Pituitary-dependent Hyperadrenocorticism Research Articles

Ki-67 and minichromosome maintenance-7 (MCM7) expression in canine pituitary corticotroph adenomas

Pituitary-dependent hyperadrenocorticism (PDH) caused by pituitary corticotroph adenoma is a common endocrine disorder in dogs. The ratio between pituitary height and the area of the brain (P/B) has been used to evaluate the pituitary size. A P/B ratio > 0.31 indicates an enlarged pituitary, whereas a P/B ratio ≤ 0.31 indicates a nonenlarged pituitary. The aim of this study was to investigate the expression of proliferation markers Ki-67 and minichromosome maintenance-7 (MCM7) in canine corticotroph adenomas in enlarged and in nonenlarged pituitaries and to evaluate their relation with the size of canine pituitary corticotroph adenomas. Ki-67 and MCM7 expression in ACTH-positive tumor cells was determined by dual-labeling immunohistochemistry in resected corticotroph adenomas from 15 dogs with PDH. The mean ± SD Ki-67 labeling index (LI) was 0.55% ± 0.59% in corticotroph adenomas with nonenlarged pituitaries and 1.6% ± 0.6% in adenomas with enlarged pituitaries. The MCM7 LI in corticotroph adenomas with nonenlarged pituitaries and in adenomas with enlarged pituitaries was 2.9% ± 2.2% and 10.9% ± 3.7%, respectively. The Ki-67 LI and MCM7 LI were significantly greater in the adenomas with enlarged pituitaries than in the adenomas with nonenlarged pituitaries ( P < 0.01 and P < 0.01, respectively). The MCM7 LI was significantly greater than the Ki-67 LI in adenomas ( P < 0.01). The Ki-67 LI was positively correlated with the MCM7 LI ( r = 0.820, P < 0.01), and the P/B ratio was positively correlated with the Ki-67 LI ( r = 0.560, P = 0.03) and the MCM7 LI ( r = 0.854, P < 0.01). In conclusion, canine corticotroph adenomas in enlarged pituitaries show greater proliferation potential than do adenomas in nonenlarged pituitaries. MCM7 expression was significantly greater than Ki-67 expression in canine pituitary corticotroph adenomas. Thus, MCM7 may be superior to Ki-67 as a proliferation marker in pituitary tumors.

Low dose of insulin detemir controls glycaemia, insulinemia and prevents diabetes mellitus progression in the dog with pituitary-dependent hyperadrenocorticism

Diabetes is often associated with pituitary-dependent hyperadrenocorticism (PDH). Hypercortisolism causes insulin resistance and affects β-cell function. The purpose of this study was to test if daily administration of a long-acting insulin analogue during the first month of anti-PDH treatment can prevent progress to diabetes in these animals. Twenty-six PDH dogs were divided into three groups: one group with glycaemia <5.83mmol/L and two groups with glycaemia >5.83mmol/L and <9.35mmol/L, one of which received insulin detemir during 4months. Dogs with glycaemia <5.83mmol/L and those with glycaemia >5.83mmol/L which received insulin did not develop diabetes. In the non-insulin group, 6/7 dogs developed diabetes after the third month. There is a 13-fold higher risk of diabetes in dogs with glycaemia >5.83mmol/L and no insulin treatment. Administering insulin detemir to dogs with PDH and glycaemia >5.83mmol/L could prevent progression to diabetes.

The European Registry on Cushing's syndrome: 2-year experience. Baseline demographic and clinical characteristics

The European Registry on Cushing's syndrome (ERCUSYN) is designed to collect prospective and follow-up data at EU level on Cushing's syndrome (CS). Baseline data on 481 CS patients (390 females, 91 males; mean age (±s.d.): 44±14 years) collected from 36 centres in 23 countries, including new patients from 2008 and retrospective cases since 2000. Patients were divided into four major aetiologic groups: pituitary-dependent CS (PIT-CS) (66%), adrenal-dependent CS (ADR-CS) (27%), CS from an ectopic source (ECT-CS) (5%) and CS from other aetiologies (2%). Proportion of men in the ECT-CS group was higher than in the other groups (P<0.05). The ADR-CS group was older than the PIT-CS (P<0.05). Prevalence of hirsutism (92%) and diabetes (74%) in ECT-CS was higher than in the other groups (P<0.05 and P<0.01 respectively). PIT-CS had more skin alterations, menstrual irregularities and hirsutism than ADR-CS (P<0.01). Reduced libido was more prevalent in men than women (P<0.01). Prevalence of spine osteoporosis was higher in men than women (P<0.05), and males had more vertebral and rib fractures than females (52 vs 18% for vertebrae; P<0.001 and 34 vs 23% for ribs; P<0.05). ECT-CS consulted a diabetologist more frequently than ADR-CS (P<0.05), while a gynaecologist was consulted more often by women with PIT-CS or ADR-CS than with ECT-CS (P<0.05). Overall, weight gain was more common in women than men (P<0.01). CushingQoL and EuroQoL visual analogue scale scores did not differ between the groups. The ERCUSYN project demonstrates a heterogeneous clinical presentation of CS at a European level, depending on gender and aetiology.

Evaluation of twice-daily lower-dose trilostane treatment administered orally in dogs with naturally occurring hyperadrenocorticism

To evaluate effectiveness and incidence of adverse reactions to twice-daily lower-dose oral administration of trilostane in the treatment of dogs with naturally occurring hyperadrenocorticism (NOH). Clinical trial. 47 dogs with NOH. 47 dogs were treated orally with trilostane (0.21 to 1.1 mg/kg [0.1 to 0.5 mg/lb], q 12 h). All dogs were reevaluated at 2 weeks and 2 months, 38 dogs at 6 months, and 28 dogs at 1 year of treatment. 9 of 47 dogs had an adrenocortical tumor causing NOH, and all had good responses after 2 months (mean trilostane dosage, 0.89 mg/kg [0.40 mg/lb], q 12 h). All successfully underwent surgical adrenal tumor extirpation. Thirty-eight dogs had pituitary-dependent hyperadrenocorticism (PDH); 15 dogs did not require a dose increase during the study, and at each of 4 reevaluations, 10 of 15, 13 of 15, 14 of 15, and 11 of 11 had a good response. Twenty-three dogs with PDH had their dose or frequency of trilostane administration increased during the study. Mean trilostane dosage at 1-year reevaluation in dogs with a good response was 1.7 mg/kg (0.8 mg/lb), twice daily, or 1.1 mg/kg, 3 times daily. At each of 4 reevaluations, 17 of 23, 14 of 23, 17 of 23, and 13 of 17 dogs with PDH had a good response. Five dogs became ill because of trilostane-induced adverse effects, but only 1 required hospitalization. Administration of initial lower doses of trilostane to dogs with NOH is effective.

Blindness in dogs with pituitary dependent hyperadrenocorticism: Relationship with glucose, cortisol and triglyceride concentration and with ophthalmic blood flow

Pituitary dependent hyperadrenocorticism (PDH) shows a high morbidity and blindness is one of its complications. Compression of the optic chiasm (OC) by the hypophysis adenoma is one of the causes. Another cause could be due to vascular and metabolic alterations of the PDH. Out of a total of 70 dogs with confirmed diagnosis of PDH, 12/70 showed blindness. In only 2/12 the OC was compromised.Electroretinography in dogs without the OC being compromised showed altered A and B wave patterns. Ophthalmological Doppler showed an alteration of the blood flow only in blind dogs without OC compression. Cortisol concentrations (Co), triglycerides (Tg) and glycaemia (G) were greater in 10 dogs with non-compressive blindness vs. dogs with conserved vision. Loss of vision correlated with the increase in these variables. Blindness in dogs with PDH would be related to changes in retinal blood flow, associated to higher Co, Tg and G concentrations.

A Comparison of Factors that Influence Survival in Dogs with Adrenal‐Dependent Hyperadrenocorticism Treated with Mitotane or Trilostane

Trilostane is a recognized treatment for canine pituitary-dependent hyperadrenocorticism (PDH); however, its efficacy in dogs with adrenal-dependent hyperadrenocorticism (ADH) is unknown. To examine factors that might influence survival in the medical management of ADH, with particular emphasis on treatment selection. Thirty-seven animals referred to 4 centers over a period of 12 years that had been diagnosed with ADH and treated with either trilostane (22/37), mitotane (13/37), or both (2/37). Retrospective analysis of clinical records. There was no statistically significant difference between the survival times of 13 dogs treated only with mitotane when compared with 22 dogs treated only with trilostane. The median survival time for animals treated with trilostane was 353 days (95% confidence interval [CI] 95-528 days), whereas it was 102 days (95% CI 43-277 days) for mitotane. Metastatic disease was detected in 8 of 37 dogs. There was a significantly lower probability of survival for dogs with metastatic disease when compared with those without metastatic disease (P < .001). The choice of medical treatment for ADH may not have a major effect on survival times. However, the presence of metastatic disease considerably decreases survival time regardless of the choice of medical treatment.

Ultrasonographic Adrenal Gland Measurements in Clinically Normal Small Breed Dogs and Comparison with Pituitary-Dependent Hyperadrenocorticism

Ultrasonography is a sensitive and specific screening method for assessing the adrenal glands. The upper limit of the normal adrenal gland width is used as 7.5 mm. It is not known if adrenal gland width remains consistent with body weight. A reliable criterion of adrenal gland width in small breed dogs should be established. Small breed dogs with body weights of less than 10 kg were divided into two groups: 189 normal dogs and 22 dogs with pituitary-dependent hyperadrenocorticism (PDH). A retrospective study was conducted on dogs seen between January 1, 2006, and February 10, 2008. One hundred eighty-nine dogs of 14 different small breeds were enrolled in the normal adrenal gland group; the median gland width was 4.20 mm. Twenty-two dogs were in the PDH group; the median gland width was 6.30 mm. The cut-off value between normal adrenal glands and PDH was 6.0 mm. This figure gave a sensitivity and specificity of 75 and 94%, respectively, for detecting PDH. The adrenal gland appeared as a peanut shape with homogeneous hypoechoic parenchyma in normal dogs and in most dogs with PDH as well. This study was performed in a large population of small breed dogs and suggests that the normal adrenal gland size in small breed dogs is smaller than previously reported. We believe that a cut-off of 6.0 mm may be used as the criterion for differentiating a normal adrenal gland from adrenal hyperplasia.

Abdominal Aortic Chondrosarcoma in a Dog

A 14-year-old, mixed breed dog was presented with acute pain and paresis of the hindlimbs. Ultrasonography revealed an intraluminal mass and an abrupt halt of blood flow signal in the distal abdominal aorta. The mass had homogeneous hyperechoic echotexture compared with blood flow. Although clinical presentation suggested a thromboembolism and pituitary dependent hyperadrenocorticism was suspected as a predisposing cause based on adrenal function tests and ultrasonography, an aortic chondrosarcoma originating from the distal abdominal aorta was diagnosed with histologic examination. Primary aortic sarcoma is extremely rare, and extraskeletal chondrosarcoma is only reported in 2 cases previously. Aortic neoplasm should be included in differential diagnosis when an intraluminal aortic mass is observed on ultrasonography and acute paresis of hindlimbs is shown.

Magnetic Resonance Imaging Assessment of Pituitary Posterior Lobe Displacement in Dogs with Pituitary-Dependent Hyperadrenocorticism

The displacement and signal intensity (SI) of the pituitary posterior lobe were evaluated on T1 weighted magnetic resonance (MR) images in 28 dogs with pituitary dependent hyperadrenocorticism (PDH). Compared with normal dogs, the posterior lobe was displaced dorsally in the pituitary of the PDH dogs. Correlation between the pituitary height/brain area (P/B) ratio and the displacement of the posterior lobe in the PDH dogs suggests that dorsal displacement of the posterior lobe increases in accordance with enlargement of the pituitary. As to the SI of the posterior lobe, the PDH dogs showed significantly lower SI in comparison to the normal dogs. Taken together, these results suggest that assessment of the displacement and SI of the posterior lobe of the pituitary on T1-weighted MR images is useful for the diagnosis of pituitary adenoma. In pituitary microadenoma that presents no apparent tumorigenesis on MRI, evaluation of these values may be useful for diagnosis and selection of an appropriate therapy.

INTRA- AND INTEROBSERVER VARIABILITY OF ULTRASONOGRAPHIC MEASUREMENTS OF THE ADRENAL GLANDS IN HEALTHY BEAGLES

The aim of the present study was to establish which adrenal gland measurement was characterized by the least variations. To do this, we quantified the variability of seven different size measurements of the canine adrenal gland (maximal length, maximal height at the cranial and caudal poles on longitudinal and transverse images, and maximal width of the cranial and caudal poles) within observer, between observer, and between dogs based on three different measurements made by each of the three observers in six healthy Beagle dogs. The height of the caudal pole of both adrenal glands measured on longitudinal images had the lowest intra- and interobserver variability, while measurements of the length had the highest intra- and interobserver variability. Other measurements that were characterized by low intra- and interobserver variability were: height and width of the caudal pole on transverse images and height of the cranial pole on longitudinal images only. These results provide a basis for further study of the changes in adrenal gland size in dogs with pituitary-dependent hyperadrenocorticism.

Pituicytoma in a patient with Cushing’s disease: case report and review of the literature

Pituicytoma is an exceptionally rare low-grade glioma (WHO grade I) of the neurohypophysis and infundibulum. We are reporting the case of a 48-year-old man who presented with severe Cushing's syndrome. Endocrinological evaluation unequivocally confirmed pituitary-dependent Cushing's syndrome (=Cushing's disease). Cranial MR-imaging displayed a conspicuous area in the dorsal and basal pituitary gland and a minimal bulging of the pituitary gland paramedian of the pituitary stalk on the right side. Transsphenoidal inspection revealed a small tumor in the basal and dorsal pituitary gland. Surprisingly, the definite postoperative histopathological diagnosis of the removed tumor was pituicytoma and not pituitary adenoma. Hence, the microadenoma responsible for Cushing's disease was not yet removed and persistent hypercortisolism necessitated transsphenoidal re-operation. During re-operation, hemihypophysectomy was performed on the right side. The non-tumorous specimen of the adeno-hypophysis showed signs of Crooke's hyalinization consistent with Cushing's disease. Undetectable postoperative ACTH- and cortisol levels provided clear evidence that the underlying ACTH-source was successfully removed during re-operation. Coincidence of pituicytoma and pituitary-dependent Cushing's disease has not previously been reported.

Canine hyperadrenocorticism: Part 1

Companion AnimalVolume 15, Issue 2 p. 51-57 Canine hyperadrenocorticism: Part 1 Rosario Cerundolo DVM CertVD DipECVD MRCVS, Rosario Cerundolo DVM CertVD DipECVD MRCVS EUROPEAN AND RCVS RECOGNISED SPECIALIST IN VETERINARY DERMATOLOGY DICK WHITE REFERRALS, VETERINARY SPECIALIST CENTRE, STATION FARM, LONDON ROAD, SIX MILE BOTTOM, SUFFOLK. CB8 0UHSearch for more papers by this author Rosario Cerundolo DVM CertVD DipECVD MRCVS, Rosario Cerundolo DVM CertVD DipECVD MRCVS EUROPEAN AND RCVS RECOGNISED SPECIALIST IN VETERINARY DERMATOLOGY DICK WHITE REFERRALS, VETERINARY SPECIALIST CENTRE, STATION FARM, LONDON ROAD, SIX MILE BOTTOM, SUFFOLK. CB8 0UHSearch for more papers by this author First published: 30 September 2010 https://doi.org/10.1111/j.2044-3862.2010.tb00450.xAboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume15, Issue2March 2010Pages 51-57 RelatedInformation

Pituitary-dependent hyperadrenocorticism and generalised toxoplasmosis in a cat with neurological signs

A 12-year-old female neutered cat presented with acute onset unilateral vestibular syndrome, a spontaneous cutaneous wound, polyuria, polydipsia, and diabetes mellitus. Hyperadrenocorticism was demonstrated by means of hyper-responsiveness to adrenocorticotropic hormone stimulation, elevated urine cortisol-to-creatinine ratio, bilaterally enlarged adrenal glands on abdominal ultrasound, and pituitary enlargement on computed tomography imaging. The cat was euthanased and post-mortem histological examination revealed feline skin fragility syndrome; confirmed a pituitary cromophobe macroadenoma; and generalised toxoplasmosis with tachyzoites in the pancreas, bowel and brain. This report is the first to describe the concurrence of macroadenoma pituitary-dependent hyperadrenocorticism and generalised toxoplasmosis in a cat with central vestibular syndrome.

Computed tomography and low-field magnetic resonance imaging of the pituitary gland in dogs with pituitary-dependent hyperadrenocorticism: 11 cases (2001–2003)

To compare the results of computed tomography (CT) and magnetic resonance imaging (MRI) of the pituitary gland in dogs with pituitary-dependent hyperadrenocorticism (PDH) caused by histologically confirmed pituitary adenoma. Retrospective case series. 11 dogs with PDH that underwent transsphenoidal hypophysectomy. Medical records of dogs examined between January 2001 and March 2003 were reviewed. Dogs were included in this study if they had clinical signs of hypercortisolism at the time of admission (for which PDH was diagnosed) and underwent transsphenoidal hypophysectomy. Pre- and postcontrast CT and low-field MRI (0.2-Tesla magnet) were performed on the same day as surgery for each dog. An abnormal pituitary gland was found in 7 dogs by use of MRI and in the same 7 dogs by use of CT. Significant differences were found between postcontrast CT and MR images for height, width, and length of the pituitary gland; brain area; and thickness of the sphenoid bone. However, the pituitary gland height-to-brain area ratio determined from postcontrast CT and MR images was not significantly different. The signal-to-noise ratio and contrast-to-noise ratio of pre- and postcontrast MR images were significantly higher than those of the CT images. Low-field MRI and dynamic CT imaging of the pituitary gland provided comparable information on the presence of pituitary adenomas in dogs with PDH.

A comparative study by age and gender of the pituitary adenoma and ACTH and α-MSH secretion in dogs with pituitary-dependent hyperadrenocorticism

Pituitary-dependent hyperadrenocorticism (PDH) is frequent in dogs. Little is known about its presentation in different age groups and its characteristics. Dividing the population under study ( n = 107) into three age groups we observed that 11.2% were young, 51.4% adults and 37.4% aged. Using magnetic resonance, pituitary tumours were intra-sellar (IS) in 30.8% and extra-sellar (ES) in 62.6% and the pars intermedia (PI) was affected in 6.5%. ES are predominant in females and IS in males ( p < 0.0001). In the adult-aged population, the ES and PI are predominant, while in the young, the IS predominate ( p < 0.0001). ACTH concentration was greater in the ES vs. IS ( p < 0.05). α-MSH did not present significant differences according to tumour size, showing a negative correlation ( r = −0.47; p < 0.01) vs. ACTH. Differences in adenoma size according to gender and their age-related frequency of apparition could be because of different origins of the corticotrophinoma.

Assessing the immune state of dogs suffering from pituitary gland dependent hyperadrenocorticism by determining changes in peripheral lymphocyte subsets

In order to evaluate the immune state of dogs suffering from pituitary-dependent hyperadrenocorticism (PDH), peripheral lymphocyte subsets were examined. Twenty seven PDH dogs and eight healthy control dogs were used in the current study. Eight healthy dogs served as the control group. Twenty seven PDH dogs were categorized into 4 groups based on their post serum cortisol concentrations by ACTH stimulation test: 2-5, excellent control (n = 8); 5-20, fair control (n = 7); >20, poor control (n = 4); and untreated (n = 8). Cell counts were executed with white blood cells (WBC), lymphocytes, CD3(+) (T lymphocytes), CD4(+) (Helper T lymphocytes), CD8(+) (Cytotoxic T lymphocytes), CD21(+) (B lymphocytes) cells in addition to calculating CD4(+)/CD8(+) ratio. Results indicated a significant difference in lymphocyte numbers and lymphocyte subset populations (CD3(+), CD4(+), CD8(+), and CD21(+) cells) between PDH and control dogs. Moreover, comparison of the PDH groups (excellent control; fair control; poor control; untreated) demonstrated that all groups had a significant decrease in lymphocytes numbers (CD3(+), CD4(+) and CD21(+) cell counts) as compared to control group. Meanwhile, no significant differences were observed in WBC counts and CD4(+)/CD8(+) ratio between groups. Furthermore, lymphocyte subset distribution in excellent control PDH dogs without concurrent disease (n = 4) better resembled that of control dogs as compared to PDH dogs with concurrent disease (n = 4). PDH dogs may be suffering from an immuno-depressed state as evidenced by significant differences in lymphocyte subset populations. Furthermore, treatment of both PDH and concurrent disease might improve lymphocyte subset distribution.

Pneumothorax secondary to pulmonary thromboembolism in a dog

To describe a case of spontaneous pneumothorax secondary to pulmonary thromboembolism possibly associated with pituitary dependent hyperadrenocorticism. A 7-year-old spayed female Collie weighing 26 kg was referred for evaluation of spontaneous pneumothorax. An exploratory thoracotomy was performed and revealed 2 lung lobes to be diffusely hemorrhagic and they were resected. Histologic examination of multiple sections documented diffuse thromboembolism. A 2-3 cm thrombus was visualized distal to the bifurcation of the pulmonary artery during an echocardiographic examination postoperatively. The dog was discharged to the owner after recovery from surgery. The thrombus had resolved at the 4-week recheck examination. Diagnosis of pituitary dependent hyperadrenocorticism was confirmed based on follow-up endocrine testing. This is the first report of pulmonary thromboembolism causing spontaneous pneumothorax in the dog.

Use of ketoconazole to treat dogs with pituitary-dependent hyperadrenocorticism: 48 cases (1994–2007)

To evaluate the effectiveness of ketoconazole as a treatment for dogs with pituitary-dependent hyperadrenocorticism (PDH). Retrospective case series. 48 client-owned dogs in which PDH was diagnosed. Medical records of dogs with PDH that were treated with ketoconazole were examined. Data collected from each record included signalment, clinical signs, results of ACTH stimulation tests before and after treatment with ketoconazole, serum alkaline phosphatase (ALP) and alanine aminotransferase (ALT) activities, dosage of ketoconazole, clinical response, and survival time. 43 of 48 (90%) dogs had evidence of clinical improvement during the treatment period. In all dogs, treatment with ketoconazole resulted in significantly lower serum cortisol concentrations as measured before and after ACTH stimulation testing; 69% (33/48) of serum cortisol concentrations measured after ACTH stimulation were within the reference range. Serum ALP and ALT activities significantly decreased after treatment with ketoconazole. Survival time after diagnosis of PDH ranged from 2 to 61 months (mean, 26.9 months; median, 25 months). Ketoconazole was a safe and effective option for treating dogs with PDH. Additional research is needed to evaluate the effects of long-term treatment with ketoconazole on adrenal glands.

Persistent isolated hypocortisolism following brief treatment with trilostane

A 12-year-old male neutered Miniature Poodle with confirmed pituitary-dependent hyperadrenocorticism was treated with trilostane. After three doses, it developed clinical and laboratory changes suggestive of isolated hypocortisolism ('atypical hypoadrenocorticism'), which persisted and progressed for more than 3 months despite immediate withdrawal of the trilostane. The clinical signs of hyperadrenocorticism resolved without further trilostane. After 3 months, prednisolone treatment was started and the clinical signs of hypocortisolism resolved. Prednisolone therapy was required for more than 1 year. Ultrasonography initially demonstrated large hypoechoic adrenal cortices, typical of dogs with hyperadrenocorticism, which then became small and heteroechoic, consistent with the development of adrenal necrosis. Persistent isolated hypocortisolism has not been reported previously as a complication of trilostane therapy. The case is also remarkable for the very short duration of trilostane therapy that elicited this complication. Clinicians should be aware that trilostane therapy may result in adrenal necrosis, even in the very earliest stages of therapy, but prompt action can prevent a life-threatening situation.

Serum concentrations of cortisol and cortisone in healthy dogs and dogs with pituitary-dependent hyperadrenocorticism treated with trilostane

The serum concentrations of cortisol and cortisone were measured in 19 healthy dogs and in 13 dogs with pituitary-dependent hyperadrenocorticism (pdh) before and one hour after an injection of synthetic...