (Table 2). There were two intraoperative and 7 post-operative complications. 43 patients were available for follow-up. All had resolution of symptoms, BMI changes, and only two patients continued to receive one antihypertensive medication. Episodes of steroid deficiency occurred in 7 patients while steroid excess occurred in 3 patients. Quality of life was satisfactory in all patients in all domains. CONCLUSIONS: Bilateral synchronous adrenalectomy is safe and feasible in patients with functional adrenal tumors. It leads to symptom resolution with amelioration of hypertension and BMI changes with satisfactory overall quality of life. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e77 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Keshav Agarwal More articles by this author Rashmi Ramachandran More articles by this author Nikhil Tandon More articles by this author Rajeev Kumar More articles by this author Expand All Advertisement PDF downloadLoading ...

Primary bilateral macronodular adrenal hyperplasia: A series of 32 cases and literature review

Primary bilateral macronodular adrenal hyperplasia (PBMAH) accounts for <2% of cases of Cushing's syndrome. The majority of patients present with no obvious steroid excess it means with autonomous cortisol secretion (ACS). The classic treatment for patients with overt Cushing's syndrome is bilateral adrenalectomy, but unilateral resection of the larger adrenal gland can result in clinical and/or biochemical remission in >90% of cases, especially in cases of ACS. In this article, a series of 32 cases with PBMAH is described. Most of the cases of PBMAH had ACS, except for one case with overt Cushing's syndrome. A study of aberrant receptors was performed in six patients, being negative in three cases, positive in the metoclopramide test in two cases and positive in the metoclopramide test and in the mixed meal test in another patient. The patient with overt Cushing's syndrome was treated with adrenostatic therapy achieving biochemical control, while two patients with ACS underwent unilateral adrenalectomy with resection of the largest adrenal gland, demonstrating hypercortisolism remission and improvement of cardiovascular risk factors after surgery. This article describes a series of 32 cases of PBMAH and offers a comprehensive review of PBMAH.

Congenital Optic Disc Drusen Misdiagnosed As Benign Idiopathic Intracranial Hypertension

A 16 year old female, was referred by the neuro-physician for the evaluation and management of decrease visual acuity in the left eye and papilledema, she was diagnosed Benign Idiopathic Intracranial Hypertension. She was under treatment for 4 years for papilledema. Visual acuity was 6/6 in the right eye and 1/60 in the left eye. Slit lamp examination was normal. Fundoscopy showed lumpy appearances of the optic nerve heads with vessels and macula normal, in both eyes. Her B scan ultrasonography and Computerized Tomography scan were carried out that revealed buried optic disc drusen a cause of pseudo-papilledema. On General examination she had typical Cushingoid features that she developed due to excess steroid therapy she was prescribed.This casehighlights the importance of identifying buried optic disc drusen, being misdiagnosed and treated as true papilledema secondary to Benign Idiopathic Intracranial Hypertension.

Primary bilateral macronodular adrenal hyperplasia: A series of 32 cases and literature review

Primary bilateral macronodular adrenal hyperplasia (PBMAH) accounts for <2% of cases of Cushing's syndrome. The majority of patients present with no obvious steroid excess it means with autonomous cortisol secretion (ACS). The classic treatment for patients with overt Cushing's syndrome is bilateral adrenalectomy, but unilateral resection of the larger adrenal gland can result in clinical and/or biochemical remission in >90% of cases, especially in cases of ACS. In this article, a series of 32 cases with PBMAH is described. Most of the cases of PBMAH had ACS, except for one case with overt Cushing's syndrome. A study of aberrant receptors was performed in six patients, being negative in three cases, positive in the metoclopramide test in two cases and positive in the metoclopramide test and in the mixed meal test in another patient. The patient with overt Cushing's syndrome was treated with adrenostatic therapy achieving biochemical control, while two patients with ACS underwent unilateral adrenalectomy with resection of the largest adrenal gland, demonstrating hypercortisolism remission and improvement of cardiovascular risk factors after surgery. This article describes a series of 32 cases of PBMAH and offers a comprehensive review of PBMAH.

Testolactone: The Rise and Fall of a Drug

Testolactone is structurally related to testosterone and belongs to the first generation of aromatase inhibitors. It is a non-selective irreversible aromatase enzyme inhibitor that was one of the first steroids used in the clinical treatment of breast cancer. The use of testolactone in the treatment of breast cancer started in 1970, although its ability to inhibit aromatase was not discovered until 1975. Its use was primarily based on the inhibition of estrogen synthesis, which was applied in the treatment of estrogen-dependent breast cancers, in the treatment of disorders of sex steroid excess, familial male-limited precocious puberty, or in the treatment of patients with McCune–Albright syndrome, etc. The weak inhibitory activity of testolactone, and the moderate clinical response, prevented its widespread use, which ultimately resulted in withdrawal from the drug market in 2008. This review paper is dedicated to testolactone, its rise in the second half of the 20th century, and its fall in the first decade of the 21st century. Regardless of withdrawal from the market, for many years testolactone was a drug that improved the quality of life of patients facing one of the most serious diseases today, and for this reason, this paper describes medicinal application, synthesis, and modifications of testolactone.

Healthcare Utilization Patterns and Excessive Steroid Use in Late Adolescence Age and Young Adults With Crohn's Disease and Ulcerative Colitis.

Late adolescents and young adults (AYA) with inflammatory bowel disease (IBD) are a vulnerable population as they transition to adult healthcare. We aim to provide a real-world data on their healthcare utilization patterns and medication use through a large database. We performed a retrospective cohort study from January 1, 2012, to June 30, 2020, using OneFlorida Data-Trust, an electronic health record-based data repository representing over half of the Florida population. Outcomes of interest included demographics, healthcare utilization, medications, and disease severity. Chi-square tests and logistic regression were used to compare the rates of medication use, healthcare utilization, and disease severity by age groups. The number of patients who met our inclusion criteria was 10,578 with 2731 (25.8%) in the 17-25-year-old group. AYA patients had fewer ambulatory visits vs children (90% vs 95%; P value <.05). AYA patients were admitted more frequently from emergency facilities vs children (22.3% vs 10.9%; P value <.05). AYA patients received steroids more often than adults and younger patients (48.9% vs 45.3 vs 44.3% P value <.05, respectively). AYA patients received more narcotic (41.1% vs 22.3 % P value <.05) and antidepressant prescriptions (15.9% vs 9.5%; P value <.05) compared with children. With advancing age, a decrease in biologic use was noted (51% vs 40% vs 25.4% P value <.05, respectively). AYA patients with IBD have higher rates of hospital admissions from emergency department, fewer ambulatory health visits and they receive more steroids compared to children. Our study demonstrates the need for age-specific IBD programs for AYA patients.

Too much of a good thing? Iatrogenic Cushing syndrome secondary to excessive topical steroid use in lichen sclerosus.

We report a patient using excessive quantities of topical steroid treatment for lichen sclerosus without supervision who developed Cushing syndrome. These treatments are very safe when used appropriately and this highlights the importance of good follow-up and patient education.

Mammalian Target of Rapamycin Inhibition Decreases Angiotensin II-Induced Steroidogenesis in HAC15 Human Adrenocortical Carcinoma Cells.

Mammalian target of rapamycin (mTOR) inhibitors suppress adrenal cortical carcinoma cell proliferation and cortisol production; the relationship between mTOR and aldosterone production has not been examined. HAC15 cells were incubated with an mTOR activator and several inhibitors including AZD8055 (AZD) in the presence and absence of angiotensin II (AngII). The expression of rapamycin-sensitive adapter protein of mTOR (Raptor) and rapamycin-insensitive companion of mTOR (Rictor), adaptor proteins of mTOR complex 1 and 2, respectively, were studied in the HAC15 cells and deleted by CRISPR/gRNA. The mTOR inhibitors decreased aldosterone induced by AngII. Inhibition of mTOR by AZD significantly suppressed AngII-induced aldosterone and cortisol formation in a dose-dependent manner, whereas the mTOR activator MHY had no effect. AZD did not alter forskolin-induced aldosterone production showing that it is specific to the AngII signaling pathway. AngII-mediated ERK and mTOR activation were suppressed by AZD, along with a concomitant dose-dependent reduction of AngII-induced steroidogenic enzymes including steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase-type 2, CYP17A1, and aldosterone synthase protein. Furthermore, mTOR components ribosomal protein S6 kinase (P70S6K) and protein kinase B phosphorylation levels were decreased by AZD. As mTOR exerts its main effects by forming complexes with adaptor proteins Raptor and Rictor, the roles of these individual complexes were studied. We found an increase in the phosphorylation of Raptor and Rictor by AngII and that their CRISPR/gRNA-mediated knockdown significantly attenuated AngII-induced aldosterone and cortisol production. mTOR signaling has a critical role in transducing the AngII signal initiating aldosterone and cortisol synthesis in HAC15 cells and that inhibition of mTOR could be a therapeutic option for conditions associated with excessive renin-angiotensin system-mediated steroid synthesis.