Increased risk of preneoplastic colonic lesions and colorectal carcinoma in acromegaly: multicenter case-control study.

PURPOSE: Current international guidelines recommend colonoscopy in patients with acromegaly at the time of diagnosis, even though the risk of developing colorectal neoplasm is still controversial. The main objective of this Argentine multicenter study was to analyze through screening colonoscopy the presence of advanced neoplastic lesions considered as precancerous, in patients with acromegaly compared to a control group. METHODS: This is a case-control retrospective study. Full length colonoscopy of 70 acromegalic patients and 128 control subjects were studied. Polyps were classified into non pre-cancerous lesions and advance neoplastic lesions which included advanced adenomas (preneoplastic) and colorectal carcinomas. RESULTS: Thirty three out of 70 acromegalic patients and 32 out of 128 subjects controls presented polyps in the colonoscopy [47.1% vs 25%, p = 0.002, OR 2.68]. Non precancerous polyps were found in 11 (15.7%) and 23 (17.9%) (p = 0.690), while advanced neoplastic lesions were found in 22 (31.4%) and 9 (7.0%) (p = 0,0001 - OR: 6.06) patients and controls respectively. Advanced adenomas and colorectal carcinomas were found in 18 (27.3%) and 9 (7.0%) (p = 0,0006-OR: 4,57), and 4 (5.7%) and 0 (0.0%) p = 0.0063) of patients and controls respectively. The presence of insulin resistance was the only statistically significant associated factor among acromegalic patients with and without colonic polyps. CONCLUSIONS: Our findings show an increased risk of preneoplastic colonic lesions and colorectal carcinoma in patients with chronic and sustained GH excess compared to a control group. This supports the recommendation to perform screening colonoscopy at diagnosis of acromegaly.

Comparison of two immunoassays in the determination of IGF-I levels and its correlation with oral glucose tolerance test (OGTT) and with clinical symptoms in acromegalic patients.

The aim of our study was to evaluate two different methodologies in IGF-I levels determination, its correlation with GH nadir in OGTT <1 and <0.4 ng/ml and with clinical symptoms in acromegalic patients. We analyzed 37 patients. Sixteen patients had not undergone any kind of treatment (Group 1). Twenty-one patients underwent surgery as primary treatment, and after that, some of them another kind of treatment (except pegvisomant) (Group 2). Serum IGF-I levels were measured by Immulite-1000 (IMM) and by an immunoradiometric assay (DSL) and, GH by immunochemiluminometric assay. IGF-I levels by IMM and by DSL showed a significant difference. When we analyzed in both groups the concordance by crosstabs-Kappa coefficients, between different parameters, GH nadir <1 and <0.4 ng/ml with IGF-I by DSL and IMM showed concordance in group 1, but in group 2 only GH nadir <1 and <0.4 ng/ml had a weak concordance with IGF-I by IMM. When we analyzed clinical symptoms in the patients and, GH nadir <1 and <0.4 ng/ml and IGF-I levels by both methodologies, more than 90% of clinically active patients had abnormal GH response or/and elevated IGF-I levels in group 1, but less than 70% in group 2. In the 8 patients under medical treatment, GH nadir was higher than 0.4 ng/ml in all patients, and IGF-I levels were elevated in 8/8 by DSL and in 6/8 by IMM. In conclusion, discrepant GH and IGF-I levels in the diagnosis and follow-up of patients with acromegaly requires consideration of many factors that influence these parameters.

Effects of cabergoline on pregnancy and embryo-fetal development: retrospective study on 103 pregnancies and a review of the literature.

The aim of the study is to assess the rate of any potential adverse effects on women who became pregnant under cabergoline (CAB) treatment and to evaluate any effects on the embryo-fetal development and on children who were born from mothers exposed to CAB in early weeks of gestation. Observational, retrospective and multicenter study on 103 pregnancies in 90 women with hyperprolactinemia. All patients were under CAB at conception. Serum prolactin at baseline was between 30 and 1921 ng/ml. Duration of therapy before pregnancy ranged from 1 to 120 months and doses ranged from 0.125 to 5 mg/week. Fetal exposure ranged from 3 to 25 weeks, 96.9% of patients received CAB during the first trimester of pregnancy and the rest until the second one. No significant complications during pregnancy were found. Seven women (7.2%) had spontaneous abortions. Preterm deliveries were recorded in eight (8.8%), only one with low weight for gestational age. Neonatal abnormalities were observed in 3 (3.6%): 1 major (Down syndrome) and 2 minor malformations (umbilical and inguinal hernia). We were able to asses the children's development in 61. Two had epilepsy and two had Pervasive Developmental Disorder (PDD). No significantly higher frequency of complications was found in pregnancies and/or offspring exposed to CAB than in the normal population. We registered 2 abnormalities in the development of the children: epilepsy and PDD. Larger series of patients are needed to assess the safety of this drug during pregnancy.

[Coexistence of acromegaloidism and lung cancer]. / Coexistencia de acromegaloidismo y cáncer de pulmón.

Acromegaloidism is a condition characterized by features of acromegaly without biochemical evidence of excessive growth hormone (GH) production. Insulin resistance is one of the possible etiologies. We report the case of a patient with acromegalic features, a left lung neoplastic process, generalized acanthosis nigricans and severe insulin resistance. Normal IGF 1 and GH inhibition below 1 ng/ml by the oral glucose tolerance test ruled out the diagnosis of acromegaly. Acanthosis nigricans (AN) may be present as a paraneoplastic syndrome or may be associated to benign pathology in which insulin resistance is involved. Acromegaloidism has been reported in patients with severe insulin resistance as we are describing here. It is possible that very high insulin levels can stimulate excessive acral growth acting through insulin receptors that retain the ability to mediate anabolic effects, or alternatively through the IGF1 receptor. We found no data of acromegaloidism as a paraneoplastic syndrome. To summarize, we report a case of severe insulin resistance, pseudoacromegaly and AN, coexisting with a lung carcinoma. Acromegaloidism and AN appear to be due to insulin resistance, even though in this patient we cannot exclude that AN could be a paraneoplastic syndrome.

Invasive giant prolactinoma with loss of therapeutic response to cabergoline: expression of angiogenic markers.

The present study reports the case of a 70-year-old Caucasian man who was referred to the Military Hospital of Buenos Aires for evaluation of a giant sellar-extrasellar mass with extension in the right temporal lobe and compression of the third ventricle. Patient was initially responsive to cabergoline with reduction of prolactin levels and shrinkage of tumor burden for at least 36 months. Thereafter, prolactin levels and tumor size increased even though cabergoline dosage was increased. Transcraneal surgery was performed at 56 months of treatment. Prolactin levels and tumor proliferation did not subside and the patient died 14 months later. High GH and IGF-I levels were observed in the late stages of tumor development, with no evidence of acromegalic features. Immunohistochemistry of the excised tumor revealed strong immunoreactivity for VEGF and FGF-2, two potent angiogenic factors, and CD31 (an endothelial marker) indicating high vascularization of the adenoma.

[Pituitary adenomas in elderly patients]. / Adenomas hipofisarios en pacientes añosos.

Clinical presentation, treatment and its results were evaluated during long-term follow-up of 37 patients older than 65 years with pituitary adenoma. Causes of death were also evaluated. It was a retrospective and cross-sectional study. Prevalence of incidentalomas was 43% (16), macroadenomas 70.3% (26) and giant adenomas 16.2% (6). The most frequent tumor phenotype was the non-functioning adenoma (76%). The prevalence of visual field defects and neurological symptoms was 56% and 57% respectively. We found normal pituitary function in 54%, partial deficiency in 30% and panhypopituitarism in 16%. Thirty-two patients were treated, 5 were lost to follow-up without receiving treatment. Surgery was indicated in 18. Of those operated by trans-sphenoidal approach, 23% had postsurgical complications and 54% improved the visual field. By trans-craneal approach, 50% had post-surgical complications and 33% visual field improvement. During follow-up (55.1 ± 48.7 months) no tumor regrowth was observed, except in a giant adenoma. Four operated patients died, two due to causes related to tumor. Fourteen were not operated, 11 with non-functioning adenoma and normal visual field were periodically controlled and 3 with secreting adenomas received medical treatment. No tumor growth was observed during follow-up (43.7 ± 38.0 months). We did not observe tumor progression in elderly patients with non-functioning adenoma and normal visual field, so we suggest watchful approach and periodic control. When there are visual field defects, trans-sphenoidal surgery can be considered safe and effective. In secreting adenomas and depending on the associated comorbidities, medical treatment would be the appropriate approach.

Se evaluó la presentación clínica, tratamiento y sus resultados durante el seguimiento prolongado de 37 pacientes mayores de 65 años con adenomas hipofisarios, y sus causas de muerte. El estudio fue retrospectivo y transversal. La prevalencia de incidentalomas fue 43% (16), macroadenomas 70.3% (26) y adenomas gigantes 16.2% (6). El fenotipo tumoral más frecuente fue el adenoma no funcionante (76%). La prevalencia de alteraciones en el campo visual y síntomas neurológicos fue 56% y 57% respectivamente. El 54% tuvo función hipofisaria normal, deficiencia parcial el 30% y panhipopituitarismo el 16%. Fueron tratados 32, 5 se perdieron en el seguimiento sin recibir tratamiento. Indicamos cirugía en 18. De los operados por vía transesfenoidal, el 23% tuvo complicaciones postquirúrgicas y el 54% mejoría del campo visual. Por vía transcraneal el 50% sufrió complicaciones post quirúrgicas y el 33% mejoró el campo visual. Durante el seguimiento (55.1 ± 48.7 meses) no observamos recrecimiento tumoral, excepto en un adenoma gigante. Cuatro pacientes operados murieron, dos por causas al tumor. Catorce no fueron operados, 11 con adenomas no funcionantes y campo visual normal fueron controlados periódicamente y 3 con adenomas funcionantes recibieron tratamiento médico. No observamos crecimiento tumoral durante el seguimiento (43.7 ± 38.1 meses). No observamos crecimiento tumoral en adenomas no funcionantes y campo visual normal, por lo que sugerimos conducta expectante y control periódico. Cuando existe alteración del campo visual, la cirugía transesfenoidal es segura y efectiva. En los adenomas secretantes y dependiendo de las comorbilidades, sería apropiado optar por tratamiento médico.

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

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.

Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families.

CONTEXT: An association between germline aryl hydrocarbon receptor-interacting protein (AIP) gene mutations and pituitary adenomas was recently shown. OBJECTIVE: The objective of the study was to assess the frequency of AIP gene mutations in a large cohort of patients with familial isolated pituitary adenoma (FIPA). DESIGN: This was a multicenter, international, collaborative study. SETTING: The study was conducted in 34 university endocrinology and genetics departments in nine countries. PATIENTS: Affected members from each FIPA family were studied. Relatives of patients with AIP mutations underwent AIP sequence analysis. MAIN OUTCOME MEASURES: Presence/absence and description of AIP gene mutations were the main outcome measures. INTERVENTION: There was no intervention. RESULTS: Seventy-three FIPA families were identified, with 156 patients with pituitary adenomas; the FIPA cohort was evenly divided between families with homogeneous and heterogeneous tumor expression. Eleven FIPA families had 10 germline AIP mutations. Nine mutations, R16H, G47_R54del, Q142X, E174frameshift, Q217X, Q239X, K241E, R271W, and Q285frameshift, have not been described previously. Tumors were significantly larger (P = 0.0005) and diagnosed at a younger age (P = 0.0006) in AIP mutation-positive vs. mutation-negative subjects. Somatotropinomas predominated among FIPA families with AIP mutations, but mixed GH/prolactin-secreting tumors, prolactinomas, and nonsecreting adenomas were also noted. Approximately 85% of the FIPA cohort and 50% of those with familial somatotropinomas were negative for AIP mutations. CONCLUSIONS: AIP mutations, of which nine new mutations have been described here, occur in approximately 15% of FIPA families. Although pituitary tumors occurring in association with AIP mutations are predominantly somatotropinomas, other tumor types are also seen. Further study of the impact of AIP mutations on protein expression and activity is necessary to elucidate their role in pituitary tumorigenesis in FIPA.

Prolactinomas: evolution after menopause.

OBJETIVE: The aim was to assess the evolution of tumor size and prolactin (PRL) levels in patients with micro and macroprolactinomas diagnosed and treated with dopamine agonists during fertile age, and the effects of suspension of drugs after menopause. SUBJECTS AND METHODS: Retrospective study, 29 patients with prolactinomas, 22 microadenomas and 7 macroadenomas, diagnosed during their fertile age were studied in their menopause; treatment was stopped in this period. Age at menopause was 49 ± 3.6 years. The average time of treatment was 135 ± 79 months. The time of follow-up after treatment suspension was 4 to 192 months. Results: Pre-treatment PRL levels in micro and macroadenomas were 119 ± 57 ng/mL and 258 ± 225 ng/mL, respectively. During menopause after treatment suspension, and at the latest follow-up: in microadenomas PRL levels were 23 ± 13 ng/mL and 16 ± 5.7 ng/mL, respectively; in macroadenomas, PRL levels were 20 ± 6.6 ng/mL 5t5and 25 ± 18 ng/mL, respectively. In menopause after treatment suspension, the microadenomas had disappeared in 9/22 and had decreased in 13/22. In the group of patients whose tumor had decreased, in the latest follow-up, tumors disappeared in 7/13 and remained unchanged in 6/13. In macroadenomas, after treatment suspension 3/7 had disappeared, 3/7 decreased and 1/7 remained unchanged. In the latest control in the 3 patients whose tumor decreased, disappeared in 1/3, decreased in 1/3 and there was no change in the remaining. CONCLUSIONS: Normal PRL levels and sustained reduction or disappearance of adenomas were achieved in most of patients, probably due to the decrease of estrogen levels. Dopamine agonists might be stopped after menopause in patients with prolactinomas.

Adenomas hipofisarios en pacientes añosos / Pituitary adenomas in elderly patients

Se evaluó la presentación clínica, tratamiento y sus resultados durante el seguimiento prolongado de 37 pacientes mayores de 65 años con adenomas hipofisarios, y sus causas de muerte. El estudio fue retrospectivo y transversal. La prevalencia de incidentalomas fue 43% (16), macroadenomas 70.3% (26) y adenomas gigantes 16.2% (6). El fenotipo tumoral más frecuente fue el adenoma no funcionante (76%). La prevalencia de alteraciones en el campo visual y síntomas neurológicos fue 56% y 57% respectivamente. El 54% tuvo función hipofisaria normal, deficiencia parcial el 30% y panhipopituitarismo el 16%. Fueron tratados 32, 5 se perdieron en el seguimiento sin recibir tratamiento. Indicamos cirugía en 18. De los operados por vía transesfenoidal, el 23% tuvo complicaciones postquirúrgicas y el 54% mejoría del campo visual. Por vía transcraneal el 50% sufrió complicaciones post quirúrgicas y el 33% mejoró el campo visual. Durante el seguimiento (55.1 ± 48.7 meses) no observamos recrecimiento tumoral, excepto en un adenoma gigante. Cuatro pacientes operados murieron, dos por causas al tumor. Catorce no fueron operados, 11 con adenomas no funcionantes y campo visual normal fueron controlados periódicamente y 3 con adenomas funcionantes recibieron tratamiento médico. No observamos crecimiento tumoral durante el seguimiento (43.7 ± 38.1 meses). No observamos crecimiento tumoral en adenomas no funcionantes y campo visual normal, por lo que sugerimos conducta expectante y control periódico. Cuando existe alteración del campo visual, la cirugía transesfenoidal es segura y efectiva. En los adenomas secretantes y dependiendo de las comorbilidades, sería apropiado optar por tratamiento médico.

Clinical presentation, treatment and its results were evaluated during long-term follow-up of 37 patients older than 65 years with pituitary adenoma. Causes of death were also evaluated. It was a retrospective and cross-sectional study. Prevalence of incidentalomas was 43% (16), macroadenomas 70.3% (26) and giant adenomas 16.2% (6). The most frequent tumor phenotype was the non-functioning adenoma (76%). The prevalence of visual field defects and neurological symptoms was 56% and 57% respectively. We found normal pituitary function in 54%, partial deficiency in 30% and panhypopituitarism in 16%. Thirty-two patients were treated, 5 were lost to follow-up without receiving treatment. Surgery was indicated in 18. Of those operated by trans-sphenoidal approach, 23% had postsurgical complications and 54% improved the visual field. By trans-craneal approach, 50% had post-surgical complications and 33% visual field improvement. During follow-up (55.1 ± 48.7 months) no tumor regrowth was observed, except in a giant adenoma. Four operated patients died, two due to causes related to tumor. Fourteen were not operated, 11 with non-functioning adenoma and normal visual field were periodically controlled and 3 with secreting adenomas received medical treatment. No tumor growth was observed during follow-up (43.7 ± 38.0 months). We did not observe tumor progression in elderly patients with non-functioning adenoma and normal visual field, so we suggest watchful approach and periodic control. When there are visual field defects, trans-sphenoidal surgery can be considered safe and effective. In secreting adenomas and depending on the associated comorbidities, medical treatment would be the appropriate approach.

Pituitary adenomas in elderly patients

Clinical presentation, treatment and its results were evaluated during long-term follow-up of 37 patients older than 65 years with pituitary adenomas. Causes of death were also evaluated. It was a retrospective and cross-sectional study. Prevalence of incidentalomas was 43% (16), macroadenomas 70.3% (26) and giant adenomas 16.2% (6). The most frequent tumor phenotype was the non-functioning adenoma (76%). The prevalence of visual field defects and neurological symptoms was 56% and 57%, respectively. We found normal pituitary function in 54%, partial deficiency in 30% and panhypopituitarism in 16%. Thirty-two patients were treated, 5 were lost to follow-up without receiving treatment. Surgery was indicated in 18. Of those operated by trans-sphenoidal approach, 23% had postsurgical complications and 54% improved the visual field. By trans-craneal approach, 50% had post-surgical complications and 33% visual field improvement. During follow-up (55.1 ± 48.7 months) no tumor regrowth was observed, except in a giant adenoma. Four operated patients died, two due to causes related to tumor. Fourteen were not operated, 11 with non-functioning adenomas and normal visual field were periodically controlled, and 3 with secreting adenomas received medical treatment. No tumor growth was observed during follow-up (43.7 ± 38.1 months). We did not observe tumor progression in elderly patients with non-functioning adenomas and normal visual field, so we suggest watchful approach and periodic control. When there are visual field defects, trans-sphenoidal surgery can be considered safe and effective. In secreting adenomas and depending on the associated comorbidities, medical treatment would be the appropriate approach.

Se evaluó la presentación clínica, tratamiento y sus resultados durante el seguimiento prolongado de 37 pacientes mayores de 65 años con adenomas hipofisarios, y sus causas de muerte. El estudio fue retrospecti vo y transversal. La prevalencia de incidentalomas fue 43% (16), macroadenomas 70.3% (26) y adenomas gigantes 16.2% (6). El fenotipo tumoral más frecuente fue el adenoma no funcionante (76%). La prevalencia de alteraciones en el campo visual y síntomas neurológicos fue 56% y 57% respectivamente. El 54% tuvo función hipofisaria normal, deficiencia parcial el 30% y panhipopituitarismo el 16%. Fueron tratados 32, 5 se perdieron en el seguimiento sin recibir tratamiento. Indicamos cirugía en 18. De los operados por vía transesfenoidal, el 23% tuvo complicaciones postquirúrgicas y el 54% mejoría del campo visual. Por vía transcraneal el 50% sufrió complicaciones post quirúrgicas y el 33% mejoró el campo visual. Durante el seguimiento (55.1 ± 48.7 meses) no observamos recrecimiento tumoral, excepto en un adenoma gigante. Cuatro pacientes operados murieron, dos por causas al tumor. Catorce no fueron operados, 11 con adenomas no funcionantes y campo visual normal fueron controlados periódicamente y 3 con adenomas funcionantes recibieron tratamiento médico. No observamos crecimiento tumoral durante el seguimiento (43.7 ± 38.1 meses). No observamos crecimiento tumoral en adenomas no funcionantes y campo visual normal, por lo que sugerimos conducta expectante y control periódico. Cuando existe alteración del campo visual, la cirugía transesfenoidal es segura y efectiva. En los adenomas secretantes y dependiendo de las comorbilidades, sería apropiado optar por tratamiento médico.

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

Riesgo aumentado de lesiones colónicas preneoplásicas en acromegalia: estudio multicéntrico caso control. Resultados preliminares / Increased risk of pre-cancerous bowel lesions in acromegaly: Multicentre case-control study. Preliminary results

Introducción: El riesgo de desarrollar neoplasias colónicas en pacientes acromegálicos y su relación directa con los niveles elevados de GH/IGF-1 no están bien establecidos y continúan siendo motivo de controversia en la literatura mundial. El objetivo de este trabajo fue evaluar el riesgo de desarrollar lesiones neoplásicas avanzadas (LNA) (adenomas mayores a 1 cm, componente velloso mayor del 75% y/o displasia de alto grado), en pacientes con acromegalia, comparado con un grupo control. Materiales y métodos: Estudio multicéntrico caso-control retrospectivo. Ciento treinta y siete pacientes con acromegalia que realizaron videocolonoscopia (VCC) fueron incluidos inicialmente, aunque solo 69 cumplieron criterios de inclusión. Sesenta y dos controles fueron obtenidos: por cada caso (paciente con acromegalia) 2 «controles¼ fueron seleccionados aleatorizadamente e igualados por edad y sexo. El riesgo se expresó en odds ratio (OR) y su correspondiente intervalo de confianza (IC) del 95%. La significación estadística fue considerada una p < 0,05. Resultados: De los 69 pacientes con VCC completa y datos adecuados para su análisis, 28 presentaron VCC positiva con hallazgos de pólipos (40%) y 41 VCC negativa o normal (60%). Dentro del grupo con VCC positiva, 14 presentaron LNA (20%) y solo un paciente presentó diagnóstico de cáncer colorrectal. Para el análisis caso-control se incluyó a 31 pacientes frente al grupo control (n = 62) que cumplieron con los criterios de inclusión. La presencia de pólipos colónicos, adenomas y LNA en los pacientes con acromegalia fue de 19/31 (61,9%), 14/31 (45,16%) y 10/31 (32,25%), y en el grupo control de 18/62 (29,03%), 11/62 (17,74%) y 4/62 (6,45%), respectivamente. El riesgo de adenomas y LNA fue mayor en el grupo de acromegalia en comparación con el grupo control, siendo ambos resultados estadísticamente significativos: adenomas OR 2,54 (IC 1,22-5,25) p = 0,005, LNA OR: 7,3 (2,4-25), p = 0,00. Conclusión: La acromegalia se asocia a un mayor riesgo de lesiones colónicas preneoplásicas. Este hallazgo justifica el cribado con VCC al diagnóstico en pacientes con acromegalia.

Background: The risk of developing cancerous lesions in the colon of acromegaly patients and their direct relationship with elevated growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels is not well established, and is still controversial in the international literature. The objective of this study was to evaluate the risk of developing advanced neoplastic lesions (ALN: greater than 1 cm adenomas, villous component greater than 75% and/or high grade dysplasia) in patients with acromegaly compared to a control group. Materials and methods: A multicentre, retrospective case-control study was conducted initially on 137 patients with acromegaly (cases) who underwent videocolonoscopy (VCC), although only 69 met inclusion criteria. Sixty-two controls were obtained, and for each case two "controls" were randomly selected and matched by age and gender. Risk was expressed as odds ratio (OR) and its corresponding 95% con"dence interval (CI). P values < .05 were considered statistical significantly. Results: Of the 69 acromegaly patients with a completed VCC and adequate data for their analysis, 28 had a positive VCC with findings of polyps (40%), and 41 VCC negative with no lesions (60%). Within the group with positive VCC, 14 were ALN (20%) and one a colorectal cancer. In the case-control analysis, 31 cases were to be analysed against the control group (n = 62). The presence of colonic polyps, adenomas, and ALN in patients with acromegaly was 19/31 (61.9%), 14/31 (45.16%), and 10/31 (32.25%), respectively, and in the control group, it was 18/62 (29.03%), 11/62 (17.74%), and 4/62 (6.45%), respectively. The risk of adenomas and ALN was higher in the acromegaly group compared to the control group: adenomas OR: 2.54 (95% CI 1.22-5.25) P=.005, ALN OR: 7.3 (2.4-25) P=.00. Conclusion: This preliminary case control study showed an increased risk of pre-cancerous colprectal lesions in patients with acromegaly, supporting the VCC screening at diagnosis.

Prolactinomas: evolution after menopause

ABSTRACT Objetive The aim was to assess the evolution of tumor size and prolactin (PRL) levels in patients with micro and macroprolactinomas diagnosed and treated with dopamine agonists during fertile age, and the effects of suspension of drugs after menopause. Retrospective study, 29 patients with prolactinomas, 22 microadenomas and 7 macroadenomas, diagnosed during their fertile age were studied in their menopause; treatment was stopped in this period. Age at menopause was 49 ± 3.6 years. The average time of treatment was 135 ± 79 months. The time of follow-up after treatment suspension was 4 to 192 months. Results Pre-treatment PRL levels in micro and macroadenomas were 119 ± 57 ng/mL and 258 ± 225 ng/mL, respectively. During menopause after treatment suspension, and at the latest follow-up: in microadenomas PRL levels were 23 ± 13 ng/mL and 16 ± 5.7 ng/mL, respectively; in macroadenomas, PRL levels were 20 ± 6.6 ng/mL 5t5and 25 ± 18 ng/mL, respectively. In menopause after treatment suspension, the microadenomas had disappeared in 9/22 and had decreased in 13/22. In the group of patients whose tumor had decreased, in the latest follow-up, tumors disappeared in 7/13 and remained unchanged in 6/13. In macroadenomas, after treatment suspension 3/7 had disappeared, 3/7 decreased and 1/7 remained unchanged. In the latest control in the 3 patients whose tumor decreased, disappeared in 1/3, decreased in 1/3 and there was no change in the remaining. Conclusions Normal PRL levels and sustained reduction or disappearance of adenomas were achieved in most of patients, probably due to the decrease of estrogen levels. Dopamine agonists might be stopped after menopause in patients with prolactinomas.

Coexistencia de acromegaloidismo y cáncer de pulmón / Coexistence of acromegaloidism and lung carcinoma

El acromegaloidismo es una entidad en la cual se encuentran presentes algunos rasgos acromegálicos sin evidencia bioquímica de hipersecreción de hormona de crecimiento (GH), siendo la resistencia insulínica una de las posibles etiologías. Se presenta un paciente con rasgos acromegálicos, proceso neoplásico en pulmón izquierdo, acantosis nigricans (AN) generalizada y marcada resistencia a la insulina (IR). Se descartó acromegalia ante la presencia de una IGF1 normal y GH < 1 ng/ml a los 120 min en el test de tolerancia oral a la glucosa (TTOG). La acantosis nigricans puede presentarse como síndrome paraneoplásico (SPN) o puede estar asociada a enfermedad benigna en la cual está involucrada la insulinorresistencia (IR). El acrome-galoidismo está descripto en pacientes con IR grave como el caso que estamos presentando, postulándose que niveles muy elevados de insulina podrían estimular el crecimiento tisular o acral actuando a través del receptor de insulina que conservaría el mecanismo de mediar efectos anabólicos, o alternativamente a través del receptor de IGF1. No encontramos en la literatura la presencia de acromegaloidismo como SPN. En conclusión, presentamos un paciente con IR grave, pseudoacromegalia y AN, coexistiendo con un cáncer de pulmón. Tanto el acromegaloidismo como la AN parecen ser consecuencia de la marcada hiperinsulinemia. Aún así, no podemos descartar que la AN pudiera corresponder a un SPN.

Acromegaloidism is a condition characterized by features of acromegaly without biochemical evidence of excessive growth hormone (GH) production. Insulin resistance is one of the possible etiologies. We report the case of a patient with acromegalic features, a left lung neoplastic process, generalized acanthosis nigricans and severe insulin resistance. Normal IGF 1 and GH inhibition below 1 ng/ml by the oral glucose tolerance test ruled out the diagnosis of acromegaly. Acanthosis nigricans (AN) may be present as a paraneoplastic syndrome or may be associated to benign pathology in which insulin resistance is involved. Acromegaloidism has been reported in patients with severe insulin resistance as we are describing here. It is possible that very high insulin levels can stimulate excessive acral growth acting through insulin receptors that retain the ability to mediate anabolic effects, or alternatively through the IGF1 receptor. We found no data of acromegaloidism as a paraneoplastic syndrome. To summarize, we report a case of severe insulin resistance, pseudoacromegaly and AN, coexisting with a lung carcinoma. Acromegaloidism and AN appear to be due to insulin resistance, even though in this patient we cannot exclude that AN could be a paraneoplastic syndrome.

Pituitary stalk tuberculoma.

Pituitary tuberculomas are exceptionally rare. Even with no evidence of systemic tuberculosis, it is important to recognize these lesions in the differential diagnosis of the intrasuprasellar tumors because they are curable. At present, in developed countries the frequency of intracranial tuberculomas of nervous system tumors is around 0.5-4%, whereas in under developed countries is 15-30%. It mainly affects children and young adults. In some cases, an accurate diagnosis may lead to an efficient medical therapy on the basis of biological, hormonal and imaging scans examinations. The case we studied shows the difficulties encountered in the diagnosis of a thickened stalk having normal pituitary image. It is to be highlighted the usage of the Polymerase Chain Reaction (PCR) technique.

Retrospective multicentric study of pituitary incidentalomas.

Previously unsuspected pituitary tumors (incidentalomas) were analyzed in autopsies (4.8-27%) and magnetic resonance imaging (MRI) (10-37%), most of them being micro-pituitary incidentalomas (PI). However, patients with PIs sometimes had macroadenomas which may relate to previously unsuspected neurological and/or endocrine abnormalities. This study aims to establish the incidence of macro- vs. micro-PIs, the need for medical and/or surgical treatment and the neurological and endocrine dysfunction in a retrospective evaluation of patients with PIs studied over six years (1994-2000). Thirty-eight of 46 patients with PIs (22 males), aged 16-77, were followed for a mean of 3.2 years. Initial hormonal testing, ophthalmologic evaluation and MRI were repeated during follow-up. Twenty-nine (63%) of 46 patients had macro-PIs and 17 (17%) micro-PIs. Twenty-three males (75%) had macro-PIs, 10 (34.5%) with visual field defects. Consultations leading to PI diagnosis were chronic headache (28%), cranial trauma (15.3%), sinusitis (13%) and stroke (13%). Partial deficiencies of the anterior pituitary function were confirmed in 19 PIs (41.3%), with secondary hypogonadism prevailing (30%). Seven PIs (15%) were prolactinomas treated with dopamine agonists. Seventeen PIs (37%) underwent surgery. Immunohistochemical analysis showed gonadotrophinomas (30%), plurihormonal non-secreting adenomas (40%), and pituitary adenomas not reacting to any of the anterior pituitary hormone antibodies (30%). One operated macro-PI was a craniopharyngioma. Our data show a high percentage of PIs are macro-incidentalomas against expectations from necropsy and imaging studies. Most macro-PIs are found in males and are clinically non-functioning adenomas, 37% requiring surgery and hormonal substitution.

Hipopituitarismo originado por metastasis de carcinoma de colon asociado con aspergilosis hipofisaria / Hypopituitarism originating to colonic carcinoma metastasis associated with hypophysial aspergillosis

Las metástasis hipofisiarias constituyen el 1 al 8,3 por ciento del total de tumores metastásicos cerebrales. La localización más frecuente es en el lóbulo posterior y la diabetes insípida puede ser el único síntoma de disfunción. La aspergilosis cerebral es una enfermedad inusual y ha sido descripta complicando una malignidad preexistente, o posteriormente a una cirugía intracraneal. Describimos un hipopituitarismo e hiperprolactinemia en una paciente quien presentó metástasis hipofisarias de un carcinoma de colon y aspergilosis coexistente. Dos años antes, se le había resecado un adenocarcinoma de colon (clase Cl de Duke). Ningún signo clínico de hipopituitarismo o galactorrea estaban presentes. Los hallazgos de laboratorio reflejan déficit de corticotrofina (ACTH), hormona luteinizante (LH), hormona folículo estimulante (FSH), y una leve hiperprolactinemia (PRL). Una resonancia magnética cerebral reveló una massa intra y supraselar la cual se extendía a hipotálamo. La radiografía de tórax y la tomografía computada confirmó una massa macronodular en el segmento apical del lóbulo pulmonar inferior izquierdo con nódulos hipertróficos meidastinales. Fue diagnosticado un tumor hipofisario no funcionante realizándose cirugía transfenoidal. El examen microscópico confirmó una proliferación maligna que sugería diferenciación colónica. Fragmentos de tejido ipofisário tumoral mostraron hifas de aspergilus formando abscesos. La aspergilosis como complicación de enfermedades neoplásicas, es mayor en leucemias y linfomas que en tumores sólidos. El diagnóstico de aspergilosis del SNC es dificultoso, siendo éste generalmente confirmado durante la necropsia. Esta localización puede aparecer como parte de una aspergilosis diseminada, o como una infección única del SNC, aunque la mayoría de los casos está asociada a una aspergilosis pulmonar. Hasta la fecha, no hemos encontrado publicada la asociación de hipopituitarismo y moderada hiperprolactinemia cuya etiología fue metástasis hipofisaria de carcinoma de colon y aspergilosis coexistente