Isolated hypoaldosteronism is a cause of hypovolemic but not euvolemic hyponatremia.

Introduction: Hypoaldosteronism is characterized by hyperkalemia, and/or hypovolemic hyponatremia (HH), often accompanied by metabolic acidosis. HH is typical of hypoaldosteronism, whereas euvolemic hyponatremia (EH) is not. The purpose of the current study is to describe the characteristics of hyponatremia in hypoaldosteronism and elucidate whether EH can be considered part of the disease's spectrum. Methods: In a hypoaldosteronism cohort, we analyzed the factors associated with hyponatremia, comparing the characteristics of EH and HH and their associated factors. Correlation analyses of mineralocorticoid biomarkers, such as the transtubular potassium gradient (TTKG), the urinary Na+/K+ ratio (UNa+/UK+) with serum, and urinary electrolytes were performed in both types of hyponatremia. Results: Of 112 hypoaldosteronism episodes, 77.7% were ≥65 years old, 44.6% were women, and 80 (71.4%) had hyponatremia. Hyponatremia was negatively associated with the presence of chronic kidney disease, and positively with a hypovolemic state, malnutrition, a prior history of hyponatremia, and glucocorticoid therapy. HH: 61/80 and EH: 19/80 episodes. HH was associated with an age ≥65 years and the use of diuretics, as well as factors related to an aldosterone deficit and/or mineralocorticoid resistance. In HH but not in EH, urinary potassium was correlated with the TTKG, and urinary sodium with both the TTKG and the UNa+/UK+. Conclusion: Both HH and EH can be observed in hypoaldosteronism. However, only the former would be related to insufficient mineralocorticoid activity. Significance statement: Isolated hypoaldosteronism is a poorly understood and underdiagnosed endocrinological disorder, classically recognized only when hyperkalemia is present. The development of hypovolemic hyponatremia, however, is also easily explained by the physiopathology of the disorder. The current study addresses the features of hyponatremia when found in the context of mineralocorticoid insufficiency, and confirms an association between hypovolemic hyponatremia and isolated hypoaldosteronism. Thus, the clinical spectrum of hypoaldosteronism is extended to include hypovolemic hyponatremia as a frequent manifestation of the disorder.

Clinical manifestations and associated factors in acquired hypoaldosteronism in endocrinological practice.

Introduction: Hypoaldosteronism can be congenital or acquired, isolated or part of primary adrenal insufficiency, and caused by an aldosterone deficit, resistance, or a combination of both. Reduced mineralocorticoid action can induce a decrease in urine K+ and H+ excretion and an increase in urine Na+ excretion, leading to hyperkalemia, and/or hyponatremia, often combined with metabolic acidosis. We aimed to characterize the clinical manifestations of hypoaldosteronism, and their associated factors. Methods: Retrospective analysis of 112 episodes of hypoaldosteronism diagnosed in 86 adult patients from 2012-2019 by the Endocrinology and Nutrition Department of a tertiary hospital. The frequency of hyperkalemia, hypovolemic hyponatremia (HH) and metabolic acidosis (MA), and their associated factors were evaluated. Results: Patients had a median age of 77 [65 - 84], 55.4% were male. 94.6% cases showed hyperkalemia, 54.5% HH, and 60.3% MA. The mean serum K+ of all cases was 5.4 ± 0.5 mmol/L, Na+: 132.1 ± 6.3 mmol/L, HCO3: 22.6 ± 3.3 mmol/L. Hypoaldosteronism was isolated in the majority of cases: only 6/112 (5%) had primary adrenal insufficiency. Hypovolemia was associated with hyponatremia and a more florid clinical presentation. HH was associated with a combined presence of aldosterone-lowering and mineralocorticoid resistance factors. MA was associated with the presence of mineralocorticoid resistance factors. Conclusions: Hypoaldosteronism in adult endocrinological clinical practice is primarily isolated, and acquired. It predisposes not only to the development of hyperkalemia and MA, but also to that of HH. Hypoaldosteronism must be considered in the differential diagnosis of HH with urinary sodium wasting.

ACROSTART: A retrospective study of the time to achieve hormonal control with lanreotide Autogel treatment in Spanish patients with acromegaly.

OBJECTIVES: The ACROSTART study was intended to determine the time to achieve normalization of GH and IGF-I levels in responding patients with acromegaly administered different dosage regimens of lanreotide Autogel (Somatuline® Autogel®). METHODS: From March 2013 to October 2013, clinical data from 57 patients from 17 Spanish hospitals with active acromegaly treated with lanreotide for ≥4 months who achieved hormonal control (GH levels <2.5ng/ml and/or normalized IGF-I levels in ≥2 measurements) were analyzed. The primary objective was to determine the time from start of lanreotide treatment to hormonal normalization. RESULTS: Median patient age was 64 years, 21 patients were male, 39 patients had undergone surgery, and 14 patients had received radiotherapy. Median hormonal values at start of lanreotide treatment were: GH, 2.6ng/ml; IGF-I, 1.6×ULN. The most common starting dose of lanreotide was 120mg (29 patients). The main initial regimens were 60mg/4 weeks (n=13), 90mg/4 weeks (n=6), 120mg/4 weeks (n=13), 120mg/6 weeks (n=6), and 120mg/8 weeks (n=9). An initial treatment regimen with a long interval (≥6 weeks) was administered in 25 patients. Mean duration of lanreotide treatment was 68 months (7-205). Median time to achieve hormonal control was 4.9 months. Injections were managed without healthcare assistance in 13 patients. Median number of visits to endocrinologists until hormonal control was achieved was 3. Fifty-one patients were "satisfied"/"very satisfied" with treatment and 49 patients did not miss any dose. CONCLUSIONS: Real-life treatment with lanreotide Autogel resulted in early hormonal control in responding patients, with high treatment adherence and satisfaction despite disparity in starting doses and dosing intervals.

[Gastroenteropancreatic neuroendocrine tumors: clinical characteristics, diagnosis and prognosis at Hospital Universitario Clínico San Carlos (Madrid)]. / Tumores neuroendocrinos gastroenteropancreáticos: características clínicas, proceso diagnóstico y pronóstico en el Hospital Universitario Clínico San Carlos (Madrid).

INTRODUCTION: Neuroendocrine tumors are a group of neoplasms arising from the neural crest and endoderm and very heterogeneous as regards localization, clinical behavior, aggressiveness, and prognosis. Pancreas and gastrointestinal tract are the most common sites where neuroendocrine tumors can be found. MATERIAL AND METHODS: A review was made of all cases of neuroendocrine tumors diagnosed at Hospital Universitario Clínico San Carlos (HUCSC) from January 2007 to May 2012. Data were compared to the results provided by the Registry of the Spanish Group on Neuroendocrine Tumors (RGETNE). RESULTS: The study cohort comprised 78 patients. Gastroenteric nonfunctional tumors were the most common neoplasms. Metastases were found at diagnosis in50.6% of patients, with nodal involvement being most prevalent. Tumors located in the rectum were associated to the highestrate of metastasis. Overall 2-year survival rate was 74.8% and was related to sex, Ki-67 expression, and presence of metastasis.

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

Objetivo Distintos estudios ya han señalado la prevalencia importante de disfunción tiroidea inducida por sunitinib. No obstante, se desconoce el mecanismo de acción subyacente y el beneficio del tratamiento sustitutivo. Con el objeto de evaluar la función tiroidea en los pacientes con carcinoma de células renales avanzado tratados con sunitinib, se realizó el estudio descriptivo presentado. Material y métodos Se incluyeron 24 pacientes tratados entre 2006 y 2008 en el Hospital Clínico San Carlos. Los datos recogidos de forma retrospectiva se analizaron con el paquete estadístico SPSS 15.0.ResultadosLa duración del tratamiento fue de 30 (18–42) semanas (mediana [RIQ]). Cinco pacientes (20,8%) desarrollaron hipotiroidismo subclínico, y 3 (12,5%) hipotiroidismo clínico. El número de semanas necesarias para observar elevación de TSH fue 15 (6–20) (mediana [RIQ]). Cinco pacientes (20,8%) presentaron TSH disminuida previa al tratamiento o durante el mismo, sin poder establecer el diagnóstico de hipertiroidismo subclínico dados los factores intercurrentes. Catorce pacientes (58,3%) presentaron toxicidad, sin encontrarse una asociación con el desarrollo de hipotiroidismo (p=0,388).Conclusiones La elevada prevalencia de hipotiroidismo inducido por sunitinib hace necesario un seguimiento sistemático de la función tiroidea en estos pacientes. No obstante, dicho estudio puede estar interferido por distintos factores fisiopatológicos y farmacológicos, por lo que podría ser útil determinar no solo TSH y T4 libre, sino también T3 libre e, idealmente, T3 reversa. A día de hoy carecemos de recomendaciones para el manejo del hipotiroidismo en el paciente oncológico basadas en la evidencia (AU)

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.ResultsTreatment 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 (AU)

[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.