The onset time of amiodarone-induced thyrotoxicosis (AIT) depends on AIT type

Objective: Considering the different pathogenic mechanisms of the two main forms of amiodarone-induced thyrotoxicosis (AIT), we ascertained whether this results in a different onset time as well. Design and methods: We retrospectively analyzed the clinical records of 200 consecutive AIT patients (157 men and 43 women; mean age 62.2G12.6 years) referred to our Department from 1987 to 2012. The onset time of AIT was defined as the time elapsed from the beginning of amiodarone therapy and the first diagnosis of thyrotoxicosis, expressed in months. Factors associated with the onset time of AIT were evaluated by univariate and multivariate analyses. Results: The median onset time of thyrotoxicosis was 3.5 months (95% CI 2–6 months) in patients with type 1 AIT (AIT1) and 30 months (95% CI 27–32 months, P!0.001) in those with type 2 AIT (AIT2). Of the total number of patients, 5% with AIT1 and 23% with AIT2 (PZ0.007) developed thyrotoxicosis after amiodarone withdrawal. Factors affecting the onset time of thyrotoxicosis were the type of AIT and thyroid volume (TV). Conclusions:ThedifferentpathogenicmechanismsofthetwoformsofAITaccountfordifferentonsettimesofthyrotoxicosisin the two groups. Patients with preexisting thyroid abnormalities (candidate to develop AIT1) may require a stricter follow-up during amiodarone therapy than those usually recommended. In AIT1, the onset of thyrotoxicosis after amiodarone withdrawal is rare, while AIT2 patients may require periodic tests for thyroid function longer after withdrawing amiodarone

Continuation of amiodarone delays restoration of euthyroidism in patients with type 2 amiodarone-induced thyrotoxicosis treated with prednisone: a pilot study

Context: Type 2 amiodarone-induced thyrotoxicosis (AIT) is a destructive thyroiditis usually re- sponsive to glucocorticoids. Whether continuation of amiodarone affects treatment outcome is unsettled. Objective: The objective of the study was to compare the outcome of glucocorticoid treatment in type 2 AIT patients who continued or withdrew amiodarone. Design: This was a matched retrospective cohort study. Setting: The study was conducted at a university center. Patients: Eighty-three consecutive patients with untreated type 2 AIT participated in the study. After matching with patients continuing amiodarone (AMIO-ON, n 8), patients interrupting amiodarone were randomly selected in a 4:1 ratio (AMIO-OFF, n 32). Intervention: All patients were treated with oral prednisone. Patients whose thyrotoxicosis re- curred after glucocorticoid withdrawal were treated with a second course of prednisone. Main Outcome Measure: Time and rate of cure were measured. Results: Median time to the first normalization of serum thyroid hormone levels did not signifi- cantly differ in AMIO-ON and AMIO-OFF patients (24 and 31 d, respectively; P 0.326). Conversely, median time for stably restoring euthyroidism was 140 d in AMIO-ON patients and 47 d in AMIO- OFF patients (log rank, P 0.011). In fact, AIT recurred in five of seven AMIO-ON patients (71.4%) and in only three of 32 AMIO-OFF patients (9.4%, P 0.002), requiring readministration of pred- nisone. One AMIO-ON patient never reached thyroid hormone normalization during the study period. Factors associated with glucocorticoid failure were thyroid volume and amiodarone continuation. Conclusions: Prednisone restores euthyroidism in most type 2 AIT patients, irrespective of amio- darone continuation or withdrawal. However, continuing amiodarone increases the recurrence rate of thyrotoxicosis, causing a delay in the stable restoration of euthyroidism and a longer exposure of the heart to thyroid hormone exces

Minimally Invasive Video-Assisted Thyroidectomy versus Conventional Thyroidectomy in Pediatric Patients

Background Minimally invasive video-assisted thyroidectomy (MIVAT) proved to be safe and effective in the treatment of both benign and malignant disease. The aim of the present study is to compare MIVAT approach with conventional approach for total thyroidectomy in a group of 99 pediatric patients operated in the Department of General Surgery of the University of Pisa between March 2007 and July 2012. Patients A total of 99 pediatric patients under the age of 18 years with thyroid disease referred to our Department to undergo total thyroidectomy. Patients were divided into two groups according to the surgical technique performed: 34/99 (34.3%) patients (MIVAT group [MG]) and 65/99 (65.7%) patients, (conventional group [CG]) who underwent total thyroidectomy, respectively, with MIVAT approach and conventional approach. Results In MG mean operative time for total thyroidectomy was 40 ± 6.57 minutes (range 30-60 min); postoperative hospital stay was 1 day for 18 patients (53%), 2 days for 12 patients (35.25%), 3 days for 4 patients (11.8%); transient hypoparathyroidism (hypoPTH) was observed in 12 cases (35.3%) and permanent hypoPTH in 2 cases (5.9%); transient postoperative unilateral vocal cord palsy was observed in 2 patients (5.9%). In CG mean operative time for total thyroidectomy was 49.3 ± 12.9 minutes (range 30-80 min); postoperative hospital stay was 1 day for 16 patients (24.6%), 2 days for 40 patients (61.5%), 3 days for 8 patients (12.3%), and 4 days for 1 patient (1.6%); transient hypoPTH was observed in 23 cases (35.4%) and permanent hypoPTH in 4 cases (6.1%), who needed therapy with calcitriol and calcium carbonate; transient postoperative unilateral vocal cord palsy was observed in 4 patients (6.1%). There were no cases of permanent vocal cord paralysis in both groups. The correlation between two groups of patients showed that mean operative time was significantly lower in MG (p = 0.0007). Conclusion Pediatric patients of MG showed a significantly lower operative time and postoperative hospital stay with respect to pediatric patients of CG if compared with conventional technique. This result with the evidence of similar degree of completeness and rate of postoperative complications make MIVAT a valid option for the treatment of pediatric patients when performed by a well-trained staff in a third referral center. © Georg Thieme Verlag KG

Divergent effects of dioxin- or non- dioxin- Like polychlorinated biphenyls on the apoptosis of primary cell culture from the mouse dioxin pituitary gland

Polychlorinated biphenyls (PCBs) can disrupt the endocrine function, promote neoplasms and regulate apoptosis in some tissues; however, it is unknown whether PCBs can affect the apoptosis of pituitary cells. The study evaluated the effect of PCBs on the apoptosis of normal pituitary cells and the underlying mechanisms. Primary cell cultures obtained from mouse pituitary glands were exposed to Aroclor 1254 or selected dioxin-like (PCB 77, PCB 126) or non-dioxin-like (PCB 153, PCB 180) congeners. Apoptosis was evaluated by Annexin V staining, DNA fragmentation, and TUNEL assay. Both the expression and activity of caspases were analyzed. Selective thyroid hormone receptor (TR) or aryl-hydrocarbon receptor (AhR) or CYP1A1 antagonist were used to explore the mechanisms underlying PCBs action. Our results showed that Aroclor 1254 induced the apoptosis of pituitary cells as well as the final caspase-3 level and activity through the extrinsic pathway, as shown by the increased caspase-8 level and activity. On the other hand, the intrinsic pathway evaluated by measuring caspase-9 expression was silent. The selected non-dioxin- like congeners either increased (PCB 180) or reduced (PCB 153) pituitary cell apoptosis, affecting the extrinsic pathway (PCB 180), or both the extrinsic and intrinsic pathways (PCB 153), respectively. In contrast, the dioxin-like congeners (PCB 77 and PCB 126) did not affect apoptosis. The anti-apoptotic phenotype of PCB 153 was counteracted by a TR or a CYP1A1 antagonist, whereas the pro-apoptotic effect of PCB 180 was counteracted by an AhR antagonist. The induced apoptosis of Aroclor 1254 or PCB 180 was associated with a reduction of cell proliferation, whereas the decreased apoptosis due to PCB 153 increased cell proliferation by 30%. In conclusion, our data suggest that non-dioxin-like PCBs may modulate apoptosis and the proliferation rate of pituitary cells that have either pro- or anti-apoptotic effects depending on the specific congeners. However, the impact of PCBs on the process of pituitary tumorigenesis remains to be elucidated

Vitamin D status may contribute to serum insulin-like growth factor I concentrations in healthy subjects

OBJECTIVE: The aim of the study was to evaluate whether vitamin D [25-(OH) D3] status affects serum IGFI concentrations in healthy subjects. DESIGN AND PATIENTS: Two hundred and forty-one consecutive healthy subjects were included in the present study. MEASUREMENTS: Serum IGF-I and 25-(OH) D3 concentrations. RESULTS: As expected, serum IGF-I concentrations progressively decreased with age (r=-0.55, p<0.0001); on the contrary, gender was not related to serum IGF-I levels. A positive relationship was identified between serum 25-(OH) D3 and IGF-I concentrations (r=0.33, p<0.0001); the 25-(OH) D3-dependent changes of serum IGF-I concentrations were observed also when subjects were divided on the basis of vitamin D deficiency; in fact, those with severe 25-(OH) D3 deficiency (<20 ng/ml) had lower (185 ± 83 μg/l) IGF-I values than those with mild-to absent 25-(OH) D3 deficit (225 ± 83 μg/l, p=0.0004). CONCLUSIONS: 25-(OH) D3 status may contribute to determine serum IGF-I levels in healthy population

Total thyroidectomy in patients with amiodarone-induced thyrotoxicosis and severe left ventricular systolic dysfunction.

Context: Patients with amiodarone-induced thyrotoxicosis (AIT) and left ventricular (LV) systolic dysfunction have a high mortality rate. Usually, medical therapy is the first choice for AIT patients, whereas the role of the thyroidectomy is unsettled. Objective: The objective of the study was to evaluate the effect of a total thyroidectomy on cardiac function and survival of AIT patients with severe LV systolic dysfunction. Design: This was a retrospective cohort study. Settings: The study was conducted at a tertiary university center. Patients: All AIT patients (n 24; nine patients with type 1 AIT, 15 patients with type 2 AIT) referred to the Department of Endocrinology and submitted to a total thyroidectomy at the Department of Surgery, both at the University of Pisa, during the years 1997–2010. Intervention: The intervention was a total thyroidectomy. Main Outcome Measure: LV ejection fraction (EF) after the thyroidectomy and survival in December 2011 were measured. Results: All enrolled patients had previously undergone to medical treatment for AIT, as appropriate, without achieving euthyroidism. Patients with moderate to severe LV systolic dysfunction (EF 40%, group 1, n 9) or with mild systolic dysfunction (40% EF 50%, group 2, n 5) were compared with patients with normal systolic function (EF 50%, group 3, n 10). Two months after thyroidectomy, under levothyroxine replacement therapy, LVEF improved in patients with LV systolic dysfunction, particularly in those of group 1, in whom it increased from 28.2 7.2 to 38.3 6% (P 0.007). On the contrary, LVEF did not significantly change in group 3 (from 57.1 3.0 to 59.8 6.6%, P 0.242). The mean follow-up was 67 42 months. No death occurred during and 2 months after surgery. One death occurred in one patient of group 1, 30 months after the thyroidectomy, due to acute myocardial infarction. No patient had relevant complications of thyroidectomy. Conclusions: Total thyroidectomy, by rapidly restoring euthyroidism, may improve cardiac function and reduce the risk of mortality in AIT patients with severe LV dysfunctio

DISEASE ACTIVITY AND LIFESTYLE INFLUENCE COMORBIDITIES AND CARDIOVASCULAR EVENTS IN PATIENTS WITH ACROMEGALY

Objective: The primary objective of this study is to identify the predictors of comorbidities and major adverse cardiovascular events (MACE) that can develop after diagnosis of acromegaly. The role of therapy for acromegaly in the event of such complications was also evaluated. Design and methods: Retrospective cohort study was conducted on 200 consecutive acromegalic patients in a tertiary referral center. The following outcomes were evaluated: diabetes, hypertension and MACE. Each patient was included in the analysis of a specific outcome, unless they were affected when acromegaly was diagnosed, and further classified as follows: (i) in remission after adenomectomy (Hx), (ii) controlled by somatostatin analogues (SSA) (SSAc) or (iii) not controlled by SSA (SSAnc). Data were evaluated using Cox regression analysis. Results: After diagnosis of acromegaly, diabetes occurred in 40.8% of patients. The SSAnc group had a three-fold higher risk of diabetes (HR: 3.32, P = 0.006), whereas the SSAc group had a 1.4-fold higher risk of diabetes (HR: 1.43, P = 0.38) compared with the Hx group. Hypertension occurred in 35.5% of patients, after diagnosis. The determinants of hypertension were age (HR: 1.06, P = 0.01) and BMI (HR: 1.05, P = 0.01). MACE occurred in 11.8% of patients, after diagnosis. Age (HR: 1.09, P = 0.005) and smoking habit (HR: 5.95, P = 0.01) were predictors of MACE. Conversely, therapy for acromegaly did not influence hypertension or MACE. Conclusion: After diagnosis of acromegaly, control of the disease (irrespective of the type of treatment) and lifestyle are predictors of comorbidities and major adverse cardiovascular events

Efficacy of Convalescent Plasma to Treat Long-Standing COVID-19 in Patients with B-Cell Depletion

The use of antivirals, corticosteroids, and IL-6 inhibitors has been recommended by the WHO to treat COVID-19. CP has also been considered for severe and critical cases. Clinical trials on CP have shown contradictory results, but an increasing number of patients, including immunocompromised ones, have shown benefits from this treatment. We reported two clinical cases of patients with prolonged COVID-19 infection and B-cell depletion who showed rapid clinical and virological recovery after the administration of CP. The first patient in this study was a 73-year-old female with a history of follicular non-Hodgkin lymphoma previously treated with bendamustine followed by maintenance therapy with rituximab. The second patient was a 68-year-old male with chronic obstructive pulmonary disease, bipolar disorder, alcoholic liver disease, and a history of mantellar non-Hodgkin lymphoma treated with rituximab and radiotherapy. After the administration of CP, both patients showed a resolution of symptoms, improvement of their clinical conditions, and a negative result of the nasopharyngeal swab test. The administration of CP might be effective in resolving symptoms and improving clinical and virological outcomes in patients with B-cell depletion and prolonged SARS-CoV2 infections

Changes in the activity of caspases during exposure to PCBs.

<p>Caspase activity was assessed by fluorimetric or luminometric assays, as described in the Materials and Methods. Cisplatin (32 μM) was included as a positive control. The activity of the three individual caspases decreased by exposure to PCB 153 (A, B, C). On the other hand, the activity of both caspase-3 and caspase-8 increased after treatment with Aroclor 1254 or PCB 180 (A, B), while the activity of caspase-9 was unaffected (C). To confirm the specificity of PCB action on caspases, cells were also pre-treated with caspase inhibitors prior to PCB exposure. 20 μM Ac-DEVD-CHO (A), Ac-IETD-CHO (B) or Ac-LEHD-CHO (C) were used as inhibitors of caspase -3, -8 or -9, respectively. Data (mean ± SD of five independent experiments) were expressed as arbitrary units (A.U.); the value of 1 was attributed to the caspase activity of vehicle-exposed cells. **, p<0.001, ***, p<0.0001, compared with the vehicle, according to ANOVA followed by Dunnett’s post hoc test. ##, p<0.005, ###, p<0.0005, p = n.s. (not significant), according to Student’s t-test adjusted for multiple comparisons following the Bonferroni method.</p