Mineralocorticoid Activity Research Articles

Severe Hyperandrogenism in 46,XX Congenital Adrenal Hyperplasia: Molecular Physiopathology, Late Diagnoses, and Personalized Management

Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive endocrine disorders characterized by alteration in adrenal hormonal secretions. The most common form is caused by CYP21A2 mutations that result in 21-hydroxylase deficiency. Clinical features can vary, from salt-wasting forms, characterized by a lack of mineralocorticoid activity with a risk of perinatal-onset adrenal crises, to “simple-virilizing” forms with sufficient aldosterone secretion, up to milder “non-classical” forms, with a variable grade of hyperandrogenism but no severe hormonal deficiencies. During pregnancy, CAH 46,XX fetuses are exposed to elevated androgen levels, leading to a variable grade of virilization and potential central nervous system effects if untreated. These patients are usually (but not always) assigned female at birth, but some cases may be misdiagnosed and assigned male, potentially inducing fertility, gender identity, and sexual behavior issues in adulthood. In these patients, the benefits and risks of a late gender transition should be carefully evaluated. In this paper, we reviewed the literature concerning the most interesting peculiarities of these conditions.

5074 Licorice Root Supplement As A Cause Of Hypokalemic Hypertension

Abstract Disclosure: G. Gill: None. S.M. Harman: None. L.A. Robles: None. A 67-year-old female Veteran presented to an emergency room with a one-day history of high blood pressure, chest tightness, and exertional dyspnea. Her blood pressure was 162/90 mm Hg, pulse regular at 71 BPM, and pain level 5/10. She had a history of hypertension, stable on hydrochlorothiazide alone, hyperlipidemia, anxiety, and depression. Physical exam was benign. EKG revealed normal sinus rhythm at 60 BPM, normal axis, a prolonged QT interval of 510 ms, and no ST changes. Lab evaluation showed a low potassium of 2.4 mEq/L, sodium 145 mEq/L. Other lab measurements (CBC, liver function tests and cardiac enzymes) were within laboratory reference ranges. Medications included topiramate for migraine and over-the-counter supplements for constipation, “thyroid health,” and a topical “testosterone booster” prescribed by a non-allopathic practitioner. Her hypokalemia was attributed to hydrochlorothiazide and topiramate and both were discontinued. She was started on nifedipine for blood pressure control and 40 mEq/day of potassium for hypokalemia. Within 2 weeks of discharge, she presented again with elevated blood pressure and a plasma potassium of 4.0 mMol/L. Further history revealed that her constipation supplement consisted of licorice root (glycyrrhiza glabra) extract 900 mg per capsule, of which she took 3 to 4 capsules daily. The patient was advised to discontinue all supplements. Thyroid function tests were within normal limits. Due to a suspicion of hyperaldosteronism, the ED physician requested an abdominal CT scan which showed a 1 cm, -17.5 Hounsfield unit, right adrenal nodule. Also consistent with hyperaldosteronism, plasma renin activity (PRA) was suppressed at 0.07 ng/mL/hr. However, a serum aldosterone level was less than 1 ng/dL. Her 24-hour urinary metanephrines were normal and a 24-hour urine free cortisol was 31.6 mcg/dL. Morning plasma cortisol was 5.1 mcg/dL. A tentative diagnosis of licorice-induced hyperaldosteronism was made and the patient was treated with a taper of spironolactone. After discontinuing spironolactone, blood pressure was 116/70mmHg and serum potassium was 4.5 mMol/L with a PRA of 0.66 ng/mL/hr and serum aldosterone of <5.0 ng/dL. The syndrome of factitious hyperaldosteronism due to licorice consumption has been well described. The mechanism, inhibition of renal (type 2) 11-beta-hydroxysteroid dehydrogenase by glycyrrhizic acid, allowing cortisol to exercise its considerable mineralocorticoid action, is well understood. Most prior reports have been in patients habitually consuming licorice candy, usually imported, since conventional licorice sold in the U.S. is artificially flavored. Our report illustrates the importance of obtaining a history of use of over-the-counter supplements and assessing their ingredients and the fact that presence of an adrenal nodule and a low PRA does not always indicate endogenous hyperaldosteronism. Presentation: 6/2/2024

9296 A Novel LC-MS/MS Salivary Fludrocortisone Method With Potential for Monitoring in Adrenal Insufficiency Patients

Abstract Disclosure: M. Dolan: None. D. Marshall: None. J. Hawley: None. N. Reisch: None. B.G. Keevil: None. Fludrocortisone (FC) is a fluorinated exogenous mineralocorticoid used to treat conditions associated with adrenal insufficiency including Addison’s disease and classic congenital adrenal hyperplasia (CAH). The mineralocorticoid action of FC allows the drug to compensate for aldosterone deficiency, thus helping to maintain blood pressure and other homeostatic mechanisms. Optimising FC replacement is vital as under-replacement can cause dizziness and hypotension, whereas over-replacement can lead to cardiometabolic disturbances. Treatment in classic CAH patients, who are typically diagnosed as new-borns, is even more complex as the requirement for mineralocorticoid replacement decreases with age. Endocrine Society guidelines recommend that FC monitoring should involve the clinical assessment of symptoms, which can be non-specific, and regular blood pressure measurements. Plasma renin activity (PRA) should be measured if clinical changes occur, aiming towards the upper end of the reference range. The utility of PRA is debated due to methodological issues and the inherent variability of the analyte itself, which may not always represent FC replacement status. Therefore, investigation into alternative biochemical markers of FC replacement is required. Here we aimed to facilitate this by developing an LC-MS/MS method for the measurement of salivary FC. Method: A salivary FC LC-MS/MS assay has been developed and validated for use according to FDA and EMA guidelines. Passive drool samples from 10 clinical trial patients with classic CAH were collected on two separate occasions at select time points throughout the day (0800, 1200, 1600, 2000 and 2300h). In most patients the 0800h sample was taken pre-FC dose. Once in the laboratory the patient samples were extracted and analysed using the FC method to produce a FC concentration day curve. Results: The method analysis time was 2.1 minutes, with a mean recovery of 102% and limit of quantification of 5 pmol/L (2.1 pg/mL). No analytical interference was identified. Analysis of patient samples using the method showed the presence of FC allowing the production of day curves. In most patients, the pre-dose sample contained no FC, with the subsequent samples showing a peak FC concentration corresponding to the Cmax. After this the FC concentration gradually tapered off throughout the remainder of the day. Conclusions: We have developed a novel assay for the measurement of salivary FC, which may allow the calculation of the area under the curve. As an optimal FC dose has yet to be determined this method may facilitate more in-depth pharmacokinetic studies into FC metabolism and blood pressure control. Thereby identifying patients that are fast metabolisers or poor absorbers of the medication, enabling a non-invasive strategy to optimise patient care. Presentation: 6/1/2024

Plasma Renin: A Useful Marker for Mineralocorticoid Adjustment in Patients With Primary Adrenal Insufficiency.

Renin is a marker of blood volume. There is no consensus on the validity of plasma renin measurement for adjusting mineralocorticoid (MC) substitution in patients with primary adrenal insufficiency (PAI). This work aimed to investigate if plasma renin could be used to adjust MC substitution in patients with PAI. A total of 150 patients with at least one measurement of plasma renin followed for PAI at 2 tertiary expert centers between 2008 and 2022 were retrospectively included. As supraphysiological hydrocortisone might have additional MC activity, we integrated the individual hydrocortisone dose to obtain the MC equivalent dose (Eq-MC). Renin less than 20 mIU/L was considered oversubstituted, renin between 20 and 60 mIU/L as correctly substituted, and renin over 60 mIU/L as undersubstituted. The mean dose of fludrocortisone was 82.3 ± 46 μg/day. Plasma renin was abnormal in 56.7% of cases (7 patients oversubstituted and 78 patients undersubstituted). Abnormalities in electrolyte levels were observed in only 12.7% of patients. Plasma renin correlated negatively with sodium (P < .01) and systolic blood pressure (P = .026), and positively with potassium (P < .01). Doses changes in Eq-MC had a statistically significant effect on renin levels (P = .0037), with an increase of MC dose correlating with a decrease in renin level and vice versa; no correlation was observed using electrolytes or blood pressure. Plasma renin correlates with electrolytes and blood pressure. While dose changes significantly alter renin levels, electrolytes and blood pressure do not, suggesting that renin may provide more information about MC replacement therapy than electrolytes and blood pressure.

Late-onset Schmidt's Syndrome Presenting with Severe Hyponatremia: A Case Report.

Schmidt's syndrome (SS) is a subtype of polyglandular autoimmune syndrome type-2 combining autoimmune thyroiditis (AIT) and autoimmune Addison's disease (aAD). It occurs most frequently in young adult females, and aAD is the most common initial manifestation [1]. We present a rare case of SS with late-onset aAD and severe hyponatremia as the first sign. A 73-year-old woman presented to the emergency department (ED) with a 10-day history of vomiting, diarrhea, and altered mental status. Her past medical history was remarkable for AIT and hypokinetic cardiomyopathy. Moreover, she had recently undergone a 2-week course of corticosteroid therapy for vertiginous symptoms, reporting subjective well-being. In ED, she appeared confused and hypotensive. Blood tests revealed a sodium level of 99 mEq/l with normal potassium. Initial treatment with saline infusions were started, followed by ex juvantibus intravenous hydrocortisone awaiting hormone results, which proved consistent with primary adrenal insufficiency (ACTH 1314 pg/ml, cortisol 4.72 ug/dL). Replacement therapy with both hydrocortisone and fludrocortisone was then implemented, with substantial clinical improvement and normalization of sodium levels. However, the patient later developed right heart failure and hypokalemia, which were likely caused by overreplacement and resolved after adjusting the treatment regimen. The final diagnosis of aAD was confirmed by positive adrenal autoantibodies. aAD should be suspected in each case of severe hyponatremia [2], especially in patients with AIT independent of age. Furthermore, caution is needed in managing high-dose glucocorticoids along with fludrocortisone in elderly patients with cardiac disease to limit the risk of excessive mineralocorticoid activity and heart failure [3].

Tratamiento de la insuficiencia suprarrenal

Adrenal insufficiency is an endocrine disorder with a low prevalence, though it can potentially be severe if not treated. Hemodynamic collapse and refractory hypotension characterize an acute adrenal crisis. Treatment must never be delayed while awaiting biochemical results in these cases. Hydrocortisone, the pharmacological name for cortisol, is the drug of choice, as it has greater mineralocorticoid activity than other synthetic glucocorticoids. During an acute crisis, clearly supraphysiological doses should be used together with aggressive fluid replacement until hemodynamic stabilization is achieved. In patients with chronic manifestations, the maintenance dose is 15 to 25mg, accompanied by mineralocorticoid replacement if the origin of the AI is primary. Clinical response is the best indicator of treatment response. Patient education is fundamental and should be aimed at recognizing an acute crisis and how to act in stressful situations in order to prevent them.

#2026 Hypokalemia associated to neuroendocrine carcinoma of the cervix

Abstract Background and Aims Hypokalemia is one of the most common electrolyte disorders seen in clinical practice. Hypokalemia can be caused by decreased intake of potassium, redistribution of potassium (K+) in cells or by excessive gastrointestinal losses or renal losses. In this setting, hypokalemia may also be caused by the paraneoplastic production of ectopic adrenocorticotropic hormone (ACTH) by some tumors. Cancer of the uterine cervix is the fourth common cancer affecting women worldwide and the fourth most common gynecologic cancer in Spain. Neuroendocrine carcinoma of the cervix represents about 2% of all cervical neoplasms. Method We report the case of a 44-year-old Peruvian woman with hypokalemia who was diagnosed with Cushing syndrome secondary to paraneoplastic production of ACTH by neuroendocrine carcinoma of cervix. Results Patient was overweight and affected by uterine myoma and anemia without further investigations. She was admitted to our hospital due to lower back pain, leg swelling and constipation. Blood pressure was normal, chest radiography did not show abnormal findings and ECG showed the U wave. Laboratory tests at admission revealed hypokalemia (2.3 mmol/L), metabolic alkalosis, anemia (hemoglobin 9.5 g/dL), hyperkaliuria (K+ urine/Creatinine urine 70 mmol/g) with an elevated transtubular potassium gradient (TTKG=12) and normal renal function. Laboratory data are presented in Table 1. She developed hypertension in the first day of hospitalization. Renin, aldosterone and cortisol tests was performed. Hypercortisolism was observed and confirmed with 24-hour urinary cortisol excretion. Because of an elevated ACTH (263 pg/mL), pituitary magnetic resonance imaging was performed without lesions. Whole-body computed tomography revealed a cervical mass. PET scan showed pelvic, adrenal, hepatic and local lymphadenopathy activity (see Fig. 1). After the histopathological study, diagnostic of small cell neuroendocrine carcinoma of the cervix was made. Chemotherapy therapy was initiated with cisplatin/etoposide regimen. The patient decide to return to Peru because of the poor prognosis of her illness. At discharge, potassium level was 3 mmol/L despite the treatment with spironolactone, ramipril, losartan and oral potassium chloride (160 mmol). Conclusion Hypokalemia is a common clinical disorder. In some patients it may be caused by an increased mineralocorticoid activity due to ectopic ACTH-secreting tumors. Applying diagnostic algorithms to electrolyte disorders, beyond their simple treatment, can unmask secondary causes and serious diseases.

Isolated hypoaldosteronism is a cause of hypovolemic but not euvolemic hyponatremia.

Hypoaldosteronism is characterized by hyperkalemia, and/or hypovolemic hyponatremia (HH), often accompanied by metabolic acidosis. HH is typical of hypoaldosteronism, whereas euvolemic hyponatremia (EH) is not. The purpose of the current study is to describe the characteristics of hyponatremia in hypoaldosteronism and elucidate whether EH can be considered part of the disease's spectrum. In a hypoaldosteronism cohort, we analyzed the factors associated with hyponatremia, comparing the characteristics of EH and HH and their associated factors. Correlation analyses of mineralocorticoid biomarkers, such as the transtubular potassium gradient (TTKG), the urinary Na+/K+ ratio (UNa+/UK+) with serum, and urinary electrolytes were performed in both types of hyponatremia. Of 112 hypoaldosteronism episodes, 77.7% were ≥65 years old, 44.6% were women, and 80 (71.4%) had hyponatremia. Hyponatremia was negatively associated with the presence of chronic kidney disease, and positively with a hypovolemic state, malnutrition, a prior history of hyponatremia, and glucocorticoid therapy. HH: 61/80 and EH: 19/80 episodes. HH was associated with an age ≥65 years and the use of diuretics, as well as factors related to an aldosterone deficit and/or mineralocorticoid resistance. In HH but not in EH, urinary potassium was correlated with the TTKG, and urinary sodium with both the TTKG and the UNa+/UK+. Both HH and EH can be observed in hypoaldosteronism. However, only the former would be related to insufficient mineralocorticoid activity. Isolated hypoaldosteronism is a poorly understood and underdiagnosed endocrinological disorder, classically recognized only when hyperkalemia is present. The development of hypovolemic hyponatremia, however, is also easily explained by the physiopathology of the disorder. The current study addresses the features of hyponatremia when found in the context of mineralocorticoid insufficiency, and confirms an association between hypovolemic hyponatremia and isolated hypoaldosteronism. Thus, the clinical spectrum of hypoaldosteronism is extended to include hypovolemic hyponatremia as a frequent manifestation of the disorder.

P-08 Ectopic Cushing Syndrome in a patient with small cell lung cancer

Abstract Introduction Ectopic Cushing's syndrome (ECS) is a rare endocrine disorder caused by the autonomous secretion of ACTH from a tumor apart from the hypophysis. ECS is the second most common paraneoplastic syndrome associated with small cell lung cancer (SCLC). Due to the aggressive nature of the syndrome, ECS is difficult to diagnose. Most patients present electrolyte disturbances and muscle weakness rather than the typical clinical features of CS. Clinical Case A 70-year-old female patient hospitalized due to pleural effusion was referred for worsening hyperglycemia. She had no previous history of diabetes mellitus. She had a history of 90 pack-years of smoking and chronic obstructive pulmonary disease. The laboratory results were: fasting plasma glucose 216 mg/dl; creatinine, 0.81 mg/dl; sodium, 138 mmol/l; potassium, 3.1 mmol/l; HbA1c, 8.3%; Arterial blood gas analysis revealed metabolic alkalosis (pH 7.63, HCO3 53.6 meq/L). Due to resistant hypokalemia, the patient was evaluated for CS. The patient's ACTH level was 415.5 pg/ml and cortisol level was 63.44 μg/dl. Table 1 shows the tests perfomed for the diagnosis of CS. Pituitary MRG revealed no pathology. IPSS could not be performed as it is not available at our center. A suspicious mass in the right lung was observed on the thorax CT. The pathology of the cytology sample from the pleural effusion revealed SCLC. A chemotherapy regimen containing cisplatin was initiated. Intravenous potassium and acetazolamide treatment were administered for resistant hypokalemia. However, the patient died one month after diagnosis due to type 2 respiratory failure. Conclusion Ectopic secretion of ACTH accounts for 10–15% of CS. ECS is usually caused by mainly SCLC (45%), thymic carcinoma (15%), bronchial carcinoid (10%) and pancreas islet-cell carcinoma (10%). ECS is reported to occur in 1.6%–4.5% of patients with SCLC. IPSS is the most reliable examination for ECS. For ECS, surgery remains the optimal treatment. Some reports showed that metyrapone, ketoconazole and octreotide are effective but not widely used. In our case, the presence of resistant hypokalemia, metabolic alkalosis, and worsening hyperglycemia with the lack of classic clinical features of CS led us to suspect ECS. ECS has a higher incidence of hypokalemic alkalosis than other causes of Cushing's syndrome (&amp;gt;90% vs. 10%). Excessive amounts of adrenal steroids with the inhibition of the enzyme 11β-hydroxysteroid dehydrogenase may cause this pathology. This enzyme normally converts cortisol to cortisone avoiding the mineralocorticoid action of cortisol. In conclusion, although rare, in cases where conditions such as metabolic alkalosis, resistant hypokalemia, with the absence of classic clinical features of CS, the possibility of ectopic CS should be kept in mind.Table 1.Laboratory results of the patient

Congenital dysfunction of the adrenal cortex on the background of 11β-hydroxylase deficiency

Congenital adrenal dysfunction (CHD) is a variant of hereditary fermentopathies that lead to a violation of the synthesis of cortisol in the adrenal cortex. Late diagnosis of this pathology significantly impairs the quality of life of patients, and in some cases can lead to fatal consequences. The most common form of CHD, occurring in more than 90% of cases, is due to a deficiency of 21-hydroxylase, which is responsible for the synthesis of deoxycorticosterone and 11-deoxycortisol. The prevalence of this form is 1:10,000 to 1:20,000 newborns in the world, in Russia — 1:9500. In second place is the deficiency of 11β-hydroxylase (hypertonic form of HCHD), which affects the synthesis of cortisol. This form of the disease occurs in about 1:100,000 newborns in the world, and in Russia the prevalence of this form is unknown [1].The cause of any form of CHD is mutations in the genes responsible for the synthesis of enzymes or transport proteins involved in the synthesis of cortisol. 11β-hydroxylase is synthesized in the zona fasciculata of the adrenal cortex and is regulated by adrenocorticotropic hormone by a negative feedback mechanism. 11β-hydroxylase deficiency (hypertonic form of HCHD) develops as a result of mutations in the CYP11B gene located on chromosome 8. This mutation blocks the enzymatic conversion of 11-deoxycortisol to cortisol, as well as deoxycorticosterone (DOC) to corticosterone, leading to the accumulation of DOC, which has mineralocorticoid activity. It is the excess of deoxycorticosterone that causes an increase.In 21-hydroxylase deficiency, the clinical picture is primary adrenal insufficiency (deficiency of glucoand mineralocorticoids). The clinical picture of mineralocorticoid deficiency includes salt loss syndrome: arterial hypotension, tachycardia, adynamia, fibrillary muscle twitching, dryness and decreased skin turgor, cyanosis and marbling of the skin. Glucocorticoid deficiency is manifested by muscle weakness, fatigue, hyperpigmentation of the skin. With a deficiency of 11β-hydroxylase, due to an increase in the level of deoxycorticosterone, there is no deficiency of mineralocorticoid activity, on the contrary, against the background of clinical signs of glucocorticoid insufficiency, an increase in blood pressure may be observed. Hyperandrogenism is characteristic of both forms of CHD. Symptoms of hyperandrogenism in females: virilization of the external genitalia, amenorrhea, severe alopecia and hirsutism. In undiagnosed cases of CHD, patients with a female karyotype have a male phenotype.

FRI159 Syndrome of Apparent Mineralocorticoid Excess (AME) from Licorice Tea

Abstract Disclosure: P.C. Lambert: None. We report a patient who had Syndrome of Apparent Mineralocorticoid Excess (AME) from licorice tea. Pt is a 65 y/o man with past medical history of HLD, HTN who presented to clinic for routine follow up. BMP was normal. Six months later patient reported diarrhea, bloating and gas after visiting family. To alleviate symptoms, he tried apple cider vinegar, herbal teas and stopped coffee and caffeinated drinks. His BP was 162/92. BMP showed Na 145, K 3.1, CO 37 and 20 meq of potassium daily was started. Follow up in 5/2020 found persistent elevated BP of 160/102 with elevated BP on home monitor and leg edema. Lisinopril-HCTZ was changed to amlodipine 5 mg. BMP showed Na 146, K 2.2, CO 44. Potassium was increased to 40 meq bid. Two weeks later BP was 160/90. Amlodipine was increased to 10 mg daily. He reported resolution of his edema. BMP showed Na 131, K 3.1, CO 33. At this point, the renin/aldosterone axis was tested with aldosterone &amp;lt;1.0 ng/dL and PRA &amp;lt;0.167 ng/mL/hr. On subsequent discussion it was found pt was taking black licorice tea. After cessation, pt’s BP improved and pt was gradually titrated off potassium supplements and blood pressure meds entirely. Repeat lab testing on 6/2020 found aldosterone 2.4 ng/dL, PRA 0.455 ng/mL/hr, Na 142, K 4.8, CO 31. On return to clinic on 8/2020 BP was 124/72 off medication. His labs were Na 143, K 4.1, CO 30. Syndrome of Apparent Mineralocorticoid Excess (AME) is caused by a deficiency in the 11-beta-hydroxysteroid dehydrogenase enzyme type 2 isoform (11-beta-HSD2). The enzyme converts cortisol to cortisone which cannot bind to the mineralocorticoid receptor. Deficiency of this enzyme will lead to more cortisol binding to the mineralocorticoid receptor which binds just as avidly as aldosterone. This leads to increased mineralocorticoid activity without increased aldosterone. Causes of AME can be genetic or induced by the steroid glycyrrhetinic acid, in licorice, that inhibits 11-beta-HSD2. Licorice candy in the USA generally does not have licorice root. It can be found in many sources including chewing tobacco and flavored chewing gum besides tea. Pt can take as low as 50 g daily of confectionery licorice for two weeks to produce elevated blood pressure. Patients will present with hypokalemia hypertension, metabolic alkalosis, low plasma renin activity and low plasma aldosterone levels. Urinary free cortisone and cortisol levels can assist with diagnosis but as in this case review of history was enough to diagnose and treat the patient. Presentation Date: Friday, June 16, 2023

A Severe Case of Hypokalemic Metabolic Alkalosis: A Quiz

A Severe Case of Hypokalemic Metabolic Alkalosis: A Quiz

Efficacy of topical mineralocorticoids in a rabbit model of ocular inflammation

Objectives: The aim of this study was to determine the efficacy of mineralocorticoids in the treatment of ocular inflammation, whose potential use has not been assessed. Methods: Thirty-five New Zealand albino rabbits were used in the study. Rabbits were divided into five groups. Only one eye was used for experimental purposes and the other eye was used as control. 11-deoxycortisol, deoxycorticosterone acetate, fludrocortisone acetate, aldosterone and 11-deoxycorticosterone were studied in a rabbit model of ocular inflammation. All animals in a group received the same corticosteroid. Paired t-tests and analysis of variance between subjects (ANOVA) were used to evaluate efficacy. Results: The eyes treated with 11-deoxycortisol, deoxycorticosterone acetate, and fludrocortisone acetate had statistically significant lower fluorescence compared to control eyes. 11-deoxycortisol and deoxycorticosterone acetate provided a greater reduction in fluorescence compared to other corticosteroids. Conclusions: Topical use of corticosteroids, especially those with mineralocorticoid activity can decrease ocular inflammation in a rabbit model. Clinical application of topical mineralocorticoids in human ocular inflammation needs to be performed.

Pathophysiology and clinical management of hyperkalemia in chronic kidney disease.

Adaptive increases in kidney and gastrointestinal excretion of K+ help to prevent hyperkalemia in patients with chronic kidney disease (CKD) as long as the glomerular filtration rate (GFR) remains >15-20 mL/min. K+ balance is maintained by increased secretion per functioning nephron, which is mediated by elevated plasma K+ concentration, aldosterone, increased flow rate, and enhanced Na+-K+-ATPase activity. Fecal losses of potassium also increase in CKD. These mechanisms are effective in preventing hyperkalemia if urine output is in excess of 600 mL/day and the GFR exceeds 15 mL/min. Development of hyperkalemia with only mild to moderate reductions in GFR should prompt a search for intrinsic disease of the collecting duct, disturbances in mineralocorticoid activity, and/or decreased delivery of sodium to the distal nephron. The initial approach to treatment is to review the patient's medication profile and whenever possible discontinue drugs that impair kidney K+ excretion. Patients should be educated on sources of K+ in the diet and should be strongly encouraged to avoid the use of K+ containing salt substitutes as well as herbal remedies since herbs may be a hidden source of dietary K+. Effective diuretic therapy and correction of metabolic acidosis are effective strategies to minimize the potential for hyperkalemia. Discontinuation or use of submaximal doses of renin-angiotensin blockers should be discouraged given the cardiovascular protective effect these drugs provide. Potassium binding drugs can be useful to enable use of these drugs and potentially allow liberalization of the diet in CKD patients.

Synthetic glucocorticoids instead of hydrocortisone do not increase mineralocorticoid needs in adult patients with salt wasting congenital adrenal hyperplasia

It has been postulated that in patients with congenital adrenal hyperplasia (CAH) with salt wasting (SW), fludrocortisone needs might be higher in those on synthetic glucocorticoid replacement therapy in comparison to conventional hydrocortisone due to the lower mineralocorticoid activity. Here we report the results of a cross-sectional single center study comparing mineralocorticoid needs between patients taking synthetic glucocorticoids (S-GC) (N = 24) and those on conventional hydrocortisone (HC) (N = 16). We could show that while both groups took comparable HC-equivalent dosages, there was no significant difference in FC dosage (GC: 0.075 mg; IQR 0.05–0.1; HC: 0.1 mg; IQR 0.05–0.1; p = 0.713). Although there was a trend for higher renin levels in the S-GC group (67.1 µU/ml; IQR 40.5–113.9 vs. 40.4 IQR 14.2–73.1; p = 0.066), this failed to reach significance. With regard to blood pressure, those taking S-GC had even significantly elevated mean systolic (125.0 mmHg, IQR 117.5–130.0 vs 116.5 mmHg IQR 111.8–124.8; p = 0.036) and diastolic (78.0 mmHg, IQR 74.3–83.8 vs 74.5mmHG, IQR 69.3–76.0; p = 0.044) during the day. Systolic dipping was however more pronounced in those on GC in comparison to those taking HC (11.3%; IQR 8.7–14.6 vs. 6.4 IQR 3.4–12.7; p = 0.031). In conclusion, we could show in this small, albeit well-balanced cohort that mineralocorticoid dosage does not significantly differ between patients receiving synthetic glucocorticoids or conventional hydrocortisone. Higher blood pressure values despite the tendency for higher renin levels in those on S-GC support the notion that the assessment of MR adequacy should be guided by the clinical picture and blood pressure on a regular basis.

ВАРИАБЕЛЬНОСТЬ СЕРДЕЧНОГО РИТМА И ГИПОФИЗАРНО-НАДПОЧЕЧНИКОВАЯ ФУНКЦИЯ У ПАЦИЕНТОВ С ПСОРИАЗОМ

The study of heart rate variability and the function of the pituitary-adrenal axis was carried out in 91 patients with various forms of psoriasis. The tension of the regulatory systems of the heart rhythm and disorders of the autonomic nervous system observed in conditions of an active orthostatic test were established. Impairment of the autonomic nervous system was associated with high glucocorticoid and mineralocorticoid activity of the adrenal glands. The difference in the heart rate, pituitary and adrenal hormones was revealed in patients with streptococcus-associated psoriasis and psoriasis without streptococcal association.

Оцінка стану ренін-ангіотензин-альдостеронової системи у ранній діагностиці гормонально-активних пухлин кіркового шару наднирників

The purpose of the study was to determine the markers of the state of the renin-angiotensin-aldosterone system in patients with hormonally active tumors of the adrenal cortex layer as predictors of the choice of surgical intervention tactics. Materials and methods. The results of analyzes of clinical and laboratory research of 38 patients with tumors of the adrenal glands in the conditions of the department of endocrine surgery were analyzed. Depending on the type of hormonally active adrenocortical adenoma, all patients were divided into three groups: group I – patients who developed aldosteromas; group II – patients with corticosteromas; group III – patients with corticoaldosteromas. Results and discussion. As a result of research, it was found that the development of hormonally active adrenocortical adenomas in the body is accompanied by an increase in the blood plasma of the concentration of the main adrenal hormones: mineralocorticoid – aldosterone and glucocorticoid – cortisol. These changes are accompanied by dysfunction of the renin-angiotensin-aldosterone system, which is most pronounced in patients with aldosteromas and corticoaldosteromas, which is expressed by an increase in the aldosterone/renin ratio. At the same time, in patients with corticosteromas, as well as with corticoaldosteromas, hormonal imbalance is expressed by an increase in the level of adrenocorticotropic hormone in the blood serum. Hypernatremia and hypokalemia found in patients with corticosteromas may be due to some mineralocorticoid activity of cortisol, which is manifested when it is in excess in the body. In this group of patients, arterial hypertension may also be observed, although it may be less pronounced. Therefore, in order to maintain a normal level of sodium and potassium and prevent an increase in blood pressure, it is necessary to simultaneously determine the concentration of aldosterone, cortisol and renin in the blood, since the functioning of these biologically active substances are closely interconnected. Thus, the determination of the level of aldosterone and cortisol in the blood plasma of patients with hormonally active adrenocortical adenomas serves as a marker for the early diagnosis of the type of hormonally active tumors, the detection of which, along with the study of the renin-angiotensin system and the level of adrenocorticotropic hormone, makes it possible to predict the direction of water-salt exchange in the body Timely establishment of these changes will prevent the risk of developing complications from other organs and systems (cardiovascular, urinary, nervous). Conclusion. It was established that the imbalance of the renin-angiotensin-aldosterone system and the pituitary-adrenal system contributes to the violation of the water-electrolyte balance, which is expressed by hypernatremia and hypokalemia and is most pronounced in patients with a mixed type of adrenocortical adenoma

Challenges in the treatment of late-identified untreated congenital adrenal hyperplasia due to CYP11B1 deficiency: Lessons from a developing country.

Congenital Adrenal Hyperplasia (CAH) due to CYP11B1 is a rare autosomal recessive adrenal disorder that causes a decrease in cortisol production and accumulation of adrenal androgens and steroid precursors with mineralocorticoid activity. Clinical manifestations include cortisol deficiency, ambiguous genitalia in females (differences of sex development (DSD)), and hypertension. Medical treatment recommendations are well defined, consisting of glucocorticoid treatment to substitute glucocorticoid deficiency and consequently normalize adrenal androgen and precursors levels. Current guidelines also emphasize the need for specialized multidisciplinary DSD teams and psychosocial support. In many developing countries, care for DSD patients, especially when caused by an adrenal disease, is challenging due to the lack of infrastructure, knowledge, and medication. The study aims to report the conflicting decision-making process of medical treatment and sex assignment in late-identified CAH patients in developing countries. We describe the clinical and biochemical findings and the psychological assessment of five affected but untreated family members with CAH due to CYP11B1 deficiency. All patients had a 46,XX karyotype, ambiguous genitalia, low cortisol levels, and hypertension. Two identified as males, two as females, and one had undecided gender. The patients were counselled that refusing treatment will lead to infertility and the potential risk of developing Addisonian crisis and severe hypertension. However, all 46,XX CAH males refused treatment with glucocorticoids due to the expected lowering of adrenal androgens as their main source of testosterone. None of the patients developed Addisonian crisis, probably due to some residual cortisol activity and glucocorticoid activity of elevated adrenal steroid precursors. Medical treatment and sex assignment in late-identified 46,XX CAH patients in Indonesia may often depend on local and cultural factors. The management of DSD conditions may have to be individualized and integrated into the psychological and social context of the affected family.

920: METHYLPREDNISOLONE VERSUS DEXAMETHASONE FOR COVID-INDUCED ACUTE RESPIRATORY DISTRESS SYNDROME

Introduction: The COVID-19 pandemic has led to devastating outcomes, especially among patients who progress to Acute Respiratory Distress Syndrome (ARDS). Corticosteroids improve survival and ventilator-free days in hospitalized patients with COVID-19 pneumonia requiring supplemental oxygen therapy. Though currently dexamethasone (DEX) is a first line corticosteroid due to its longer half-life and relative lack of mineralocorticoid activity, it is unclear whether alternate corticosteroids can demonstrate similar benefit. Historically, methylprednisolone (MP) has been the default treatment for pre-COVID ARDS and has shown benefit in severe Community Acquired Pneumonia due to its’ high lung tissue penetration. Given increasing incidence of ARDS observed in severe COVID pneumonia, the goal of our study is to compare efficacy of MP vs DEX in moderate to severe ARDS. Methods: This is a single center, multi-location, retrospective, observational study of 575 adult patients admitted to OSF Hospitals between 02/01/2020 and 03/31/2021 for treatment of confirmed COVID-19 pneumonia and moderate to severe ARDS defined as PaO2:FiO2< 200. Patients were grouped based on steroid regimen into one of three treatment arms: those receiving at least 6 mg of DEX (N=360) or 30 mg of MP (N=136) as single or divided daily dose, or sequential use of both DEX+MP (N=79). Demographic data, symptoms, laboratory values, steroid dosing and clinical outcomes were collected. Results: The three treatment groups were similar in terms of baseline CRP, SAPS scores and procalcitonin levels. There was no difference in 28-day all-cause mortality rate among the three groups. The DEX+MP group demonstrated higher in-hospital mortality rate compared to either DEX or MP alone (60.8% vs 41.7% and 44.1%, respectively, p=0.008). The DEX+MP combination group had longer duration of stay compared to DEX or MP alone (21 days vs 12 and 13 days, respectively, p< 0.001) and spent more days in the ICU (14 days vs 6.5 and 7 days, respectively, p< 0.001). Conclusions: We did not observe 28-day mortality lowering effect across any of the three treatment groups. Dexamethasone was associated with reduced ICU and total hospital length of stay. A prospective, randomized trial comparing DEX and MP is warranted to further investigate potential superiority.

Phytoadaptogen reverses the adverse effects of Naftussya bioactive water on dynamic muscle performance in healthy rats

Background.. Muscular performance is considered one of the attributes of health and non-specific resistance. Phytoadaptogens occupy an important place in the arsenal of means of increasing non-specific resistance and stress resistance. Many years of research of the Truskavetsian Scientific School of Balneology have demonstrated the adaptogenic properties of the main therapeutic factor of the resort, Naftussya bioactive water, as well as ozokerite and mineral baths. However, in contrast to the beneficial effect of the latter on stress resistance and the neuro-endocrine-immune complex, the effect on the physical performance is ambiguous. The purpose of this study is to test the ability of phytocomposition to prevent the adverse actotropic effect of Naftussya bioactive water at rats. Material and methods. The experimentt have been carried out at 42 female rats. Rats of the control group for 7 days loaded through a tube with tap daily water (2 mL once), while the animals of the other groups received according to a similar scheme daily water with the addition of 0,1 mL of Balm; bioactive Naftussya water per se or with the addition of 0,1 mL of Balm. The day after completion the course of water loads in the animal determined the urinary excretion of 17-ketosteroids, assessed the mineralocorticoid activity (MCA) by the urine K/Na ratio as well as the state of neutrophil phagocytosis by the number of absorbed latex particles. Results. It was found that the weekly use of Naftyssya bioactive water reduces the duration of swimming of rats to exhaustion by 30% compared to the daily water control. Addition of phytoadaptogen to Naftyssya softens its negative actotropic effect by up to -9%, and adding Balsam to daily water prolongs the maximum duration of swimming compared to the control by 11%. A positive correlation of the swimming test with 17-KS excretion and water diuresis was revealed, but a negative correlation with MCA, spontaneous diuresis and neutrophils phagocytosis. Conclusion. Phytoadaptogen reverses the adverse effects of Naftussya bioactive water on dynamic muscle performance in healthy rats by mitigating the decrease in the excretion of 17-ketosteroids and increased mineralocorticoid activity.