Late orbital radiotherapy combined with intravenous methylprednisolone in the management of long-lasting active graves' orbitopathy: a case report and literature review.

PURPOSE: To present a case and review the literature on Orbital Radiotherapy (OR) combined with intravenous methylprednisolone, focusing on its late application in patients with long-lasting active Graves' Orbitopathy (GO). Additionally, we suggest emerging perspective for future research in this context. METHOD: Relevant literature (randomized controlled studies, retrospective studies and reviews) was explored on PubMed from January 1973 to January 2024, searching "orbital radiotherapy" & "Graves disease". RESULTS: OR is a well-established second-line treatment for moderate-to-severe active GO, providing response rates comparable to glucocorticoids. Its anti-inflammatory effect makes OR particularly suitable for early active GO, and when combined with glucocorticoids, outcomes are synergistically improved. The emergence of the new Volumetric Modulated Arc Image-Guided Radiation Therapy (VMAT-IGRT) technique enables precise radiation delivery to the target, significantly reducing associated toxicity. This technological advancement enhances the feasibility of radiotherapy in benign diseases like GO. A retrospective study indicated that late OR in patients with long-lasting active GO may improve diplopia and visual acuity, decreasing disease activity. Our case report supports this conclusion. CONCLUSIONS: This report and literature review underscores the importance of considering late OR combined with intravenous methylprednisolone as a viable treatment option for GO patients with prolonged disease activity, emphasizing the crucial role of personalized therapy in managing GO. However, further investigations are warranted to validate this approach in cases of long-lasting active GO.

A Prospective Multicenter Study Examining the Relationship Between Thyroid Cancer Treatment Outcomes and the Presence of Autoimmune Thyroiditis.

Background: There is some controversy on the potential relationship between autoimmune processes and clinicopathologic features as well as prognosis of differentiated thyroid cancer (DTC), and the evidence is limited by its largely retrospective nature. We examined the relationship between the presence of autoimmune thyroiditis (AT) and 1-year thyroid cancer treatment outcomes in a large multicenter study using prospectively collected data. Methods: We included data from consecutive DTC patients enrolled in the Italian Thyroid Cancer Observatory (ITCO) database (NCT04031339). We divided the groups according to the presence (AT) or absence (no autoimmune thyroiditis [noAT]) of associated AT. We used propensity score matching to compare the clinical features and outcomes between the two groups at 1-year follow-up. Results: We included data from 4233 DTC patients, including 3172 (75%) females. The American Thyroid Association (ATA) risk levels were as follows: 51% (2160/4233) low risk, 41.3% (1750/4233) intermediate risk, and 7.6% (323/4233) high risk. There were 1552 patients (36.7%) who had AT. Before propensity score matching, AT patients were significantly younger and had a smaller and bilateral tumor (p < 0.0001). Patients with AT more frequently fell into the low- and intermediate-risk categories, while the ATA high risk was more frequent among noAT patients (p = 0.004). After propensity score matching, patients with AT more frequently showed evidence of disease (structural/biochemical incomplete response) versus excellent/indeterminate response, compared with patients without AT (7.3% vs. 4.5%, p = 0.001), with an odds ratio of 1.86 ([confidence interval: 1.3-2.6], p = 0.0001). However, when considering only structural persistence as the outcome, no statistically significant differences were observed between patients with or without AT (3.4% vs. 2.7%, p = 0.35). The elevated risk associated with the ATA intermediate and high risk at diagnosis remained consistently statistically significant. Conclusions: In this large prospective series, biochemical persistence was more frequent, at 1-year follow-up, in AT patients. However, there was no significant association between the presence of AT and structural persistence of disease. These findings may be explained by the presence of a residual thyroid tissue.

Cholecalciferol Use Is Associated With a Decreased Risk of Incident Morphometric Vertebral Fractures in Acromegaly.

CONTEXT: Skeletal fragility is observed in 30% to 60% of acromegaly patients, representing an emerging complication of the disease that increases disability. Despite several studies having investigated the clinical and hormonal prognostic factors for the occurrence of vertebral fractures (VFs) in acromegaly, very few data are available on their prevention/treatment including the effect of vitamin D (VD) supplementation, which has been reported to have a fracture-protective effect in several studies in patients with osteoporosis. OBJECTIVE: We aimed to investigate the role of cholecalciferol (D3) supplementation in the prevention of incident VFs (i-VFs) in acromegaly. METHODS: A longitudinal, retrospective and multicenter study was performed on 61 acromegaly patients treated and untreated with D3 supplementation. RESULTS: Twenty-six patients were treated with D3 supplementation according to clinical guidelines. The median D3 weekly dosage was 8500 IU (interquartile range [IQR]: 3900). The median duration of D3 supplementation was 94 months (IQR: 38). At last follow-up, i-VFs were diagnosed in 14 patients (23%). I-VFs were less prevalent in patients on D3 supplementation (14.3% of cases) compared to patients not treated with D3 (85.7%; P = .02). The final level of serum V25OH-D was significantly lower in patients who developed i-VFs (28.6 ng/mL, IQR: 4.1) compared to patients who did not develop i-VFs (34.2 ng/mL, IQR: 9.6; P = .05). The logistic regression confirmed the protective role of D3 supplementation on the occurrence of i-VFs (odds ratio: 0.16; 95% CI, 0.03-0.79; P = .01). CONCLUSION: It is likely that D3 supplementation could lead to a reduction in i-VFs in acromegaly.

Long-term low-dose tolvaptan efficacy and safety in SIADH.

PURPOSE: Tolvaptan, a selective vasopressin V2-receptor antagonist, is approved for the treatment of SIADH-related hyponatremia, but its use is limited. The starting dose is usually 15 mg/day, but recent clinical experience suggests a lower starting dose (<15 mg/day) to reduce the risk of sodium overcorrection. However, long-term low-dose efficacy and safety has not been explored, so far. Aim of our study is to characterize safety and efficacy of long-term SIADH treatment with low-dose Tolvaptan. METHODS: We retrospectively evaluated 11 patients receiving low-dose Tolvaptan (<15 mg/day) for chronic SIADH due to neurological, idiopathic and neoplastic causes. Plasma sodium levels were measured before and 1, 3, 5, 15 and 30 days after starting Tolvaptan and then at 3-month intervals. Anamnestic and clinical data were collected. RESULTS: Mean time spanned 27.3 ± 29.8 months (range 6 months-7 years). Mean plasma sodium levels were within normal range 1, 3 and 6 months after starting Tolvaptan as well as after 1, 2, 3, 5 and 7 years of therapy. Neither osmotic demyelination syndrome nor overcorrection were observed. Plasma sodium levels normalization was associated with beneficial clinical effects. Neurological patients obtained seizures disappearance, improvement in neurological picture and good recovery from rehabilitation. Neoplastic patients were able to start chemotherapy and improved their general condition. Patients did not show hypernatremia during long-term follow-up and reported mild thirst and pollakiuria. CONCLUSIONS: The present study shows that long-term low-dose Tolvaptan is safe and effective in SIADH treatment. No cases of overcorrection were documented and mild side effects were reported.

A Data-Driven Approach to Refine Predictions of Differentiated Thyroid Cancer Outcomes: A Prospective Multicenter Study.

CONTEXT: The risk stratification of patients with differentiated thyroid cancer (DTC) is crucial in clinical decision making. The most widely accepted method to assess risk of recurrent/persistent disease is described in the 2015 American Thyroid Association (ATA) guidelines. However, recent research has focused on the inclusion of novel features or questioned the relevance of currently included features. OBJECTIVE: To develop a comprehensive data-driven model to predict persistent/recurrent disease that can capture all available features and determine the weight of predictors. METHODS: In a prospective cohort study, using the Italian Thyroid Cancer Observatory (ITCO) database (NCT04031339), we selected consecutive cases with DTC and at least early follow-up data (n = 4773; median follow-up 26 months; interquartile range, 12-46 months) at 40 Italian clinical centers. A decision tree was built to assign a risk index to each patient. The model allowed us to investigate the impact of different variables in risk prediction. RESULTS: By ATA risk estimation, 2492 patients (52.2%) were classified as low, 1873 (39.2%) as intermediate, and 408 as high risk. The decision tree model outperformed the ATA risk stratification system: the sensitivity of high-risk classification for structural disease increased from 37% to 49%, and the negative predictive value for low-risk patients increased by 3%. Feature importance was estimated. Several variables not included in the ATA system significantly impacted the prediction of disease persistence/recurrence: age, body mass index, tumor size, sex, family history of thyroid cancer, surgical approach, presurgical cytology, and circumstances of the diagnosis. CONCLUSION: Current risk stratification systems may be complemented by the inclusion of other variables in order to improve the prediction of treatment response. A complete dataset allows for more precise patient clustering.

Systemic comorbidities of acromegaly in real-life experience: which difference among young and elderly patients?

INTRODUCTION: Acromegaly is a rare but potentially life-threatening disease, if not promptly managed, for the systemic complications due to the GH/IGF-I hypersecretion. According to the increased population life span, the number of older acromegaly patients is growing. We aim to investigate clinical features of elderly acromegaly (elderly-ACRO) and to identify the risk factors for the occurrence of comorbidities in elderly-ACRO. MATERIALS AND METHODS: A retrospective and multi-center study was performed on acromegaly patients. Acromegaly comorbidities were compared among elderly-ACRO (>65 years), young acromegaly patients (young-ACRO if ≤65 years) and a control group of age and gender-matched subjects. RESULT: Fifty of the 189 enrolled patients were elderly-ACRO (26.5%). Cardiovascular, metabolic, neurological/psychiatric and joint/articular disorders, nodular thyroid disease, sleep apnoea syndrome and skeletal fragility occurred more frequently in elderly-ACRO as compared to controls. Cardiovascular and metabolic disorders, nodular thyroid disease occurred significantly more frequently in elderly-ACRO as compared to young-ACRO and controls. On the other hand, neurological/psychiatric, joint/articular disorders and bone fragility occur with a similar frequency among elderly and young-ACRO. We found that elderly-ACRO had an increased risk for the occurrence of systemic arterial hypertension (p < 0.001, OR: 5.4 95%IC:2.6-10.9), left ventricular hypertrophy (p = 0.01, OR: 3 95%IC: 1.5-5.8) and metabolic disorders (p = 0.006, OR: 4.1 95%IC: 2-8.3). CONCLUSION: Our results may suggest that some acromegaly comorbidities may be predominantly due to acromegaly "per-se" rather than to aging. On the contrary, cardiovascular and metabolic disorders seem to be due to aging as well.

Pituitary apoplexy and COVID-19 vaccination: a case report and literature review.

A 50-year-old man was admitted to our hospital for vomit, nausea, diplopia, and headache resistant to analgesic drugs. Symptoms started the day after his third COVID-19 mRNA vaccine (Moderna) whereas SARS-CoV-2 nasal swab was negative. Pituitary MRI showed recent bleeding in macroadenoma, consistent with pituitary apoplexy. Adverse Drug Reaction was reported to AIFA (Italian Medicines Agency).A stress dexamethasone dose was administered due to the risk of adrenal insufficiency and to reduce oedema. Biochemistry showed secondary hypogonadism; inflammatory markers were elevated as well as white blood cells count, fibrinogen and D-dimer. Pituitary tumour transsphenoidal resection was performed and pathology report was consistent with pituitary adenoma with focal haemorrhage and necrosis; we found immunohistochemical evidence for SARS-CoV-2 proteins next to pituitary capillaries, in the presence of an evident lymphocyte infiltrate.Few cases of pituitary apoplexy after COVID-19 vaccination and infection have been reported. Several hypotheses have been suggested to explain this clinical picture, including cross-reactivity between SARS-CoV-2 and pituitary proteins, COVID-19-associated coagulopathy, infection-driven acutely increased pituitary blood demand, anti-Platelet Factor 4/heparin antibodies development after vaccine administration. Ours is the first case of SARS-CoV-2 evidence in pituitary tissue, suggesting that endothelial infection of pituitary capillaries could be present before vaccination, possibly due to a previous asymptomatic SARS-CoV-2 infection. Our case underlines that SARS-CoV-2 can associate with apoplexy by penetrating the central nervous system, even in cases of negative nasal swab. Patients with pituitary tumours may develop pituitary apoplexy after exposure to SARS-CoV-2, therefore clinicians should be aware of this risk.

Radioligand therapy (RLT) as neoadjuvant treatment for inoperable pancreatic neuroendocrine tumors: a literature review.

In the last 10 years, several literature reports supported radioligand therapy (RLT) in neoadjuvant settings for pancreatic neuroendocrine tumors (PanNETs). Indeed, primary tumor shrinkage has been frequently reported following RLT in unresectable or borderline resectable PanNETs. Moreover, RLT-induced intratumoral modifications facilitate surgery, both on primary tumor and metastasis, having a great impact on progression free survival (PFS), overall survival (OS) and quality of life (QoL). However, prospective controlled investigations are necessary to confirm preliminary data and to define the best RLT scheme and the ideal patient that, in a multidisciplinary approach, should be referred to neoadjuvant RLT.

Impact of the diagnostic delay of acromegaly on bone health: data from a real life and long term follow-up experience.

INTRODUCTION: Acromegaly is a chronic disease with systemic complications. Disease onset is insidious and consequently typically burdened by diagnostic delay. A longer diagnostic delay induces more frequently cardiovascular, respiratory, metabolic, neuropsychiatric and musculoskeletal comorbidities. No data are available on the effect of diagnostic delay on skeletal fragility. We aimed to evaluate the effect of diagnostic delay on the frequency of incident and prevalent of vertebral fractures (i-VFs and p-VFs) in a large cohort of acromegaly patients. PATIENTS AND METHODS: A longitudinal, retrospective and multicenter study was conducted on 172 acromegaly patients. RESULTS: Median diagnostic delay and duration of follow-up were respectively 10 years (IQR: 6) and 10 years (IQR: 8). P-VFs were observed in 18.6% and i-VFs occurred in 34.3% of patients. The median estimated diagnostic delay was longer in patients with i-VFs (median: 11 years, IQR: 3), in comparison to those without i-VFs (median: 8 years, IQR: 7; p = 0.02). Age at acromegaly diagnosis and at last follow-up were higher in patients with i-VFs, with respect to those without i-VFs. The age at acromegaly diagnosis was positively associated with the diagnostic delay (p < 0.001, r = 0.216). A longer history of active acromegaly was associated with a high frequency of i-VFs (p = 0.03). The logistic regression confirmed that patients with a diagnostic delay > 10 years had 1.5-folds increased risk of developing i-VFs (OR: 1.5; 95%CI: 1.1-2; p = 0.017). CONCLUSION: Our data showed that the diagnostic delay in acromegaly has a significant impact on VF risk, further supporting the clinical relevance of an early acromegaly diagnosis.

The role of opportunistic quantitative computed tomography in the evaluation of bone disease and risk of fracture in thalassemia major.

OBJECTIVE: Dual-energy X-ray absorptiometry (DXA) remains the cornerstone for osteoporosis evaluation in Thalassemia major. However, several drawbacks have been observed in this unique setting. We sought to determine the correlation between quantitative CT (QCT) and DXA-derived parameters; secondarily, we aimed to investigate the role of the two techniques in predicting the risk of fracture. METHODS: We retrospectively included patients with ß-thalassemia major who had undergone both lumbar and femoral DXA examinations, and CT scans including the lumbar spine, performed for disparate diagnostic issues, within 4 months from the DXA. CT data were examined employing a phantom-less QCT method for bone mineral density (BMD) assessment. We also retrieved any spontaneous or fragility fractures occurring from 1 year before up to 5 years after the date of DXA scans. RESULTS: The 43 patients were included. QCT measures were significantly higher than those determined by DXA. The gap between QCT and DXA values was strongly associated with patient age. The most powerful predictive variable for risk of fracture was the ACR classification based on volumetric BMD obtained by QCT. CONCLUSIONS: DXA provided more negative measures than those determined by QCT. However, QCT seemed to evaluate thalassaemic osteopathy better than DXA, since volumetric BMD was a stronger predictor of fracture.

Risk of second brain tumour after radiotherapy for pituitary adenoma or craniopharyngioma: a retrospective, multicentre, cohort study of 3679 patients with long-term imaging surveillance.

BACKGROUND: Radiotherapy is a valuable treatment in the management algorithm of pituitary adenomas and craniopharyngiomas. However, the risk of second brain tumour following radiotherapy is a major concern. We assessed this risk using non-irradiated patients with the same primary pathology and imaging surveillance as controls. METHODS: In this multicentre, retrospective cohort study, 4292 patients with pituitary adenoma or craniopharyngioma were identified from departmental registries at six adult endocrine centres (Birmingham, Oxford, Leeds, Leicester, and Bristol, UK and Ferrara, Italy). Patients with insufficient clinical data, known genetic predisposition to or history of brain tumour before study entry (n=532), and recipients of proton beam or stereotactic radiotherapy (n=81) were excluded. Data were analysed for 996 patients exposed to 2-dimensional radiotherapy, 3-dimensional conformal radiotherapy, or intensity-modulated radiotherapy, and compared with 2683 controls. FINDINGS: Over 45 246 patient-years, second brain tumours were reported in 61 patients (seven malignant [five radiotherapy, two controls], 54 benign [25 radiotherapy, 29 controls]). Radiotherapy exposure and older age at pituitary tumour detection were associated with increased risk of second brain tumour. Rate ratio for irradiated patients was 2·18 (95% CI 1·31-3·62, p<0·0001). Cumulative probability of second brain tumour was 4% for the irradiated and 2·1% for the controls at 20 years. INTERPRETATION: Irradiated adults with pituitary adenoma or craniopharyngioma are at increased risk of second brain tumours, although this risk is considerably lower than previously reported in studies using general population controls with no imaging surveillance. Our data clarify an important clinical question and guide clinicians when counselling patients with pituitary adenoma or craniopharyngioma on the risks and benefits of radiotherapy. FUNDING: Pfizer.

Glucose Metabolism Derangements and Thyroid Nodules: Does Sex Matter?

(1) Background: Glucose metabolism derangements (GMD) and thyroid nodules (TNs) are the most frequent endocrine disorders, and their relationship is still controversial; little evidence is reported regarding sex differences. We aim to evaluate the association between GMDs and TNs according to sex and the sex differences in glucose metabolism and insulin sensitivity (IS). (2) Methods: We evaluated 342 patients (268 females and 74 males) at high GMD risk undergoing an oral glucose tolerance test and a thyroid ultrasound. (3) Results: The TN prevalence was 61% (n = 210), with no significant differences according to sex and GMD classes. The TN presence is significantly associated with age and impaired fasting glucose (IFG) in females. Males and females with normal fasting glucose (NFG) had a significantly lower OR of having TNs than females with IFG. IFG females had a significantly higher predicted probability of having TNs than NFG males and females but not IFG males. Impaired glucose tolerance/Type 2 diabetes mellitus (IGT/T2DM) is significantly associated with age and male sex, while IFG is associated with age. Females had significantly lower HOMA-index values than males. (4) Conclusions: No significant association between IGT/T2DM and TNs according to sex was found. IFG seems to play a role in TN development independently of sex. Further studies are needed to explore the relationship between TNs and GMD to identify subgroups with a higher TN risk.

Beta-thalassaemia major: Prevalence, risk factors and clinical consequences of hypercalciuria.

Regular transfusion and chelation therapy produces increased life expectancy in thalassaemic patients who may develop new complications. Since few data are available regarding hypercalciuria in ß-thalassaemia major (TM), the aim of our study was to evaluate its prevalence, risk factors and clinical consequences. We enrolled 176 adult TM patients followed at the Center of Thalassemia of Ferrara. Hypercalciuria was defined by a calciuria of 4 mg/kg/day or more in a 24-h urine sample. Anamnestic, biochemical and radiological data were collected. Hypercalciuria prevalence was reported in 69.3% of patients (females 52.5%). Hypercalciuric (HC) patients used deferasirox (DFX) more often than normocalciuric (NC) patients (47.5% vs 29.6%; p < 0.05). In HC subjects plasma parathyroid hormone (PTH) (24.1 ± 10.4 vs 30.1 ± 13.2 pg/ml) and phosphate levels (3.6 ± 0.5 vs 3.8 ± 0.7 mg/dl) were lower, whereas serum calcium (9.6 ± 0.4 vs 9.4 ± 0.4 mg/dl) and urinary 24-h phosphaturia (0.9 ± 0.4 vs 0.6 ± 0.3 g/day) were higher as compared to NC patients (p < 0.05 for all comparisons). Supplementation with oral calcium and cholecalciferol was similar between the groups. A higher rate of kidney stones was present in HC (14.8%) versus NC patients (3.7%) (p < 0.05). Hypercalciuria is a frequent complication in adequately treated adult TM patients. Hypercalciuria prevalence is increased in DFX users whereas haemoglobin level or calcium supplements play no role. A significant proportion of HC patients developed kidney stones.

Efficacy and Safety of Teriparatide in Beta-Thalassemia Major Associated Osteoporosis: A Real-Life Experience.

Osteoporosis represents a relevant cause of morbidity in adult Thalassemia Major (TM) population. Antiresorptive drugs such as bisphosphonates were demonstrated effective in preventing bone loss. Teriparatide (TP) is an anabolic agent approved for osteoporosis management in the general population, but its use has been very limited in TM patients so far. We evaluated TP efficacy and safety in TM-associated osteoporosis in real-life clinical practice. Retrospective evaluation of 11 TM patients (6 males, 5 females; mean age = 45 ± 4.38 years) with severe osteoporosis and multiple fractures under TP treatment. Mean TP treatment duration was 19 ± 7 months. TP withdrawal was due to poor compliance and side effects (fever and osteo-muscular pain) in two and three patients, respectively. After 12 and 24 months, BMD significantly increased at lumbar (+ 19% and 22%) and femoral sites (+ 13% and 13%). Osteocalcin and cross-laps levels increased after 12 and 24 months (+ 225 and + 54.2%; + 159 and 141%, respectively). No new fractures were detected during TP treatment. Baseline VAS score values (3 ± 3) did not significantly change after 12 and 24 months (3 ± 3 and 2 ± 3, respectively). Five out of eleven patients developed side effects. TP might be an effective treatment for TM-associated osteoporosis since it improves BMD, especially at the lumbar spine, and prevents fragility fractures. TM patients may have a higher frequency of side effects, especially muscle and bone pain under TP treatment, as compared to no TM population. Further studies are needed.

Resistance to Somatostatin Analogs in Italian Acromegaly Patients: The MISS Study.

Approximately 60% of acromegaly patients are not adequately controlled by first-generation somatostatin receptor ligands. This multicenter retrospective study aimed to identify the most relevant biomarkers specific for the Italian acromegaly population. Resistant patients were enrolled consecutively based on time of neurosurgery, while responders were collected in a 1:2 ratio. Clinical characteristics and T2-intensity on MRI scans at diagnosis were retrospectively re-evaluated. Histological analyses of CAM5.2 granulation patterns and SSTR2 expression were centrally performed. Sixty-three resistant patients and thirty-three responders were enrolled. A low-grade SSTR2 expression was the most relevant predictor of resistance identified (OR 4.58, p = 0.013), even considering CAM5.2 immunohistochemistry (OR 2.65, p = 0.047). T2-iso/hyperintense pattern on MRI was also associated with a 3.3-fold greater probability of poor response to medical treatment (p = 0.027), as well as a young age at diagnosis (OR 0.96, p = 0.035). In those patients treated only after neurosurgery due to persistent GH-hypersecretion (51, 53.1%) the absence of any appreciable adenomatous remnant on postoperative MRI was associated with a negligible risk of resistance (OR 0.04, p = 0.003). In the Italian acromegaly population, a low-grade SSTR2 expression seems to be the most relevant predictor of resistance to first-generation somatostatin receptor ligands, followed by a SG/intermediate cytokeratin pattern and a T2-iso/hyperintense MRI signal.

Bone health in adolescence.

Adolescence is a fundamental period for the formation of the skeleton, because is the stage in which bones grow more in both size and strength, laying a solid foundation for the future health of the skeleton. Any condition interfering with optimal peak bone mass accrual can increase fracture risk later in life. Up to 80% of peak bone mass is genetically determined while the remaining 20% is modulated by environmental factors that, if deleterious, may result in low bone mineral density (BMD) and an increased risk of fracture. The preferred test to assess bone health is dual-energy x-ray absorptiometry (spine or total body less head) using Z scores instead of T scores, even though in short stature or growth delay, should be used the height Z-score. The correction of risk factors is the first treatment for low BMD in children and adolescents. It's necessary having a correct lifestyle for preserving bone health: a proper nutrition, an adequate physical weight-bearing activity and avoidance of alcohol intake and tobacco smoke. Bisphosphonates could be used in children who sustained osteoporotic fractures, impairing quality of life, when spontaneous recovery is low for the persistence of osteoporosis risk factors. This clinical review discusses factors affecting bone health during childhood and adolescence and deals with diagnosis and treatment of low bone mass or osteoporosis in this age group.

Multidimensional geriatric evaluation in acromegaly: a comparative cross-sectional study.

BACKGROUND: Improvement in acromegaly management increased disease survival and prevalence. Evidence regarding acromegaly in older adults are sparse. We aim to explore acromegaly impact on aging process quality. METHODS: Multicenter case-control study conducted on 42 older adults (≥ 65 years) acromegaly patients (ACRO) compared to an age- and gender-matched control group (CTR). Each participant underwent a multidimensional geriatric evaluation. RESULTS: Mean age in both groups was 73 ± 6 years and female gender was most represented (69%). All comorbidities were more frequent in ACRO than CTR. Thirteen ACRO were in remission and 29 had active disease controlled by medical therapy except for one patient. ACRO showed worse physical performance and mobility skills worsening with age as compared to CTR. ACRO performed poorly in functional status assessment, and age negatively correlated with instrumental and basic daily activities execution. Cognitive evaluation scores were significantly lower in ACRO vs. CTR, worsening with age. No difference was found concerning nutritional and psychological status. Musculoskeletal and bone diseases were more frequent in ACRO than in CTR (52% vs. 12%; 64% vs. 10%; P < 0.05) and independently associated with geriatric outcomes in ACRO. ACRO reported a less satisfactory quality of life concerning physical activity and pain, general health, vitality, social activities. CONCLUSIONS: Our study demonstrates increased frailty of older acromegaly patients as compared to non-acromegaly patients with a consequent negative impact on their quality of life. Therefore, it seems advisable to include physical, functional, cognitive, nutritional, and psychological status assessments in routine clinical practice. Further studies are needed to identify the most appropriate geriatric tools.

Minimal Extrathyroidal Extension in Predicting 1-Year Outcomes: A Longitudinal Multicenter Study of Low-to-Intermediate-Risk Papillary Thyroid Carcinoma (ITCO#4).

Background: The role of minimal extrathyroidal extension (mETE) as a risk factor for persistent papillary thyroid carcinoma (PTC) is still debated. The aims of this study were to assess the clinical impact of mETE as a predictor of worse initial treatment response in PTC patients and to verify the impact of radioiodine therapy after surgery in patients with mETE. Methods: We reviewed all records in the Italian Thyroid Cancer Observatory database and selected 2237 consecutive patients with PTC who satisfied the inclusion criteria (PTC with no lymph node metastases and at least 1 year of follow-up). For each case, we considered initial surgery, histological variant of PTC, tumor diameter, recurrence risk class according to the American Thyroid Association (ATA) risk stratification system, use of radioiodine therapy, and initial therapy response, as suggested by ATA guidelines. Results: At 1-year follow-up, 1831 patients (81.8%) had an excellent response, 296 (13.2%) had an indeterminate response, 55 (2.5%) had a biochemical incomplete response, and 55 (2.5%) had a structural incomplete response. Statistical analysis suggested that mETE (odds ratio [OR] 1.16, p = 0.65), tumor size >2 cm (OR 1.45, p = 0.34), aggressive PTC histology (OR 0.55, p = 0.15), and age at diagnosis (OR 0.90, p = 0.32) were not significant risk factors for a worse initial therapy response. When evaluating the combination of mETE, tumor size, and aggressive PTC histology, the presence of mETE with a >2 cm tumor was significantly associated with a worse outcome (OR 5.27 [95% confidence interval], p = 0.014). The role of radioiodine ablation in patients with mETE was also evaluated. When considering radioiodine treatment, propensity score-based matching was performed, and no significant differences were found between treated and nontreated patients (p = 0.24). Conclusions: This study failed to show the prognostic value of mETE in predicting initial therapy response in a large cohort of PTC patients without lymph node metastases. The study suggests that the combination of tumor diameter and mETE can be used as a reliable prognostic factor for persistence and could be easily applied in clinical practice to manage PTC patients with low-to-intermediate risk of recurrent/persistent disease.