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Feline hypersomatotropism (HST) is typically associated with diabetes mellitus (DM), whereas HST without concurrent DM has only been reported in a few cases. Weight gain may be observed in cats with HST. The aims of this study were to evaluate circulating insulin-like growth factor-1 (IGF-1) in non-diabetic cats with overweight/obesity, to screen this population for the presence of HST, and to assess whether there is a correlation between body weight/body condition score (BCS) and serum IGF-1 concentration in overweight/obese cats. In this prospective study, 80 overweight/obese cats from referral centers in Buenos Aires (Argentina) were evaluated. Serum IGF-1 was measured as part of the routine tests for overweight/obesity. Non-diabetic cats were included in the study if they had a BCS>6/9. Twenty-nine cats were classified as overweight (BCS 7/9), whereas 51 were classified as obese (BCS 8-9/9). Median serum IGF-1 concentrations of cats with BCS 7/9, 8/9, and 9/9 were 570 ng/ml (range 123-1456 ng/ml), 634 ng/ml (range 151-1500 ng/ml), and 598 ng/ml (range 284-2450 ng/ml), respectively. There was a positive linear correlation between serum IGF-1 concentrations and body weight (r= 0.24, 95% CI 0.01-0.44 P=0.03), and between IGF-1 and BCS (r= 0.27, 95% CI 0.08-0.44 P=0.004). In total, 8.75% (95% confidence interval 3.6-17.2%) of the cats with overweight/obesity had IGF-1 concentrations >1000 ng/ml. Pituitary enlargement was detected on computed tomography in 4/7 cases. These seven cats showed varying degrees of phenotypic changes consistent with acromegaly. A proportion of 8.75 % of overweight/obese non-diabetic cats from referral centers in Buenos Aires had serum IGF-1 concentration in a range consistent with HST in diabetic cats. Likewise, 5% of overweight/obese cats were likely to be diagnosed with HST, supported by evidence of pituitary enlargement. Serum IGF-1 concentrations were positively correlated with body weight and BCS in this population of cats. This study highlights the relevance of screening different populations of non-diabetic cats to increase the detection of HST/acromegaly.

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OBJECTIVE: Acromegaly is a disorder associated with excessive levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). In general, GH/IGF-1 excess leads to morphologic craniofacial and acral changes as well as cardiometabolic complications, but the phenotypic changes and clinical presentation of acromegaly differ across species. Here, we review the pathophysiology, clinical presentation and management of acromegaly in humans and cats, and we provide a systematic comparison between this disease across these different species. DESIGN: A comprehensive literature review of pathophysiology, clinical features, diagnosis and management of acromegaly in humans and in cats was performed. RESULTS: Acromegaly is associated with prominent craniofacial changes in both species: frontal bossing, enlarged nose, ears and lips, and protuberant cheekbones are typically encountered in humans, whereas increased width of the head and skull enlargement are commonly found in cats. Malocclusion, prognathism, dental diastema and upper airway obstruction by soft tissue enlargement are reported in both species, as well as continuous growth and widening of extremities resulting in osteoarticular compromise. Increase of articular joint cartilage thickness, vertebral fractures and spine malalignment is more evident in humans, while arthropathy and spondylosis deformans may also occur in cats. Generalized organomegaly is equally observed in both species. Other similarities between humans and cats with acromegaly include heart failure, ventricular hypertrophy, diabetes mellitus, and an overall increased cardiometabolic risk. In GH-secreting pituitary tumours, local compressive effects and behavioral changes are mostly observed in humans, but also present in cats. Cutis verticis gyrata and skin tags are exclusively found in humans, while palmigrade/plantigrade stance may occur in some acromegalic cats. Serum IGF-1 is used for acromegaly diagnosis in both species, but an oral glucose tolerance test with GH measurement is only useful in humans, as glucose load does not inhibit GH secretion in cats. Imaging studies are regularly performed in both species after biochemical diagnosis of acromegaly. Hypophysectomy is the first line treatment for humans and cats, although not always available in veterinary medicine. CONCLUSION: Acromegaly in humans and cats has substantial similarities, as a result of common pathophysiological mechanisms, however species-specific features may be found.

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Previously, radioimmunoassay (RIA) has been the only assay to measure insulin-like growth factor-1 (IGF-1) to diagnose hypersomatotropism (HS). Due to radiation concerns, availability, and the cost of IGF-1 RIA, validation of assays for automated analysers such as a chemiluminescent immunoassay (CLIA) is needed. The aim of this study was to validate a CLIA for measurement of feline IGF-1 (IMMULITE 2000® XPi, Siemens Medical Solutions Diagnostics, Malvern, PA, USA) compared to IGF1 RIA, establish reference interval (RI), and determine a cut-off value for diagnosis of HS in diabetic cats. Validation of assay performance included precision, linearity, and recovery studies. Right-sided RI was determined using surplus serum of 50 healthy adult cats. Surplus serum samples of diabetic cats with known IGF-1 concentration with (n = 32/68) and without HS (n = 36/68) were used for method comparison with RIA. The cut-off for diagnosis of HS was established using receiver operating characteristic (ROC) analysis. The intra-assay coefficient of variation (CV) was ≤4.7%, and the inter-assay CV was ≤5.6% for samples with low, medium, and high IGF-1 concentration. Linearity was excellent (R2 > 0.99). The correlation between CLIA and RIA was very high (rs = 0.97), with a mean negative bias for CLIA of 24.5%. The upper limit of RI was 670 ng/mL. ROC analysis showed an area under the curve of 0.94, with best cut-off for diagnosis of HS at 746 ng/mL (sensitivity, 84.4%; specificity, 97.2%). The performance of CLIA was good, and the RI and cut-off for HS diagnosis established in this study allow for CLIA to be used in routine work-up of diabetic cats.

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True insulin resistance should be differentiated from management-related difficulties (eg, short insulin duration, inappropriate insulin injection, inappropriate storage). Hypersomatotropism (HST) is the number one cause of insulin resistance in cats, with hypercortisolism (HC) occupying a more distant second place. Serum insulinlike growth factor-1 is adequate for screening for HST, and screening at the time of diagnosis, regardless of presence of insulin resistance, is advocated. Treatment of either disease centers on removal of the overactive endocrine gland (hypophysectomy, adrenalectomy) or inhibition of the pituitary or adrenal glands by using drugs such as trilostane (HC), pasireotide (HST, HC) or cabergoline (HST, HC).

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OBJECTIVES: The aim of this study was to estimate the prevalence of hypersomatotropism (HST) and hyperthyroidism in cats with diabetes mellitus (DM) from referral centers in Buenos Aires, Argentina. METHODS: This was a prospective study. Systematic screening of serum insulin-like growth factor 1 (IGF-1) and total thyroxine was performed in all cats diagnosed with DM at referral centers in Buenos Aires between February 2020 and February 2022. RESULTS: In total, 154 diabetic cats were evaluated (99 males and 55 females; median age 12 years [range 3-21]; mean body weight 5 kg [range 2-12]). Altogether, there were 115 (75%) domestic shorthairs and one domestic longhair; the remaining 38 cats were purebred (mainly Siamese, n = 25 [16%]). Twenty (12.9%) cats had IGF-1 concentrations >1000 ng/ml, and three (1.9%) had IGF-1 concentrations between 800 and 1000 ng/ml along with pituitary enlargement on CT, resulting in a 14.9% HST prevalence rate in diabetic cats. Intracranial imaging was performed in all cats with HST; median pituitary dorsoventral height was 5.8 mm (range 3.1-9.5). Fourteen of 23 (61%) cats had phenotypic changes consistent with acromegaly at the time of diagnosis of HST. Four of 154 (2.5%) cats had concurrent hyperthyroidism. CONCLUSIONS AND RELEVANCE: To date, this is the first study outside of Europe to have evaluated the prevalence of HST and hyperthyroidism in cats with DM. In Buenos Aires referral centers, feline HST is the most common concurrent endocrinopathy in cats with DM but with a lower prevalence than has previously been reported. Hyperthyroidism is a rare concurrent endocrinopathy in diabetic cats from referral centers in Buenos Aires.

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CASE SUMMARY: Three diabetic cats presented with polyuria, polydipsia, polyphagia and poor glycemic control. Cat 1 displayed prognathia inferior and had a body condition score (BCS) of 4/5; cat 2 had a BCS of 5/5; and cat 3 had broad facial features. Serum insulin-like growth factor 1 concentrations were compatible with hypersomatotropism in cat 1 and cat 2 (>1500 ng/ml and 1200 ng/ml, respectively) and just below the cut-off of 1000 ng/ml (947 ng/ml) in cat 3; in this last cat diagnosis was further supported by the presence of pituitary enlargement on MRI. Oral cabergoline (10 µg/kg q48h) was initiated. Insulin requirements progressively reduced, as evidenced by daily blood glucose monitoring and weekly blood glucose curves. Diabetic remission occurred in all three cats between the second and third months of cabergoline treatment. At the time of writing, remission has persisted thus far (cat 1: 23 months; cat 2: 14 months; cat 3: 38 months). RELEVANCE AND NOVEL INFORMATION: To our knowledge, these are the first reported cases of diabetic remission in cats with hypersomatotropism after cabergoline treatment, despite previous reports of this being an ineffective treatment. Further work is indicated to determine why some cats do, and others do not, respond to this treatment.

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Acromegaly is an endocrine disease that leads to elevated production and secretion of growth hormone (GH). It can occur in adult and aged cats and is usually associated with neoplasms, such as functional pituitary macroadenoma of somatotropic cells. In dogs it is usually related to an increase in serum progesterone that induces production of GH by the mammary glands. The main clinical signs are related to insulin resistance and the anabolic effect induced by GH: polyuria, polydipsia, polyphagia, increased tissue growth, weight gain, prognathism, and other changes. The condition can be diagnosed from clinical signals and imaging associated to measurement of serum concentrations of GH and insulin-like growth factor 1 (IGF-1, also known as somatomedin C). The main therapeutic modalities are radiotherapy, hypophysectomy, and several drugs such as somatostatin analogs, dopaminergic agonists and GH receptor antagonists. The present review aims to provide a relevant animal model of acromegaly with an update on the therapeutic approach that may help clinicians to consider the GH axis-IGF-1 system, its pathogenesis and the clinical signs induced by this hormonal disorder.

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Pituitary tumours are common in dogs and are being increasingly recognized in cats. Pituitary tumours are usually classified as adenomas and should only be classified as carcinomas when there is evidence of metastatic spread of the tumour, which is rare. Despite the benign nature of most pituitary tumours, they can still compress or invade neighbouring tissues. Pituitary tumours can be functional (hormonally active) or non-functional (hormonally silent). The aim of this review was to provide an overview of the different pituitary tumour types in dogs and cats that have been reported in the literature. In dogs, the most common pituitary tumour type is the corticotroph adenoma, which can cause pituitary-dependent hypercortisolism. In cats, the most common pituitary tumour is the somatotroph adenoma, which can cause hypersomatotropism, and the second-most common is the corticotroph adenoma. A lactotroph adenoma has been described in one dog, while gonadotroph, thyrotroph and null cell adenomas have not been described in dogs or cats. Hormonally silent adenomas are likely underdiagnosed because they do not result in an endocrine syndrome. Tools used to classify pituitary tumours in humans, particularly immunohistochemistry for lineage-specific transcription factors, are likely to be useful to classify canine and feline pituitary tumours of unknown origin. Future studies are required to better understand the full range of pituitary adenoma pathology in dogs and cats and to determine whether certain adenoma subtypes behave more aggressively than others. Currently, the mechanisms that underlie pituitary tumorigenesis in dogs and cats are still largely unknown. A better understanding of the molecular background of these tumours could help to identify improved pituitary-targeted therapeutics.

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OBJECTIVES: The aim of the study was to document whether a proportion of non-diabetic cats with left ventricular hypertrophy (LVH) previously diagnosed with hypertrophic cardiomyopathy (HCM) have elevated circulating insulin-like growth factor 1 (IGF-1) concentrations. METHODS: A retrospective analysis of residual blood samples obtained at the time of echocardiographic diagnosis of HCM from a population of 60 non-diabetic cats were analysed for circulating IGF-1 concentrations using a validated radioimmunoassay and compared with a control group of 16 apparently healthy cats without LVH. Clinical and echocardiographic data for cats with an IGF-1 level >1000 ng/ml were compared with those with an IGF-1 level <800 ng/ml. RESULTS: In total, 6.7% (95% confidence interval 1.8-16.2%) of cats with HCM had an IGF-1 level >1000 ng/ml. The prevalence of an IGF-1 level >1000 ng/ml in the control group was zero. CONCLUSIONS AND RELEVANCE: A small proportion of non-diabetic cats previously diagnosed with HCM had an IGF-1 concentration at a level that has been associated with feline hypersomatotropism (fHS) in the diabetic cat population. Further prospective research is required to confirm or refute the presence of fHS in non-diabetic cats with LVH and increased IGF-1.

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Pituitary glands from 141 feline autopsy cases were reviewed histologically. Adenoma and hyperplasia were the most common lesions at 13 cases each. Pituitary adenoma was more likely than hyperplasia to be associated with clinical evidence of endocrinopathy or an intracranial mass (P < .001). A histochemical and immunohistochemical panel was applied to 44 autopsy- or hypophysectomy-derived pituitary adenomas in 43 cats from 2 diagnostic laboratories. Adenomas were differentiated from hyperplasia by the presence of disrupted reticulin fibers. One cat had a double (somatotroph and melanotroph) adenoma. Twenty somatotroph adenomas consisted of periodic acid-Schiff (PAS)-negative acidophils that expressed growth hormone; 16/20 had hypersomatotropism; 17/20 had diabetes mellitus. Eleven melanotroph adenomas consisted of PAS-positive basophils or chromophobes that expressed melanocyte-stimulating and adrenocorticotrophic hormones; 5/11 had hypercortisolism; 6/11 had diabetes mellitus. Eleven gonadotroph adenomas consisted of PAS-negative chromophobes that expressed follicle-stimulating and/or luteinizing hormones. Two thyrotroph adenomas consisted of PAS-negative basophils or chromophobes that expressed thyroid-stimulating hormone. Pituitary-dependent disease was not recognized in cats with gonadotroph or thyrotroph adenomas. The Ki-67 proliferation index in hypophysectomy specimens was lower in somatotroph than in melanotroph adenomas. Fourteen cats with hypophysectomy-treated somatotroph or melanotroph adenoma had an 899-day median survival time versus 173 days in 17 nonsurgical cases. After adjusting for age, adenoma size and type, hypophysectomized cats had an overall better survival time than nonsurgical cases (P = .029). The study results underscore the value of hypophysectomy and trophic hormone immunohistochemistry in the treatment and classification of feline pituitary adenomas.

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CASE SUMMARY: A 17-year-old neutered male European Shorthair cat was presented owing to an inability to jump and respiratory stridor. The owner did not report any other clinical signs. On physical examination, the main findings were plantigrade stance, broad facial features and inspiratory stridor. Neurological examination revealed posterior paraparesis, hypotonia and right hindlimb muscle atrophy. Laboratory findings were unremarkable and glycaemia was normal. Serum insulin-like growth factor 1 concentration was elevated (>1000 ng/ml). A total body CT scan showed an enlarged pituitary gland, thickening of the nasal turbinates and an L7-S1 right foraminal stenosis. Electrodiagnostic testing confirmed the presence of a neuropathy affecting both sciatic nerves. The cat was treated with gabapentin only and was still alive and euglycaemic 16 months after the diagnosis. RELEVANCE AND NOVEL INFORMATION: This case describes for the first time sciatic neuropathy, an occasional complication of acromegaly in people, as a possible clinical presentation in acromegalic cats without concurrent diabetes mellitus.

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The prevalence of GH-secreting pituitary tumors in domestic cats (Felis catus) is 10-fold greater than in humans. The predominant inhibitory receptors of GH-secreting pituitary tumors are somatostatin receptors (SSTRs) and D2 dopamine receptor (DRD2). The expression of these receptors is associated with the response to somatostatin analog and dopamine agonist treatment in human patients with acromegaly. The aim of this study was to describe pathological features of pituitaries from domestic cats with acromegaly, pituitary receptor expression, and investigate correlates with clinical data, including pituitary volume, time since diagnosis of diabetes, insulin requirement, and serum IGF1 concentration. Loss of reticulin structure was identified in 15 of 21 pituitaries, of which 10 of 15 exhibited acinar hyperplasia. SSTR1, SSTR2, SSTR5, and DRD2 mRNA were identified in the feline pituitary whereas SSTR3 and SSTR4 were not. Expression of SSTR1, SSTR2, and SSTR5 was greater in acromegalic cats compared with controls. A negative correlation was identified between DRD2 mRNA expression and pituitary volume. The loss of DRD2 expression should be investigated as a mechanism allowing the development of larger pituitary tumors.

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Transsphenoidal surgery is an option for dogs and cats with functional and nonfunctional pituitary masses or other sellar and parasellar masses. An adrenocorticotropic hormone-secreting tumor causing Cushing disease is the most common clinically relevant pituitary tumor in dogs, and the most common pituitary tumor seen in cats is a growth hormone-secreting tumor causing acromegaly. Transsphenoidal surgery can lead to rapid resolution of clinical signs and provide a cure for these patients. Because of the risks associated with this surgery, it should only be attempted by a cohesive pituitary surgery group with a sophisticated medical and surgical team.

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Abstract Anamnesis: Three cats diagnosed with diabetes mellitus (DM) were referred for examination due to the presence of insulin resistance signs, which included polyuria, polydipsia, polyphagia and high fructosamine levels, even with insulin glargine doses greater than 2 U/Kg/application. Clinical and laboratory findings: All patients had enlarged facial features along with increased interdental space. The biochemical tests revealed high IGF-1 concentrations. The magnetic resonance imaging displayed enlarged pituitary gland in one of the cats and images compatible with a pituitary macroadenoma in the other two. Acromegaly was the final diagnosis. Treatment approach: Oral cabergoline at 10 µg/Kg every 48 h was administered. Conclusion: The treatment with cabergoline successfully decreased IGF-1 concentrations and all insulin resistance signs, and it enhanced glycemic control for the DM in the three cats. Our results suggest cabergoline could be used for the treatment of acromegaly in cats.

Resumen Anamnesis: Tres gatos diagnósticados con diabetes mellitus (DM) fueron referidos para ser examinados debido a la presencia de signos de resistencia a la insulina, que incluían poliuria, polidipsia, polifagia, y de valores elevados de fructosamina, incluso con dosis de insulina glargina mayor a 2 U/Kg/aplicación. Hallazgos clínicos y de laboratorio: Los tres gatos presentaron amplios rasgos faciales con aumento de los espacios interdentales. En la bioquímica sanguínea, la concentración de IGF-1 fue hallada elevada. La imagen por resonancia magnética mostró agrandamiento de la glándula hipófisis en uno de los gatos, e imágenes compatibles con un macroadenoma de hipófisis en los otros dos. El diagnóstico final fue de acromegalia. Abordaje terapéutico: Se administraron 10 µg/Kg de cabergolina cada 48 h, via oral. Conclusión: El tratamiento con cabergolina logró disminuir las concentraciones de IGF-1 y todos los signos de resistencia a la insulina con mejor control glucémico de la DM en los tres gatos. Los anteriores hallazgos sugieren que la cabergolina es una opción viable para el tratamiento de la acromegalia en gatos.

Resumo Anamnese: Três gatos diagnosticados com diabetes mellitus (DM) foram encaminhados para exame devido à presença de sinais de resistência à insulina, que incluíram poliúria, polidipsia, polifagia e altos níveis de fructosamina, mesmo com doses de insulina glargina superiores a 2 U/Kg/aplicação. Achados clínicos e de laboratório: Os três gatos apresentavam mudanças dos rasgos faciais e aumento do espaço interdental. As provas bioquímicas revelaram altas concentrações de IGF-1. A ressonância magnética mostrou incremento do tamanho da glândula pituitária em um dos gatos e imagens compatíveis com um macroadenoma pituitário nos outros dois. Com estes dados chegou-se ao diagnóstico de acromegalia. Enfoque terapêutico: Foram dadas 10 µg/Kg de cabergolina a cada 48 h, via oral. Conclusão: O tratamento com cabergolina diminuiu com sucesso as concentrações de IGF-1 e todos os sinais de resistência à insulina e aumentou o controlo glicémico para a DM nos três gatos. Conclusões anteriores evidenciam que a cabergolina é uma opção viável para o tratamento da acromegalia em gatos.

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Acromegaly in humans is usually sporadic, however up to 20% of familial isolated pituitary adenomas are caused by germline sequence variants of the aryl-hydrocarbon-receptor interacting protein (AIP) gene. Feline acromegaly has similarities to human acromegalic families with AIP mutations. The aim of this study was to sequence the feline AIP gene, identify sequence variants and compare the AIP gene sequence between feline acromegalic and control cats, and in acromegalic siblings. The feline AIP gene was amplified through PCR using whole blood genomic DNA from 10 acromegalic and 10 control cats, and 3 sibling pairs affected by acromegaly. PCR products were sequenced and compared with the published predicted feline AIP gene. A single nonsynonymous SNP was identified in exon 1 (AIP:c.9T > G) of two acromegalic cats and none of the control cats, as well as both members of one sibling pair. The region of this SNP is considered essential for the interaction of the AIP protein with its receptor. This sequence variant has not previously been reported in humans. Two additional synonymous sequence variants were identified (AIP:c.481C > T and AIP:c.826C > T). This is the first molecular study to investigate a potential genetic cause of feline acromegaly and identified a nonsynonymous AIP single nucleotide polymorphism in 20% of the acromegalic cat population evaluated, as well as in one of the sibling pairs evaluated.

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La acromegalia es una enfermedad crónica multisistémica, de baja prevalencia, cuyo diagnóstico y tratamiento deben adecuarse a las realidades actuales. No obstante, continúa siendo una enfermedad subdiagnosticada, que evoluciona con una elevada tasa de mortalidad, generalmente por causas cardiovasculares y cerebrovasculares, lo cual reduce la esperanza de vida de la persona que la padece. En el presente artículo se describen las formas de presentación del hipersomatotropismo, los métodos de diagnóstico y las modalidades terapéuticas, que incluyen la quirúrgica, la farmacológica y la radioterapia.

Acromegaly is a multisystem chronic disease, of low prevalence which diagnosis and treatment should be adapted to the current realities. Nevertheless, it continues being an underdiagnosed disease with a clinical course of high mortality rate, generally due to cardiovascular and cerebrovascular causes, which reduce the life expectancy of the person suffering it. In this work, the forms of presentation of hypersomatotropism, the methods of diagnosis and the therapeutic modalities are described, that include the surgical one, the pharmacological one and the radiotherapy.

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La acromegalia puede estar asociada a cáncer de pulmón, mama, próstata, colon y tiroides. entre los más importantes. La colonoscopía permite la detección temprana de pólipos adenomatosos, cuya localización predominante es el colon descendente. El hipersomatotrofismo activa mecanismos tumorogénicos: apoptosis, proliferación celular y angiogénesis. Ello puede inducir la transformación maligna de los pólipos intestinales. El incremento del ácido deoxycólico del líquido biliar de los acromegálicos, puede estimular la proliferación y transformación de las células del epitelio colónico. El dolicocolon y el codo pronunciado del colon sigmoideo de estos pacientes retardan el tránsito intestinal, prolonga la exposición al mencionado ácido, aumentando así, la predisposición de los pólipos a su degeneración maligna. El 45-50 % de los pólipos son visualizados en el colon descendente y generalmente exceden los 10 mm. El carcinoma de colon afecta aproximadamente al 5,5 % de los acromegálicos, siendo generalmente diagnosticados a una edad promedio de 65 años y con un tiempo de evolución mayor de 5 años. Frecuentemente presentan tres o más manchas dérmicas ("skin tags"). Su presencia puede orientar hacia un diagnóstico precoz de esta complicación. La somatostatina es capaz de modificar la cinética celular del epitelio intestinal. Si bien, no se ha visualizado mediante la colonoscopía una sensible mejoría, se ha observado que la administración del análogo octreotide, induce una estabilización de la evolución tumoral en el 45 % de los enfermos. Conclusión: Prolongar la sobrevida de los acromegálicos requiere, entre otras medidas de prevención, un seguimiento clínico y colonoscópico periódico. Este debe ser realizado con intervalos de tiempo adecuados, ya que el tratamiento precoz de esta patología intestinal es primordial. El autor declara no poseer conflictos de interés.(AU)

Acromegaly can be associated with lung, breast, prostate, colon and thyroid cancers, among the most impor-tant malignancies. Colonoscopy allows for an early detection of adenomatous polyps, which are most commonly found in the descending colon. Hypersomatotrophism activates important tumorigenic mechanisms: apoptosis, increased cell proliferation and angiogenesis. These histological and structural changes may lead to the transformation of benign polyps into malignant carcinomas of the colon. Increased deoxycholic acid in the bile in acromegalic subjects can stimulate the proliferation and transformation of colonic epithelial cells. The presence of a redundant colon and the pronounced sigmoid flexure delay gastrointestinal transit, thus increasing the time of exposure to this acid. This increases the susceptibility of polyps to malignancy. From 45 to 50 % of polyps detected by colonoscopy are found in the descending colon and, in general, they are larger than 10 mm in diameter. Colon cancer affects approximately 5.5 % of subjects with acromegaly, being diagnosed at an average age of 65 years and with a history of disease longer than 5 years. These patients frequently have 3 or more skin tags. Their presence may lead to an early diagnosis of this complication. Somatostatin may affect the cell kinetics of the intestinal epithelium. Even if no considerable improvement in the tumor lesions has been viewed on colonoscopy, stabilization of tumor progression has been seen in 45 % of those patients who were treated with high doses of somatostatin analog, octreotide. Conclusion. In order to extend acromegalic patients survival, regular colonoscopy follow-up, among other measures, should be performed at appropriate intervals, since an early treatment of this disease is vital. No financial conflicts of interest exist.(AU)

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La acromegalia puede estar asociada a cáncer de pulmón, mama, próstata, colon y tiroides. entre los más importantes. La colonoscopía permite la detección temprana de pólipos adenomatosos, cuya localización predominante es el colon descendente. El hipersomatotrofismo activa mecanismos tumorogénicos: apoptosis, proliferación celular y angiogénesis. Ello puede inducir la transformación maligna de los pólipos intestinales. El incremento del ácido deoxycólico del líquido biliar de los acromegálicos, puede estimular la proliferación y transformación de las células del epitelio colónico. El dolicocolon y el codo pronunciado del colon sigmoideo de estos pacientes retardan el tránsito intestinal, prolonga la exposición al mencionado ácido, aumentando así, la predisposición de los pólipos a su degeneración maligna. El 45-50 % de los pólipos son visualizados en el colon descendente y generalmente exceden los 10 mm. El carcinoma de colon afecta aproximadamente al 5,5 % de los acromegálicos, siendo generalmente diagnosticados a una edad promedio de 65 años y con un tiempo de evolución mayor de 5 años. Frecuentemente presentan tres o más manchas dérmicas ("skin tags"). Su presencia puede orientar hacia un diagnóstico precoz de esta complicación. La somatostatina es capaz de modificar la cinética celular del epitelio intestinal. Si bien, no se ha visualizado mediante la colonoscopía una sensible mejoría, se ha observado que la administración del análogo octreotide, induce una estabilización de la evolución tumoral en el 45 % de los enfermos. Conclusión: Prolongar la sobrevida de los acromegálicos requiere, entre otras medidas de prevención, un seguimiento clínico y colonoscópico periódico. Este debe ser realizado con intervalos de tiempo adecuados, ya que el tratamiento precoz de esta patología intestinal es primordial. El autor declara no poseer conflictos de interés.

Acromegaly can be associated with lung, breast, prostate, colon and thyroid cancers, among the most impor-tant malignancies. Colonoscopy allows for an early detection of adenomatous polyps, which are most commonly found in the descending colon. Hypersomatotrophism activates important tumorigenic mechanisms: apoptosis, increased cell proliferation and angiogenesis. These histological and structural changes may lead to the transformation of benign polyps into malignant carcinomas of the colon. Increased deoxycholic acid in the bile in acromegalic subjects can stimulate the proliferation and transformation of colonic epithelial cells. The presence of a redundant colon and the pronounced sigmoid flexure delay gastrointestinal transit, thus increasing the time of exposure to this acid. This increases the susceptibility of polyps to malignancy. From 45 to 50 % of polyps detected by colonoscopy are found in the descending colon and, in general, they are larger than 10 mm in diameter. Colon cancer affects approximately 5.5 % of subjects with acromegaly, being diagnosed at an average age of 65 years and with a history of disease longer than 5 years. These patients frequently have 3 or more skin tags. Their presence may lead to an early diagnosis of this complication. Somatostatin may affect the cell kinetics of the intestinal epithelium. Even if no considerable improvement in the tumor lesions has been viewed on colonoscopy, stabilization of tumor progression has been seen in 45 % of those patients who were treated with high doses of somatostatin analog, octreotide. Conclusion. In order to extend acromegalic patients survival, regular colonoscopy follow-up, among other measures, should be performed at appropriate intervals, since an early treatment of this disease is vital. No financial conflicts of interest exist.

RESUMEN

La acromegalia es una enfermedad poco frecuente producida en más del 95% de los casos por un tumor hipofisario secretor de hormona de crecimiento (GH). Las manifestaciones clínicas están asociadas a síntomas locales por crecimiento del tumor o a las consecuencias orgánicas y metabólicas secundarias a la hipersecreción de GH. Debido a la alta morbilidad y mortalidad asociadas a la acromegalia, un tratamiento individualizado y optimizado para cada paciente es fundamental. Informamos el enfoque terapéutico de nuestro servicio de endocrinología en la atención de 154 pacientes con acromegalia. Utilizando criterios bioquímicos estrictos, con la cirugía logramos un 32% de remisión global, tasa relativamente baja debido fundamentalmente a que la mayor parte de los pacientes presentaban macroadenomas con un alto porcentaje de invasividad local. Con radioterapia complementaria o como tratamiento inicial se logró la remisión en el 65.4% de los pacientes irradiados. El 14.0% de los pacientes controlaron la enfermedad utilizando agonistas dopaminérgicos solos o combinados con otra droga, mientras que aquellos que utilizaron análogos de la somatostatina normalizaron los parámetros bioquímicos en un 45.7% de los casos. En conclusión, con los diferentes tratamientos utilizados obtuvimos el control de la acromegalia en el 55.2% de los casos, esperando optimizar el tratamiento de estos pacientes en la medida en que contemos con y tengamos acceso a nuevas herramientas terapéuticas.

Acromegaly is a chronic, invalidating disease due in over 95% of cases to a growth hormone (GH) secreting pituitary adenoma. Its clinical manifestations are associated to local complications related to the tumor growth and/or to the metabolic consequences of GH excess. We report here our experience on 154 acromegalic patients. Surgical remission rate using stringent biochemical criteria was 32%, a figure relatively low due to the great number of patients bearing macroadenomas with invasive complications. Primary or adjuvant radiotherapy was able to obtain normalization of biochemical parameters in as much as 65.4% of treated patients. In only 14.0% of acromegalics drug therapy with dopaminergic agents was effective in controlling the disease. By contrast, somatostatinergic analogues were more effective, obtaining a clinical and biochemical remission in 45.7% of the patients. In summary, multimodal therapy of acromegaly can lead to a global safe control of the disease in 55.2% of the cases. The ongoing development of new drugs represents promising alternatives in the management of this disabling condition.

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