The interpretation of immunometric, chromatographic and mass spectrometric data for steroids in diagnosis of endocrine disorders.

The analysis of steroids for endocrine disorders is in transition from immunoassay of individual steroids to more specific chromatographic and mass spectrometric methods with simultaneous determination of several steroids. Gas chromatography (GC) and liquid chromatography (LC) coupled with mass spectrometry (MS) offer unrivalled analytical capability for steroid analysis. These specialist techniques were often judged to be valuable only in a research laboratory but this is no longer the case. In a urinary steroid profile up to 30 steroids are identified with concentrations and excretion rates reported in a number of ways. The assays must accommodate the wide range in steroid concentrations in biological fluids from micromolar for dehydroepiandrosterone sulphate (DHEAS) to picomolar for oestradiol and aldosterone. For plasma concentrations, panels of 5-20 steroids are reported. The profile results are complex and interpretation is a real challenge in order to inform clinicians of likely implications. Although artificial intelligence and machine learning will in time generate reports from the analysis this is a way off being adopted into clinical practice. This review offers guidance on current interpretation of the data from steroid determinations in clinical practice. Using this approach more laboratories can use the techniques to answer clinical questions and offer broader interpretation of the results so that the clinician can understand the conclusion for the steroid defect, and can be advised to program further tests if necessary and instigate treatment. The biochemistry is part of the patient workup and a clinician led multidisciplinary team discussion of the results will be required for challenging patients. The laboratory will have to consider cost implications, bearing in mind that staff costs are the highest component. GC-MS and LC-MS/MS analysis of steroids are the choices. Steroid profiling has enormous potential to improve diagnosis of adrenal disorders and should be adopted in more laboratories in favour of the cheap, non-specific immunological methods.

An update on the endocrine manifestations of antiphospholipid syndrome.

Antiphospholipid Syndrome (APS), characterized by hypercoagulability and pregnancy morbidity, poses a significant clinical challenge when involving organ systems, such as the endocrine system. APS can directly and indirectly influence the anterior and posterior lobes of the pituitary gland. The thyroid gland exhibits involvement, especially in patients with positive anticardiolipin antibodies, yet the clinical significance of the relationship with APS remains elusive. The pancreas, often overlooked, manifests in diverse ways, from pancreatitis to implications in diabetes. Adrenal insufficiency emerges as a common endocrine manifestation of APS, with adrenal hemorrhage or infarction being a presenting manifestation. Adrenal gland involvement has also been reported in the context of catastrophic APS. Pregnancy complications and infertility might be effects of APS on the female ovaries, while testicular torsion and decreased sperm concentration and total sperm count have been reported as rare effects of APS on male testes.

Female Reproductive Endocrine Disorders.

This article is a summary of normal menstrual bleeding and how to recognize abnormalities based on patient's symptoms as well as identify possible causes in order to direct treatment. This article discusses abnormal uterine bleeding including the definition, etiology, evaluation, and treatment. It also discusses primary ovarian insufficiency, transgender medicine, and menopause.

Male Reproductive Endocrine Disorders.

The endocrine system intricately regulates male sexual development and health which influences masculinization, sexual libido, muscle mass, bone density, and overall vitality. Disorders in the hypothalamic-pituitary-gonadal axis can lead to hypogonadism, gynecomastia, sexual dysfunction, and infertility. Testosterone replacement therapy can be considered for symptomatic hypogonadism but poses risks for azoospermia and polycythemia, along with uncertain impact on cardiovascular disease. Gynecomastia results from a high estrogen-to-androgen ratio, mostly from either excess estrogen or decreased androgens. Sexual dysfunction is more commonly secondary to psychological or metabolic disorders; consider workups to rule out endocrine etiologies including hypogonadism if indicated.

Endocrine Emergencies.

Endocrine emergencies encompass a group of conditions that occur when hormonal deficiency or excess results in acute presentation. If these endocrine disorders are not rapidly identified or if specific treatment is delayed, significant complications or even death may occur. This article outlines the basics of endocrine emergencies involving the thyroid, parathyroid, pituitary, pancreas, and adrenal glands. It discusses various causative factors, diagnostic approaches, and treatment modalities, emphasizing the significance of preventive measures. This article is aimed at guiding health care professionals, and this overview seeks to enhance understanding and improve patient outcomes in managing endocrine emergencies.

Endocrine Entropy.

This communication defines and describes the novel concept of endocrine entropy. The authors share insights regarding the various facets of entropy in endocrine epidemiology, physiology, clinical presentation and management. The discussion opens up a new way of approaching endocrinology. Recent advances in artificial intelligence, assessment and addressal of entropy may become integral part of endocrine diagnostics and therapeutics.

Endocrine Entropy.

This communication defines and describes the novel concept of endocrine entropy. The authors share insights regarding the various facets of entropy in endocrine epidemiology, physiology, clinical presentation and management. The discussion opens up a new way of approaching endocrinology. Recent advances in artificial intelligence, assessment and addressal of entropy may become integral part of endocrine diagnostics and therapeutics.

Challenges in genetic screening for inherited endocrinopathy affecting the thyroid, parathyroid and adrenal glands in Singapore.

Significant progress has been made in the understand-ing of many human diseases, especially cancers, which has contributed to improved and increased survival. The Human Genome Project and The Cancer Genome Atlas project brought about a new era, with an understanding of inherited diseases at a molecular level, which subsequently facilitated the option of precision medicine. Precision medicine has helped tailor treatment decisions at an individual level, for instance in terms of surgical treatments or targeted therapies in advanced diseases. Despite the increasing advances in genetic-lead precision medicine, this has not translated into increasing uptake among patients. Reasons for this may be potential knowledge gaps among clinicians; on reasons for poor uptake of genetic testing such as for cultural, religious or personal beliefs; and on financial implications such as lack of support from insurance companies. In this review, we look at the current scenario of genetic screening for common inherited endocrine conditions affecting the thyroid, parathyroid and adrenal glands in Singapore, and the implications associated with it.

Immune Checkpoint Inhibitors-Induced Endocrinopathies: Assessment, Management and Monitoring in a Comprehensive Cancer Centre.

OBJECTIVES: To determine the incidence, presentation, frequency and management of immune checkpoint inhibitors (ICI)-related endocrinopathies in a comprehensive cancer centre in Oman, particularly with programme death 1/programme death-ligand 1 (PD-1/PD-L1) inhibitors. BACKGROUND: A high number of patients treated with PD-1/PD-L1 inhibitors for the management of solid tumours developed endocrinopathies. METHODS: This is a retrospective study of patients admitted to Sultan Qaboos Comprehensive Cancer Care and Research Centre (SQCCCRC) from August 2021 to December 2022. All adults diagnosed with solid cancers and have received at least one dose of ICIs were included. Patients with incomplete data were excluded from the analysis. Data regarding the ICI-induced endocrinopathy were collected. RESULTS: A total of 139 patients were included in the study of which 58% were females. The median age of the cohort was 56 years. The incidence of endocrine-related adverse events was 28%. The mean time for the development of endocrine adverse events after treatment initiation was 4.1 ± 2.8 months. Of the patients who developed toxicity, 90% had hypothyroidism. Ten patients developed hyperthyroidism, two patients were diagnosed with secondary adrenal insufficiency/hypophysitis and one patient developed Type 1 diabetes mellitus (DM). Using univariable logistic regression weight and body mass index (BMI) significantly impacted the development of endocrine immune-related adverse events (irAEs). CONCLUSIONS: This is the first study from the Sultanate of Oman to assess PD-1/PDL-1 ICI-induced endocrinopathies. The most common endocrine adverse event is thyroid dysfunction, mainly hypothyroidism followed by hyperthyroidism. Hypophysitis, primary adrenal insufficiency and CIADM occur less frequently, but have a more significant effect on the patient's health. The treating physician should be aware of ICI-induced endocrinopathies, screening and treatment. Furthermore, our study showed that patients with a higher BMI have a greater risk of developing irAES. Further studies are needed to establish the predictors of endocrine irAEs.

Endocrine Fever.

Fever is usually thought to be of an infectious or inflammatory etiology. In this brief communication, we explore the multifaceted connections between fever and endocrine dysfunction. Impaired resistance to infection often leads to fever in conditions like diabetes and Cushing's syndrome. Additionally, several endocrine disorders, including hyperthyroidism, subacute thyroiditis, carcinoid syndrome, and pheochromocytoma, can manifest as fever. Furthermore, fever can be an adverse effect of various endocrine treatments, such as bisphosphonates and antithyroid drugs. We refer to these scenarios as 'endocrine fever.' Increased awareness of these clinical associations can aid in prompt diagnosis and management of these conditions.

Artificial intelligence facial recognition system for diagnosis of endocrine and metabolic syndromes based on a facial image database.

AIM: To build a facial image database and to explore the diagnostic efficacy and influencing factors of the artificial intelligence-based facial recognition (AI-FR) system for multiple endocrine and metabolic syndromes. METHODS: Individuals with multiple endocrine and metabolic syndromes and healthy controls were included from public literature and databases. In this facial image database, facial images and clinical data were collected for each participant and dFRI (disease facial recognition intensity) was calculated to quantify facial complexity of each syndrome. AI-FR diagnosis models were trained for each disease using three algorithms: support vector machine (SVM), principal component analysis k-nearest neighbor (PCA-KNN), and adaptive boosting (AdaBoost). Diagnostic performance was evaluated. Optimal efficacy was achieved as the best index among the three models. Effect factors of AI-FR diagnosis were explored with regression analysis. RESULTS: 462 cases of 10 endocrine and metabolic syndromes and 2310 controls were included into the facial image database. The AI-FR diagnostic models showed diagnostic accuracies of 0.827-0.920 with SVM, 0.766-0.890 with PCA-KNN, and 0.818-0.935 with AdaBoost. Higher dFRI was associated with higher optimal area under the curve (AUC) (P = 0.035). No significant correlation was observed between the sample size of the training set and diagnostic performance. CONCLUSIONS: A multi-ethnic, multi-regional, and multi-disease facial database for 10 endocrine and metabolic syndromes was built. AI-FR models displayed ideal diagnostic performance. dFRI proved associated with the diagnostic performance, suggesting inherent facial features might contribute to the performance of AI-FR models.

Genetic diagnosis of endocrine disorders in Cyprus through the Cyprus Institute of Neurology and Genetics: an ENDO-ERN Reference Center.

The report covers the current and past activities of the department Molecular Genetics-Function and Therapy (MGFT) at the Cyprus Institute of Neurology and Genetics (CING), an affiliated Reference Center for the European Reference Network on Rare Endocrine Conditions (Endo-ERN).The presented data is the outcome of > 15 years long standing collaboration between MGFT and endocrine specialists from the local government hospitals and the private sector. Up-to-date > 2000 genetic tests have been performed for the diagnosis of inherited rare endocrine disorders. The major clinical entities included Congenital Adrenal Hyperplasia (CAH) due to pathogenic variants in CYP21A2 gene and Multiple Endocrine Neoplasia (MEN) type 2 due to pathogenic variants in the RET proto-oncogene. Other rare and novel pathogenic variants in ANOS1, WDR11, FGFR1, RNF216, and CHD7 genes were also found in patients with Congenital Hypogonadotropic Hypogonadism. Interestingly, a few patients with Disorders of Sexual Differentiation (DSD) shared rare pathogenic variants in the SRD5A2, HSD17B3 and HSD3B2 while patients with Glucose and Insulin Homeostasis carried theirs in GCK and HNF1A genes. Lastly, MGFT over the last few years has established an esteemed diagnostic and research program on premature puberty with emphasis on the implication of MKRN3 gene on the onset of the disease and the identification of other prognosis biomarkers.As an Endo-ERN member MGFT department belongs to this large European network and holds the same humanistic ideals which aim toward the improvements of health care for patients with rare endocrine conditions in respect to improved and faster diagnosis.

Occult endocrine disorders newly diagnosed in patients with post-COVID-19 symptoms.

Determination of long COVID requires ruling out alternative diagnoses, but there has been no report on the features of alternative diagnoses. This study was a single-center retrospective study of outpatients who visited our clinic between February 2021 and June 2023 that was carried out to determine the characteristics of alternative diagnoses in patients with post-COVID-19 symptoms. In a total of 731 patients, 50 patients (6.8%) were newly diagnosed with 52 diseases requiring medical intervention, and 16 (32%) of those 50 patients (2.2% of the total) were considered to have priority for treatment of the newly diagnosed disorders over long COVID treatment. The proportion of patients with a new diagnosis increased with advance of age, with 15.7% of the patients aged 60 years or older having a new diagnosis. Endocrine and metabolic diseases and hematological and respiratory diseases were the most common, being detected in eight patients (16%) each. Although 35 of the 52 diseases (67%) were related to their symptoms, endocrine and metabolic diseases were the least associated with specific symptoms. Other disorders that require attention were found especially in elderly patients with symptomatic long COVID. Thus, appropriate assessment and differentiation from alternative diagnoses are necessary for managing long COVID.