Application of radiomics and machine learning to thyroid diseases in nuclear medicine: a systematic review.

BACKGROUND: In the last years growing evidences on the role of radiomics and machine learning (ML) applied to different nuclear medicine imaging modalities for the assessment of thyroid diseases are starting to emerge. The aim of this systematic review was therefore to analyze the diagnostic performances of these technologies in this setting. METHODS: A wide literature search of the PubMed/MEDLINE, Scopus and Web of Science databases was made in order to find relevant published articles about the role of radiomics or ML on nuclear medicine imaging for the evaluation of different thyroid diseases. RESULTS: Seventeen studies were included in the systematic review. Radiomics and ML were applied for assessment of thyroid incidentalomas at 18 F-FDG PET, evaluation of cytologically indeterminate thyroid nodules, assessment of thyroid cancer and classification of thyroid diseases using nuclear medicine techniques. CONCLUSION: Despite some intrinsic limitations of radiomics and ML may have affect the results of this review, these technologies seem to have a promising role in the assessment of thyroid diseases. Validation of preliminary findings in multicentric studies is needed to translate radiomics and ML approaches in the clinical setting.

Thyroid impairment and male fertility: a narrative review of literature.

PURPOSE: To evaluate the effect of thyroid function on male fertility, focusing on hypo- and hyperthyroidism. METHODS: A PubMed/MEDLINE, Web of Science, and Scopus research was performed. Original studies in English published online up to 31 May 2023 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 in animals (31 studies) and human (26 studies) showed conflicting results. However, thyroid dysfunction altered erection and ejaculation both in animal models than in men. CONCLUSION: Both hypothyroidism and hyperthyroidism seem to cause ejaculation and erectile dysfunction. Hence, Guidelines recommend against the systematic screening for thyroid disorders in the men in sub-fertile couples, but only in men with ejaculation and erectile dysfunction and/or altered semen parameters.

Role of Body Composition in the Prediction of Skeletal Fragility Induced by Hormone Deprivation Therapies in Cancer Patients.

PURPOSE OF REVIEW: This review paper is intended to show that changes in body composition are key in the pathogenesis of bone fragility amongst patients with breast and prostate cancer receiving hormone deprivation therapies (HDTs) and that the mechanism is based on the development of alterations in bone quality rather than in bone quantity. RECENT FINDINGS: Preclinical and clinical data suggest a tight connection amongst bone, adipose and muscular tissues by means of several soluble mediators, potentially leading to (1) bone resorption and bone quality deterioration in sarcopenic obese subjects, (2) bone mineral deposition in healthy trained subjects. Cancer patients treated with HDTs frequently fall into the first condition, named osteosarcopenic obesity. Current clinical guidelines for the prevention of treatment-induced osteoporosis focus on bone mineral density (BMD) as a main predictive factor for fracture risk; however, the pathophysiology underlying HDT-induced bone fragility differs from that of primary and postmenopausal osteoporosis, suggesting a prevalent role for bone quality alterations. Focusing on available data from clinical trials, in our review we suggest osteosarcopenic obesity as a common target for the prevention and treatment of HDTs-related metabolic and skeletal complications, beyond a BMD-centred approach.

Interference or Noninterference Between Soy and Levothyroxine: That Is the Question. A Narrative Review of Literature.

OBJECTIVE: To evaluate the effect of soy intake on levothyroxine (L-T4) absorption among different L-T4 formulations. METHODS: A PubMed/MEDLINE, Web of Science, and Scopus research was performed. Case reports, case series, and original studies written in English and published online up to November 30, 2022, were selected and reviewed. The final reference list was defined based on the relevance of each study to the scope of this review. RESULTS: Few data, mainly case reports, seemed to suggest a possible interference of soy products on L-T4 tablets absorption. However, the only prospective randomized cross-over study showed no differences in L-T4 absorption when L-T4 and soy isoflavones were assumed concomitantly. The very little data available on liquid L-T4 formulations did not allow for any conclusions to be made, even if a double-blind placebo-controlled trial showed no impaired L-T4 absorption. CONCLUSION: The inference of soy products on L-T4 absorption, if present, seems to have little clinical impact. Considering this fact, the Hamlet-like question whether soy milk interferes with L-T4 absorption remains unanswered.

Assessment of respiratory function and exercise tolerance at 4-6 months after COVID-19 infection in patients with pneumonia of different severity.

BACKGROUND: The evaluation of COVID-19 systemic consequences is a wide research field in which respiratory function assessment has a pivotal role. However, the available data in the literature are still sparse and need further strengthening. AIM: To assess respiratory function 4-6 months after hospital discharge based on lung disease severity in patients who overcome COVID-19 pneumonia. METHODS: Patients hospitalised either in the Internal Medicine Department (IMD) for moderate to severe disease or in the Intensive Care Unit (ICU) for critical disease underwent spirometry with maximal flow-volume curve, lung volumes, lung diffusion capacity (DLCO ) and six-minute walking test (6-MWT). RESULTS: Eighty-eight patients were analysed: 40 from the IMD and 48 from the ICU. In both cohorts, there was a greater prevalence of male patients. In the IMD cohort, 38% of patients showed at least one altered respiratory parameter, while 62% in the ICU cohort did so (P < 0.05). Total lung capacity (TLC) and DLCO were the most frequently altered parameters: 15% and 33% from IMD versus 33% and 56% from ICU, respectively (P < 0.05). In IMD patients, 5% had only restrictive deficit, 22% had only lung diffusion impairment and 10% had both. In ICU patients, 6% had only restrictive deficit, 29% had only lung diffusion impairment and 27% had both (P < 0.05). ICU patients showed a higher frequency of abnormal 6-MWT (P < 0.05). CONCLUSION: Lung function tests and 6-MWT are highly informative tools for monitoring the negative consequences of COVID-19 pneumonia, which were more frequent and more complex in patients discharged from ICU.

Usefulness of routine assessment of free testosterone for the diagnosis of functional male hypogonadism.

OBJECTIVE: To investigate whether routine assessment of free testosterone improves the diagnostic accuracy of functional hypogonadism. METHODS: Total and free testosterone (calculated on SHBG levels) were determined in 188 patients with sexual symptoms and 184 with infertility. RESULTS: Hypogonadism (calculated free testosterone <63 pg/ml) was found in 47/188 (25.0%) patients with sexual symptoms and in 21/184 (11.4%) with infertility. Total testosterone determination misdiagnosed hypogonadism in 8.4% (12/143) of men with sexual symptoms and in 2% (3/152) with infertility. In subjects with borderline total testosterone, only 24.7% (19/77) had hypogonadism confirmed by free testosterone levels. Free testosterone levels significantly correlated with age, haematocrit, gonadotropins, gynecomastia, BMI, and number of co-morbidities, whereas total testosterone associated only with the latter two. Furthermore, age, haematocrit, BMI, and the presence of erectile dysfunction and of low libido were significantly different between men with normal and low free testosterone, whereas only BMI and low libido were significantly different between patients with normal and low total testosterone. CONCLUSION: Routine assessment of free testosterone allows a more accurate diagnosis of functional hypogonadism, especially in men with sexual symptoms. Free testosterone levels associate with clinical and biochemical parameters of androgen deficiency better than total testosterone levels.

Ultrasound of benign thyroid nodules: A 120 months follow-up study.

OBJECTIVE: Some evidence suggests that most benign nodules exhibit no significant size increase during 5 years of follow-up, although conflicting results have emerged. The aim of the present study is to evaluate the frequency and the magnitude of growth in benign nodules during 120 months of follow-up. DESIGN: We reviewed the medical and imaging records of patients who were submitted to ultrasound-guided FNA of thyroid nodules at our hospital from January 2007 to March 2009. We selected only patients with benign nodules who underwent annual ultrasound evaluation in our Department. RESULTS: Among 966 selected patients, 289 were lost during follow-up, meaning that the total number of patients analysed was 677 (474 women and 203 men), with a mean age of 45.6 (16-71) years. In 559/677 patients (82.7%), the size of the nodule remained stable during follow-up; 42 (6.2%) patients experienced spontaneous nodule shrinkage, and 75 (11.1%) patients showed nodule growth. Patients with or without nodule growth during follow-up were superimposable at baseline for age, gender, TSH values, number of patients on levothyroxine treatment and nodule characteristics. All baseline variables in predicting nodular growth were entered to an adjusted multivariate logistic regression model. None of the parameters taken into account was associated with nodular growth. CONCLUSIONS: In conclusion, the majority of benign nodules remained stable over the period of monitoring. On the basis of our experience, we recommend ultrasound examination at a distance of 2 and 5 years following cytological evaluation, then every 4-5 years from then on.

The importance of SHBG and calculated free testosterone for the diagnosis of symptomatic hypogonadism in HIV-infected men: a single-centre real-life experience.

PURPOSE: The prevalence of low testosterone and symptoms of hypogonadism in HIV-infected men is still debated. We aimed to estimate the prevalence and type of hypogonadism in HIV-infected males complaining about sexual symptoms, and to evaluate the role of calculated free testosterone (cFT) vs total testosterone (TT) for diagnosis. Furthermore, we evaluated relationship between sex hormone-binding globulin (SHBG), gonadal status and clinical and virologic parameters. METHODS: We retrospectively evaluated 169 HIV-infected men with sexual symptoms, with TT available. Among them, we selected 94 patients with TT, SHBG, cFT, and luteinizing hormone (LH) available, and classified hypogonadism into overt (low TT and/or low cFT) and compensated (high LH, normal TT and cFT). Comparison was performed by non-parametric Kruskal-Wallis test and Spearman's correlation was calculated to verify the possible associations. RESULTS: Overt and compensated hypogonadism were found in 20.2% and 13.8% of patients, respectively. With reliance on TT alone, only 10.6% of patients would have met diagnosis. SHBG values were elevated in one third of patients, and higher in men with compensated hypogonadism. Significant positive correlation was found between SHBG and HIV infection duration, TT and LH. CONCLUSION: Only a complete hormonal profile can properly diagnose and classify hypogonadism in HIV-infected men complaining about sexual symptoms. TT alone reliance may lead to half of diagnoses missing, while lack of gonadotropin prevents the identification of compensated hypogonadism. This largely comes from high SHBG, which seems to play a central role in the pathogenesis of hypogonadism in this population.

Atypical parathyroid adenoma: clinical and anatomical pathologic features.

BACKGROUND: Primary hyperparathyroidism is an endocrine pathology that affects calcium metabolism. Patients with primary hyperparathyroidism have high concentrations of serum calcium or high concentrations of parathyroid hormone, or incorrect parathyroid hormone levels for serum calcium values. Primary hyperparathyroidism is due to the presence of an adenoma/single-gland disease in 80-85%. Multiple gland disease or hyperplasia accounts for 10-15% of cases of primary hyperparathyroidism. Atypical parathyroid adenoma and parathyroid carcinoma are both responsible for about 1.2-1.3% and 1% or less of primary hyperparathyroidism, respectively. METHODS: We performed a retrospective cohort study and enrolled 117 patients with primary hyperparathyroidism undergoing minimally invasive parathyroidectomy. Histological and immunohistochemical examination showed that 107 patients (91.5%) were diagnosed with typical adenoma (group A), while 10 patients (8.5%) were diagnosed with atypical parathyroid adenoma (group B). None of the patients were affected by parathyroid carcinoma. RESULTS: Significant statistical differences were found in histological and immunohistochemical parameters as pseudocapsular invasion (p <  0.001), bands of fibrosis (p <  0.001), pronounced trabecular growth (p <  0.001), mitotic rates of > 1/10 high-power fields (HPFs) (p <  0.001), nuclear pleomorphism (p = 0.036), thick capsule (p <  0.001), Ki-67+ > 4% (p <  0.001), galectin-3 + (p = 0.002), and protein gene product (PGP) 9.5 + (p = 0.038). CONCLUSIONS: Atypical parathyroid adenoma is a tumor that has characteristics both of typical adenoma and parathyroid carcinoma. The diagnosis is reached by excluding with strict methods the presence of malignancy criteria. Atypical parathyroid adenoma compared to typical adenoma showed significant clinical, hematochemical, histological, and immunohistochemical differences. We did not find any disease relapse in the 10 patients with atypical parathyroid adenoma during 60 months of follow-up time.

Thyroid scintigraphy in the era of fine-needle aspiration cytology.

PURPOSE: To evaluate whether thyroid scintigraphy would alter the clinical management of patients referred for fine-needle aspiration cytology (FNA). METHODS: We reviewed the medical and imaging records of patients referred to our Department between 2016 and 2019. All the patients had to take a serum thyrotropin test administered in our hospital at least two months before the FNA; where the TSH level was ≤1.5 mIU/L, the patients were subjected to a scan and subsequently to FNA, where indicated. We selected only healthy patients with no previous history of thyroid disease, who were not taking any drugs and who had a TSH level of ≤1.5 mIU/L. We excluded patients with multinodular goitre. RESULTS: A total of 176 patients were analysed. A total of 67/176 patients (38%) showed a serum of TSH ≤ 0.27 mIU/L. Scintigraphy identified a hot nodule in 142 lesions (80.7%), a warm nodule in 8 lesions (4.5%) and a cold nodule in 26 lesions (14.8%). The ROC curve analysis indicated that a TSH value of ≤0.42 mIU/L identified patients with hyperfunctioning nodules with a sensitivity of 65% and a specificity of 77%. All patients with cold and warm nodules were submitted to FNA: 22/26 (85%) and 5/8 (63%) lesions showed suspected malignancy or were compatible with malignancy, respectively. CONCLUSION: Speculating on our data, if we had subjected our patients to FNA as indicated by the 2015 ATA guidelines, we would have subjected 117 patients to cytology, from whom 83 had undetected hot nodules. Conversely, by adopting scintigraphy for all patients with TSH ≤ 1.5 mIU/L, 109 patients have avoided FNA. However, our study was performed in a region with a history of mild iodine deficiency. Therefore, we cannot claim that our observation is valid for patients born and living in areas with sufficient iodine uptake. We recommend thyroid scintigraphy for treating single thyroid nodules in euthyroid patients born and living in regions with an iodine deficiency, when TSH levels are below 1.5 mIU/L before FNA.

Pituitary adenomas and neuropsychological status: a systematic literature review.

Neurocognitive and psychological dysfunctions associated with pituitary adenomas (PAs) are clinically relevant, though probably under-reported. The aim of the current review is to provide an update on neuropsychological status, psychopathology, and perceived quality of life (QoL) in patients with PAs. A systematic research was performed in PubMed and Scopus in order to identify reports on neurocognitive, psychiatric, and psychological disorders in PAs. Prevalence of alterations, QoL evaluation, and used tests were also recorded. PRISMA guidelines were followed. Of 62,448 identified articles, 102 studies were included in the systematic review. The prevalence of neurocognitive dysfunctions was 15-83% in Cushing's Disease (CD), 2-33% in acromegaly, mostly affecting memory and attention. Memory was altered in 22% of nonfunctioning (NF) PAs. Worsened QoL was reported in 40% of CD patients. The prevalence of psychiatric disorders in CD reached 77% and in acromegaly 63%, mostly involving depression, followed by psychosis, and anxiety. The prevalence of psychopathology was up to 83% in CD, and 35% in acromegaly. Postoperative improvement in patients with CD was observed for: learning processes, overall memory, visuospatial skills, and language skills. Short-term memory and psychomotor speed improved in NFPAs. Postoperative improvement of QoL, somatic symptoms, obsessive-compulsive disorder, and coping strategies was seen in CD and acromegaly. Reports after radiotherapy are discordant. There is wide variability in used tests. PAs have been recently shown to be associated with altered neurocognitive and neuropsychological functions, as well as QoL. These data suggest the importance of a multidisciplinary evaluation for an optimal management.

p.Ser891Ala RET gene mutations in medullary thyroid cancer: Phenotypical and genealogical characterization of 28 apparently unrelated kindreds and founder effect uncovering in Northern Italy.

Applying genetic screening in medullary thyroid cancer (MTC) patients we identified an unexpectedly high frequency of c.2671T>G, p.Ser891Ala RET mutation carriers. Our aim was to: (a) deeply characterize the clinical expression of this mutation, (b) identify the presence of a founder effect in our region. Genetic analysis was performed in 251 relatives from 28 Ser891Ala kindreds, among 108 p.Ser891Ala asymptomatic carriers, 64 were submitted to thyroidectomy: mean age for 10 subjects presenting C-cells hyperplasia was 30.2 ± 13.7 years, raising to 37.9 ± 10.3 in 14 subjects with micro-MTC and to 55.0 ± 14.7 years in 39 subjects with MTC. Age-related progression across histopathological groups CCH/microMTC and MTC were statistically significant: genetic screening in Ser891Ala families could be safely postponed at the age of 14. To investigate the hypothesis of a common ancestor for Ser891Ala mutation we genotyped for 18 polymorphic microsatellite markers encompassing RET locus all subjects belonging to Ser891Ala families and we identified a founder effect, estimating the age of a common ancestor, dating back to 1493 AD. Ethnographic data collected in historical archives support laboratory results; the high prevalence of this mutation in our region could suggest the hypothesis of a population study to realize a preventive intervention in a rare neoplastic disease.

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.

Thyroiditis process as a predictive factor of sternotomy in the treatment of cervico-mediastinal goiter.

BACKGROUND: About 10% of cervico-mediastinal goiter need to associate cervicotomy with a total or partial sternotomy to allow a safe removal of the goiter. Aim of this study is to identify preoperative predictors of sternotomy for mediastinal goiter. METHODS: Between January 2008 and December 2015, 586 patients were submitted to total thyroidectomy at Surgical Clinic of Brescia, Italy. Among these, patients with cervico-mediastinal goiter have been divided in two groups based on the necessity of an associated sternotomy in the operating field: Group 1 (n = 40 patients) did not need sternotomy and Group 2 (n = 4 patients) underwent cervicotomy associated with sternotomy. Clinical and pathological characteristics of patients were retrospectivelly recorded. RESULTS: Among study group, 44 patients had cervico-mediastinal goiter. Thoracic CT was performed in all patients: an extension above aortic arch was found in 41 patients (93.18%) while an extention below aortic arch was found in 3 patients (6.82%). The extension of the goiter below the aortic arch resulted as a predictive value in the choice of surgical treatment (p = 0.0001). The thyroiditis process was found to be a significant predictive of the extention to a sternotomic approach (p = 0.029). The years of goiter's presence were on average 8.40 years in Group 1 and 14.75 years in Group 2. These parameters proved to be predictive when choosing a cervicotomy with sternotomy. CONCLUSIONS: Our study, despite limitations posed by small sample and its retrospective analisys, highlights the role of goiter's extention (below the aortic arch), disease length (for more than 14.75 years) and flogistic process (positivity of Tg Ab and anti-TPO-Ab) in the choice of combined (cervicotomic and sternotomic) approach to goiter's removal.

Levothyroxine liquid solution versus tablet form for replacement treatment in pregnant women.

OBJECTIVE: To evaluate the need and the magnitude of levothyroxine (LT4) increase in hypothyroid pregnant women on liquid compared to tablet formulations. METHODS: Patients were recruited by searching our "thyroid patients" database. The selection criteria were as follows: a) pregnant women on treatment for hypothyroidism (both liquid and tablet LT4) who gave birth at our hospital between February 2012 and January 2014; b) thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels obtained at least 3 months before missed menstrual cycle, with a TSH value less than 2.5 mIU/L and c) TSH and FT4 obtained within 12 weeks of pregnancy, and each month subsequently. RESULTS: During pregnancy, 8/31 (25.5%) of the women had to increase the dosage of LT4. Of these, 7/17 (41.2%) were on LT4 replacement therapy with tablets, and 1/14 (7.1%) with liquid formulation (p = 0.038). Daily LT4 was significantly increased in the liquid group only (52.9 ± 19.5 versus 67.5 ± 19.2 mcg/day (p = 0.013). A logistic regression analysis showed that the treatment with LT4 tablets was the only predictor of LT4 increase (OR: 0.44; 95% CI: 0.04-0.83; p = 0.031). CONCLUSION: Pregnant women on optimal replacement therapy before pregnancy require an increase of LT4 dosage more often when on a tablet than liquid formulation.

Type 1 diabetes mellitus and sperm quality: A case-control study.

BACKGROUND: The potential impact of diabetes mellitus type 1 (DM1) on male fertility is currently poorly defined. Hyperglycaemia and insulin deficiency may affect spermatogenesis. Some evidence suggests that men with DM1 have a significant reduction in progressive sperm motility, sperm morphology and semen volume, without significant changes in sperm concentration and count, but definite data are lacking. OBJECTIVES: To evaluate the impact of DM1 on clinical parameters related to male fertility and semen analysis. MATERIALS AND METHODS: We compared a court of 42 male DM1 patients with 43 nondiabetic subjects overlapping in age and remaining clinical data in an observational case-control study. All subjects underwent a comprehensive andrological reproductive evaluation, including medical history, physical examination, and semen analysis. We collected biochemical data in all patients with DM1, while diabetic patients with any alteration in semen parameters underwent sperm culture and scrotal ultrasound. In addition, all men completed the IIEF-5 questionnaire (International Index of Erectile Function-5) and the AMS (Aging Male Symptom score) questionnaire. RESULTS: Patients with DM1 had a higher prevalence of infertility, erectile dysfunction and worse semen parameters compared with controls. In particular, semen volume, total sperm count, and total and progressive sperm motility were significantly lower (p < 0.001, p = 0.003, p = 0.048, and p = 0.022 respectively). In addition, the rate of semen anti-sperm antibody positivity, the AMS score and FSH levels were higher. DISCUSSION AND CONCLUSION: Several mechanisms may contribute to these semen alterations in DM1 patients, such as oxidative damage to spermatogenesis, seminal infections and pelvic neurological changes. These data suggest that patients with DM1 should be counselled from an andrological-reproductive point of view.

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.

Levothyroxine personalized treatment: is it still a dream?

Levothyroxine is a milestone in the treatment of all causes of hypothyroidism. From 19th century till today, Levothyroxine experienced a great advancement, from hypodermic injections of an extract of the thyroid gland of a sheep to novel formulations, known to circumvent malabsorption issue. However, the rate of patients on suboptimal therapy is still high. Current Guidelines are clear, daily Levothyroxine dosage should be calculated based on body weight. However, we are still far away from the possibility to administer the right dosage to the right patient, for several reasons. We retrace the history of treatment with levothyroxine, pointing out strengths and weaknesses of different formulations, with particular attention to what keeps us away from tailored therapy. In the age of digitalization, the pharmaceutical industry has been giving rising importance to Digital therapeutics, that are known to be effective in reaching target therapies. By combining current knowledge of hypothyroidism therapy with cutting-edge technology, we also hypothesized what could be the future strategies to be developed in this field.

Osteoporosis in men with hypogonadism because of ApoA-I Leu75Pro amyloidosis under long-term testosterone therapy.

BACKGROUND: Apo A-I Leu75Pro amyloidosis is a rare systemic hereditary disease, whose hallmark and earliest involvement is testicular impairment, characterized by hypogonadism and macrorchidism; renal and hepatic involvement are the other characteristics. OBJECTIVE: To evaluate for the first time the prevalence of osteopenia, osteoporosis and vertebral fractures (VFs) in men with this form of amyloidosis affected by hypogonadism and under long-term testosterone replacement therapy (TRT). MATERIALS AND METHODS: Retrospective study on 50 men >50 years (median age 64.5) with dual-energy X-ray absorptiometry (DXA), hormonal, and biochemical data available at least 3 years after the start of TRT. Serum gonadal hormones and bone markers, lumbar and femoral DXA-scan with morphometric assay for evaluation of VFs were assessed. RESULTS: At 7.5 years from start of TRT, lumbar and/or femoral osteopenia and osteoporosis were found in 54% and 10% of patients, respectively. Of the men who had the morphometric assay performed, five of 34 (14.7%) had VFs. Compared to patients with normal bone mineral density, men with osteopenia and osteoporosis were older, had lower body mass index, higher sex hormone binding globulin and showed more frequently renal involvement. Multiorgan involvement, without different TRT dosage, was associated with lower testosterone levels. DISCUSSION AND CONCLUSION: Men with hypogonadism because of Apo A-I Leu75Pro amyloidosis under long-term TRT had a high burden of low bone mass (64%) and VFs (almost 15%). Osteopenia-osteoporosis was more frequently observed in older patients with multi-organ disease, which might contribute to impair bone health beyond hypogonadism.

Gonadal Function in Male Patients With Metastatic Renal Cell Cancer Treated With Sunitinib.

BACKGROUND/AIM: Single-agent tyrosine kinase inhibitors are still prescribed as first-line treatment to a relevant subgroup of patients with metastatic renal cell carcinoma (mRCC). These agents are known to cause disfunction of many endocrine glands (e.g., thyroid). In this two-step trial, we aimed to assess gonadal function among male patients with mRCC treated with sunitinib. PATIENTS AND METHODS: We enrolled a first cross-sectional cohort of pre-treated (>6 months) patients and a subsequent cohort of treatment-naïve patients who were prospectively followed-up. All patients were screened for hypogonadism and received a Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire at study entry and after 6 months of therapy. Patients who were candidates for testosterone replacement therapy (TRT) also received a FACT-G questionnaire at baseline and 3 months after supplementation. RESULTS: Among the 30 enrolled patients, the prevalence of hypogonadism was found to be higher in those receiving sunitinib for a longer period (27.3% at baseline, 41.7% in the first 6 months, and 68.4% after 9 months of therapy). The testosterone level of patients correlated with quality of life (R=0.32). A total of six patients received TRT, with a significant improvement in their global quality of life after the first 3 months of treatment. CONCLUSION: An increasing prevalence of hypogonadism was seen among male patients who received long-term treatment with sunitinib. TRT was associated with relevant improvements in quality of life. These findings corroborate similar published observations and encourage the assessment of gonadal function in male patients with mRCC under treatment with sunitinib.