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.

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.

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.

Predictive model of pheochromocytoma based on the imaging features of the adrenal tumours.

The purpose of our study was to develop a predictive model to rule out pheochromocytoma among adrenal tumours, based on unenhanced computed tomography (CT) and/or magnetic resonance imaging (MRI) features. We performed a retrospective multicentre study of 1131 patients presenting with adrenal lesions including 163 subjects with histological confirmation of pheochromocytoma (PHEO), and 968 patients showing no clinical suspicion of pheochromocytoma in whom plasma and/or urinary metanephrines and/or catecholamines were within reference ranges (non-PHEO). We found that tumour size was significantly larger in PHEO than non-PHEO lesions (44.3 ± 33.2 versus 20.6 ± 9.2 mm respectively; P < 0.001). Mean unenhanced CT attenuation was higher in PHEO (52.4 ± 43.1 versus 4.7 ± 17.9HU; P < 0.001). High lipid content in CT was more frequent among non-PHEO (83.6% versus 3.8% respectively; P < 0.001); and this feature alone had 83.6% sensitivity and 96.2% specificity to rule out pheochromocytoma with an area under the receiver operating characteristics curve (AUC-ROC) of 0.899. The combination of high lipid content and tumour size improved the diagnostic accuracy (AUC-ROC 0.961, sensitivity 88.1% and specificity 92.3%). The probability of having a pheochromocytoma was 0.1% for adrenal lesions smaller than 20 mm showing high lipid content in CT. Ninety percent of non-PHEO presented loss of signal in the "out of phase" MRI sequence compared to 39.0% of PHEO (P < 0.001), but the specificity of this feature for the diagnosis of non-PHEO lesions low. In conclusion, our study suggests that sparing biochemical screening for pheochromocytoma might be reasonable in patients with adrenal lesions smaller than 20 mm showing high lipid content in the CT scan, if there are no typical signs and symptoms of pheochromocytoma.

[Thyroid dysfunction in patients with advanced renal cell carcinoma treated with sunitinib: a multifactorial issue]. / Disfunción tiroidea en los pacientes con carcinoma de células renales avanzado en tratamiento con sunitinib: un problema multifactorial.

OBJECTIVE: Several studies have reported the substantial prevalence of sunitinib-induced thyroid dysfunction. However, the underlying mechanism and the benefit of thyroid hormone replacement therapy remain to be determined. To evaluate the effect of sunitinib on thyroid function, we carried out a descriptive study in patients with advanced renal cell carcinoma. PATIENTS AND METHODS: A total of 24 patients treated by sunitinib between 2006 and 2008 at Hospital Clínico San Carlos were included. The data were collected retrospectively and analyzed with SPSS 15.0. RESULTS: Treatment duration was 30 weeks (18-42) [median (IQR)]. Five patients (20.8%) developed subclinical hypothyroidism and three (12.5%) developed overt hypothyroidism. The number of weeks needed to observe an increase in thyroid-stimulating hormone (TSH) values in these patients was 15 (6-20) [median (IQR)]. TSH levels were below the normal range in five patients (20.8%) before or during the treatment period, but the diagnosis of subclinical hyperthyroidism could not be established because of concomitant factors. Fourteen patients (58.3%) showed sunitinib adverse events, but these were not related to the development of hypothyroidism (p=0.388). CONCLUSIONS: Because of the high prevalence of sunitinib-induced hypothyroidism, thyroid function should be systematically monitored in patients with renal cell carcinoma treated with this drug. However, several pathophysiological and pharmacological factors may interfere with monitoring. Consequently, it might be useful to determine not only TSH and free T4 but also free T3 and, ideally, reverse T3. Evidence-based recommendations to manage hypothyroidism in oncology patients are not available at present.

Hormonal effects in infants conceived by assisted reproductive technology.

OBJECTIVE: The purpose of this report is to describe 7 infants conceived by assisted reproductive technology (ART) who presented with breast development and/or pubic hair. The clinical presentation in these infants raises awareness that an altered intrauterine hormonal milieu may impact the fetal and infant stages of children conceived by ART. METHODS: Between May 2001 and April 2004, 7 children between the ages of 5 and 21 months conceived by ART were referred by their pediatricians to the Division of Pediatric Endocrinology at the New York University School of Medicine for evaluation of possible precocious puberty. Patients were evaluated for the possibility of centrally mediated precocious puberty and pseudoprecocious puberty, with a possible ovarian or adrenal origin. RESULTS: Endocrine evaluation in all patients indicated sex-steroid and hormone levels in the prepubertal range; pelvic sonography confirmed prepubertal ovaries with unstimulated uteri. Clinical follow-up of our patients thus far has not revealed progression of breast development, pubarche, or elevation in sex steroids. CONCLUSIONS: It is well established that the developing endocrine system in the fetus and maturation of endocrine-control systems are influenced by hormone concentrations in the fetus. Whether ART alters the intrauterine hormonal milieu for the growing fetus conceived by ART is as yet unknown and is an area of ongoing investigation. Patients conceived through ART, including our patients who presented with hormonal manifestations, will need to be monitored throughout childhood and into adolescence and adulthood to determine if any perturbation exists on the timing of puberty and later fertility.