Publications by authors named "Marek Bolanowski"

144 Publications

Complications and Comorbidities of Acromegaly-Retrospective Study in Polish Center.

Front Endocrinol (Lausanne) 2021 16;12:642131. Epub 2021 Mar 16.

Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Wrocław, Poland.

Introduction: In acromegaly, chronic exposure to impaired GH and IGF-I levels leads to the development of typical acromegaly symptoms, and multiple systemic complications as cardiovascular, metabolic, respiratory, endocrine, and bone disorders. Acromegaly comorbidities contribute to decreased life quality and premature mortality. The aim of our study was to assess the frequency of acromegaly complications and to evaluate diagnostic methods performed toward recognition of them.

Materials And Methods: It was a retrospective study and we analyzed data of 179 patients hospitalized in the Department of Endocrinology, Diabetes and Isotope Therapy in Wroclaw Medical University (Poland) in 1976 to 2018 to create a database for statistical analysis.

Results: The study group comprised of 119 women (66%) and 60 men (34%). The median age of acromegaly diagnosis was 50.5 years old for women (age range 20-78) and 46 for men (range 24-76). Metabolic disorders (hyperlipidemia, diabetes, and prediabetes) were the most frequently diagnosed complications in our study, followed by cardiovascular diseases and endocrine disorders (goiter, pituitary insufficiency, osteoporosis). BP measurement, ECG, lipid profile, fasting glucose or OGTT were performed the most often, while colonoscopy and echocardiogram were the least frequent.

Conclusions: In our population we observed female predominance. We revealed a decrease in the number of patients with active acromegaly and an increase in the number of well-controlled patients. More than 50% of patients demonstrated a coexistence of cardiac, metabolic and endocrine disturbances and only 5% of patients did not suffer from any disease from those main groups.
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http://dx.doi.org/10.3389/fendo.2021.642131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009182PMC
March 2021

The Effect of 6 Months' Treatment With Pasireotide LAR on Glucose Metabolism in Patients With Resistant Acromegaly in Real-World Clinical Settings.

Front Endocrinol (Lausanne) 2021 10;12:633944. Epub 2021 Mar 10.

Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Wroclaw, Poland.

Objective: The aim of the study was to evaluate glucose metabolism, as measured by glycated hemoglobin (HbA1c) levels and the need for antidiabetic medical treatment, in patients with acromegaly resistant to first-generation somatostatin receptors ligands (SRLs) treated with pasireotide long-acting release (LAR) in real-world clinical practice. Biochemical control of acromegaly, as measured by growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, was also assessed.

Study Design: Two-center retrospective cohort of consecutive patients with acromegaly treated with first-generation SRLs at maximum doses, who had not achieved biochemical disease control. After SRLs were discontinued, patients were given pasireotide LAR 40 mg i.m. every 28 days. The dose was increased to 60 mg i.m. in patients for whom adequate control was not achieved after 3 months. Patients were given dietary and lifestyle advice, and antihyperglycemic treatment was modified as needed.

Main Outcome Measures: Biochemical disease control parameters (GH and IGF-1 concentration), as well as HbA1c level at baseline and after 6 months.

Results: In total, 39 patients with acromegaly were enrolled. GH concentration decreased (Δ =-1.56 µg/L, range -21.38-3.62, p <0.001) during 6 months of pasireotide LAR treatment. A worsening of metabolic status was observed, with an increase of median HbA1c (Δ =0.40%, range -0.20%-2.30%, p <0.001), and antihyperglycemic treatment intensification in 23 (59.0%) patients. The median decline in IGF-1 concentration was: -283.0 µg/L, range -682.7-171.6, p <0.001. IGF-1 reached the age- and gender-specific upper level of normal in 23 (59%) patients.

Conclusions: Pasireotide LAR is an effective therapeutic option in patients with acromegaly refractory to first-generation SRLs. However, this therapy may result in pasireotide LAR-associated hyperglycemia, which requires early and aggressive antidiabetic medical therapy to prevent glucose homeostasis alterations.
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http://dx.doi.org/10.3389/fendo.2021.633944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988223PMC
March 2021

Decreased Trabecular Bone Score in Patients With Active Endogenous Cushing's Syndrome.

Front Endocrinol (Lausanne) 2020 21;11:593173. Epub 2021 Jan 21.

Department and Clinic of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Wrocław, Poland.

Introduction: The impairment in bone microarchitecture and reduced bone quality are relevant mechanisms underlying the increased fracture risk in Cushing's syndrome (CS). The trabecular bone score (TBS) is a relatively novel textural index of bone microarchitecture.

Purpose: The objective of the study was to compare TBS, bone mineral density (BMD), and fracture risk in patients with endogenous CS to controls. We have investigated the association of TBS with anthropometric parameters and 25(OH) vitamin D concentrations.

Materials And Methods: The study group comprised 19 consecutive patients with CS (14 women and 5 men; mean age 45.84 ± 13.15 years) and sex-, age-matched 36 controls (25 women and men; mean age 52.47 ± 8.98 years). Anthropometric parameters, biochemical and hormonal data were compared between groups. Lumbar spine (L1-L4) and femoral neck BMD (LS BMD, FN BMD) measurements were performed. TBS values were obtained from lumbar spine DXA images.

Results: TBS was significantly lower in patients with CS compared to controls (p = 0.0002). The 10-year probability of hip fracture and the 10-year probability of a major osteoporotic fracture were significantly higher in the CS group than in controls (p = 0.03, p < 0.0001, respectively). All subjects from the CS group with fractures had low TBS value (degraded microarchitecture). TBS correlated negatively with the duration of disease in patients with CS (r = -0.590 p = 0.008).

Conclusions: The patients with active CS have altered bone microstructure as indicated by the decreased TBS and are at higher risk of hip and a major osteoporotic fractures. TBS seems to be a very important analytical tool facilitating fracture risk assessment in endogenous hypercortisolism.
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http://dx.doi.org/10.3389/fendo.2020.593173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874075PMC
January 2021

in Endocrine System Tumours.

Anticancer Res 2021 Feb;41(2):557-565

Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Wroclaw, Poland.

Long non-coding RNAs (lncRNAs) are over 200 nucleotides long recently discovered RNA molecules that are not involved in the translation process. Accumulating evidence shows that H19 lncRNA is an important regulator of gene expression and its altered expression contributes to carcinogenesis. The aim of this review was to reveal current knowledge about H19 lncRNA and its impact on tumours of the endocrine system. We present findings about H19 altered regulation and its association with tumorigenesis, cancer progression and differentiation, and its potential use in diagnostics, prognostics and therapy. The mechanism and molecular pathways involved in these processes are discussed.
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http://dx.doi.org/10.21873/anticanres.14808DOI Listing
February 2021

Cornelian cherry extract ameliorates osteoporosis associated with hypercholesterolemia in New Zealand rabbits.

Adv Clin Exp Med 2020 Dec;29(12):1389-1397

Department of Pharmacology, Wroclaw Medical University, Poland.

Background: Results of animal studies show that a high-cholesterol diet increases bone resorption and decreases bone formation, thus leading to osteoporosis. Previously, we reported on the beneficial influence of Cornelian cherry (Cornus mas L.) fruit on lipid profile in an animal model of diet-induced hipercholesterolemia.

Objectives: To investigate the influence of Cornus mas L. extract and loganic acid (LA) on cholesterol-induced bone changes.

Material And Methods: The study was conducted on 50 New Zealand rabbits. The animals were given either standard chow (group P) or the same standard chow enriched with 1% cholesterol (other groups). Additionally, the group CHOL+EX received Cornus mas L. extract, group CHOL+LA - loganic acid, and group CHOL+SIM - simvastatin. Serum concentration of bone turnover markers, bone mineral density (BMD) and bone micro-computed tomography (microCT) were assessed.

Results: In the CHOL group, a decrease in osteocalcin (OC) and an increase in C-terminated telopeptide of type I collagen (CTX) levels were detected (CHOL vs P 0.674 ±0.159 ng/mL vs 1.003 ±0.297 ng/mL and 10.049 ±1.276 ng/mL vs 7.721 ±1.187 ng/mL, respectively). The EX and LA ameliorated cholesterol-induced changes in serum OC (0.857 ±0.160 ng/mL and 1.103 ±0.356 ng/mL, respectively) and CTX (7.735 ±1.045 ng/mL and 8.128 ±1.106 ng/mL, respectively). There was a significant decrease in femoral BMD in CHOL group (0.429 ±0.11 g/cm² vs 0.449 ±0.020 g/cm²). The EX and LA ameliorated those changes (0.458 ±0.016 g/cm² and 0.449 ±0.021 g/cm², respectively). The microCT revealed increased bone volume ratio (BV/TV) and trabecular thickness (Tb.Th.) in the CHOL+EX group.

Conclusions: Cornus mas L. inhibited bone resorption and stimulated bone formation, thereby preventing the development of cholesterol-induced osteoporosis.
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http://dx.doi.org/10.17219/acem/127683DOI Listing
December 2020

Laboratory interference in the thyroid function test.

Endokrynol Pol 2020 ;71(6):551-560

Department of Endocrinology, Diabetes, and Isotope Therapy, Wroclaw Medical University, Wroclaw, Poland.

Thyroid hormones and thyroid-stimulating hormone (TSH) laboratory tests are commonly used worldwide, and their results have an important influence on decisions about treatment and further diagnostic processes. Any discrepancies between symptoms and laboratory results or between results of different tests should be closely investigated to avoid misdiagnosis and unnecessary treatment. Inconsistencies in hormone tests might be a result of physiological changes in hormonal balance, a disease, drug intake, or laboratory interference. Major factors that interfere with thyroid function tests are: heterophilic antibodies, macro TSH, biotin, thyroid hormones autoantibodies, anti-streptavidin, and anti-ruthenium antibodies. In this paper we discuss the influence of different factors on the procedures of hormonal immunoassays, as well as methods to minimise the risk of false results and misdiagnoses.
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http://dx.doi.org/10.5603/EP.a2020.0079DOI Listing
January 2020

Effects of efavirenz and tenofovir on bone tissue in Wistar rats.

Adv Clin Exp Med 2020 11;29(11):1265-1275

Department of Pharmacology, Wroclaw Medical University, Poland.

Background: Clinical trials indicate an increased risk of osteoporosis and bone fractures in people infected with human immunodeficiency virus (HIV). The pathogenesis of bone disturbances in HIV-positive patients is unknown, but it is suggested that antiretroviral drugs may be involved.

Objectives: To assess the effects of efavirenz (EF) and tenofovir (T) on bone remodeling in rats.

Material And Methods: The study involved 36 male Wistar rats divided into 3 groups, receiving normal saline (control group - group C), efavirenz (group EF) or tenofovir disoproxil (group T).

Results: After 24 weeks of the study, the following observations were made: In blood serum of the EF group compared to group C, there were increased levels of tartrate-resistant acid phosphatase form 5b (TRAP) and inorganic phosphorus. In the densitometric examination, group T showed a lower total body (TB) bone mineral density (BMD) than group C. In the immunohistochemical assessment, group EF showed a higher intensity and extension of anti-tartrate resistant acid phosphatase antibodies (abTRAP) compared to group C. In the histopathological examination of the second lumbar vertebra (L2), group EF showed a lower bone surface/volume ratio (BS/BV) and higher trabecular thickness (Tb.Th) than the control group. In the histopathological examination of the femur, a lower bone surface/tissue volume (BS/TV) and lower trabecular number (Tb.N) were found in group T compared to in group C. A lower value of the Young's modulus was observed in the four-point bending trial in groups EF and T compared to group C.

Conclusions: The results of this study indicate that EF affects bone microarchitecture and leads to impaired biomechanical properties of bones in rats. Additionally, the negative effect of T on bone tissue was confirmed.
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http://dx.doi.org/10.17219/acem/127684DOI Listing
November 2020

Bone densitometry by radiofrequency echographic multi-spectrometry (REMS) in acromegaly patients.

Endokrynol Pol 2020 18;71(6):524-531. Epub 2020 Sep 18.

Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Wrocław, Poland.

Introduction: Radiofrequency echographic multi-spectrometry (REMS) is a recently introduced non-ionising technology employed in the evaluation of osteoporosis. The aim of our study was to compare bone mineral density (BMD) in acromegaly patients and healthy controls by performing novel REMS densitometry. The second objective was to analyse the correlation between results of REMS and classical dual-energy X-ray absorptiometry (DXA) in acromegaly patients.

Material And Methods: We enrolled 33 patients with acromegaly (AG) and 24 controls (CG). The acromegaly patients were divided into two subgroups: well-controlled acromegaly (WCA) and surgery-cured acromegaly (SCA). REMS was performed in all participants, while DXA was performed only in the acromegaly group. IGF-I and GH levels were measured in acromegaly patients.

Results: Bone mineral density of the lumbar spine (LS) and the femoral neck (FN) obtained from REMS did not reveal significant differences between AG, CG, WCA, and SCA. Similarly, there were no significant differences in BMD measured by DXA at the LS and at the FN between WCA and SCA. Significant positive correlations between IGF-I concentrations and BMD obtained from both REMS and DXA were detected in the AG and WCA. In the AG and WCA, there were positive correlations between T-scores and LS BMD obtained from both methods.

Conclusions: Radiofrequency echographic multi-spectrometry is a potential method in assessment of bone status in acromegaly. Further studies with participation of active disease patients are needed.
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http://dx.doi.org/10.5603/EP.a2020.0056DOI Listing
September 2020

Multidisciplinary management of acromegaly: A consensus.

Rev Endocr Metab Disord 2020 12 10;21(4):667-678. Epub 2020 Sep 10.

Medical Research Unit in Endcrine Diseases, Hospital de Especialidades, Centro Médico Nacional, Siglo XXI, IMSS, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.
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http://dx.doi.org/10.1007/s11154-020-09588-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942783PMC
December 2020

Therapeutic effect of presurgical treatment with longacting octreotide (Sandostatin® LAR®) in patients with acromegaly.

Endokrynol Pol 2020 ;71(4):285-291

Department of Endocrinology, Diabetes, and Isotope Therapy, Wrocław Medical University, Wroclaw, Poland.

Introduction: The aim of this study was to assess the therapeutic effect and the safety of pre-surgical treatment with long-acting octreotide in patients with acromegaly.

Material And Methods: This project was conducted in 25 centres across Poland as a non-interventional, multicentre, observational study in patients with acromegaly, in which long-acting octreotide Sandostatin® LAR®) was administered before surgery. They were 148 patients included into the study: 88 females and 60 males aged 18-86 years (51.3 ± 13.4).

Results: Eighty patients completed the study (underwent tumour surgery). The CRF included: baseline visit, four follow-up visits every three months before surgery, and two follow-up visits every three months after surgery. Sandostatin® LAR® was administered every four weeks. The efficacy measures were as follows: change of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, number of patients fulfilling criteria of cure, and change of adenoma (micro- and macroadenomas) size during the treatment. Normalisation of GH and IGF-1 concentrations were obtained in 42.4 and 49.1% of patients at the end of medical therapy, respectively. Normalisation of GH and IGF-1 concentrations were obtained in 77.9 and 83.8% of patients after surgery, respectively. Reduction of microadenoma size was documented in 58.8% of patients, and in 70% of patients with macroadenomas at the end of medical therapy. In 74.0% of patients no pituitary tumour was shown on MRI after surgery.

Conclusion: We have shown good surgical outcome in patients with acromegaly after pre-treatment with somatostatin analogue, and good tolerance and safety of the therapy, supporting the national recommendation for pre-surgical treatment with long-acting somatostatin analogues in acromegaly patients.
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http://dx.doi.org/10.5603/EP.a2020.0050DOI Listing
January 2020

Maintenance of Acromegaly Control in Patients Switching From Injectable Somatostatin Receptor Ligands to Oral Octreotide.

J Clin Endocrinol Metab 2020 10;105(10)

Cedars-Sinai Medical Center, Los Angeles, California, USA.

Purpose: The phase 3 CHIASMA OPTIMAL trial (NCT03252353) evaluated efficacy and safety of oral octreotide capsules (OOCs) in patients with acromegaly who previously demonstrated biochemical control while receiving injectable somatostatin receptor ligands (SRLs).

Methods: In this double-blind study, patients (N = 56) stratified by prior SRL dose were randomly assigned 1:1 to OOC or placebo for 36 weeks. The primary end point was maintenance of biochemical control at the end of treatment (mean insulin-like growth factor 1 [IGF-1] ≤ 1.0 × upper limit of normal [ULN]; weeks 34 and 36). Time to loss of IGF-1 response and proportion requiring reversion to injectable SRLs were assessed as broader control measures.

Results: Mean IGF-1 measurements were 0.80 and 0.97 × ULN for OOC and 0.84 and 1.69 × ULN for placebo, at baseline and end of treatment, respectively. Mean growth hormone (GH) changed from 0.66 to 0.60 ng/mL for OOCs and 0.90 to 2.57 ng/mL for placebo. Normalization of IGF-1 levels (≤ 1.0 × ULN) was maintained in 58.2% for OOCs vs 19.4% for placebo (P = .008); GH levels were maintained (< 2.5 ng/mL) in 77.7% for OOC vs 30.4% for placebo (P = .0007). Median time to loss of response (IGF-1 > 1.0 or ≥ 1.3 × ULN definitions) for patients receiving placebo was 16 weeks; for patients receiving OOCs, it was not reached for both definitions during the 36-week trial (P < .0001). Of the patients in the OOC group, 75% completed the trial on oral therapy. The OOC safety profile was consistent with previous SRL experience.

Conclusions: OOCs may be an effective therapy for patients with acromegaly who previously were treated with injectable SRLs.
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http://dx.doi.org/10.1210/clinem/dgaa526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470473PMC
October 2020

Etiology, baseline clinical profile and comorbidities of patients with Cushing's syndrome at a single endocrinological center.

Endocrine 2020 12 3;70(3):616-628. Epub 2020 Sep 3.

Department and Clinic of Endocrinology, Diabetes, and Isotope Therapy, Wroclaw Medical University, Wroclaw, Poland.

Purpose: The aim of this study was to compare phenotype of patients with pituitary, adrenal and ectopic CS and identify the differences regarding biochemical parameters, clinical presentations, and comorbidities in CS patients who were diagnosed at the single endocrinological center in Wroclaw.

Methods: The study population involved 64 patients with CS (53 women and 11 men) diagnosed in Department of Endocrinology, Diabetes and Isotope Therapy in 2000-2018. Patients were divided into three etiologic groups: pituitary dependent-CS (P-CS) (64%), adrenal dependent CS (A-CS) (25%), and CS from an ectopic source (E-CS) (11%).

Results: Percentage of men in the A-CS group was significantly higher than in the other etiologic groups. ACTH, UFC, and cortisol in DST were significantly higher in E-CS group compare to P-CS and A-CS (p < 0.05). Mean potassium level in E-CS group was significantly lower than in P-CS and A-CS (p < 0.05). Median of time elapsed to diagnosis was significantly lower in the E-CS group compared with either the P-CS and the A-CS group (p < 0.01). The most frequently symptoms in CS patients were skin alterations (82.8%), weight gain (81.2%), and hypertension (81.2%).

Conclusions: The epidemiology of CS is changing toward a growing proportion of A-CS. All patients with E-CS presented a profound hypokalemia. Salient hypokalemia could be a biochemical marker more suggestive for E-CS rather than P-CS. The incidence of diabetes is more frequent in E-CS group than in P-CS and A-CS groups.
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http://dx.doi.org/10.1007/s12020-020-02468-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674323PMC
December 2020

Editorial: Health-Related Complications of Acromegaly.

Front Endocrinol (Lausanne) 2020 29;11:496. Epub 2020 Jul 29.

Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Wrocław, Poland.

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http://dx.doi.org/10.3389/fendo.2020.00496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403215PMC
July 2020

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

Endokrynol Pol 2020 29;71(5):376-381. Epub 2020 Jun 29.

Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Wroclaw, 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.
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http://dx.doi.org/10.5603/EP.a2020.0039DOI Listing
June 2020

Adequate timing and constant supervision are the keys for successful implementation of levothyroxine or levothyroxine/paracetamol absorption test.

Thyroid Res 2020 18;13. Epub 2020 May 18.

1Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, Rzgowska 281/289, 93-338 Lodz, Poland.

Background: Levothyroxine (LT) pseudomalabsorption due to medication non-adherence results in significant costs for Health Service. High dose LT or LT/paracetamol absorption test is used in such cases. Hence, establishment of an optimal test protocol and timing of sample collection is of utmost importance.

Case Presentation: A 34-year old woman was admitted to our Department because of severe hypothyroidism [on admission thyrotropin (TSH) > 100 μIU/ml, free thyroxine (FT) 0.13 ng/dl (ref. range 0.93-1.7)] despite apparently taking 1000 μg of LT a day. Autoimmune hypothyroidism had been diagnosed 4 years before during post-partum thyroiditis. Subsequently, it was not possible to control her hypothyroidism despite several admissions to two University Hospitals and despite vehement denial of compliance problems. There was no evidence of coeliac disease or other malabsorption problems, though gluten-free and lactose-free diet was empirically instigated without success. A combined paracetamol (1000 mg)/LT (1000 μg) absorption test was performed in one of these Hospitals. This showed good paracetamol absorption (from < 2 μg/ml to 14.11 μg/ml at 120 min), with inadequate LT absorption (FT increase from 5.95 pmol/l to 9.92 pmol/l at 0 and 120 min respectively). About 2 years prior to admission to our Department the patient was treated with escalating doses of levothyroxine [up to 3000 μg of T and 40 μg of triiodothyronine (T) daily] without significant impact on TSH (still > 75 μIU/ml, and FT still below reference range).After admission to our Department we performed a 2500 μg LT absorption test with controlled ingestion of crushed tablets, strict patient monitoring and sampling at 30 min intervals. We observed a quick and striking increase in FT from 0.13 to 0.46, 1.78, 3.05 and 3.81 ng/dl, at 0, 30, 60, 90 and 120 min, respectively. Her TSH concentration decreased to 13.77 μIU/ml within 4 days. When informed, that we had managed to "overcome" her absorption problems, she discharged herself against medical advice and declined psychiatric consultation.

Conclusions: Adequate patient supervision and frequent sampling (e.g. every 30 min for 210 min) is the key for successful implementation of LT absorption test. Paracetamol coadministration appears superfluous in such cases.
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http://dx.doi.org/10.1186/s13044-020-00079-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236172PMC
May 2020

Acromegaly due to ectopic growth hormone-releasing hormone secretion by lung carcinoid.

Pol Arch Intern Med 2020 08 1;130(7-8):685-687. Epub 2020 May 1.

Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Wrocław, Poland

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http://dx.doi.org/10.20452/pamw.15337DOI Listing
August 2020

Surgical implications of recent modalities for parathyroid imaging.

Gland Surg 2020 Feb;9(Suppl 2):S86-S94

Department of Endocrine Surgery, Third Chair of General Surgery, Jagiellonian University Medical College, Krakow, Poland.

Clinical or subclinical primary hyperparathyroidism (PHPT) is one of the most common endocrine disorders in the world. Parathyroidectomy is the treatment of choice in symptomatic patients, stabilizing the progression of complications caused by the destruction activity of parathyroid hormone (PTH). Parathyroid surgical techniques have evolved over the years from bilateral neck exploration, to minimally invasive single parathyroid gland exploration, to minimally invasive video-assisted parathyroidectomy. Localization of the abnormal parathyroid gland before surgery is crucial for the operation to be effective. Increased incidences of reoperations of the parathyroid glands and the rapid development of minimally invasive methods led to the development of new localization techniques. The noninvasive studies include ultrasound (US), computed tomography (CT), magnetic resonance (MR) and Tc-methoxyisobutylisonitrile (MIBI) scintigraphy combined with single-photon emission CT (SPECT/CT). Among the latest technologies, the four-dimensional (4D)-CT scan, positron emission tomography (PET)/CT and PET/MR are very promising, and are going to have surgical implications in the future.
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http://dx.doi.org/10.21037/gs.2019.11.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044083PMC
February 2020

A case of gastrinoma associated with ectopic Cushing syndrome.

Pol Arch Intern Med 2020 04 20;130(4):328-329. Epub 2020 Feb 20.

Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Wrocław, Poland

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http://dx.doi.org/10.20452/pamw.15201DOI Listing
April 2020

Importance of Illness Acceptance Among Other Factors Affecting Quality of Life in Acromegaly.

Front Endocrinol (Lausanne) 2019 14;10:899. Epub 2020 Jan 14.

Department of Psychiatry, Wroclaw Medical University, Wroclaw, Poland.

The aim of this study was to analyze psychological factors of patients with acromegaly and assessment of their relationship with the quality of life (QoL) in the context of the control of the disease. A total sample of 50 patients (62% of females; mean age = 51.66 ± 14.5) with acromegaly underwent a comparative, cross-sectional cohort assessment including the QoL (AcroQoL, WHOQoL-BREF), psychiatric morbidity (GHQ-28), the acceptance of illness (AIS) as well as influence of treatment, comorbidities and symptoms in the relation of disease activity. Acromegaly group was divided in two subgroups: patients with uncontrolled acromegaly (UA, = 28) and patients with controlled acromegaly (CA, = 22). The acromegaly groups did not differ in health-related QoL measured with AcroQoL and WHOQoL questionnaires. However, obtained results showed QoL impairments in all subscales and the study participants had decreased scores compared to reference values. The interaction of the relationship between the AIS and disease activity as well as the prevalence of all psychopathological symptoms and disease activity were tested and the statistically significantly differences in the context of QoL in AcroQoL questionnaires and its domains were observed in relation to the course of the disease. No difference in acromegaly symptoms as well as in number of comorbidities were found between CA and UA but these two parameters affected the results QoL scores in AcroQol questionnaires and their domains, regardless the disease activity. Similarly, the prevalence of psychopathological symptoms (GHQ-28) contributed the level of acceptance of the disease, regardless the disease activity. The strongest predictors of QoL were related to the level of illness acceptance ( = 0.01) as well as serum growth hormone concentration. Minding people with UA, the control of biochemical factors seemed to be more important for the QoL perception, while among CA, psychological variables such as AIS are observed to play a fundamental role in QoL. Moreover, inclusion of patient's acceptance of the illness into clinical routine would promote holistic, patient-centered care and empower doctor-patient partnership where patients' expectations and perceptions are constantly tracked. Obtaining biochemical control should not be considered as the only measure of treatment success.
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http://dx.doi.org/10.3389/fendo.2019.00899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972500PMC
January 2020

Low back pain and osteosclerotic bone lesions suggestive of metastases: a mask of osteopoikilosis.

Pol Arch Intern Med 2020 03 24;130(3):249-251. Epub 2020 Jan 24.

Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Wrocław, Poland

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http://dx.doi.org/10.20452/pamw.15158DOI Listing
March 2020

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

Adv Clin Exp Med 2020 Jan;29(1):25-32

Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, 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.
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http://dx.doi.org/10.17219/acem/111811DOI Listing
January 2020

Association of Vitamin D Receptor Polymorphisms With Activity of Acromegaly, Vitamin D Status and Risk of Osteoporotic Fractures in Acromegaly Patients.

Front Endocrinol (Lausanne) 2019 24;10:643. Epub 2019 Sep 24.

Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Wrocław, Poland.

The vitamin D receptor gene is one of the most widely studied tumorigenesis-related genes. The primary objective of this study was assessment of possible roles of gene polymorphisms in acromegaly, with regard to the activity of the disease and compared them with a control group. Furthermore, we have assessed the associations between these polymorphisms with vitamin D status as well as with TBS (trabecular bone score) and risk for osteoporotic fracture in acromegaly patients. We studied 69 patients with acromegaly and 51 healthy controls (CG). Acromegaly patients were divided into three subgroups on the basis of disease activity (AA, active acromegaly; CD, controlled disease; CA, cured acromegaly). In all patients, blood samples were obtained to assess the hormonal and metabolic status as well as genetic analysis. polymorphisms were determined by means of two methods, Polymerase Chain Reactions (PCR) and minisequencing (SNaPshot). Genotype frequencies for ApaI, TaqI, BsmI, and FokI polymorphisms did not deviate significantly from Hardy-Weinberg equilibrium (HWE) in the acromegaly group as well as in the control group. There was no statistically significant difference in distributions of these four VDR genotypes between acromegaly patients and the control group. This study revealed statistically significant negative correlation between risk of major osteoporotic fractures and genotypes tt (), aa () and bb ( in acromegaly groups. Furthermore, the negative correlations were observed between TBS and risk for major osteoporotic fractures and hip fractures. Our study suggests that tt (), aa () and bb () of gene may be associated with better bone quality and microarchitecture (higher TBS), which lead to a lower risk of osteoporotic fractures in acromegaly patients. TBS may be a useful tool for predicting risk of fractures in acromegaly patients.
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http://dx.doi.org/10.3389/fendo.2019.00643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768940PMC
September 2019

A Consensus on the Diagnosis and Treatment of Acromegaly Comorbidities: An Update.

J Clin Endocrinol Metab 2020 04;105(4)

Department of Medicine, CIBERER, Universidad Autónoma de Madrid, Madrid, Spain.

Objective: The aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013.

Participants: The Consensus Group, convened by 11 Steering Committee members, consisted of 45 experts in the medical and surgical management of acromegaly. The authors received no corporate funding or remuneration.

Evidence: This evidence-based consensus was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence following critical discussion of the current literature on the diagnosis and treatment of acromegaly comorbidities.

Consensus Process: Acromegaly Consensus Group participants conducted comprehensive literature searches for English-language papers on selected topics, reviewed brief presentations on each topic, and discussed current practice and recommendations in breakout groups. Consensus recommendations were developed based on all presentations and discussions. Members of the Scientific Committee graded the quality of the supporting evidence and the consensus recommendations using the GRADE system.

Conclusions: Evidence-based approach consensus recommendations address important clinical issues regarding multidisciplinary management of acromegaly-related cardiovascular, endocrine, metabolic, and oncologic comorbidities, sleep apnea, and bone and joint disorders and their sequelae, as well as their effects on quality of life and mortality.
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http://dx.doi.org/10.1210/clinem/dgz096DOI Listing
April 2020

Trabecular bone score (TBS) as a noninvasive and complementary tool for clinical diagnosis of bone structure in endocrine disorders.

Endokrynol Pol 2019 ;70(4):350-356

Department and Clinic of Endocrinology, Diabetes, and Isotope Therapy, Wrocław Medical University, Poland.

Trabecular bone score (TBS) index has recently been obtained as a result of textural greyscale analysis of DXA images. Because it enables the assessment of bone microarchitectural texture, TBS may be useful in evaluating bone quality. This study explores the current knowledge of the use of TBS in patients with endocrine disorders with co-occurring bone structure changes. Currently, the clinical importance TBS was verified in terms of disorders of the growth hormone/insulin-like growth factor 1 (GH/IGF-I) axis, glucocorticoid excess, thyroid and parathyroid disease, as well as in diabetes mellitus type 1 and 2. It has been clarified that patients suffering from various endocrinopathies are a group in which TBS should be used routinely because it correlates with clinical factors and may improve patient management in various endocrine disorders.
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http://dx.doi.org/10.5603/EP.a2019.0022DOI Listing
February 2020

Efficacy and safety of high-dose long-acting repeatable octreotide as monotherapy or in combination with pegvisomant or cabergoline in patients with acromegaly not adequately controlled by conventional regimens: results of an open-label, multicentre study.

Endokrynol Pol 2019 5;70(4):305-312. Epub 2019 Jul 5.

Department of Endocrinology, Diabetes and Isotope Therapy, Medical University, Wroclaw, Poland.

Introduction: Long-acting repeatable (LAR) octreotide i.m. is a potent, synthetic somatostatin analogue (SSA) that requires less frequent dosing and offers quality of life (QoL) benefits in acromegaly patients compared to its shorter-acting predecessor. This study investigated the efficacy and safety of high-dose Sandostatin® LAR® as monotherapy or in combination with pegvisomant or cabergoline in acromegalic patients with pituitary adenomas following previous failure of conventional SSA treatment.

Material And Methods: After three months of high-dose Sandostatin® LAR® monotherapy (40 mg), patients who achieved biochemical control (n = 7) continued to receive the same treatment for an additional four months, whereas uncontrolled patients were randomised to receive high-dose Sandostatin® LAR® in combination with pegvisomant (n = 31) or cabergoline (n = 32). Outcomes included biochemical response at eight months, QoL, and safety.

Results: After three months, 3 of 68 (4.4%) evaluable patients achieved a biochemical control (BC) as assessed by levels of growth hormone and insulin-like growth factor-1. At eight months, 4 of 67 (6.0%) patients achieved BC, including one receiving monotherapy and three receiving Sandostatin® LAR® plus cabergoline. Partial response rate, improvements in acromegaly signs and symptoms, and changes in QoL were similar for all three groups. All treatments were well tolerated with a slight excess of adverse events in the combination arms. There were no deaths or serious adverse events leading to treatment discontinuation.

Conclusion: These data demonstrate that high-dose Sandostatin® LAR® as monotherapy or in combination with pegvisomant or cabergoline is a feasible salvage option in patients with pituitary adenomas not adequately controlled on conventional SSA regimens.
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http://dx.doi.org/10.5603/EP.a2019.0023DOI Listing
February 2020

Turner syndrome and Cushing disease - the coexistence with overlapping complications: case report and literature review.

Gynecol Endocrinol 2019 Dec 27;35(12):1015-1020. Epub 2019 Jun 27.

Department and Clinic of Endocrinology, Diabetology and Isotope Therapy, Wroclaw Medical University, Wroclaw, Poland.

We present an unusual case of Turner syndrome (TS) and Cushing disease (CD) in a young woman, admitted to our department seven years after a successful surgical removal of ACTH-secreting pituitary tumor. To our knowledge, this is the first ever report of these two disorders coexisting. Our patient was diagnosed with TS at the age of 16 due to primary amenorrhea and short stature. Hormone replacement therapy with estrogen was initiated, but she did not receive growth hormone therapy. At the age of 28, she developed clinical and biochemical abnormalities consistent with hypercortisolism, but the definitive diagnosis of CD was established nine years later when she was admitted to our department. Appropriate treatment was applied, however, the patient developed serious complications: a myocardial infarction, diabetes and osteoporosis. Surgical treatment appeared to improve some, but not all of the symptoms, indicating a significant contribution of concomitant TS to the severity of adverse cardiovascular and bone turnover outcomes in a subject with a genetic susceptibility to these complications. Thus, multidisciplinary evaluation in such patients is strongly indicated, particularly if more predisposing conditions are present.
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http://dx.doi.org/10.1080/09513590.2019.1631281DOI Listing
December 2019

Long-term administration of fenspiride has no negative impact on bone mineral density and bone turnover in young growing rats.

Adv Clin Exp Med 2019 Jun;28(6):771-776

Department of Pharmacology, Wroclaw Medical University, Poland.

Background: Fenspiride is an antagonist of H1-histamine receptors that is used to treat acute and chronic respiratory tract infections and otitis media in children and adolescents.

Objectives: The aim of the study was to assess the influence of long-term administration of fenspiride on bone mineral density (BMD) and bone turnover in young growing rats.

Material And Methods: The experiment was carried out on 18 young (8-week-old) male Wistar rats receiving either fenspiride 15 mg/kg intragastrically (ig) (group F) or saline solution 4 mL/kg ig (group C) for 3 months. On days 1 and 93, blood samples were collected and serum levels of calcium, phosphorus and markers of bone turnover were measured. On days 2 and 92, BMD was measured with dual-energy x-ray absorptiometry (DXA) using small animal software.

Results: We detected no influence of fenspiride on weight gain, total body BMD (0.212 ±0.010 g/cm2 vs 0.204 ±0.024 g/cm2), hind limb BMD (0.264 ±0.016 g/cm2 vs 0.252 ±0.027 g/cm2), or bone macroscopic parameters. There were no significant differences between group F and group C in serum levels of osteocalcin (group F: 0.42 ±0.09 ng/mL vs group C: 0.43 ±0.08 ng/mL), C-terminal telopeptide of type I collagen (F: 0.31 ±0.08 ng/mL vs C: 0.29 ±0.08 ng/mL), osteoprotegerin (F: 5.47 ±0.78 pg/mL vs C: 5.35 ±1.65 pg/mL), receptor activator of nuclear factor kappa B ligand (F: 0.65 ±0.85 pg/mL vs C: 0.56 ±0.86 pg/mL), parathormone (F: 237 ±182 pg/mL vs C: 289 ±200 pg/mL), total calcium (F: 6.38 ±1.50 mg/dL vs C: 6.83 ±1.71 mg/dL), or inorganic phosphorus (F: 5.19 ±1.76 mg/dL vs C: 5.50 ±1.32 mg/dL).

Conclusions: Long-term administration of fenspiride has no negative impact on BMD and bone metabolism in young growing rats.
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http://dx.doi.org/10.17219/acem/93729DOI Listing
June 2019

Diagnostics and treatment of acromegaly - updated recommendations of the Polish Society of Endocrinology.

Endokrynol Pol 2019 ;70(1):2-18

Department of Endocrinology and Metabolic Disorders, Medical University, Lodz, Poland.

Acromegaly is a rare disease caused by excessive production of growth hormone (GH), typically by a pituitary tumour. The diagnosis is usually delayed, and patients frequently develop various complications that cause premature mortality. In patients with hypertension, heart failure, diabetes, and arthropathies that are not age-specific, attention should be paid to signs of acromegaly. Insulin-like growth factor 1 (IGF-1) assay should be used as a screening test whenever acromegaly is suspected. Further diagnostic investigations and treatment should be carried out at specialist centres. First-line treatment involves selective excision of pituitary adenoma using transsphenoidal access. Patients with chances of cure with surgical removal of the pituitary tumour should be referred to centres that have experience in this type of procedure, following pharmacological preparation. Other patients, as well as patients after failed neurosurgical treatment, should first receive chronic treatment with first-generation somatostatin analogues. For second-line treatment, pasireotide, pegvisomant, cabergoline, or combinations thereof should be considered. In every case, acromegaly sequelae require life-long monitoring and active treatment. Current recommendations, being an updated version of the recommendations published in Endokrynologia Polska in 2014, which take into account the Polish situation, should prove useful in the management of patients with acromegaly.
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http://dx.doi.org/10.5603/EP.a2018.0093DOI Listing
July 2019