[Acromegaly due to a pituitary tumor in a dog - diagnosis, therapy and long-term follow-up]. / Akromegalie aufgrund eines Hypophysentumors bei einem Hund ­ Diagnose, Therapie und Verlauf.

INTRODUCTION: Acromegaly due to a pituitary tumor has so far only been described in 3 dogs. The present case report describes a 7-year-old male-castrated Labrador Retriever which was referred because of difficult-to-control diabetes. Physical examination revealed markedly enlarged head, tongue and paws, widened interdental spaces and thickening of the skin in the head and neck area. IGF-1 and GH were increased and the latter continued to be abnormal after somatostatin application. Computed tomography demonstrated a space-occupying lesion in the pituitary gland and the diagnosis of acromegaly due to a GH-producing tumor of the pituitary was made. The dog underwent radiation therapy with a 6MV linear accelerator (3×8Gy) and improved substantially. Two and a half years after radiation therapy the dog developed lethargy and anorexia and was euthanized. Necropsy was not permitted. This case report represents the description of a dog suffering from pituitary-dependent acromegaly which was successfully treated and had a long-term survival.

INTRODUCTION: L'acromégalie due à une tumeur hypophysaire n'a jusqu'à présent été décrite que chez 3 chiens. Le présent rapport de cas décrit un Labrador Retriever de 7 ans mâle castré, qui a été référé en raison d'un diabète difficile à contrôler. L'examen physique a révélé une tête, une langue et des pattes de taille nettement augmentée, des espaces interdentaires élargis et un épaississement de la peau dans la région de la tête et du cou. L'IGF-1 et la GH étaient augmentées et la seconde restait anormale après l'application de somatostatine. La tomodensitométrie a mis en évidence une masse dans la région de l'hypophyse et le diagnostic d'acromégalie due à une tumeur de l'hypophyse productrice de GH a été posé. Le chien a subi une radiothérapie avec un accélérateur linéaire de 6MV (3×8Gy) et son état s'est considérablement amélioré. Deux ans et demi après la radiothérapie, le chien développa une léthargie et une anorexie et fut euthanasié. L'autopsie n'a pas été autorisée. Ce rapport de cas représente la description d'un chien souffrant d'acromégalie dépendant de l'hypophyse, traité avec succès et ayant une survie à long terme.

Altered Serum Thyrotropin Concentrations in Dogs with Primary Hypoadrenocorticism before and during Treatment.

BACKGROUND: Thyrotropin (TSH) can be increased in humans with primary hypoadrenocorticism (HA) before glucocorticoid treatment. Increase in TSH is a typical finding of primary hypothyroidism and both diseases can occur concurrently (Schmidt's syndrome); therefore, care must be taken in assessing thyroid function in untreated human patients with HA. OBJECTIVE: Evaluate whether alterations in cTSH can be observed in dogs with HA in absence of primary hypothyroidism. ANIMALS: Thirty dogs with newly diagnosed HA, and 30 dogs in which HA was suspected but excluded based on a normal ACTH stimulation test (controls) were prospectively enrolled. METHODS: cTSH and T4 concentrations were determined in all dogs and at selected time points during treatment (prednisolone, fludrocortisone, or DOCP) in dogs with HA. RESULTS: cTSH concentrations ranged from 0.01 to 2.6 ng/mL (median 0.29) and were increased in 11/30 dogs with HA; values in controls were all within the reference interval (range: 0.01-0.2 ng/dL; median 0.06). There was no difference in T4 between dogs with increased cTSH (T4 range 1.0-2.1; median 1.3 µg/dL) compared to those with normal cTSH (T4 range 0.5-3.4, median 1.4 µg/dL; P=0.69) and controls (T4 range 0.3-3.8, median 1.8 µg/dL; P=0.35). After starting treatment, cTSH normalized after 2-4 weeks in 9 dogs and after 3 and 4 months in 2 without thyroxine supplementation. CONCLUSIONS AND CLINICAL RELEVANCE: Evaluation of thyroid function in untreated dogs with HA can lead to misdiagnosis of hypothyroidism; treatment with glucocorticoids for up to 4 months can be necessary to normalize cTSH.

Cortisol Response in Healthy and Diseased Dogs after Stimulation with a Depot Formulation of Synthetic ACTH.

BACKGROUND: The ACTH stimulation test is used to evaluate the adrenocortical reserve. Recently, the availability of the synthetic ACTH formulation was limited, causing major problems in clinical practice. OBJECTIVES: The objective of this study was to evaluate poststimulation peak cortisol concentrations and the duration of the stimulatory effect of a depot ACTH preparation in dogs. ANIMALS: Twenty-two healthy dogs, 10 dogs with suspected hypoadrenocorticism (HA) and 15 dogs with suspected hyperadrenocorticism (HC). METHODS: Prospective study. An ACTH stimulation test using a synthetic depot tetracosactide, administered intramuscularly (5 µg/kg or at least 0.1 mL) was performed. Blood samples for determination of cortisol were taken immediately before and 1, 2, 3, 4, 6, and 24 hours after stimulation. RESULTS: Peak cortisol concentrations were reached after 2-4 hours in all dogs. Cortisol concentrations 1 hour after stimulation were >9 µg/dL in all healthy dogs and >5 µg/dL in all dogs in which HA was excluded. None of the dogs with HA showed a cortisol-increase above the detection-limit of the assay. After 6 hours, cortisol concentrations had decreased in the healthy and HC group and were back to baseline after 24 hours. CONCLUSIONS AND CLINICAL IMPORTANCE: The depot formulation can be used in place of the short-acting ACTH to evaluate the adrenocortical reserve. Blood for peak cortisol concentrations should be drawn 3 hours after stimulation in cases in which HC is suspected; in HA-suspected cases, blood sampling can take place after 1 hour. As the stimulatory effect is gone after 24 hours, interference with other hormonal tests is unlikely after that time.

Evaluation of the Cortisol-to-ACTH Ratio in Dogs with Hypoadrenocorticism, Dogs with Diseases Mimicking Hypoadrenocorticism and in Healthy Dogs.

BACKGROUND: The adrenocorticotropic hormone (ACTH) stimulation test is the gold standard for diagnosing hypoadrenocorticism (HA) in dogs. However, problems with the availability of synthetic ACTH (tetracosactrin/cosyntropin) and increased costs have prompted the need for alternative methods. OBJECTIVES: To prospectively evaluate the cortisol-to-ACTH ratio (CAR) as a screening test for diagnosing canine HA. ANIMALS: Twenty three dogs with newly diagnosed HA; 79 dogs with diseases mimicking HA; 30 healthy dogs. METHODS: Plasma ACTH and baseline cortisol concentrations were measured before i.v. administration of 5 µg/kg ACTH in all dogs. CAR was calculated and the diagnostic performance of ACTH, baseline cortisol, CAR and sodium-to-potassium ratios (SPRs) was assessed based on receiver operating characteristics (ROC) curves calculating the area under the ROC curve. RESULTS: The CAR was significantly lower in dogs with HA compared to that in healthy dogs and in those with diseases mimicking HA (P < .0001). There was an overlap between HA dogs and those with HA mimicking diseases, but CAR still was the best parameter for diagnosing HA (ROC AUC 0.998), followed by the ACTH concentration (ROC AUC 0.97), baseline cortisol concentration (ROC AUC 0.96), and SPR (ROC AUC 0.86). With a CAR of >0.01 the diagnostic sensitivity and specificity were 100% and 99%, respectively. CONCLUSION AND CLINICAL IMPORTANCE: Calculation of the CAR is a useful screening test for diagnosing primary HA. As a consequence of the observed overlap between the groups, however, misdiagnosis cannot be completely excluded. Moreover, additional studies are needed to evaluate the diagnostic reliability of CAR in more dogs with secondary HA.

Evaluation of baseline cortisol, endogenous ACTH, and cortisol/ACTH ratio to monitor trilostane treatment in dogs with pituitary-dependent hypercortisolism.

BACKGROUND: The effectiveness of trilostane treatment is currently monitored by regular ACTH stimulation tests, which are time-consuming and expensive. Therefore, a monitoring system without a stimulation protocol and with less client expense would be preferable. HYPOTHESIS/OBJECTIVES: The aim of our study was to evaluate if baseline cortisol, endogenous ACTH (ACTH) concentration or the baseline cortisol to ACTH ratio (cortisol/ACTH ratio) could replace the ACTH stimulation test. ANIMALS: Forty trilostane-treated dogs with pituitary-dependent hypercortisolism (PDH) were included in this prospective study. METHODS: A total of 148 ACTH stimulation tests and 77 ACTH concentrations and cortisol/ACTH ratios were analyzed. Control of cortisol release was classified according to cortisol concentration after ACTH administration as excessive (<1.5 µg/dL; group 1), adequate (1.5-5.4 µg/dL; group 2), or inadequate (>5.4 µg/dL; group 3). RESULTS: Baseline cortisol concentrations had considerable overlap between excessively, adequately, and inadequately controlled dogs. Only baseline cortisol >4.4 µg/dL (in 12% of tests) was a reliable diagnosis of inadequate control. Endogenous ACTH concentrations did not differ between groups. The overlap of the cortisol/ACTH ratio between groups was large. Correct classification was only possible if the cortisol/ACTH ratio was >15, which occurred in 4% of tests. CONCLUSIONS AND CLINICAL IMPORTANCE: To monitor trilostane treatment the ACTH stimulation test cannot be replaced by baseline cortisol, ACTH concentration, or the cortisol/ACTH ratio.

Diagnostic exercise: Submucosal gastric masses in a cat.

A 14-year-old neutered male cat presenting with chronic vomiting had 2 masses within the submucosa of the stomach that were excised. They presented histologically as circumscribed, submucosal masses consisting of diffusely arranged medium-sized round cells with a moderate amount of cytoplasm and interspersed eosinophils, separated by trabecular fibroblastic stroma. The overlying mucosa was diffusely infiltrated by the same round cells, and marked epitheliotropism was present. Neoplastic cells labelled positive for CD3 and negative for CD79a and CD117. Giemsa staining and silver staining (SNOBA) were also negative. A T-cell lymphoma with reactive fibroplasia was diagnosed, and differential diagnoses including mast cell tumor and feline gastrointestinal eosinophilic sclerosing fibroplasia could be excluded.

Adrenocorticotropic hormone, but not trilostane, causes severe adrenal hemorrhage, vacuolization, and apoptosis in rats.

Adrenal necrosis has been reported as a complication of trilostane application in dogs with hyperadrenocorticism. One suspicion was that necrosis results from the increase of adrenocorticotropic hormone (ACTH) during trilostane therapy. The aim of the current study was to assess the effects of ACTH and trilostane on adrenal glands of rats. For experiment 1, 36 rats were divided into 6 groups. Groups 1.1 to 1.4 received ACTH in different doses (60, 40, 20, and 10 µg/d) infused subcutaneously with osmotic minipumps for 16 wk. Group 1.5 received saline, and group 1.6 received no therapy. For experiment 2, 24 rats were divided into 3 groups. Group 2.1 and 2.2 received 5 and 50 mg/kg trilostane/d orally mixed into chocolate pudding for 16 wk. Eight control rats received pudding alone. At the end of the experiments, adrenal glands were assessed for necrosis by histology and immunohistochemistry; levels of endogenous ACTH and nucleosomes were assessed in the blood. Rats treated with 60 µg ACTH/d showed more hemorrhage and vacuolization and increased numbers of apoptotic cells in the adrenal glands than rats treated with 20 or 10 µg ACTH/d, trilostane, or control rats. Rats treated with 60 µg ACTH/d had a higher amount of nucleosomes in the blood compared with rats treated with 10 µg ACTH/d, trilostane, or saline. We conclude that in healthy rats ACTH, but not trilostane, causes adrenal degeneration in a dose-dependent manner. Results of this study support the hypothesis that adrenal gland lesions seen in trilostane-treated dogs are caused by ACTH and not by trilostane.