Levels of small extracellular vesicles in patients treated with hyperbaric oxygenation.

Introduction: Hyperbaric oxygen (HBO2) therapy involves the inhalation of pure oxygen in a pressure chamber under increased ambient pressure. Recent research indicates that circulating small extracellular vesicles (sEVs) play important roles in human physiology and pathology. Therefore, the objective of this pilot study was to monitor the impact of HBO2 therapy on the levels of circulating sEVs in the serum of patients with necrotizing soft-tissue infections (NSTI), aseptic bone necrosis (ABN) or idiopathic sudden sensory neural hearing loss (ISSNHL). Material and methods: Serum-derived sEVs were isolated and quantified in 80 patients before and after HBO2 therapy applied for NSTI, ISSNHL and ABN patients as well as in normal controls who received neither HBO2 therapy nor steroids. Results: We observed a significant increase of circulating sEVs in patients with ISSNHL after HBO2 therapy (p < 0.05), as well as significantly elevated levels of sEVs after HBO2 therapy compared to patients with NSTI (p < 0.05) and ABN (p < 0.01). Conclusions: The increase in the levels of sEVs in ISSNHL may be evidence for both the intended reduction of inflammation as a result of steroid therapy and the inhibitory effect of oxidative stress induced by HBO2 therapy. Thus, sEVs released during HBO2 therapy might play an important biological role in mediating the response to therapy and might be a promising approach to gain further insights into the therapeutic efficacy of HBO2 therapy.

Presentation of Graves' orbitopathy within European Group On Graves' Orbitopathy (EUGOGO) centres from 2012 to 2019 (PREGO III).

BACKGROUND: Graves' orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves' Orbitopathy (EUGOGO) tertiary referral centres and initial management over time. METHODS: Prospective observational multicentre study. All new referrals with diagnosis of GO within September-December 2019 were included. Clinical and demographic characteristics, referral timelines and initial therapeutic decisions were recorded. Data were compared with a similar EUGOGO survey performed in 2012. RESULTS: Besides age (mean age: 50.5±13 years vs 47.7±14 years; p 0.007), demographic characteristics of 432 patients studied in 2019 were similar to those in 2012. In 2019, there was a decrease of severe cases (9.8% vs 14.9; p<0.001), but no significant change in proportion of active cases (41.3% vs 36.6%; p 0.217). After first diagnosis of GO, median referral time to an EUGOGO tertiary centre was shorter (2 (0-350) vs 6 (0-552) months; p<0.001) in 2019. At the time of first visit, more patients were already on antithyroid medications (80.2% vs 45.0%; p<0.001) or selenium (22.3% vs 3.0%; p<0.001). In 2019, the initial management plans for GO were similar to 2012, except for lid surgery (2.4% vs 13.9%; p<0.001) and prescription of selenium (28.5% vs 21.0%; p 0.027). CONCLUSION: GO patients are referred to tertiary EUGOGO centres in a less severe stage of the disease than before. We speculate that this might be linked to a broader awareness of the disease and faster and adequate delivered treatment.

Treatment Results of Endoscopic Transnasal Orbital Decompression for Graves' Orbitopathy-A Single-Center Retrospective Analysis in 28 Orbits of 16 Patients.

Graves' orbitopathy (GO) is an extrathyroidal manifestation of Graves' disease (GD), which can be associated with corneal ulcerations or optic neuropathy in severe forms. Transnasal endoscopic orbital decompression (TEOD) is a surgical procedure performed in order to decrease the intraorbital pressure by removing part of its bony borders in cases with excessive mass in orbit. The aim of this study was to present the results and evaluate the efficacy of TEOD for GO. The retrospective study included 28 orbits (16 patients) who underwent TEOD from 2017 to 2020. Outcome was evaluated based on visual acuity improvement, clinical activity score (CAS) decrease, proptosis, and intraocular pressure (IOP) reduction. A preoperative best-corrected visual acuity (BCVA) increased from 0.69 ± 0.385 (mean ± standard deviation) to 0.74 ± 0.332 (p = 0.17) postoperatively. CAS decreased in 15 orbits postoperatively. Proptosis decreased from 22.89 ± 1.873 mm to 21.25 ± 2.053 mm (p < 0.05). IOP decreased from a preoperative 16.11 ± 3.93 mmHg to 14.40 ± 3.27 mmHg (p < 0.05) postoperatively. In addition, postoperative relief of exposure keratitis was observed. The analysis of development of iatrogenic diplopia revealed increasing in degree of diplopia. TEOD shows rare complications, but significant improvements in BCVA, CAS, proptosis, and IOP.

Decrease in Bone Formation and Bone Resorption during Intravenous Methylprednisolone Pulse Therapy in Patients with Graves' Orbitopathy.

Background: Treatment with glucocorticoids (GCs) is associated with side effects. In contrast to the well-known negative impact on bone tissue exerted by oral GCs, few data are available regarding intravenous GCs. We investigated the influence of intravenous methylprednisolone (IVMP) on bone turnover markers (BTM): amino-terminal propeptide of type I procollagen (P1NP) and the C-terminal telopeptide of type I collagen (CTX), and on calcium metabolism parameters: 1,25-dihydroxyvitamin D (1,25(OH)2D), 25-hydroxyvitamin D (25(OH)D), calcium (Ca), phosphate (P), and intact parathormone (iPTH). Methods: In a prospective study, 23 consecutive subjects with Graves' orbitopathy were included and treated with IVMP according to the European Group on Graves' Orbitopathy recommendations. We evaluated effects on BTM occurring during the first 7 days after 0.5 g IVMP, and after the therapy with 12 IVMP pulses with a cumulative dose of 4.5 g. Results: We observed prompt but transient decrease of P1NP (p < 0.001) and the reduction of CTX (p = 0.02) after the first IVMP pulse. Following the full course of IVMP therapy, both P1NP and CTX were found decreased (p < 0.05 and p < 0.01, respectively). Conclusions: A single pulse of 0.5 g IVMP already decreases bone formation and resorption; however, this change is transient. The full therapy is associated with suppression of bone turnover.

Therapy With Intravenous Methylprednisolone Pulses Is Associated With Loss of Bone Microarchitecture in Trabecular Bone Score -Assessment Among Patients With Moderate-to-Severe Graves' Orbitopathy: A Pilot Study.

Background: Therapy with intravenous glucocorticoids (GCs) is associated with various side effects, however, the impact on bone remains elusive. Trabecular bone score (TBS) is a diagnostic tool providing information on bone microarchitecture based on images obtained from dual-energy X-ray absorptiometry. We investigated the influence of the intravenous methylprednisolone (IVMP) pulse administration on TBS in patients with moderate-to-severe Graves' orbitopathy (GO). Methods: Fifteen patients with GO were treated with 12 IVMP pulses (6x0.5g, 6x0.25 g on a weekly schedule). They received supplementation with 2000 IU of vitamin D and 1.0 g of calcium throughout the study period. TBS was assessed at baseline and after last IVMP pulse. To determine the difference between values at baseline and after treatment the least significant change (LSC) methodology was used. We compared pre- and posttreatment mean TBS values. Results: We found a significant decrease of TBS in 5 out of 15 (33%) patients. Mean TBS value decreased becoming 2.4% lower than at baseline (p<0.05). Conclusions: IVMP pulse therapy exerts negative effect on bone microarchitecture in TBS assessment. The analysis of the clinical risk factors for osteoporosis and the evaluation of bone mineral density and TBS should be considered before initiating IVMP therapy.

Dysthyroid Optic Neuropathy: Treatment with Additional Intravenous Methylprednisolone Pulses after the Basic Schedule Is Associated with Stabilization or Further Improvement of Clinical Outcome.

Background: Dysthyroid optic neuropathy (DON) is a sight-threatening complication of Graves' orbitopathy (GO). Treatment of DON consists of the urgent administration of intravenous methylprednisolone (ivMP) in very high doses followed by orbital decompression if the response is poor or absent. It is advised to continue the therapy with pulses of ivMP in a weekly schedule. The purpose of this study was to evaluate the impact of the additional treatment with ivMP in a 12-week protocol on visual acuity (VA), color vision, clinical activity score (CAS) and proptosis in patients with DON. Methods: This study was performed on 19 patients with DON (26 eyes) treated with ivMP in very high doses, with further orbital decompression in 11 individuals (15 eyes). VA, color vision, CAS and proptosis were evaluated prior to the DON treatment, before and after the 12-week ivMP (first and last pulse). Additionally follow up was performed (22 eyes). Results: VA and color vision improved between the first and last pulse of the additional ivMP treatment (p = 0.04 and p = 0.003, respectively). CAS and proptosis were reduced at the end of the 12-week ivMP therapy compared to observations at the beginning (p < 0.001 and p = 0.04, respectively). Follow up confirmed stabilization of this achievement. Conclusions: The results of this study suggest that additional treatment with 12 pulses of ivMP improves or stabilizes the outcome of basic therapy in patients with DON.

Prevention of Iodinated Contrast Media-Induced Hyperthyroidism in Patients with Euthyroid Goiter.

INTRODUCTION: Iodinated contrast media (ICM)-induced hyperthyroidism is an underestimated, potentially severe condition; however, its prevention has not been sufficiently investigated. The aim of this study was to evaluate the influence of ICM on thyroid status, the advantages of prophylactic therapy for iodine-induced hyperthyroidism (IIH) in patients with euthyroid goiter and cardiovascular comorbidities, and the association between the incidence of IIH and thyroid volume. METHODS: Thirty-six euthyroid patients undergoing procedures involving ICM administration were divided into 2 groups: the first group (n = 13) received prophylactic treatment with thiamazole or thiamazole combined with sodium perchlorate during ICM exposure; the second group (n = 23) did not receive prophylaxis. Thyroid-stimulating hormone levels were evaluated before and after ICM, and thyroid hormone levels were assessed after ICM at different points in time. The morphology of the thyroid was evaluated by ultrasonography. RESULTS: Twenty-one patients (58%) developed hyperthyroidism after ICM. Hyperthyroidism was observed more frequently in the group without prophylactic treatment than in the group with prophylaxis (65 vs. 15%, respectively; p = 0.006). No cases of overt hyperthyroidism were observed in the group receiving thiamazole with sodium perchlorate. IIH persisted for a median time of 52.5 days. Larger thyroid volume was associated with a significantly higher occurrence of ICM-induced hyperthyroidism (p = 0.04). CONCLUSIONS: Patients with euthyroid goiter receiving ICM are at risk of developing hyperthyroidism. The occurrence of hyperthyroidism after ICM in euthyroid patients with goiter is higher in those with larger thyroid volume. The frequency of ICM-induced hyperthyroidism in euthyroid patients with goiter is lower in those receiving prophylactic therapy with thiamazole in monotherapy or in combination with sodium perchlorate than in those not receiving prophylactic treatment.

"Small Thyroid Gland" in Reproductive Women without Autoimmune Thyroid Disease-Ultrasonographic Evaluation as a Useful Screening Tool for Hypothyroidism.

Proper thyroid function is important for women of childbearing age, as hypothyroidism affects fertility, pregnancy and offspring. The upper reference limit for thyrotropin (TSH) in pregnancy was defined as <2.5 mU/L in the first trimester. Recommendations include either universal screening of TSH before pregnancy, or identifying individuals at "high risk" for thyroid illness. "Small thyroid gland" not associated with autoimmune thyroid disease (AITD) seems to be a reason for hypothyroidism and probably should be included in target case finding procedure before pregnancy. The purpose of this cross-sectional study was to analyze relationships between the thyroid volume and its function, and to determine the thyroid volume as a predictive factor for TSH levels above 2.5 µIU/mL in reproductive women without AITD. We included 151 women without AITD, and aged 18-40. Blood and urine samples were analyzed for parameters of thyroid function. Ultrasound examination of the thyroid was performed. The thyroid volume was negatively correlated with TSH. Women with a thyroid volume in the 1st quartile for the study population presented higher TSH levels versus women in the 4th quartile (p = 0.0132). A thyroid volume cut-off point of 9 mL was the predictive factor for TSH levels above 2.5 µIU/mL (p = 0.0037).

Glucocorticoid Withdrawal-An Overview on When and How to Diagnose Adrenal Insufficiency in Clinical Practice.

Glucocorticoids (GCs) are widely used due to their anti-inflammatory and immunosuppressive effects. As many as 1-3% of the population are currently on GC treatment. Prolonged therapy with GCs is associated with an increased risk of GC-induced adrenal insufficiency (AI). AI is a rare and often underdiagnosed clinical condition characterized by deficient GC production by the adrenal cortex. AI can be life-threatening; therefore, it is essential to know how to diagnose and treat this disorder. Not only oral but also inhalation, topical, nasal, intra-articular and intravenous administration of GCs may lead to adrenal suppression. Moreover, recent studies have proven that short-term (<4 weeks), as well as low-dose (<5 mg prednisone equivalent per day) GC treatment can also suppress the hypothalamic-pituitary-adrenal axis. Chronic therapy with GCs is the most common cause of AI. GC-induced AI remains challenging for clinicians in everyday patient care. Properly conducted GC withdrawal is crucial in preventing GC-induced AI; however, adrenal suppression may occur despite following recommended GC tapering regimens. A suspicion of GC-induced AI requires careful diagnostic workup and prompt introduction of a GC replacement treatment. The present review provides a summary of current knowledge on the management of GC-induced AI, including diagnostic methods, treatment schedules, and GC withdrawal regimens in adults.

RAGE and HMGB1 Expression in Orbital Tissue Microenvironment in Graves' Ophthalmopathy.

Graves' ophthalmopathy (GO) is a chronic autoimmune inflammatory disorder involving orbital tissues. A receptor for advanced glycation end products (RAGE) and its ligand high mobility group box 1 (HMGB1) protein trigger inflammation and cell proliferation and are involved in the pathogenesis of various chronic inflammatory diseases. This study was aimed to evaluate RAGE and HMGB1 expression in GO to determine its potential clinical significance. To the best of our knowledge, this is the first study showing RAGE and HMGB1 expression in orbital tissue using immunohistochemistry. Sections of orbital adipose tissue obtained from patients diagnosed with GO (23 patients; 36 orbits) and normal controls (NC) (15 patients; 15 orbits) were analyzed by immunohistochemistry for RAGE and HMGB1 expression. Expression profiles were then correlated with clinical data of the study group. RAGE and HMGB1 expression were elevated in GO patients in comparison with NC (p = 0.001 and p = 0.02, respectively). We observed a correlation between RAGE expression and occurrence of dysthyroid optic neuropathy (DON) (p = 0.05) and levels of TSH Receptor Antibodies (TRAb) (p = 0.01). Overexpression of RAGE and HMGB1 might be associated with GO pathogenesis. In addition, RAGE and HMGB1 proteins may be considered as promising therapeutic targets, but this requires further research.

Treatment with Intravenous Methylprednisolone in Patients with Graves' Orbitopathy Significantly Affects Adrenal Function: Assessment of Serum, Salivary Cortisol and Serum Dehydroepiandrosterone Sulfate.

Treatment of active, moderate-to-severe Graves' orbitopathy (GO) is the administration of intravenous methylprednisolone (IVMP). IVMP may be followed by additional therapy with oral prednisone. The aim of this study was to analyze the impact of IVMP on adrenal function by evaluation of serum, salivary cortisol and serum dehydroepiandrosterone sulfate (DHEA-S). Fourteen patients received IVMP treatment (cumulative dose of 4.5 g in 12 weekly infusions) followed by oral prednisone (for three months). All patients showed normal adrenal function before the 12th IVMP pulse and one patient was diagnosed with secondary adrenal insufficiency (AI) after prednisone treatment. DHEA-S was significantly lower before the 12th IVMP pulse and after oral prednisone (p = 0.015 and p = 0.00002, respectively) in comparison to evaluation before therapy. DHEA-S levels were below the reference range in one and three patients before the 12th IVMP pulse and after prednisone therapy, respectively. We observed decreased serum (p = 0.05) and salivary (p = 0.011) cortisol levels after oral prednisone therapy in comparison to evaluation before therapy. Treatment with IVMP in a cumulative dose of 4.5 g affects adrenal function, causing more severe impairment of DHEA-S secretion than that of cortisol but does not cause secondary AI. Additional therapy with oral glucocorticoids after IVMP can cause secondary AI.

Exposure to Bisphenol A Analogs and the Thyroid Function and Volume in Women of Reproductive Age-Cross-Sectional Study.

Bisphenols (BPs) are commonly known plastifiers that are widely used in industry. The knowledge about the impact of BPs on thyroid function is scarce. Proper thyroid functioning is especially important for women of reproductive age, as hypothyroidism affects fertility, pregnancy outcomes and the offspring. There are no studies analyzing the influence of BPs on thyroid function and volume in non-pregnant young women. The aim of this cross-sectional study was to evaluate the relationship between bisphenol A and its 10 analogs (BPS, BPC, BPE, BPF, BPG, BPM, BPP, BPZ, BPFL, and BPBP) on thyroid function and volume in women of reproductive age. Inclusion criteria were: female sex, age 18-40 years. Exclusion criteria were history of any thyroid disease, pharmacotherapy influencing thyroid function, pregnancy or puerperium, and diagnosis of autoimmune thyroid disease during this study. Venous blood was drawn for measurement of thyrotropin (TSH), free thyroxine, thyroid peroxidase antibodies, thyroglobulin antibodies, BPs. Urine samples were analyzed for: ioduria and BPs. Ultrasound examination of thyroid gland was performed. One hundred eighty participants were included into the study. A negative correlation was found between urine BPC and the thyroid volume (R = -0.258; p = 0.0005). Patients with detected urine BPC presented smaller thyroid glands than those with not-detected urine BPC (p = 0.0008). A positive correlation was found between TSH and urine BPC (R = 0.228; p = 0.002). Patients with detected urine BPC presented higher concentrations of TSH versus those with not-detected urine BPC (p = 0.003). There were no relationships between any of serum BPs as well as the other urine BPs and thyroid function and its volume. The only BP that demonstrated the relationship between thyroid function and its volume was BPC, probably because of its chemical structure that most resembles thyroxine. Exposure to this BP may result in the development of hypothyroidism that could have a negative impact on pregnancy and the offspring.

Immunological Aspects of Graves' Ophthalmopathy.

The body's autoimmune process is involved in the development of Graves' disease (GD), which is manifested by an overactive thyroid gland. In some patients, autoreactive inflammatory reactions contribute to the development of symptoms such as thyroid ophthalmopathy, and the subsequent signs and symptoms are derived from the expansion of orbital adipose tissue and edema of extraocular muscles within the orbit. The autoimmune process, production of antibodies against self-antigens such as TSH receptor (TSHR) and IGF-1 receptor (IGF-1R), inflammatory infiltration, and accumulation of glycosaminoglycans (GAG) lead to edematous-infiltrative changes in periocular tissues. As a consequence, edema exophthalmos develops. Orbital fibroblasts seem to play a crucial role in orbital inflammation, tissue expansion, remodeling, and fibrosis because of their proliferative activity as well as their capacity to differentiate into adipocytes and myofibroblasts and production of GAG. In this paper, based on the available medical literature, the immunological mechanism of GO pathogenesis has been summarized. Particular attention was paid to the role of orbital fibroblasts and putative autoantigens. A deeper understanding of the pathomechanism of the disease and the involvement of immunological processes may give rise to the introduction of new, effective, and safe methods of treatment or monitoring of the disease activity.

High dose intravenous methylprednisolone pulse therapy causes transient increase of serum calcium and phosphate levels.

High and very high doses of intravenous methylprednisolone (IVMP) administered in pulses are the first-line treatment for active, moderateto- severe, as well as sight-threatening Graves' orbitopathy (GO). However, glucocorticoid therapy is associated with side effects, among others, it affects bone metabolism. AIM: The aim of study was to assess the acute effects of high and very high doses of IVMP on calcium (Ca) and phosphate (P) balance in euthyroid patients with moderate-to-severe GO and sight-threatening GO due to dysthyroid optic neuropathy (DON). MATERIALS AND METHODS: Thirty-six patients with active, moderate-tosevere GO were treated with twelve once-weekly pulses (with cumulative dose of 4.5 g IVMP) and 11 patients with DON received 3 intravenous pulses of 1.0 g IVMP on three consecutive days. We measured serum levels of Ca and P at baseline and on the following days after the beginning of the IVMP therapy. RESULTS: We observed a significant increase in serum Ca level on the next day after the 1st IVMP pulse both in patients with moderate-tosevere GO and with DON. Then, on the day 3, the decrease of serum Ca was noticed. In patients with moderate-to-severe GO, on the day 2 serum P showed a significant increase and then, it returned to basal level on the day 3. CONCLUSIONS: We observed a significant increase in serum Ca level on the next day after the 1st IVMP pulse both in patients with moderate-tosevere GO and with DON. Then, on the day 3, the decrease of serum Ca was noticed. In patients with moderate-to-severe GO, on the day 2 serum P showed a significant increase and then, it returned to basal level on the day 3.

[Endoscopic decompression of orbit in Graves' orbitopathy]. / Endoskopowa dekompresja oczodolu w orbitopatii tarczycowej.

Graves' orbitopathy (GO) is an extrathyroidal manifestation of Graves' disease (GD). The majority of patients has mild form of the disease, with no need of additional treatment. A few percent of patients can have a severe or very severe course of disease. In severe forms of GO there might occur considerable exophthalmos complicated in some cases with corneal ulceration or pressure on optic nerve leading to neuropathy (DON, dysthyroid optic neuropathy). In therapy of severe forms of GO different types of treatment are used depending on diagnosis and activity of disease. The pharmacological (among the others very high doses of intravenous methylprednisolone) and surgery treatment (orbit decompression) are used. The orbital decompression is a procedure performed in order to decrease the intraorbital pressure by removing part of its bony borders in cases with excessive mass in orbit. For decades many external approaches have been used. With the progress of the endoscopic techniques the endoscopic orbit decompression has become the first line treatment. The lack of facial incisions is connected with many benefits for patients. In our article endoscopic decompression technique in GO was described, as well as available medical literature concerning this technique and its outcomes was performed.

Paediatric-onset and adult-onset Graves' disease share multiple genetic risk factors.

BACKGROUND: Graves' disease (GD) is an autoimmune thyroid disease (AITD) with a peak incidence between 30 and 50 years of age. Although children and adolescents may also develop the disease, the genetic background of paediatric-onset GD (POGD) remains largely unknown. Here, we looked for similarities and differences in the genetic risk factors for POGD and adult-onset GD (AOGD) as well as for variants associated with age of GD onset. MATERIALS AND METHODS: A total of 1267 GD patients and 1054 healthy controls were included in the study. Allele frequencies of 40 established and suggested GD/AITD genetic risk variants (39 SNPs and HLA-DRB1*03) were compared between POGD (N = 179), AOGD (N = 1088) and healthy controls. Subsequently, multiple linear regression was used to explore the relationship between age of GD onset and genotype for each locus. RESULTS: We identified six POGD risk loci, all of them were also strongly associated with AOGD. Although for some of the analysed variants, including HCP5 (rs3094228), PRICKLE1 (rs4768412) and SCGB3A2 (rs1368408), allele frequencies differed nominally between POGD and AOGD patients, these differences were not significant after applying multiple testing correction (Pcor  = 0.05/40 = 1.25 × 10-3 ). Regression analysis showed that patients with higher number of HCP5 risk alleles tend to have a significantly earlier onset of GD (P = 6.9 × 10-5 ). CONCLUSIONS: The results of our study revealed that POGD and AOGD share multiple common genetic risk variants. Moreover, we demonstrated for the first time that HCP5 polymorphism is associated with an earlier age of GD onset in a dose-dependent manner.

Therapy of moderate-to-severe Graves' orbitopathy with intravenous methylprednisolone pulses is not associated with loss of bone mineral density.

PURPOSE: To evaluate the influence of intravenous methylprednisolone (IVMP) pulse administration on bone mineral density (BMD) of the lumbar spine and the femoral neck in patients with moderate-to-severe Graves' orbitopathy (GO). METHODS: Thirty-five patients with GO in euthyreosis were treated with 12 IVMP pulses (6 × 0.5 g, 6 × 0.25 g on a weekly schedule). Supplementation with 1.0 g of calcium and 800 IU of vitamin D was initiated in all patients before beginning therapy. BMD of the lumbar spine (L1-L4) and the femoral neck were assessed at baseline and after the last IVMP pulse using dual-energy X-ray absorptiometry. To determine differences in BMD between values at baseline and after treatment, we used the least significant change (LSC) methodology. LSC values were calculated to be 3 and 5% for the lumbar spine and the femoral neck, respectively. Change in BMD equal to or exceeding the LSC was assessed as either increase or decrease of BMD. We then compared pre-treatment and post-treatment mean BMD values at the lumbar spine and the femoral neck. RESULTS: We did not observe a decrease of BMD at any site equal to or exceeding the LSC. We found an increase of BMD in at least one measurement site equal to or exceeding the LSC value in 43% of patients, mostly in the lumbar spine (31%). Mean femoral neck BMD did not change while mean lumbar BMD increased. CONCLUSIONS: IVMP given in weekly intravenous pulses does not lead to loss of BMD of the lumbar spine and the femoral neck.

Influence of Methylprednisolone Pulse Therapy on Liver Function in Patients with Graves' Orbitopathy.

PURPOSE: Intravenous methylprednisolone (IVMP) pulse therapy is the first-line treatment in active moderate-to-severe Graves' orbitopathy (GO) and dysthyroid optic neuropathy (DON). One of the adverse effects of this therapy is liver dysfunction that can be mild (ALT < 100 U/L), moderate (ALT: 100-300 U/L), and severe defined as acute liver injury (ALI) (ALT > 300 U/L). ALI can be irreversible and fatal. The aim of the study was to evaluate the influence of two different schemes of therapy with IVMP in moderate-to-severe GO and DON on biochemical liver parameters. MATERIALS AND METHODS: 49 patients with moderate-to-severe GO were treated with IVMP in every week schedule (cumulative dose 4.5 g), and 19 patients with DON received 3.0 g IVMP (1.0 g/day for 3 consecutive days). AST, ALT, and total bilirubin were measured before treatment and after IVMP in the following selected pulses: after 0.5 g (A1), 3.0 g (A2), and 4.5 g (A3) in the group with moderate-to-severe GO and after 3.0 g IVMP in the group with DON (B1). RESULTS: We observed a statistically higher level of AST and ALT after therapy with 3.0 g of IVMP (B1) than after 0.5 g (A1), 3.0 g (A2), and 4.5 g of IVMP (A3). Mild elevation of ALT was found in 4% and 11% of patients with moderate-to-severe GO and DON, respectively. Moderate elevation of ALT was found in 0% and 21% of patients with moderate-to-severe GO and DON, respectively. There were no cases of ALI. CONCLUSION: Therapy of GO with higher doses (1.0 g) of IVMP in consecutive days is associated with higher risk of liver damage than treatment with moderate doses (≤0.5 g) in every week schedule. This trial is registered with NCT03667157.