Veterinary Clinics of North America-small Animal Practice, Mar 1, 2010
Hypercortisolism is a common condition in dogs and can be defined as the physical and biochemical... more Hypercortisolism is a common condition in dogs and can be defined as the physical and biochemical changes that result from prolonged exposure to inappropriately high plasma concentrations of (free) cortisol, whatever its' cause. This disorder is often called Cushing's syndrome, after Harvey Cushing, the neurosurgeon who first described the human syndrome in 1932. Cushing's syndrome is sometimes iatrogenic, in most cases due to administration of glucocorticoids for the treatment of a variety of allergic, autoimmune, inflammatory, or neoplastic diseases. The development of clinical signs of glucocorticoid excess depends on the severity and duration of the exposure. The effects also vary among animals owing to interindividual differences in cortisol sensitivity. Corticosteroid administration causes prompt and sustained suppression of the hypothalamic-pituitary-adrenocortical axis. Depending on the dose and the intrinsic glucocorticoid activity of the corticosteroid, the schedule and duration of its administration, and the preparation or formulation, this suppression may exist for weeks or months after cessation of the corticosteroid administration. This article focuses on the diagnosis of spontaneous hypercortisolism. In 80% to 85% of the spontaneous cases, hypercortisolism is adrenocorticotropic hormone (ACTH)-dependent, usually arising from hypersecretion of ACTH by a pituitary corticotroph adenoma. Ectopic ACTH-secretion syndrome is rare in dogs. 1 The remaining 15% to 20% of cases of spontaneous hypercortisolism are ACTH-independent and result from autonomous hypersecretion of glucocorticoids by an adrenocortical adenoma or adenocarcinoma. In addition to an adrenocortical tumor, ACTH-independent hypercortisolism can be caused by bilateral (macro)nodular adrenocortical
Pituitary tumours are common in dogs and are being increasingly recognized in cats. Pituitary tum... more 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.
IntroductionTranssphenoidal hypophysectomy is the standard surgical technique for the excision of... more IntroductionTranssphenoidal hypophysectomy is the standard surgical technique for the excision of pituitary neoplasms. Anatomy may be more obscured in brachycephalic skull types due to the crowding of soft tissue and osseous structures. We describe the unique challenges to approach the sphenoid bone and localize the correct burr hole site in severe brachycephalic dogs.Materials and methodsA single institution retrospective case series of brachycephalic dogs with pituitary-dependent hypercortisolism (PDH). Preoperative computed tomography enabled 3D-, and cross-sectional reconstruction to plan and dry-practice the position of the ideal burr hole in relation to the sella turcica, pterygoid hamular processes, and hard palate. Rostral burring of the caudal hard palate obscuring the direct sphenoid approach necessitated adaptations to the original transsphenoidal hypophysectomy procedure. Postoperative outcomes and complications with respect to those seen in mesocephalic dogs are describ...
A 7‐month‐old Boxer puppy was referred for growth retardation. Cushing's syndrome was diagnos... more A 7‐month‐old Boxer puppy was referred for growth retardation. Cushing's syndrome was diagnosed based on clinical signs, physical appearance, elevated urine cortisol/creatinine ratios and unsuppressed plasma cortisol after a low dose of dexamethasone. At the time, there was no evidence of pituitary or adrenal neoplasia on imaging studies. After 60 days of trilostane treatment, the clinical signs of Cushing's syndrome had disappeared. Thirty months later, the dog died of cardiac disease. Pathological examination revealed a pituitary macroadenoma with bilateral adrenocortical hyperplasia. Immunostaining for adrenocorticotropic hormone confirmed a corticotroph adenoma. High Ki‐67 staining denoted the aggressiveness of the tumour. Haematoxylin–eosin, periodic acid‐Schiff and cytokeratin 7 staining revealed a perinuclear hyaline ring in the neoplastic cells, compatible with a Crooke's cell adenoma. This is the first case of Crooke's cell pituitary adenoma causing Cushing&...
BackgroundPheochromocytoma (PCC) is rare in cats and plasma (PL) and urinary (U) metanephrines (m... more BackgroundPheochromocytoma (PCC) is rare in cats and plasma (PL) and urinary (U) metanephrines (metanephrine [MN]; normetanephrine [NMN]) measurement is rarely described in cats.ObjectivesWe evaluated the utility of PL and U MNs measurement in 10 healthy cats and a cat with a confirmed diagnosis of pheochromocytoma (PheoCat), using liquid chromatography with tandem mass spectrometry (LC‐MS‐MS).MethodsUrine and EDTA PL samples collected from each of the 10 cats and the PheoCat were promptly stored at −80°C and remained frozen until analysis. To evaluate U MNs stability, an additional urine sample collected from the healthy cats was refrigerated for 24 hours before freezing. Urinary creatinine concentration (Creat) was assessed using the same spot urine samples to calculate U MNs‐to‐creatinine ratios.ResultsThe PL‐MN and PL‐NMN median concentrations of the healthy cats were 2.73 and 7.02 nmol/L, respectively. The median U‐MN/Creat and U‐NMN/Creat ratios were 70 and 139 μg/g, respectiv...
Pheochromocytoma in cats is a rare clinical condition characterised by the development of a secre... more Pheochromocytoma in cats is a rare clinical condition characterised by the development of a secretory endocrine tumour that arises from the adrenal medulla. An 8‐year‐old castrated male, domestic shorthair cat was referred for further investigation of a 4‐month history of progressive weight loss with normal appetite, polyuria/polydipsia, generalised weakness, and severe hypertension. Sonography and computed tomography of the abdomen disclosed a mass arising from the left adrenal gland. The contralateral adrenal gland was normal in size and shape. Results from a low dose dexamethasone suppression test and measurements of plasma aldosterone concentration and plasma renin activity ruled out a cortisol‐secreting tumour and aldosteronoma. The clinical presentation made a sex‐steroid secreting tumour unlikely. Increased plasma metanephrine and normetanephrine concentrations prioritised the differential diagnosis of pheochromocytoma. The cat underwent adrenalectomy of the left gland and hi...
This retrospective study aimed to assess the prevalence of ultrasonographic detected adrenomegaly... more This retrospective study aimed to assess the prevalence of ultrasonographic detected adrenomegaly in clinically ill cats, evaluating the final established diagnosis, describe adrenal ultrasound findings and if the adrenomegaly was suspected or incidental. Abdominal ultrasonography reports of cats presenting to a veterinary teaching hospital between October 2018 and February 2021 were retrospectively reviewed. Cats showing adrenomegaly (one or both glands having a dorsoventral axis >4.8 mm) were selected and medical records respectively evaluated. Nine-hundred and eighty-three ultrasonographical reports were selected, of which, 68 (7%) disclosed adrenomegaly. European/Domestic Short-Hair (62/68; 91%) male (44/68; 65%) castrated (35/44; 80%) cats were overrepresented. Adrenomegaly was an incidental finding in 62/68 (91%) cats while in 6/68 (9%) it was identified in the context of investigating a potential adrenal disease. Concerning established diagnosis, chronic kidney disease was...
Objectives The aims of this study were to validate a commercially available chemiluminescent assa... more Objectives The aims of this study were to validate a commercially available chemiluminescent assay for measurement of feline plasma adrenocorticotropic hormone concentration (ACTH), to determine the normal reference interval (RI) of plasma ACTH in healthy cats, to assess plasma ACTH in cats with naturally occurring hypercortisolism (HC), primary hypoadrenocorticism (PH) and other diseases (OD), and to evaluate the effect of aprotinin on plasma ACTH degradation. Methods Forty healthy cats, 10 with HC, 11 with PH and 30 with OD, were included. The chemiluminescent enzyme immunometric assay was evaluated by measurement of intra-assay precision, interassay precision and linearity. The RI for plasma ACTH in healthy cats was established using robust methods. Plasma ACTH of samples collected with and without aprotinin, stored at 4°C and assayed over a 6-day period, was measured. Results The intra-assay coefficients of variance (CVs) ranged from 2.7% to 4.3% and interassay CVs from 3.3% to ...
The medical records of 63 dogs with pituitary-dependent hypercortisolism (PDH) before and during ... more The medical records of 63 dogs with pituitary-dependent hypercortisolism (PDH) before and during treatment with trilostane were reviewed retrospectively. The correct trilostane dosage in dogs with PDH was based on the resolution of clinical signs and the results of an adrenocorticotropic hormone (ACTH) stimulation test. The mean (+/-SD) dose rate of trilostane to achieve good clinical control was 2.8+/-1.0mg/kg bodyweight.
Measurement of the urinary corticoid : creatinine (C : C) ratio provides an assessment of cortiso... more Measurement of the urinary corticoid : creatinine (C : C) ratio provides an assessment of cortisol secretion over a period of time. Therefore, this test is a very sensitive measure of adrenocortical function. The stress of the diagnostic procedure and nonadrenal disease may increase the urinary C : C ratio. In addition, diseases such as hyperthyroidism may influence the metabolic clearance of cortisol. To evaluate the effect of thyroid hormone excess, urinary C : C ratios were measured in 32 cats with hyperthyroidism and 45 healthy household cats. In 7 cats, urinary C : C ratios were measured both before and after treatment for hyperthyroidism. With data from the healthy cats, the reference range for the urinary C : C ratio was determined to be 8.0 to 42.0 X 10(-6). The urinary C : C ratios in the cats with hyperthyroidism (median, 37.5 x 10(-6); range, 5.9-169.5 x 10(-6)) were significantly (P = .001) higher than those in the healthy cats (median, 16 x 10(-6); range, 4.8-52.5 x 10(-6)). In 15 cats with hyperthyroidism, the urinary C : C ratios exceeded the upper limit of the reference range. Treatment for hyperthyroidism led to a marked decrease in urinary C : C ratios. The results of this study demonstrate that the urinary C : C ratio may be abnormally high in cats with hyperthyroidism, probably because of increased metabolic clearance of cortisol and activation of the pituitary-adrenocortical axis by disease. Although the clinical features of hyperthyroidism and hyperadrenocorticism in cats are different, hyperthyroidism should be ruled out when cats are suspected of hyperadrenocorticism on the basis of abnormally high urinary C : C ratios.
Zusammenfassung Endokrinologische Erkrankungen sind in vielfacher Hinsicht ein aktuelles Thema in... more Zusammenfassung Endokrinologische Erkrankungen sind in vielfacher Hinsicht ein aktuelles Thema in der Kleintierpraxis. Hund und Katze leben heutzutage oft erfreulich lange und gut umsorgt. Damit spielen Probleme der endokrinen Drüsen, die oft erst im fortgeschrittenen Alter manifest werden, in der Patientenpopulation eine immer größere Rolle. Gleichzeitig sind immer mehr Tierbesitzer gewillt, die teils aufwendigen und langwierigen Behandlungen zu unterstützen. Man muss sagen: zum Glück, denn die ...
Canine Cushing's syndrome (hypercortisolism) can be caused by a pituitary tumor (pituitary-de... more Canine Cushing's syndrome (hypercortisolism) can be caused by a pituitary tumor (pituitary-dependent hypercortisolism; PDH) or a cortisol-secreting adrenocortical tumor (csACT). For both cases, noninvasive biomarkers that could pre-operatively predict the risk of recurrence after surgery would greatly impact clinical decision making. The aim of this study was to determine whether circulating microRNAs (miRNAs) can be used as noninvasive biomarkers for canine Cushing's syndrome. After a pilot study with 40 miRNAs in blood samples of healthy dogs (n = 3), dogs with PDH (n = 3) and dogs with a csACT (n = 4), we selected a total of 20 miRNAs for the definitive study. In the definitive study, these 20 miRNAs were analyzed in blood samples of healthy dogs (n = 6), dogs with PDH (n = 19, pre- and post-operative samples) and dogs with a csACT (n = 26, pre-operative samples). In dogs with PDH, six miRNAs (miR-122-5p, miR-126-5p, miR-141-3p, miR-222-3p, miR-375-3p and miR-483-3p) were...
Background: Transsphenoidal hypophysectomy is one of the treatment strategies in the comprehensiv... more Background: Transsphenoidal hypophysectomy is one of the treatment strategies in the comprehensive management of dogs with pituitary-dependent hypercortisolism (PDH). Objectives: To describe the influence of pituitary size at time of pituitary gland surgery on long-term outcome. Animals: Three-hundred-and-six dogs with PDH. Methods: Survival and disease-free fractions were analyzed and related to pituitary size; dogs with and without recurrence were compared. Results: Four weeks after surgery, 91% of dogs were alive and remission was confirmed in 92% of these dogs. The median survival time was 781 days, median disease-free interval was 951 days. Over time, 27% of dogs developed recurrence of hypercortisolism after a median period of 555 days. Dogs with recurrence had significantly higher pituitary height/brain area (P/B) ratio and pre-operative basal urinary corticoid-to-creatinine ratio (UCCR) than dogs without recurrence. Survival time and disease-free interval of dogs with enlarged pituitary glands was significantly shorter than that of dogs with a nonenlarged pituitary gland. Pituitary size at the time of surgery significantly increased over the 20-year period. Although larger tumors have a less favorable prognosis, outcome in larger tumors improved over time. Conclusions and Clinical Importance: Transsphenoidal hypophysectomy is an effective treatment for PDH in dogs, with an acceptable long-term outcome. Survival time and disease-free fractions are correlated negatively with pituitary gland size, making the P/B ratio an important pre-operative prognosticator. However, with increasing experience, and for large tumors, pituitary gland surgery remains an option to control the pituitary mass and hypercortisolism.
Abstract Background The use of adrenocorticotropic hormone stimulation test as method to monitor ... more Abstract Background The use of adrenocorticotropic hormone stimulation test as method to monitor efficacy of trilostane treatment of hypercortisolism (HC) in dogs has been questioned. Objectives To evaluate and compare 12 methods with which to monitor efficacy of trilostane treatment in dogs with HC. Animals Forty‐five client‐owned dogs with HC treated with trilostane q12h. Methods Prospective cross‐sectional observational study. The dogs were categorized as well‐controlled, undercontrolled, and unwell through a clinical score obtained from an owner questionnaire. The ability to correctly identify trilostane‐treatment control of dogs with HC with the following variables was evaluated: before trilostane serum cortisol (prepill), before‐ACTH serum cortisol, post‐ACTH serum cortisol, plasma endogenous ACTH concentrations, prepill/eACTH ratio, serum haptoglobin (Hp) concentration, serum alanine aminotransferase (ALT), gamma‐glutamyl transferase (γGT) and alkaline phosphatase activity, urine specific gravity, and urinary cortisol : creatinine ratio. Results Ninety‐four re‐evaluations of 44 dogs were included; 5 re‐evaluations of 5 unwell dogs were excluded. Haptoglobin was significantly associated with the clinical score (P < .001) and in the receiver operating characteristic analysis, Hp cutoff of 151 mg/dL correctly identified 90.0% of well‐controlled dogs (specificity) and 65.6% of undercontrolled dogs (sensitivity). Alanine aminotransferase (P = .01) and γGT (P = .009) were significantly higher in undercontrolled dogs. Cutoff of ALT and γGT greater than or equal to 86 U/L and 5.8 U/L, respectively, were significantly associated with poor control of HC by trilostane. Conclusions and Clinical Importance Of all the 12 variables, Hp, and to a lesser degree ALT and γGT, could be considered additional tools to the clinical picture to identify well‐controlled and undercontrolled trilostane‐treated dogs.
Veterinary Clinics of North America-small Animal Practice, Mar 1, 2010
Hypercortisolism is a common condition in dogs and can be defined as the physical and biochemical... more Hypercortisolism is a common condition in dogs and can be defined as the physical and biochemical changes that result from prolonged exposure to inappropriately high plasma concentrations of (free) cortisol, whatever its' cause. This disorder is often called Cushing's syndrome, after Harvey Cushing, the neurosurgeon who first described the human syndrome in 1932. Cushing's syndrome is sometimes iatrogenic, in most cases due to administration of glucocorticoids for the treatment of a variety of allergic, autoimmune, inflammatory, or neoplastic diseases. The development of clinical signs of glucocorticoid excess depends on the severity and duration of the exposure. The effects also vary among animals owing to interindividual differences in cortisol sensitivity. Corticosteroid administration causes prompt and sustained suppression of the hypothalamic-pituitary-adrenocortical axis. Depending on the dose and the intrinsic glucocorticoid activity of the corticosteroid, the schedule and duration of its administration, and the preparation or formulation, this suppression may exist for weeks or months after cessation of the corticosteroid administration. This article focuses on the diagnosis of spontaneous hypercortisolism. In 80% to 85% of the spontaneous cases, hypercortisolism is adrenocorticotropic hormone (ACTH)-dependent, usually arising from hypersecretion of ACTH by a pituitary corticotroph adenoma. Ectopic ACTH-secretion syndrome is rare in dogs. 1 The remaining 15% to 20% of cases of spontaneous hypercortisolism are ACTH-independent and result from autonomous hypersecretion of glucocorticoids by an adrenocortical adenoma or adenocarcinoma. In addition to an adrenocortical tumor, ACTH-independent hypercortisolism can be caused by bilateral (macro)nodular adrenocortical
Pituitary tumours are common in dogs and are being increasingly recognized in cats. Pituitary tum... more 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.
IntroductionTranssphenoidal hypophysectomy is the standard surgical technique for the excision of... more IntroductionTranssphenoidal hypophysectomy is the standard surgical technique for the excision of pituitary neoplasms. Anatomy may be more obscured in brachycephalic skull types due to the crowding of soft tissue and osseous structures. We describe the unique challenges to approach the sphenoid bone and localize the correct burr hole site in severe brachycephalic dogs.Materials and methodsA single institution retrospective case series of brachycephalic dogs with pituitary-dependent hypercortisolism (PDH). Preoperative computed tomography enabled 3D-, and cross-sectional reconstruction to plan and dry-practice the position of the ideal burr hole in relation to the sella turcica, pterygoid hamular processes, and hard palate. Rostral burring of the caudal hard palate obscuring the direct sphenoid approach necessitated adaptations to the original transsphenoidal hypophysectomy procedure. Postoperative outcomes and complications with respect to those seen in mesocephalic dogs are describ...
A 7‐month‐old Boxer puppy was referred for growth retardation. Cushing's syndrome was diagnos... more A 7‐month‐old Boxer puppy was referred for growth retardation. Cushing's syndrome was diagnosed based on clinical signs, physical appearance, elevated urine cortisol/creatinine ratios and unsuppressed plasma cortisol after a low dose of dexamethasone. At the time, there was no evidence of pituitary or adrenal neoplasia on imaging studies. After 60 days of trilostane treatment, the clinical signs of Cushing's syndrome had disappeared. Thirty months later, the dog died of cardiac disease. Pathological examination revealed a pituitary macroadenoma with bilateral adrenocortical hyperplasia. Immunostaining for adrenocorticotropic hormone confirmed a corticotroph adenoma. High Ki‐67 staining denoted the aggressiveness of the tumour. Haematoxylin–eosin, periodic acid‐Schiff and cytokeratin 7 staining revealed a perinuclear hyaline ring in the neoplastic cells, compatible with a Crooke's cell adenoma. This is the first case of Crooke's cell pituitary adenoma causing Cushing&...
BackgroundPheochromocytoma (PCC) is rare in cats and plasma (PL) and urinary (U) metanephrines (m... more BackgroundPheochromocytoma (PCC) is rare in cats and plasma (PL) and urinary (U) metanephrines (metanephrine [MN]; normetanephrine [NMN]) measurement is rarely described in cats.ObjectivesWe evaluated the utility of PL and U MNs measurement in 10 healthy cats and a cat with a confirmed diagnosis of pheochromocytoma (PheoCat), using liquid chromatography with tandem mass spectrometry (LC‐MS‐MS).MethodsUrine and EDTA PL samples collected from each of the 10 cats and the PheoCat were promptly stored at −80°C and remained frozen until analysis. To evaluate U MNs stability, an additional urine sample collected from the healthy cats was refrigerated for 24 hours before freezing. Urinary creatinine concentration (Creat) was assessed using the same spot urine samples to calculate U MNs‐to‐creatinine ratios.ResultsThe PL‐MN and PL‐NMN median concentrations of the healthy cats were 2.73 and 7.02 nmol/L, respectively. The median U‐MN/Creat and U‐NMN/Creat ratios were 70 and 139 μg/g, respectiv...
Pheochromocytoma in cats is a rare clinical condition characterised by the development of a secre... more Pheochromocytoma in cats is a rare clinical condition characterised by the development of a secretory endocrine tumour that arises from the adrenal medulla. An 8‐year‐old castrated male, domestic shorthair cat was referred for further investigation of a 4‐month history of progressive weight loss with normal appetite, polyuria/polydipsia, generalised weakness, and severe hypertension. Sonography and computed tomography of the abdomen disclosed a mass arising from the left adrenal gland. The contralateral adrenal gland was normal in size and shape. Results from a low dose dexamethasone suppression test and measurements of plasma aldosterone concentration and plasma renin activity ruled out a cortisol‐secreting tumour and aldosteronoma. The clinical presentation made a sex‐steroid secreting tumour unlikely. Increased plasma metanephrine and normetanephrine concentrations prioritised the differential diagnosis of pheochromocytoma. The cat underwent adrenalectomy of the left gland and hi...
This retrospective study aimed to assess the prevalence of ultrasonographic detected adrenomegaly... more This retrospective study aimed to assess the prevalence of ultrasonographic detected adrenomegaly in clinically ill cats, evaluating the final established diagnosis, describe adrenal ultrasound findings and if the adrenomegaly was suspected or incidental. Abdominal ultrasonography reports of cats presenting to a veterinary teaching hospital between October 2018 and February 2021 were retrospectively reviewed. Cats showing adrenomegaly (one or both glands having a dorsoventral axis >4.8 mm) were selected and medical records respectively evaluated. Nine-hundred and eighty-three ultrasonographical reports were selected, of which, 68 (7%) disclosed adrenomegaly. European/Domestic Short-Hair (62/68; 91%) male (44/68; 65%) castrated (35/44; 80%) cats were overrepresented. Adrenomegaly was an incidental finding in 62/68 (91%) cats while in 6/68 (9%) it was identified in the context of investigating a potential adrenal disease. Concerning established diagnosis, chronic kidney disease was...
Objectives The aims of this study were to validate a commercially available chemiluminescent assa... more Objectives The aims of this study were to validate a commercially available chemiluminescent assay for measurement of feline plasma adrenocorticotropic hormone concentration (ACTH), to determine the normal reference interval (RI) of plasma ACTH in healthy cats, to assess plasma ACTH in cats with naturally occurring hypercortisolism (HC), primary hypoadrenocorticism (PH) and other diseases (OD), and to evaluate the effect of aprotinin on plasma ACTH degradation. Methods Forty healthy cats, 10 with HC, 11 with PH and 30 with OD, were included. The chemiluminescent enzyme immunometric assay was evaluated by measurement of intra-assay precision, interassay precision and linearity. The RI for plasma ACTH in healthy cats was established using robust methods. Plasma ACTH of samples collected with and without aprotinin, stored at 4°C and assayed over a 6-day period, was measured. Results The intra-assay coefficients of variance (CVs) ranged from 2.7% to 4.3% and interassay CVs from 3.3% to ...
The medical records of 63 dogs with pituitary-dependent hypercortisolism (PDH) before and during ... more The medical records of 63 dogs with pituitary-dependent hypercortisolism (PDH) before and during treatment with trilostane were reviewed retrospectively. The correct trilostane dosage in dogs with PDH was based on the resolution of clinical signs and the results of an adrenocorticotropic hormone (ACTH) stimulation test. The mean (+/-SD) dose rate of trilostane to achieve good clinical control was 2.8+/-1.0mg/kg bodyweight.
Measurement of the urinary corticoid : creatinine (C : C) ratio provides an assessment of cortiso... more Measurement of the urinary corticoid : creatinine (C : C) ratio provides an assessment of cortisol secretion over a period of time. Therefore, this test is a very sensitive measure of adrenocortical function. The stress of the diagnostic procedure and nonadrenal disease may increase the urinary C : C ratio. In addition, diseases such as hyperthyroidism may influence the metabolic clearance of cortisol. To evaluate the effect of thyroid hormone excess, urinary C : C ratios were measured in 32 cats with hyperthyroidism and 45 healthy household cats. In 7 cats, urinary C : C ratios were measured both before and after treatment for hyperthyroidism. With data from the healthy cats, the reference range for the urinary C : C ratio was determined to be 8.0 to 42.0 X 10(-6). The urinary C : C ratios in the cats with hyperthyroidism (median, 37.5 x 10(-6); range, 5.9-169.5 x 10(-6)) were significantly (P = .001) higher than those in the healthy cats (median, 16 x 10(-6); range, 4.8-52.5 x 10(-6)). In 15 cats with hyperthyroidism, the urinary C : C ratios exceeded the upper limit of the reference range. Treatment for hyperthyroidism led to a marked decrease in urinary C : C ratios. The results of this study demonstrate that the urinary C : C ratio may be abnormally high in cats with hyperthyroidism, probably because of increased metabolic clearance of cortisol and activation of the pituitary-adrenocortical axis by disease. Although the clinical features of hyperthyroidism and hyperadrenocorticism in cats are different, hyperthyroidism should be ruled out when cats are suspected of hyperadrenocorticism on the basis of abnormally high urinary C : C ratios.
Zusammenfassung Endokrinologische Erkrankungen sind in vielfacher Hinsicht ein aktuelles Thema in... more Zusammenfassung Endokrinologische Erkrankungen sind in vielfacher Hinsicht ein aktuelles Thema in der Kleintierpraxis. Hund und Katze leben heutzutage oft erfreulich lange und gut umsorgt. Damit spielen Probleme der endokrinen Drüsen, die oft erst im fortgeschrittenen Alter manifest werden, in der Patientenpopulation eine immer größere Rolle. Gleichzeitig sind immer mehr Tierbesitzer gewillt, die teils aufwendigen und langwierigen Behandlungen zu unterstützen. Man muss sagen: zum Glück, denn die ...
Canine Cushing's syndrome (hypercortisolism) can be caused by a pituitary tumor (pituitary-de... more Canine Cushing's syndrome (hypercortisolism) can be caused by a pituitary tumor (pituitary-dependent hypercortisolism; PDH) or a cortisol-secreting adrenocortical tumor (csACT). For both cases, noninvasive biomarkers that could pre-operatively predict the risk of recurrence after surgery would greatly impact clinical decision making. The aim of this study was to determine whether circulating microRNAs (miRNAs) can be used as noninvasive biomarkers for canine Cushing's syndrome. After a pilot study with 40 miRNAs in blood samples of healthy dogs (n = 3), dogs with PDH (n = 3) and dogs with a csACT (n = 4), we selected a total of 20 miRNAs for the definitive study. In the definitive study, these 20 miRNAs were analyzed in blood samples of healthy dogs (n = 6), dogs with PDH (n = 19, pre- and post-operative samples) and dogs with a csACT (n = 26, pre-operative samples). In dogs with PDH, six miRNAs (miR-122-5p, miR-126-5p, miR-141-3p, miR-222-3p, miR-375-3p and miR-483-3p) were...
Background: Transsphenoidal hypophysectomy is one of the treatment strategies in the comprehensiv... more Background: Transsphenoidal hypophysectomy is one of the treatment strategies in the comprehensive management of dogs with pituitary-dependent hypercortisolism (PDH). Objectives: To describe the influence of pituitary size at time of pituitary gland surgery on long-term outcome. Animals: Three-hundred-and-six dogs with PDH. Methods: Survival and disease-free fractions were analyzed and related to pituitary size; dogs with and without recurrence were compared. Results: Four weeks after surgery, 91% of dogs were alive and remission was confirmed in 92% of these dogs. The median survival time was 781 days, median disease-free interval was 951 days. Over time, 27% of dogs developed recurrence of hypercortisolism after a median period of 555 days. Dogs with recurrence had significantly higher pituitary height/brain area (P/B) ratio and pre-operative basal urinary corticoid-to-creatinine ratio (UCCR) than dogs without recurrence. Survival time and disease-free interval of dogs with enlarged pituitary glands was significantly shorter than that of dogs with a nonenlarged pituitary gland. Pituitary size at the time of surgery significantly increased over the 20-year period. Although larger tumors have a less favorable prognosis, outcome in larger tumors improved over time. Conclusions and Clinical Importance: Transsphenoidal hypophysectomy is an effective treatment for PDH in dogs, with an acceptable long-term outcome. Survival time and disease-free fractions are correlated negatively with pituitary gland size, making the P/B ratio an important pre-operative prognosticator. However, with increasing experience, and for large tumors, pituitary gland surgery remains an option to control the pituitary mass and hypercortisolism.
Abstract Background The use of adrenocorticotropic hormone stimulation test as method to monitor ... more Abstract Background The use of adrenocorticotropic hormone stimulation test as method to monitor efficacy of trilostane treatment of hypercortisolism (HC) in dogs has been questioned. Objectives To evaluate and compare 12 methods with which to monitor efficacy of trilostane treatment in dogs with HC. Animals Forty‐five client‐owned dogs with HC treated with trilostane q12h. Methods Prospective cross‐sectional observational study. The dogs were categorized as well‐controlled, undercontrolled, and unwell through a clinical score obtained from an owner questionnaire. The ability to correctly identify trilostane‐treatment control of dogs with HC with the following variables was evaluated: before trilostane serum cortisol (prepill), before‐ACTH serum cortisol, post‐ACTH serum cortisol, plasma endogenous ACTH concentrations, prepill/eACTH ratio, serum haptoglobin (Hp) concentration, serum alanine aminotransferase (ALT), gamma‐glutamyl transferase (γGT) and alkaline phosphatase activity, urine specific gravity, and urinary cortisol : creatinine ratio. Results Ninety‐four re‐evaluations of 44 dogs were included; 5 re‐evaluations of 5 unwell dogs were excluded. Haptoglobin was significantly associated with the clinical score (P < .001) and in the receiver operating characteristic analysis, Hp cutoff of 151 mg/dL correctly identified 90.0% of well‐controlled dogs (specificity) and 65.6% of undercontrolled dogs (sensitivity). Alanine aminotransferase (P = .01) and γGT (P = .009) were significantly higher in undercontrolled dogs. Cutoff of ALT and γGT greater than or equal to 86 U/L and 5.8 U/L, respectively, were significantly associated with poor control of HC by trilostane. Conclusions and Clinical Importance Of all the 12 variables, Hp, and to a lesser degree ALT and γGT, could be considered additional tools to the clinical picture to identify well‐controlled and undercontrolled trilostane‐treated dogs.
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