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Context: Patients with amiodarone-induced thyrotoxicosis (AIT) often receive initial therapy for thyrotoxicosis in several different medical settings before admission to a referral center. Objective: This work aimed to determine whether first-line medical therapy (ie, therapies for thyrotoxicosis at first diagnosis of AIT) affects the outcome of AIT patients. Methods: A single-center historical-prospective cohort study was conducted on 313 AIT patients. Clinical and biochemical data were collected at first diagnosis, at a referral center, and during the course of AIT. Primary outcomes were cardiovascular (CV) events and hospitalizations. First-line therapies were considered appropriate when they included glucocorticoids for type 2 AIT and methimazole for type 1 AIT at the approved dose, either alone (optimal medical therapy, OMT) or in combination (right-dose combination therapy, RCT). Other therapies were considered not appropriate, including no therapy. Duration of exposure to thyrotoxicosis was the time from first diagnosis of AIT to its remission. Results: A total of 34.5% patients received appropriate therapies (28.1% OMT, 6.4% RCT), whereas the remaining (65.5%) received inappropriate therapies. CV events and hospitalizations were more frequent in patients who received inappropriate therapies (33.2% vs 4.5%, and 24.9% vs 6.5%, respectively; P<.0001 for both). Appropriate therapies reduced serum thyroid hormone concentrations (P=.018) from first diagnosis to referral, unlike the inappropriate therapies. The duration of exposure to thyrotoxicosis was longer in patients receiving inappropriate therapies and was a risk factor for arrhythmias (hazard ratio [HR] 1.004; P=.0008), major acute CV events (HR 1.004; P= .020), and hospitalizations (HR 1.006; P<.0001). Conclusion: The first medical therapy of AIT influences the exposure time to thyrotoxicosis and the occurrence of CV events and hospitalizations. [ABSTRACT FROM AUTHOR]

Objective: Acromegaly is associated with somatic disfigurements which impair self-perception of well-being and quality of life. Nowadays, limited data are available on the interplay between hormonal excess and psychological discomfort. The study aimed at investigating the psychological profile, sleep quality, sexual function, cognitive functions, and quality of life in patients with acromegaly. Methods: In 223 acromegaly patients from 5 referral centres, global psychological profile, sleep quality, sexual function, cognitive function, and quality of life were investigated. Results: Depression was found in ~30% of patients, and anxiety in two-thirds, together with severe discomfort in body image mainly in women. Obstructive sleep apnoea syndrome risk and sleep disorders were found in >50% of patients and daily sleepiness in ~20%. Sexual dysfunction was reported in most of the patients, with the most severe impairment in women. Cognitive functions were compromised in ~10% of cases. Disease duration and patient's age and gender were the main determinants of these psychopathological conditions. Depression (P = 0.047), somatic-affective mood lowering (P = 0.021), state (P < 0.001) and trait (P = 0.013) anxiety, and body image distortion in body uneasiness test A (P < 0.001) and B (P = 0.006) were significantly worsened in patients <45 years and slightly worsened in those with disease duration less than 2 years. Male (P < 0.001) and female (P < 0.001) sexual function scores were significantly worsened in patients aged >64 years and slightly worsened in those with disease duration for more than 10 years, particularly in presence of cardiometabolic and respiratory complications. Cognitive symptoms were slightly worsened in older patients and in those with long disease duration. Conclusions: Acromegaly is associated with a relevant impairment of psychological profile persisting despite remission and long-term medical treatment. [ABSTRACT FROM AUTHOR]

Context: Patients with amiodarone-induced thyrotoxicosis (AIT) and severely reduced left ventricular ejection fraction (LVEF) have a high mortality rate that may be reduced by total thyroidectomy. Whether in this subset of patients thyroidectomy should be performed early during thyrotoxicosis or later after restoration of euthyroidism has not yet been settled.Objectives: Mortality rates, including peritreatment mortality and 5-year cardiovascular mortality, and predictors of death, evaluated by Cox regression analysis.Methods: Retrospective cohort study of 64 consecutive patients with AIT selected for total thyroidectomy from 1997 to 2019. Four groups of patients were identified according to serum thyroid hormone concentrations and LVEF: Group 1 (thyrotoxic, LVEF <40%), Group 2 (thyrotoxic, LVEF ≥40%), Group 3 (euthyroid, LVEF < 40%), Group 4 (euthyroid, LVEF ≥40%).Results: Among patients with low LVEF (Groups 1 and 3), mortality was higher in patients undergoing thyroidectomy after restoration of euthyroidism (Group 3) than in those submitted to surgery when still thyrotoxic (Group 1): peritreatment mortality rates were 40% versus 0%, respectively (P = .048), whereas 5-year cardiovascular mortality rates were 53.3% versus 12.3%, respectively (P = .081). Exposure to thyrotoxicosis was longer in Group 3 than in Group 1 (112 days, interquartile range [IQR] 82.5-140, vs 76 days, IQR 24.8-88.5, P = .021). Survival did not differ in patients with LVEF ≥40% submitted to thyroidectomy irrespective of being thyrotoxic (Group 2) or euthyroid (Group 4): in this setting, peritreatment mortality rates were 6.3% versus 4% (P = .741) and 5-year cardiovascular mortality rates were 12.5% and 20% (P = .685), respectively. Age (hazard ratio [HR] 1.104, P = .029) and duration of exposure to thyrotoxicosis (HR 1.004, P = .039), but not presurgical serum thyroid hormone concentrations (P = .577 for free thyroxine, P = .217 for free triiodothyronine), were independent predictors of death.Conclusions: A prolonged exposure to thyrotoxicosis resulted in increased mortality in patients with reduced LVEF, which may be reduced by early thyroidectomy. [ABSTRACT FROM AUTHOR]

Introduction: Autoimmune hypophysitis (AH) has a variable clinical presentation and natural history; likewise, its response to glucocorticoid therapy is often unpredictable. Objective: To identify clinical and radiological findings associated with response to glucocorticoids. Design and methods: 12 consecutive patients with AH, evaluated from 2008 to 2016. AH was the exclusion diagnosis after ruling out other pituitary masses and secondary causes of hypophysitis. Mean follow-up time was 30 ± 27 months (range 12-96 months). Results: MRI identified two main patterns of presentation: global enlargement of the pituitary gland or panhypophysitis (n = 4, PH) and pituitary stalk abnormality only, or infundibulo-neuro-hypophysitis (n = 8, INH). Multiple tropin defects were more common in PH (100%) than those in INH (28% P = 0.014), whereas diabetes insipidus was more common in INH (100%) than that in PH (50%; P = 0.028). All 4 PH and 4 out of 8 INH were treated with glucocorticoids. Pituitary volume significantly reduced in all PH patients (P = 0.012), defective anterior pituitary function recovered only in the two patients without diabetes insipidus (50%) and panhypopituitarism persisted, along with diabetes insipidus, in the remaining 2 (50%). In all INH patients, either treated or untreated, pituitary stalk diameter reduced (P = 0.008) but diabetes insipidus persisted in all. Conclusions: Glucocorticoid therapy may improve anterior pituitary function in a subset of patients but has no effect on restoring posterior pituitary function. Diabetes insipidus appears as a negative prognostic factor for response to glucocorticoids. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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: The different pathogenic mechanisms of the twoforms of AITaccount for different onset times of thyrotoxicosis in 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. [ABSTRACT FROM AUTHOR]

Objective: Acromegalic patients have an increased risk of mortality. The objective of this study was to compare the effect of different therapies for acromegaly on mortality. Design and methods: The mortality rate of 438 consecutive acromegalic patients was compared with that of the general population using the standardized mortality ratio (SMR); the effect of different therapies on survival was evaluated using Cox regression analysis. Results: Twenty patients (4.5%) died between 1999 and 2009. Age- and sex-adjusted SMR was 0.70 (95% CI 0.43-1.08). The Cox regression analysis revealed that, in the whole population, both general risk factors (age and physical status) and specific factors for acromegaly (macroadenoma, hypopituitarism and uncontrolled disease) were associated with death. The most compromised patients at diagnosis had a higher mortality rate (P=0.001), which also occurred in patients with controlled acromegaly. Death occurred in 2.4% (adenomectomy), 2.6% (adenomectomy followed by somatostatin analogue (SSA) therapy) and 11.4% (SSA therapy as the primary therapy) of the patients. The risk of death was higher in patients receiving SSA therapy as the primary therapy (hazard ratio (HR) 5.52, 95% CI 1.06-28.77, P=0.043) than in all patients submitted to adenomectomy; however, a higher risk of death occurred only in diabetic patients treated with SSAs alone (HR 21.94, 95% CI 1.56-309.04, P=0.022). Radiotherapy was associated with an increased risk of mortality, which occurred in patients with the more locally advanced disease. Conclusions: Therapies for acromegaly and comorbidities have lowered the risk of mortality to the level of the general population; the effect of SSA therapy alone or that following pituitary adenomectomy was comparable to that of curative neurosurgery on survival in non-diabetic patients; on the contrary, SSA therapy as the primary therapy may be less effective than adenomectomy in reducing mortality rate in diabetic patients. [ABSTRACT FROM AUTHOR]

Objective: Several tests have been proposed to diagnose patients with Cushing's syndrome (CS). The aims of the study were: i) to evaluate the performance of salivary cortisol (SC) in hypercortisolism and ii) to compare SC with serum cortisol (SeC) and urinary cortisol. Design and patients: This was a diagnostic study. Twenty-seven patients with untreated Cushing's disease (CD untr), 21 women consuming oral contraceptive pill (OCP), 18 pregnant women, and 89 healthy subjects (controls) were enrolled. Methods: SC and SeC at baseline and after the low-dose dexamethasone suppression test (LDDST) and urinary free cortisol (UFC) were measured. Results: Midnight SC had a sensitivity of 100% in the CD untr group and a specificity of 97.7% in the controls. Specificity remained high (95.2%) in women taking OCP, while in pregnant women, it decreased to 83.3%. SC after the LDDST showed a sensitivity of 96.3% in the CD untr group; specificity was 97.7% in the controls and 90.5% in OCP women. Midnight SeC had a sensitivity of 100% in the CD untr group. SeC after the LDDST had a sensitivity of 100% in the CD untr group while specificity was 97.7% in the controls and 61.9% in women taking OCP. For UFC, sensitivity was 92.6% in the CD untr group while specificity was 97.7% in the controls and 100% in the OCP group. Conclusions: SC is a reliable parameter for the diagnosis of severe hypercortisolism, with high sensitivity and specificity. In women during pregnancy or taking OCP, the measurement of SC, identifying the free fraction, could be helpful to exclude CS [ABSTRACT FROM AUTHOR]