Incidentalomas o no incidentalomas: ¿cuál es la relevancia de los adenomas hipofisarios en el adulto? / Incidentalomas or Non-Incidentalomas: What is the Relevance of Pituitary Adenomas in the Adult?

Introducción: desde el punto de vista anatómico, los adenomas hipofisarios (AH) se observan en el 10% de la población. Son en su mayoría pequeños y no funcionantes. La mayoría de los incidentalomas descubiertos en estudios de imágenes con alta resolución pedidos en situaciones clínicas frecuentes, como el traumatismo craneoencefálico, el accidente cerebrovascular y las demencias, corresponden a AH indolentes. Nos preguntamos cuál es la relevancia clínica de los adenomas hipofisarios. Desarrollo: los AH clínicamente relevantes son tumores en su mayoría benignos que conllevan, en diferentes proporciones, aumento en la morbilidad y/o mortalidad de los pacientes por mecanismos relacionados con la hipersecreción hormonal, la insuficiencia hormonal y/o los efectos de masa ocupante. La prevalencia de los AH clínicamente relevantes es mayor de la que se suponía hace 20 años. Afecta aproximadamente a 1/1000 habitantes. Los más prevalentes son los prolactinomas y los adenomas no funcionantes. La acromegalia, la enfermedad de Cushing y los tumores agresivos se traducen en pacientes complejos con mayor morbimortalidad. El diagnóstico temprano y el tratamiento multimodal proveen una razonable mejoría de la sobrevida. El estudio epidemiológico de los AH clínicamente relevantes es importante para la estimación del impacto en los sistemas de salud. Conclusiones: los estudios por imágenes de mejor resolución continuarán señalando incidentalomas hipofisarios. Una evaluación cuidadosa de los pacientes podrá identificar aquellos AH clínicamente relevantes. (AU)

Introduction: from the anatomical point of view, pituitary adenomas (HA) are observed in 10% of the population. They are mostly small and non-functioning. Most incidentalomas discovered in high-resolution imaging studies ordered in frequent clinical situations, such as head trauma, stroke and dementia, correspond to indolent HA. We wonder what is the clinical relevance of pituitary adenomas. Development: clinically relevant HAs are mostly benign tumors that lead, in different degrees, to an increased morbidity and/or mortality in patients by mechanisms related to hormone hypersecretion, hormone insufficiency and/or occupying mass effects. The prevalence of clinically relevant HA is higher from what was assumed 20 years ago. It affects approximately 1/1000 of the population. The most prevalent are prolactinomas and non-functioning adenomas. Acromegaly, Cushing's disease and aggressive tumors make for complex patients with increased morbidity and mortality. Early diagnosis and multimodal treatment provide a reasonable improvement in survival. Epidemiological study of clinically relevant HAs is important for estimating the impact on health systems. Conclusions: Higher-resolution imaging studies will continue to highlight pituitary incidentalomas. Careful evaluation of patients will identify clinically relevant HAs. (AU)

Patient characteristics, disease burden, treatment patterns and outcomes in patients with acromegaly: Real-world evidence from the Malaysian acromegaly registry / Journal of the ASEAN Federation of Endocrine Societies

Objective@#This study aims to report the demographic features of patients with acromegaly the disease burden, and the corresponding treatment patterns and outcomes in Malaysia.@*Methodology@#This is a retrospective study that included patients from the Malaysian Acromegaly registry who were diagnosed with acromegaly from 1970 onwards. Data collected included patient demographics, clinical manifestations of acromegaly, biochemical results and imaging findings. Information regarding treatment modalities and their outcomes was also obtained.@*Results@#Registry data was collected from 2013 to 2016 and included 140 patients with acromegaly from 12 participating hospitals. Median disease duration was 5.5 years (range 1.0 – 41.0 years). Most patients had macroadenoma (67%), while 15% were diagnosed with microadenoma. Hypertension (49.3%), diabetes (37.1%) and hypopituitarism (27.9%) were the most common co-morbidities for patients with acromegaly. Majority of patients had surgical intervention as primary treatment (65.9%) while 20.7% were treated medically, mainly with dopamine agonists (18.5%). Most patients had inadequate disease control after first-line treatment regardless of treatment modality (79.4%).@*Conclusion@#This registry study provides epidemiological data on patients with acromegaly in Malaysia and serves as an initial step for further population-based studies.

Disfunção Ventricular e do Átrio Esquerdo Subclínica em Pacientes com Acromegalia: Um Estudo de Ecocardiograma de Rastreamento de Manchas / Subclinical Left Atrial and Ventricular Dysfunction in Acromegaly Patients: A Speckle Tracking Echocardiography Study

Resumo Fundamento Embora se saiba que a fração de ejeção (FE) do ventrículo esquerdo (VE) medida por eletrocardiograma seja preservada em pacientes com acromegalia, não há informação suficiente sobre deformação longitudinal global e deformação do átrio esquerdo (SLG-VE e SAE). Objetivo O objetivo deste estudo foi avaliar as funções do ventrículo esquerdo (VE) e do átrio esquerdo (AE) por ecocardiograma strain (ES) em pacientes com acromegalia. Métodos Este estudo incluiu 50 pacientes com acromegalia na forma ativa da doença e 50 controles saudáveis com idade, sexo e área de superfície corporal similares. Além dos ecocardiogramas de rotina, medições de SLG-VE e SAE foram realizadas com o ES. Resultados Os valores dos SAE e SLG-VE foram significativamente mais baixos em pacientes com acromegalia (p<0,05 para todos). Na análise bivariada, a pressão arterial sistólica, o pró-hormônio N-terminal do peptídeo natriurético cerebral, o fator de crescimento semelhante à insulina tipo 1, e detectou-se que os níveis de IMVE tinham correlação positiva com SAE e SLG-VE (p<0,05). O nível de IGF-1 tinha forte correlação com SAE e SLG-VE (p<0,001 e β=0,5 vs. p<0,001 e β=0,626, respectivamente); 48% dos pacientes com acromegalia têm SLG-VE reduzido (<20%). O índice de massa do ventrículo esquerdo (IMVE) determina independentemente a presença de SLG-VE reduzido, e cada 1g/m2 de aumento no nível de IMVE aumenta a probabilidade de redução de SLG-VE em 6%. Conclusão Embora a fração de ejeção de VE seja normal em pacientes com acromegalia, os valores de SAE e SLG-VE são significativamente mais baixos. Além do aumento em IMVE, outro achado do envolvimento cardíaco pode ser a redução de SAE e SLG-VE. Portanto, além do ecocardiograma de rotina, SAE e SLG-VE podem ser úteis para avaliar os sinais iniciais de envolvimento cardíaco antes da ocorrência de alterações cardíacas irreversíveis.

Abstract Background Although it is known that the left ventricular (LV) ejection fraction (EF) measured by echocardiography is preserved in patients with acromegaly, there is not enough information about the LV and left atrial strain (LV-GLS and LAS). Objective This study aimed to evaluate the left ventricular (LV) and left atrial (LA) functions with strain echocardiography (SE) in patients with acromegaly. Methods This study included 50 acromegaly patients with active disease and 50 healthy controls with similar age, gender, and body surface area. In addition to routine echocardiography examinations, LV-GLS and LAS measurements were performed with SE. Results LAS and LV-GLS values were significantly lower in patients with acromegaly (p<0.05 for all). In bivariate analysis, systolic blood pressure, N-terminal prohormone of brain natriuretic peptide, Insulin-like growth factor-1, LA diastolic diameter, and LVMI levels were found to be positively correlated with both LAS and LV-GLS (p <0.05). IGF-1 level was strongly correlated with LAS and LV-GLS (p<0.001 and β=0.5 vs. p<0.001 and β=0.626, respectively); 48% of patients with acromegaly have reduced LV-GLS (<20%). Left ventricular mass-index (LVMI) independently determines the presence of reduced LV-GLS and each 1g/m2increase in LVMI level increases the likelihood of reduced LV-GLS by 6%. Conclusion Although LV ejection fraction is normal in patients with acromegaly, LAS and LV-GLS values were significantly reduced. Apart from LVMI increase, another finding of cardiac involvement may be LAS and LV-GLS decrease. Therefore, in addition to routine echocardiography, LAS and LV-GLS may be useful to evaluate early signs of cardiac involvement before the occurrence of irreversible cardiac changes.

Enfermedad nodular tiroidea en personas con diagnóstico de acromegalia / Nodular thyroid disease in people diagnosed with acromegaly

La aparición de nódulos tiroideos en las personas con acromegalia es una consecuencia de la elevación crónica de la hormona de crecimiento y el factor de crecimiento similar a la insulina tipo 1. Su naturaleza varía según la zona geográfica, suficiencia de yodo y antecedentes patológicos familiares, entre otros factores. No se han publicado estudios cubanos sobre la enfermedad nodular tiroidea en estas personas. Objetivos: Describir las características clínicas, bioquímicas y ultrasonográficas de la glándula tiroidea, según la presencia o no de la enfermedad nodular tiroidea. Métodos: Estudio observacional descriptivo, transversal, que incluyó 73 pacientes con acromegalia entre enero de 2003 y diciembre de 2017. Se estudiaron las variables: edad, sexo, color de la piel, antecedentes familiares de la enfermedad nodular tiroidea, niveles de la hormona de crecimiento, hormona estimulante del tiroides, T4 libre, anticuerpos contra la peroxidasa tiroidea y contra la tiroglobulina, volumen tiroideo, patrón ecográfico nodular y estudio citológico. Resultados: La enfermedad nodular tiroidea se presentó en el 75,3 por ciento de los casos, con predominio del bocio multinodular. La edad al diagnóstico fue menor en los pacientes con la enfermedad (43,53 ± 9,67), que en los que no la tenían (49,33 ± 6,96 años) (p = 0,02). La hormona de crecimiento al diagnóstico de acromegalia, resultó menor en los pacientes con este padecimiento (18,73 ± 11,33 µg/L vs. 35,91 ± 21,68 µg/L; (p = 0,00). El volumen tiroideo mostró diferencias significativas entre ambos grupos (14,2 ± 4,5 mL en los casos positivos de la enfermedad nodular tiroidea y 10,5 ± 2,8 mL en los casos negativos; p = 0,002), siendo el nódulo de baja sospecha de malignidad el más frecuente. El resto de las variables resultaron similares entre los pacientes con y sin la enfermedad. La citología se informó como benigna en el 75 por ciento en los nódulos únicos, el 80 por ciento de los bocios nodulares y el 90 por ciento de los bocios multinodulares (p = 0,51). Conclusiones: La enfermedad nodular tiroidea fue frecuente en los casos de acromegalia, y se asoció a la menor edad y los niveles inferiores de la hormona de crecimiento al diagnóstico. El bocio multinodular constituyó la forma clínica más frecuente y los parámetros hormonales y de autoinmunidad no se asociaron al tipo de la enfermedad nodular tiroidea(AU)

The appearance of thyroid nodules in people with acromegaly is a consequence of chronic elevation of growth hormone (GH) and insulin-like growth factor type 1 (IGF-1). Its nature varies according to the geographical area, the iodine sufficiency and family pathological history, among other factors. No Cuban studies on thyroid nodular disease (TND) in these people have been published. Objectives: Describe some clinical characteristics, as well as biochemical and ultrasonographic ones related to the thyroid gland, according to the presence or not of TND, and to identify the possible association of clinical, biochemical, ultrasonographic and cytological factors with the different types of TND in patients with acromegaly. Methods: A descriptive, cross-sectional observational study that included 73 patients with acromegaly between January 2003 and December 2017. The following variables were studied: age, sex, skin color, family history of TND, GH levels, thyroid stimulating hormone, free T4, antibodies against thyroid peroxidase and thyroglobulin, thyroid volume, nodular ultrasound pattern and cytological study. Results: TND occurred in 75.3 percent of cases, with a predominance of multinodular goiter. The age at diagnosis time was lower in patients with TND (43.53 ± 9.67) than in those who did not have it (49.33 ± 6.96 years) (p=0.02). GH at diagnosis time of acromegaly was lower in patients with TND (18.73±11.33µg/L vs 35.91±21.68µg/L; (p=0.00). The thyroid volume showed significant differences between both groups (14.2±4.5mL in positive cases of TND and 10.5±2.8mL in negative cases; p=0.002), being the most frequent the nodule with low suspicion of malignancy. The rest of the variables were similar between patients with and without TNDs. Cytology was reported as benign in 75 percent in single nodules, 80 percent of nodular goiters and 90 percent of multinodular goiters (p=0.51). Conclusions: TND was frequent in cases of acromegaly, and was associated with lower age and lower GH levels at diagnosis time. Multinodular goiter was the most frequent clinical form and hormonal and autoimmunity parameters were not associated with the type of TND(AU)

A novel mutation in PRKAR1A gene in a patient with Carney complex presenting with pituitary macroadenoma, acromegaly, Cushing's syndrome and recurrent atrial myxoma

SUMMARY Carney complex (CNC) is a rare syndrome of multiple endocrine and non-endocrine tumors. In this paper we present a 23-year-old Iranian woman with CNC who harbored a novel mutation (c.642dupT) in PRKAR1A gene. This patient presented with pituitary macroadenoma, acromegaly, recurrent atrial myxoma, Cushing's syndrome secondary to primary pigmented nodular adrenocortical disease and pigmented schwanoma of the skin. PRKAR1A gene was PCR amplified using genomic DNA and analyzed for sequence variants which revealed the novel mutation resulting in substitution of amino acid cysteine instead of the naturally occurring valine in the peptide chain and a premature stop codon at position 18 (V215CfsX18). This change leads to development of tumors in different organs due to lack of tumor suppressive activity secondary to failure of synthesis of the related protein.

Growth hormone-releasing hormone-secreting pulmonary neuroendocrine tumor associated with pituitary hyperplasia and somatotropinoma

SUMMARY Acromegaly caused by ectopic growth hormone-releasing hormone (GHRH)-secreting tumor is exceedingly rare. We report a case of acromegaly secondary to GHRH secretion by an incidentally diagnosed pulmonary neuroendocrine tumor (NET) and review 47 similar cases in literature. A 22-year-old male patient presented with symptoms of pituitary apoplexy. Magnetic resonance imaging (MRI) showed apoplexy of a pituitary adenoma. Routinely prior to surgery, a chest radiography was performed which revealed a mass in the left lung. During investigation, the patient was diagnosed with metastatic GHRH-secreting pulmonary NET. In retrospect, it was noted that the patient had pituitary hyperplasia 20 months prior to the MRI which showed the presence of a pituitary adenoma. The histological findings confirmed somatotroph hyperplasia adjacent to somatotropinoma. This case suggests that GHRH secretion can be associated with pituitary hyperplasia, which may be followed by pituitary adenoma formation.

Acromegalia en Paciente con Cáncer Papilar de Tiroides. Reporte de caso / Acromegaly in a patient with papillary thyroid cancer. Case report

Introducción: El cáncer de tiroides es la neoplasia endocrina más frecuenteyel Carcinoma Papilar de tiroides representa el 80% de los casos. Por otro lado, la acromegalia es un trastorno poco diagnosticado con una incidencia estimada anual de 4 casos por millón de personas. Presentamos un caso en el que se presentan las dos entidades al mismo tiempo en un paciente y la discusión del posible nexobio químico. Caso clínico: Mujer de 23 años, con masa nodular pétrea de 3 centímetros, en polo superior de lóbulo derecho de tiroides; sometida a tiroidectomía radical y linfadenectomía cervical bilateral, reporte histopatológico de carcinoma papilar. Evoluciona con cambios visuales en ojo izquierdo, cefalea, amenorrea de 1 año, galactorrea negativa, características morfo-anatómicas de acromegalia, campimetría hemianopsia homónima izquierda. IRM de cerebro lesión sellar y suprasellar hiperintensa en T2 en relación a macroadenoma hipofisario. Bioquímicos: Prolactina 131.20, GH 2.7, ACTH 18.5, IGF1 434, IGFBP 35.8, TTOG para GH que se informa: GH 0 min: 10.7, GH 30 min: 9.24, GH 60 min: 7.9. Evolución: La paciente fue sometida a hipofisectomía transesfenoidal endoscópica parcial. En tratamiento con cabergolina 0.5 mg bisemanal, levotiroxina 225 mcg día y octreótide 20 mg mensual. Conclusión: Se concluye que siendo la acromegalia una enfermedad rara se asocia a cáncer de tiroides, implicando posibles mutaciones en la subunidad α de la proteína G.

Introduction:Thyroid cancer is the most frequent endocrine neoplasia and Papillary thyroid carcinoma represents 80% of cases. On the other hand, acromegaly is a poorly diagnosed disorder with an estimated annual incidence of 4 cases per million people. We present a case in which the two entities occur at the same time in a patient and the discussion of the possible biochemical link. Clinical case: 23-year-old woman, with a 3 cm stone nodular mass in the upper pole of the right thyroid lobe; submitted to radical thyroidectomy and bilateral cervical lymphadenectomy, histopathological report of papillary carcinoma. It evolves with visual changes in the left eye, headache, 1-year amenorrhea, negative galactorrhea, morpho-anatomical characteristics of acromegaly,left homonymous hemianopia campimetry. T2 hyperintense seal and suprasellar lesion brain MRI in relation to pituitary macroadenoma. Biochemicals: Prolactin 131.20, GH 2.7, ACTH 18.5, IGF1 434, IGFBP 35.8, TTOG for reported GH: GH 0 min: 10.7, GH 30 min: 9.24, GH 60 min: 7.9. Evolution: The patient underwent partial endoscopic transsphenoidal hypophysectomy. In treatment with cabergoline 0.5 mg twice weekly, levothyroxine 225 mcg day and octreotide 20 mg monthly. Conclusion: It is concluded that, being acromegaly a rare disease, it is associated with thyroid cancer, involving possible mutations in the α subunit of the G protein.

Caso Clínico: Manejo Perioperatorio en Pacientes con Acromegalia / Case Report: Perioperative Management in Patients with Acromegaly

INTRODUCCIÓN: La acromegalia es una enfermedad crónica, progresiva y multisistémica causada por la hipersecreción de la hormona de crecimiento de un macroadenoma hipofisario en funcionamiento. Ciertas características clínicas de esta patología son de interés anestésico sobre todo aquellas que afectan la vía aérea superior, los sistemas respiratorio y cardíaco y el sistema metabólico. CASO CLÍNICO: Paciente de sexo masculino de 34 años de edad, que presentó incremento progresivo de tamaño de pies, manos, nariz, huesos del cráneo y aumento del tamaño de la lengua, diagnosticado de acromegalia por macroadenoma hipofisiario productor de hormona de crecimiento. Se sumaron más tarde SAHOS severo, insuficiencia mitral y tricúspidea leve; motivo por el cual se programa para resección de macroadenoma hipofisiario por acceso transepto-esfenoidal. Durante la evaluación preanestésica el paciente fue catalogado como Riesgo Quirúrgico ASA III, Riesgo Cardiaco de Lee 0.04 %, NYHA I, probabilidad alta de vía aérea difícil. Transquirúrgico: Inducción anestésica con propofol, 120 mg, remifentanilo 0.2 mcg/kg/min, rocuronio 50 mg. Se logró intubación orotraqueal atraumática utilizando McCoy hoja N4, con tubo endotraqueal reforzado N 7.5. EVOLUCIÓN: Fue llevado a Terapia Intensiva donde permaneció para control posquirúrgico. El paciente permaneció hospitalizado durante 7 días y fue dado de alta en condiciones estables, sin déficit neurológico. Se mantiene aún en seguimiento por el SAHOS severo que presenta. Se ha reportado que han mejorado sus episodios de apnea nocturna. CONCLUSION: Los pacientes con enfermedad de la glándula pituitaria sometidos a cirugía pueden presentar una serie de desafíos anestésicos, desde el manejo de la vía aérea hasta cambios hemodinámicos y ventilatorios importantes durante el procedimiento quirúrgico. Es importante prever y prevenir las complicaciones y corregirlas a tiempo, para evitar lesiones irreversibles que aumenten la morbilidad del paciente.(au)

BACKGROUND: Acromegaly is a chronic, progressive and multisystemic disease caused by growth hormone hypersecretion by a functioning pituitary macroadenoma. Some clinical features of this disease are important for anesthetic management, especially those that affect the upper airway, and the cardiac, respiratory and metabolic systems. CASE REPORT: Male 34 year old patient, with progressive increase of feet, hands, nose, skull bone and tongue size, diagnosed with acromegaly caused by growth hormone producing pituitary macroadenoma. Later he presents with severe SAHOS, mitral and mild tricuspid insufficiency; so transsphenoidal resection of pituitary macroadenoma was programed. During preanesthetic evaluation was classified as ASA III Surgical Risk, Lee Cardiac Risk 0.04%, NYHA I, and high probability of difficult airway. The anesthetic induction scheme was: propofol 120 mg, remifentanil 0.2 mcg / kg / min, rocuronium 50 mg. Atraumatic orotracheal intubation using McCoy leaf N4, with reinforced endotracheal tube N 7.5 was achieved. EVOLUTION: The patient was taken to Intensive Care Unit for post-surgical control. The patient remained hospitalized for 7 days and was discharged in stable condition without neurological deficit. He is still in follow up of the severe SAHOS. It has been reported improvement of the episodes of night apnea. CONCLUSION: Patients with pituitary gland disease undergoing surgery can present some anesthetic challenges, from the airway management, to the important hemodynamic and ventilatory challenges during the surgical procedure. It is important to anticipate and prevent the possible complications and correct them in time in order to avoid irreversible injuries that increase the patient's morbidity.(au)

Thyroid gland changes in patients with acromegaly

ABSTRACT Objective Acromegaly is characterized by high neoplastic morbidity as a side effect of growth hormone (GH) hypersecretion. Increased incidence of goiter, thyroid carcinoma, and thyroid dysfunction is also reported. The aim of the present study was to find the prevalence of thyroid dysfunction and goiter in patients with acromegaly and determine its relationship to disease activity, disease duration, and the presence of secondary hypothyroidism. Subjects and methods In a cross-sectional study of the period 2008-2012 were included 146 patients with acromegaly (56 men, 90 women) of mean age 50.3 ± 12.4 years. Acromegaly disease activity and thyroid function were evaluated in all patients. Thyroid ultrasonography was performed to calculate thyroid volume and detect the presence of nodular goiter. Results Ninety-one patients were determined to have an active disease, and 55, a controlled disease. The mean thyroid volume in patients without previous thyroid surgery was 37.6 ± 38.8 mL. According to disease activity, thyroid volume was significantly higher in patients with active disease (38.5 ± 45.4 mL vs. 27.2 ± 18.4 mL, p = 0.036). A weak positive correlation was found between thyroid volume and insulin-like growth factor 1 (IGF-1) in the whole group and in females (R = 0.218; p = 0.013, and R = 0.238; p = 0.037, respectively). There was no significant correlation of thyroid volume with disease duration and GH level in the whole group and in both sexes. The patients with secondary hypothyroidism had twofold smaller thyroid volume, relative to the rest of the group. The prevalence of thyroid dysfunction was 39%, with a female to male percentage ratio of 1.73. Goiter was diagnosed in 87% of patients, including diffuse goiter (17.1%) and nodular (69.9%), with no significant difference between patients with active and controlled disease or the presence of secondary hypothyroidism. Conclusions Thyroid volume in patients with acromegaly depends on disease activity and the presence of secondary hypothyroidism as a complication. The increased prevalence of nodular goiter determines the need of regular ultrasound thyroid evaluation in the follow-up of patients with acromegaly. Arch Endocrinol Metab. 2020;64(3):269-75

Therapeutic Effect of a Novel Chimeric Molecule Targeting Both Somatostatin and Dopamine Receptors on Growth Hormone-Secreting Pituitary Adenomas

BACKGROUND: Acromegaly is a rare disease primarily caused by growth hormone (GH)-secreting pituitary adenomas, and its treatment is costly. Moreover, some patients are unresponsive to treatment. Hence, there are increasing efforts to develop new drugs with improved effectiveness for this disease. BIM23B065 is a novel chimeric molecule that acts on both somatostatin and dopamine receptors. This study aimed to investigate the effects of BIM23B065 compared with those of a somatostatin receptor analog and a dopamine agonist.METHODS: The effects of BIM23B065 on the proliferation, GH and insulin-like growth factor-1 (IGF-1) levels, and extracellular signal-regulated kinase (ERK) 1/2 and cyclic AMP response element binding (CREB) phosphorylation of GH3 cells were investigated with MTS assay, enzyme-linked immunosorbent assay, and Western blotting, respectively. The dosage and treatment duration of BIM23B065 were tested in animal models of GH-secreting pituitary adenoma. The effect of BIM23B065 (3 mg/kg/day) on changes in IGF-1 levels before and after treatment was further investigated.RESULTS: In vitro, BIM23B065 treatment decreased GH release in the culture media and downregulated ERK 1/2 and CREB phosphorylation to 22% and 26%, respectively. In vivo, IGF-1 expression decreased to 50 % after 4 weeks of treatment with BIM23B065 using an osmotic pump implant. Moreover, magnetic resonance imaging results showed that the tumor size decreased significantly following treatment with BIM23B065 for 4 weeks.CONCLUSION: The novel chimeric molecule was effective in decreasing IGF-1 and GH levels and may serve as an effective therapeutic agent for acromegaly.

The position of combined medical treatment in acromegaly

ABSTRACT Advances in combination medical treatment have offer new perspectives for acromegaly patients with persistent disease activity despite receiving the available medical monotherapies. The outcomes of combination medical treatment may reflect both additive and synergistic effects. This review focuses on combination medical treatment and its current position in acromegaly, based on clinical studies evaluating the efficacy and safety of combined medical treatment(s) and our own experiences with combination therapy. Arch Endocrinol Metab. 2019;63(6):646-52

Acromegaly in the elderly patient

ABSTRACT Acromegaly is an insidious disease, usually resulting from growth hormone hypersecretion by a pituitary adenoma. It is most often diagnosed during the 3rd to 4th decade of life. However, recent studies have shown an increase in the incidence and prevalence of acromegaly in the elderly, probably due to increasing life expectancy. As in the younger population with acromegaly, there is a delay in diagnosis, aggravated by the similarities of the aging process with some of the characteristics of the disease. As can be expected elderly patients with acromegaly have a higher prevalence of comorbidities than younger ones. The diagnostic criteria are the same as for younger patients. Surgical treatment of the pituitary adenoma is the primary therapy of choice unless contraindicated. Somatostatin receptor ligands are generally effective as both primary and postoperative treatment. The prognosis correlates inversely with the patient's age, disease duration and last GH level. Arch Endocrinol Metab. 2019;63(6):638-45

Determinants of morbidities and mortality in acromegaly

ABSTRACT Acromegaly is a systemic disease associated with increased morbidity, presenting cardiovascular, metabolic, respiratory, neoplastic, endocrine, articular and bone complications. Most of these comorbidities can be prevented or delayed with adequate disease treatment and, more recent studies with the use of modern treatments of acromegaly, have shown a change in the severity and prevalence of these complications. In addition, acromegaly is associated with increased mortality, but recent studies (especially those published in the last decade) have shown a different scenario than older studies, with mortality no longer being increased in adequately controlled patients and a change in the main cause of death from cardiovascular disease to malignancy. In this review, we discuss this changing face of acromegaly summarizing current knowledge and evidence on morbimortality of the disease. Arch Endocrinol Metab. 2019;63(6):630-7

Serie de Casos Clínicos: Acromegalia, Presentación Clínica y Evolución en los Pacientes del Hospital "Vicente Corral Moscoso". Cuenca - Ecuador, Mayo 2015 - Abril 2017 / Case Series: Acromegaly, Clinical Presentation and Evolution in Patients of Hospital "Vicente Corral Moscoso". Cuenca - Ecuador, May 2015 - April 201

INTRODUCCIÓN:La acromegalia es una enfermedad sistémica caracterizada por la elevada producción de hormona del crecimiento, su etiología más común es el adenoma hipofisiario. En Ecuador existe una prevalencia de 18.7 casos por millón de habitantes y una incidencia de 1.3 casos por millón de individuos cada año. Se considera que existe un retraso de aproximadamente una década entre el inicio de los síntomas y el reconocimiento de los mismos por parte del equipo de salud. CASO CLÍNICO: Se presentan a continuación tres pacientes con acromegalia, atendidos por el servicio de Endocrinología del Hospital Vicente Corral Moscoso desde Mayo del 2015 hasta Abril del 2017. En esta serie, la edad de diagnóstico fue alrededor de los 34 años. Los motivos de consulta fueron molestias visuales, dolores articulares y complicaciones microvasculares. En todos los casos, la etiología fue un adenoma hipofisario productor de hormona del crecimiento en los que era necesaria la corrección quirúrgica; sin embargo, la paciente del caso 3 rechazó este tratamiento. EVOLUCIÓN: Se presentan a continuación tres pacientes con acromegalia, atendidos por el servicio de Endocrinología del Hospital Vicente Corral Moscoso desde Mayo del 2015 hasta Abril del 2017. En esta serie, la edad de diagnóstico fue alrededor de los 34 años. Los motivos de consulta fueron molestias visuales, dolores articulares y complicaciones microvasculares. En todos los casos, la etiología fue un adenoma hipofisario productor de hormona del crecimiento en los que era necesaria la corrección quirúrgica; sin embargo, la paciente del caso 3 rechazó este tratamiento. CONCLUSIÓN: Es importante reconocer la característica insidiosa de la acromegalia y sus variables manifestaciones clínicas, puesto que un diagnóstico oportuno permite mejorar el pronóstico y la calidad de vida. Hay diversas opciones terapéuticas, siendo el tratamiento quirúrgico complementado con terapia farmacológica, el de mayor eficacia. El manejo debe ser multidisciplinario e individualizado(au)

BACKGROUND: Case Series: Acromegaly, Clinical Presentation and Evolution in Patients of Hospital "Vicente Corral Moscoso". Cuenca - Ecuador, May 2015 - April 2017. CASE REPORTS: Three patients with acromegaly are presented, attended by the Endocrinology service of the Hospital Vicente Corral Moscoso from May 2015 to April 2017. In this series, the diagnosis age was around 34 years. Patients consulted because of visual discomfort, joint pain and microvascular complications. In all cases, the etiology was a pituitary adenoma producing growth hormone, in which surgical correction was necessary; however, patient number 3 rejected surgical treatment. EVOLUTION: In the present series, case 1 is undergoing treatment with Octreotide-Cabergoline and hormone replacement therapy, case 2 achieved biochemical remission with postoperative adjuvant treatment based on somatostatin analogues and case 3 has poor expectation of cure due to her medical history and lack of adherence to treatment. CONCLUSIONS: It is important to recognize the insidious characteristic of acromegaly and its varia-ble clinical manifestations, because a timely diagnosis allows a better prognosis and quality of life. There are several therapeutic options, being the surgical treatment supplemented with pharmacological therapy, the most effective. The management must be multidisciplinary and individualize(au)

Brazilian multicenter study on pegvisomant treatment in acromegaly

ABSTRACT Objective Investigate the therapeutic response of acromegaly patients to pegvisomant (PEGV) in a real-life, Brazilian multicenter study. Subjects and methods Characteristics of acromegaly patients treated with PEGV were reviewed at diagnosis, just before and during treatment. All patients with at least two IGF-I measurements on PEGV were included. Efficacy was defined as any normal IGF-I measurement during treatment. Safety data were reviewed. Predictors of response were determined by comparing controlled versus uncontrolled patients. Results 109 patients [61 women; median age at diagnosis 34 years; 95.3% macroadenomas] from 10 Brazilian centers were studied. Previous treatment included surgery (89%), radiotherapy (34%), somatostatin receptor ligands (99%), and cabergoline (67%). Before PEGV, median levels of GH, IGF-I and IGF-I % of upper limit of normal were 4.3 µg/L, 613 ng/mL, and 209%, respectively. Pre-diabetes/diabetes was present in 48.6% and tumor remnant in 71% of patients. Initial dose was 10 mg/day in all except 4 cases, maximum dose was 30 mg/day, and median exposure time was 30.5 months. PEGV was used as monotherapy in 11% of cases. Normal IGF-I levels was obtained in 74.1% of patients. Glycemic control improved in 56.6% of patients with pre-diabetes/diabetes. Exposure time, pre-treatment GH and IGF-I levels were predictors of response. Tumor enlargement occurred in 6.5% and elevation of liver enzymes in 9.2%. PEGV was discontinued in 6 patients and 3 deaths unrelated to the drug were reported. Conclusions In a real-life scenario, PEGV is a highly effective and safe treatment for acromegaly patients not controlled with other therapies.

Pegvisomant in acromegaly: a multicenter real-life study in Argentina

ABSTRACT Objective To describe the long term safety and efficacy of pegvisomant (PEGV), and the predictors of treatment response in patients with acromegaly in the real life setting. Subjects and methods We retrospectively reviewed the clinical, hormonal and radiological data of acromegalic patients treated with PEGV in 17 Argentine centers. Results Seventy-five patients (age range 22-77, 51 females) with acromegaly have been treated with PEGV for up to 118 months (median 27 months). Before PEGV, 97.3% of patients had been treated with medical therapy, surgery and/or radiotherapy, two patients had no previous treatment. At that time, all patients had an IGF-1 above the upper normal limit (ULN) (mean 2.4 x ULN ± 0.98, range 1.25-7). At diagnosis of acromegaly 84% presented macroadenomas, prior to PEGV only 23,5% of patients remained with tumor remnant > 1 cm, the remaining showed normal or less than 1 cm images. Disease control (IGF-1 ≤ 1.2 x ULN) was achieved in 62.9% of patients with a mean dose of 11.8 mg/day. Thirty-four patients (45%) received PEGV monotherapy, while 41 (55%) received combined therapy with either somatostatin analogues and/or cabergoline. Adverse events related to PEGV were: local injection site reaction in 5.3%, elevated liver enzymes in 9.3%, and tumor size growth in 9.8%. Pre-PEGV IGF-I level was the only predictor of treatment response: 2.1 x ULN vs 2.8 x ULN in controlled and uncontrolled patients respectively (p < 0.001). Conclusion this long term experience indicates PEGV treatment was highly effective and safe in our series of Argentine patients with acromegaly refractory to standard therapies. Arch Endocrinol Metab. 2019;63(4):320-7

Acromegalia y silla turca vacía: una asociación infrecuente: presentación de un caso / Acromegaly and empty sella syndrome: an infrequent association: presentation of a case

La acromegalia, originada por un exceso de producción de Hormona de crecimiento (Gh), se caracteriza por crecimiento somático exagerado, alto riesgo cardio-metabólico, así como reducción de la expectativa de vida. Tiene una incidencia de 3-4 casos por millón de habitantes. El diagnóstico se retrasa hasta 10 años aumentando la morbi-mortalidad. Las alternativas terapéuticas incluyen medicamentos y cirugía, que van encaminados a reducir los efectos de masa tumoral, normalizar los parámetros bioquímicos y resolver las manifestaciones clínicas. En casos muy infrecuentes, el tumor hipofisario que la origina se asocia a silla turca vacía.

Acromegaly, caused by an excess production of growth hormone (Gh), it is characterized by exaggerated somatic growth, high cardio-metabolic risk, as well as reduction of life expectancy. It has an incidence of 3-4 cases per million population. The diagnosis is delayed up to 10 years increasing morbidity and mortality. The therapeutic alternatives include medications and surgery, which are aimed at reduce the effects of tumor mass, normalize biochemical parameters and resolve clinical manifestations. In very infrequent cases, the pituitary tumor that originates it is associated with empty sella syndrome. Key words: Acromegaly, Empty sella syndrome, Pituitary tumor.

Clinical and functional variables can predict general fatigue in patients with acromegaly: an explanatory model approach

ABSTRACT Objective To evaluate whether hormonal profile, arterial function, and physical capacity are predictors of fatigue in patients with acromegaly. Subjects and methods: This is a cross-sectional study including 23 patients. The subjects underwent a Modified Fatigue Impact Scale (MFIS) assessment; serum growth hormones (GH) and IGF-1 measurements; pulse wave analysis comprising pulse wave velocity (PWV), arterial compliance (AC), and the reflection index (IR1,2); dominant upper limb dynamometry (DYN); and the six-minute walking distance test (6MWT). Multiple linear regression models were used to identify predictors for MFIS. The coefficient of determination R2 was used to assess the quality of the models' fit. The best model was further analyzed using a calibration plot and a limits of agreement (LOA) plot. Results The mean ± SD values for the participants' age, MFIS, PWV, AC, IR1,2, DYN, and the distance in the 6MWT were 49.4 ± 11.2 years, 31.2 ± 18.9 score, 10.19 ± 2.34 m/s, 1.08 ± 0.46 x106 cm5/din, 85.3 ± 29.7%, 33.9 ± 9.3 kgf, and 603.0 ± 106.1 m, respectively. The best predictive model (R2 = 0.378, R2 adjusted = 0.280, standard error = 16.1, and P = 0.026) comprised the following regression equation: MFIS = 48.85 - (7.913 × IGF-I) + (1.483 × AC) - (23.281 × DYN). Conclusion Hormonal, vascular, and functional variables can predict general fatigue in patients with acromegaly.

Correlation analysis between short-term insulin-like growth factor-I and glucose intolerance status after transsphenoidal adenomectomy in acromegalic patients: a large retrospective study from a single center in China

ABSTRACT Objectives: Our study aimed to investigate the associations of glucose tolerance status with insulin-like growth factor-I (IGF-I) and other clinical laboratory parameters of acromegalic patients before and after the patients underwent transsphenoidal adenomectomy (TSA) by conducting a single-center, retrospective study. Subjects and methods: A total of 218 patients with acromegaly who had undergone TSA as the first treatment were retrospectively analyzed. Serum IGF-I, growth hormone (GH) and glucose levels were measured before and after surgery. Results: The follow-up levels for random GH, GH nadir, and the percentage of the upper limit of normal IGF-I (%ULN IGF-I) were decreased significantly. The percentages of normal (39.0%), early carbohydrate metabolism disorders (33.0%) and diabetes mellitus (28.0%) changed to 70.2%, 16.5% and 13.3%, respectively, after TSA. %ULN IGF-I at baseline was higher in the diabetes mellitus (DM) group than in the normal glucose tolerance group and impaired glucose tolerance (IGT) /impaired fasting glucose (IFG) groups before TSA, and the DM group exhibited a greater reduction in %ULN IGF-I value after surgery. The follow-up %ULN IGF-I value after surgery was significantly lower in the improved group, and Pearson's correlation analysis revealed that the reductions in %ULN IGF-I corresponded with the reductions in glucose level. Conclusion: This study examined the largest reported sample with complete preoperative and follow-up data. The results suggest that the age- and sex-adjusted IGF-I level, which reflects altered glucose metabolism, and the change of it are associated with improved glucose tolerance in acromegalic patients both before and after TSA.