Diagnosis and therapeutic approach to bone health in patients with hypopituitarism.

The results of many studies in recent years indicate a significant impact of pituitary function on bone health. The proper function of the pituitary gland has a significant impact on the growth of the skeleton and the appearance of sexual dimorphism. It is also responsible for achieving peak bone mass, which protects against the development of osteoporosis and fractures later in life. It is also liable for the proper remodeling of the skeleton, which is a physiological mechanism managing the proper mechanical resistance of bones and the possibility of its regeneration after injuries. Pituitary diseases causing hypofunction and deficiency of tropic hormones, and thus deficiency of key hormones of effector organs, have a negative impact on the skeleton, resulting in reduced bone mass and susceptibility to pathological fractures. The early appearance of pituitary dysfunction, i.e. in the pre-pubertal period, is responsible for failure to achieve peak bone mass, and thus the risk of developing osteoporosis in later years. This argues for the need for a thorough assessment of patients with hypopituitarism, not only in terms of metabolic disorders, but also in terms of bone disorders. Early and properly performed treatment may prevent patients from developing the bone complications that are so common in this pathology. The aim of this review is to discuss the physiological, pathophysiological, and clinical insights of bone involvement in pituitary disease.

Challenges in the diagnosis of pheochromocytoma and paraganglioma syndrome.

OBJECTIVES: Adrenal pheochromocytomas are rare neuroendocrine tumours, however their prevalence is probably underestimated - in some series 50% were diagnosed at autopsy. The clinical presentation varies among patients, that is why diagnosis might be difficult to establish. Pheochromocytoma may coexist with paraganglioma and when paraganglioma is diagnosed, the patient should be screened for pheochromocytoma too, especially in people with hypertension. We present a case of woman with pheochromocytoma, but diagnosed after incidence of stroke, who had also paraganglioma in the past. Additionally, a teratoma was diagnosed simultaneously. CASE REPORT: 49-year old woman with hypertension was referred to the Department of Endocrinology, Diabetology and Isotope Therapy in Wroclaw with suspected pheochromocytoma. She was operated twice because of paraganglioma of the right and left carotid artery, second operation was complicated with stroke. After administration of anticoagulants a bleeding from gastrointestinal tract occurred. During diagnostic process CT of the abdomen showed tumour in the right adrenal gland and a tumour in pelvis. Significantly elevated catecholamines and their metabolites in blood and urine confirmed the diagnosis of pheochromocytoma. Both tumours were removed surgically, the second was teratoma maturum. Genetic screening for hereditary pheochromocytoma was proceeded. A mutation in SDHD gene was revealed in patient's DNA and subsequently in blood samples of her sister and daughter. CONCLUSIONS: Occurrence of paraganglioma with hypertension suggest need of screening for pheochromocytoma-paraganglioma syndrome, especially in case of paragangliomas in family history. Early treatment is crucial to avoid life-threatening cardiovascular complications. The association between pheochromocytoma and teratoma is unclear.

[Psoriasis as metabolic and cardiovascular risk factor]. / Luszczyca jako czynnik ryzyka schorzen metabolicznych I sercowo-naczyniowych.

Psoriasis is a chronic, inflammatory and proliferative disease which has a tendency to recur. Metabolic disturbances occur more often in patients with psoriasis in comparison to the general population. Due to the systemic inflammation and metabolic disturbances in psoriasis the risk of cardiovascular diseases is significantly higher. The data on higher cardiovascular risk which accompanies psoriasis suggest that every patient with psoriasis or psoriatic arthritis should be screened for metabolic disturbances. Patients with psoriasis should be under special care of general practitioner in order to prevent, diagnose and treat metabolic disturbances early.

Cushing's Syndrome in the Elderly.

Management of Cushing's syndrome (CS) can be particularly challenging in older patients, compared with younger individuals, due to the lack of several clinical features associated with cortisol excess along with a greater burden of associated comorbidities. Moreover, the interpretation of diagnostic tests could be influenced by age-related physiological changes in cortisol secretion. While mortality is higher and quality of life is more impaired in the elderly with CS as compared with the younger, there is currently no agreement on the most effective therapeutic options in aged individuals, and safety data concerning medical treatment are scanty. In this review, we summarize the current knowledge about age-related differences in CS etiology, clinical presentation, treatment, and outcomes and describe the potential underlying mechanisms.

Health-Related Quality of Life in Patients with Primary Adrenal Insufficiency.

(1) Background: Patients with primary adrenal insufficiency (PAI) suffer from a reduced quality of life. However, clinical factors associated with this impairment remain unclear. The aim of this study was to assess the health-related quality of life (HRQoL) and to evaluate the associations with clinical and hormonal parameters in a group of patients with PAI. (2) Methods: The study included 32 patients with autoimmune PAI, who answered the quality of life in Addison's disease questionnaire (AddiQoL). Clinical data and hormonal measurements were collected from the patients. (3) Results: The total AddiQoL score of males was significantly higher than that of females (p = 0.011). Furthermore, males reached significantly higher scores in each of the four subscales (fatigue-p = 0.013, emotional sphere-p = 0.048, adrenal insufficiency symptoms-p = 0.039, and miscellaneous questions-p = 0.034). There was a negative correlation between HRQoL and gonadotropin levels (FSH and fatigue r = (-)0.38, p = 0.032; FSH and emotional sphere r = (-)0.416, p = 0.018). This study found no significant associations between AddiQoL scores and the presence of autoimmune comorbidities; only fatigue scores were worse in the presence of autoimmune thyroiditis (p = 0.034). The doses of hydrocortisone and fludrocortisone in the replacement therapy were not associated with AddiQoL scores. AddiQoL scores correlated negatively with the age of diagnosis (p = 0.015). (4) Conclusions: Female sex, higher gonadotropins level, and older age at diagnosis were associated with impaired HRQoL in the studied group of patients with PAI.

Trabecular bone score and sclerostin concentrations in patients with primary adrenal insufficiency.

Background: Patients with primary adrenal insufficiency need lifelong replacement therapy with glucocorticoids and mineralocorticoids, which may influence their bone quality. Aim: The aim of the study was to evaluate densitometry parameters, trabecular bone score and sclerostin concentrations in patients with primary adrenal insufficiency in comparison to control group. Materials and methods: We included 29 patients (62% females) with diagnose of autoimmune primary adrenal insufficiency (mean age 49.7 ± 11.7 years, mean duration of the disease 13.2± 13.6 years) and 33 healthy subjects (adjusted with age, sex and body mass index). Bone mineral density at the femoral neck, lumbar spine, total body and trabecular bone score were evaluated. Serum sclerostin concentrations were measured. Results: There were no significant differences in densitometry parameters (T-score, Z-score, bone mineral density in all locations) as well as in trabecular bone score in patients with adrenal insufficiency in comparison to control group. Mean serum sclerostin concentration was significantly higher in patients with adrenal insufficiency than in control group (44.7 ± 23.5 vs 30.7 ± 10.4 pmol/l, p=0.006). There was a negative correlation between trabecular bone score and the duration of adrenal insufficiency and age, also a negative correlation between femoral neck and total densitometry parameters and 24-hour urine cortisol as a marker of hydrocortisone daily dose in patients with adrenal insufficiency. Conclusions: The bone status in patients with primary adrenal insufficiency was not impaired in comparison to control group, while sclerostin concentration was higher. The duration of the disease and higher hydrocortisone doses may affect negatively bone status.

COVID-19 and the urological practice: changes and future perspectives.

INTRODUCTION: The COVID-19 pandemic has brought great challenges to the management of urological patients. Like most surgical specialties, urology has shifted towards an emergency mentality. Currently, the beginning of the de-escalation phase of the pandemic has been observed, which will certainly pose new challenges to the urological community. MATERIAL AND METHODS: A non-systematic search was conducted through the Medline and Web of Science databases. The main keywords used in the search were: 'COVID-19', 'SARS-CoV-2', 'urology'. The search included articles without time and language limitation. RESULTS: During the peak of the COVID-19 pandemic urological services had to focus on maintaining urgent-oncological and emergency-trauma procedures. First adapted recommendations were released at the end of March 2020. Primarily, they included information regarding the prioritization of surgical procedures. Currently, the beginning of the de-escalation phase in many countries has forced the necessity of establishing new degrees of priority for surgical interventions.During the COVID-19 pandemic, cancellations and rescheduling significantly extend the waiting time for outpatient appointments and surgical procedures. A network of expert high-volume centres, at every level of referentiality, should guarantee the continuity of oncological care, supported with telemedicine systems.The COVID-19 pandemic has caused a substantial decrease in clinical activity of urology residents. There also is huge potential for remote technology to address and improve education and training continuation in this field. CONCLUSIONS: Urological care has been severely impaired by the COVID-19 pandemic. Urologists must adapt to the dynamically changing reality, prioritizing the safety and well-being of their patients and their clinic workforce.

The FTO gene is not associated with weight gain during six years of observation in the population of the PURE study in Poland.

INTRODUCTION: We present the first longitudinal study in Poland analysing the association between fat mass and obesity-associated gene (FTO) polymorphism and changes in anthropometric parameters. MATERIAL AND METHODS: 1120 participants of the Prospective Urban Rural (PURE) study in Poland (mean age 53.7 years) were genotyped for FTO gene polymorphism (rs9939609, rs9930506, rs1421085, rs1121980). Anthropometric parameters were measured at three time points (baseline, after three years, and after six years of observation). RESULTS: The mean body mass index (BMI) in the study group was 28 kg/m². Overall, there was a significant increase in the mean weight, BMI, and waist size during the six years (p≈0). Although males initially weighed more than females (p = 0), over the whole six-year period women had a greater tendency to increase in weight (p = 0.068), BMI (p = 0.014), and waist size (p = 0.041). Subjects with at least one A allele at rs9939609 initially weighed more on average (77.5vs. 74.7 kg, p = 0.027) and had a greater waist size (92 vs. 89.5 cm, p = 0.025) than those with the TT genotype. The differences in baseline results were more expressed in males than in females. There is no association between the changes in anthropometric parameters over the whole study period of six years and the FTO gene. CONCLUSIONS: FTO gene polymorphism is associated with anthropometric parameters in participants from the PURE study in Poland. However, there is no association between the presence of risk alleles and changes of anthropometric parameters over six years of observation.

The association between FTO gene polymorphism rs9939609 and obesity is sex-specific in the population of PURE study in Poland.

BACKGROUND: Fat mass and obesity-associated gene (FTO) polymorphism remains the strongest known genetic determinant of common obesity. However, its influence depends on ethnicity, and the FTO-mediated predisposition to other metabolic disturbances is questionable. OBJECTIVES: The aim of our study was to evaluate the association between FTO rs9939609 polymorphism and metabolic syndrome in a population of Prospective Urban Rural Epidemiology (PURE) study in Poland. MATERIAL AND METHODS: We enrolled 1,097 participants of the PURE study (683 women and 414 men) from the Lower Silesian voivodeship. Anthropometrical parameters and blood pressure were measured. Blood samples were taken for an examination of lipid profile and fasting glucose level. Genomic DNA was isolated and FTO polymorphism rs9939609 was genotyped. RESULTS: Male A-allele carriers had significantly higher mean body mass, body mass index (BMI), waist-to-hip ratio (WHR), and waist and hip circumferences than men without risk allele. They were also more often diagnosed with obesity on the basis of BMI and central obesity parameters. No such influence was observed in women. There were no significant associations between FTO polymorphism and metabolic syndrome or its components. CONCLUSIONS: Our results suggest a sex-specific association between FTO polymorphism and obesity traits. The occurrence of metabolic syndrome or its components was not related with FTO gene variation in our cohort.

Restaging Transurethral Resection of Bladder Tumours after BCG Immunotherapy Induction in Patients with T1 Non-Muscle-Invasive Bladder Cancer Might not Be Associated with Oncologic Benefit.

BACKGROUND AND PURPOSE: The European Association of Urology guidelines recommend restaging transurethral resection of bladder tumours (reTURB) 2-6 weeks after primary TURB. However, in clinical practice some patients undergo a second TURB procedure after Bacillus Calmette-Guérin immunotherapy (BCG)induction. To date, there are no studies comparing post-BCG reTURB with the classic pre-BCG approach. The aim of this study was to assess whether the performance of reTURB after BCG induction in T1HG bladder cancer is related to potential oncological benefits. MATERIALS AND METHODS: Data from 645 patients with primary T1HG bladder cancer treated between 2001 and 2019 in 12 tertiary care centres were retrospectively reviewed. The study included patients who underwent reTURB before BCG induction (Pre-BCG group: 397 patients; 61.6%) and those who had reTURB performed after BCG induction (Post-BCG group: 248 patients, 38.4%). The decision to perform reTURB before or after BCG induction was according to the surgeon's discretion, as well as a consideration of local proceedings and protocols. Due to variation in patients' characteristics, both propensity-score-matched analysis (PSM) and inverse-probability weighting (IPW) were implemented. RESULTS: The five-year recurrence-free survival (RFS) was 64.7% and 69.1% for the Pre- and Post-BCG groups, respectively, and progression-free survival (PFS) was 82.7% and 83.3% for the Pre- and Post-BCG groups, respectively (both: p > 0.05). Similarly, neither RFS nor PFS differed significantly for a five-year period or in the whole time of observation after the PSM and IPW matching methods were used. CONCLUSIONS: Our results suggest that there might be no difference in recurrence-free survival and progression-free survival rates, regardless of whether patients have reTURB performed before or after BCG induction.

The Influence of FTO Polymorphism rs9939609 on Obesity, Some Clinical Features, and Disturbance of Carbohydrate Metabolism in Patients with Psoriasis.

BACKGROUND: Psoriasis is often accompanied by obesity, hyperlipidemia, diabetes, and metabolic syndrome as risk factors of cardiovascular conditions and premature mortality. OBJECTIVE: The study was aimed at investigating whether psoriatic patients, who carry risk allele of obesity-related FTO gene, are more predisposed to obesity and metabolic disturbances and whether it influences the severity of psoriasis. METHODS: 197 patients with psoriasis, representing Lower Silesia region of Poland, underwent physical examination and anthropometric measurements. Blood samples for biochemical and genetic analysis were collected. All patients were genotyped for FTO gene rs9939609 variant. Identification of SNP was conducted with the use of minisequencing method. RESULTS: Around 63% of patients were carriers of at least one risk allele A and 20% were AA homozygotes. The A allele was associated with increased BMI and hip and waist circumferences. The carriers of risk allele had increased PASI and CRP values and tended to have an increased insulin concentration. CONCLUSION: Psoriatic patients, carriers of risk allele of FTO gene rs9939609, have an increased risk for more severe psoriasis and obesity and may develop obesity-induced insulin resistance.

Determinants of obesity in population of PURE study from Lower Silesia.

INTRODUCTION: The knowledge about obesity pathogenesis is insufficient. The aim of our study was to investigate environmental and individual determinants of obesity in population of PURE study from Lower Silesia. MATERIAL AND METHODS: This was a cross sectional observation of 1064 inhabitants of Wroclaw and neighbouring rural area (671 women, 393 men), who took part in PURE study in years 2007-2010. Each participant answered PURE questionnaire and International Physical Activity Questionnaire providing information about obesity risk factors. Anthropometric measurements were collected, blood samples were taken for assessment of FTO gene polymorphism. A stepwise logistic regression analysis was performed to identify the most significant predictors of obesity. RESULTS: 31% of the study group had obesity (BMI over 30 kg/m², no difference between men and women), overweight (BMI 25-29.9 kg/m²) affected 48.1% of men and 36.7% of women. Determinants of obesity in female group were: rural inhabitancy, chronic medication, unemployment, age, sedentary leisure time activity, non-smoking, hypertension in family, family related stress (p = 0.66 in the Hosmer-Lemeshow test). Determinants of obesity in male group were rural inhabitancy, chronic medication, family related stress, diabetes in family (p = 0.27 in the Hosmer-Lemeshow test). Risk factors for central obesity were similar, however in women oral contraception and physical activity were associated with lower obesity risk. CONCLUSIONS: Environmental factors, especially rural inhabitancy and family related stress were associated with higher obesity risk in our study. Employment, smoking, physical activity and use of oral contraception seemed to have protective role in women.

Evaluation of Selected Atherosclerosis Risk Factors in Women with Subclinical Hypothyroidism Treated with L-Thyroxine.

BACKGROUND: Subclinical hypothyroidism (SCH) is a common endocrine disorder, probably increasing cardiovascular (CV) risk. However, the relation between SCH and atherosclerosis risk factors remains unclear. OBJECTIVES: The aim of the study was to evaluate selected atherosclerosis risk factors in women with SCH in comparison to a group of healthy women and women with overt hypothyroidism, as well as to investigate the influence of L-thyroxine replacement on those risk factors. MATERIAL AND METHODS: The study group consisted of 187 obese women aged between 50 and 70 years: 100 women with SCH, 45 women with overt hypothyroidism and 42 women with TSH level in reference ranges. Anthropometric parameters were evaluated. Laboratory tests included thyroid hormones concentrations, lipid profile with apolipoproteins, CRP, homocysteine. Atherosclerotic indexes were calculated: LDL C/HDL C ratio, apoA1/apoB ratio and Castelli risk index. Women with hypothyroidism were given L-thyroxine treatment and after 6 months in euthyroidism the evaluation was repeated. RESULTS: Total cholesterol, LDL-cholesterol and triglycerides concentrations as well as LDL-C/HDL-C ratio and Castelli index were higher in SCH than in controls and decreased after L-thyroxin substitution. All of the calculated atherosclerosis indexes showed significant positive correlations with TSH concentration in SCH group. Also in this group the systolic and diastolic blood pressure decreased significantly after treatment. CONCLUSIONS: Dyslipidemia in obese SCH women is not severe, but if untreated for many years, it may lead to atherosclerosis. Substitution therapy improves the lipid profile, changing the relations between protective and proatherogenic fractions of serum lipids, and optimises blood pressure.

The Frequencies of Haplotypes of FTO Gene Variants and Their Association with the Distribution of Body Fat in Non-Obese Poles.

BACKGROUND: The minor allele frequencies (MAFs) of the FTO gene vary substantially among different ethnic groups, and this variation may explain, to some degree, the differences between estimates of the effects of these alleles on body fat distribution indicators. OBJECTIVES: The aim of this study was to investigate the prevalence of fat mass and obesity associated (FTO) gene variants characterizing the structure of FTO haplotypes in a large Polish population, and to examine the influence of FTO gene variants on body fat distribution among metabolically obese normal weight (MONW) individuals, i.e. those with a normal BMI and visceral obesity. MATERIAL AND METHODS: A total of 854 non-obese individuals aged from 20 to 40 years, residing in three different regions in Poland, were studied. All the patients from this group were genotyped for four FTO gene variants (rs9939609, rs9930506, rs1421085 and rs1121980). Simultaneous identification of all single nucleotide polymorphisms (SNPs) was conducted using the minisequencing method with a pair of designed specific primers. RESULTS: Over 90% of the diplotypes contain only the two most common haplotypes, in three combinations of haplotype pairs: CTAT/CTAT comprised 26.9% in women and 30.9% in men; CTAT/TCGA comprised 45.0% in women and 44.4% in men; and TCGA/TCGA comprised 19.3% in woman and 14.8% in men. The analysis of the variance in body fat distribution parameters shows no statistically significant differences between the three common haplotype pairs in either men or women. CONCLUSIONS: The young Polish population is characterized by two disparate haplotypes of common FTO gene variants: TCGA (a risk SNP haplotype), and CTAT (a protective haplotype). No significant differences were found between fat distribution indicators in relation to haplotypes in either women and men.

The role of fat mass and obesity-associated gene (FTO) in obesity - an overview.

Obesity is an epidemic of the 21st century. The magnitude of this problem stems from its increasing prevalence and numerous metabolic complications caused by excessive fat accumulation. The pathogenesis involves both environmental and genetic factors, and FTO (fat mass and obesity-associated gene) is one of the most significant among genes predisposing to obesity. The role of FTO polymorphism in the development of obesity has been confirmed in many studies, but the effect varies significantly in different ethnic groups. Moreover, the exact mechanisms of FTO influence are yet to be explained. The association between FTO and lifestyle factors such as diet and physical activity has been extensively studied in recent years. This paper presents current knowledge about the role of FTO gene in the development of obesity and type 2 diabetes in different ethnic groups and the association between FTO polymorphism and lifestyle modifications predisposing to adiposity.

Accumulation of abdominal fat in relation to selected proinflammatory cytokines concentrations in non-obese Wroclaw inhabitants.

INTRODUCTION: Metabolically obese normal weight (MONW) subjects, despite their normal BMI, present metabolic disturbances characteristic of abdominal obesity. One of the reasons might be subclinical inflammation caused by the fat tissue excess. The aim of this study was to assess the association between the accumulation of fat (especially abdominal) and the concentration of selected proinflammatory cytokines - interleukins (IL-6, IL-18) and C-reactive protein (CRP). MATERIAL AND METHODS: The study population consisted of 342 subjects (218 women, 124 men; age 20-40 years, BMI < 27 kg/m2) recruited from a community centre in Wroclaw. The group was divided based on the homeostasis assessment insulin resistance index (HOMA) value: 90 MONW subjects with HOMA > 1.69 and 252 subjects as control group. Anthropometric parameters, serum IL-6, IL-18, CRP, glucose, insulin concentrations and insulin sensitivity/resistance indexes were evaluated. RESULTS: CRP levels were significantly higher (3.26 vs. 1.97, p = 0.03) in MONW women than in the control group. Serum IL-6, IL-18 levels in males and females did not differ in both groups. IL-6 showed a significant correlation with the abdominal to gynoidal fat tissue deposit ratio in women. There were correlations between the CRP and BMI, WHR, waist circumference, total fat, abdominal fat deposit, and abdominal to gynoidal fat deposit ratio in both sexes. In women, positive correlations between CRP and HOMA, FIRI and negative with QUICKI index were present. CONCLUSIONS: Increased accumulation of abdominal adipose tissue in non-obese, young and healthy subjects is related to increased CRP levels.