Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) mainly afflicting young women. Various steroids can influence the onset and development of the disease or, on the contrary, mitigate its course; however, a systematic review of steroidomic changes in MS patients is lacking. Based on the gas chromatography tandem mass spectrometry (GC-MS/MS) platform and, in the case of estradiol, also using immunoassay, this study performed a comprehensive steroidomic analysis in 25 female MS patients aged 39(32, 49) years compared to 15 female age-matched controls aged 38(31, 46) years. A significant trend towards higher ratios of conjugated steroids to their unconjugated counterparts was found in patients, which is of particular interest in terms of the balance between excitatory and inhibitory steroid modulators of ionotropic receptors. Patients showed altered metabolic pathway to cortisol with decreased conversion of pregnenolone to 17-hydroxypregnenolone and 17-hydroxypregnenolone to 17-hydroxyprogesterone and increased conversion of 17-hydroxypregnenolone to dehydroepiandrosterone (DHEA), resulting in lower levels of 17-hydroxyprogesterone, as well as indications of impaired conversion of 11-deoxy-steroids to 11β-hydroxy-steroids but reduced conversion of cortisol to cortisone. Due to over-activation of hypothalamic-pituitary-adrenal axis (HPAA), however, cortisol and cortisone levels were higher in patients with indications of depleted cortisol synthesizing enzymes. Patients showed lower conversion of DHEA to androstenedione, androstenedione to testosterone, androstenedione to estradiol in the major pathway, and testosterone to estradiol in the minor pathway for estradiol synthesis at increased conversion of androstenedione to testosterone. They also showed lower conversion of immunoprotective Δ5 androstanes to their more potent 7α/β-hydroxy metabolites and had lower circulating allopregnanolone and higher ratio 3β-hydroxy-steroids to their neuroprotective 3α-hydroxy-counterparts.
- MeSH
- Adult MeSH
- Hydrocortisone metabolism blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Gas Chromatography-Mass Spectrometry MeSH
- Multiple Sclerosis * metabolism blood MeSH
- Steroids metabolism MeSH
- Case-Control Studies MeSH
- Tandem Mass Spectrometry MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Cytokines physiology classification MeSH
- Inflammasomes physiology MeSH
- Humans MeSH
- Lipids * biosynthesis physiology classification MeSH
- Receptors, Pattern Recognition classification MeSH
- Hypothalamo-Hypophyseal System physiology MeSH
- Inflammation * physiopathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
V klinické praxi bývá problém odlišit návykovou (habituální či psychogenní) polydipsii od skutečné organicky podmíněné polyurie. Vyšetření první linie: moč chemicky, glykemie – hyperglykemie, glykosurie a ketonurie potvrdí diabetes mellitus. Kalemie a kalcemie – chronická hypokalemie nebo hyperkalcemie vedou ke ztrátě koncentrační schopnosti ledvin. Hladina kreatininu v plazmě a ultrazvukové zobrazení urotraktu – vyloučí renální postižení s možnou ztrátou koncentrační schopnosti. Osmolalita séra a moči z časově co nejbližších vzorků – náhodné zachycení vysoké osmolality moče při normální osmolalitě séra svědčí pro návykovou polydipsii. Hyperosmolární sérum a hypostenurická moč potvrzují diabetes insipidus (DI). Pokud první linie nevede k rozhodnutí, je zapotřebí postupovat v diferenciální diagnostice dále. Vyšetření druhé linie: Test s odnětím tekutin bez podání desmopresinu (DDAVP). Během testu monitorujeme diurézu, hmotnost pacienta, osmolalitu moče z každé porce během testu a první porce moče po jeho ukončení. Frekvence měření osmolality séra během testu závisí na stavu pacienta a sledované diuréze. Klesá-li během testu diuréza a vzrůstá osmolalita moče, blížíme se pravděpodobně k diagnóze psychogenní polydipsie a můžeme snížit frekvenci vyšetřování osmolality séra. Přetrvávající vysoká diuréza hypostenurické moči svědčí pro DI. U kojence s DI mohou i 3 hodiny žíznění vést k hypernatremické dehydrataci! Test ukončíme, je-li splněna jedna z následujících podmínek: 1. známky dehydratace; 2. nezvladatelná žízeň (etický důvod); 3. průkaz dostatečné koncentrační schopnosti ledvin, tj. vysoká osmolalita moče. Obvykle se spokojíme s nálezem osmolality moči > 500 u kojenců, resp. > 600 u batolat a > 750 mOsm/kg u starších dětí. Nenaplní-li se během 12 hodin podmínka pro ukončení testu, je téměř jistá nespolupráce pacienta. Vyšetření třetí linie: Test s odnětím tekutin po podání DDAVP. Slouží k rozlišení mezi centrálním a renálním DI. Použijeme stejný test, ale po podání DDAVP. Snížení diurézy a zvýšení osmolality moči při zachování osmolality séra svědčí pro centrální DI. Vyšetření čtvrté linie: Při centrálním DI provedeme zobrazení CNS pomocí MR, posoudíme ostatní endokrinní funkce osy hypotalamus–hypofýza a doplníme techneciovou scintigrafii skeletu k vyloučení osteolytických ložisek při histiocytóze z Langerhansových buněk. Přesnější diagnostické zařazení renálního DI je možné molekulárně geneticky.
In clinical practice, it is often difficult to distinguish psychogenic (or habitual) polydipsia from true organic polyuria. First-line tests: urine chemistry, glycaemia: hyperglycaemia, glycosuria and ketonuria confirm diabetes mellitus. Kalemia and calcemia: chronic hypokalaemia or hypercalcaemia lead to loss of renal concentrating capacity. Plasma creatinine level and ultrasound imaging of the kidney: exclude renal impairment with possible loss of concentrating capacity. Serum and urine osmolality from samples as close in time as possible: incidental detection of high urine osmolality with normal serum osmolality is indicative of psychogenic polydipsia. Hyperosmolar serum and hypostenuric urine confirm diabetes insipidus (DI). The differential diagnosis needs to proceed further if the first line does not lead to a decision. Second-line test: the fluid withdrawal test without desmopresin (DDAVP) administration. During the test are monitored diuresis, patient weight, urine osmolality of each portion during the test and the first portion of urine after its completion. The frequency of serum osmolality measurements during the test depends on the patient‘s condition and the diuresis being monitored. If diuresis decreases during the test and urine osmolality increases, we are probably approaching a diagnosis of psychogenic polydipsia and can reduce the frequency of serum osmolality testing. Persistent high diuresis of hypostenuric urine is suggestive of DI. In an infant with DI, even 3 hours of thirst can lead to hypernatremic dehydration! Terminate the test if one of the following conditions is met: 1. signs of dehydration; 2. uncontrollable thirst (ethical reason); 3. evidence of sufficient renal concentrating ability i.e. high urine osmolality. Usually we are satisfied with the finding of urine osmolality > 500 in infants and > 600 in toddlers and > 750 mOsm/kg in older children. If the condition for test termination is not met within 12 hours, patient non-cooperation is almost certain. Third-line test: the fluid withdrawal test after DDAVP administration. It is used to differentiate between central and nephrogenic DI. The same test is used but after DDAVP administration. A decrease in diuresis and an increase in urine osmolality while maintaining serum osmolality is indicative of central DI. Fourth-line examinations: in central DI, we perform CNS imaging by MR, assess other endocrine functions of the hypothalamic-pituitary axis, and add technetium skeletal scintigraphy to exclude osteolytic foci in Langerhans cell histiocytosis. A more precise diagnostic classification of nephrogenic DI is possible by molecular genetics.
- Keywords
- test žízněním, návykové pití,
- MeSH
- Diabetes Insipidus * diagnosis MeSH
- Diagnosis, Differential MeSH
- Child MeSH
- Humans MeSH
- Polydipsia * diagnosis MeSH
- Polyuria * diagnosis MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Review MeSH
Microbiota plays a role in shaping the HPA-axis response to psychological stressors. To examine the role of microbiota in response to acute immune stressor, we stimulated the adaptive immune system by anti-CD3 antibody injection and investigated the expression of adrenal steroidogenic enzymes and profiling of plasma corticosteroids and their metabolites in specific pathogen-free (SPF) and germ-free (GF) mice. Using UHPLC-MS/MS, we showed that 4 hours after immune challenge the plasma levels of pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone (CORT), 11-dehydroCORT and their 3α/β-, 5α-, and 20α-reduced metabolites were increased in SPF mice, but in their GF counterparts, only CORT was increased. Neither immune stress nor microbiota changed the mRNA and protein levels of enzymes of adrenal steroidogenesis. In contrast, immune stress resulted in downregulated expression of steroidogenic genes (Star, Cyp11a1, Hsd3b1, Hsd3b6) and upregulated expression of genes of the 3α-hydroxysteroid oxidoreductase pathway (Akr1c21, Dhrs9) in the testes of SPF mice. In the liver, immune stress downregulated the expression of genes encoding enzymes with 3β-hydroxysteroid dehydrogenase (HSD) (Hsd3b2, Hsd3b3, Hsd3b4, Hsd3b5), 3α-HSD (Akr1c14), 20α-HSD (Akr1c6, Hsd17b1, Hsd17b2) and 5α-reductase (Srd5a1) activities, except for Dhrs9, which was upregulated. In the colon, microbiota downregulated Cyp11a1 and modulated the response of Hsd11b1 and Hsd11b2 expression to immune stress. These data underline the role of microbiota in shaping the response to immune stressor. Microbiota modulates the stress-induced increase in C21 steroids, including those that are neuroactive that could play a role in alteration of HPA axis response to stress in GF animals.
- MeSH
- Cholesterol Side-Chain Cleavage Enzyme genetics metabolism MeSH
- Corticosterone metabolism MeSH
- Microbiota * MeSH
- Mice MeSH
- Steroids metabolism MeSH
- Pituitary-Adrenal System metabolism MeSH
- Hypothalamo-Hypophyseal System * metabolism MeSH
- Tandem Mass Spectrometry MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
INTRODUCTION: Regular cocaine use has been associated with hormonal dysfunction including hypogonadism, which can lead to fatigue, reduced stamina, sexual dysfunction, and impaired quality of life. However, cocaine's endocrine effects are largely under-reported in the scientific addiction literature and, in many cases, are not addressed within treatment services. The low profile of these adverse effects might be attributable to a lack of awareness and linkage with cocaine use, such that they are recognized only when an acute/emergency problem arises. METHODS: We assessed endocrine diurnal function (adrenocorticotrophic hormone [ACTH], cortisol, and testosterone) in 26 healthy and 27 cocaine-dependent men and examined changes in hormone levels in response to a single 40 mg dose of the noradrenaline re-uptake inhibitor atomoxetine in a double-blind, placebo-controlled experimental medicine study. RESULTS: When compared with healthy controls, diurnal and atomoxetine-induced changes in ACTH and cortisol showed greater variability in cocaine-dependent men. Interestingly, despite an exaggerated rise in ACTH following atomoxetine, an attenuated cortisol response was observed, and one-third of cocaine-dependent men had subnormal testosterone levels. CONCLUSION: Our findings point to a potential disconnection between the pituitary and adrenal responses in cocaine-dependent men, a higher rate of hypogonadism, and a pressing need for more research into the endocrine effects of cocaine and their clinical implications.
- MeSH
- Adrenocorticotropic Hormone MeSH
- Atomoxetine Hydrochloride pharmacology MeSH
- Hydrocortisone MeSH
- Hypogonadism * MeSH
- Cocaine * MeSH
- Quality of Life MeSH
- Humans MeSH
- Cocaine-Related Disorders * MeSH
- Substance-Related Disorders * MeSH
- Pituitary-Adrenal System MeSH
- Hypothalamo-Hypophyseal System MeSH
- Testosterone MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Randomized Controlled Trial MeSH
- News MeSH
- MeSH
- Leptin * physiology metabolism MeSH
- Humans MeSH
- Menstrual Cycle physiology MeSH
- Hypothalamo-Hypophyseal System MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
OBJECTIVES: Thus far, the diagnosis of insomnia is based on purely clinical criteria. Although a broad range of altered physiological parameters has been identified in insomniacs, the evidence to establish their diagnostic usefulness is very limited. Purpose of this WFSBP Task Force consensus paper is to systematically evaluate a series of biomarkers as potential diagnostic tools for insomnia. METHODS: A newly created grading system was used for assessing the validity of various measurements in establishing the diagnosis of insomnia; these measurements originated from relevant studies selected and reviewed by experts. RESULTS: The measurements with the highest diagnostic performance were those derived from psychometric instruments. Biological measurements which emerged as potentially useful diagnostic instruments were polysomnography-derived cyclic alternating pattern, actigraphy, and BDNF levels, followed by heart rate around sleep onset, deficient melatonin rhythm, and certain neuroimaging patterns (mainly for the activity of frontal and pre-frontal cortex, hippocampus and basal ganglia); yet, these findings need replication, as well as establishment of commonly accepted methodology and diagnostic cut-off points. Routine polysomnography, EEG spectral analysis, heart rate variability, skin conductance, thermoregulation, oxygen consumption, HPA axis, and inflammation indices were not shown to be of satisfactory diagnostic value. CONCLUSIONS: Apart from psychometric instruments which are confirmed to be the gold standard in diagnosing insomnia, six biomarkers emerge as being potentially useful for this purpose.
- MeSH
- Biomarkers MeSH
- Humans MeSH
- Sleep Initiation and Maintenance Disorders * diagnosis MeSH
- Sleep physiology MeSH
- Pituitary-Adrenal System MeSH
- Hypothalamo-Hypophyseal System MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
[Anorexia nervosa from an endocrinologist's point of view]
Mentální anorexie je komplexní psychiatricko-metabolicko-endokrinní onemocnění, které má z psychiatrických onemocnění nejvyšší úmrtnost. Při mentální anorexii dochází k alteraci téměř všech orgánů a systémů. Změny endokrinního systému představují většinou adaptaci organismu na hladovění a po znovunabytí potřebné hmotnosti a tukové hmoty dochází k jejich spontánní úpravě. Ale neplatí to pro všechny změny. Dochází k poruše hypothalamo-hypofyzární osy s projevy hypogonadotropního hypogonadismu a hyperkortizolemie, k rezistenci k růstovému hormonu, poruše tyroidální funkce, hyponatremii a hypooxytocinemii. Může být narušena i produkce antidiuretického hormonu a poměrně brzy lze diagnostikovat poruchu kostního metabolismu, která často přetrvává i po vyléčení mentální anorexie. V poslední době byly popsány i změny ve střevním mikrobiomu, v lipidovém metabolismu, poruchy produkce cytokinů s rozvojem autoimunity a poruchy imunitních funkcí.
Anorexia nervosa is a complex psychiatric-metabolic-endocrine disease that has the highest mortality rate among psychiatric diseases. Almost all organs and systems are altered by this disease. Changes in the endocrine system mostly represent the body‘s adaptation to starvation, and after regaining the necessary weight and fat mass, they are spontaneously adjusted. However, it does not apply to all changes. There is a disorder of the hypothalamic-pituitary axis with manifestations of hypogonadotropic hypogonadism, hypercortisolemia, resistance to growth hormone, thyroid dysfunction, hyponatremia and hypooxytocinemia. The production of antidiuretic hormone can also be altered, and a bone metabolism disorder can be diagnosed relatively early and often persists even after recovering from anorexia nervosa. Recently, changes in the intestinal microbiome, lipid metabolism, cytokine production disorders with the development of autoimmunity, and immune function disorders have also been described.
