Thymic Hyperplasia and Graves Disease: A Nonincidental Association.

We present 2 cases referred for evaluation of Graves disease (GD) associated with an incidental mediastinal mass. Chest computed tomography (CT) scans showed a 1.2 × 2.4 × 4.3 cm and a 5.7 × 2.6 × 7 cm thymic enlargement, respectively, consistent with thymic hyperplasia (TH) in the 2 patients. Patient 1 had been assessed by thoracic surgery for the mediastinal mass, and thymectomy had been performed to exclude thymoma, with an anatomopathological diagnosis consistent with thymic hyperplasia. Patient 2 was treated with methimazole. CT scan was repeated after he maintained a euthyroid state, which revealed total regression of the mass. There is a well-documented association between these 2 entities, but it is often underdiagnosed and unrecognized in routine clinal practice. The benign evolution, as evidenced by regression of thymic hyperplasia after resolution of the hyperthyroidism, is characteristic. These cases highlight the importance of recognizing the association of GD and TH and warrant a conservative approach, preventing unnecessary thymic evaluation and surgery.

Effect of Obesity on Clinical Characteristics of Primary Aldosteronism Patients at Diagnosis and Postsurgical Response.

CONTEXT: Patients with obesity have an overactivated renin-angiotensin-aldosterone system (RAAS) that is associated with essential hypertension. However, the influence of obesity in primary aldosteronism (PA) is unknown. OBJECTIVE: We analyzed the effect of obesity on the characteristics of PA, and the association between obesity and RAAS components. METHODS: A retrospective study was conducted of the Spanish PA Registry (SPAIN-ALDO Registry), which included patients with PA seen at 20 tertiary centers between 2018 and 2022. Differences between patients with and without obesity were analyzed. RESULTS: A total of 415 patients were included; 189 (45.5%) with obesity. Median age was 55 years (range, 47.3-65.2 years) and 240 (58.4%) were male. Compared to those without obesity, patients with obesity had higher rates of diabetes mellitus, chronic kidney disease, obstructive apnea syndrome, left ventricular hypertrophy, prior cardiovascular events, higher means of systolic blood pressure, and required more antihypertensive drugs. Patients with PA and obesity also had higher values of serum glucose, glycated hemoglobin A1c, creatinine, uric acid, and triglycerides, and lower levels of high-density lipoprotein cholesterol. Levels of blood aldosterone (PAC) and renin were similar between patients with and without obesity. Body mass index was not correlated with PAC nor renin. The rates of adrenal lesions on imaging studies, as well as the rates of unilateral disease assessed by adrenal vein sampling or I-6ß-iodomethyl-19-norcholesterol scintigraphy, were similar between groups. CONCLUSION: Obesity in PA patients involves a worse cardiometabolic profile, and need for more antihypertensive drugs but similar PAC and renin levels, and rates of adrenal lesions and lateral disease than patients without obesity. However, obesity implicates a lower rate of hypertension cure after adrenalectomy.

Autonomous cortisol secretion in patients with primary aldosteronism: prevalence and implications on cardiometabolic profile and on surgical outcomes.

Purpose: The aim of this study was to evaluate the prevalence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) and its implications on cardiometabolic and surgical outcomes. Methods: This is a retrospective multicenter study of PA patients who underwent 1 mg dexamethasone-suppression test (DST) during diagnostic workup in 21 Spanish tertiary hospitals. ACS was defined as a cortisol post-DST >1.8 µg/dL (confirmed ACS if >5 µg/dL and possible ACS if 1.8-5 µg/dL) in the absence of specific clinical features of hypercortisolism. The cardiometabolic profile was compared with a control group with ACS without PA (ACS group) matched for age and DST levels. Results: The prevalence of ACS in the global cohort of patients with PA (n = 176) was 29% (ACS-PA; n = 51). Ten patients had confirmed ACS and 41 possible ACS. The cardiometabolic profile of ACS-PA and PA-only patients was similar, except for older age and larger tumor size of the adrenal lesion in the ACS-PA group. When comparing the ACS-PA group (n = 51) and the ACS group (n = 78), the prevalence of hypertension (OR 7.7 (2.64-22.32)) and cardiovascular events (OR 5.0 (2.29-11.07)) was higher in ACS-PA patients than in ACS patients. The coexistence of ACS in patients with PA did not affect the surgical outcomes, the proportion of biochemical cure and clinical cure being similar between ACS-PA and PA-only groups. Conclusion: Co-secretion of cortisol and aldosterone affects almost one-third of patients with PA. Its occurrence is more frequent in patients with larger tumors and advanced age. However, the cardiometabolic and surgical outcomes of patients with ACS-PA and PA-only are similar.

Predictive model of hypertension resolution after adrenalectomy in primary aldosteronism: the SPAIN-ALDO score.

PURPOSE: To develop a predictive model of hypertension resolution after adrenalectomy in patients with primary aldosteronism (PA), based on their presurgical characteristics. METHODS: A retrospective multicenter study of PA patients in follow-up in 20 Spanish tertiary hospitals between 2018 and 2021 was performed (SPAIN-ALDO Register). Clinical response postadrenalectomy was classified according to the primary aldosteronism surgical outcome (PASO) consensus criteria. The predictive model was developed using a multivariate logistic regression model with the estimation of all possible equations. RESULTS: A total of 146 patients (54.8% females; mean age of 51.5 ± 10.9 years) with PA who underwent unilateral adrenalectomy were included. After a mean follow-up of 29.1 ±â€Š30.43 months after surgery, hypertension cure was obtained in 37.7% ( n  = 55) of the patients. The predictive model with the highest diagnostic accuracy to predict hypertension cure combined the variables female sex, use of two or fewer antihypertensive medications, hypertension grade 1, without type 2 diabetes and nonobesity. The area under the receiver operating characteristic curve of this model was 0.841 [0.769-0.914]. Based on this model, the group of patients with a higher probability of cure (80.4%) were those without type 2 diabetes, BMI <30 kg/m 2 , female sex, hypertension grade 1 and who use two or fewer antihypertensives. Our predictive model offered a slightly higher diagnostic accuracy than Wachtel's (area under the curve [AUC]: 0.809), Utsumi's (AUC: 0.804) and Zarnegar's (AUC: 0.796) models and was similar than the Burello's (AUC: 0.833) model. CONCLUSION: Female sex, use of two or fewer antihypertensive medications, hypertension grade 1, no type 2 diabetes and nonobesity may predict hypertension cure after adrenalectomy in patients with PA. Our score provides a potential tool to guide preoperative patient counseling.

Adrenal venous sampling in primary aldosteronism: Experience of a Spanish multicentric study (Results from the SPAIN-ALDO Register).

OBJECTIVE: The aim of this study was to evaluate the rate of adrenal venous sampling (AVS) performance in patients with primary aldosteronism (PA), the main reasons for its non-performance, and the success and complications rate of this procedure in Spain. Moreover, the concordance between CT/MRI and AVS for PA subtyping was evaluated. METHODS: A retrospective multicenter study of PA patient follow-up in 20 Spanish tertiary hospitals between 2018-2021 was performed (SPAIN-ALDO Register). RESULTS: Of the 440 patients with PA included in the study, 153 underwent AVS (34.8%). The main reasons for not performing AVS were: patient rejection to the procedure, low catheterization rate in the center and unilateral disease based on CT/MRI. The overall success rate was 44.4% (the left adrenal vein was properly canulated in 77.8% and the right adrenal vein in 48.4%). Only 3 patients experienced minor complications. In the 45 patients with unilateral disease according to AVS, CT/MRI indicated bilateral disease or normal adrenal glands in 17. In the 23 patients with bilateral disease, CT/MRI indicated unilateral disease in 14. However, no significant differences were observed in biochemical response (P = 0.051) and hypertension resolution (P = 0.150) between patients who underwent surgery based on CT/MRI results and those who underwent surgery based on AVS results. CONCLUSION: In our setting, AVS is still an underused technique in patients with PA. The low experience and success rate in AVS partially justify these results. More training for providers and patients needs to be done to include appropriate well performed AVS in the diagnosis algorithm of PA.

Differences in the presentation and evolution of primary aldosteronism in elderly (≥65 years) and young patients (<65 years).

Objective: To compare the presentation and evolution of primary aldosteronism (PA) in the elderly (≥65 years) and young patients (<65 years). Methods: A retrospective multicenter study was performed in 20 Spanish hospitals of PA patients in follow-up between 2018 and 2021. Results: Three hundred fifty-two patients with PA <65 years and 88 patients ≥65 years were included. Older PA patients had a two-fold higher prevalence of type 2 diabetes, dyslipidemia, and cerebrovascular disease, but these differences disappeared after adjusting for hypertension duration. At diagnosis, diastolic blood pressure was lower than in young patients (83.3 ± 11.54 vs 91.6 ± 14.46 mmHg, P < 0.0001). No differences in the rate of overall correct cannulation (56.5% vs 42.3%, P = 0.206) or the diagnosis of unilaterality (76.9% vs 62.5%, P = 0.325) in the adrenal venous sampling (AVS) was observed between the elderly and young groups. However, there was a lower proportion of PA patients who underwent adrenalectomy in the elderly group than in the younger group (22.7% (n = 20) vs 37.5% (n = 132), P = 0.009). Nevertheless, no differences in the rate of postsurgical biochemical (100% (n = 14) vs 92.8% (n = 90), P = 0.299) and hypertension cure (38.6% (n = 51) vs 25.0% (n = 5), P = 0.239) were observed between both groups. Conclusion: Older patients with PA have a worse cardiometabolic profile than young patients with PA that it is related to a longer duration of hypertension. However, the results of the AVS, and adrenalectomy are similar in both groups. Therefore, the management of elderly patients with PA should be based not only on age, but rather on the overall medical, physical, social, and mental characteristics of the patients.

Evolution of the cardiometabolic profile of primary hyperaldosteronism patients treated with adrenalectomy and with mineralocorticoid receptor antagonists: results from the SPAIN-ALDO Registry.

OBJECTIVE: To analyze the evolution of the cardiometabolic profile of patients with primary hyperaldosteronism (PA) after the treatment with surgery and with mineralocorticoid receptor antagonists (MRA). DESIGN: Retrospective multicentric study of patients with PA on follow-up in twelve Spanish centers between 2018 and 2020. RESULTS: 268 patients with PA treated by surgery (n = 100) or with MRA (n = 168) were included. At baseline, patients treated with surgery were more commonly women (54.6% vs 41.7%, P = 0.042), had a higher prevalence of hypokalemia (72.2% vs 58%, P = 0.022) and lower prevalence of obesity (37.4% vs 51.3%, P = 0.034) than patients treated with MRA. Adrenalectomy resulted in complete biochemical cure in 94.0% and clinical response in 83.0% (complete response in 41.0% and partial response in 42.0%). After a median follow-up of 23.6 (IQR 9.7-53.8) months, the reduction in blood pressure (BP) after treatment was similar between the group of surgery and MRA, but patients surgically treated reduced the number of antihypertensive pills for BP control more than those medically treated (∆antihypertensives: -1.3 ± 1.3 vs 0.0 ± 1.4, P < 0.0001) and experienced a higher increased in serum potassium levels (∆serum potassium: 0.9 ± 0.7 vs 0.6 ± 0.8mEq/ml, P = 0.003). However, no differences in the risk of the onset of new renal and cardiometabolic comorbidities was observed between the group of surgery and MRA (HR = 0.9 [0.5-1.5], P = 0.659). CONCLUSION: In patients with PA, MRA and surgery offer a similar short-term cardiovascular protection, but surgery improves biochemical control and reduces pill burden more commonly than MRA, and lead to hypertension cure or improvement in up to 83% of the patients.

Alpelisib-Induced Diabetes Mellitus: Case Report, Pharmacodynamics and Management Considerations.

Introduction: Alpelisib is an orally selective PI3K alpha inhibitor recently available for the treatment of advanced breast cancer. PI3K pathway is an intracellular signaling pathway that plays an important role in regulating glucose metabolism. Hyperglycemia is the most common adverse event associated. Methods: We describe the case of a severe hyperglycemia associated with alpelisib treatment in a patient with metastatic breast cancer and previously near-normal glycemia. We analyze the clinical presentation, PI3K inhibitor pharmacodynamic aspects, its influence in glycemic control and the required treatment approach. Results: An important impairment of glycemic control was observed after initiation of alpelisib. In addition to insulin sensitizers drugs, intensive insulin regimen was necessary. Flash glucose monitoring (FGM) information has been helpful in understanding the pharmacodynamic aspects of alpelisib and insulin titration. Development of hyperglycemia is fast, already observed 24 hours after initiation of therapy. FGM shows severe and persistent hyperglycemia during most of the day, with a significant downward effect in the 4 hours after each daily intake, which evidences the strong but transitory effect of the drug enzyme blockade. C-peptide level is remarkable in accordance with drug pharmacodynamics, consistent with a significant insulin resistance. Conclusions: Glucose monitoring should always be performed in patients treated with alpelisib, especially in patients with diabetes and prediabetes. It is crucial to anticipate in these patients. Any delay can lead to a worsening in metabolic control resulting in the discontinuation or reduction of alpelisib, which would lead to a decrease in its effectiveness, and consequently would deny patients an effective treatment with an impact on survival.