Jerzy S. Tarach

Toll-like receptor 4 gene polymorphism and early onset of diabetic retinopathy in patients with type 2 diabetes

Toll-like receptor 4 (TLR4) is an important mediator of innate immunity. Type 2 diabetes (DM2) might be associated with changed innate immune response. We investigated whether the polymorphisms in the TLR4 gene are associated with diabetic retinopathy (DR). The study group of 864 patients with DM2 and 420 healthy individuals were genotyped. In the patient group 352 subjects were diagnosed with DR. Out of the remaining 512, 140 had DM2 for > or = 10 years but no DR. In the DM2 group 7.4% of patients were heterozygous for the Asp299Gly polymorphism compared with 6.5% controls. For Thr399Ile polymorphism there were 7.2% heterozygotes vs 6.2% controls. In most cases, the linkage disequilibrium between the minor alleles Gly299 and Ile399 was confirmed. Increased frequency of both heterozygous genotypes was observed in patients with retinopathy (11.2% for the Asp299Gly). The frequency of the G allele was significantly higher in patients with early onset retinopathy (n = 80) vs patients without DR (odds ratio = 5.0, and 95% confidence interval = 2.33-10.71). In contrast, in the entire retinopathy group, the odds ratio for the G allele was 1.88 (95% confidence interval = 0.93-3.79). In the multivariate logistic regression analysis, the G allele of Asp299Gly was an independent risk factor of early onset DR (p < 0.001). In conclusion, our results suggest an association between the Asp299Gly polymorphism of the TLR4 gene and early onset of DR in the DM2 patients. Thus the G allele may be a predictor of increased risk of retinopathy.

Fetuin-A (AHSG) and its usefulness in clinical practice. Review of the literature

BACKGROUND Fetuin-A, also called Alpha 2-Heremans Schmid Glycoprotein, is a multifunctional plasma agent what has been proven in animal and human studies. It plays a role as a physiological inhibitor of insulin receptor tyrosine kinase associated with insulin resistance and a negative acute phase reactant. It also regulates bone remodeling and calcium metabolism being an important inhibitor of calcium salt precipitation and vascular calcifications. METHODS PubMed database was searched for articles from 2002 up to December 2014 to identify the role of fetuin-A in the pathogenesis of selected internal diseases. RESULTS Due to secretion of fetuin-A mainly by the liver, it may be a marker of liver function and predictor of mortality in patients with cirrhosis and hepatocellular cancer. The associations between high fetuin-A and metabolic syndrome as well as its hepatic manifestation- nonalcoholic fatty liver disease and atherogenic lipid profile have been well proven. However, fetuin-A relation with BMI is not so clear. Contrary to few reports, many authors suggest that fetuin-A may be an independent risk factor for type 2 diabetes and marker of diabetic complications. Close associations of high and low fetuin-A concentrations with cardiovascular diseases and mortality risk have been reported which is explained by differences in analyzed populations, stages of atherosclerosis and calcifications, coexistence of type 2 diabetes or kidney dysfunction and different main pathways of fetuin-A actions in various diseases. CONCLUSIONS Fetuin-A has a diagnostic potential as a biomarker for liver dysfunction, cardiovascular diseases and disorders associated with metabolic syndrome.

Quality of Life in Patients with Type 2 Diabetes in Poland – Comparison with the General Population Using the EQ-5D Questionnaire

BACKGROUND Complications of type 2 diabetes (T2D) lead to increased mortality and reduced quality of life (QOL). OBJECTIVES The aim of the study was to compare health-related quality of life (HRQoL) in Polish patients with type 2 diabetes (T2D) and in a matched sample from the general population. MATERIAL AND METHODS Data on HRQoL came from two non-interventional studies: a prospective study of patients with T2D and an EQ-5D study of Polish general population norms. The HRQoL analysis was conducted in four separate age groups: 32-44, 45-54, 55-64 and over 65 years old. We analyzed both subjective and objective assessment of HRQoL (EQ VAS and EQ-5D index) and the presence of restrictions within five dimensions of the EQ-5D descriptive part. RESULTS A total of 274 patients with T2D and 214 representatives from the study of population norms were included. EQ VAS was systematically lower in diabetic patients as compared to the general population and decreased with age (68.2 vs 83.9, 62.4 vs 79.2; 54.9 vs 78.1, 50.2 vs 69.8 in consecutive age groups). A similar relationship was observed with the EQ-5D index. The largest mean differences were observed among subjects aged 55-64 years (EQ VAS: 23.2, EQ-5D index: 0.085). In three domains, i.e. self-care, usual activities and anxiety/depression, patients with diabetes who were over 45 years of age reported significantly more problems than respondents from the general population. CONCLUSIONS Both subjective and objective HRQoL in patients with T2D was lower than in respondents similar in age from the general population. Compared with type 2 diabetic populations from other countries, Polish patients are characterized by relatively high HRQoL objective assessment and very low subjective assessment.

Thyroid diseases in patients with acromegaly

Acromegaly often involves the presence of different pathologies of the thyroid gland. Long-lasting stimulation of the follicular epithelium by growth hormone (GH) and insulin-like growth factor 1 (IGF-1) can cause disorders in thyroid function, an increase in its mass and the development of goitre. Acromegalic patients present most frequently with non-toxic multinodular goitre. Nodules are more prevalent in patients with active acromegaly. It has been suggested that then thyroid size increases and it can be reduced through treatment with somatostatin analogues. The relationship between thyroid volume and the level of IGF-1 and the duration of the disease is unclear. Each acromegalic patient requires a hormonal and imaging evaluation of the thyroid when the diagnosis is made, and an accurate evaluation during further observation and treatment. Although the data concerning the co-occurrence of acromegaly and thyroid cancer still remain controversial, it is particularly important to diagnose the patient early and to rule out thyroid cancer.

Validation of the Polish version of Diabetes Quality of Life - Brief Clinical Inventory (DQL-BCI) among patients with type 2 diabetes.

Introduction The aim of the study was to develop a Polish version of the Diabetes Quality of Life Brief Clinical Inventory (DQL-BCI) and to perform validating evaluation of selected psychometric aspects. Material and methods The translation process was performed in accordance with generally accepted international principles of translation and cultural adaptation of measurement tools. Two hundred and seventy-four subjects with type 2 diabetes completed the Polish version of DQL-BCI, the generic EQ-5D questionnaire and the diabetes-specific DSC-R. The examination provides information about the reliability (internal consistency, test-retest) and the construct validity of the studied tool (the relationship between the DQL-BCI score and EQ-5D and DSC-R scales, as well as selected clinical patient characteristics). Results Cronbachs α (internal consistency) for the translated version of DQL-BCI was 0.76. Test-retest Pearson correlation coefficient was 0.96. Spearmans coefficient correlation between DQL-BCI score and EQ-5D index and EQ-VAS were 0.6 (p = 0.0000001) and 0.61 (p = 0.0000001) respectively. The correlation between scores of the examined tool and DSC-R total score was –0.6 (p = 0.0000001). Quality of life was lower among patients with microvascular as well as macrovascular complications and with occurring hypoglycemic episodes. Conclusions The result of this study is the Polish scale used to test the quality of life of patients with diabetes, which includes the range of problems faced by patients while maintaining a patient-friendly form. High reliability of the scale and good construct validity qualify the Polish version of DQL-BCI as a reliable tool in both research and individual diagnostics.

Temozolomide-Induced Shrinkage of Invasive Pituitary Adenoma in Patient with Nelson’s Syndrome: A Case Report and Review of the Literature

Introduction. Invasive tumours in Nelsons syndrome need aggressive therapy. Recent reports have documented the efficacy of temozolomide (TMZ) in the treatment of adenomas resistant to conventional management. Objective. The review of the literature concerning TMZ treatment of atypical corticotroph adenomas and a case study of 56-year-old woman who developed Nelsons syndrome. Treatment Proceeding. The patient with Cushings disease underwent transsphenoidal adenomectomy followed by a 27-month-long period of remission. Due to a regrowth of the tumor, she underwent two reoperations followed by stereotactic radiotherapy. Because of treatment failures, bilateral adrenalectomy was performed. Then she developed Nelsons syndrome. A fourth transsphenoidal adenomectomy was performed, but there was a rapid recurrence. Five months later, she underwent a right frontotemporal craniotomy. Due to a rapid regrowth of the tumour, the patient did not receive gamma-knife therapy and was treated with cabergoline and somatostatin analogue for some time. Only TMZ therapy resulted in marked clinical, biochemical, and radiological improvement. To date, this is the first case of invasive corticotroph adenoma in Nelsons syndrome treated with temozolomide in Poland. Conclusion. In our opinion, temozolomide can be an effective treatment option of invasive adenomas in Nelsons syndrome.

Polycystic ovary syndrome: clinical implication in perimenopause.

Polycystic ovary syndrome (PCOS), a hyperandrogenic disorder, is the commonest endocrinopathy in premenopausal women. This syndrome is associated with fertility problems, clinical manifestations of hyperandrogenism and metabolic disturbances, particularly insulin resistance and obesity. There is a great body of evidence that patients with PCOS present multiple cardiovascular risk factors and cluster components of metabolic syndrome from early ages. The presence of comorbidities such as abdominal obesity, insulin resistance, type 2 diabetes, hypertension places these females at an increased risk of future cardiovascular events. However, the extent to which PCOS components are present in perimenopausal women and the degree to which PCOS increases various risk factors in addition to the known risk of the perimenopausal period have not been fully determined. The perimenopausal period per se is associated with weight gain and an increased cardiovascular risk, which may be additionally aggravated by the presence of metabolic disturbances connected with PCOS. The phenotype of PCOS may improve with aging and it is still uncertain whether the presence of PCOS significantly increases the cardiovascular risk later in womens life. Most recent data suggest that the prevalence of cardiovascular diseases and the related long-term consequences in females with PCOS seem to be lower than expected. This manuscript reviews long-term consequences of PCOS and considers their clinical implications in perimenopause.

Concentrations of fetuin-A, osteoprotegerin and α-Klotho in patients with alcoholic liver cirrhosis

The aim of the present study was to evaluate the concentrations of fetuin-A, osteoprotegerin (OPG) and α-Klotho protein in patients with alcoholic cirrhosis at different stages of the disease, and to demonstrate that fetuin-A, osteoprotegin and α-Klotho may be used as markers of the severity of cirrhosis. A total of 54 patients with alcoholic liver cirrhosis treated in various hospitals in the Lublin region of Poland were randomly enrolled. The control group consisted of 18 healthy individuals without liver disease, who did not drink alcohol. Serum levels of fetuin-A, OPG and α-Klotho were measured by ELISA kits. Levels of fetuin-A were significantly reduced in patients with alcoholic liver cirrhosis compared with the control group. OPG levels were higher in patients with alcoholic liver cirrhosis than in the controls, whereas the levels of α-Klotho were comparable in the cirrhosis and control groups. No statistically significant differences in the concentrations of fetuin-A, OPG and α-Klotho protein were demonstrated according to type of liver cirrhosis. The findings of the present study revealed a significant negative correlation between the level of α-Klotho protein and C-reactive protein in the patients with alcoholic liver cirrhosis. Concentrations of fetuin-A were lower, whereas those of OPG were higher, in the alcoholic liver cirrhosis group compared with the control group. Fetuin-A, OPG and α-Klotho may not be good indicators of liver cirrhosis severity. In conclusion, fetuin-A and OPG may be used in the diagnosis of liver cirrhosis.

Long-term complete remission of Crooke’s corticotropinoma after temozolomide treatment

INTRODUCTION Crookes corticotropinomas are the unique cause of Cushings disease. The majority of them are aggressive macroadenomas, refractory to conventional therapy, with a high recurrence rate. The aim of the study was the presentation, in relation to data from the literature, of a case of a patient with ACTH-dependent Cushings syndrome caused by recurrent Crookes cells corticotropinoma, who achieved 33-month complete remission after treatment with temozolomide (TMZ). CASE REPORT A 54-year-old man was diagnosed with Cushings disease five years earlier on the basis of a typical clinical picture and hormonal tests. MRI revealed 32 × 29 × 24 mm macroadenoma. The patient underwent three subtotal selective transsphenoidal adenomectomies without retirement of hypercortisolaemia. A postoperative pathologic exploration revealed a densely granulated corticotroph Crookes cells adenoma with MIB-1 index < 1%. Because of the large size of the tumour with its expansion to both cavernous sinuses and suprasellar region together with a compression of the optic chiasm, the patient was disqualified for gamma-knife. Due to an exhaustion of all conventional therapeutic options the patient was qualified to TMZ therapy. The standard dose of TMZ (150 g/m²) for five days every 28 days was implemented. After three courses of TMZ pronounced regression of tumour size with a marked hormonal and clinical improvement was certified. After six courses, consecutive tumour regression was observed. Nine courses resulted in a total radiological tumour shrinkage and hormonal normalisation. Despite the cassation of TMZ treatment the complete remission of the disease maintained for 33 months. CONCLUSION Temozolomide can be an effective treatment option in invasive Crookes cell corticotropinoma. (Endokrynol Pol 2016; 67 (5): 526-533).

Primary hyperparathyroidism due to parathyroid cancer — a diagnostic and management challenge

Parathyroid carcinoma (PC) is a rare endocrine malignancy and the cause of primary hyperparathyroidism. It is usually associated with a high rate of local and distant recurrence. Laboratory findings and clinical symptoms may be similar to those in parathyroid adenoma. The histological features of PC may also be non-specific and the affected gland is often indistinguishable from a benign lesion. The proper diagnosis is commonly made months to years later when the disease recurs or metastases are present. Therefore, parathyroid carcinoma still remains a diagnostic and management challenge for many physicians. However, there are some features that, in combination, may help in diagnosis. Surgery still remains the only curative treatment, even in metastatic disease. In advanced, non-operable subjects, managing hypercalcaemia and controlling a tumour are the main goals. Morbidity is caused by hypercalcaemia rather than metastases. A multidisciplinary approach with experienced endocrinologists, pathologists, radiologists, nuclear medicine doctors, oncologists, and surgeons is needed to optimize patient outcome.