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Case Presentation: A 22-year-old female presented to the emergency department with a two-month history of worsening fatigue, unintentional weight gain, and progressive facial swelling. Physical examination findings included hirsutism, moon facies, and abdominal striae. Subsequent brain magnetic resonance imaging revealed the presence of a 2.4-centimeter pituitary macroadenoma, confirming the diagnosis of Cushing’s disease. The patient was then admitted for neurosurgical tumor resection.Discussion: Cushing’s disease is exceedingly rare and often presents with symptoms resembling more prevalent disorders, contributing to delays in diagnosis. Therefore, maintaining a high index of suspicion for this disease is crucial for emergency physicians.

We present a case series of 3 patients who developed iatrogenic hypothalamic-pituitary-adrenal axis disruption while taking Artri King, an over-the-counter supplement marketed for joint pain that is reported to contain dexamethasone not listed on the supplements label. Patient 1, a 58-year-old woman, presented with persistent hyponatremia, weight gain, proximal muscle weakness, dorsocervical fat pad, and new, red striae on her breast and abdomen in the setting of Artri King use. Her dexamethasone level was elevated (Table 1), confirming the suspicion of dexamethasone content in this supplement. Patient 2, a 55-year old woman, had presented with cushingoid features and a low morning cortisol level (Table 1) in the setting of Artri King use. Patient 3, a 59-year-old man, presented with poorly controlled diabetes in the setting of Artri King use and an elevated serum dexamethasone level. Supplements containing hidden glucocorticoids can cause not only iatrogenic Cushing syndrome, but also adrenal suppression, providing a diagnostic challenge for providers.

Cortisol-producing adrenal adenomas consist of a mixture of lipid-rich clear and lipid-poor compact cells in varying proportions. Most adenomas are mainly composed of lipid-rich clear cells and typically exhibit low computed tomography (CT) attenuation values, high uptake on 131I-adosterol scintigraphy, and mild accumulation on 18F-fluorodeoxyglucose positron emission tomography/CT. However, adenomas predominantly composed of lipid-poor compact cells are rare, with limited evidence regarding their imaging characteristics. A 27-year-old woman with weight gain and a moon face was referred to our hospital. She presented with hypertension, dyslipidemia, low plasma ACTH levels, and autonomous cortisol secretion. We diagnosed this patient with ACTH-independent Cushing syndrome with a left adrenal tumor. The adrenal tumor exhibited imaging findings atypical for an adenoma, including high CT attenuation values, negative uptake on 131I-adosterol scintigraphy, and strong accumulation on 18F-fluorodeoxyglucose positron emission tomography/CT. Histopathological analysis indicated that the tumor was a rare type of adenoma, predominantly composed of lipid-poor compact cells. These findings and recent reports suggest that the proportion of compact cells can influence the imaging findings. Therefore, in the differential diagnosis, it is important to recognize that cortisol-producing adrenal adenomas predominantly composed of compact cells can present with atypical imaging findings. [ABSTRACT FROM AUTHOR]

Secondary adrenal insufficiency is a life-threatening condition that may arise in the setting of iatrogenic Cushing syndrome. Intra-articular corticosteroid injections (IACs) are a standard treatment for osteoarthritis, and they carry a high risk of secondary central adrenal suppression (SAI). We present the case of a 43-year-old woman who was referred to reproductive endocrinology for evaluation of abnormal uterine bleeding with a provisional diagnosis of perimenopause. She reported new-onset type 2 diabetes mellitus, abdominal striae, hot flashes, and irregular menses. Laboratory evaluation revealed iatrogenic Cushing syndrome and SAI attributable to prolonged use of therapeutic IACs for osteoarthritis. Treatment included hydrocortisone replacement and discontinuation of IACs followed by hydrocortisone taper over the following 16 months that resulted in the return of endogenous ovarian and adrenal function. This case demonstrates the many hazards of prolonged IAC use, including suppression of ovarian and adrenal function and iatrogenic SAI. [ABSTRACT FROM AUTHOR]

Purpose: Two-dimensional speckle tracking echocardiography is a novel ultrasound technique, which can detect early subclinical myocardial dysfunction with high sensitivity. The purpose of this study was to explore the value of speckle tracking echocardiography in the evaluation of subclinical myocardial injury in patients with Cushing's syndrome. Methods: 35 patients with Cushing's syndrome and 29 healthy controls matched for age, sex, BMI, and systolic blood pressure were included in the study. All subjects were assessed using both conventional Doppler echocardiography and speckle tracking echocardiography. Among patients, they were further divided into inactive group (n = 7) and active group (n = 28) based on cortisol levels. Trend analysis was used among patients in different disease activity. Correlation analysis and linear regression analysis were used to explore influence factors related to subclinical myocardial dysfunction. Results: Left ventricular ejection fraction value showed no statistical difference between patients Cushing's syndrome and control group. However, GLS and LVSD, show significant differences in Cushing's syndrome group. Also, among active Cushing's syndrome group, inactive Cushing's syndrome group and control group, GLS (−15.4 ± 3.0 vs −18.1 ± 3.1 vs-19.4 ± 2.4, P < 0001) and LVSD (48.9 ± 21.5 vs 43.5 ± 17.9 vs 28.5 ± 8.3, P < 0001) changed significantly with the disease activity status. In addition, GLS and LVSD were both linearly corrected with 24-hour urinary cortisol level. Conclusion: GLS and LVSD are sensitive parameters in detecting and monitoring subclinical myocardial systolic dysfunction in patients with Cushing's syndrome. Myocardial injury is linearly correlated with cortisol level, which can be partially reversed after the biochemical control of cortisol. [ABSTRACT FROM AUTHOR]

Background: While insulin resistance and diabetes shine as the central stars in the constellation of obesity-related conditions, other common endocrine diseases are also closely associated with obesity and high body mass index. Main body: This review aims to illuminate the hormonal imbalances associated with obesity, beyond diabetes. It covers the prevalence, clinical presentation, screening, diagnosis, and treatment of some of these conditions. Conclusion: In obese patients, physicians must pay attention to hormonal disorders that may be associated with obesity. [ABSTRACT FROM AUTHOR]

We present a patient who had surgically confirmed CD but without the full cushingoid phenotype despite markedly elevated cortisol. Nonpathologic causes of elevated ACTH and cortisol were eliminated as were pathogenic variants in the glucocorticoid receptor gene. Further studies of urine metabolites, cortisol half-life, and the ratios of cortisone to cortisol conversion revealed impaired 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. There have only been 2 prior reports of impaired 11β-HSD1 resulting in lack of classic cushingoid features in the past 2 decades. Our patient's presentation and previous reports demonstrate the key role of 11β-HSD1 in modulating intracellular cortisol concentration, therefore shielding the peripheral tissues from the effects of excess cortisol. When patients present with markedly elevated cortisol but without classic cushingoid features, impaired 11β-HSD1 should be considered in the differential diagnosis. [ABSTRACT FROM AUTHOR]

Metabolism is a dynamic network of biochemical reactions that support systemic homeostasis amidst changing nutritional, environmental, and physical activity factors. The circulatory system facilitates metabolite exchange among organs, while the endocrine system finely tunes metabolism through hormone release. Endocrine disorders like obesity, diabetes, and Cushings syndrome disrupt this balance, contributing to systemic inflammation and global health burdens. They accompany metabolic changes on multiple levels from molecular interactions to individual organs to the whole body. Understanding how metabolic fluxes relate to endocrine disorders illuminates the underlying dysregulation. Cancer is increasingly considered a systemic disorder because it not only affects cells in localized tumors but also the whole body, especially in metastasis. In tumorigenesis, cancer-specific mutations and nutrient availability in the tumor microenvironment reprogram cellular metabolism to meet increased energy and biosynthesis needs. Cancer cachexia results in metabolic changes to other organs like muscle, adipose tissue, and liver. This review explores the interplay between the endocrine system and systems-level metabolism in health and disease. We highlight metabolic fluxes in conditions like obesity, diabetes, Cushings syndrome, and cancers. Recent advances in metabolomics, fluxomics, and systems biology promise new insights into dynamic metabolism, offering potential biomarkers, therapeutic targets, and personalized medicine.

Abstract Background While insulin resistance and diabetes shine as the central stars in the constellation of obesity-related conditions, other common endocrine diseases are also closely associated with obesity and high body mass index. Main body This review aims to illuminate the hormonal imbalances associated with obesity, beyond diabetes. It covers the prevalence, clinical presentation, screening, diagnosis, and treatment of some of these conditions. Conclusion In obese patients, physicians must pay attention to hormonal disorders that may be associated with obesity.

Mauriac syndrome (MS) is an exceptionally rare disorder occurring in poorly controlled Type-1 diabetic patients. The consequences include dwarfism, obesity, hepatomegaly, delayed puberty, growth failure and higher levels of transaminase enzyme. We report a case of an adolescent female with classical features of Mauriac syndrome.

Context Adrenocortical carcinomas are very rare malignancies in childhood associated with poor outcome in advanced disease. Most adrenocortical tumors (ACT) are functional, causing signs and symptoms of adrenal hormone excess. In most studies, endocrine manifestations were reported 4 to 6 months prior to diagnosis. Objective We sought to extend knowledge on endocrine manifestations with regard to age and sex to facilitate early diagnosis. Methods We retrospectively analyzed features of adrenal hormone excess in children and adolescents with ACT registered with the GPOH-MET studies between 1997 and 2022. Stage of puberty was defined as prepubertal in females < 8 years of age and males < 9 years. Results By December 2022, 155 patients (110 female, 45 male) with data on endocrine manifestations had been reported. Median age at ACT diagnosis was 4.2 years [0.1-17.8], median interval from first symptoms was 4.2 months [0-90.7]. In 63 girls of prepubertal age, the most frequently reported manifestations were pubarche (68.3%), clitoral hypertrophy (49.2%), and weight gain (31.7%); in 47 pubertal female patients, the most frequent manifestations were excessive pubic hair (46.8%), acne (36.2%), and hypertension (36.2%). Leading symptoms in 34 boys of prepubertal age were pubarche (55.9%), penile growth (47.1%), and acne (32.4%), while in 11 pubertal male patients, leading symptoms were weight gain (45.5%), hypertension (36.4%), excessive pubic hair (27.3%), and cushingoid appearance (27.3%). In pubertal patients, symptoms of androgen excess were mainly unrecognized as part of pubertal development, while symptoms of Cushing syndrome were more frequently apparent. Conclusion The endocrine phenotype induced by pediatric ACT is age- and sex-dependent. [ABSTRACT FROM AUTHOR]

Introduction: Patients with Cushing's syndrome (CS) in remission show sustained fatigue, myopathy, and an increased prevalence of sarcopenia. The mechanisms that determine these persistent muscle problems are not well known. We aimed to identify circulating microRNAs (miRNAs) with differential expression that could be potential biomarkers for the diagnosis and/or prognosis in CS. Patients and methods: Thirty-six women in sustained remission for 13 ± 7 years (mean ± SD) from CS, with a median age (IQ range) of 51 (45.2-60) years and mean ± SD BMI of 27 ± 4 Kg/m², and 36 matched healthy controls were investigated. In 7 patients sarcopenia was present according to the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. Small RNA libraries were generated and indexed using a modified Illumina TruSeq small RNA-sequencing protocol. MiRNAs were identified in plasma using bioinformatic analysis, and validation was carried out using RT-qPCR. For the validation, Taqman probes were performed on QuantStudio 5 equipment (Applied Biosystems). Results: In a first discovery group using RNA-sequencing, plasma samples of 18 CS patients and 18 healthy subjects were investigated; circulating miR-28-5p, miR-495-3p and miR-654-5p were upregulated in CS patients as compared with controls (p<0.05). In a validation study of the 3 upregulated miRNAs in 36 patients and 26 controls, no differences were observed by RT-qPCR; however, the expression of circulating miR-28-5p was upregulated in CS patients with sarcopenia as compared with those without (AUC for fold-change in the ROC analysis, 0.798; p=0.0156). The optimized cut-off value for miR-28-5p to identify CS patients with sarcopenia was 3.80, which yielded a sensitivity of 86% and a specificity of 69%. Conclusion: MiR-28-5p, a muscle-specific microRNA involved in myotube proliferation and differentiation in vivo, may serve as an independent noninvasive biomarker for identifying CS patients at high-risk of sarcopenia despite biochemical remission. [ABSTRACT FROM AUTHOR]

Objective The aim of this study is to assess whether clinical and imaging characteristics are associated with the hormonal subtype, growth, and adrenalectomy for incidental adrenal cortical adenomas (ACAs). Design This is a single-center cohort study. Methods Consecutive adult patients with incidental ACA were diagnosed between 2000 and 2016. Results Of the 1516 patients with incidental ACA (median age 59 years, 62% women), 699 (46%) had nonfunctioning adenomas (NFAs), 482 (31%) had mild autonomous cortisol secretion (MACS), 62 (4%) had primary aldosteronism (PA), 39 (3%) had Cushing syndrome, 18 (1%) had PA and MACS, and 226 (15%) had incomplete work-up. Age, sex, tumor size, and tumor laterality, but not unenhanced computed tomography Hounsfield units (HU), were associated with hormonal subtypes. In a multivariable analysis, ≥1 cm growth was associated with younger age (odds ratio [OR] = 0.8 per 5-year increase, P =.0047) and longer imaging follow-up (OR = 1.2 per year, P <.0001). Adrenalectomy was performed in 355 (23%) patients, including 38% of MACS and 15% of NFA. Adrenalectomy for NFA and MACS was more common in younger patients (OR = 0.79 per 5-year increase, P =.002), larger initial tumor size (OR = 2.3 per 1 cm increase, P <.0001), ≥1 cm growth (OR = 15.3, P <.0001), and higher postdexamethasone cortisol (OR = 6.6 for >5 vs <1.8 μg/dL, P =.002). Conclusions Age, sex, tumor size, and laterality were associated with ACA hormonal subtype and can guide diagnosis and management. Tumor growth was more common with younger age and longer follow-up. Unenhanced HU did not predict hormonal subtype or growth. Adrenalectomy for MACS and NFA was mainly performed in younger patients with larger tumor size, growth, and elevated postdexamethasone cortisol. [ABSTRACT FROM AUTHOR]

Desmopressin is increasingly used for the diagnosis of Cushing disease (CD) since corticotropin-releasing hormone became unavailable. We report the case a 32-year-old man who presented with overt Cushing syndrome. Morning blood cortisol, ACTH, 1 mg dexamethasone suppression test, 24-hour urinary free cortisol, and bedtime salivary cortisol were highly variable, reaching markedly elevated values. Intravenous desmopressin administration produced no ACTH or cortisol increase. Pituitary magnetic resonance imaging, thoracic computed tomography, and DOTATATE positron emission tomography scan identified no lesion. Inferior petrosal sinus sampling (IPSS) with desmopressin stimulation resulted in elevated central-to-peripheral ACTH ratio and prolactin co-secretion, while peripheral ACTH remained stable. No corticotroph tumor was identified on pituitary surgery pathology. Hypercortisolism persisted postoperatively. Cabergoline was initiated, after which the patient rapidly developed transient severe adrenal insufficiency (AI). Bilateral adrenalectomy was performed in view of persistent hypercortisolism. This is an unusual case of petrosal sinus ACTH response to desmopressin without any peripheral response, suggesting a central source of ACTH. Thus, desmopressin should still be used during IPSS in patients with no peripheral response. It is unclear whether the AI episode resulted from a combination of nadir of cyclic hypercortisolism, partial apoplexy, and response to cabergoline of an occult corticotroph tumor. [ABSTRACT FROM AUTHOR]

Context Cushing syndrome (CS) is a severe endocrine disease characterized by excessive secretion of cortisol with multiple metabolic disorders. While gut microbial dysbiosis plays a vital role in metabolic disorders, the role of gut microbiota in CS remains unclear. Objective The objective of this work is to examine the alteration of gut microbiota in patients with CS. Methods We performed shotgun metagenomic sequencing of fecal samples from 78 patients with CS and 78 healthy controls matched for age and body mass index. Furthermore, we verify the cortisol degradation capacity of Ruminococcus gnavus in vitro and identify the potential metabolite by LC-MC/MS. Results We observed significant differences in microbial composition between CS and controls in both sexes, with CS showing reduced Bacteroidetes (Bacteroides vulgatus) and elevated Firmicutes (Erysipelotrichaceae_bacterium_6_1_45) and Proteobacteria (Enterobacter cloacae). Despite distinct causes of hypercortisolism in ACTH-dependent and ACTH-independent CS, we found no significant differences in metabolic profiles or gut microbiota between the 2 subgroups. Furthermore, we identified a group of gut species, including R. gnavus , that were positively correlated with cortisol levels in CS. These bacteria were found to harbor cortisol-degrading desAB genes and were consistently enriched in CS. Moreover, we demonstrated the efficient capacity of R. gnavus to degrade cortisol to 11-oxygenated androgens in vitro. Conclusion This study provides evidence of gut microbial dysbiosis in patients with CS and identifies a group of CS-enriched bacteria capable of degrading cortisol. These findings highlight the potential role of gut microbiota in regulating host steroid hormone levels, and consequently host health. [ABSTRACT FROM AUTHOR]