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Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and is generally associated with an excellent prognosis. Historically, treatment strategies were uniform and frequently aggressive, including total thyroidectomy and routine radioiodine ablation, even in low-risk cases. Current Perspective: Over the past decade, the management of PTC has shifted toward a de-escalation paradigm. This transition is driven by high evidence showing that the majority of PTCs follow an indolent course, with low recurrence and mortality rates. As a result, there is increasing emphasis on tailoring the extent of surgery and adjuvant therapy to individual patient risk profiles. Active surveillance, hemithyroidectomy, and selective use of radioiodine now represent valid alternatives to traditional radical approaches, particularly for low-risk tumors. Clinical Implications: The goal of this evolution is to balance oncologic safety with quality of life, reducing overtreatment and minimizing long-term complications such as hypoparathyroidism or recurrent laryngeal nerve injury. Personalized treatment decisions are now guided by tumor biology, molecular markers, and refined risk stratification systems. Conclusions: This article will review the current evidence supporting this shift, highlight the challenges of implementation in clinical practice, and discuss future trends in the management of papillary thyroid carcinoma.

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension and is associated with a higher cardiometabolic risk than essential hypertension. The aim of this consensus is to provide practical clinical recommendations for its surgical and medical treatment, pathology study and biochemical and clinical follow-up, as well as for the approach in special situations like advanced age, pregnancy and chronic kidney disease, from a multidisciplinary perspective, in a nominal group consensus approach of experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology and Spanish Association of Surgeons (AEC). Keypoints The treatment of choice for PA is medical therapy with mineralocorticoid receptor blockade for bilateral cases and unilateral adrenalectomy for unilateral PA. The goals of PA treatment are to normalize blood pressure (BP) and excessive aldosterone production, with the final aim of improving associated comorbidities and reducing mortality. Spironolactone is usually the mineralocorticoid receptor antagonist (MRA) of choice for medical treatment of PA. However, eplerenone has a similar efficacy to that of spironolactone when used in doses 2–3 times higher than the latter and administered 2–3 times a day. Eplerenone has the advantage of not inducing the anti-androgenic side effects commonly seen with spironolactone. Adrenalectomy is the gold standard procedure used to remove the aldosterone-hypersecreting adrenal tissue. The Primary Aldosteronism Outcome (PASO) group criteria are recommended for defining the control objectives of biochemical and clinical response to treatment.

Background: Adrenal incidentalomas (AI) are frequent findings in clinical practice. About 40% of AIs are associated with hypercortisolism of variable severity. Although mild autonomous cortisol secretion (MACS) has been associated with the impaired clinical outcome of several diseases, its effect on the development of benign neoplasms is unknown. Aim: To compare the prevalence of adenomas (thyroid, parathyroid, pituitary and other locations) in patients with nonfunctioning AIs (NFAIs) and MACS. Methods: A multicenter, retrospective study of patients with AIs evaluated in four tertiary hospitals was performed. Results: A total of 923 patients were included. Most patients were male (53.6%), with a mean age at diagnosis of 62.4 ± 11.13 years; 21.7% presented with bilateral AIs. MACS was observed in 29.9% (n = 276) of patients, while 69.9% (n = 647) were NFAIs. Adenomas in locations other than the adrenal gland were observed in 36% of the studied population, with a similar distribution in patients with MACS and NFAIs (33% vs. 32%; p > 0.05). There were no statistically significant differences in the prevalence of pituitary, thyroid, parathyroid or other endocrine-related adenomas between both groups, but the prevalence of metabolic comorbidities and mortality was increased in patients with MACS, specifically in patients with thyroid and other endocrine-related adenomas (p < 0.05). Conclusions: Adenomas in locations other than the adrenal glands occur in one third of patients with AIs. Mild autonomous hypercortisolism does not affect the prevalence of other endocrine-related adenomas but is associated with increased metabolic comorbidities and mortality, especially in patients with thyroid adenomas and adenomas in other locations.

Background/Objectives: Mild autonomous cortisol secretion (MACS) can coexist with primary aldosteronism (PA). The purpose of our study was to evaluate whether (MACS) influences parameters analyzed during adrenal venous sampling (AVS) in patients with PA. Methods: Patients with PA from the SPAIN-ALDO Registry and the German Conn’s Registry with available 1 mg-dexamethasone suppression test (DST) and AVS were included. MACS was defined as a post-DST cortisol > 1.8 µg/dL in the absence of specific signs and symptoms of Cushing’s syndrome. Results: Two-hundred and twenty-five patients were included, 98 (43.6%) of whom had concomitant MACS. The mean age was 54 ± 10 years and 37.3% were women. AVS was performed by simultaneous catheterization of both adrenal veins and analysis of basal samples in 157 patients (69.8%), with both basal and post-ACTH samples in 15 patients (6.7%), and during continuous ACTH infusion in 53 patients (23.6%). AVS was considered technically unsuccessful in 40 cases (17.8%), suggesting unilateral secretion in 106 (47.1%) and bilateral secretion in 79 (35.1%). We did not find significant differences in the percentage of unilateral and bilateral results, cortisol, corrected aldosterone, or selectivity indices in the dominant and non-dominant veins, nor in the lateralization index or the contralateral suppression index between patients with and without MACS. They also had similar rates of surgical treatment and biochemical and clinical response. Conclusions: Although pathophysiological reasoning suggests that MACS could hinder AVS identification of unilateral forms of PA, our data suggest that such interference, if it exists, is of moderate clinical relevance.

Purpose To summarize the available data on the prevalence, clinical repercussion, and diagnosis of primary aldosteronism (PA) and to discuss the SPAIN-ALDO registry’s findings, which is the largest PA patient registry in Spain. Methods A comprehensive review of the literature focused on the prevalence, clinical presentation and diagnosis of PA was performed. Results PA is the most common cause of secondary arterial hypertension. In addition, PA patients have a higher cardio-metabolic risk than patients with essential arterial hypertension matched by age, sex, and blood pressure levels. However, despite its high prevalence and associated metabolic and cardiovascular complications, PA remains largely under-recognized, with less than 2% of people in at-risk populations ever tested. The diagnostic investigation is a multistep process, including screening, confirmatory testing, and subtype differentiation of unilateral from bilateral PA forms. Data from the SPAIN-ALDO registry have shed light on the cardiometabolic impact of PA and about the limitations in the PA diagnosis of these patients in Spain. Conclusions The most common cause of secondary hypertension is PA. One of the most challenging aspects of the diagnosis is the differentiation between unilateral and bilateral PA because adrenal venous sampling is a difficult procedure that should be performed in experienced centers. Data from the SPAIN-ALDO registry have provided important information on the nationwide management of this pathology.

It is estimated that about 5% of the primary aldosteronism (PA) cases are of hereditary origin (familial hyperaldosteronism, FH). To date, 4 forms of FH have been reported. However, in general little is known about the genetic causes that lead to the development of PA. This work aimed to determine the rate of genetic testing for FH in the SPAIN-ALDO Registry and to describe the clinical characteristics of patients with FH. In addition, a literature review of reports of FH cases was performed. A retrospective multicenter study of PA in patients followed in 35 Spanish tertiary hospitals (SPAIN-ALDO Registry). Twenty-five of the 855 patients (3%) with PA included in the registry underwent genetic testing for FH, with complete results available for only 24 patients. However, we found that there were 57 patients who met the criteria for performing a genetic study of PA. Only 8 out of these 57 patients were genetically tested (14.0%), while the reasons to perform a genetic study in the remaining 17 genetically studied cases were quite heterogeneous. A positive result for FH was found in only one case for FH type III (KCNJ5 pathogenic variant). A systematic review of the literature was performed and identified a total of 25 articles reporting 246 patients with FH type I, 12 articles reporting 72 patients with FH type II, 14 articles reporting 29 cases of FH type III, and 3 articles reporting 12 patients with FH type IV. The genetic study of FH is often scarce in real-world clinical practice, as 86% of patients with criteria to undergo genetic study were not evaluated in our cohort. Nevertheless, FH is an uncommon cause of PA, representing only 0.2% of cases in the SPAIN-ALDO Registry, although its prevalence may be as high as 4% among suspected cases.

ObjectiveTo study the differences in the cardiometabolic profile between patients with non-functioning adrenal incidentalomas (NFAI) and incidentalomas with autonomous cortisol secretion (ACS).MethodsA total of 149 patients with adrenal incidentalomas were retrospectively evaluated and followed-up for a mean time of 34.6 months at Departments of Endocrinology and Metabolic Diseases Units of four tertiary Spanish hospitals. Patients were grouped as NFAI or ACS adenomas based on two cutoffs in the dexamethasone suppression test (DST): 3.0 µg/dl (NFAIDST3 or ACSDST3) and 1.8 µg/dl (ACSDST1.8 and NFAIDST1.8).ResultsThe mean age of both groups was 62.0 (10.31) and was similar in ACS and NFAI. The prevalence of diabetes, high blood pressure, cardiovascular, and cerebrovascular disease was higher in ACS than in NFAI, but differences only reached statistical significance for cerebrovascular disease using the 3.0 µg/dl cutoff (15.8% vs 2.3%, p = 0.01) and for diabetes using the 1.8 µg/dl cutoff (38.0% vs 22.0%, p = 0.04). No differences were found in the prevalence of dyslipidemia. The prevalence of obesity was lower in patients with ACS than in NFAI 26.3% vs 39.2%, p = 0.18 (NFAIDST3 vs ACSDST3) and 32.1% vs 40.6%, p = 0.56 (ACSDST1.8 vs NFAIDST1.8), but the differences did not reach statistical significance. Maximum adenoma diameter (R-squared = 0.15, p < 0.001) and cerebrovascular disease (OR = 1.59, p = 0.04) were the only parameters that could be predicted by the DST. The DST was an inadequate predictor of clinical (systolic and diastolic blood pressure, body mass index), hormonal (DHEAS, ACTH, UFC, and basal serum cortisol), biochemical (glucose, cholesterol, LDL, HDL, and triglycerides), and other radiological (laterality, lipid content) parameters. Throughout the follow-up, patients did not develop overt Cushing’s Syndrome; three NFAIDST3 developed ACSDST3, eight NFAIDST1.8 developed ACSDST1.8, and one NFAIDST1.8 progressed to ACSDST3. In both groups (NFAI and ACS) the metabolic profile remained stable.ConclusionsOur data suggest higher prevalence of diabetes and cerebrovascular disease in ACS patients compared with NFAI. However, probably because of the small sample size, the differences only reached statistical significance using the cutoffs of 1.8 µg/dl for diabetes and 3.0 µg/dl for cerebrovascular disease. Patients with ACS and NFAI rarely progress to more aggressive forms of hypercortisolism, and the metabolic profile usually remains stable during the follow-up.

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension (HT), and is associated with a higher cardiometabolic risk than essential HT. However, PA remains underdiagnosed, probably due to several difficulties clinicians usually find in performing its diagnosis and subtype classification. The aim of this consensus is to provide practical recommendations focused on the prevalence and the diagnosis of PA and the clinical implications of aldosterone excess, from a multidisciplinary perspective, in a nominal group consensus approach by experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology, Spanish Association of Surgeons (AEC). Highlights Following a positive screening test, no further studies are needed for diagnosis of PA if a plasma aldosterone concentration (PAC) > 20 ng/dL and a low circulating direct renin or plasma renin activity (PRA) are detected in a patient with spontaneous hypokalemia. In all other patients, one (or more) of four different tests is (are) currently recommended: the fludrocortisone suppression test, the oral salt loading test, the intravenous saline test, and/or the captopril challenge test. In all cases, hypokalemia must be corrected prior to testing. Interfering medication must be progressively withdrawn before testing, while introducing alpha-1 adrenergic blockers, long-acting non-dihydropyridine calcium antagonists, and/or hydralazine as needed for control of hypertension. All but the captopril challenge test run the risk of inducing hypokalemia, fluid overload, and a worsening of hypertension. In the case of borderline results, the initial test employed can be repeated, or a second test performed. Patients with both a negative saline infusion and captopril challenge test appear to be at a low risk for harboring unilateral disease, whereas those positive for both are more likely to exhibit unilateral aldosterone secretion than when tests render conflicting results. Patients showing a positive screening aldosterone to renin ratio (ARR) with normal/high PAC and a low renin/PRA, yet with negative diagnostic testing, presenting mild hyperaldosteronism, can benefit from targeted therapy of hypertension with mineralocorticoid receptor antagonists.

ObjectiveTo analyze the evolution of the cardiometabolic profile of patients with primary hyperaldosteronism (PA) after the treatment with surgery and with mineralocorticoid receptor antagonists (MRA).DesignRetrospective multicentric study of patients with PA on follow-up in twelve Spanish centers between 2018 and 2020.Results268 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).ConclusionIn 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.

Purpose: To assess the risk of developing autonomous cortisol secretion (ACS) and tumour growth in non-functioning adrenal incidentalomas (NFAIs). Methods: Multicentre retrospective observational study of patients with NFAIs. ACS was defined as serum cortisol >1.8 µg/dL after 1 mg-dexamethasone suppression test (DST) without specific data on Cushing’s syndrome. Tumour growth was defined as an increase in maximum tumour diameter >20% from baseline; and of at least 5 mm. Results: Of 654 subjects with NFAIs included in the study, both tumour diameter and DST were re-evaluated during a follow-up longer than 12 months in 305 patients. After a median follow-up of 41.3 (IQR 24.7–63.1) months, 10.5% of NFAIs developed ACS. The risk for developing ACS was higher in patients with higher serum cortisol post-DST levels (HR 6.45 for each µg/dL, p = 0.001) at diagnosis. Significant tumour growth was observed in 5.2% of cases. The risk of tumour growth was higher in females (HR 10.7, p = 0.004). Conclusions: The frequency of re-evaluation with DST in NFAIs during the initial 5 years from diagnosis can probably be tailored to the serum cortisol post-DST level at presentation. Re-evaluation of NFAIs with imaging studies, on the other hand, seems unnecessary in most cases, particularly if the initial imaging demonstrates features specific to typical adenoma, given the low rate of significant tumour growth.