Exogenous Steroids Research Articles

Multiplex Nontargeted Framework Enables Tracking Metabolic Profile of Oxymetholone and Methasterone In Vivo at Nanogram Level by GC-Orbitrap-HRMS for Antidoping Purpose.

Oxymetholone and methasterone are anabolic androgenic steroids prohibited by the World Anti-Doping Agency (WADA) for both in-competition and out-of-competition use. Detecting metabolites of exogenous steroids is crucial for establishing doping violations, making the study of these metabolites essential in antidoping efforts. This study investigated the urinary metabolic profiles of oxymetholone and methasterone using gas chromatography-orbitrap high-resolution mass spectrometry (GC-Orbitrap-HRMS) in nanogram level by utilizing a novel multiplex nontargeted framework protocol. Healthy volunteers each ingested one tablet of the drug, and urine samples were collected over 50 days in postadministration phase. The complete detection of the three fractions (free fraction, glucuronide fraction, and sulfate fraction) of the metabolites was carried out. The GC-Orbitrap-HRMS full-scan mode was employed to detect postadministration urine samples, comparing these with preadministration baseline urine samples to identify newly formed substances. Electron ionization (EI) mass spectra were used to infer possible metabolite structures, leading to the discovery of three novel metabolites of oxymetholone and two novel metabolites of methasterone. Notably, the newly identified oxymetholone metabolite, 2-methylene-17α-methyl-androstane-16ξ,17β-diol-3-one (O-M6), was detectable as a glucuronide conjugate up to 4 days after administration. The methasterone metabolite, 18-nor-17β-hydroxymethyl-2α,17α-dimethyl-5α-androst-13-en-3-one (M-M4), exhibited prolonged detectability as a glucuronide conjugate, being present in urine samples from both volunteers up to 50 days after administration. These findings have significant implications for antidoping purpose, providing extended detection windows for these anabolic steroids.

Menopausal hormone therapy and the risk of systemic lupus erythematosus and systemic sclerosis: a population-based nested case-control study.

Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are more common in women, partly due to differences in female sex hormones. Menopausal hormone therapy (MHT) is widely used to alleviate climacteric symptoms. Here, the relationship between MHT and SLE/SSc was investigated in a nested case-control study. Women with SLE or SSc and controls, matched 1 up to 10 on sex, birth year, and region, from the general population of Sweden. Data on exposures and potential confounders were obtained from National Patient and Prescribed Drug Register as well as Longitudinal Integration Database for Health Insurance and Labour Market Studies. Exposure was defined as dispensation of any MHT medication prior to the diagnosis/matching. The association between MHT and SLE/SSc, and whether the strength of the association, expressed as odds ratios (OR) and 95% confidence intervals (CI), varied by type, route of administration, and duration of use, was assessed using conditional logistic regression, adjusted for education, income, and sick leave. In total, 943 women with SLE and 733 women with SSc were identified between 2009 and 2019. We detected a significant association between MHT use and risk of SLE (OR = 1.3; 95% CI: 1.1-1.6), and SSc (OR = 1.4; 95% CI 1.2-1.7). Women who had both systemic and local MHT medications dispensed exhibited highest risk of SLE (OR = 1.9; 95% CI: 1.4-2.7) and SSc (OR = 1.8; 95% CI: 1.2-2.5). These findings indicate an association between MHT and SLE/SSc, independent of socioeconomic factors, warranting further investigation into the role of exogenous female sex hormones in SLE/SSc pathogenesis.

The Fetal Environment and the Development of Hypertension-The Epigenetic Modification by Glucocorticoids.

Intrauterine growth restriction (IUGR) is a risk factor for postnatal cardiovascular, metabolic, and psychiatric disorders. In most IUGR models, placental dysfunction that causes reduced 11β-hydroxysteroid dehydrogenase 2 (11βHSD2) activity, which degrades glucocorticoids (GCs) in the placenta, resulting in fetal GC overexposure. This overexposure to GCs continues to affect not only intrauterine fetal development itself, but also the metabolic status and neural activity in adulthood through epigenetic changes such as microRNA change, histone modification, and DNA methylation. We have shown that the IUGR model induced DNA hypomethylation in the paraventricular nucleus (PVN) in the brain, which in turn activates sympathetic activities, the renin-angiotensin system (RAS), contributing to the development of salt-sensitive hypertension. Even in adulthood, strong stress and/or exogenous steroids have been shown to induce epigenetic changes in the brain. Furthermore, DNA hypomethylation in the PVN is also observed in other hypertensive rat models, which suggests that it contributes significantly to the origins of elevated blood pressure. These findings suggest that if we can alter epigenetic changes in the brain, we can treat or prevent hypertension.

Recommendations on the management of meningioma and sex hormone therapy: The results of a collaborative effort between neurosurgical, endocrine and gynecological societies.

Exogenous and endogenous sex hormones, especially Progesterone agonists, may be causally linked to meningioma progression. Cessation of treatment leads to stabilization or regression of Progestin-induced meningioma. In many cases, avoiding sex hormone therapy may be possible in the context of meningioma treatment. However, hormonal treatment is not always easily replaceable and concise real-world recommendations regarding sex hormones and meningioma are lacking. A combined effort was initiated between Neurosurgical, Gynaecological and Endocrinological societies of Belgium to gather relevant information regarding sex hormone therapies and meningioma. After complete literature review, consensual recommendations were established. Collegial recommendations regarding sex hormones therapies and meningioma in the context of oral contraceptives, menopause hormonal treatment, fertility treatment, pregnancy and gender-affirming therapies are emitted and nuanced. Withdrawal and monitoring of sex hormone therapies are discussed in detail.A decision tree regarding Meningioma and Combined contraception, Progestin Contraception, Menopause Hormonal treatment, Progestin and Gender-affirming therapy is suggested.

Personalized Antenatal Corticosteroid Therapy and Central Nervous System Development: Reflections on the Gold Standard of Fetomaternal Therapy.

The term "fetal programming" refers to the effects of endogenous and exogenous corticosteroids, whether received from the mother or the fetus, on brain development and the hypothalamic-pituitary-adrenal axis reset. The authors of this narrative review examine the WHO's guidelines for prenatal corticosteroids in pregnant women who are at high risk of premature delivery. These guidelines are regarded as the best available for preventing late-life problems resulting from preterm. In order to find full-text publications published in peer-reviewed journals between 1990 and 2023 that were written in English, the authors searched PubMed, Scopus, Cochrane Library, and Web of Science. The authors highlight the possible adverse long-term effects of prenatal corticosteroid medication on human brain development and function. This pharmacological feature is therapeutically significant because there is less evidence in the scientific literature regarding the potential role that the timing, mode, and dosage of exogenous steroid treatment may have in neurological illnesses down the road. The authors expect that these studies will shed light on the relationship between specially designed prenatal corticosteroid therapy and the molecular mechanisms underlying the prenatal programming of neurodevelopment in childhood and adulthood.

Impact of Surreptitious Glucocorticoids in Over-the-Counter Arthritis Supplements.

Adrenal dysfunction due to over-the-counter (OTC) health supplements containing unlabeled glucocorticoids has been previously reported. Here, we present a case series of 12 patients at an urban safety net medical center evaluated by endocrinology for iatrogenic adrenal dysfunction, Cushing syndrome (CS) and/or adrenal insufficiency (AI), associated with use of OTC arthritis supplements surreptitiously containing glucocorticoids. There were 12 patients using OTC arthritis supplements (Artri King [n = 8], Ardosons [n = 3], Ajo Rey [n = 1]) included. The mean age was 51.6 years and 33.3% were female. Findings of CS were identified in 10/12 (83.3%) patients, including moon facies (66%), central adiposity (66%), and abdominal striae (50%). Symptoms of AI were identified in 8/12 (66.7%) patients, including nausea/vomiting (42%), fatigue (42%), and abdominal pain (33%). Of 10/12 (83.3%) patients initially needing glucocorticoid replacement therapy, 4 continue to require treatment, 3 have successfully discontinued treatment, and 3 have been lost to follow-up. The literature reviewed identified 10 cases in 7 previously published reports, which did not include consistent follow-up data on adrenal function after discontinuation of the supplement. This case series demonstrates possible presentations of CS and/or AI from glucocorticoid exposure in patients taking these OTC arthritis supplements. Including more cases than all previously published reports combined, this series expands data for cortisol levels, cosyntropin test results, and glucocorticoid replacement needs for these patients and highlights the necessity for vigilant identification of supplement sources of exogenous steroids and the recognition of possible AI when such supplements are discontinued.

Clinical characteristics of adrenal crisis in 371 adult patients with glucocorticoid-induced adrenal insufficiency.

Glucocorticoid-induced adrenal insufficiency (GIAI) is a hypothalamic-pituitary-adrenal (HPA) axis dysfunction caused by long-term use of exogenous steroids. Adrenal crisis (AC) is an acute complication of GIAI and one of the reasons for the increased risk of death. This study aims to analyze the clinical characteristics of GIAI patients with AC and explore the related risk factors. Clinical data of adult GIAI patients treated at our hospital between January 1, 2014, and December 31, 2023 were included. The demographic characteristics, clinical characteristics, laboratory tests and comorbidities of the patients were collected. Univariate and multivariate regression analyses were used to explore the variables related to the occurrence of AC, and prediction models were constructed. 51 patients (13.75%) developed AC during hospitalization. Mortality was significantly higher in patients with AC than in those without AC. Multivariate logistic regression analysis showed that infection, psychiatric symptoms, serum sodium, albumin, neutrophil-lymphocyte ratio (NLR) and eosinophil-lymphocyte ratio (ELR) were independent risk factors for AC. Among the prediction models constructed by machine learning algorithms, logistic regression model had the best prediction effect. This study investigated the clinical characteristics of AC in GIAI patients. NLR and ELR may be effective predictors of AC in GIAI patients, and combined with other clinically significant indicators, an effective prediction model was constructed. Logistic regression model had the best performance in predicting AC in GIAI patients.

Exploring the role of sex hormones and gender diversity in multiple sclerosis.

Sex and sex hormones are thought to influence multiple sclerosis (MS) through effects on inflammation, myelination and neurodegeneration, and exogenous hormones have been explored for their therapeutic potential. However, our understanding of how sex hormones influence MS disease processes and outcomes remains incomplete. Furthermore, our current knowledge is derived primarily from studies that focus exclusively on cisgender populations with exclusion of gender-diverse people. Gender-affirming hormone therapy comprising exogenous sex hormones or sex hormone blocking agents are commonly used by transgender and gender-diverse individuals, and it could influence MS risk and outcomes at various stages of disease. A better understanding of the impact and potential therapeutic effects of both endogenous and exogenous sex hormones in MS is needed to improve care and outcomes for cisgender individuals and, moreover, for gender-diverse populations wherein an evidence base does not exist. In this Perspective, we discuss the effects of endogenous and exogenous sex hormones in MS, including their potential therapeutic benefits, and examine both established sex-based dimorphisms and the potential for gender-diverse dimorphisms. We advocate for future research that includes gender-diverse people to enhance our knowledge of the interplay of sex and sex hormones in MS, leading to the development of more effective and inclusive treatment strategies and improvement of care for all individuals with MS.

Hormone-related thrombosis: duration of anticoagulation, risk of recurrence, and the role of hypercoagulability testing.

Hormone-related venous thromboembolism (VTE) is common and entails scenarios in which VTE occurs during exposure to exogenous or endogenous female sex hormones, typically estrogen and progestogen. For the management of hormone-related VTE, it is important to realize that many patients use these hormones for a vital purpose often strongly related to the patient's well-being and quality of life. In this review we discuss clinical cases of VTE related to hormonal contraceptive use and pregnancy to illustrate key considerations for clinical practice. We cover practice points for primary VTE treatment and detail the evidence on the risk of recurrent VTE and bleeding in this population. The potential value of thrombophilia testing is described, including "who, why, when, what, and how." We also discuss key aspects of shared decision-making for anticoagulant duration, including a reduced-dose anticoagulant strategy in hormone-related VTE.

Diagnostic and management challenges in paediatric Cushing's syndrome.

Cushing syndrome (CS) is the result of chronic exposure to glucocorticoid excess. CS in children is most often caused by the administration of exogenous steroids. Endogenous CS is rare in the paediatric population and is caused mainly by tumours of the pituitary and adrenal glands, with ectopic sources being extraordinarily rare before the age of 18 years. In addition, children and young adults with CS present with different epidemiology, management issues, prognosisand outcomes than older adult patients. This complex disorder needs early diagnosis and management to avoid the significant morbidity and even mortality that can result from chronic untreated CS. In this review, we present the complex case of a 7-year-old boy with CS that highlights the diagnostic and management challenges of paediatric CS patients, including the considerations for genetic predisposition and life-long consequences of CS in children and young adults. The diagnostic protocols for the evaluation of CS have been devised for adults and tested predominantly on adults. In this review, we discuss necessary modifications so that the testing can be adjusted for use in children. Additionally, pituitary adenomas in children are generally smaller and thus more difficult to recognize on pituitary imaging. The management of the case and its complexities underline the need for children with CS to be managed in a centre with experienced paediatric endocrinologists and skilled neurosurgeons both for their initial diagnosis and treatment as well as for their long-term follow-up and management.

The Complex of Steroid Hormones in Invertebrate Hydrobionts

The presence of a complex of biologically active steroid compounds (BASC) – hydrocortisone, corticosterone, progesterone, testosterone and estrogens (vertebrate hormones) in invertebrate hydrobionts of different phylogenetic levels was revealed in the experiments. The features of the quantitative content of BASC in different organs/tissues of hydrobionts and their changes at different stages of development are shown. The level of BASC in organisms or their organs is largely due to their own steroidogenesis, but at the same time, organisms can accumulate exogenous steroid compounds. The adaptive role of ALS in some invertebrates in changing conditions of the aquatic environment has been found. The similarity of the concentration of steroid compounds in different groups of bionts leads to the idea of a certain “physiological constant” of this complex of compounds in all organisms.

Diagnosis and approach to glucocorticoid-induced adrenal insufficiency and glucocorticoid withdrawal syndrome

Introduction and purpose: Primary adrenal insufficiency can result from diseases affecting the adrenal glands, while secondary adrenal insufficiency is caused by suppression of the hypothalamic-pituitary-adrenal axis. The most common cause of adrenal suppression is exogenous steroids, a condition recently termed glucocorticoid-induced adrenal insufficiency (GIAI). Glucocorticoid-induced adrenal suppression is a common adverse effect of glucocorticoid therapy, which can have severe consequences. This review provides a comprehensive overview of the diagnosis and management of glucocorticoid-induced adrenal insufficiency and glucocorticoid withdrawal syndrome. Material and methods: An extensive examination of articles published in scientific journals was carried out through online research platforms PubMed and Google Scholar. We searched articles by entering keywords in appropriate configuration: “glucocorticoid-induced adrenal insufficiency”, “glucocorticoids”, “steroids”, “adrenal crisis”, “substitution therapy”, “glucocorticoid withdrawal”. Description of the state of knowledge: Glucocorticoids are widely used in the treatment of various inflammatory and autoimmune disorders due to their potent anti-inflammatory and immunosuppressive effects. However, chronic glucocorticoid therapy can lead to a number of adverse effects, including adrenal suppression, which can result in adrenal insufficiency. Summary: Primary care clinicians should recognize the high prevalence of glucocorticoid-induced adrenal insufficiency in patients receiving non-oral glucocorticoid formulations. The glucocorticoid withdrawal syndrome exhibits symptoms analogous to glucocorticoid-induced adrenal insufficiency. Additional data on the morbidity and mortality linked to glucocorticoid-induced adrenal insufficiency is needed to comprehend the associated health risks, which will ultimately guide the approach to care for patients tapering long-term glucocorticoid therapy.

Systemic Effects and Absorption of Subepithelial Dexamethasone Vocal Fold Injections.

To compare the systemic changes following two office-based procedures-subepithelial vocal fold steroid injections (VFSI) and vocal fold augmentation (VFA), and to characterize the magnitude and chronicity of the effects observed. Prospective, controlled before-after comparative study. Patients prospectively underwent VFSI with 0.8-2 mg of dexamethasone or VFA. Serum cortisol, white cell count (WCC), and C-reactive protein (CRP) were measured at day 0 (pre-procedure), 1 and 7. Salivary cortisol was measured at baseline and daily for 7 days post-procedure. Fourteen patients underwent VFSI and 36 VFA. At baseline serum cortisol measured 304.6 ± 116.6 nmol/L and fell significantly to 48.1 ± 41.8 nmol/L 1 day following dexamethasone injection (p = 0.001) and recovered by day 7 to 303.7 ± 78.7 nmol/L. Salivary cortisol demonstrated a similar pattern with significant recovery demonstrated by day 3 (p = 0.001). White cell counts were affected by the systemic absorption of exogenous steroid and normalized by day 7. Patients who underwent VFA demonstrated no significant change in their serum or salivary cortisol and no significant change in their WCC. No significant changes in CRP or patient's physiological parameters were observed in either procedure. Our findings demonstrate systemic absorption of dexamethasone following VFSI, with acute hypothalamic-pituitary-adrenal (HPA) axis suppression which normalizes day 3 post-procedurally. 3 Laryngoscope, 135:801-808, 2025.

Role of Na+-K+ ATPase Alterations in the Development of Heart Failure.

Na+-K+ ATPase is an integral component of cardiac sarcolemma and consists of three major subunits, namely the α-subunit with three isoforms (α1, α2, and α3), β-subunit with two isoforms (β1 and β2) and γ-subunit (phospholemman). This enzyme has been demonstrated to transport three Na and two K ions to generate a trans-membrane gradient, maintain cation homeostasis in cardiomyocytes and participate in regulating contractile force development. Na+-K+ ATPase serves as a receptor for both exogenous and endogenous cardiotonic glycosides and steroids, and a signal transducer for modifying myocardial metabolism as well as cellular survival and death. In addition, Na+-K+ ATPase is regulated by different hormones through the phosphorylation/dephosphorylation of phospholemman, which is tightly bound to this enzyme. The activity of Na+-K+ ATPase has been reported to be increased, unaltered and depressed in failing hearts depending upon the type and stage of heart failure as well as the association/disassociation of phospholemman and binding with endogenous cardiotonic steroids, namely endogenous ouabain and marinobufagenin. Increased Na+-K+ ATPase activity in association with a depressed level of intracellular Na+ in failing hearts is considered to decrease intracellular Ca2+ and serve as an adaptive mechanism for maintaining cardiac function. The slight to moderate depression of Na+-K+ ATPase by cardiac glycosides in association with an increased level of Na+ in cardiomyocytes is known to produce beneficial effects in failing hearts. On the other hand, markedly reduced Na+-K+ ATPase activity associated with an increased level of intracellular Na+ in failing hearts has been demonstrated to result in an intracellular Ca2+ overload, the occurrence of cardiac arrhythmias and depression in cardiac function during the development of heart failure. Furthermore, the status of Na+-K+ ATPase activity in heart failure is determined by changes in isoform subunits of the enzyme, the development of oxidative stress, intracellular Ca2+-overload, protease activation, the activity of inflammatory cytokines and sarcolemmal lipid composition. Evidence has been presented to show that marked alterations in myocardial cations cannot be explained exclusively on the basis of sarcolemma alterations, as other Ca2+ channels, cation transporters and exchangers may be involved in this event. A marked reduction in Na+-K+ ATPase activity due to a shift in its isoform subunits in association with intracellular Ca2+-overload, cardiac energy depletion, increased membrane permeability, Ca2+-handling abnormalities and damage to myocardial ultrastructure appear to be involved in the progression of heart failure.

8768 Initiation of Exogenous Sex Hormones in a Pediatric Gender Clinic

Abstract Disclosure: C.M. Roberts: None. M.M. Knoll: None. G. Robertson: None. A. Egan: None. C. Moser: None. Introduction: The demographics of patients seeking care for gender dysphoria have changed significantly since care was started in 1987. The criteria for prescribing sex hormones have also evolved to allow a greater range of patients to receive gender-affirming hormones. We examined factors associated with prescription of gender-affirming hormones to patients presenting for gender-affirming care our clinic. Methods: Secondary analysis of sex hormone initiation as a minor among 14-17-year-old adolescents diagnosed with gender dysphoria, seen in the pediatric gender clinic between 2/19/2018 and 7/20/2022. We extracted demographic variables, appointment dates, and sex hormone prescription data from our electronic medical record. We collected patient reports of gender identity and suicidal behavior, and parent and adolescent reports of general adolescent well-being, months of gender dysphoria and social transition, and parental support for the adolescent’s gender identity from electronic clinic surveys. Results: We identified 273 adolescent-parent dyads with complete data. Most of our sample were assigned female at birth (74.4%), transgender male (59.3%), and white (83.5%) adolescents who lived in urban (86.4%) and lower-middle-income (64.5%) areas. The average age was 15.9+/-1.1 years. A minority of adolescents reported recent suicidal ideation 60/273 (22%), and prior suicide attempts 20/273 (7%). Parents reported a shorter duration of gender dysphoria (-16.7 months (95%CI: -22.0, -11.5)) and social transition (-4.7: -6.5, -3.0), and higher levels of parental support than adolescents. Approximately half, 146/273 (53.5%), of adolescents started sex hormones. The average age at initiation was 16.5 years +/- 0.9. Age at presentation, length of gender dysphoria or social transition, and the presence of suicidal ideation or attempts were not associated with initiation of sex hormones. Assigned males (OR:1.82:95%CI 1.04, 3.19), adolescents with higher parent-reported parental support for the adolescent’s identity (1.03:1.01, 1.04), and adolescents with private insurance rather than Medicaid (Blue Cross- 5.39:2.73, 10.64) were more likely to start sex hormones as a minor. Conclusion: Published criteria for the initiation of sex hormones among adolescents with gender dysphoria, including age, persistence of dysphoria, and the presence of suicidality, did not predict the prescription of sex hormones to minors in our clinic. Parent-reported support for the adolescent’s gender identity played a small role in predicting the prescription of hormones, but male sex assigned at birth and having private health insurance played larger roles. Further exploration of these findings is needed to ensure equity in the treatment of gender dysphoria. Presentation: 6/3/2024

7741 Artri King As A Cause Of Adrenal Insufficiency

Abstract Disclosure: Q. Aziz: None. S. Fatima: None. A.L. Champion: None. K.E. Izuora: None. IntroductionDietary supplements are highly unregulated and may have substance that can be harmful. Due to its easy availability, more patients may have access to these supplements which can cause detrimental health outcomes, such as adrenal insufficiency. Clinical Case Patient is a 46 year old female with past medical history of hypertension and obesity presents to the hospital for worsening left hip pain, which started 2 weeks ago. She heard a crack in her left hip and denied any trauma or injury prior. She was found to have subtrochanteric fracture. Nine months ago, she had right hip pain and was unable to bear weight. Physical exam was notable for alopecia in frontal and temporal region, dorsocervical fat pad, multiple bruises, round facies, and multiple purple straie. She also reported a 50 pound weight gain in the last year. She stated that she took an over the counter “pain medication”, but denied any supplements. Due to the non-traumatic fracture and physical features, AM cortisol was ordered for suspicion of Cushing’s Syndrome by primary team and was low at 2.4. Endocrinology team was consulted. Cosyntropin stimulation test showed baseline AM cortisol level 1.4 and 1 hour after cosyntropin, cortisol was 8.3. ACTH 3.4, testosterone undetectable, androstendione undetectable, Aldosterone 42.2, DHEA undetectable. It was found later that patient was taking an over the counter supplement called Artri King, up to 4 tablets a day. Artri King has been advertised as a supplement for joint and muscle pain and contains unknown amount of dexamethasone and diclofenac. She was soon placed on hydrocortisone for adrenal insufficiency and was titrated down. The hypothalamic-pituitary-adrenal (HPA) axis can be suppressed with as low as 5 mg prednisone equivalent a day. This can lead to inadequate adrenal response to stress. If a patient has prolonged exposure to exogenous steroids, insufficient ACTH secretion can lead to atrophy of the zona fasciculata and reticularis, resulting in reduced ability to secrete cortisol. Therefore, it is important to help withdraw patient from glucocorticoids. When initiating glucocorticoid withdrawal, hydrocortisone may be helpful due to short half life, allowing HPA axis more opportunity to recover. Adrenal atrophy may be slowly reversible, but 4 years after diagnosis of glucocorticoid induced adrenal insufficiency, recovery of adrenal function is unlikely to occur. ConclusionsIt is important to obtain a thorough history, especially for supplements. Many supplements are not regulated and can pose harm to our patients. Adrenal insufficiency due to glucocorticoids may not only occur from steroid injections, long course of prescription glucocorticoids, but can include supplements if it is hidden from the ingredient list. Presentation: 6/3/2024

5165 Cushing’s Disease And Primary Aldosteronism Confounded By A Non-functioning Solitary Adrenal Incidentaloma

Abstract Disclosure: J.G. Friedman: None. W. Huang: None. Background: Adrenal incidentalomas are common, affecting ∼2% of the general population. The presence of adrenal incidentaloma necessitates biochemical testing for hypersecretion, however hypercortisolism and/or hyperaldosteronism may not necessarily originate from the nodule that prompted the initial workup. Clinical Case: A 53-year-old man with a history of obesity and hypertension was referred for workup of a 2.4 x 1.4 cm R adrenal nodule that was incidentally discovered on an abdominal CT to rule out pancreatitis. He was noted on examination to have some Cushingoid features. He was on three antihypertensives (amlodipine 10 mg, carvedilol 50 mg, and spironolactone 50 mg) with adequate blood pressure control and no hypokalemia. He denied spells nor exogenous steroid exposure. Initial testing for hypersecretion showed an elevated cortisol 8.7 ug/dL (<1.8) after 1 mg dexamethasone with adequate dexamethasone level, aldosterone concentration (PAC) 9 ng/dL (3-16), plasma renin activity (PRA) 0.7 ng/mL/h (0.25-5.82), potassium of 3.8 mmol/L (3.5-5.1), and normal plasma metanephrines. Further testing revealed elevated 24-hour urinary free cortisol 81.3 mcg/24h (4-50) and elevated late night salivary cortisol 0.10 and 0.13 mg/dL (<0.09). Baseline 8 AM ACTH was not suppressed 16.3 pg/mL (7.2-63.6). DDAVP stimulation resulted in an increase in cortisol and ACTH suggestive of Cushing’s disease, which was confirmed by inferior petrosal sinus sampling (IPSS). Pituitary MRI showed a 3.6 mm L-sided microadenoma. He underwent transsphenoidal resection with pathology consistent with an ACTH-staining pituitary adenoma. Immediate post-op cortisol nadir was 4.9 ug/dL. A few weeks after surgery, he underwent retesting for primary aldosteronism notable for PAC 14 ng/dL, PRA 0.58 ng/mL/h, and K 4.0 mmol/L. After oral salt loading, 24-hour urine aldosterone was 14.4 mcg/24h (<12) with urine sodium 247 mmol/L/24h (>200). He completed AVS which lateralized to the L adrenal gland despite a R adrenal nodule. He underwent L adrenalectomy with significant improvement in blood pressure which is now well-controlled on carvedilol monotherapy with normalization of PRA to 1.94 ng/ml/h. The R adrenal nodule remains stable in size and appearance on follow up imaging. Conclusion: The presence of an adrenal adenoma with concomitant biochemical evidence of hormonal excess cannot inherently be attributed to nodular autonomous function without further workup. Other hormonal assessment including ACTH level and localization studies are necessary prior to any surgical procedure to avoid missed diagnoses of Cushing’s disease and contralateral primary aldosteronism in the presence of a non-functioning adrenal nodule. Presentation: 6/1/2024

6977 Unraveling Secondary Adrenal Insufficiency and an Invasive Pituitary Macroadenoma in a COVID-19 Positive Patient

Abstract Disclosure: F. El Sayed: None. A.A. Banka: None. Invasive pituitary macroadenomas extend into the extrasellar region and invade surrounding dural, periosteal, or mucosal tissues, often exceeding 1 centimeter and potentially compressing adjacent structures. Nonfunctioning pituitary adenomas (NFPAs), as they enlarge, can cause visual field impairment and ophthalmoplegia, with the decision for surgical intervention influenced by the degree of optic chiasm compression. NFPAs are sometimes associated with impaired endocrine function, particularly secondary adrenal insufficiency (sAI), which, warrants specific clinical attention. Management involves a combination of surgical interventions, such as transsphenoidal surgery, and medical approaches, including tailored hormone therapy or radiation therapy based on the tumor's characteristics. Clinical case: A 51-year-old female with a history of Sjogren's disease presented with a one-week duration of nausea, vomiting, diarrhea, and fatigue. Upon admission, she tested positive for COVID-19. Her vital signs indicated hypotension with a blood pressure in the 80s/40s range, a heart rate in the 90s, and she was afebrile on room air. Laboratory findings revealed significant hyponatremia (Na+ 118), K+ 4.3, HCO3- 19, and glucose 80. Workup for hyponatremia included a cortisol stimulation test, revealing secondary adrenal insufficiency with baseline cortisol of 3.5 ug/dl, 10.7ug/dl after 30 minutes, and 12.7ug/dl after 60 minutes. The patient denied exogenous steroid use, hypothyroid symptoms, polyuria, or polydipsia, and reported no headaches or visual symptoms. Endocrine evaluation showed hypogonadism despite post-menopausal status, with low estrone, estradiol, LH, and FSH levels. She was initiated on Cortef (hydrocortisone) with symptomatic improvement. Further investigation through an MRI revealed a large lobulated sellar mass measuring 3.2 x 2.8 x 3.5 cm compressing the optic chiasm and partially encasing the right internal carotid artery, leading to peripheral visual defects confirmed on perimetry. Following endoscopic endonasal pituitary macroadenoma resection, there was no evidence of interval growth on a one-year follow-up MRI scan. Discussion: The presented case highlights the importance of considering invasive pituitary macroadenomas in the differential diagnosis of patients with hyponatremia, particularly when accompanied by suggestive symptoms and an atypical cortisol response. The coexistence of COVID-19 adds a layer of complexity to the clinical scenario, necessitating a comprehensive approach to both infectious and endocrine management. Timely recognition, appropriate endocrine assessment, and targeted interventions, such as hydrocortisone replacement and surgical resection, are crucial for optimizing outcomes in patients with this intricate interplay of pituitary pathology and infectious states Presentation: 6/1/2024

A comparative study of hormonal contraceptive use and vitamin D levels at Gondar Town 2023.

Vitamin D deficiency is an emerging public health problem globally, with devastating health consequences. Some studies suggest that exogenous sex hormones, found in hormonal contraceptives, may enhance vitamin D levels. However, the reasons for this association are not fully understood, as women using hormonal contraception may have different lifestyle habits affecting their vitamin D status. Therefore, this study seeks to explore the relationship between hormonal contraceptive use and vitamin D levels. A Facility based comparative cross-sectional study was conducted in Gondar town from February to April 2023, involving a total of 162 women using three types of hormonal contraceptives (Norplant, DMPA, and COC) and 162 age and BMI-matched non-users as controls in a 1:1 ratio. Participants were selected using systematic random sampling. A semi-structured questionnaire was used to collected data regarding the socio-demographic, economic, obstetric, lifestyle, and clinical information. 5 milliliters of blood samples were collected from each participant for Laboratory analysis of serum vitamin D, calcium, and alkaline phosphates using a Beckman Coulter chemistry analyzer. Independent t-tests, ANOVA with post hoc Bonferroni test was used to compare statistics between the two groups, and logistic regression models to identify factors associated with Vitamin D deficiency. The mean serum Vitamin D levels of Norplant, DMPA, and COC users were 24.08 (± 5.17), 24.83 (± 5.52), and 31.90 (± 6.94) respectively; whereas control group has mean Vitamin D level of 22.00 (± 7.97). On the current study the prevalence of Vitamin D deficiency (< 20 ng/ml) among hormonal contraceptive users was found to be 21.6% (35/162), whereas 48.14% (78/162) of non-user controls had vitamin D deficiency. The odds of having Vitamin D deficiency was higher among participants who attained higher education, who never eat fish and have never been used vitamin D Supplements. However, the use of combined oral contraceptives (COC) shown to reduce the odd of having vitamin D deficiency by 90%. Similarly, individuals with normal and hypercalcemia state shown to have lower odd of having Vitamin D deficiency. Users of combined oral contraceptives (COC) had significantly higher mean serum Vitamin D levels compared to users of Norplant and DMPA, as well as non-users. The prevalence of Vitamin D deficiency was lower among COC users compared to non-users, highlighting a potential protective effect of COC use against Vitamin D deficiency.

Pseudo-precocious puberty in children exposed to exogenous sex hormone: case report series

Pseudo-precocious puberty in children exposed to exogenous sex hormone: case report series