Cushing's syndrome caused by intra-adrenocortical adrenocorticotropic hormone in a dog.

A 13-year-old Labrador retriever was diagnosed with Cushing's syndrome (CS) caused by primary bilateral nodular adrenocortical hyperplasia with adrenocorticotropic hormone (ACTH) expression. The pituitary origin of CS was ruled out by suppression of plasma ACTH concentration and absence of a proliferative lesion on histological evaluation of the pituitary gland using periodic acid-Schiff (PAS) staining, reticulin staining, and immunostaining for ACTH. A pheochromocytoma also was found at necropsy examination. On histological evaluation of both adrenal glands, at the junction of the fascicular and glomerular zones, multiple cell clusters distributed in both hyperplastic adrenal cortices expressed ACTH, whereas the pheochromocytoma cells did not. These results indicate that a disease similar to primary bilateral macronodular adrenocortical hyperplasia in humans also occurs in dogs, with intra-adrenocortical expression of ACTH, glucocorticoids excess, and clinical signs of CS. Therefore, the term ACTH-independent could be inappropriate in some cases of bilateral adrenocortical hyperplasia and suppressed plasma ACTH concentration in dogs.

Adrenal cortex stimulation with hCG in spayed female dogs with Cushing's syndrome: Is the LH-dependent variant possible?

Background: The expression and overexpression of luteinizing hormone (LH) receptors in the canine adrenal gland cortex have been reported. Therefore, it was hypothesized that a LH-dependent form of Cushing's syndrome (CS) could exist in dogs. Aim: To assess whether the adrenal gland post-ovariectomy (OVx) exhibits a greater response to adrenocorticotrophin (ACTH) stimulation; to evaluate whether the adrenal gland responds to human chorionic gonadotropin (hCG) stimulation by increasing the release of cortisol; and to consider whether hCG stimulus testing would be useful as a diagnosis for possible cases of LH-dependent CS. Methods: Cortisol concentrations were measured from healthy female dogs (n=16) at baseline and following ACTH stimulation before and 2 months after gonadectomy (OVx). Cortisol concentrations were also measured for female dogs with CS (n = 14) following administration of hCG (5000 IU). A post-hCG cortisol concentration greater than 140 nmol/l was used to define dogs with LH-dependent Cushing's syndrome. Results: In normal female dogs, both pre- and post-stimulation cortisol concentrations increased following OVx (p = 0.002 and p = 0.0003, respectively). In female dogs with CS, cortisol concentrations increased following stimulation with hCG in 57% (8/14; p = 0.002). Age at the time of OVx was associated (p = 0.015) with the cortisol response to hCG [8 (5-9) years vs. 3.5 (2-6) years, p = 0.0013). Conclusion: Based on these results, an LH-dependent form of CS occurs in spayed female dogs, and that it is more likely to occur when female dogs are spayed later in life.

Diabetes mellitus remission in three cats with hypersomatotropism after cabergoline treatment.

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.

Pharmacological treatment with cabergoline in three cats with acromegaly / Tratamiento farmacológico con cabergolina en tres gatos con acromegalia / Tratamento farmacológico com cabergolina em três gatos com acromegalia

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.

Molecular cloning of ion channels in Felis catus that are related to periodic paralyses in man: a contribution to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis.

Neck ventroflexion in cats has different causes; however, the most common is the hypokalemia associated with flaccid paralysis secondary to chronic renal failure. In humans, the most common causes of acute flaccid paralysis are hypokalemia precipitated by thyrotoxicosis and familial forms linked to mutations in sodium, potassium, and calcium channel genes. Here, we describe the sequencing and analysis of skeletal muscle ion channels in Felis catus that could be related to periodic paralyses in humans, contributing to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis. We studied genomic DNA from eleven cats, including five animals that were hyperthyroid with hypokalemia, although only one presented with muscle weakness, and six healthy control domestic cats. We identified the ion channel ortholog genes KCNJ2, KCNJ12, KCNJ14, CACNA1S and SCN4A in the Felis catus genome, together with several polymorphic variants. Upon comparative alignment with other genomes, we found that Felis catus provides evidence for a high genomic conservation of ion channel sequences. Although we hypothesized that neck ventroflexion in cats could be associated with a thyrotoxic or familial periodic paralysis channel mutation, we did not identify any previously detected human channel mutation in the hyperthyroid cat presenting hypokalemia. However, based on the small number of affected cats in this study, we cannot yet rule out this molecular mechanism. Notwithstanding, hyperthyroidism should still be considered as a differential diagnosis in hypokalemic feline paralysis.

Immune-endocrine interactions in treated and untreated cats naturally infected with FIV.

Feline immunodeficiency virus (FIV) is a lentivirus that causes a progressive disruption of immune function in cats. The neuroendocrine and immune systems communicate bidirectionally, mediated by cytokines such as tumour necrosis factor-α (TNF), several interleukins (IL-1, IL-6, IL-10), and through signals induced by the ratio of IL-10 to IL-12. FIV can affect both pituitary adrenal and thyroid axis function. Twenty FIV-infected cats in similar stages of the disease were evaluated for six months. A cross-sectional study in which the twenty cats were divided into two groups was performed. Ten were treated with Zidovudine (ZDV: 5mg/kg/d, PO, q12h, for six months) and 10 were untreated. Plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, T4, FT4, T3, IL-10, IL-12 and viral load (VL) were evaluated after six months. ACTH was found in significantly lower concentrations (p<0.0001) in the treated group whereas cortisol did not show significant differences between the two groups. Both T4 and FT4 had high values in untreated individuals (p<0.001) compared with Zidovudine treated cats. T3 did not show significant differences between the two groups. Both IL-10 and IL-12 were found in significantly higher concentrations in ZDV treated cats (p<0.001). By contrast, the IL10/IL-12 ratio values were significantly lower in untreated cats. Viral load was significantly lower in the treated cats after six months of therapy, compared with values detected pre-treatment (p<0.002). Untreated cats showed a significant increase of VL (p<0.04) compared with the values at the beginning of the study. In treated cats, VL showed lower numbers of viral copies than in untreated cats (p<0.01). In summary, Zidovudine treatment appeared to contribute to the normalization of both the adrenal and thyroid axes. This effect could be attributed to the decrease observed in VL, resulting in a change in cytokine patterns.

Clinical applications of scintigraphy in small animals in Buenos Aires, Argentina / Indicaciones y aplicaciones clínicas de la centellografía realizada en pequeños animales en Buenos Aires, Argentina / Indicações e aplicações clínicas da cintilografia de pequenos animais realizada em Buenos Aires, Argentina

Scintigraphy (CGF) is a diagnostic imaging tool utilizing specific radiopharmaceuticals to assess the anatomical and functional status for each organ or tissue. This technology allows the veterinarian to anticipate, supplement or complete the diagnosis, and also to monitor the treatment. Unfortunately, this diagnostic method is little known, and its lack of dissemination among clinical veterinarians prevents its optimal use. In order to understand the benefits of CGF as an effective imaging tool in the city of Buenos Aires during the years 2004-2006, we analyzed the studies that utilized CGF in canine and cats during this period. From a total of 142 studies, it was found that 38.6% of the assessments corresponded to thyroid disorders, while 61.4% of the remaining studies that involved CGF included, in descending order, pathologies associated with liver, bone, kidneys, parathyroid gland and lungs. The main findings in this paper highlight the use of CGF in the diagnosis of functional thyroid carcinoma followed by portosystemic shunt, bone neoplasms, evaluation of individual kidney function, parathyroid hyperplasia, parathyroid adenoma and pulmonary embolism.

La centellografía (CGF) es una ayuda diagnóstica a través de imágenes, que permite evaluar el estado anatómico-funcional por medio del empleo de radiofármacos específicos para cada órgano o tejido en los animales de compañía, permitiendo anticipar, complementar o concluir un diagnóstico, al igual que permite hacer el seguimiento al tratamiento instaurado. Lamentablemente es un método diagnóstico muy poco conocido y difundido entre los clínicos veterinarios, llegando a omitirse su realización. Con el propósito de conocer los diferentes tipos de estudios, aportes e indicaciones que se obtuvieron mediante el uso de la cámara gamma en la ciudad de Buenos Aires durante los años 2004-2006, se analizaron los informes de los estudios CGF que fueron realizados a caninos y felinos durante este periodo. Al finalizar el estudio se logro determinar que el 38.6% del total de los 142 estudios correspondía a evaluaciones de la glándula tiroides, mientras el 61.37% estaba constituido por cinco diferentes estudios entre los que se mencionan en orden decreciente, CGF hepática, ósea, renal, paratiroidea y pulmonar. Las principales indicaciones encontradas en el presente trabajo se destacó el diagnóstico de carcinoma de glándula tiroides funcional seguido por el shunt porto sistémico, neoplasias de tejido óseo, evaluación de la función renal individual, hiperplasia paratiroidea, adenoma paratiroides y embolismo pulmonar.

A cintilografia (CGF) é um auxílio diagnóstico através de imagens, que avalia o estado anatômico e funcional através do uso de radiofármacos específicos para cada órgão ou tecido em animais domésticos, permitindo antecipar, complementar ou completar o diagnóstico, Também permite monitorar o tratamento iniciado. Infelizmente é um método de diagnóstico pouco conhecido e divulgado entre os clínicos veterinários. Com o propósito de compreender os diferentes tipos de estudos, aportes e indicações que foram realizados utilizando-se uma câmara gamma, na cidade de Buenos Aires, durante o período de 2004-2006. Foram analisados os informes dos estudos de CGF que foram conduzidos para cães e gatos durante este período. No final do estudo foi determinado que o 38,6% do total de 142 estudos correspondem às avaliações da glândula tireóide, enquanto que 61,37% era composto por cinco diferentes estudos entre os listados em ordem decrescente, fígado, ósseo, renal , paratireóide e pulmão. As principais indicações encontrados neste trabalho destacaram o diagnóstico de carcinoma da tiróide funcional, seguido pelo shunt sistêmico, neoplasias ósseas, da função renal individual, hiperplasia da paratireóide, adenoma da paratireóide e embolia pulmonar.