Developing clinical reasoning in continuing medical education as a major landmark in achieving success in medical practice

Although primary aldosteronism is considered the most common form of endocrine hypertension, the diagnostic rate of primary aldosteronism in the territory is unknown. The aims of the current study were to compare the number of patients discharged with International Classification of Diseases 9 Clinical Modification codes compatible with primary aldosteronism from all the hospitals in Emilia-Romagna during 16 years (from 2000 to 2015) with the number of expected cases of primary aldosteronism, and to compare the number of patients with primary aldosteronism who underwent adrenalectomy in the period 2000-2015 with the number of expected cases of unilateral primary aldosteronism. We accessed the Database of the Emilia-Romagna Health Service to select all patients from the age of 20 years discharged with International Classification of Diseases 9 Clinical Modification codes compatible with primary aldosteronism and, among them, those who underwent adrenalectomy in the same period. The prevalence of hypertension in Emilia-Romagna from the age of 20 years was drawn from the Health Search Database. The population from the age of 20 years in Emilia-Romagna has been drawn from the Italian National Statistical Institute. We hypothesized a prevalence of primary aldosteronism of 5% among hypertensive patients and a prevalence of unilateral subtypes of 30% among the primary aldosteronism patients. A total of 992 patients have been discharged with codes consistent with primary aldosteronism during 16 years in Emilia-Romagna, that is 1.9% of the expected cases of primary aldosteronism. A total of 160 of them underwent adrenalectomy in the same period, which corresponds to 1% of the expected cases of unilateral primary aldosteronism in Emilia-Romagna. Our results clearly indicate that primary aldosteronism is dramatically underdiagnosed and undertreated.

Comparison of steroidogenesis in adrenal tissue and adrenal adenoma from a case of primary aldosteronism

Urinary citrate output was studied in 5 cases of primary aldosteronism, in 3 of Addison's disease and in 8 of normal subjects. The urinary citrate output was decreased in 4 of 5 cases of primary aldosteronism, and the citrate output could not be normalized by removal of adrenocortical adenoma. In patients with primary aldosteronism citrate excretion was somewhat increased by admini-stration of potassium chloride, but rather decreased by spironolactone. In these patients urinary citrate output could not be correlated with either plasma CO2 content or plasma potassium concentration. The low urinary citrate excretion in primary aldosteronism may not be satisfactorily explained either by direct action of aldosterone on the kidney or by intracellular acidosis.

IN THE great majority of the reported cases of primary aldosteronism, the diagnosis has been suggested by finding abnormal serum electrolytes in a hypertensive patient. Recently, Conn and his associates have shown that some cases of primary aldosteronism do not evidence the classic abnormality of serum electrolytes.¹ At this time, patients with primary aldosteronism with normal electrolytes may be suspected by the demonstration of suppressed plasma rennin activity in conjunction with increased aldosterone production.²The determination of plasma rennin activity is a highly specialized laboratory technique as is the determination of the aldosterone production rate. Both of these techniques can be performed in a very limited number of research laboratories at this time. The determination of urinary aldosterone in itself is a rather specialized laboratory procedure. Elevated levels are not specific for primary aldosteronism and some cases of primary aldosteronism have had normal urinary aldosterone levels.^3,4 We will present studies

Introduction. The professional culture and competence of future military doctor encompasses professional, general-cultural, ethical values and is of great practical importance.Purpose. To analyze the scientific sources and publications of NATO and Western European scientists on the formation of the professional culture and competencies of future military doctors at NATO medical universities. The article reveals which areas of the professional culture of NATO military doctors are common and what are the differences.Research methods. Methods of theoretical, empirical analysis scientific literature, publications, comparison, classification, generalization and systematization of the material were used to solve the problems of the research.Results. The article covers aspects of the training of future military doctors at NATO and Northern European institutions of higher education. The example of the USA, Great Britain, Germany and Nordic countries shows the scientific experience and experience of forming the professional culture and competence of doctors. The pedagogical features of the process of educational and training of future military doctors are highlighted, with emphasis on the criteria of improving their professional competence and culture. The results of recent scientific studies of the North Atlantic countries in the field of the study of the professional culture and ethics of physicians in the course of their education and medical practice have been shown quite deeply.Scientific novelty and practical significance of research results. An attempt was made to show and analyze the amount of scientific work in NATO Western Europe on the formation of professional culture and ethics of the military doctor, his professional competence in the face of today`s global challenges related to the increasing military threats, increasing migration processes. The novelty of the study is the display analytical material based on the results and conclusions of studies on professional culture and competence, especially in countries such as United States and North European countries.It summarizes the similarity of experience, methodologies and approaches acquired in NATO`s medical universities in ethical education, professional competence, and highlights the existing differences. The author emphasizes the need to constantly study the experience of the countries the North Atlantic Alliance in matters of competence formation and professional culture of military doctors, taking into account the course of Ukraine on joining NATO. What is also important is that the process of reforming the military-medical service of the Armed Forces of Ukraine is continuing, and the work on achieving the goals of NATO partnerships and standards is increasing, which requires comprehensive scientific justification and recommendations in solving the set tasks.Conclusions and prospects for future research. Scientific research at NATO and Western Europe show that the growth of the professional culture and competence of future military doctors greatly improves the quality of provided medical care in the countries where doctors are trained, and enables them to perform peacefully peacekeeping missions.The experience of NATO countries in the training of military doctors is of practical importance for Ukraine, in view of the continuation of Russian – Ukrainian war in the eastern Ukraine, which required not only a sufficient number of highly qualified military doctors, but also the acquisition of appropriate professional competence and professional culture. Continuation of research on the enhancement of the professional culture and competence of military physicians is time consuming.Conclusions on the results of future research on the formation of professional culture in the processes of training future military doctors for the Armed Forces of Ukraine are of practical importance for the optimization of the educational process, the use in the daily work of doctors in part and medical institution of the Armed Forces and other security forces of Ukraine.

In most cases of primary aldosteronism (PA), An adrenal aldosterone-secreting tumor cannot be reasonably proven, so these patients undergo medical treatment. Controversial data exist about the evolution of PA after medical therapy: long-term treatment with mineralocorticoid antagonists has been reported to normalize aldosterone levels but other authors failed to find remission of mineralocorticoid hypersecretion. Thus, we planned to retest aldosterone secretion in patients with medically treated PA diagnosed at least 3 years before. Retrospective, cross-sectional study. The same workup for PA as at diagnosis (basal aldosterone to renin activity ratio (ARR) and aldosterone suppression test) was performed after stopping interfering drugs and low-salt diet, in 34 subjects with PA diagnosed between 3 and 15 years earlier, by case finding from subgroups of hypertensive patients at high risk for PA. Criteria for persistence of PA were the same as at diagnosis (ARR (pg/ml per ng per ml per h) >400, aldosterone >150 pg/ml basally, and >100 pg/ml after saline infusion) or less restrictive. PA was not confirmed in 26 (76%) of the patients and also not in 20 (59%) using the least restrictive criteria suggested by international guidelines. Unconfirmed PA was positively associated with female sex, higher potassium levels, longer duration of hypertension, and follow-up, but not with adrenal mass, aldosterone levels at diagnosis, and treatment with mineralocorticoid antagonists. This study suggests that mineralocorticoid hyperfunction in patients with PA after medical treatment may decline spontaneously. Higher potassium concentration and duration of treatment seem to increase the probability of this event.

Primary aldosteronism usually shows mild hypertension and is characterized by suppression of plasma renin activity (PRA) and elevation of plasma aldosterone concentration (PAC). Almost all previously reported cases of malignant hypertension associated with primary aldosteronism showed low PRA.3)-6) However, only I case which showed high PRA was reported by Baglin et al in 1973.2) The patient reported below is the second case of primary aldosteronism with high PRA.A 34-year-old man was admitted to our clinic because of severe hypertension, renal insufficiency, and papilledema. Both PRA and PAC were abnormally high, 4.6ng/ml/hr and 23.0ng/100ml, respectively. Serum cortisol levels and urinary catecholamine excretion were within normal ranges. Serum K was normal ranging from 3.6 to 4.9mEq/L. In spite of strong anti-hypertensive drugs, peritoneal, and hemodialysis, the patient died of pulmonaly infection about 3 months later.Postmortem examination revealed a right adrenocortical tumor of 8mm in diameter. Histologically, the tumor consisted of large clear cells; that was adenomatous hyperplasia characteristic in primary aldosteronism. Neither juxtaglomerular tumor nor renal artery stenosis was found.We thought that PRA in primary aldosteronism could rise with progress of renal involvement as secondary changes due to long-standing and untreated hypertension. Normal serum K could be explained by the fact that retention of potassium due to severely disturbed renal function exceeded its loss through aldosterone action. It must be kept in mind that normokalemia and elevated PRA can be encountered under these circumstances.

Eleven patients with primary aldosteronism (PA) and 7 patients with essential hypertension were hospitalized, and blood samples were collected every 4 hours for measurement of plasma aldosterone concentration (PAC), plasma renin activity (PRA) and plasma cortisol concentration. A total of 6 mg of dexamethasone was administered for 2 days and blood samples were drawn. In 6 cases of primary aldosteronism, spironolactone was administered for more than 3 months, and the examination was repeated. The hormonal circadian rhythms were analyzed by the Cosinor method.PAC in PA was high in mesor (420.2 ± 127.7pg/ml) with a significant rhythm (p <0.05); the acrophase was 6 : 15 (clock time). Dexamethasone slightly decreased the mesor, while PAC circadian rhythm was observed. PRA was suppressed in patients with PA, and had a significant circadian rhythm only before dexamethasone administration.PAC in essential hypertension showed a significant circadian rhythm (p <0.05); the acrophase was 5 : 44 (clock time). The rhythm was also observed after dexamethasone administration. No circadian rhythm of PRA was observed in essential hypertension.Following long term spironolactone treatment, PAC in PA was observed to still be high and showed an apparent circadian rhythm identical to that observed before spironolactone treatment. ACTH suppression with dexamethasone caused a forward shift in the acrophase (p <0.05). Spironolactone treatment increased PRA but its circadian rhythm was not observed.These results suggest that the renin-angiotensin-aldosterone system play no role in regulation of the circadian rhythm of PAC in PA with long term spironolactone treatment. ACTH seemed to participate in phase shifts of the circadian rhythm of PAC.

The mechanisms inducing steroidogenesis in primary aldosteronism (PA) remain poorly defined. It was recently demonstrated that some G-protein-coupled receptors are abnormally expressed in aldosterone-producing adenomas (APA). We evaluated the potential role of LH and GNRH receptors (LHR (or LHCGR) and GNRHR) in regulating aldosterone secretion in a patient with APA arising during pregnancy (index case) and in a subset of other patients with PA. GNRH test was performed in the index case, 11 other PA, and 5 controls. GNRHR and LHR expressions were examined in 23 APA and 6 normal tissues. Aldosterone response increased significantly (114%) in the index case after GNRH test was performed preoperatively, while it was blunted after adrenalectomy. Aldosterone also increased after human chorionic gonadotropin and triptorelin stimulation. A partial aldosterone response to GNRH was observed in other 7/11 PA, while a significant response was observed in two patients. Controls did not respond to GNRH test. GNRHR was overexpressed and LHR expression was moderate in the APA tissue from the index case. Moreover, LHR was found in normal adrenals and overexpressed in 6/22 APA. GNRHR was overexpressed in 6/22 APA, 2 of them with a 95- and 109-fold higher expression than normal. A correlation between the clinical and molecular findings was observed in five out of seven patients. We describe a case of PA diagnosed during pregnancy, which appeared to correlate with aberrant LHR and GNRHR expression. Our findings suggest that a subset of patients with PA has aberrant LHR and GNRHR expression, which could modulate aldosterone secretion.

The problem of diagnosing primary hyperaldosteronism remains relevant. A rare manifestation of primary hyperaldosteronism is secondary hypokalemic myoplegia, which may be the initial manifestation and cause difficulties in diagnosing primary hyperaldosteronism. It is expedient to describe new cases of primary hyperaldosteronism with an analysis of clinical features, possible diagnostic errors and difficulties. A clinical case of a patient with hypokalemic myopathic syndrome is presented. The level of potassium, aldosterone, renin in blood plasma was studied, and the aldosterone-renin ratio was determined. Adrenal adenoma was con-firmed by multispiral computed tomography and histology. Clinical observation demonstrates differential diagnostic difficulties of primary hyperaldosteronism, which were associated with a variety of clinical manifestations, nonspecificity of symptoms, dependence on the presence of hypokalemia, and erroneous diagnoses in anamnesis. Attention is drawn to the longterm normocaliemic course of primary hyperaldosteronism with arterial hypertension, which was regarded as a hypertensive disease. Primary hyperaldosteronism was suspected when myopathic syndrome appeared and dominated the clinical picture of the disease. Primary hyperaldosteronism, determining the occurrence of secondary hypokalemic myoplegia, presents significant differential diagnostic difficulties and requires physicians to be aware of the features of the clinical manifestations of primary hyperaldosteronism, alertness to the adrenal tumor, adequate assessment of the clinical picture, the use of a modern complex of diagnostic tools, internosological diagnostics and a multidisciplinary approach to therapy.

Disclosure: U.D. Gupta: None. M. Al-Ghuraibawi: None. R. Abdulhussein: None. K. Panigrahi: None. Z. Deribe: None. Distinguishing between the various subtypes of primary hyperaldosteronism (PHA) poses a clinical challenge. Nevertheless, it is notable that primary hyperaldosteronism is a prominent contributor to secondary hypertension, accounting for less than 1% of cases. The triad of hypertension, hypokalemia, and metabolic alkalosis demands screening for PHA. While bilateral adrenal hyperplasia and aldosterone-producing adenomas (APA) are common, rarer forms like unilateral adrenal hyperplasia and glucocorticoid-responsive aldosteronism can also occur. In our case, a 61-year-old patient has been diagnosed and treated for primary hyperaldosteronism for last 10-years. Presently, the patient is undergoing management for blood pressure with a medication regimen comprising Amiloride, Nifedipine, Minoxidil, Atenolol, and Eplerenone over the past decade. No abnormal findings were observed in the computed tomography or magnetic resonance imaging of the adrenal gland, and adrenal venous sampling test results were non-conclusive. The patient has exhibited favorable outcomes with medications, also subsequent imaging has not revealed the presence of an adrenal mass. This case is presented as unique due to its atypical presentation, characterized by the absence of anatomical lesions in the adrenal gland and non-conclusive sampling test results. Nevertheless, the patient responded positively to treatment, supported by the diagnostic significance of preliminary lab tests for primary hyperaldosteronism (aldosterone level: 20.5; plasma renin activity: 0.19, initially aldosterone levels were 17 and 7 before and after saline infusion). Notably, literature acknowledges that the aldosterone-producing adenomas (APAs) can be very small, sometimes &amp;lt;3 mm in diameter, and lesions &amp;lt;1 cm may be overlooked on CT scans. The limitation of adrenal venous sampling (AVS) is the challenge in obtaining good sample due to technical difficulties and variations in local expertise, success rates in AVS may vary. This case exemplifies the diagnostic complexities encountered in primary hyperaldosteronism cases, where imaging and adrenal venous sampling, though frequently recommended, may pose challenges. In conclusion, we share insights from this case and its treatment outcome. Clinically, a thorough assessment of symptoms, along with laboratory results, is crucial for diagnosis and treatment and further categorization may be challenging without imaging and adrenal venous sampling. Presentation: 6/3/2024

A 56-year-old man with primary aldosteronism and chronic renal failure undergoing hemodialysis is described. He complained of numbness of the extremities and showed persistent hypopotassemia in spite of anuria. In the endocrinological examination, a very high plasma aldosterone concentration was observed, while plasma renin activity was within the normal range. From the abdominal Computed Tomography (CT), adrenal scintigraphy, and segmental venous sampling data, he was diagnosed as primary aldosteronism due to left adrenocortical adenoma. In this case, hypopotassemia could not be explained by potassium loss through the kidneys, which suggests potassium excretion in the gastrointestinal tract as the mechanism of hypopotassemia. This was clearly shown from a potassium-balance study and the results of spironolactone administration. Our report is on the first case showing hypopotassemia due to primary aldosteronism in spite of anuria. If a patient treated with maintenance dialysis should have persistent hypopotassemia, as in the present report, it is necessary to consider an association with primary aldosteronism.

Objectives: Primary aldosteronism is sometimes complicated with hyperparathyroidism, which can be classified into secondary hyperparathyroidism due to increased urinary calcium excretion. Low calcium intake has been reported to be a risk of primary hyperparathyroidism, however, it is unclear whether primary aldosteronism is causally related to the occurrence of primary hyperparathyroidism. Herein, we report an interesting case of primary aldosteronism complicated with primary hyperparathyroidism. Methods: This is a case report. Results: A 58-year-old woman, who had a history of parathyroidectomy for primary hyperparathyroidism due to parathyroid adenoma at the age of 43, was admitted for 20-years history of hypertension without remarkable family histories including hypertension. Her hypertension had been gradually worsening and was not improved by the parathyroidectomy. The laboratory findings were as follows: creatinine, 0.61 mg/dL; potassium, 4.0 mEq/L; corrected alcium, 8.9 mg/dL; plasma aldosterone concentration, 156 pg/mL; plasma renin activity, < 0.1 ng/mL/h; intact PTH, 73 pg/mL. Confirmatory tests and adrenal venous sampling revealed idiopathic hyperaldosteronism. Conclusion: We presented a case of primary aldosteronism, who experienced primary hyperparathyroidism. Her hyperaldosteronism might have contributed to the development of primary hyperparathyroidism through high urinary calcium excretion. We may need to carefully consider a possible complication of not only secondary but also primary hyperparathyroidism in patients with primary aldosteronism.

Unilateral multiple adrenocortical micronodules (UMNs) constitute a rare subset of primary aldosteronism (PA) characterized by the hypersecretion of aldosterone derived from multiple small nodules in the zona glomerulosa of the unilateral adrenal grand. This case study describes a 49-year-old man with PA and UMNs who presented with muscle cramps at rest due to hypokalemia. The patient had a 6-year history of hypertension treated with antihypertensive drugs. Imaging studies revealed bilateral adrenal nodules as large as 5 mm. Adrenal venous sampling confirmed unilateral PA; therefore, the patient underwent the removal of the affected adrenal gland. Macroscopically, the removed adrenal gland exhibited irregular adrenocortical thickening accompanied by ill-defined, adrenocortical macronodules as large as 6 mm. The zona glomerulosa was histologically hyperplastic. However, an immunohistochemistry test of the steroidogenic enzymes revealed that these macronodules and the hyperplastic glomerular layer tested negative for CYB11B2. Moreover, we observed adrenocortical micronodules as large as 0.5 mm that tested immunohistochemically positive for CYP11B2 and HSD3B2 but negative for CYP17A1 and CYP11B1. Thus, UMNs were diagnosed. This case instructively indicates that a grossly or histologically detectable nodular lesion is not necessarily a culprit lesion for PA. Therefore, functional histopathology is indispensable for the correct subclassification of PA.

SummaryA 43-year-old Japanese woman was admitted to our hospital with weakness. Laboratory findings showed hypokalemia, hypocalcemia and elevation of the serum creatinine phosphokinase levels, but intact parathyroid hormone levels. Further evaluations suggested that she had primary aldosteronism (PA), secondary hyperparathyroidism and bilateral adrenal tumors. She was treated successfully by laparoscopic right adrenalectomy. This case not only serves to the diagnosis of bilateral adrenal tumors in which selective adrenal venous sampling (SAVS) proved to be useful, but also for physicians to be aware of secondary hyperparathyroidism and the risk of secondary osteoporosis caused by PA.Learning pointsThe classic presenting signs of PA are hypertension and hypokalemia.Hypokalemia can induce rhabdomyolysis.PA causes secondary hyperparathyroidism.Patients with PA have the risk of osteoporosis with secondary hyperparathyroidism.SAVS is useful in bilateral adrenal tumors.