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)

Radiographic findings in acromegaly: pictorial essay / Achados radiográficos da acromegalia: ensaio iconográfico

Abstract Acromegaly is an uncommon metabolic disorder, often diagnosed after a long delay. One symptom seen in many patients with acromegaly is arthralgia, a finding that calls for the use of conventional radiography, which can reveal subtle changes that can go unnoticed. The objective of this pictorial essay is to portray the radiographic aspects of acromegaly, seeking to demonstrate the importance of conventional radiography, which, despite its simplicity, can suggest the diagnosis, even in the early stages, thus altering the clinical course of the disease.

Resumo A acromegalia é um distúrbio metabólico pouco frequente, muitas vezes apresentando grande atraso diagnóstico. A artralgia é um dos sintomas mais comumente encontrados nos pacientes acromegálicos, motivando a realização de radiografias convencionais, as quais podem apresentar achados sutis que podem passar despercebidos. O objetivo deste ensaio é retratar os achados radiográficos da acromegalia, buscando demonstrar a importância deste método que, apesar de simples, pode sugerir o diagnóstico, mesmo em fases iniciais, alterando assim o curso clínico da doença.

Endoscopic endonasal approach for acromegaly: surgical outcomes using 2018 consensus criteria for remission

ABSTRACT Objective: The primary aim is to analyze the endoscopic endonasal surgical results in short-term and two-year follow-ups according to the 11th Acromegaly Consensus statement (2018). Indeed, prognostic factors and complications were analyzed. Subjects and methods: 40 patients who underwent endoscopic endonasal surgery by acromegaly between 2013 to 2020 was analyzed. Patients were considered in remission if an upper limit of normal (ULN) IGF-1 was less than 1.0 at the six-month and two-year follow-ups. Moreover, we assessed the Knosp grade, tumor volumetry, ULN, T2 signal in MRI, reoperation, and complications. Results: The mean age of admission was 46.7 years. Thirty-two patients were in remission after six months of surgery (80%), decreasing to 76.32% at the two-year follow-up. All microadenomas presented remission (n = 6). Regarding the complications, three patients had permanent panhypopituitarism (7.5%); postoperative cerebrospinal fluid (CSF) leaks did not occur in this series. The hyperintense signal on the T2 MRI and a higher tumor volumetry were the single predictor's factors of non-emission in a multivariate regression logistic analysis (p < 0.05). Preoperative hormone levels (GH and IGF-1) were not a prognostic factor for remission. The re-operated patients who presented hypersignal already had a high predictor of clinical-operative failure. Conclusion: The endoscopic endonasal surgery promotes high short-term and two-year remission rates in acromegaly; the tumor's volumetry and the T2 hypersignal were statistically significant prognostic factors in non-remission - the complications presented at similar rates in comparison to the literature. In invasive GH-secreting tumors, we should offer these patients a multi-disciplinary approach to improve acromegalic patients' remission rates.

Clinical Research Progress of the Non-Peptide Oral Somatostatin Receptor Ligand Paltusotine / 罕见病研究

The research and development of somatostatin analogues is a hot area in endocrinology and metabolism. The first generation octreotide, lanreotide and the second generation pareotide have been approved to be effective for the treatment of neuroendocrine tumors such as acromegaly. However, paltusotine, a somatostatin receptor ligand, is a novel non-peptide small molecule drug which can be administered orally and inhibits excessive secretion of growth hormone and insulin-like growth factor 1. This review summarizes the research progress of the pharmacokinetics, pharmacodynamics, clinical efficacy, telerability, and safety of paltusotine.

Causal Relationship Between Acromegaly and Colon Cancer: A Two-sample Mendelian Randomization Study / 肿瘤防治研究

Objective To determine the causal relationship between acromegaly and colon cancer by using two-sample Mendelian randomization. Methods Genetic loci closely related to acromegaly in the whole genome-wide association study (GWAS) were selected as tool variables, and the genetic data of colon cancer from different GWASs were analyzed by two-sample Mendelian randomization (MR).The inverse variance weighting method (IVW) of the random effect model was used for analysis, and MR-weighted median and MR-Egger methods were used to supplement the analysis. Results were presented as OR values. Results Four SNPs closely related to acromegaly were obtained as tool variables, and the multiplicity test of tool variables showed that P=0.59.Three methods were used to estimate causal effects.The IVW analysis were OR=1.00(0.99-1.001) and P=0.42;the MR-Egger analysis results were OR=1.00(0.99-1.001) and P=0.42;and the Weighted median analysis results were OR=1.00(1.00-1.001) and P=0.03.The sensitivity test showed that the confidence interval of the tool variable SNP passed through 0, indicating the robustness of the MR results. Conclusion Acromegaly is not an independent risk factor for colon cancer.

The state of Sergipe contribution to GH research: from Souza Leite to Itabaianinha syndrome

ABSTRACT In the late 19th century, José Dantas de Souza Leite, a physician born in Sergipe, published the first detailed clinical description of acromegaly under the guidance of the French neurologist Pierre Marie. In 2014, the Brazilian Society of Endocrinology and Metabolism created the "José Dantas de Souza Leite Award", which is granted every two years to a Brazilian researcher who has contributed to the development of endocrinology. In 2022, the award was given to another physician from Sergipe, Manuel Hermínio de Aguiar Oliveira, from the Federal University of Sergipe for the description of "Itabaianinha syndrome" in a cohort of individuals with isolated GH deficiency due to a homozygous inactivating mutation in the GH-releasing hormone receptor gene. This research, which was carried out over almost 30 years, was performed in partnership with Roberto Salvatori from Johns Hopkins University and in collaboration with other researchers around the world. This review article tells the story of Souza Leite, some milestones in the history of GH, and summarizes the description of Itabaianinha syndrome.

Impact of the COVID-19 pandemic in the treatment of patients with acromegaly in a tertiary center: a wake-up call on the importance of telemedicine

ABSTRACT Objective: The COVID-19 pandemic has profoundly disrupted health care worldwide. We aimed to evaluate the impact of the first COVID-19 wave on the treatment of our patients with acromegaly. Subjects and methods: A standard questionnaire was systematically applied to all patients and included questions on general health status, whether all laboratory workup had been done, common signs and symptoms of acromegaly, treatment adherence, and previous COVID-19 symptoms and diagnosis. Results: We attempted to contact 136 patients with acromegaly at regular follow-up at our institution and contacted 101 of them successfully. In all, 37% of the patients reported symptoms of acromegaly, which was more common among women. A total of 27 patients were lost to follow-up (including 19 who interrupted treatment during the pandemic) mainly for fear of becoming infected by the SARS-CoV-2. Of these, 24 resumed follow-up after our contact. Conclusions: The current COVID-19 pandemic has strongly impacted the follow-up of patients with acromegaly. Telemedicine can be an important tool to maintain regular treatment in the current or future pandemics.

Complicaciones cardiovasculares asociadas a la acromegalia. Estado del arte / Cardiovascular complications associated with acromegaly. A state-of-the-art

Resumen La acromegalia es una enfermedad rara, causada principalmente por un tumor hipofisiario secretor de hormona de crecimiento (GH), se caracteriza por tener progresión lenta y asociarse a un compromiso multisistémico, siendo el aparato cardiovascular uno de los más comprometidos, llegando, incluso, desde hace más de 10 años a representar la principal causa de muerte. Las complicaciones cardiovasculares se desarrollan como resultado de las concentraciones sanguíneas elevadas de la GH y del factor de crecimiento similar a la insulina tipo 1 (IGF-1), los cuales ejercen efectos directos e indirectos sobre el endotelio, grandes vasos, riñón y los cardiomiocitos; produciendo hipertensión arterial, enfermedad valvular, arritmia cardiaca y una cardiopatía propia de la acromegalia denominada miocardiopatía acromegálica. Luego de la revisión bibliográfica actualizada relacionada con la fisiopatología, manifestaciones clínicas, diagnóstico y tratamiento del compromiso cardiovascular, encontramos que desde el punto de vista cardiovascular los pacientes con acromegalia pueden variar desde un estado asintomático hasta presentar disfunción cardiaca severa, siendo los marcadores bioquímicos y exámenes de imagen herramientas diagnósticas que permiten evaluar el grado de afección cardiovascular para poder brindar un tratamiento individualizado. La normalización de los valores de la GH y del IGF-1 mejora los parámetros cardiovasculares y, por tanto, su pronóstico.

Abstract Acromegaly is a rare disease, mainly caused by a pituitary tumor secreting growth hormone. It is characterized by slow progression and is associated with a multisystemic involvement, being the cardiovascular system, one of the most involved, even reaching, more than 10 years ago, to represent the main cause of death. Cardiovascular complications develop as a result of elevated blood concentrations of growth hormone and insulin-like growth factor 1, which exert direct and indirect effects on the endothelium, large vessels, kidney and cardiomyocytes; causing arterial hypertension, valve disease, cardiac arrhythmia and a specific heart disease called acromegalic cardiomyopathy. After the literature overview related to the pathophysiology, clinical manifestations, diagnosis and treatment of cardiovascular involvement, we found that from a cardiovascular point of view, patients with acromegaly can range from an asymptomatic state to severe cardiac dysfunction, being the biochemical markers and imaging studies diagnostic tools that allow assessment the degree of cardiovascular disease in order to provide individualized treatment. The normalization of growth hormone and insulin-like growth factor 1 levels improves cardiovascular parameters, and therefore its prognosis.

Efficacy of cabergoline add-on therapy in patients with acromegaly resistance to somatostatin analogs treatment and the review of literature

ABSTRACT Objective: It is reported that adding cabergoline to somatostatin analog (SSA) normalizes IGF-1 levels approximately in one-third of patients with acromegaly. We investigated the effect of combination therapy and potential predictors of response in patients with acromegaly who do not respond to SSA therapy alone. Subjects and methods: Fifty acromegaly patients (M/F 23/27, mean age 50.88 ± 12.34 years) were divided into two groups as the active and control groups in this connection. Before and after treatment, we not only evaluated serum GH and IGF-1 levels and tumor size but also analyzed the factors relevant to the effect of the combined therapy. Results: Adding cabergoline to SSA treatment led to IGF-1 normalization in 42% (21/50) of patients. Mean GH levels decreased from 2.64 ± 1.79 to 1.34 ± 0.99 ng/mL (p < .0001) and IGF-1 levels decreased from 432.92 ± 155.61 to 292.52 ± 126.15 ng/mL (p < .0001). GH and IGF-1 reduction in percent (%) were significantly higher in the controlled group (63% to 40%, p = 0.023 and 45% to 19%, p = 0.0001). Moreover, tumor size decrease was significantly higher in controlled group (-3.6 cm to -1.66 cm, p = 0.005). Conclusions: According to the results of our study, the addition of cabergoline to SSA normalized IGF-1 levels in a considerable amount of acromegaly patients with a moderately elevated IGF-1 level, regardless of serum PRL levels. Besides, cabergoline treatment was also influential in patients with higher IGF-1 levels despite a lower remission rate.

Complejo de Carney: reporte de un caso y revisión de la literatura / Carney complex: a case report and literature review

Resumen El complejo de Carney es una enfermedad caracterizada por lesiones en la piel, tumores endocrinos, cardiacos, gonadales y en otros órganos, que está asociada con mutaciones del gen PRKAR1A. Presentamos el caso clínico de una paciente con varias de las manifestaciones más características de este síndrome. Finalmente, se hace una revisión de la literatura.

Abstract Carney complex is a disease characterized by skin lesions, endocrine, cardiac, gonadal and other organ tumors, associated with mutations of the PRKAR1A gene. We present the clinical case of a patient with several of the most characteristic manifestations of this syndrome. Finally, there will be a review of the literature.

Patient's point of view on the diagnosis, treatment, and follow-up in acromegaly: single-center study from a tertiary center

SUMMARY OBJECTIVE: We aimed to evaluate the awareness and perspectives of acromegaly patients in the diagnosis and treatment processes and to evaluate basic clinical and demographic features. METHODS: This cross-sectional study was conducted at the Endocrinology Department of Yildirim Beyazit University between March 2019 and April 2020. A total of 58 acromegalic patients were enrolled. All patients were identified from our database and called for a clinical visit and filling the questionnaire forms. RESULTS: A total of 58 patients were included in this study (41.4% female). The mean age of the patients was 52±10.8 years. Median year from symptom to diagnosis (min-max) was 2 (1-12). Notably, 55.2% of the patients did not graduate from high school. Of the 58 patients, 30 (51.7%) patients had knowledge about the etiology of their disease. While 12 (20.7%) patients identified their initial symptoms themselves, 75% of the patients reported their symptoms during the clinical history taken by a health care professional. The majority of patients were diagnosed by an endocrinologist (69%). Acromegaly did not affect social life but affected work life and caused early retirement. Transsphenoidal surgery was performed as primary treatment in 96.6% of the patients (n=56). In all, 46 (79.3%) patients received medical treatment with somatostatin receptor ligands (e.g., octreotide or lanreotide long-acting release [LAR]) with or without cabergoline. Overall disease control was achieved in 38 (65.5%) patients. CONCLUSIONS: Acromegaly is usually detected incidentally by clinicians. The diagnosis of acromegaly is delayed in most patients and disease-related complications have already developed at the time of diagnosis. Therefore, increasing the awareness of the society and health care professionals will reduce both disease-related comorbidities and the economic burden on the health system.

Acromegalia por macroadenoma hipofisiario en paciente con síndrome de McCune-Albright. Reporte de caso y revisión de la literatura / Acromegaly due to pituitary macroadenoma in a patient with McCune-Albright syndrome. Case report and literature overview

Introducción: El síndrome de McCune-Albright (SMA) es una enfermedad rara caracterizada por la triada: manchas cutáneas de color café con leche, displasia fibrosa poliostótica y pubertad precoz. Puede afectar a diversos ejes hormonales, entre ellos el de la hormona de crecimiento (GH), pudiendo asociarse a acromegalia. Reporte de caso: describimos el caso de una mujer de 44 años, con pubertad precoz periférica, hemorragia uterina anormal, crecimiento de manos y pies, prognatismo, prominencia frontal, manchas café con leche y tumoraciones pétreas en cara y antebrazos. Resultados: Apoyados con exámenes laboratoriales y de imágenes, se llegaron a los diagnósticos de acromegalia, hipogonadismo hipogonadotropo y síndrome de McCune-Albright. La paciente fue sometida a tratamiento quirúrgico con persistencia de enfermedad clínica y laboratorial. Conclusión: El diagnóstico y tratamiento oportunos de la acromegalia y sus complicaciones brindará un mejor pronóstico a los pacientes con SMA.

Background: McCune-Albright syndrome (MAS) is a rare disease characterized by the triad: café-au-lait skin spots, polyostotic fibrous dysplasia, and precocious puberty. It can affect various hormonal axes, including growth hormone (GH), and may be associated with acromegaly. We describe the case Case report:of a 44-year-old woman with peripheral precocious puberty, abnormal uterinebleeding, growthof thehands and feet, prognathism, frontal prominence, café-au-lait spots, and stony tumorsonthefaceandforearms.Supportedby Results:laboratory and imaging tests, the diagnoses of acromegaly, hypogonadotropic hypogonadism and McCune-Albright syndrome were reached. The patient underwent surgical treatment with persistence of clinical and laboratory disease. Conclusion: Timely diagnosis and treatment of acromegaly and its complications will provide a better prognosis for patients with MAS

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.

Gigantismo acromegaloide. Presentación de un caso

RESUMEN Tanto el gigantismo como la acromegalia pueden deberse a una secreción excesiva de hormona del crecimiento por parte de la hipófisis anterior. Cuando los afectados son jóvenes en edades próximas al cierre de los cartílagos se manifiestan signos y síntomas de gigantismo y de acromegalia. Se presenta el caso de un paciente masculino de 20 años de edad atendido en el Servicio de Endocrinología del Hospital Gustavo Aldereguia Lima de Cienfuegos con manifestaciones clínicas de alta talla, crecimiento acral e hipertensión arterial. Se le realizó prueba de tolerancia oral a la glucosa que midió hormona de crecimiento y confirmó el exceso hormonal. La resonancia magnética contrastada con gadolinio informó macroadenoma hipofisario. Se diagnosticó como gigantismo acromegaloide por un tumor hipofisario productor de hormona del crecimiento. Se realizó exéresis del macroadenoma, con evolución favorable. Es indiscutible la importancia del diagnóstico precoz de esta enfermedad, pues acorta la esperanza de vida, aumenta la mortalidad global no solo por la hipersecreción hormonal, sino también por el efecto de masa del tumor.

ABSTRACT Both gigantism and acromegaly can be due to excessive secretion of growth hormone by the anterior pituitary. When those affected are young, close to cartilage closure, signs and symptoms of gigantism and acromegaly appear. The case of a 20-year-old male patient treated in the Endocrinology Service of the Gustavo Aldereguia Lima Hospital in Cienfuegos with clinical manifestations of tall stature, acral growth and arterial hypertension is presented. An oral glucose tolerance test was performed that measured growth hormone and confirmed the excess of hormones. Gadolinium-enhanced MRI reported pituitary macroadenoma. It was diagnosed as acromegaloid gigantism due to a growth hormone-producing pituitary tumor. The macroadenoma was excised, with a favorable evolution. The importance of early diagnosis of this disease is indisputable, since it shortens life expectancy, increases global mortality not only due to hormonal hypersecretion, but also due to the mass effect of the tumor.

Gamma knife radiosurgery in pituitary adenomas. A single-center experience / Radiocirugía gamma knife en adenomas hipofisarios: experiencia en un centro

Abstract Stereotactic radiosurgery with gamma knife (GKS) is a treatment option for persistent or recurrent pituitary adenoma. The aim of our study was to report Argentine experience in GKS, assessing the efficacy and safety in our patients with pituitary adenomas. We performed a retrospective analysis of patients with pituitary adenomas treated with GKS between 2002 and 2017 in a single institution. Patient characteristics, biochemical remission rate (for functioning tumors), tumor control rate and adverse effects with GKS were inves tigated. The study cohort comprised 99 patients with a mean follow-up of 63 months: 51 somatotropinomas, 28 non-functioning adenomas, 15 corticotropinomas, 2 prolactinomas and 3 mixed pituitary tumors. The mean radiation dose was 30.6Gy for corticotropinomas, 29.3Gy for somatotropinomas and 19.6Gy for non-secreting adenomas. Global tumor control rate was 94.2%. Biochemical remission rate was 55.9%, being higher in acromegaly than in Cushing's disease (OR4.7, 95%Ci 2.1-10.4, p<0.0001). The mean time to remission was 29.5 months (range: 6-156). Hypopituitarism occurred in 26% of patients and those with Cushing's disease were more prone to develop new hormone deficiency after GKS (OR 2.93, 95%Ci 1.2-7.2, p = 0.019). This study shows argentine experience with the use of GKS in patients with pituitary adenomas, with similar results to those reported by centers with large radiosurgical experience. We achieved biochemical remission in more than 50% of patients and global tumor control in most of them. Hypopituitarism was the most frequent adverse effect, while others were infrequent.

Resumen La radiocirugía gamma-knife (GKS) constituye una alternativa de tratamiento en adenomas hipofisarios persis tentes o recurrentes. El objetivo de nuestro trabajo fue comunicar la experiencia argentina con GKS, evaluando eficacia y seguridad en nuestros pacientes con adenomas hipofisarios. Realizamos un análisis retrospectivo de pacientes con adenomas hipofisarios tratados con GKS entre 2002 y 2017. Se investigaron: características basales, tasa de remisión bioquímica, tasa de control tumoral y efectos adversos del GKS. Estudiamos 99 pa cientes adultos con un seguimiento medio de 63 meses: 51 somatotropinomas, 28 adenomas no funcionantes, 15 corticotropinomas, 2 prolactinomas y 3 tumores mixtos. La do sis media de radiación fue 30.6 Gy para cortico tropinomas, 29.3 Gy para somatotropinomas y 19.6 Gy para adenomas no secretores. La tasa global de control tumoral fue 94.2%. La tasa de remisión bioquímica fue 55.9%, si endo mayor en acromegalia que en enfermedad de Cushing (OR4.7, 95% Ci 2.1-10.4, p < 0.0001). El tiempo medio hasta la remisión fue 29.5 meses (rango: 6-156). Se produjo hipopituitarismo en el 26% de los pacientes. Aquellos con enfermedad de Cushing fueron más propensos a desarrollar nuevas deficiencias hormonales después del GKS (OR2.93, 95% Ci 1.2-7.2, p = 0.019). Este trabajo muestra la experiencia argentina con GKS en pacientes con adenomas hipofisarios, con resultados similares a los reportados por centros con amplia experiencia radioquirúrgica. Logramos remisión bioquímica en más del 50% de los pacientes y control tumoral global en la mayoría de ellos. El hipopituitarismo fue el efecto adverso más frecuente, mientras que otros fueron infrecuentes.

Cutis verticis gyrata: a cutaneous finding in acromegaly

Abstract Acromegaly is a rare disease characterized by changes in the bone and soft tissue systems, induced by excess growth hormone and insulin-like growth factor type 1. Among the skin lesions associated with acromegaly is cutis verticis gyrata, an hypertrophic, and coarse folding of the skin of the scalp, an association of uncommon incidence and unknown prevalence. This case report describes the case of a patient diagnosed with acromegaly at age 60 with previously unidentified cutis verticis gyrata. This report aims to review the literature on cutis verticis gyrata and its unusual association with acromegaly.

Value of octreotide suppression test in predicting the efficacy of long-acting somatostatin receptor ligands in pituitary GH adenomas / 中华内分泌代谢杂志

Objective:To explore the value of octreotide suppression test(OST) in predicting the efficacy of somatostatin receptor ligands(SRLs) in the treatment of active acromegaly.Methods:The clinical data of 76 patients with active acromegaly from 2011 to 2020 was retrospectively analyzed. OST was carried out as follows: After an overnight fasting and baseline sampling of growth hormone(GH), 100 μg octreotide was subcutaneously injected, and sampling for GH was obtained every 2 hours for 8 hours. All patients were treated with SRLs for at least 3 months. A good GH response is defined as a post-treatment random GH<1 μg/L or >80% fall compared with the baseline GH. A good insulin-like growth factor Ⅰ(IGF-Ⅰ) response is defined as IGF-Ⅰ<1.3 upper limit of normal(ULN) or >50% reduction compared with the baseline. If both GH and IGF-Ⅰ fulfill the criteria of a good response, it is defined as a good GH and IGF-Ⅰ response.Results:The baseline level of GH during OST was 15.00(6.38, 34.20) μg/L, the median time to reach the nadir GH was(3.65±1.65) hours, and the nadir GH level was 1.47(0.50, 4.19) μg/L. The median GH suppression rate was 89.12%(72.71%, 95.09%). When the cutoff value of GH suppression rate in predicting a good GH response was 89.32%, the area under the curve(AUC) was 0.74, with a sensitivity of 81.80% and specificity of 66.00%. When the cutoff value of GH suppression rate in predicting a good IGF-Ⅰ response was 93.14%, the AUC was 0.64, with a sensitivity of 50.00% and specificity of 75.60%. When the GH suppression rate was 90.71%, the AUC was 0.78, with the sensitivity of 83.30% and specificity of 70.00% in predicting a good GH and IGF-Ⅰ response. Compared with GH/IGF-Ⅰ non-responders, GH/IGF-Ⅰ responders displayed lower nadir GH during OST, higher GH suppression rate and IGF-Ⅰ reduction rate, and lower ratio of IGF-1 to ULN( P<0.05). Conclusion:GH suppression rate during the OST is a valuable predictor to evaluate the efficacy of SRLs in patients with acromegaly, with the highest sensitivity and specificity when the cutoff value is 90.71%.

Effects of somatostatin receptor ligands on bone metabolism in acromegaly / 中华内分泌代谢杂志

Objective:To investigate the effect of somatostatin receptor ligands (SRLs) on bone metabolism in patients with acromegaly.Methods:Retrospective analysis of clinical data of acromegaly patients( n=100) received surgery or SRLs alone for 3 months. The changes of growth hormone (GH), insulin-like growth factor-1 (IGF-1), osteocalcin (OC), N-mid fragment of osteocalcin (N-MID), amino-terminal peptide of type I procollagen (P1NP) and C-terminal peptide degradation product of type I collagen(CTX) were compared before and after treatment. Patients were divided into drug treatment group and surgical group according to treatment methods. According to the decline of GH after medication, patients in the drug treatment group were further divided into drug sensitive group and drug insensitive group. Results:The average dynamic GH and IGF-1 indexes in the drug treatment group were significantly decreased after treatment compared with before treatment (both P<0.05), and CTX was also significantly decreased after treatment [1.25 (0.67, 1.40) ng/mL vs 1.34 (0.57, 1.68) ng/mL, P<0.05]. The mean dynamic GH, IGF-1 index, OC, N-MID, P1NP, and CTX in surgical group were significantly decreased after treatment compared with before treatment (all P<0.01). In the surgical group, there was a positive correlation between GH difference (ΔGH) and N-mid difference (ΔN-MID; r=0.454, P=0.026), and there was a positive correlation between IGF-1 index difference (ΔIGF-1 index) and CTX difference (ΔCTX; r=0.339, P=0.036). After treatment, the mean dynamic GH, IGF-1 index, CTX, P1NP, and N-MID in drug treatment group were significantly higher than those in surgical group (all P<0.001). CTX and N-MID decreased significantly after treatment in drug sensitive group compared with drug insensitive group (35.3% vs 7.2%, P<0.001; 24.1% vs 11.8%, P<0.05), and ΔGH was positively correlated with ΔCTX ( r=0.328, P=0.004). Conclusion:SRLs treatment can reduce bone formation marker N-MID and bone resorption marker CTX, improving the high turnover state of bone metabolism in patients with acromegaly, which may attribute to the reduction of GH and IGF-1 levels.

Acromegalia. A propósito de un caso

RESUMEN La acromegalia es un síndrome clínico producido por la secreción excesiva de hormona del crecimiento que afecta a prácticamente todos los órganos y tejidos. Tiene una baja incidencia (30 a 60 casos por millón de habitantes) y se requiere tener un alto nivel de sospecha por lo que su diagnóstico continúa siendo tardío a pesar de que físicamente los pacientes inician los signos y síntomas entre cinco y diez años previos al diagnóstico. Se presenta el caso de una paciente femenina, de 57 años, atendida en el Servicio de Endocrinología del Hospital Gustavo Aldereguia Lima de Cienfuegos con manifestaciones clínicas de crecimiento acral, hipertensión y diabetes mellitus. Se le realizó prueba de tolerancia oral a la glucosa midiendo hormona de crecimiento que confirmó el exceso hormonal, resonancia magnética contrastada con gadolinio que informó macroadenoma hipofisario. Se diagnosticó como acromegalia por un tumor hipofisario productor de hormona de crecimiento. Es indiscutible la importancia del diagnóstico precoz, dado que su asociación a comorbilidades como la hipertensión y la diabetes es muy importante, lo que resulta en una disminución de la esperanza y la calidad de vida. Estas razones motivaron la presentación del caso.

ABSTRACT Acromegaly is a clinical syndrome caused by excessive secretion of growth hormone that affects virtually all organs and tissues. It has a low incidence (30 to 60 cases per million inhabitants) and a high level of suspicion is required, which is why its diagnosis continues to be late despite the fact that patients physically initiate signs and symptoms between five and ten years prior to the diagnosis. A 57-years-old female patient treated at the Endocrinology Service of the Gustavo Aldereguia Lima Hospital in Cienfuegos with clinical manifestations of acral growth, hypertension and diabetes mellitus it is presented. She underwent an oral glucose tolerance test measuring growth hormone that confirmed hormonal excess, magnetic resonance imaging contrasted with gadolinium that reported pituitary macroadenoma. She was diagnosed as acromegaly from a growth hormone-producing pituitary tumor. The importance of early diagnosis is undoubted, since its association with comorbidities such as hypertension and diabetes is very important, which results in a decrease in hope and quality of life.

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)