Effectiveness of Combined First-Line Medical Treatment in Acromegaly with Prolactin Co-secretion.

OBJECTIVE: To compare the response to first-line medical treatment in treatment-naive acromegaly patients with pure growth hormone (GH)-secreting pituitary adenoma (GH-PA) and those with GH and prolactin co-secreting PA (GH&PRL-PA). DESIGN: Retrospective multicentric study of acromegaly patients followed from 2003 to 2023 in 33 tertiary Spanish hospitals with at least six months of first-line medical treatment. METHODS: Baseline characteristics, first-line medical treatment strategies, and outcomes were analysed. We employed a multiple logistic regression full model to estimate the impact of some baseline characteristics on disease control after each treatment modality. RESULTS: Of the 144 patients included, 72.9% had a GH-PA, and 27.1% had a GH&PRL-PA. Patients with GH&PRL-PA were younger (43.9 ± 15.0 vs. 51.9 ± 12.7 years; p < 0.01) and harboring more frequently macroadenomas (89.7% vs. 72.1%, p = 0.03). First generation somatostatin receptor ligand (fgSRL) as monotherapy was given to 106 (73.6%) and a combination treatment with fgSRL and cabergoline in the remaining 38 (26.4%). Patients with GH&PRL-PA received more frequently a combination therapy (56.4% vs. 15.2%; p < 0.01). After 6 months of treatment, in the group of patients under fgSRL as monotherapy, those patients with GH&PRL-PA had worse control compared to GH-PAs (29.4% vs. 55.1%, p = 0.04). However, these differences in the rate of disease control between both groups disappeared when both received combination treatment with fgSRL and cabergoline. CONCLUSION: In GH&PRL-PA the biochemical control achieved with fgSRL as monotherapy is substantially worse than in patients harboring GH-PA, supporting the inclusion of cabergoline as first line medical treatment in combination with fgSRLs in these subgroups of patients.

Pegvisomant and pasireotide in PRL and GH co-secreting vs GH-secreting Pit-NETs.

The objective of the study was to evaluate the efficacy of second-line therapies in patients with acromegaly caused by a growth hormone (GH) and prolactin (PRL) co-secreting pituitary neuroendocrine tumor (GH&PRL-Pit-NET) compared to their efficacy in patients with acromegaly caused by a GH-secreting pituitary neuroendocrine tumor (GH-Pit-NET). This is a multicenter retrospective study of patients with acromegaly on treatment with pasireotide and/or pegvisomant. Patients were classified in two groups: GH&PRL-Pit-NETs when evidence of hyperprolactinemia and immunohistochemistry (IHC) for GH and PRL was positive or if PRL were >200 ng/dL regardless of the PRL-IHC and GH-Pit-NETs when the previously mentioned criteria were not met. A total of 28 cases with GH&PRL-Pit-NETs and 122 with GH-Pit-NETs met the inclusion criteria. GH&PRL-Pit-NETs presented at a younger age, caused hypopituitarism, and were invasive more frequently than GH-Pit-NETs. There were 124 patients treated with pegvisomant and 49 with pasireotide at any time. The efficacy of pegvisomant for IGF-1 normalization was of 81.5% and of pasireotide of 71.4%. No differences in IGF-1 control with pasireotide and with pegvisomant were observed between GH&PRL-Pit-NETs and GH-Pit-NETs. All GH&PRL-Pit-NET cases treated with pasireotide (n = 6) and 82.6% (n = 19/23) of the cases treated with pegvisomant normalized PRL levels. No differences in the rate of IGF-1 control between pegvisomant and pasireotide were detected in patients with GH&PRL-Pit-NETs (84.9% vs 66.7%, P = 0.178). We conclude that despite the more aggressive behavior of GH&PRL-Pit-NETs than GH-Pit-NETs, no differences in the rate of IGF-1 control with pegvisomant and pasireotide were observed between both groups, and both drugs have shown to be effective treatments to control IGF-1 and PRL hypersecretion in these tumors.

Differences between GH and PRL co-secreting and GH-secreting pituitary adenomas. A series of 604 cases.

PURPOSE: To evaluate differences in clinical presentation and in surgical outcomes between growth hormone-secreting pituitary adenomas (GH-PAs) and GH and prolactin co-secreting pituitary adenomas (GH&PRL-PAs). METHODS: Multicenter retrospective study of 604 patients with acromegaly submitted to pituitary surgery. Patients were classified into two groups according to serum PRL levels at diagnosis and immunohistochemistry (IHC) for PRL: a) GH&PRL-PAs when PRL levels were above the upper limit of normal and IHC for GH and PRL was positive or PRL levels were >100ng/and PRL IHC was not available (n=130) and b) GH-PAs who did not meet the previously mentioned criteria (n=474). RESULTS: GH&PRL-PAs represented 21.5% (n=130) of patients with acromegaly. The mean age at diagnosis was lower in GH&PRL-PAs than in GH-PAs (P<0.001). GH&PRL-PAs were more frequently macroadenomas (90.6% vs. 77.4%, P=0.001) and tended to be more invasive (33.6% vs. 24.7%, P=0.057) than GH-PAs. Furthermore, they had presurgical hypopituitarism more frequently (OR 2.8, 95% CI 1.83-4.38). IGF-1 upper limit of normality (ULN) levels at diagnosis were lower in patients with GH&PRL-PAs (median 2.4 [IQR 1.73-3.29] vs. 2.7 [IQR 1.91-3.67], P=0.023). There were no differences in the immediate (41.1% vs 43.3%, P=0.659) or long-term post-surgical acromegaly biochemical cure rate (53.5% vs. 53.1%, P=0.936) between groups. However, there was a higher incidence of permanent arginine-vasopressin deficiency (AVP-D) (7.3% vs. 2.4%, P=0.011) in GH&PRL-PAs patients. CONCLUSIONS: GH&PRL-PAs are responsible for 20% of acromegaly cases. These tumors are more invasive, larger and cause hypopituitarism more frequently than GH-PAs and are diagnosed at an earlier age. The biochemical cure rate is similar between both groups, but patients with GH&PRL-PAs tend to develop permanent postsurgical AVP-D more frequently.

Evaluación endocrinológica del paciente con enfermedad nodular tiroidea / Endocrinologic approach to the patient with thyroid nodules

Llamamos nódulo tiroideo a aquella lesión concreta palpable o radiológicamente distinguible del parénquima tiroideo. La enfermedad nodular tiroidea tiene una prevalencia progresivamente creciente a medida que ha mejorado la calidad de las técnicas de imagen, principalmente la ecografía. El objetivo de la presente revisión es señalar cuales son los pasos en la evaluación endocrinológica del paciente con enfermedad nodular tiroidea. Más concretamente, cual es la mejor estrategia coste/efectiva para diagnosticar los nódulos tiroideos malignos. Tras una buena anamnesis y exploración clínica, el estudio se completa con una determinación de TSH y la realización de una ecografía tiroidea, que es la prueba diagnóstica que más criterios aporta para poder hacer la indicación de PAAF. La muestra obtenida se estudiará según el sistema Bethesda

Thyroid nodule is defined as a palpable lesion o radiologically distinguishable from thyroid parenchyma. Its prevalence is increasing with the improvement of the imagine techniques, mainly the ultrasonography. The aim of this review is to indicate the steps for the endocrinology evaluation of the patient with thyroid nodules, particularly to choose the best cost/effective strategy to diagnose the malignant thyroid nodules. After having the anamnesis and physical examination done, a TSH determination and an thyroid ultrasound are needed. The sample obtained will be studied according to the Bethesda system

Tratamiento médico del hipertiroidismo / Medical treatment of hyperthyroidism

El hipertiroidismo es una enfermedad común que afecta a un 0.2 % de la población en Europa. Aun siendo un síndrome, el tratamiento varía dependiendo de la causa. Los mecanismos patogénicos de cada una de las etiologías dictan la selección del tratamiento, siendo el hipertiroidismo un buen modelo de medicina de precisión, por cuanto una vez conocida la patogenia se personaliza el tratamiento. En este capítulo se considera el tratamiento de las causas más comunes como son la enfermedad de Graves-Basedow, el bocio multinodular y adenoma tóxico, causas menos frecuentes que incluyen diverso tipo de tiroiditis y causas raras como los tirotropinomas, e hipertiroidismo por patologías obstétricas y ginecológicas. Para el tratamiento médico de estas condiciones disponemos de un arsenal que incluye drogas antitiroideas, beta-bloqueadores, glucocorticoides, análogos de la somatostatina, agonistas dopaminérgicos, ácido iopanoico e, incluso, agentes antineoplásicos. El tratamiento con radioyodo es objeto de otro trabajo aparte

Hyperthyroidism is a rather common disease that affects 0.2 % of general population in Europe. There are many causes as well as various pathogenic mechanisms inducing a hypersecretion of thyroid hormones. Therefore, treatments are selected for each cause to obtain the highest therapeutic benefit. Is this chapter we consider the treatment of common causes such as Graves-disease, toxic multinodular goiter, toxic adenoma and other more infrequent entities such as several subtypes of thyroiditis and, finally, we briefly comment on rare cases of thyroid hyperfunction

Seguimiento posterapéutico del paciente con carcinoma tiroideo / Post-therapeutic follow-up of thyroid carcinoma

El cáncer de tiroides es la neoplasia endocrina más frecuente. Su incidencia en los últimos años ha aumentado, requiriendo estrategias de vigilancia que garanticen un manejo individualizado y efectivo de los pacientes. El objetivo principal de la siguiente revisión es brindar pautas de seguimiento a corto y largo plazo, guiándonos por una adecuada estratificación de riesgo de los pacientes y reclasificación de su respuesta al tratamiento

Thyroid cancer is the most common endocrine neoplasia. Its incidence in recent years has increased, requiring surveillance strategies that guarantee individualized and effective patient management. The main objective of the following review is to provide short-term and long-term follow-up guidelines, guiding us through adequate stratification of patient risk and reclassification of their response to treatment

Estudio observacional de infusión subcutánea continua de insulina a lo largo de 7 años en el tratamiento de la diabetes mellitus tipo 1 / An observational 7-year study of continuous subcutaneous insulin infusion for the treatment of type 1 diabetes mellitus

En este trabajo se aporta la experiencia adquirida con el tratamiento con bombas de infusión subcutánea continua de insulina (ISCI) en 112 pacientes con diabetes mellitus a lo largo de 7 años, que previamente venían siendo tratados con múltiples dosis de insulina bolo-basal. MATERIAL Y MÉTODOS: Estudio retrospectivo observacional de 112 pacientes con diabetes mellitus, tratados antes con pauta de insulina bolo-basal y luego con ISCI, desde de 2005 a 2012 que recibieron educación diabética individualizada con un protocolo específico. Se estudiaron las siguientes variables: frecuencia porcentual de las distintas indicaciones autorizadas para aplicar este tratamiento; valor medio anual de HbA1c y de fructosamina el año anterior a la instauración del tratamiento con la bomba de insulina y en los 7 años siguientes de seguimiento; frecuencia y sintomatología de las hipoglucemias. RESULTADOS: La causa más común de indicación fue la diabetes inestable (74,1%), seguida de hipoglucemias graves, frecuentes o inadvertidas (44,6%). Otras indicaciones fueron: horarios de ingesta variables o imprevisibles por razones profesionales (20,2%), fenómeno del alba (15,7%), gestación (12,3%), requerimiento de dosis muy bajas de insulina (8,9%) y diabetes gestacional (0,9%). La HbA1c descendió entre 0,6 y 0,9%, en tanto que la fructosamina lo hizo entre 5,1 y 12,2%. El 9% de pacientes presentaron hipoglucemias semanales, el 24% cada 2 semanas y en el 48% fueron mensuales; el 19% no presentó hipoglucemias. Solo el 10% presentó síntomas neuroglucopénicos y en el 21% fueron asintomáticas. Las hipoglucemias fueron más frecuentes al comienzo del tratamiento, disminuyendo rápidamente poco tiempo después. CONCLUSIÓN: La terapia con ISCI proporciona una mejoría del control glucémico en comparación con tratamiento de múltiples inyecciones. Requiere adiestramiento específico del paciente y ajustes de la dosificación de insulina para prevenir las hipoglucemias, que son las complicaciones más frecuentes, sobre todo al comienzo del tratamiento

This work reports the experience with use of continuous subcutaneous insulin infusion (CSII) in 112 type 1 diabetic patients followed up for 7 years and previously treated with multiple daily insulin injections (MDII). MATERIAL AND METHODS: A retrospective, observational study in 112 patients with diabetes mellitus treated with CSII from 2005 to 2012, previously treated with MDII and receiving individualized diabetic education with a specific protocol. Variables analyzed included: prevalence of the different indications of pump treatment; mean annual HbA1c and fructosamine values before and after CSII treatment; and hypoglycemia frequency and symptoms. RESULTS: The most common reason for pump treatment was brittle diabetes (74.1%), followed by frequent or severe hypoglycemia or hypoglycemia unawareness (44.6%). Other indications were irregular food intake times for professional reasons (20.2%), dawn phenomenon (15.7%), pregnancy (12.3%), requirement of very low insulin doses (8.9%), and gestational diabetes (0.9%). HbA1c decreased by between 0.6% and 0.9%, and fructosamine by between 5.1% and 12.26%. Nine percent of patients experienced hypoglycemia weekly, 24% every two weeks, and 48% monthly. No hypoglycemia occurred in 19% of patients. Only 10% had neuroglycopenic symptoms. Hypoglycemia unawareness was found in 21%. Hypoglycemia was more common at treatment start, and its frequency rapidly decreased thereafter. CONCLUSIÓN: CSII therapy provides a better glycemic control than MDII treatment. Specific patient training and fine adjustment of insulin infusion doses are required to prevent hypoglycemic episodes, which are the most common complications, mainly at the start of treatment

Documento de consenso del área de conocimiento de Neuroendocrinología de la Sociedad Española de Endocrinología y Nutrición para el abordaje del hipopituitarismo durante la transición / Consensus document of the Neuroendocrinology area of the Spanish Society of Endocrinology and Nutrition on management of hypopituitarism during transition

Se entiende por periodo de transición del niño al adulto a una etapa de cambios físicos y psicológicos que, de forma arbitraria, se extiende desde el final de la pubertad hasta que la maduración adulta se completa. Comprende, habitualmente, los 6 a 7 años posteriores al momento en que el niño adquiere la talla adulta. Con esta documento pretendemos poner de manifiesto la importancia de la adecuada sustitución de los diferentes déficits hipotálamo-hipofisarios durante este período. Para ello revisamos la reevaluación del status hipofisario en los pacientes deficitarios durante la infancia, tratamos de dar respuesta a las preguntas que pueden surgir y ofrecemos unas recomendaciones claras de cómo abordar la deficiencia de GH en este período. Posteriormente abordamos también la evaluación y la sustitución del eje adrenal, tiroideo y gonadal

The transition period from child to adult represents a crucial phase in the growth process where multiple physical and psychosocial changes occur. It has been arbitrarily defined as the period extending from late puberty to full adult maturity (i.e., from mid to late teenage years until 6-7 years after achievement of final height).The aim of this guideline is to emphasize the importance of adequate hormone replacement during this period and to review reassessment of pituitary function. In patients with GH deficiency diagnosed in childhood, an attempt is made to answer when to retest GH secretion, when to treat and how they should be monitored. Thyroxine, glucocorticoid, and sex steroid replacement are also reviewed

Consensus document of the Neuroendocrinology area of the Spanish Society of Endocrinology and Nutrition on management of hypopituitarism during transition.

The transition period from child to adult represents a crucial phase in the growth process where multiple physical and psychosocial changes occur. It has been arbitrarily defined as the period extending from late puberty to full adult maturity (i.e., from mid to late teenage years until 6-7 years after achievement of final height). The aim of this guideline is to emphasize the importance of adequate hormone replacement during this period and to review reassessment of pituitary function. In patients with GH deficiency diagnosed in childhood, an attempt is made to answer when to retest GH secretion, when to treat and how they should be monitored. Thyroxine, glucocorticoid, and sex steroid replacement are also reviewed.

An observational 7-year study of continuous subcutaneous insulin infusion for the treatment of type 1 diabetes mellitus.

UNLABELLED: This work reports the experience with use of continuous subcutaneous insulin infusion (CSII) in 112 type 1 diabetic patients followed up for 7 years and previously treated with multiple daily insulin injections (MDII). MATERIAL AND METHODS: A retrospective, observational study in 112 patients with diabetes mellitus treated with CSII from 2005 to 2012, previously treated with MDII and receiving individualized diabetic education with a specific protocol. Variables analyzed included: prevalence of the different indications of pump treatment; mean annual HbA1c and fructosamine values before and after CSII treatment; and hypoglycemia frequency and symptoms. RESULTS: The most common reason for pump treatment was brittle diabetes (74.1%), followed by frequent or severe hypoglycemia or hypoglycemia unawareness (44.6%). Other indications were irregular food intake times for professional reasons (20.2%), dawn phenomenon (15.7%), pregnancy (12.3%), requirement of very low insulin doses (8.9%), and gestational diabetes (0.9%). HbA1c decreased by between 0.6% and 0.9%, and fructosamine by between 5.1% and 12.26%. Nine percent of patients experienced hypoglycemia weekly, 24% every two weeks, and 48% monthly. No hypoglycemia occurred in 19% of patients. Only 10% had neuroglycopenic symptoms. Hypoglycemia unawareness was found in 21%. Hypoglycemia was more common at treatment start, and its frequency rapidly decreased thereafter. CONCLUSION: CSII therapy provides a better glycemic control than MDII treatment. Specific patient training and fine adjustment of insulin infusion doses are required to prevent hypoglycemic episodes, which are the most common complications, mainly at the start of treatment.

[Spontaneous hypothyroidism in 4 patients with Graves-Basedow disease]. / Hipotiroidismo espontáneo en 4 pacientes con enfermedad de Graves-Basedow.

We present 4 patients with Graves' disease who developed spontaneous hypothyroidism during follow-up. The two most plausible physiopathologic mechanisms for this development were progressive autoimmune-mediated destruction of the thyroid follicular epithelium and a predominance of blocking antibodies to the thyroid-stimulating hormone (TSH) receptor at the expense of stimulating antibodies in the same patient. Description of these patients not only illustrates the heterogeneous nature of this disease, but also the interrelation among its distinct clinical forms.

Hipotiroidismo espontáneo en 4 pacientes con enfermedad de Graves-Basedow / Spontaneous hypothyroidism in 4 patients with gravesbasedow disease

Presentamos los casos de 4 pacientes con enfermedad de Graves- Basedow que, durante el curso de su proceso patológico, sufrieron hipotiroidismo espontáneo. Los dos mecanismos fisiopatológicos más probables para explicar esta evolución son la destrucción autoinmunitaria progresiva del epitelio folicular tiroideo y la predominancia de anticuerpos inhibidores de los receptores de tirotropina (TSH) frente a anticuerpos estimulantes en un mismo paciente con enfermedad de Graves-Basedow. La exposición de estos 4 casos ilustra la heterogeneidad de esta enfermedad, así como la interrelación de las distintas formas clínicas de la enfermedad tiroidea autoinmunitaria (AU)

We present 4 patients with Graves’ disease who developed spontaneous hypothyroidism during follow-up. The two most plausible physiopathologic mechanisms for this development were progressive autoimmune-mediated destruction of the thyroid follicular epithelium and a predominance of blocking antibodies to the thyroidstimulating hormone (TSH) receptor at the expense of stimulating antibodies in the same patient. Description of these patients not only illustrates the heterogeneous nature of this disease, but also the interrelation among its distinct clinical forms (AU)

Liver metastases 9 years after removal of a malignant insulinoma which was initially considered benign.

CONTEXT: Insulinomas may be regarded as potentially malignant. A long follow-up period is needed to detect any possible recurrence, even if the initial diagnosis was of a benign insulinoma. CASE REPORT: We present the case of a 76-year-old woman with liver metastases due to a malignant insulinoma, which had been diagnosed as benign after its complete removal 9 years earlier. CONCLUSIONS: This case shows the difficulty of distinguishing between benign and malignant insulinomas when there is no initial evidence of metastases. This fact poses the need to conduct a long follow-up period in order to detect any possible recurrence even if the initial diagnosis was one of a benign insulinoma.