Fat Body Mass and Vertebral Fracture Progression in Women With Breast Cancer.

Importance: Women with early breast cancer (EBC) exposed to aromatase inhibitors (AIs) may experience fragility fractures despite treatment with bone-active drugs. Risk factors for fractures in patients receiving AIs and denosumab have not been explored to date. Objectives: To evaluate whether an association exists between dual x-ray absorptiometry (DXA)-measured fat body mass (FBM) and vertebral fracture (VF) progression in postmenopausal women with EBC undergoing adjuvant therapy with AIs in combination with denosumab and to examine whether VF was associated with common risk factors for bone fracture and parameters of body composition other than FBM. Design, Setting, and Participants: For this prospective, single-center, cohort study, 237 patients with EBC who were undergoing adjuvant treatment with AIs and denosumab (60 mg every 6 months) were enrolled at the Breast Unit of the ASST Spedali Civili of Brescia from September 2014 to June 2018. Data analysis was conducted in June 2022. Exposure: Body composition parameters, bone mineral density, and morphometric VFs were assessed by DXA at study entry and after 18 months of therapy. Main Outcomes and Measures: VF progression, defined as either new or worsening of preexisting VFs, between the 2 time points. Results: Of the 237 patients enrolled (median [range] age, 61 [28-84] years), 17 (4.4%) reported VF progression. Univariable analysis found an association between VF progression and a history of clinical fractures (odds ratio [OR], 3.22; 95% CI, 1.19-8.74; P = .02), Fracture Risk Assessment Tool (FRAX) score for major fractures (OR, 4.42; 95% CI, 1.23-13.79; P = .04), percentage of FBM (OR, 6.04; 95% CI, 1.69-21.63; P = .006), and android fat (OR, 9.58; 95% CI, 1.17-78.21; P = .04) and an inverse association with appendicular lean mass index-FBM ratio (OR, 0.25, 95% CI, 0.08-0.82; P = .02). Multivariable analysis revealed percentage of FBM (OR, 5.41; 95% CI, 1.49-19.59; P = .01) and FRAX score (OR, 3.95; 95% CI, 1.09-14.39; P = .04) as independent variables associated with VF progression. Conclusions and Relevance: The findings of this study suggest that baseline FBM is an independent factor for VF progression in patients with EBC treated with adjuvant AIs and denosumab. This observation is new and indicates that diet and exercise may synergize with denosumab in the management of bone health in this patient setting.

Liquid levothyroxine formulations in patients taking drugs interfering with L-T4 absorption.

Purpose: To describe the current knowledge on thyroid hormonal profile in patients on liquid L-T4 therapy and drugs known to interfere with L-T4 absorption. Methods: A PubMed/MEDLINE, Web of Science, and Scopus research was performed. Case reports, case series, original studies and reviews written in English and published online up to 31 August 2022 were selected and reviewed. The final reference list was defined based on the relevance of each paper to the scope of this review. Results: The available data showed that novel levothyroxine formulations circumvent gastric pH impairment due to multiple interfering drugs such as proton pump inhibitors, calcium or iron supplements, sevelamer, aluminum/magnesium hydroxide and sodium alginate. Conclusion: New formulations can be taken simultaneously with drugs interfering with L-T4 absorption, in particular liquid formulations. Softgel capsules need more studies to support these data.

Graves' disease treated by complementary medicine leading to thyroid storm: A case report.

BACKGROUND: Thyroid storm is a rare, life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis and can be precipitated by several factors. We described a thyroid storm precipitated by a long-term treatment using homeopathic medicine containing iodine. CASE PRESENTATION: A 55-year-old Italian woman was admitted to our Sub-Intensive Care Unit with the diagnosis of congestive heart failure and thyrotoxicosis. She has been diagnosed with Graves' disease two years before; she refused conventional therapy and in the preceding six months had been using phytotherapeutic and homeopathic medicine. We found serum and urine iodine levels consistent with severe intoxication by iodine (serum iodine: 42100 mcg/L and urinary iodine: 4223 mcg/L, respectively). After a few hours, the patient went into cardiac arrest. She was subjected to invasive ventilation, dialyzed with continuous veno-venous hemofiltration and treated with vasoactive amines. CONCLUSION: The high level of iodemia manifested in our patient - around a thousand times greater than the normal range and itself associated with fatal outcomes - was caused by long-term homeopathic treatment. This long-term treatment has two consequences: first, iodine load-precipitated hyperthyroidism in thyroid storm, and secondly, it prevents us from treating patients with inorganic iodide.

Positive effect of nutraceuticals on sperm DNA damage in selected infertile patients with idiopathic high sperm DNA fragmentation.

BACKGROUND: The use of nutraceuticals to improve sperm parameters and male fertility is debatable, even if evidence suggests that selected infertile patients might benefit from their use. In particular, oxidative stress might play a role in idiopathic male infertility, leading to sperm membrane damage and high sperm DNA fragmentation (SDF). The aim of this study was to evaluate, in selected idiopathic infertile men with high SDF, the effect on sperm DNA damage and on standard semen parameters of a nutraceutical formulation containing myoinositol, alpha lipoic acid, coenzyme Q10, selenium, zinc and B vitamins. METHODS: The study included 60 idiopathic infertile men with DNA fragmentation index (DFI) >20%. Semen analysis and DFI determination were assessed at baseline and after three months of nutraceutical treatment. Primary outcome was change in DFI. RESULTS: Semen volume, sperm concentration, total sperm count, sperm motility and sperm morphology did not change after treatment. Instead, sperm vitality significantly increased (65.9±11.8% pre-treatment vs. 69.4±9.4% post-treatment, P<0.05) and DFI significantly decreased (33.5±10.1% pre-treatment vs. 26.8±8.7% post-treatment, P=0.0001) after treatment. The percentage of men with normal standard sperm parameters significantly increased (15% vs. 30%, P<0.05). The mean decrease in DFI was -6.7±1.4% and the percentage of men with DFI ≤30% after treatment was 75.0% compared to 48.3% pre-treatment (P<0.005). Higher pre-treatment DFI (and no other parameters) correlated with greater DFI reduction after treatment. CONCLUSIONS: Nutraceuticals might be effective in idiopathic infertile men with high DFI to reduce SDF, increase sperm vitality and globally improve semen parameters.

Selenium supplementation in patients with subclinical hypothyroidism affected by autoimmune thyroiditis: Results of the SETI study.

OBJECTIVE: The purpose of this prospective study was to assess the effects of selenium supplementation on TSH and interferon-γ inducible chemokines (CXCL9, CXCL10 and CXCL11) levels in patients with subclinical hypothyroidism due to Hashimoto's thyroiditis. PATIENTS AND METHODS: Patients with subclinical hypothyroidism due to Hashimoto thyroiditis were prospectively enrolled in the SETI study. They received 83mcg of selenomethionine/day orally in a soft gel capsule for 4 months with water after a meal. No further treatment was given. All patients were measured thyroid hormone, TPOAb, CXCL9, CXCL10, CXCL11, iodine, and selenium levels at baseline and at study end. RESULTS: 50 patients (43/7 female/male, median age 43.9±11.8 years) were enrolled, of which five withdrew from the study. At the end of the study, euthyroidism was restored in 22/45 (48.9%) participants (responders), while 23 patients remained hypothyroid (non-responders). There were no significant changes in TPOAb, CXCL9, CXCL10, CXCL11, and iodine levels from baseline to the end of the study in both responders and non-responders. TSH levels were re-tested six months after selenomethionine withdrawal: 83.3% of responding patients remained euthyroid, while only 14.2% of non-responders became euthyroid. CONCLUSIONS: The SETI study shows that short-course supplementation with selenomethionine is associated to a normalization of serum TSH levels which is maintained 6 months after selenium withdrawal in 50% of patients with subclinical hypothyroidism due to chronic autoimmune thyroiditis. This TSH-lowering effect of selenium supplementation is unlikely to be related to changes in humoral markers of autoimmunity and/or circulating CXCL9.

LATERAL NECK DISSECTION FOR AGGRESSIVE VARIANTS OF WELL-DIFFERENTIATED THYROID CANCER.

Objective: Well-differentiated thyroid cancer (WDTC) is characterized by favorable disease course and excellent survival. However, some histologic subtypes, known as aggressive histologic variants (AHVs), present a more aggressive behavior than conventional WDTC. The aim of this study was to evaluate the pattern of nodal involvement and factors influencing prognosis in N1b patients with AHVs. Methods: A multicentric retrospective analysis of patients who underwent therapeutic lateral neck dissection (ND) for WDTC between 1994 and 2015 was accomplished. AHVs included the following subtypes: tall cell, Hürtle cell, diffuse sclerosing, and poorly differentiated papillary thyroid cancer. Results: The study included a total of 352 N1b patients, 40 (11.4%) of whom had AHVs. AHVs present a similar distribution of positive nodes if compared with conventional WDTC. In AHV patients, 5-year overall survival (OS), disease-specific survival (DSS), locoregional control, and metastasis-free survival were 82.2%, 93.6%, 80.3%, and 87.3%, respectively. Advanced age (>55 years) was the only significant factor affecting survival (OS, P<.001; DSS, P = .011) in this group. In the AHV group, there were 9 (22.5%) recurrences; patients with regional recurrence and without distant metastases were effectively treated by surgery. Conclusion: The distribution of positive lymph nodes in case of AHVs is similar to that of conventional WDTC, with only level V at a relatively greater risk of harboring metastases in the former group. Survival outcomes in N1b patients with AHVs remain optimal. Total thyroidectomy, ND, and adjuvant radioiodine administration have been demonstrated to be effective treatments in the setting of AHVs. Abbreviations: AHV = aggressive histologic variant; DOD = died of disease; DSS = disease-specific survival; DSV = diffuse sclerosing variant; ETE = extrathyroidal extension; HCC = Hürthle cell carcinoma; LRC = locoregional control; LVI = lymphovascular invasion; MFS = metastasis-free survival; ND = neck dissection; NED = no evidence of disease; OS = overall survival; PDA = poorly differentiated areas; PTC = papillary thyroid carcinoma; RAI = radioiodine therapy; TCV = tall cell variant; WDTC = well-differentiated thyroid cancer.

Selenium supplementation could restore euthyroidism in subclinical hypothyroid patients with autoimmune thyroiditis.

INTRIDUCTION: The thyroid is an organ with one of the highest selenium concentrations, containing many selenoproteins implicated in thyroid hormone metabolism. Treatment with levothyroxine has been recommended for all subclinical hypothyroid patients with TSH levels > 10 mU/L, whereas for those with TSH< 10 mU/L treatment remains controversial. AIM: A randomised controlled prospective study was performed to investigate the effects of Se treatment on patients with autoimmune thyroiditis and mild sub-clinical hypothyroidism (TSH < 10 mU/L). MATERIAL AND METHODS: A total of 196 patients with autoimmune thyroiditis were recruited in the study. Patients were assigned to receive (case) or not receive (control) an oral selenomethionine treatment. Cases received 83 mcg selenomethionine/day orally for four months. All the patient's charts were submitted to thyroid hormonal profile (TSH, fT4) and TPOAb evaluation upon enrolment and at the end of the study. RESULTS: In total 192 patients completed the study. Cases and controls were superimposable for age, gender, thyroid hormonal profile, and TPOAb levels. At the end of the study, 33/192 (17.2%) participants restored euthyroidism (Responders). Responders were significantly more frequent among Cases than Controls (30/96 [31.3%] vs. 3/96 [3.1%], p < 0.0001). CONCLUSION: Selenium supplementation could restore euthyroidism in one third of subclinical hypothyroidism patients with autoimmune thyroiditis. (Endokrynol Pol 2016; 67 (6): 567-571).

Oral liquid levothyroxine treatment at breakfast: a mistake?

OBJECTIVE: Taking levothyroxine (L-T4) with coffee or with water followed by coffee intake within a few minutes results in poor TSH response in many patients. T4 is available in tablet form worldwide, but novel formulations in soft gel capsule or liquid form are now available. DESIGN: We fortuitously identified a euthyroid patient who wrongly consumed liquid L-T4 with coffee at breakfast; after changing the time of consumption to 30 min before breakfast, no change in TSH, free T4 (fT4), and free tri-iodothyronine (fT3) concentrations was observed. Once the first patient was identified, additional stable euthyroid patients who consumed liquid L-T4 with coffee were identified. METHODS: Patients were recruited by searching our 'thyroid patients' database. All the patients on liquid L-T4 treatment were contacted by phone to ask them whether they took L-T4 at breakfast. We identified 54 patients who were submitted to TSH, fT4, and fT3 evaluation, with the indication that the same dosage of L-T4 be consumed 30 min before breakfast. We determined their TSH, fT4, and fT3 concentrations after 3 and 6 months again. RESULTS: no significant difference in thyroid hormone concentrations was observed in patients when they consumed L-T4 at breakfast or when they consumed it 30 min before breakfast for 3 and 6 months (TSH: 2.5±1.1 vs 2.5±1.1 and 2.4±1.1 mIU/l respectively, fT4: 12.4±2.4 vs 12.5±2.4 and 12.3±2.1 pg/ml respectively, and fT3: 3.4±0.6 vs 3.4±0.6 and 3.3±0.5 pg/ml respectively). CONCLUSION: Oral liquid L-T4 formulations could diminish the problem of L-T4 malabsorption caused by coffee when using traditional tablet formulations.