Publications by authors named "Rosario Le Moli"

12 Publications

  • Page 1 of 1

Evidence That Baseline Levels of Low-Density Lipoproteins Cholesterol Affect the Clinical Response of Graves' Ophthalmopathy to Parenteral Corticosteroids.

Front Endocrinol (Lausanne) 2020 22;11:609895. Epub 2020 Dec 22.

Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Medical Center, Catania, Italy.

Background: High dose intravenous glucocorticoid (ivGC) therapy is the first line treatment in moderate to severe Graves' ophthalmopathy (GO) and is associated with a clinical response rate ranging from 50% to 80%. Recently, a positive correlation between total cholesterol and low-density lipoproteins cholesterol (LDLc) with GO presentation and activity has been described.

Objective: We aimed at evaluating whether, in patients with moderate to severe active GO treated with ivGC therapy, cholesterol, and LDLc could represent valuable predictive factors of medium-term GO outcome.

Methods: This single center retrospective study was conducted in a consecutive series of 87 patients undergone ivGC therapy because affected by moderate to severe active GO. Clinical outcome of GO was evaluated at week 6 (W6) and 12 (W12) in respect to baseline conditions (week 0) by the seven points CAS according to EUGOGO recommendations. Univariate analysis and binary logistic regression were performed for the outcome variable W12CAS.

Results: In patients with active GO, an early positive clinical response to ivGC therapy (as evaluated by CAS at 6W) was a strong determinant (OR=13) of the clinical outcome at week 12. Moreover, high levels of LDLc at baseline were positively associated with a reduction in the likelihood of being classified as improved at 12W. Patients with LDLc >193.6 mg/dl were very likely to respond negatively to ivGC therapy independently from the response at 6W. Based on these results, we propose a predictive decision-making model to be tested in future prospective studies.

Discussion: We found that, in patients with active GO, both an early clinical response to ivGC therapy and baseline LDLc levels are significant determinants of GO outcome (W12CAS). These data support the need of a cholesterol-lowering treatment before addressing these patients to ivGC therapy.
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http://dx.doi.org/10.3389/fendo.2020.609895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784376PMC
May 2021

Role of selenium and myo-inositol supplementation on autoimmune thyroiditis progression.

Endocr J 2020 Nov 15;67(11):1093-1098. Epub 2020 Jul 15.

Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Medical Center, Via Palermo 636, 95122 Catania, Italy.

Previous reports indicate that selenium supplementation may be useful to reduce cell oxidative stress. In particular, selenium may decrease the level of thyroid autoantibodies in patients with Hashimoto's thyroiditis (HT). Recent studies also indicate that myo-inositol may have beneficial effects on thyroid function in patients with HT. Hence, the aim of the present study is to evaluate whether myo-inositol may enhance the protective effect of selenium on HT progression to hypothyroidism. The study was designed as observational and retrospective. Thyroid hormones were evaluated in patients with HT who were either euthyroid or subclinically hypothyroid. These patients were subdivided into three groups: untreated, treated with selenomethionine alone (Se-meth: 83 μg/day) and treated with Se-meth plus myo-inositol (Se-meth + Myo-I: 83 μg/day + 600 mg/day). Outcome evaluation was performed at baseline and after 6 and 12 months of treatment. High-resolution ultrasound of the thyroid gland was performed to evaluate changes in thyroid echoic pattern during the study. Compared to baseline, levels of thyroid-stimulating hormone (TSH) increased significantly in untreated patients but decreased by 31% and 38%, respectively, in those treated with Se-meth and Se-meth + Myo-I. Moreover, in the latter group the TSH reduction was observed earlier than in the Se-meth-treated group. Densitometric analysis of thyroid ultrasonography showed an echoic pattern improvement in both treated groups compared to untreated patients, although this difference was not statistically significant. Thus, Se-meth treatment is effective in patients with HT and its effect may be improved in combination with Myo-I through earlier achievement of TSH levels closer to physiological concentrations.
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http://dx.doi.org/10.1507/endocrj.EJ20-0062DOI Listing
November 2020

Corticosteroid Pulse Therapy for Graves' Ophthalmopathy Reduces the Relapse Rate of Graves' Hyperthyroidism.

Front Endocrinol (Lausanne) 2020 11;11:367. Epub 2020 Jun 11.

Endocrinology, Department of Clinical and Experimental Medicine, Garibaldi-Nesima Medical Center, University of Catania, Catania, Italy.

A course of anti-thyroid drugs (ATD) is the most common first line treatment for Graves' hyperthyroidism. However, hyperthyroidism relapse is frequent (30-70%). Due to the autoimmune nature of Graves' disease, the immunosuppressive treatment used for active Graves' orbitopathy (GO) may reduce the relapses after ATD discontinuation. To evaluate the recurrence rate in Graves' patients who, in addition to standard ATD, were treated or not treated with parenteral methylprednisolone (MPDS) for GO. Single-center retrospective study in a continuous series of 162 newly diagnosed Graves' patients, with or without GO, all gone into remission and followed-up until hyperthyroidism recurrence or at least 4 years after ATD discontinuation. Patients with moderate-severe active GO underwent middle dose MPDS treatment according to the EuGoGo guidelines. Cox proportional-hazard model was used to comparatively evaluate the risk of recurrence and the predictive factors in patients treated or not treated with MPDS pulse therapy. MPDS treatment was the most significant factor that independently correlated with a reduced risk of hyperthyroidism relapse (HR = 0.53, 95% C.I. = 0.31-0.89). FT3 and female sex were also independent protective factors, while age almost reached the significance level, = 0.062. The efficacy of MPDS was very high in patients aged <40 years (42.1% decrease in relapses, < 0.01) but it was not significant in older patients. Our study found that after ATD discontinuation the frequency of Graves' hyperthyroidism relapse was reduced in patients treated with MPDS pulse therapy for GO. This effect was more marked in young patients.
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http://dx.doi.org/10.3389/fendo.2020.00367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301650PMC
May 2021

Onset of Marine-Lenhart syndrome and Graves' ophthalmopathy in a female patient treated with alemtuzumab for multiple sclerosis.

Hormones (Athens) 2021 Mar 5;20(1):161-165. Epub 2020 Jun 5.

Department of Clinical and Experimental Medicine, Endocrinology Unit, University of Catania, Garibaldi-Nesima Hospital, Via Palermo 636, 95122, Catania, Italy.

Background: Immune checkpoint blockade therapy may lead to thyroid dysfunction in 3-7% of treated patients. Alemtuzumab is a CD52 inhibitor leading to thyroid dysfunction in approximately 40% of patients. A female patient was affected by multiple sclerosis (MS) and subclinical hyperthyroidism due to an autonomously functioning thyroid nodule (AFTN). After alemtuzumab treatment, she developed aggressive clinical hyperthyroidism consistent with Marine-Lenhart syndrome.

Case Presentation: A 36-year-old woman presented in July 2019 with symptoms of hyperthyroidism and eye complaints. Three years earlier, she was diagnosed with MS. Subclinical hyperthyroidism was diagnosed in April 2017. Thyroid scintigraphy showed an intranodular distribution of Tc-pertechnatate consisting of an AFTN in the right lobe of the thyroid. In June 2018, because of the MS, she was treated with alemtuzumab. In November 2018, she was started on methimazole treatment because of the symptoms of hyperthyroidism. In December 2018, thyroid function was normal under methimazole treatment. In June 2019, the patient received a second round of alemtuzumab administration. One month later, she developed symptoms of hyperthyroidism. These symptoms were accompanied by diplopia. Blood tests showed severe hyperthyroidism. Thyroid scintigraphy showed a diffuse distribution of Tc-pertechnatate and the presence of a "cool" area in the right lobe of the thyroid, confirmed by ultrasonography. The nodule was diagnosed as a low-risk indeterminate lesion.

Conclusion: We present a case of Graves' disease with active, moderate-to-severe Graves' ophthalmopathy in a patient with pre-existing AFTN presenting with a coexisting, rare case of Marine-Lenhart syndrome associated with immune reconstitution after alemtuzumab treatment.
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http://dx.doi.org/10.1007/s42000-020-00215-9DOI Listing
March 2021

Efficacy of Botulinum Toxin A for Treating Cramps in Diabetic Neuropathy.

Ann Neurol 2018 11 16;84(5):674-682. Epub 2018 Oct 16.

Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Medical Center, Catania, Italy.

Objective: Muscle cramps occur in >50% of diabetic patients and reduce the quality of life. No effective treatment is available. We evaluated the clinical effectiveness of botulinum toxin A (BTX-A) injections for treating cramps in diabetic patients with neuropathy.

Methods: This single-center, double-blind, placebo-controlled perspective study investigated the efficacy and safety of BTX-A intramuscular injection for treating calf or foot cramps refractory to common pharmacological drugs. Fifty diabetic patients with peripheral neuropathy and cramps were randomly assigned to 2 matched groups. BTX-A (100 or 30 units) or saline was injected on each side into the gastrocnemius or the small flexor foot muscles. Changes in pain intensity (primary outcome) and cramp frequency were evaluated over the course of 20 weeks after BTX-A administration. Cramp interference in daily life and the electrophysiological cramp threshold frequency were also measured. The treatment was repeated 5 months after first injection in 19 responders.

Results: All outcome measures improved significantly after BTX-A compared with placebo. The changes with respect to baseline were already significant after 1 week and persisted up to week 14. Only 5 of 25 (20%) patients were nonresponders (<50% decrease of the primary outcome). The responses to a second BTX-A injection provided results similar to the first administration. Mild pain at the injection site (4/25 cases) was the only adverse event, and it disappeared within 2 to 3 days.

Interpretation: Local BTX-A infiltration is an efficacious and safe procedure for obtaining a sustained amelioration of muscle cramps associated with diabetic neuropathy. Ann Neurol 2018;84:682-690.
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http://dx.doi.org/10.1002/ana.25340DOI Listing
November 2018

Integrated insulin pump therapy with continuous glucose monitoring for improved adherence: technology update.

Patient Prefer Adherence 2015 7;9:1263-70. Epub 2015 Sep 7.

Endocrinology, Garibaldi-Nesima Hospital, Catania, Italy.

Insulin pump therapy combined with real-time continuous glucose monitoring, known as sensor-augmented pump (SAP) therapy, has been shown to improve metabolic control and to reduce the rate of hypoglycemia in adults with type 1 diabetes compared to multiple daily injections or standard continuous subcutaneous insulin infusion. Glycemic variability is also reduced in patients on SAP therapy. This approach allows patients to monitor their glucose levels being informed of glycemic concentration and trend. Trained diabetic patients, therefore, can appropriately modify insulin infusion and/or carbohydrate intake in order to prevent hypo- or hyperglycemia. For these reasons, SAP therapy is now considered the gold standard for type 1 diabetes treatment. To be clinically effective, however, devices and techniques using advanced technology should not only have the potential to theoretically ameliorate metabolic control, but also be well accepted by patients in terms of satisfaction and health-related quality of life, because these factors will improve treatment adherence and consequently overall outcome. SAP therapy is generally well tolerated by patients; however, many clinical trials have identified significant noncompliance in the use of this device, most notably in the pediatric and adolescent populations. In this review we aim to analyze the main reasons for good or poor adherence to SAP therapy and to provide useful tips in order to fully benefit from this kind of novel therapeutic approach.
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http://dx.doi.org/10.2147/PPA.S69482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567238PMC
September 2015

Insulin analogs and cancer.

Front Endocrinol (Lausanne) 2012 10;3:21. Epub 2012 Feb 10.

Endocrinology Section, Department of Clinical and Molecular Biomedicine, University of Catania, Garibaldi-Nesima Hospital Catania, Italy.

Today, insulin analogs are used in millions of diabetic patients. Insulin analogs have been developed to achieve more physiological insulin replacement in terms of time-course of the effect. Modifications in the amino acid sequence of the insulin molecule change the pharmacokinetics and pharmacodynamics of the analogs in respect to human insulin. However, these changes can also modify the molecular and biological effects of the analogs. The rapid-acting insulin analogs, lispro, aspart, and glulisine, have a rapid onset and shorter duration of action. The long-acting insulin analogs glargine and detemir have a protracted duration of action and a relatively smooth serum concentration profile. Insulin and its analogs may function as growth factors and therefore have a theoretical potential to promote tumor proliferation. A major question is whether analogs have an increased mitogenic activity in respect to insulin. These ligands can promote cell proliferation through many mechanisms like the prolonged stimulation of the insulin receptor, stimulation of the IGF-1 receptor (IGF-1R), prevalent activation of the extracellular-signaling-regulated kinase (ERK) rather than the protein kinase B (PKB/AKT) intracellular post-receptor pathways. Studies on in vitro models indicate that short-acting analogs elicit molecular and biological effects that are similar to those of insulin. In contrast, long-acting analogs behave differently. Although not all data are homogeneous, both glargine and detemir have been found to have a decreased binding to receptors for insulin but an increased binding to IGF-1R, a prevalent activation of the ERK pathway, and an increased mitogenic effect in respect to insulin. Recent retrospective epidemiological clinical studies have suggested that treatment with long-acting analogs (specifically glargine) may increase the relative risk for cancer. Results are controversial and methodologically weak. Therefore prospective clinical studies are needed to evaluate the possible tumor growth-promoting effects of these insulin analogs.
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http://dx.doi.org/10.3389/fendo.2012.00021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355935PMC
July 2012

Severe Graves' ophthalmopathy after percutaneous ethanol injection in a nontoxic thyroid nodule.

Thyroid 2012 Feb 23;22(2):210-3. Epub 2011 Dec 23.

Endocrinology Unit, Department of Clinical and Molecular Bio-Medicine, University of Catania Medical School, Garibaldi-Nesima Hospital, Catania, Italy.

Background: Percutaneous ethanol injection (PEI) is used to treat cystic or mixed benign thyroid nodules. This treatment can result in rare complications, and three cases of Graves' disease (GD) without Graves' ophthalmopathy (GO) have been reported after PEI treatment of toxic thyroid adenomas. Here we present a 55-year-old male patient who developed GD and severe GO after PEI treatment of a mixed cystic-solid, nontoxic thyroid nodule.

Patient Findings: Six months after PEI, the nodule volume had decreased from 8.9 to 3.0 mL, but we observed severe hyperthyroidism with elevated serum free triiodothyronine, free thyroxine, and thyrotropin receptor antibody levels. We also observed ophthalmopathy with symmetrical orbit and soft tissue involvement (grade b/c) and a clinical activity score of 4/7. The diagnosis of GO was confirmed by bilateral corneal damage, increased intraocular pressure on upgaze, and inconstant diplopia. A computed tomography scan showed that the inferior, medial, and superior extraocular muscles were bilaterally enlarged, the perineural space at the orbital cone was slightly reduced and the ophthalmic vein was congested.

Summary: A cause-effect relationship between PEI and GD/GO was likely in this patient because of the temporal sequence. Although the mechanism was unknown, we speculated that the thyroid tissue damage caused by PEI released a large amount of antigenic materials from follicular thyroid cells, including thyrotropin receptor protein, which triggered the autoimmune inflammatory response against the thyroid itself and the orbital soft tissues. The patient did not have any risk factors for either GD or GO.

Conclusions: This observation raises the concern, therefore, that unpredictable and severe complications, such as GD and GO, may occur in a few patients treated with PEI.
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http://dx.doi.org/10.1089/thy.2011.0315DOI Listing
February 2012

Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients.

PLoS One 2011 1;6(8):e22552. Epub 2011 Aug 1.

Endocrine Unit, Department of Clinical and Molecular Biomedicine, University of Catania Medical School, Garibaldi-Nesima Hospital, Catania, Italy.

Context: Levothyroxine monotherapy is the treatment of choice for hypothyroid patients because peripheral T4 to T3 conversion is believed to account for the overall tissue requirement for thyroid hormones. However, there are indirect evidences that this may not be the case in all patients.

Objective: To evaluate in a large series of athyreotic patients whether levothyroxine monotherapy can normalize serum thyroid hormones and thyroid-pituitary feedback.

Design: Retrospective study.

Setting: Academic hospital.

Patients: 1,811 athyreotic patients with normal TSH levels under levothyroxine monotherapy and 3,875 euthyroid controls.

Measurements: TSH, FT4 and FT3 concentrations by immunoassays.

Results: FT4 levels were significantly higher and FT3 levels were significantly lower (p<0.001 in both cases) in levothyroxine-treated athyreotic patients than in matched euthyroid controls. Among the levothyroxine-treated patients 15.2% had lower serum FT3 and 7.2% had higher serum FT4 compared to euthyroid controls. A wide range of FT3/FT4 ratios indicated a major heterogeneity in the peripheral T3 production capacity in different individuals. The correlation between thyroid hormones and serum TSH levels indicated an abnormal feedback mechanism in levothyroxine-treated patients.

Conclusions: Athyreotic patients have a highly heterogeneous T3 production capacity from orally administered levothyroxine. More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion. The long-term effects of chronic tissue exposure to abnormal T3/T4 ratio are unknown but a sensitive marker of target organ response to thyroid hormones (serum TSH) suggests that this condition causes an abnormal pituitary response. A more physiological treatment than levothyroxine monotherapy may be required in some hypothyroid patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0022552PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148220PMC
December 2011

Graves' orbitopathy: extraocular muscle/total orbit area ratio is positively related to the Clinical Activity Score.

Eur J Ophthalmol 2012 May-Jun;22(3):301-8

Department of Internal Medicine, Endocrinology, University of Catania, Garibaldi-Nesima Hospital, Catania, Italy.

Background And Objective: Both extraocular muscle (EOM) and orbital fat are involved in Graves' orbitopathy (GO) but their enlargement might occur with a different temporal pattern. Two GO subtypes have been described, one with predominant EOM enlargement and the other with prevalent fat tissue involvement. We longitudinally investigated the EOM in patients with GO and their relationship with clinical activity.

Patients And Methods: By using commercial software with a segmentation technique, we calculated from computed tomography (CT) scan EOM coronal area (CA) and total orbit coronal area (TOA) in 23 control subjects and in 32 patients with GO. The latter were studied both at presentation and 18 months later. Superior, lateral, inferior, and medial EOM areas and TOA were selected by 3 different contiguous CT slices: A, B, and C, chosen at globe pole tangent and 2 and 4 mm backward. The Clinical Activity Score (CAS) was also measured.

Results: Orbital EOM CA/TOA ratio (OM/TOA ratio) after 18 months decreased in most patients with GO, indicating that EOM area decrement contributed significantly to OM/TOA ratio reduction. Clinical Activity Score decrease was significantly correlated to the OM/TOA ratio decrease.

Conclusions: An easy method to measure CA of EOM and orbit allowed us to observe that in most patients with GO the OM/TOA ratio decreases with time, suggesting that macroscopic EOM involvement occurs initially and resolves as the other clinical signs and symptoms of the disease resolve, as indicated by the significant OM/TOA ratio correlation with CAS.
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http://dx.doi.org/10.5301/ejo.5000018DOI Listing
July 2012

A diffuse sclerosing variant of papillary thyroid carcinoma: clinical and pathologic features and outcomes of 34 consecutive cases.

Thyroid 2011 Apr;21(4):383-9

Endocrinology, Department of Clinical and Molecular Medicine of the University of Catania, Garibaldi-Nesima Hospital, Catania, Italy.

Background: The diffuse sclerosing variant of papillary thyroid carcinoma (DSPC) is a relatively rare variant of papillary thyroid cancer. Large studies of patients with DSPC have been infrequently performed, and controversy still exists concerning some DSPC features and outcomes. The aim of the present study was to retrospectively evaluate the clinicopathologic features and outcomes in a series of 34 consecutive patients with DSPC and to compare them with a larger group of 245 consecutive patients with the classic variant of papillary thyroid carcinoma (cPTC) that were evaluated in the same period.

Patients And Methods: Clinical and histological features (sex, age, tumor size,multifocality, bilaterality, extra thyroid extension, and local and distant metastases) were recorded in all patients, as well as any persistent or recurrent disease and the patients' disease status at last observation. Patients with cPTC were classified as either low (122) or high risk (123). DSPC and high-risk patients were all treated with the same protocol, including ¹³¹I treatment. All patients were included in a Cox regression model analysis to investigate the effect of each variable on the hazard ratio.

Results: As expected, multifocality, bilaterality, and extra thyroid extension were more frequently noted at presentation, and the pT1 category of TNM classification was less frequently noted in DSPC and high-risk patients with cPTC compared with low-risk patients with cPTC. No significant difference was found between patients with DSPC and those with high-risk cPTC, except that extra thyroid extension was found more frequently in the patients with DSPC. Using multivariate analysis, diffuse sclerosing variant was an independent variable for predicting a high risk of persistent and recurrent disease during initial follow-up. However, at a later time, and after further treatment, the disease status was not different between patients with DSPC and those with high-risk cPTC, and only the presence of distant metastases affected the final outcome.

Conclusions: DSPC is a thyroid papillary carcinoma variant characterized by high aggressiveness. In patients with DSPC, the outcome is worse than in patients with low-risk cPTC; and, at presentation, characteristics are somewhat worse than for patients with high-risk cPTC.At medium term, the outcome is similar to that observed in patients with high-risk cPTC, provided aggressive treatment is used (additional surgical intervention, when required, and/or ¹³¹I radiotherapy).
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http://dx.doi.org/10.1089/thy.2010.0331DOI Listing
April 2011

Determinants of liver damage associated with intravenous methylprednisolone pulse therapy in Graves' ophthalmopathy.

Thyroid 2007 Apr;17(4):357-62

Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands.

Background: Intravenous methylprednisolone pulses (IVMP) are more efficacious and better tolerated than oral prednisone in Graves' ophthalmopathy (GO) patients. However, acute and severe liver damage has been reported in sporadic cases during IVMP, resulting in fatal acute liver failure in four patients so far. The mechanism causing the liver damage is incompletely understood.

Design: We performed a prospective observational study in 13 patients with dysthyroid optic neuropathy (group A) and in 14 patients with moderately severe GO (group B) who were treated with high-dose (group A) or low-dose (group B) IVMP; cumulative steroid doses were 8.45 g in group A and 4.5 g in group B, and follow-up time was 24 weeks.

Main Outcome: Slight increases in serum aminotransferases (in alanine aminotransferase [ALAT] more than in aspartate aminotransferase [ASAT]) were observed, in seven patients exceeding the upper normal limit of 40 U/L. These changes were more prominent in group A than in group B as was also evident from a decrease in ASAT/ALAT ratio in group A but not in group B. Changes in serum aminotransferases occurred especially in the first 6 weeks of IVMP, becoming smaller thereafter with the decrease in steroid dosage. Pretreatment liver steatosis or diabetes were not related to liver damage, but preexistent viral hepatitis was.

Conclusion: IVMP in GO patients causes dose-dependent liver damage by a direct toxic effect of glucocorticoids on hepatocytes. Nevertheless, IVMP seems to be pretty safe if cumulative doses exceeding 8 g are avoided and liver function is checked before and at regular intervals during pulse therapy.
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http://dx.doi.org/10.1089/thy.2006.0267DOI Listing
April 2007
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