Adrenocorticotropic hormone-producing pituitary adenoma with pituitary apoplexy treated by surgical decompression: a case report.

BACKGROUND: Pituitary-dependent hypercortisolism (PDH) is one of the most common endocrine disorders in veterinary medicine. However, there are few reports on pituitary tumor apoplexy (PTA) in dogs and no reports on its surgical intervention in veterinary medicine. Accordingly, the appropriate treatment is unknown. Herein, a case of PDH and PTA in a dog treated surgically is described. CASE PRESENTATION: A mongrel female dog (spayed; age, 8 years and 8 months; weight, 6.1 kg) with persistently elevated alkaline phosphatase underwent adrenocorticotropic hormone (ACTH) stimulation testing (post-stimulation cortisol: 20.5 µg/dL), abdominal ultrasonography (adrenal gland thickness: left, 5.7 mm; right, 8.1 mm), and brain magnetic resonance imaging (MRI) (pituitary-to-brain ratio [PBR], 0.61) at the referral hospital, resulting in a diagnosis of PDH (day 0). On day 9, the dog visited XXXX for the preparation of pituitary surgery to treat PDH. However, on days 10-15, the dog developed a loss of energy and appetite, bloody diarrhea, vomiting, and a decreased level of consciousness. However, on day 16, the dog's condition recovered. A preoperative MRI scan performed on day 52 (the day of surgery) showed apoplexy in the dorsal pituitary region (PBR, 0.68). Based on the PTA findings, the risks of surgery were described to the owner, and approval was obtained. At the time of trans-sphenoidal surgery, a partial pituitary resection was performed with preservation of the PTA area due to adhesions between the PTA area of the right side of the pituitary and surrounding tissues. The resected pituitary tissue was diagnosed as an ACTH-producing adenoma, with necrotic and hemorrhagic findings. As of day 290, endogenous ACTH and cortisol levels did not exceed the reference range. CONCLUSIONS: The acute signs that occurred on days 10-15 were most likely caused by PTA. Therefore, when signs similar to those detected in acute hypoadrenocorticism are observed in dogs with PDH, it is necessary to include PTA as a differential diagnosis. Trans-sphenoidal surgery may be effective in PDH-affected dogs that develop PTA, but careful attention should be paid to tissue adhesions secondary to hemorrhage that may occur after PTA.

Diagnostic utility of clinical and laboratory test parameters for differentiating between sudden acquired retinal degeneration syndrome and pituitary-dependent hyperadrenocorticism in dogs.

OBJECTIVE: To identify discriminating factors, using clinical ophthalmic examination findings and routine laboratory testing, that differentiate dogs with early sudden acquired retinal degeneration (SARDS; vision loss <6 weeks' duration), age- and breed-matched control dogs, and dogs with pituitary-dependent hyperadrenocorticism (PDH). ANIMALS: Client-owned dogs: 15 with SARDS with <6 weeks duration of vision loss, 14 age- and breed-matched control dogs, and 13 dogs with confirmed PDH. PROCEDURES: Dogs underwent ophthalmic examination, electroretinography (ERG) fundus photography, and spectral-domain optical coherence tomography (SD-OCT) in addition to physical examination, urinalysis, serum biochemistry, complete blood count, and adrenocorticotrophic hormone (ACTH) stimulation testing. Statistical analysis was performed using receiver operating curve area under the curve analysis, principal component analysis with sparse partial least squares analysis, and one-way ANOVA. RESULTS: Dogs with SARDS all had absent vision and ERG a- and b-waves. SD-OCT demonstrated that dogs with SARDS had significantly thicker inner retina, thinner outer nuclear layer, and thicker photoreceptor inner/outer segment measurements than either controls or dogs with PDH. Discriminating laboratory parameters between dogs with SARDS and PDH with high specificity included post-ACTH serum cortisol (<19.3 µg/dL), AST:ALT ratio (>0.343), and urine specific gravity (>1.030). CONCLUSIONS AND CLINICAL RELEVANCE: We have identified significant discriminators between SARDS and PDH. This work provides the basis for future studies that could identify and examine dogs with SARDS prior to vision loss, which may extend the potential therapeutic window for SARDS.

Histopathologic Findings in Canine Pituitary Glands.

To optimize the histologic evaluation of hypophysectomy specimens, sections of 207 canine pituitary glands (196 postmortem, 11 hypophysectomy specimens) were reviewed. Adenohypophyseal proliferation was the most common (n = 79) lesion. Proliferative lesions were sparsely to densely granulated; the granules were usually basophilic to chromophobic and periodic acid-Schiff-positive. Adenohypophyseal proliferation was classified as hyperplasia (n = 40) if ≤2 mm diameter with intact reticulin network, as microadenoma (n = 22) for 1-5 mm homogeneous nodules with lost reticulin network, or as macroadenoma (n = 17) for larger tumors. Craniopharyngeal duct cysts were common incidental lesions and the only lesion in 15 dogs. Uncommon diagnoses included lymphoma (n = 4), hemorrhagic necrosis (n = 4), metastatic carcinoma (n = 3), hypophysitis (n = 3), ependymoma (n = 2), craniopharyngioma (n = 2), and 1 case each of metastatic melanoma, pituicytoma, gliomatosis, germ cell tumor, meningioma, and atrophy. The pituitary histologic diagnosis was associated with hyperadrenocorticism (HAC; P < .001) and adrenocortical histologic diagnosis ( P = .025). Both HAC and adrenocortical hyperplasia showed a positive trend with the degree of adenohypophyseal proliferation. The association of adrenocortical hyperplasia with HAC was not significant ( P = .077). Dogs with adenohypophyseal proliferations were older than dogs with normal pituitary glands ( P < .05). Brachycephalic breeds were overrepresented among dogs with pituitary macroadenoma or craniopharyngeal duct cysts, but the association was not statistically significant ( P = .076). Adenohypophyseal hyperplasia was more common than adenoma among postmortem specimens, but was unexpected in >80% of cases. Pituitary macroadenoma was the most common diagnosis in hypophysectomy specimens.

Update on the use of trilostane in dogs.

Many articles published in the past few years have contributed to a better understanding of the use of trilostane in dogs. Trilostane is a competitive inhibitor of 3ß-hydroxysteroid dehydrogenase, the enzyme essential for synthesis of cortisol and all other steroids. Trilostane is reported to be safe and effective in the treatment of pituitary-dependent hyperadrenocorticism (HAC), adrenal-dependent HAC, and alopecia X. While trilostane controls most of the clinical signs associated with HAC, abnormalities such as hypertension, hypercoagulability, and proteinuria may persist despite therapy. Because the duration of cortisol suppression after a dose of trilostane is often less than 12 hours, many dogs with HAC could benefit from low dose trilostane treatment every 12 hours. Many controversies regarding trilostane still exist. This review provides a comprehensive commentary on trilostane's indications, mode of action, dose, monitoring, efficacy, and adverse effects.

Mise à jour sur l'utilisation du trilostane chez les chiens. De nombreux articles publiés au cours des dernières années ont contribué à une meilleure compréhension de l'utilisation du trilostane chez les chiens. Le trilostane est un inhibiteur compétitif de la 3ß-hydroxystéroïde déshydrogénase, l'enzyme essentiel pour la synthèse du cortisol et de tous les autres stéroïdes. On signale que le trilostane est sûr et efficace pour le traitement de l'hyperadrénocorticisme pituitaire (HAC), le HAC adrénal et l'alopécie X. Bien que le trilostane maîtrise la plupart des signes cliniques associés au HAC, des anomalies comme l'hypertension, l'hypercoagulabilité et la protéinurie peuvent persister malgré la thérapie. Parce que la durée de la suppression du cortisol après une dose de trilostane est souvent de moins de 12 heures, plusieurs chiens atteints de HAC pourraient bénéficier d'un traitement à faible dose de trilostane toutes les 12 heures. Il subsiste encore beaucoup de controverse concernant le trilostane. Cet examen fournit un commentaire exhaustif sur les indications, le mode d'action, la dose, la surveillance, l'efficacité et les effets secondaires du trilostane.(Traduit par Isabelle Vallières).

PITUITARY PARS INTERMEDIA DYSFUNCTION (EQUINE CUSHING'S DISEASE) IN NONDOMESTIC EQUIDS AT MARWELL WILDLIFE: A CASE SERIES. ONE CHAPMAN'S ZEBRA ( EQUUS QUAGGA CHAPMANI) AND FIVE PRZEWALSKI's HORSES ( EQUUS FERUS PRZEWALSKII).

Pituitary pars intermedia dysfunction (PPID), also known as equine Cushing's disease, is widely reported in middle-aged to older domestic equids but to date reported in only one nondomestic equid, the onager ( Equus hemionus onager). This case series reports clinical, hematological, and pathological findings consistent with PPID in two further equid species: one Chapman's zebra ( Equus quagga chapmani) and five Przewalski's horses ( Equus ferus przewalskii). The case series reports basal adrenocorticotropic hormone (ACTH) testing as a method to diagnose and monitor PPID in zoological equids and the use of pergolide mesylate to reduce basal ACTH concentration and reduce clinical signs associated with PPID. Gross and histopathological examinations of the pituitary gland in four of these cases revealed either pars intermedia adenomas or adenomatous hyperplasia, similar to pathological findings in domestic equids affected by PPID. These findings suggest that clinicians working with nondomestic equids should be aware of this condition and consider screening for it routinely, particularly given that improvements in management and veterinary care for exotic animals are resulting in a more aged captive population. Early diagnosis and treatment of PPID may prevent the development of painful clinical sequelae and therefore improve the welfare of zoo equids.

Transsphenoidal surgery using a high definition video telescope for pituitary adenomas in dogs with pituitary dependent hypercortisolism: methods and results.

OBJECTIVE: To (1) establish a technique for transsphenoidal removal of pituitary adenomas in dogs with pituitary dependent hypercortisolism (PDH) using a high definition video telescope, and (2) report initial outcomes. STUDY DESIGN: Prospective case series. ANIMALS: Dogs with pituitary dependent hypercortisolism (PDH; n = 26) with suprasellar masses. METHODS: Pituitary tumors were removed using a modification of a transoral transsphenoidal approach. Surgery was observed using a high definition video telescope (VITOM™) and localization of the sella was performed by drilling pilot holes in the basisphenoid bone followed by computed tomography (CT). RESULTS: Dogs had PDH confirmed by urinary cortisol to creatinine ratio (UCCR) and endogenous ACTH assays, and tumors confirmed by MRI. There were no postoperative cerebrospinal fluid leaks, wound dehiscence, or surgical site infections. Overall postoperative mortality was 19% with no mortality observed in the last 16 dogs, indicating an initial "learning curve" followed by good surgical results. All dogs that survived the immediate postoperative period (1 week) returned to their owners in good health, on hormonal replacement therapy. Follow-up ranged from 3 to 36 months. Sustained tumor control and hormonal remission based on normalized ACTH and UCCR measurements were observed in 20/21 (95%) dogs at 1-year follow-up. CONCLUSIONS: Modifications of a trans-oral transsphenoidal technique for surgical removal of pituitary tumors provides a safe and effective strategy for long-term remission of PDH with acceptable morbidity and mortality.

Functional ectopic adrenal carcinoma in a dog.

An 11-year-old spayed female pit bull terrier was presented with a 2-month history of polyuria, polydipsia, polyphagia, and panting. Serum chemistry, blood and urine analysis, and tests for hyperadrenocorticism suggested an adrenal tumor. Abdominal ultrasound identified a mass caudal to the right kidney. The mass was completely excised and histopathology was consistent with endocrine carcinoma. Three years later there was no evidence of recurrence or metastasis.

Carcinome surrénal ectopique fonctionnel chez un chien. Une chienne Pit-bull terrier stérilisée âgée de 11 ans a été présentée avec une anamnèse de 2 mois de polyurie, de polydipsie, de polyphagie et de halètements. La chimie sérique, l'analyse du sang et de l'urine et des tests pour hyperadrénocorticisme ont suggéré une tumeur surrénale. Une échographie abdominale a identifié une masse caudale au rein droit. La masse a été entièrement excisée et l'histopathologie était conforme à un carcinome endocrinien. Trois ans plus tard, il n'y avait aucune preuve de récurrence ni de métastase.(Traduit par Isabelle Vallières).

Comparison of two treatment regimens with trilostane in dogs with pituitary-dependent hyperadrenocorticism.

Trilostane is used to treat dogs with pituitary-dependent hyperadrenocorticism (PDH). In our institution, it was initially dosed based on bodyweight (BW) categories, since April 06 it is dosed per kg BW. Our objectives were to compare effectiveness, number of dose adjustments and side effects of the two dose regimens in dogs with PDH. Dogs of group 1 (28 dogs) received trilostane based on BW categories (< 5 kg, 30 mg; 5 - 20 kg, 60 mg and > 20 kg, 120 mg; SID); dogs of group 2 (20 dogs) received 2 - 5 mg/kg SID. Treatment goal was a post-ACTH cortisol of 1 - 2.5 and 1.5 - 5.4 µg/dl in group 1 and 2, respectively. Starting doses were significantly higher in group 1 and stayed higher until re-check at 4 - 7 months. Baseline and post-ACTH cortisol were significantly decreased compared to pre-treatment at all time points in both groups. Significantly more dogs of group 2 (5/20) needed a dose increase at the first re-check and significantly more dogs of group 1 (10/23) a dose reduction at the last re-check. Intermittent discontinuation was necessary in 25 and 10 % of dogs of group 1 and 2, respectively. We conclude that dosing per kg BW results in comparable clinical improvement, decrease in cortisol, but lower risk of side effects.

Le trilostane est en Suisse le seul médicament enregistré pour le traitement de l'hyperadrénocorticisme hypophysaire. Dans les débuts, le trilostane a été dosé dans notre clinique selon les catégories de poids; depuis avril 2006 nous le dosons en fonction du poids exact. Le but du présent travail était de comparer l'efficacité, le nombre d'ajustement de la dose et les effets secondaires des deux schémas de dosage chez des chiens souffrant d'hyperadrénocorticisme hypophysaire. Chez les chiens du groupe 1 (28 chiens), le dosage à été fait de la façon suivante: < 5 kg, 30 mg; 5 ­ 20 kg, 60 mg; > 20 kg, 120 mg; q24h. Les chiens du groupe 2 (20 chiens) recevaient 2 ­ 5 mg/kg q24h. Le but du traitement était d'atteindre un taux de cortisol après ACTH entre 1 et 2.5 ug/dl dans le groupe 1 et entre 1.5 ­ 5.4 ug/dl dans le groupe 2. Les doses initiales étaient significativement plus hautes dans le groupe 1 et restaient plus élevées jusqu'au contrôle après 4 à 7 mois. Les taux de cortisol basal et après ACTH étaient significativement plus bas par rapport à ceux mesurés avant le traitement dans les 2 groupes, et ce à tout moment. La dose a du être augmentée lors du premier contrôle de façon significativement plus fréquente (5/20) dans le groupe 2. La dose a du être réduite lors des derniers contrôles de façon significativement plus fréquente (10/23) dans le groupe 1. Des interruptions de courte durée du traitement ont été nécessaires chez 25 respectivement 10 % des chiens des groupes 1 réspectivement 2. Le dosage du trilostane en fonction du poids en kilo amène une réponse thérapeutique et une chute du taux de cortisol comparables, mais avec moi s d'effets secondaires.

[Equine Cushing's disease; an update]. / De Ziekte van Cushing bij het paard; een up- date.

Lately there has been a tendency to discuss Equine Cushing's disease and its related phenomena, due to the amount of recently acquired research data. The author has composed a brief overview of the present situation emphasizing relevance for practitioners.

Clinical features of muscle stiffness in 37 dogs with concurrent naturally occurring hypercortisolism.

BACKGROUND: Severe muscle stiffness (SMS) in dogs with hypercortisolism (HC) is uncommon. OBJECTIVES: To evaluate signalment, presentation, treatments, and long-term outcomes of dogs with concurrent HC and SMS. ANIMALS: Thirty-seven dogs. METHODS: Medical records of dogs with HC and concurrent SMS were recruited from 10 institutions. Clinical information, test results, therapeutic responses, and survival times were reviewed. RESULTS: All 37 dogs with HC and SMS had pituitary-dependent hypercortisolism (PDH); 36/37 weighed <20 kg. Signs and test results were typical of PDH aside from SMS, initially diagnosed in all 4 limbs in 9, pelvic limbs of 22, and thoracic limbs of 6 dogs. Hypercortisolism and SMS were diagnosed together in 3 dogs; HC 1-36 months before SMS in 23; SMS 1-12 months before HC in 11. Mitotane or trilostane, given to control HC in 36/37 dogs, improved or resolved HC signs in 28; SMS did not resolve, remaining static or worsening in 31/36 dogs, mildly improving in 5/19 dogs given additional therapies. Progression of SMS included additional limbs in 10 dogs and the masticatory muscles of 2. The median survival time from diagnosis of SMS was 965 days (range, 8-1188). CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent SMS and HC is uncommon, possibly affecting only dogs with PDH. Development of SMS might occur before or after diagnosis of HC. Apart from SMS, the clinical picture and survival time of these dogs seem indistinguishable from those of dogs with HC in general. However, while muscle weakness usually resolves with HC treatment SMS does not.

Effect of pituitary-dependent hypercortisolism on the survival of dogs treated with radiotherapy for pituitary macroadenomas.

BACKGROUND: Radiotherapy (RT) is an effective treatment for dogs presented with neurologic signs caused by pituitary tumors. However, its impact on the outcome of concurrent pituitary-dependent hypercortisolism (PDH) is controversial. OBJECTIVES: Determine whether dogs with PDH have longer survival after pituitary RT compared with dogs with nonhormonally active pituitary masses and to evaluate whether clinical, imaging, and RT variables affect survival. ANIMALS: Ninety-four dogs divided into 2 groups: PDH and non-PDH, based on the presence of hypercortisolism. Forty-seven dogs were allocated to the PDH group and 47 to the non-PDH group. METHODS: Retrospective cohort study in which clinical records of dogs undergoing RT for pituitary macroadenomas between 2008 and 2018 at 5 referral centers were retrospectively evaluated. RESULTS: Survival was not statistically different between PDH and non-PDH groups (median survival time [MST], 590 days; 95% confidence interval [CI], 0-830 days and 738 days; 95% CI, 373-1103 days, respectively; P = .4). A definitive RT protocol was statistically associated with longer survival compared with a palliative protocol (MST 605 vs 262 days, P = .05). The only factor statistically associated with survival from multivariate Cox proportional hazard analysis was total radiation dose (Gy) delivered (P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: No statistical difference in survival was identified between the PDH and non-PDH groups, and longer survival was associated with higher Gy delivered.

Invasive aspergillosis in a putty-nosed monkey (Cercopithecus nictitans) with adrenocortical Cushing's syndrome.

BACKGROUND: An 18-year-old captive female putty-nosed-monkey (Cercopithecus nictitans) with a history of long-term infertility and hyperglucocorticism was euthanized because of perforating thoracic trauma induced by group members and subsequent development of neurological signs. METHODS: Complete necropsy and histopathological examination of formalin-fixed tissue samples was carried out. RESULTS: The monkey showed invasive pulmonary and cerebral infection with Aspergillus fumigatus together with adrenocortical neoplasia and signs of Cushing's syndrome, such as alopecia with atrophic skin changes, evidence for diabetes mellitus and marked immunosuppression. CONCLUSIONS: Spontaneous endocrinopathies are rarely described in non-human primates. Here we report the first case of spontaneous adrenocortical hyperglucocorticism predisposing to systemic aspergillosis in a putty-nosed monkey.

Evaluation of the ACTH stimulation test using a low dose of a depot formulation in healthy dogs and in dogs with untreated Cushing's syndrome.

The sensitivity of the adrenocorticotropic hormone (ACTH) stimulation test to detect Cushing's Syndrome (CS) using a depot formulation needs to be evaluated. The aims of this study were to propose a reference interval (RI) for cortisol values 1-hour after administration of a low-dose of depot ACTH in healthy dogs, and to evaluate the sensitivity of this test to detect CS, differentiating among types of CS based on ultrasound findings. Forty-one healthy dogs (20 males, 21 females) were prospectively included. Additionally, 90 dogs with CS (31 males, 59 females) were retrospectively included. Dogs with CS were ultrasonographically classified as follows: 44 dogs with symmetrical adrenomegaly consistent with pituitary-dependent hypercortisolism (PDH), 8 dogs with unilateral adrenomegaly and atrophy of the contralateral adrenal gland or unilateral or bilateral adrenomegaly with malignancy features consistent with adrenal-dependent hypercortisolism (ADH), 34 dogs with equivocal adrenal asymmetry (EAA) and 4 dogs with normal adrenal thickness. In healthy dogs, lower and upper limit of the 95% RI for 1-hour post-ACTH cortisol concentration and their 90% confidence intervals, were 4.4 (2.7-5.8) µg/dl and 18.4 (16.5-20.0) µg/dl, respectively. Post-ACTH cortisol concentration was above the RI in 90.0% (ci95%, 76.1-100) of dogs with CS. An elevated post-ACTH cortisol concentration was detected in 95.5% (ci95%, 76.1-100) of dogs with PDH, 62.5% (ci95%, 46.1-78.9) of dogs with ADH and 88.2% (ci95%, 69.1-100) of dogs with EAA. The sensitivity of the ACTH stimulation test using a low-dose of depot ACTH in high in dogs with CS.

Assessment of selegiline and trilostane combined therapy efficacy for canine pituitary-dependent hypercortisolism treatment: A pilot randomized clinical trial.

Canine pituitary-dependent hypercortisolism (PDH) management with trilostane usually demands lifelong therapy. The greater the dose needed, the greater the risk of side effects. Selegiline therapy has been previously described but not commonly used for PDH treatment. The present work aimed to assess the efficacy of selegiline and trilostane combined therapy for canine PDH treatment. Fifteen client-owned dogs diagnosed with spontaneous PDH were enrolled. The patients were treated with trilostane (Tri group, n = 8, initial dose of 0.5 mg/kg, PO, q12h), or with trilostane and selegiline (Tri + Sel group, n = 7, initial trilostane dose of 0.5 mg/kg, PO, q12h and selegiline 1 mg/kg, PO, q24h). Dogs underwent clinical examination, serum biochemical analysis, urinalysis, abdominal ultrasound, and eACTH and post-ACTH cortisol measurements on treatment days zero (D0), 30 (D30), 90 (D90), and 180 (D180). There was a lack of adverse effects due to the combined therapy. Both groups showed a similar clinical response and lower post-ACTH cortisol levels at the study's end. There was no significant difference in trilostane dosage at D180 between groups. There was no documented increase in either right or left adrenal gland thickness in the Tri + Sel group in contrast with patients in the Tri group. However, there was no statistical difference between the groups regarding eACTH at D0 and D180. Patients in the Tri + Sel group achieved better serum triglycerides control at the end of the study. The association of selegiline with trilostane might be a feasible therapy for canine PDH; however, its eventual advantages need larger studies.

Central diabetes insipidus after transsphenoidal surgery in dogs with Cushing's disease.

Transsphenoidal surgery (TSS) is an effective treatment for canine Cushing's disease, as well as human Cushing's disease. In humans, only the pituitary adenoma tissue is resected by TSS. However, in dogs, the whole pituitary including normal tissue is resected. Hence, central diabetes insipidus (CDI) may complicate the postoperative course in almost all dogs with Cushing's disease treated by TSS. However, it is difficult to assess the duration of the postoperative CDI, and whether it may be transient or permanent. In this study, postoperative CDI in 21 dogs with Cushing's disease and its predicted prognosis by preoperative parameters was investigated. In this study, CDI after TSS was classified as either transient or permanent based on the requirement for desmopressin. Preoperative circulating serum cortisol concentrations and pre- and post-operative plasma AVP concentrations were not significantly different between the transient CDI dogs and permanent CDI dogs. The duration of postoperative CDI was not correlated to the signal intensity ratio (posterior lobe of the pituitary/cerebral cortex), which is obtained from preoperative magnetic resonance imaging (MRI). However, the pituitary height/brain area (P/B) ratio of the permanent CDI dogs was significantly greater than that of the transient CDI dogs. In addition, there was a significant difference between the enlarged-pituitary (P/B ratio > 0.31) transient CDI dogs and the permanent CDI dogs. These results suggest that the incidence of postoperative permanent CDI is strongly influenced by the pituitary size.

[Diagnostic efficacy of plasma ACTH-measurement by a chemiluminometric assay in canine hyperadrenocorticism]. / Klinische Anwendung einer chemiluminometrischen ACTH-Bestimmung beim caninen Hyperadrenokortizismus.

This retrospective study was performed to investigate the diagnostic efficacy of the chemiluminometric ACTH-measurement to differentiate between pituitary and adrenal dependent hyperadrenocorticism (HAC) in dogs. 49 dogs with pituitary HAC, 10 dogs with adrenal HAC and 1 dog with a combination of both pathologies were included. Dogs with HAC like symptoms, where HAC had been ruled out, served as controls (n = 18). All dogs with adrenal HAC, as well as 9 dogs with pituitary HAC had an ACTH concentration below the detection limit of 2.2 pmol/l (10 pg/dl) plasma. Using 2.2 pmol/l as a cut-off the sensitivity and specificity to diagnose pituitary HAC was 0.82 (95 % CI 0.686 - 0.914) and 1 (95 % CI 0.692 - 1), respectively. With the help of the chemiluminometric assay, a correct classification was possible in 85 % of patients with HAC. As an ACTH-concentration below the detection limit was found in dogs with adrenal as well as pituitary HAC, additional discriminatory tests are necessary in these cases.

Metabolic profiling of serum from dogs with pituitary-dependent hyperadrenocorticism.

Hyperadrenocorticism (HAC) is one of the most common endocrine diseases in dogs characterized by excessive cortisol production caused by an adrenocorticotropic hormone (ACTH)-secreting tumor, namely pituitary-dependent HAC (PDH) or cortisol-secreting adrenal tumor. Metabolomics presents the ability to identify small molecule metabolites. Thus, the use of metabolomics techniques in canine PDH can provide information about the pathophysiology and metabolic changes in this disease. This study aimed to identify and compare differences in serum metabolites between dogs with PDH and healthy dogs. The metabolomic profile of 20 dogs diagnosed with PDH was compared with 20 healthy dogs using liquid chromatography/mass spectrometry (LC/MS), and metabolite discrimination was performed using partial least squares-discriminant analysis (PLS-DA), the variable important in projection (VIP) and fold changes (FC) group-wise comparisons. The hypergeometric test identified the significantly altered pathways. A total of 21 metabolites were found to be significantly different between the two groups. The major alterations were found in arachidonic and decanoic acid, and phospholipids related to phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI). These metabolites are related to insulin resistance and other complications (i.e. hypertension). Our results indicate that PDH produces changes in serum metabolites of dogs, and the knowledge of these changes can aid to better understanding of pathophysiological processes involved and contribute to potentially detect new biomarkers for this disease.

A case of chronic lymphocytic leukemia masked by Cushing's disease in a dog.

A 12-year-old, 3.5-kg, intact female dog was presented with polyuria, polydipsia, and a pendulous abdomen. Laboratory examinations showed elevated hepatobiliary enzyme levels and neutrophilic leukocytosis. The adrenocorticotropic hormone stimulation test confirmed hyperadrenocorticism (HAC). Trilostane therapy managed the clinical condition and cortisol concentration. However, lymphocytosis and nonregenerative anemia developed after HAC remission. Bone marrow aspiration analysis revealed a lymphoproliferative disorder with a clonal T-cell population. Accordingly, the patient was diagnosed with T-cell chronic lymphocytic leukemia (CLL) and concurrent HAC. Thereafter, chemotherapy was initiated, which improved the lymphocytosis. However, euthanasia was performed because of worsening quality of life at 45 weeks after the first presentation. These results suggested that CLL could be masked by excessive endogenous cortisol and discovered after HAC remission.

Efficacy of transsphenoidal surgery on endocrinological status and serum chemistry parameters in dogs with Cushing's disease.

Postoperative changes in endocrinological status and serum chemistry during the 4 years after transsphenoidal surgery (TSS) in 25 dogs with Cushing's disease were investigated in a prospective study. In all 25 dogs, Cushing's disease was diagnosed from resected pituitary tissues as a corticotroph adenoma in the anterior lobe of the pituitary. Prior to TSS, all 25 dogs showed hypercortisolemia. After TSS, the ACTH stimulation test showed continued low serum cortisol concentrations in 21 dogs (84%). In addition, the serum thyroid stimulating hormone concentrations decreased sequentially, while the serum T4 concentrations tended to increase due to the postoperative hormone substitution therapy utilized to avoid secondary hypothyroidism. In regard to serum chemistry, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and total cholesterol are commonly increased in canine Cushing's disease. In this study, ALP, ALT and total cholesterol were increased in 23 cases (92%), 19 cases (76%) and 20 cases (80%), respectively. However, postoperatively, these concentrations gradually decreased. The postoperative serum concentrations of ALP at 1 year, that of ALT at six months to 2 years and that of total cholesterol over the course of the 4 years decreased significantly compared with the concentrations before TSS. These results show that TSS is an effective treatment for canine Cushing's disease and for long-term improvement of hypercortisolemia. Moreover, TSS is effective in improvement of hypercortisolism, such as increased concentrations of serum ALP, ALT and total cholesterol.

Hypophysectomy for a dog with coexisting Cushing's disease and diabetes mellitus.

An 11-year-old male mixed breed dog diagnosed with Cushing's disease and diabetes mellitus was treated by hypophysectomy. After surgery, the hypercortisolemia disappeared and the diabetes status improved. The insulin requirement to control hyperglycemia gradually decreased. At 12 weeks after surgery, there was no requirement for insulin and we suspected the diabetes was completely resolved. In the present case, diabetes mellitus seems to be secondary to Cushing's disease. In conclusion, this mixed breed dog with coexisting Cushing's disease and diabetes mellitus is the first case showing the effectiveness of hypophysectomy to treat diabetes mellitus secondary to Cushing's disease in dogs.