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Nodal metastases in the central compartment are frequent in papillary thyroid cancer (PTC). However, they are mostly micrometastases with no impact on survival and their relevance on the risk of locoregional relapse is controversial.

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.

Purpose: To evaluate whether the clinical, biochemical and radiological features of patients with primary aldosteronism (PA) can predict both main subtypes of PA. Methods: A retrospective multicenter study of PA patients followed in 27 Spanish tertiary hospitals (SPAIN-ALDO Register). Only patients with confirmed unilateral or bilateral PA based on adrenal venous sampling (AVS) and/or postsurgical biochemical cure after adrenalectomy were included. Supervised regression techniques were used for model development. Results: 328 patients [270 unilateral PA (UPA), 58 bilateral PA (BPA)] were included. The area under the curve (AUC) for aldosterone/potassium ratio and aldosterone responses following saline infusion test were 0.602 [95%CI 0.520 to 0.684] and 0.574 [95% CI 0.446–0.701], respectively, to differentiate UPA from BPA. The AUC was 0.825 [95% 0.764–0.886] when the prediction model with seven parameters – comorbidities (dyslipidemia, cerebrovascular disease, sleep apnea syndrome [SAS]), systolic blood pressure (SBP), plasma aldosterone levels (PAC), hypokalemia and unilateral adrenal nodule >1 cm and normal contralateral adrenal gland on CT/MRI – was used. In patients without comorbidities, hypokalemia, SBP > 160 mmHg, PAC > 40 ng/dL, and unilateral adrenal lesions were associated with a likelihood of having a UPA of 98.5%. The chance of BPA was higher in individuals with comorbidities, SBP < 140 mmHg, normokalemia, low PAC levels, and no adrenal tumors on the CT/MRI (91.5%). Conclusion: A combination of high PAC, SBP > 160 mmHg, low serum potassium, a unilateral adrenal nodule>1 cm and no comorbidities could predict a UPA with a 98.5% accuracy.

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).

To evaluate the indication and the resources for the screening/diagnosis of primary aldosteronism (PA) in Endocrinology units in Spain.

Purpose: To analyze the differences in the cardiometabolic profile in patients with nonfunctioning adrenal incidentalomas (NFAI) with post-dexamethasone suppression test (DST) cortisol ≤1.4 µg/dL (NFAI ≤ 1.4) and those with post-DST cortisol >1.4 µg/dL (NFAI > 1.4) and between NFAI with post-DST cortisol ≤0.9 µg/dL (NFAI ≤ 0.9) and those with levels >0.9 µg/dL (NFAI > 0.9). Methods: Multicenter retrospective observational study of patients with NFAIs. NFAI was defined as an adrenal incidentaloma with negative hormonal study (including metanephrines, post-DST cortisol ≤1.8 µg/dL and aldosterone/renin ratio when screening was indicated). Autonomous cortisol secretion (ACS) development was defined as an NFAIs in which post-DST serum cortisol >1.8 µg/dL were evidenced during hormonal follow-up evaluation. Results: A total of 593 NFAI were included. Based on the 1.4 µg/dL threshold in the DST, most of the NFAI were classified as NFAI ≤ 1.4 (74.5%). Patients in the NFAI > 1.4 group were older than those in the NFAI ≤ 1.4 group, but there was no difference in the cardiometabolic profile after adjusting for age. A total of 69.5% of the patients had DST > 0.9 µg/dl. They were older and had a higher prevalence of cardiovascular disease than NFAI ≤ 0.9, even after adjusting by age (adjusted OR = 2.23 [1.10–4.53]). Patients in the NFAI > 1.4 group developed ACS more commonly than the NFAI ≤ 1.4 group (23.5% vs. 7.44%, P< 0.001). However, when the threshold of 0.9 µg/dL was considered, no difference was found between NFAI ≤ 0.9 and NFAI > 0.9 (P= 0.126). Conclusion: The threshold of 1.4 µg/dL in the DST is useful to predict which patients with NFAI had a higher risk of ACS development during follow-up; and the threshold of 0.9 µg/dL to identify those patients with NFAI with a higher cardiovascular risk.

Video Abstract16VV1Marta Araujo-Castro

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.

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.

El hiperaldosteronismo primario (HAP) es la forma más frecuente de hipertensión arterial secundaria, y se asocia a un mayor riesgo cardiometabólico que el observado en pacientes con HTA esencial. Por tanto, es preceptivo mantener un alto índice de sospecha clínica para HAP. Si se confirma un cociente aldosterona/renina elevado se deben realizar pruebas de confirmación, habitualmente una prueba de sobrecarga salina intravenosa o de captopril, salvo en pacientes con HAP franco, con hipopotasemia espontánea, aldosterona plasmática > 20 ng/dL y renina suprimida, en los que no sería estrictamente necesario este paso para confirmar el diagnóstico de HAP. El último paso en el diagnóstico del HAP es el estudio de localización, siendo la tomografía axial computarizada (TC) de suprarrenales la prueba inicial de elección, y el cateterismo de venas adrenales (CVA), la prueba definitiva de localización en la mayor parte de los casos. En esta revisión se resumen los datos sobre el diagnóstico del HAP, desde el cribado al estudio de confirmación y de localización.

Purpose: The aim of this study was to evaluate the diagnostic accuracy of the 1 mg dexamethasone suppression test (DST) for the prediction of autonomous cortisol secretion (ACS)-related comorbidities in patients with adrenal incidentalomas (AIs). Methods: This was a retrospective multicenter study. We recruited patients with AI/s ≥ 1 cm, excluding those who, during the study, were found during the extension study of an extra-adrenal cancer, with a known diagnosis of hereditary syndromes characterized by adrenal tumors, those presenting with overt hormonal excess syndromes, and those in whom the DST results were missing. Results: A total of 823 patients met the inclusion criteria. Based on the 1.8, 3.0, and 5.0 µg/dl post-DST cortisol thresholds, the prevalence of ACS was 33.5%, 13.7%, and 5.6%, respectively. The prevalence of hypertension (OR = 1.8, 95% CI = 1.3–2.4), diabetes (OR = 1.6, 95% CI = 1.2–2.2), and dyslipidemia (OR = 1.4, 95% CI = 1.0–1.9) was higher with cortisol post-DST ≥ 1.8 µg/dl; the prevalence of hypertension (OR = 2.1, 95% CI = 1.4–3.3) and diabetes (OR = 1.7, 95% CI = 1.1–2.6) was higher with values ≥ 3.0 µg/dl; and the prevalence of hypertension (OR = 2.0, 95% CI = 1.0–3.7) was higher with levels ≥ 5.0 µg/dl. However, the diagnostic accuracy of the DST for the prediction of cardiometabolic comorbidities in patients with AIs was poor, with areas under the ROC curve < 0.61. Conclusions: The DST is a poor predictor of cardiometabolic comorbidities in patients with AIs regardless of the cortisol cut-off values applied. This finding suggests that the diagnosis of ACS should not be based solely on the results of the DST. Other clinical, metabolic, or imaging markers showing a better performance for the prediction of the development and progression of cardiometabolic comorbidities in AIs need to be identified.

Initial evaluation of adrenal incidentalomas (AIs) should be aimed at ruling out malignancy and functionality. For this, a detailed clinical history should be taken, and an adequate radiographic assessment and a complete blood chemistry and hormone study should be performed. The most controversial condition, because of the lack of consensus in its definition, is autonomous cortisol secretion (ACS). Our recommendation is that, except when cortisol levels <1.8 µg/dL in the dexamethasone suppression test (DST) rule out diagnosis and levels ≥5 µg/dL establish the presence of ACS, diagnosis should be based on a combined definition of DST ≥ 3 µg/dL and at least one of the following: elevated urinary free cortisol (UFC), ACTH level <10 pg/mL, or elevated nocturnal cortisol (in serum and/or saliva). During follow-up, DST should be repeated, usually every year, on an individual basis depending on the results of prior tests and the presence of comorbidities potentially related to hypercortisolism.

La evaluación inicial de los incidentalomas adrenales se centra en dos objetivos: descartar malignidad y descartar funcionalidad. Para ello se debe realizar una historia clínica detallada, obtener una valoración radiológica adecuada y un estudio bioquímico-hormonal completo. La entidad que más dudas genera, por la falta de consenso en su definición, es la secreción autónoma de cortisol. Nuestra recomendación es que, salvo para valores de cortisol <1,8μg/dl en el test de supresión con dexametasona que descartan secreción autónoma de cortisol, y ≥5μg/dl que establecen el diagnóstico; se debe emplear una definición combinada de test de supresión con dexametasona ≥3μg/dl y al menos uno de los siguientes: cortisol libre urinario elevado, ACTH <10 pg/ml o cortisol nocturno (sérico y/o salival) elevado para establecer el diagnóstico de secreción autónoma de cortisol. En el seguimiento se debe repetir el test de supresión con dexametasona, generalmente de forma anual, individualizando en función de los resultados de las pruebas previas y de la presencia de comorbilidades potencialmente relacionadas con el hipercortisolismo.

Objective: To study the differences in the cardiometabolic profile between patients with non-functioning adrenal incidentalomas (NFAI) and incidentalomas with autonomous cortisol secretion (ACS). Methods: A 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 (NFAIDST3or ACSDST3) and 1.8 µg/dl (ACSDST1.8and NFAIDST1.8). Results: The 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 (NFAIDST3vs ACSDST3) and 32.1% vs 40.6%, p= 0.56 (ACSDST1.8vs NFAIDST1.8), but the differences did not reach statistical significance. Maximum adenoma diameter (R-squared = 0.15, p&lt; 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 NFAIDST3developed ACSDST3, eight NFAIDST1.8developed ACSDST1.8, and one NFAIDST1.8progressed to ACSDST3. In both groups (NFAI and ACS) the metabolic profile remained stable. Conclusions: Our 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.

We aimed to compare the effectiveness of contrast‐enhanced ultrasound (CEUS), technetium Tc 99m methoxyisobutylisonitrile (99mTc‐MIBI) single‐photon emission computed tomographic (SPECT) scintigraphy, and high‐resolution ultrasound (US) in the detection of a pathologic parathyroid gland in patients with primary hyperparathyroidism (pHPT). Twenty‐nine consecutive patients with pHPT were prospectively enrolled and underwent preoperative imaging with 99mTc‐MIBI SPECT scintigraphy, high‐resolution US, and CEUS and subsequent parathyroidectomy. Contrast‐enhanced US examinations were performed by an experienced examiner who was blinded to the results of scintigraphy and high‐resolution US. The diagnostic performance of all of the imaging tests was analyzed in comparison with the pathologic anatomic findings. All investigations were performed at La Paz University Hospital. In the 29 patients (22 female and 7 male), a total of 31 parathyroid adenomas were detected: single lesions in 27 patients and a double lesion in 2 patients. Contrast‐enhanced US revealed sensitivity of 66.7% (95% confidence interval [CI], 46%–82.7%) for detection of single adenomas in comparison with 77.8 % (95% CI, 57.3%–90.6) for 99mTc‐MIBI SPECT scintigraphy and 51.8% (95% CI, 32.3%–70.8%) for high‐resolution US (P= .100). With CEUS, double adenomas could be detected in both cases (sensitivity, 100%); however, scintigraphy and high‐resolution US did not detect any cases of double adenomas. In addition, CEUS allowed the differentiation of lymphatic nodes from parathyroid glands in 2 patients. No side effects were observed for CEUS. In our study, CEUS facilitated the detection and diagnosis of double adenomas compared with high‐resolution US and 99mTc‐MIBI SPECT scintigraphy. Additionally, CEUS was useful in the differentiation between parathyroid adenomas and lymph nodes.

To compare the presentation and evolution of primary aldosteronism (PA) in the elderly (≥65 years) and young patients (<65 years).A retrospective multicenter study was performed in 20 Spanish hospitals of PA patients in follow-up between 2018 and 2021.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.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.

Valorar la indicación y los medios para cribado/diagnóstico del hiperaldosteronismo primario (HAP) en las unidades de Endocrinología de España.