Improvement of hypertension control and left-ventricular function after cure of primary hyperparathyroidism.

Introduction: Cardiovascular mortality is significantly higher in patients with primary hyperparathyroidism (PHPT) compared to the general population. The role of the renin-angiotensin-aldosterone system (RAAS) as a mediator of cardiovascular pathology in PHPT is unclear, as is the question whether successful parathyroidectomy (PTX) mitigates hypertension (HT), and left-ventricular (LV) dysfunction. Methods: In 45 consecutive, hypercalcemic PHPT patients (91% female, 20 normotensive, mean age 54.6 ± 14.6), laboratory examinations, and 24 h ambulatory blood pressure monitoring (ABPM) were performed before, one and six months after successful PTX, while transthoracic echocardiography (TTE) pre- and six months post-PTX. Results: Both in patients with normotension (NT) and HT, lower calcemia and parathyroid hormone (PTH) as well as higher phosphatemia were observed on follow-up, while B-type natriuretic peptide, aldosterone, plasma renin activity, and aldosterone-to-renin ratios were comparable. Six months post-PTX, only in patients with HT, median 24-hour SBP/DBP decreased by 12/6 mmHg, daytime SBP by 10, and nighttime DBP by 5 mmHg. Improvement in BP was observed in approximately 78% of patients with HT. Six months post-PTX, TTE revealed: 1) decrease in median LV mass index (by 2 g/m2) and end-diastolic dimension (by 3 mm) among patients with HT; 2) normalization of global longitudinal strain in 22% of patients (comparable between those with NT and HT); 3) a mean 12.7% reduction in left-atrium volume index among patients with HT, which underlay normalization of indeterminate diastolic function in 3 out of 6 patients with HT, who exhibited it at baseline (dysfunction persisted in 2). Conclusions: PTX was shown to significantly reduce BP, LV hypertrophy and diastolic dysfunction parameters in PHPT patients with HT, and improve systolic function in all PHPT patients.

Low catestatin as a risk factor for cardiovascular disease - assessment in patients with adrenal incidentalomas.

Background: Catestatin (Cts) is a peptide derived from proteolytic cleavage of chromogranin A, which exhibits cardioprotective and anti-inflammatory properties. Cts has been proposed as a potential biomarker for cardiovascular (CV) disease. Objectives: examining Cts in patients with incidentally discovered adrenocortical adenomas (AI), and its associations with CV risk factors and blood pressure (BP). Materials and methods: In this cross-sectional study, 64 AI patients without overt CV disease other than primary hypertension were recruited along with 24 age-, sex-, and body-mass-index (BMI)-matched controls with normal adrenal morphology. Laboratory, 24-h ambulatory BP monitoring, echocardiography, and common carotid artery sonography examinations were performed. Results: Unadjusted Cts was higher in AI patients (median 6.5, interquartile range: 4.9-37 ng/ml) versus controls (4.5 (3.5 - 28)), p=0.048, however, the difference was insignificant after adjusting for confounding variables. Cts was lower in subjects with metabolic syndrome than in those without it (5.2 (3.9- 6.9) vs. 25.7 (5.8-115) ng/ml, p<0.01), and in men compared to women (4.9 (4-7.4) ng/ml vs. 7 (4.8-100), p=0.015). AI patients in the lower half of Cts levels compared to those in the upper had a higher prevalence of hypertension (OR 0.15, 95% CI: 0.041-0.5, p<0.001) and metabolic syndrome (OR 0.15, 95% CI 0.041-0.5, p<0.001). In AI patients Cts correlated positively with high-density lipoprotein cholesterol (Spearman's r=0.31), negatively with BMI (r=-0.31), and 10-year atherosclerotic CV disease risk (r=-0.42). Conclusions: Our data indicate associations between CV risk factors and Cts. More clinical research is needed to apply serum Cts as a biomarker.

Review of Diagnostic Modalities for Adrenal Incidentaloma.

Adrenal incidentalomas are common findings in clinical practice, with a prevalence of up to 4.2% in radiological studies. Due to the large number of focal lesions in the adrenal glands, it can be challenging to make a definitive diagnosis and determine the appropriate management. The purpose of this review is to present current diagnostic modalities used to preoperatively distinguish between adrenocortical adenoma (ACA) and adrenocortical cancer (ACC). Proper management and diagnosis are crucial in avoiding unnecessary adrenalectomies, which occur in over 40% of cases. A literature analysis was conducted to compare ACA and ACC using imaging studies, hormonal evaluation, pathological workup, and liquid biopsy. Before deciding on surgical treatment, the nature of the tumor can be accurately determined using noncontrast CT imaging combined with tumor size and metabolomics. This approach helps to narrow down the group of patients with adrenal tumors who require surgical treatment due to the suspected malignant nature of the lesion.

The role of selected adipokines in tumorigenesis and metabolic disorders in patients with adrenal tumors.

Recently, more and more attention has been directed to the role of adipose tissue and adipocytokines in the pathogenesis of metabolic and inflammatory disorders in humans. Excess fat tissue has also been associated with a higher risk of malignancies. Advances in the research on the role of adipokines in adrenal tumors may elucidate the relationship between various types of adipose tissue (visceral, subcutaneous, and periadrenal) and metabolic disorders observed in hormonally active adrenal tumors, as well as associations with adrenal cortex cancer. In patients with active or cured Cushing syndrome, increased leptin and resistin concentrations as well as release of pro-inflammatory cytokines can be associated with cardiovascular risk. Also, the renin-angiotensin-aldosterone system in patients with primary hyperaldosteronism may affect the metabolic activity of the adipose tissue. Elevated resistin concentrations in this group of patients are associated with morphological changes of the myocardium independently of the effects of the metabolic syndrome. Further, it has been suggested that hypoadiponectinemia comprises an additional factor in the pathogenesis of carbohydrate metabolism disorders and the risk of cardiovascular complications in pheochromocytoma patients. Understanding the mechanisms of action of adipokines may be important in developing prophylactic and therapeutic strategies in hormonally active and malignant tumors of the adrenal glands.

Metabolic consequences of recombinant human growth hormone therapy in patients with Turner syndrome.

INTRODUCTION: Turner syndrome (TS) predisposes to metabolic complications. Currently, TS patients are treated with recombinant human growth hormone (rGH) as standard therapy. The long-term effect of this therapy on carbohydrate metabolism remains unclear. Aim of the study: To assess possible metabolic alterations following rGH therapy. MATERIAL AND METHODS: Material and methods: We enrolled 53 TS participants, comprising 37 patients who finished rGH therapy (group 1) and 16 patients who did not receive growth promoting therapy (group 2). Several anthropometric measurements were made. Carbohydrate and lipid metabolism, adipokines, and hs-CRP were assessed basing on laboratory test. The following indices were calculated: HOMA-IR, HOMA-b, QUICKI, and Matsuda. RESULTS: There were no statistically significant differences between the 2 groups in terms of BMI or WHR. There was a statistically significant lower mean percentage of fat tissue in group 1 compared to group 2 (27.46% vs. 31.75%). Insulin resistance and sensitivity indices were not statistically different between groups. Using the Matsuda index, more patients who met criteria of insulin resistance were found in group 2 than in group 1 (56.25% vs. 37.84%); however, this difference was not statistically significant (p = 0.2). No statistically significant differences were found in lipid profile, adipokines, and hsCRP between groups. CONCLUSIONS: rGH therapy leads to a beneficial change in body composition of TS patients despite unchanged BMI. A decrease in body fat persists for several years after finishing rGH treatment; rGH treatment is connected with a trend toward increased insulin sensitivity.

Basics of prevention and management of iodine-based contrast media-induced thyroid dysfunction - position paper by the Polish Society of Endocrinology.

Medical practice involves a high number of radiological examinations using iodinated contrast media (ICM). Therefore, it is crucial for doctors of different specialties to be aware of possible adverse effects associated with ICM use. The most common and well characterized adverse effect is contrast-induced nephropathy, whereas thyroidal adverse reactions remain a diagnostic and therapeutic dilemma. ICM-induced thyroid dysfunction represents a highly heterogenous group of thyroid disorders. Due to supraphysiological iodine concentration, ICM can induce both hyper- and hypothyroidism. In most cases, the ICM-induced thyroid dysfunction is oligo- or asymptomatic, mild, and transient. In rare cases, however, the ICM-induced thyroid dysfunction may be severe and life threatening. Recently, the European Thyroid Association (ETA) Guidelines for the Management of Iodine-Based Contrast Media-Induced Thyroid Dysfunction were published. The authors advise an individualized approach to prevention and treatment of ICM-induced thyroid dysfunction, based on patient's age, clinical symptoms, pre-existing thyroid diseases, coexisting morbidities, and iodine intake. There is a geographic variation of ICM-induced thyroid dysfunction prevalence, which is linked to iodine intake. The prevalence of ICM-induced hyperthyroidism, which may pose a serious therapeutic challenge, is greater in countries with iodine deficiency. Poland is a region with a history of iodine deficiency, contributing to an increased prevalence of nodular thyroid disease, especially in the elderly. Therefore, the Polish Society of Endocrinology has proposed national, simplified principles of ICM-induced thyroid dysfunction prevention and treatment.

Autonomous Aldosterone Secretion in Patients with Adrenal Incidentaloma.

In recent years, research has emphasized the significance of mild clinical and biochemical presentations of primary aldosteronism (PA) that do not meet current diagnostic criteria of the syndrome. In this study, we assessed the prevalence of autonomous aldosterone (Ald) secretion (AAS), defined as a positive (>1.2 ng/dL/mIU/L) Ald-to-renin ratio (ADRR) combined with unsuppressed Ald (>4 ng/dL), and its associations with blood pressure (BP), cardiac function, and common carotid artery (CCA) intima-media thickness (IMT) in patients with incidentally discovered adrenal adenomas (AI), who were either normo- or hypertensive but had no other cardiovascular disease. Among 332 AI patients hospitalized between November 2018 and December 2019, 63 study participants were recruited (26 normo- and 37 hypertensive), who underwent hormonal examinations, 24 h ambulatory BP measurement, transthoracic echocardiography, and CCA IMT assessment without altering chronic medications. AAS was found in approximately 25% of subjects (seven normo- and nine hypertensive); urinary aldosterone excretion (UAldE) exceeded 10 ug/day in none of the subjects. The left ventricular mass index correlated positively with UAldE in non-diabetic patients (n = 50), and negatively with renin in those without beta blocker therapy (n = 38). The study shows that a pragmatic approach to hormonal assessment (no chronic therapy modification) may reveal patients with AAS. Screening for this subclinical PA presentation is probably more effective with a permissive ADRR than UAldE in such a setting.

Oncogenic osteomalacia - detection of the tumour site upon physical examination.

Not required for Clinical Vignette.

Prevalence and risk factors of untreated thyroid dysfunctions in the older Caucasian adults: Results of PolSenior 2 survey.

INTRODUCTION: To determine the prevalence of treated and untreated thyroid dysfunction and to identify factors associated with increased risk of undiagnosed thyroid dysfunction in older adults. METHODS: The population of 5987 community-dwelling Polish Caucasian seniors aged 60 years and above who participated in the PolSenior 2 study (2018-2019). Population-based cross-sectional multidisciplinary study in design. Data from structured questionnaires, geriatric tests, and scales were obtained from all study participants who underwent anthropometric and blood pressure measurements during three home visits. Assessment of thyroid function was based on TSH serum measurements. RESULTS: The prevalence of thyroid dysfunction in the Polish population aged 60 years or above was estimated at 15.5% (21.5% in women and 7.2% in men), with 3.2% of undiagnosed individuals among them. The prevalence of hypothyroidism and hyperthyroidism in the studied group was 13.9% (19.4% in women and 6.3% in men) and 1.6% (2.1% in women and 0.9% in men) respectively, untreated hypothyroidism was revealed in 21.9% (in 160 out of 732 subjects) and untreated hyperthyroidism in 34.2% of subjects (in 41 out of 120 participants). In multiple regression analysis independent risk factors for thyroid disorders being untreated were older age (> 75 years), male sex, a low education level (primary or lower), and low utilization of medical services. CONCLUSIONS: One-fifth of Polish Caucasian seniors with hypothyroidism and one-third with hyperthyroidism are untreated. Older, poorly educated and rarely utilizing medical services seniors, especially men, are more frequently untreated for thyroid dysfunction and some of them do not benefit from contemporary achievements in medicine.

Endocrine Autoimmunity in Pregnancy.

Human gestation leads to a number of physiological alterations which peak at the development of placentta known for, among many other functions, being a transient but highly potent endocrine organ. Hormonal activity of placenta is marked by its ability to continuously produce and secrete high levels of progesterone. Progesterone guards the well-being of the fetoplacental unit throughout the gestation and one of the proposed mechanisms of this principle involves the development of local and systemic immune tolerance mainly due to impediment of CD4+ lymphocyte activation. However, though these alterations are present and well-established, autoimmunity is not entirely rare and a wide spectrum of diseases can continue, or develop de novo, throughout the gestation or even after the delivery. Up-to-date data supports the existence of a relationship between the clinical course of chosen autoimmune diseases and levels of circulating sex steroids. The most common autoimmune endocrinopathies in pregnant women are Hashimoto's disease, Graves' disease, and, more rarely, primary adrenal insufficiency in the form of Addison's disease. Gestation can influence the clinical course of these endocrinopathies in patients who were diagnosed before conception. Multiple particles, like TSH-receptor stimulating antibodies, thyroid hormones, glucocorticoids, and anti-thyroid medications, can cross the placental barrier and evoke biological action in fetal tissues. Thyroid pathology in the form of postpartum thyroiditis is particularly prevalent in patients with positive anti-thyroperoxidase and anti-thyroglobulin antibodies. Certain populations are more at risk of developing numerous gestational complications and require regular follow-up. In our paper, we would like to address physiological, physiopathological, and clinical aspects of endocrine autoimmunity throughout human gestation, as well as special circumstances to consider in pregnant women.

Comorbidities in Mild Autonomous Cortisol Secretion - A Clinical Review of Literature.

Mild autonomous cortisol secretion (mACS) is a state of cortisol excess usually associated with existence of adrenal incidentaloma. Because of the lack of symptoms of the disease, the biochemical evaluation is the most important to determine a diagnosis. However, scientific societies have different diagnostic criteria for mACS, which makes the treatment of this disease and using results of original papers in daily practice more difficult. Chronic hypercortisolemic state, even if mild, may lead to diseases that are mostly connected with overt Cushing's syndrome. Some of them can cause a higher mortality of patients with mACS and those problems need to be addressed. In this review we describe the comorbidities associated with mACS: cardiovascular disorders, arterial hypertension, diabetes mellitus, insulin resistance, dyslipidemia, obesity, metabolic syndrome, non-alcoholic fatty liver disease, vertebral fractures and osteoporosis. The point of this paper is to characterise them and determine if and how these conditions should be managed. Two databases - PubMed and Web of Science were searched. Even though the evidence are scarce, this is an attempt to lead clinicians through the problems associated with this enigmatic condition.

Role of Catestatin in the Cardiovascular System and Metabolic Disorders.

Catestatin is a multifunctional peptide that is involved in the regulation of the cardiovascular and immune systems as well as metabolic homeostatis. It mitigates detrimental, excessive activity of the sympathetic nervous system by inhibiting catecholamine secretion. Based on in vitro and in vivo studies, catestatin was shown to reduce adipose tissue, inhibit inflammatory response, prevent macrophage-driven atherosclerosis, and regulate cytokine production and release. Clinical studies indicate that catestatin may influence the processes leading to hypertension, affect the course of coronary artery diseases and heart failure. This review presents up-to-date research on catestatin with a particular emphasis on cardiovascular diseases based on a literature search.

Effect of Glucocorticoid Administration in Intravenous Pulses on Selected Parameters of the Coagulation System.

Background: Changes of the coagulation system are promoted by serious infectious or noninfectious diseases, surgical procedures, and exogenous substances, including drugs. This study aimed to assess the effect of methylprednisolone pulses on selected parameters of the coagulation system. Methods: The study group consisted of patients suffering from multiple sclerosis, thyroid orbitopathy, or sudden sensorineural hearing loss. 48 patients and 20 healthy volunteers were examined. The hemostatic parameters: activity of coagulation factors (VIII, IX, and XI), antithrombin activity, protein C and S activity, and concentration of soluble tissue factor were analyzed at baseline and after 3 g and 5 g of methylprednisolone administration. Results: A statistically significant increase was noted in the activity of all the studied plasma coagulation factors, plasma coagulation inhibitors (except protein S activity), and the concentration of soluble tissue factor after methylprednisolone administration. Conclusion: The glucocorticoids administered in the intravenous pulses of methylprednisolone shift the balance toward thromboembolic complications.

Adrenal Tumors in Young Adults: Case Reports and Literature Review.

The current high detection rate of adrenal tumors (4-10% of general population) is attributable to a widespread use of variety of imaging studies, especially a computed tomography. Most of them represent clinically silent and biologically indolent incidentalomas, but some adrenal tumors may pose a significant clinical challenge. Thus, in every patient with an adrenal tumor, a decision on further management is made after careful hormonal and radiological evaluation. All hormonally active tumors and those with radiological features suggesting malignancy are qualified for surgery. Approximately 80% of adrenal tumors are adrenocortical adenomas, hypertrophy, or nodular adrenocortical hyperplasia. Other histopathological diagnoses include pheochromocytoma, adrenocortical carcinoma, metastases, mesenchymal tumors, lymphomas, cysts, and ganglioneuromas. Adrenal tumors are more commonly diagnosed and better studied in elderly patients. In younger patients, under 40 years old, focal adrenal lesions are relatively rare, and histological distribution of diagnoses differs from that in elderly individuals. Younger patients are more likely to display endocrine symptoms, which raise the suspicion of an adrenal mass. In the current study, we present a case series of seven adrenal tumors occurring in young patients. The cases presented below, along with the literature review, demonstrate that the diagnosis and treatment of adrenal tumors are crucial due to endocrinopathy-derived complications and a potential risk of malignancy.

Incidence of thyroid nodules in early stage autosomal polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. Defect in cilia-mediated signaling activity is a crucial factor leading to cyst formation. Hence, ADPKD is regarded as a systemic disorder with multiple extrarenal complications, including cysts in other organs, for instance, the liver, pancreas, spleen, or ovaries. Interestingly, loss-of-function of primary cilia has been recently found to contribute to a malignant transformation from degenerated thyroid follicles. However, the increased incidence of thyroid nodules in ADPKD patients has not yet been fully confirmed. OBJECTIVES: To determine the incidence of thyroid lesions in patients with ADPKD in comparison to previous population studies. Moreover, we aimed to investigate if the pace of the disease progression is associated with a higher prevalence of thyroid lesions. MATERIAL AND METHODS: In 49 early-stage ADPKD patients recruited from our center, we performed ultrasonography of the thyroid glands, and laboratory evaluation of thyroids function. We compared the results with population studies. RESULTS: Twenty-three individuals had solid, cystic-solid, or cystic lesions revealed in the ultrasonography and 2 patients had a positive past medical history for thyroidectomy due to nodular goiter. In 10 patients out of the 23, only minor cysts with no clinical significance were found and 13 out of the 23 patients had solid or cystic-solid lesions, which occurred to be benign based on three years of follow-up or the biopsy of the nodule. CONCLUSIONS: We found no increased incidence of thyroid gland lesions in early ADPKD patients in comparison to previous population studies. Plausibly, mechanisms other than defective cilia signaling are involved in the risk for focal thyroid lesions formation. Moreover, the rate of progression of kidney function decline seems to be not accompanied by the higher incidence of thyroid pathology.

The Current Role of Parathyroid Fine-Needle Biopsy (P-FNAB) with iPTH-Washout Concentration (iPTH-WC) in Primary Hyperparathyroidism: A Single Center Experience and Literature Review.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is a condition characterized by disorders of calcium-phosphate metabolism and bone metabolism caused by pathological overproduction of parathyroid hormone (PTH). The diagnosis of overt PHPT is based on the presence of clinical symptoms and laboratory abnormalities typical of this condition: hypercalcemia, hypercalciuria and elevated iPTH levels. Imaging studies are not used for diagnostic purposes; they are performed to localize the parathyroid glands prior to potential surgical treatment. Technetium 99 m sestamibi scintigraphy (Tc99 m-MIBI) is the gold standard in the assessment of pathologically altered parathyroid glands. Other diagnostic options include cervical ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). Parathyroid biopsy (P-FNAB) with iPTH washout concentration (iPTH-WC) assessment is still an underestimated method of preoperative parathyroid gland localization. Few studies have reported the utility of US-guided P-FNAB in preoperative assessment of parathyroid lesions. The aim of the study was to present our experience with 143 P-FNAB with iPTH-WC assessment. MATERIAL AND METHODS: Laboratory results, US findings, P-FNAB complications and comparison with other imaging techniques were described and analyzed. RESULTS: In 133 (93.0) patients, iPTH washout-to-serum ratio exceeded threshold level 0.5 and were classified as positive results. Median iPTH-WC in this group was 16,856 pg/mL, and the iPTH-WC to serum iPTH ratio was 158. There was no correlation between iPTH-WC and serum PTH, serum calcium, parathyroid gland volume and shape index. In the group of 46 operated patients, 44 demonstrated positive iPTH-WC results, which corresponds to a sensitivity of 95.6%. In Tc99-MIBI, radiotracer retention was found in 17 cases (in 24 MIBI performed), which corresponds to a sensitivity of 52.2%. P-FNAB did not cause any major side effects -92.5% of all patients had no or mild adverse events after this procedure. CONCLUSIONS: P-FNAB with iPTH-WC is a reliable method in parathyroid adenoma localization during PHPT. Its sensitivity for diagnosis of PHPT is much higher than that of Tc99-MIBI, and in some situations, P-FNAB with iPTH-WC may even replace that method. Furthermore, cost-effectiveness of iPTH-WC is at least similar to that of Tc99-MIBI. Complications of P-FNAB are mild and we can describe this method as a safe procedure.

Autonomous Aldosterone Secretion as a Subclinical Form of Primary Aldosteronism: Pathogenesis and Clinical Significance.

In recent years, a substantial prevalence of primary aldosteronism (PA) has been demonstrated in both normotensive and mildly hypertensive cohorts. Consequently, a classic presentation of the syndrome, i. e. moderate-to-severe and resistant hypertension with concomitant hypokalemia, should be considered a tip-of-the-iceberg phenotype of a wide PA spectrum. Its entire range encompasses the non-classic clinical forms of mild hypertension and prehypertension but also several biochemical presentations, including patients who meet PA screening and confirmation test criteria, as well as those with either of them and those with other parameters indicating mineralocorticoid excess. In the current review, research insights on the pathogenetic background and clinical significance of autonomous aldosterone secretion (AAS) are presented, which is defined as a constellation of either: 1) normotension, normokalemia, a positive PA screening (high aldosterone-to-renin ratio) and/or confirmation test, or 2) hypertension, normokalemia and a positive PA screening but negative confirmation test. For this purpose, a literature search of the PubMed database was conducted. Advances in immunohistochemistry and genetic sequencing of isolated adrenal cells are provided as probable morphologic basis of the wide range of aldosterone secretion autonomy. Also, the role of corticotropin as an aldosterone secretagogue is discussed. To date, clinical studies depict consequences of subclinical PA phenotypes, such as increased mortality and risk of developing hypertension, impaired arterial and kidney function, association with metabolic syndrome and age, as well as osteoporosis.

Safe treatment with somatostatin analogues in a woman with acromegaly whilst pregnant and lactating.

CONTEXT: Pregnancy in acromegaly is rare, there have been few case reports and series published to date. Also breastfeeding under acromegaly treatment is extremely rare. The late diagnosis of pregnancy in acromegaly will sometimes dictate the treatment and management of the patient. MATERIAL AND METHOD: We present a 32-year-old woman with acromegaly, a late diagnosed pregnancy and a completed fetal organogenesis. Due to the gestation time and bothersome headaches accompanying a pituitary macroadenoma, we decided to continue long lasting somatostatin analogues treatment but with increased injection intervals of 6 weeks. We also continued this treatment during 12 months of breastfeeding. RESULTS: Our treatment did not cause any complication of premature birth or any health problems with the newborn baby. The child has since developed normally up to the age of 5. CONCLUSION: The course of acromegaly disease and the time of pregnancy diagnosis may prompt suitable drug and treatment regimes. We administered effective and safe somatostatin analogues treatment during gestation and breastfeeding which was safe for both mother and baby.