Hipertensión arterial secundaria a enfermedad de Cushing. Reporte de Caso / Hypertension secondary to Cushing´s Disease. Report of a clinical case

INTRODUCCIÓN: La Enfermedad de Cushing es una de las causas menos prevalentes de hipertensión arterial secundaria (HTA) (0,7 a 2,4 casos por millón de personas), sin embargo conlleva un aumento de la morbi-mortalidad que se relaciona con el tiempo de exposición al exceso de corticoides 6, lo cual representa un problema debido a que la inespecificidad de los síntomas y su baja prevalencia, llevan a un retraso diagnóstico de 2 a 4 años 6, generando un incremento del riesgo cardiovascular pese a una resolución completa de la enfermedad 6-9. Este artículo tiene como objetivo describir la presentación clínica de la Enfermedad de Cushing como causa de HTA secundaria. CASO CLÍNICO: Paciente femenina de 36 años con HTA de 7 años de evolución, a quien se identificó adenoma hipofisario productor de ACTH, con posterior exéresis transesfenoidal parcial, presentando enfermedad persistente, en quien se optó manejo farmacológico a base de inhibidor de la esteroidogénesis para control de la enfermedad. DISCUSIÓN: La HTA es un problema de salud pública considerado el principal factor de riesgo para discapacidad y muerte prematura 2, con las causas secundarias como responsables de gran afectación en la calidad de vida, tomando en cuenta que estas son potencialmente curables. El manejo de la enfermedad de Cushing (EC) es principalmente quirúrgico 6,13-14, pero en caso de enfermedad persistente existen alternativas para control de la enfermedad 6,15-16, siendo los fármacos inhibidores de la esteroidogénesis los más usados. CONCLUSIONES: La EC es una causa poco frecuente hipertensión arterial secundaria, pero implica un importante compromiso de la calidad de vida, al igual que otras etiologías secundarias, por lo que es fundamental tener en cuenta las características clínicas y bioquímicas que sugieran una etiología secundaria que lleven a un diagnóstico y tratamiento oportunos.

INTRODUCTION: Cushing's Disease is one of the least prevalent causes of secondary hypertension (0.7 to 2.4 cases per million people), however it entails an increase in morbidity and mortality that is related to the chronic exposure of corticosteroids 6, which represents a problem because the no specificity of the symptoms and their low prevalence lead to a diagnostic delay of 2 to 4 years 6, increasing the cardiovascular risk despite complete resolution of the disease 6 -9. The purpose of this article aims to describe the clinical presentation of Cushing Disease (CD) as a cause of secondary hypertension. CLINICAL CASE: 36-year-old female patient with hypertension of 7 years of evolution, in whom an ACTH-producing pituitary adenoma was identified, with subsequent partial transsphenoidal excision, presenting persistent disease, in whom pharmacological management based on a steroidogenesis inhibitor was chosen. for disease control. DISCUSSION: Hypertension is a public health problem, considered the main risk factor for disability and premature death 2, with secondary causes responsible for great impact on quality of life, considering that these are potentially curative. The management of CD is mainly surgical 6,13-14, but in cases of persistent disease there are alternatives to control the disease 6,15-16, with steroidogenesis inhibitor drugs being the most used. CONCLUSIONS: CD is a rare cause of secondary hypertension, but it implies a significant compromise in quality of life, like other secondary etiologies, so it is essential to consider the clinical and biochemical characteristics that suggest a secondary etiology, which can lead to timely diagnosis and treatment.

Correlation analysis of anterior pituitary hormone and tumor size in patients with pituitary adenomas / 中华内科杂志

Objective:To summarize the correlation between anterior pituitary function and tumor size in patients with different hormone-secreting pituitary adenomas.Methods:This was a retrospective case series study. The clinical data of 1 946 patients with pituitary adenoma hospitalized in the First Medical Center of Chinese PLA General Hospital from January 1, 2005, to December 31, 2020, were collected. The correlation between tumor size and anterior pituitary hormone levels was analyzed using Spearman rank correlation analysis in different types of pituitary adenomas.Results:The median age of the 1 946 patients was 45.1 years, of which 857 (44.0%) were men. The maximum tumor diameter of the patients [ M ( Q1, Q3)] was 22 (14, 30) mm. Tumor size in nonfunctioning adenomas ( n=1 191) was negatively correlated with adrenocorticotropic hormone (ACTH) ( r=-0.11, P<0.001), growth hormone ( r=-0.13, P<0.001), and luteinizing hormone (men: r=-0.26, P<0.001, women: r=-0.31, all P<0.001). The tumor size of somatotropic adenomas ( n=297) was positively correlated with growth hormone ( r=0.46, P<0.001), but negatively correlated with male testosterone ( r=-0.41, P<0.001). The tumor size of ACTH-secreting pituitary adenomas ( n=155) was positively correlated with the ACTH level at 8∶00 AM ( r=0.25, P<0.001); however, no correlation was found with cortisol at 8∶00 AM ( P>0.05). The tumor size of prolactinomas ( n=303) was positively correlated with the prolactin level (men: r=0.34, P=0.001; women: r=0.13, P=0.070). Conclusions:The correlation between the function of the anterior pituitary and size of the tumor depends on the cellular origin of the pituitary adenoma and specific type of hormone secretion. In somatotroph adenomas, ACTH-secreting pituitary adenomas, and prolactinomas, there is a positive correlation between tumor size and level of hormones secreted by the corresponding tumors. In patients with nonfunctioning adenomas, the tumor size was negatively correlated with the hormone levels of the pituitary-adrenal and pituitary-growth hormone axes.

Sampling of the petrosal sinuses. Indications, results and usefulness / Muestreo de senos petrosos. Indicaciones, resultados y utilidad

Abstract Objectives: to analyze, evaluate and describe the usefulness of petrosal sinus sampling for diagnosing central Cushing's syndrome. Materials and methods: the technical aspects and results of bilateral venous sampling of the petrosal sinuses at the Hospital Universitario San Vicente de Paul in Medellín, Colombia, from January 1, 2012 to December 31, 2018, were analyzed. Results: the average age was 43.3 years, with a range from 19 to 69 years. Laterality could be shown in 68.2% of cases, with a tendency to be located on the left in 53.3%. The central source of ACTH production could be shown in 95.4% of cases, with a basal average central/peripheral ratio of 21.7, and 70.8 after stimulation. All samples at 3, 5 and 10 minutes were confirmatory following stimulation. Conclusion: in our retrospective study, petrosal sinus catheterization provided laboratory confirmation of the central source of ACTH production in a high percentage of patients, with no immediate complications.

Resumen Objetivos: analizar, evaluar y describir la utilidad del muestreo de senos petrosos para diagnóstico del síndrome de Cushing de origen central. Material y métodos: se analizaron los aspectos técnicos y resultados del muestreo bilateral venoso de senos petrosos, desde el 1° de enero de 2012 a 31 de diciembre de 2018 en el Hospital Universitario San Vicente de Paúl en Medellín, Colombia. Resultados: el promedio de edad fue 43.3 años con un rango de edad desde los 19 hasta los 69 años. La lateralidad pudo ser demostrada en 68.2% de los casos con una tendencia a la localización en el lado izquierdo en 53.3%. El origen central de producción de ACTH logró ser demostrado en 95.4% de los casos, con una relación central/periferia basal promedio de 21.7 y postestimulación de 70.8. Todas las muestras a los 3, 5 y 10 minutos fueron confirmatorias tras la estimulación. Conclusión: en nuestro estudio retrospectivo el cateterismo de senos petrosos confirmó la fuente central de producción de ACTH por laboratorio en un alto porcentaje de pacientes sin ninguna complicación inmediata.

A rare case of duodenal carcinoid presenting as ectopic Cushing’s syndrome

ACTH-dependent Cushing syndrome (CS) due to an ectopic source is responsible for approximately 10-15% cases of Cushing’s syndrome. It is associated with various tumors such as small cell lung cancer and well-differentiated bronchial or gastrointestinal neuroendocrine tumors. Many a times ectopic ACTH production is difficult to manage, and identification of the source may take many years. Hormonal diagnostics include assessments in basic conditions as well as dynamic tests, such as the high-dose dexamethasone suppression test and corticotrophin releasing hormone (CRH) stimulation test. Treatment selection depends on the type of tumor and its extent. In the case of neuroendocrine tumors, the main treatments are surgery and administration of somatostatin analogues or bilateral adrenalectomy in refractory cases and if the source remains unidentified. Here, we report a case who presented with features of Cushing’s syndrome which eventually through workup led us to a diagnosis of duodenal carcinoid producing ectopic ACTH which is extremely rare and was successfully treated.

Effects of Oxytocin on Cell Proliferation in a Corticotroph Adenoma Cell Line

BACKGROUND: Oxytocin (OXT) has been reported to act as a growth regulator in various tumor cells. However, there is a paucity of data on the influence of OXT on cell proliferation of corticotroph adenomas. This study aimed to examine whether OXT affects cell growth in pituitary tumor cell lines (AtT20 and GH3 cells) with a focus on corticotroph adenoma cells. METHODS: Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were conducted with AtT20 cells to confirm the effects of OXT on hormonal activity; flow cytometry was used to assess changes in the cell cycle after OXT treatment. Moreover, the impact of OXT on proliferating cell nuclear antigen (PCNA), nuclear factor κB, and mitogen-activated protein kinase signaling pathway was analyzed by Western blot. RESULTS: OXT treatment of 50 nM changed the gene expression of OXT receptor and pro-opiomelanocortin within a short time. In addition, OXT significantly reduced adrenocorticotropic hormone secretion within 1 hour. S and G2/M populations of AtT20 cells treated with OXT for 24 hours were significantly decreased compared to the control. Furthermore, OXT treatment decreased the protein levels of PCNA and phosphorylated extracellular-signal-regulated kinase (P-ERK) in AtT20 cells. CONCLUSION: Although the cytotoxic effect of OXT in AtT20 cells was not definite, OXT may blunt cell proliferation of corticotroph adenomas by altering the cell cycle or reducing PCNA and P-ERK levels. Further research is required to investigate the role of OXT as a potential therapeutic target in corticotroph adenomas.

Efficacy and safety of pituitary adenomectomy purely endoscopically via a transsphenoidal approach in elderly patients / 中华老年医学杂志

Objective@#To investigate the clinical effect of surgical treatment of pituitary adenoma via neuroendoscopic-assisted transsphenoidal approach in elderly patients.@*Methods@#This was a prospective case-control study.Eighty-five patients with senile pituitary adenoma admitted to our hospital from May 2015 to February 2018 were consecutively enrolled in our study.Patients with pituitary adenoma were divided into the control group(n=42)undergoing conventional microsurgery and the observation group(n=43)receiving microsurgery via neuroendoscopic-assisted transsphenoidal approach.The effect of surgery, perioperative indexes(intraoperative blood loss, operation time, hospitalization time)and the serum level changes of prolactin(PRL), growth hormone(GH)and adrenocorticotropic hormone(ACTH)before and after surgery were recorded and compared between two groups.The incidences of complications in both groups and the dimensions of life quality(physical, cognitive, emotional, social activities)before and after surgery were calculated and assessed.@*Results@#The total effective rate was higher in the observation group(88.4%, 38/43)than in the control group(69.0%, 29/42)(P<0.05). The intraoperative blood loss, operation time and hospital days were less in the observation group than in the control group(P<0.05). No significant differences were found in serum levels of PRL, GH and ACTH between the two groups before and at 3 days after surgery(P>0.05). However, serum levels of PRL, GH and ACTH were deceased in both groups at 3 days after operation compared with before operation.The incidence of complications was lower in the observation group than in the control group(4.7% or 2/43 vs.21.4% or 9/42, P<0.05). The quality of life scores of the cognitive, role, physical, emotional and social dimensions were higher in the observation group than in the control group(P<0.01).@*Conclusions@#Neuroendoscopic-assisted transsphenoidal approach for surgical treatment of senile pituitary adenomas has less intraoperative blood loss, shorter operation time and lower complication rate, improves the endocrine hormone levels and the quality of life, and shortens the hospital stays.

Efficacy and safety of pituitary adenomectomy purely endoscopically via a transsphenoidal approach in elderly patients / 中华老年医学杂志

Objective To investigate the clinical effect of surgical treatment of pituitary adenoma via neuroendoscopic-assisted transsphenoidal approach in elderly patients.Methods This was a prospective case-control study.Eighty-five patients with senile pituitary adenoma admitted to our hospital from May 2015 to February 2018 were consecutively enrolled in our study.Patients with pituitary adenoma were divided into the control group(n=42)undergoing conventional microsurgery and the observation group(n=43)receiving microsurgery via neuroendoscopic-assisted transsphenoidal approach.The effect of surgery,perioperative indexes (intraoperative blood loss,operation time,hospitalization time) and the serum level changes of prolactin (PRL),growth hormone (GH) and adrenocorticotropic hormone(ACTH)before and after surgery were recorded and compared between two groups.The incidences of complications in both groups and the dimensions of life quality(physical,cognitive,emotional,social activities)before and after surgery were calculated and assessed.Results The total effective rate was higher in the observation group(88.4 ％,38/43)than in the control group (69.0 ％,29/42) (P ＜ 0.05).The intraoperative blood loss,operation time and hospital days were less in the observation group than in the control group(P＜0.05).No significant differences were found in serum levels of PRL,GH and ACTH between the two groups before and at 3 days after surgery (P＞0.05).However,serum levels of PRL,GH and ACTH were deceased in both groups at 3 days after operation compared with before operation.The incidence of complications was lower in the observation group than in the control group(4.7％ or 2/43 vs.21.4％ or 9/42,P＜0.05).The quality of life scores of the cognitive,role,physical,emotional and social dimensions were higher in the observation group than in the control group (P ＜ 0.01).Conclusions Neuroendoscopic-assisted transsphenoidal approach for surgical treatment of senile pituitary adenomas has less intraoperative blood loss,shorter operation time and lower complication rate,improves the endocrine hormone levels and the quality of life,and shortens the hospital stays.

Adenoma de hipófisis como forma infrecuente de insuficiencia suprarrenal secundaria. Presentación de un caso / Pituitary Adenoma as a Rare Form of Secondary Adrenal Insufficiency. A Case Report

Los adenomas de hipófisis son tumores benignos originados en uno de los cinco tipos celulares de la hipófisis anterior. La insuficiencia suprarrenal secundaria ocurre cuando las glándulas adrenales no producen hormonas por la falta de hormona adenocorticotrópica hipofisaria o del factor liberador de corticotropina hipotalámico. Se presenta el caso de una paciente de 37 años de edad, que un año atrás comenzó con fasciculaciones musculares de piernas y brazos, debilidad muscular, cansancio fácil, dolores musculares, cefalea hemicránea derecha, intensa y pulsátil, entre otros síntomas. Se le realizaron varios estudios (dosificación de cortisol en sangre, hormona adenocorticotrópica, calcio y fósforo en sangre y orina, resonancia magnética de cráneo) que permitieron el diagnóstico de adenoma de hipófisis con déficit aislado de hormona adenocorticotrópica e insuficiencia suprarrenal secundaria. El tratamiento con esteroides y suplementos de calcio garantizaron la evolución favorable.

Pituitary adenomas are benign tumors arising from one of the five cell types in the anterior pituitary. Secondary adrenal insufficiency occurs when the adrenal glands do not produce hormones due to the lack of pituary adrenocorticotropic hormone or hypothalamic corticotropin-releasing factor. The case of a 37-year-old female patient who started developing muscle twitching in legs and arms, muscular weakness, fatigue, muscle aches, severe and throbbing hemicrania on the right side, among other symptoms, a year ago is presented. Several tests were performed (cortisol level, adrenocorticotropic hormone, calcium and phosphorus in blood and urine, magnetic resonance imaging of the skull), leading to the diagnosis of pituitary adenoma with isolated adrenocorticotropic hormone deficiency and secondary adrenal insufficiency. Treatment with steroids and calcium supplements ensured a satisfactory recovery.

Clinical characteristics of pituitary carcinoma:one case report / 中华神经科杂志

Objective To summarize the clinical features of pituitary carcinoma and discuss the diagnosis,treatment and prognosis.Methods Clinical manifestations,imaging,pathologic features of one case of pituitary carcinoma were analyzed and literatures about diagnosis,treatment and prognosis of pituitary carcinoma were reviewed.Results The patient manifested polyuria onset,headache and anterior pituitary dysfunction and MRI showed pituitary lesions.He had been undergone two transsphenoidal surgery in our hospital,pathologic examinations were respectively non-functioning adenomas and atypical pituitary adenoma and tumor proliferation index (Ki-67) both were more than 30％.He was recommended radiation therapy but refused.Five months later,he was diagnosed as primary pituitary gland cancer due to the tumor widespread intracranial metastasis and no other malignant lesions in body.Conclusions Primary pituitary carcinoma is a very rare tumor,mostly transformed from the invasive pituitary adenoma.It helps predict tumor proliferation and prognosis to test the level of Ki-67 index.Primary pituitary adenocarcinoma needs comprehensive treatment and the prognosis is related to the treatment response.

An Adrenocorticotropic Hormone-secreting Malignant Pancreatic Neuroendocrine Tumor / 대한내과학회지

Pancreatic endocrine tumors are low-to-intermediate-grade neoplasms arising from the pancreatic islets that produce various hormones. These tumors account for a minority of pancreatic tumors and are generally considered functional if they are associated with a hormonal syndrome. Adrenocorticotropic hormone-secreting tumors (ACTHomas) are very rare and require special clinical consideration. Patients with ACTH-secreting tumors usually present with Cushing's syndrome, due to ectopic ACTH production. ACTHomas have a poor prognosis because of early metastasis and difficulty controlling corticosteroid production. We report a 62-year-old male with an ACTH-secreting metastatic pancreatic neuroendocrine tumor, who did not respond to somatostatin analogs and died.

Endocrine Outcome of Endoscopic Endonasal Transsphenoidal Surgery in Functioning Pituitary Adenomas

OBJECTIVE: Microscopic and endoscopic transsphenoidal approach (TSA) are major surgical techniques in the treatment of pituitary adenoma. Endoscopic endonasal transsphenoidal approach (EETSA) has been increasingly used for pituitary adenomas, however, its surgical outcome particularly in functioning pituitary adenoma has been debated. Here, we investigated the endocrine outcome of the patients with growth hormone (GH) and adrenocorticotropic hormone (ACTH) secreting pituitary adenoma treated by EETSA. METHODS: We treated 80 patients with pituitary adenoma by EETSA since 2004, of which 12 patients were affected by functioning pituitary adenomas (9 GH, 3 ACTH, 0 PRL; 9 macro, 3 micro). Surgical outcome of those patients treated by EETSA was compared with that of the 11 functioning pituitary adenoma patients (8 GH, 3 ACTH; 8 macro, 3 micro) who underwent sublabial microscopic TSA between 1997 and 2003. RESULTS: Imaging remission based on postoperative MRI was achieved in 8 (73%) and hormonal remission in 5 (45%) of 11 patients treated by sublabial microscopic TSA. Imaging remission was observed in 10 (83%, p=0.640) and hormonal remission in 10 (83%, p=0.081) of 12 patients by EETSA. CSF leakage was noticed in 2 (17%) of EETSA group and in 2 (18%) of sublabial microscopic TSA group. Panhypopituitarism was observed in 1 (9%) of EETSA group and in 3 (27%) of sublabial microscopic TSA group. CONCLUSION: EETSA appears to be an effective and safe method for the treatment of functioning pituitary adenomas.

A Case of Persistent Cushing's Syndrome

A case of persistent Cushing's syndrome in a 25 year-old male is presented. Inspite of bilateral total adrenalectomy twice during two years, there was no clinical improvement. Adrenal scanning revealed no adrenal remnants. ACTH secreting pituitary microadenoma is demonstrated by computed tomographic brain scan and hormonal studies. Selective transsphenoidal microadenomectomy results in clinical and endocrinological improvement.

A Case of Persistent Cushing's Syndrome

A case of persistent Cushing's syndrome in a 25 year-old male is presented. Inspite of bilateral total adrenalectomy twice during two years, there was no clinical improvement. Adrenal scanning revealed no adrenal remnants. ACTH secreting pituitary microadenoma is demonstrated by computed tomographic brain scan and hormonal studies. Selective transsphenoidal microadenomectomy results in clinical and endocrinological improvement.