Cytologic features of canine melanotroph and corticotroph pituitary adenomas.

BACKGROUND: The introduction of intraoperative cytology revolutionized neurosurgical procedures in human medicine, providing real-time diagnostic guidance to surgeons and contributing to improved patient outcomes. In the realm of veterinary medicine, the understanding of pituitary tumors in dogs and cats remains limited due to challenges in obtaining antemortem samples of central nervous system lesions. OBJECTIVES: The aim of this study was to describe the cytologic features of pituitary adenomas in 12 dogs that underwent hypophysectomy. METHODS: The series included nine melanotroph adenomas and three corticotroph adenomas. Definitive diagnosis was based on histopathology and immunohistochemistry. RESULTS: Cytologically, the adenomas had high numbers of bare nuclei and intact cells that were round to polygonal and situated individually or in small clusters. The intact cells had round to oval, eccentric nuclei with finely stippled chromatin and one to three prominent nucleoli and ample to abundant lightly basophilic to amphophilic, grainy cytoplasm with distinct borders, and variable numbers of discrete vacuoles. Mild-to-moderate anisocytosis and anisokaryosis, occasional binucleation, rare and atypical mitotic figures, and nuclear molding were also observed. CONCLUSIONS: The results suggest that intraoperative cytology of canine pituitary adenomas holds promise as a valuable diagnostic tool, aiding swift differentiation from other sellar masses before histologic confirmation. Cytologic characterization of pituitary adenomas in dogs is exceptionally rare in the scientific literature, making this study one of the first to offer a comprehensive description of these cytologic features.

Clinical characteristics and outcome in 15 dogs treated with transsphenoidal hypophysectomy for nonfunctional sellar masses.

OBJECTIVE: To characterize the clinical features, neurological examination findings, diagnostic imaging results, histopathological findings, and outcome following transsphenoidal hypophysectomy (TSH) in dogs with nonfunctional sellar masses (NFSM). STUDY DESIGN: Multi-institutional retrospective study. METHODS: Medical records of dogs that underwent TSH for a NFSM were reviewed for clinical signs, physical and neurological examination findings, diagnostic imaging results, endocrine testing, surgery reports, and outcome. Magnetic resonance (MR) imaging was rereviewed, and tumors were classified using the previously described system according to pituitary tumor extension and vascular involvement. Owners of dogs that survived to discharge were contacted. RESULTS: The majority of dogs presented for mentation change (12/15). The mean pituitary to brain ratio (P/B ratio) was 1.05 (0.6-1.4). Eight dogs had a tumor imaging classification of 5B. Eleven dogs were diagnosed with a nonfunctional pituitary adenoma (NFPA). Perioperative mortality was 33% (5/15). The median survival for all dogs was 232 days (0-1658). When dogs that did not survive to discharge were excluded, the median survival time was 708 days. Seven of 10 dogs that survived the perioperative period received adjunctive therapy. Owner assessment of outcome was excellent (6/7) to good (1/7). CONCLUSION: The common presenting complaint for dogs with large NFSM causing mass effect was mentation changes. Dogs with NFPA that survived to discharge and received adjunctive therapy had good to excellent outcomes. CLINICAL SIGNIFICANCE: Transsphenoidal debulking with adjunctive therapy can be considered for the treatment of NFSM causing clinical signs of mass effect in dogs. Successful long-term outcomes are possible.

Pituitary Surgery: Changing the Paradigm in Veterinary Medicine in the United States.

Medical management is currently the most common treatment for pituitary-dependent hyperadrenocorticism and hypersomatotropism/acromegaly in veterinary medicine. Medical management does not provide a cure for either disease process, and rarely is pituitary imaging a part of initial diagnostics. Early pituitary imaging in animals with clinically functional pituitary tumors provides a baseline assessment, allows monitoring of tumor changes, and permits radiation and surgical planning. Surgery is the only treatment for pituitary tumors that has curative intent and allows for a definitive diagnosis. Surgical removal of pituitary tumors via transsphenoidal hypophysectomy is an effective treatment for clinical pituitary tumors in patients exhibiting endocrine abnormalities associated with pituitary-dependent hyperadrenocorticism and hypersomatotropism. Surgery, however, is rarely pursued until patients have failed medical management, and often not until they are showing neurologic signs, making surgical success challenging. It is well documented that dogs surgically treated when the pituitary mass is small have a lower mortality, a lower recurrence rate, and a longer survival than those with larger pituitary masses. Providing owners with the option of early pituitary imaging in addition to medical, surgical, and radiation treatment options should be the standard of care for animals diagnosed with pituitary-dependent hyperadrenocorticism or hypersomatotropism.

Feline Pituitary Adenomas: Correlation of Histologic and Immunohistochemical Characteristics With Clinical Findings and Case Outcome.

Pituitary glands from 141 feline autopsy cases were reviewed histologically. Adenoma and hyperplasia were the most common lesions at 13 cases each. Pituitary adenoma was more likely than hyperplasia to be associated with clinical evidence of endocrinopathy or an intracranial mass (P < .001). A histochemical and immunohistochemical panel was applied to 44 autopsy- or hypophysectomy-derived pituitary adenomas in 43 cats from 2 diagnostic laboratories. Adenomas were differentiated from hyperplasia by the presence of disrupted reticulin fibers. One cat had a double (somatotroph and melanotroph) adenoma. Twenty somatotroph adenomas consisted of periodic acid-Schiff (PAS)-negative acidophils that expressed growth hormone; 16/20 had hypersomatotropism; 17/20 had diabetes mellitus. Eleven melanotroph adenomas consisted of PAS-positive basophils or chromophobes that expressed melanocyte-stimulating and adrenocorticotrophic hormones; 5/11 had hypercortisolism; 6/11 had diabetes mellitus. Eleven gonadotroph adenomas consisted of PAS-negative chromophobes that expressed follicle-stimulating and/or luteinizing hormones. Two thyrotroph adenomas consisted of PAS-negative basophils or chromophobes that expressed thyroid-stimulating hormone. Pituitary-dependent disease was not recognized in cats with gonadotroph or thyrotroph adenomas. The Ki-67 proliferation index in hypophysectomy specimens was lower in somatotroph than in melanotroph adenomas. Fourteen cats with hypophysectomy-treated somatotroph or melanotroph adenoma had an 899-day median survival time versus 173 days in 17 nonsurgical cases. After adjusting for age, adenoma size and type, hypophysectomized cats had an overall better survival time than nonsurgical cases (P = .029). The study results underscore the value of hypophysectomy and trophic hormone immunohistochemistry in the treatment and classification of feline pituitary adenomas.

Dal-induced red blood cell incompatibilities in a Doberman Pinscher with von Willebrand factor deficiency and ehrlichiosis.

OBJECTIVE: To describe a complex case involving the management of a dog with von Willebrand disease (vWD), active ehrlichiosis infection, nonregenerative anemia, and blood type incompatibility related to the Dal antigen. CASE SUMMARY: A 13-week-oldintact male Doberman Pinscher weighing 7.2 kg was presented to the emergency service for a previous hemorrhaging event and progressive nonregenerative anemia. The dog had received a fresh whole blood transfusion 8 days prior to presentation due to severe anemia. Upon presentation, the puppy was tachycardic, and his mucous membranes were pale. A CBC revealed a nonregenerative anemia with a PCV of 0.11 L/L (11%). von Willebrand factor deficiency was suspected and later confirmed. The dog's blood type was dog erythrocyte antigen (DEA) 1 positive, but cross-matching to 4 RBC units, both DEA 1 positive and negative, failed to yield any compatible units. Antibody against a possible Dal RBC antigen was suspected, and 11 blood donors (Dalmatians and Dobermans) were cross-matched to find 2 compatible donors. After an uneventful fresh whole blood transfusion, a bone marrow biopsy revealed a hypocellular bone marrow and erythroid hypoplasia. A SNAP4DxPlus test and subsequent polymerase chain reaction (PCR) testing were positive for Ehrlichia ewingii and E. canis. Treatment with doxycycline was started, and the PCV was 0.17 L/L (17%) at discharge. At the 1-week follow-up, the PCV was 0.24 L/L (24%), and the puppy was doing well. NEW OR UNIQUE INFORMATION PROVIDED: This is a unique case of a dog presenting with several challenging disorders, including vWD resulting in hemorrhage, ehrlichiosis potentially contributing to a nonregenerative anemia, and a blood type incompatibility due to the Dal antigen. Doberman Pinschers have a high prevalence of vWD- and Dal-negative phenotype, which emphasizes the value of cross-matching and the recognition of antigen prevalence in specific breeds.

Immunohistochemical Evaluation of Canine Pituitary Adenomas Obtained by Transsphenoidal Hypophysectomy.

Hypophysectomy specimens from 16 dogs with pituitary adenoma were evaluated with periodic acid-Schiff (PAS), reticulin, and immunohistochemistry for adrenocorticotrophic hormone (ACTH), melanocyte stimulating hormone (MSH), growth hormone (GH), and Ki-67. The reticulin network was obliterated in all adenomas. One adenoma expressed ACTH and GH. Eight corticotroph adenomas were basophilic to chromophobic, and PAS- and ACTH-positive. Seven melanotroph adenomas were distinguished from corticotroph adenomas by expression of MSH. Pituitary-dependent hypercortisolism was diagnosed in 5 of 8 dogs with corticotroph and 4 of 7 with melanotroph adenoma. Pituitary height/brain area (P/B) ratio was elevated in all dogs. Previous canine hypophysectomy studies suggested that melanotroph adenomas were larger and carried a worse prognosis than corticotroph adenomas; however, in this study, corticotroph adenomas in comparison to melanotroph adenomas were larger (median P/B ratio: 1.06 versus 0.76), more proliferative (median Ki-67 index: 9.47% versus 1.99%), and associated with shorter survival (median: 300 versus 793 days). Recommended immunohistochemistry for PAS-positive pituitary adenomas includes ACTH and MSH to distinguish corticotrophs from melanotrophs and Ki-67 for proliferation index.

Transsphenoidal surgery: accuracy of an image-guided neuronavigation system to approach the pituitary fossa (sella turcica).

OBJECTIVE: To determine the accuracy of locating the pituitary fossa with the Brainsight neuronavigation system by determining the mean target error of the rostral (tuberculum sellae) and caudal (dorsum sellae) margins of the pituitary fossa. STUDY DESIGN: Experimental cadaveric study. ANIMALS: Ten canine cadavers. METHODS: Computed tomography (CT) and MRI were performed on each cadaver with fiducials in place. Images were saved to the neuronavigation computer and used to plan the drilling approach. The cadavers were placed in the surgical head clamp of the Brainsight system and positioned for a transsphenoidal approach. On the basis of the planning, 2 localization points were drilled, 1 each at the rostral and caudal margins of the pituitary fossa, and CT was repeated. Error was assessed from the difference in millimeters between the targets identified during Brainsight planning and the actual location of the 2 points drilled on each cadaver skull as identified by postdrilling CT. RESULTS: The rostral and caudal margins of the pituitary fossa provided 2 target points per cadaver. The median target error (interquartile range) for all target sites (n = 20) was 3.533 mm (range, 2.013-4.745). CONCLUSION: This stereotactic system allowed the surgeon to locate the rostral and caudal margins of the pituitary fossa with clinically acceptable accuracy and confidence. CLINICAL SIGNIFICANCE: Using the Brainsight neuronavigation system for localization during transsphenoidal hypophysectomy may decrease morbidity and surgical time.

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.

Transsphenoidal Surgery for Pituitary Tumors and Other Sellar Masses.

Transsphenoidal surgery is an option for dogs and cats with functional and nonfunctional pituitary masses or other sellar and parasellar masses. An adrenocorticotropic hormone-secreting tumor causing Cushing disease is the most common clinically relevant pituitary tumor in dogs, and the most common pituitary tumor seen in cats is a growth hormone-secreting tumor causing acromegaly. Transsphenoidal surgery can lead to rapid resolution of clinical signs and provide a cure for these patients. Because of the risks associated with this surgery, it should only be attempted by a cohesive pituitary surgery group with a sophisticated medical and surgical team.

Effect of laparotomy on the pituitary-adrenal axis in dogs.

OBJECTIVE To assess effects of major abdominal surgery on serum cortisol and aldosterone and plasma canine ACTH (cACTH) concentrations. ANIMALS 39 healthy dogs undergoing laparotomy during veterinary student surgical laboratories. PROCEDURES Blood samples were obtained before and at completion of surgery. Serum cortisol and aldosterone and plasma cACTH concentrations were measured by use of validated radioimmunoassays. Changes in concentrations (postoperative concentration minus preoperative concentration) were calculated. Data were analyzed by use of the Wilcoxon signed rank test, Pearson correlation analysis, and Mann-Whitney rank sum test. RESULTS Cortisol, aldosterone, and cACTH concentrations increased significantly from before to after surgery. Although cortisol and aldosterone concentrations increased in almost all dogs, cACTH concentrations decreased in 6 of 32 (19%) dogs. All dogs had preoperative cortisol concentrations within the reference range, but 24 of 39 (62%) dogs had postoperative concentrations above the reference range. A correlation between the change in cACTH concentration and the change in cortisol concentration was not detected. CONCLUSIONS AND CLINICAL RELEVANCE Laparotomy caused a significant increase in serum cortisol and aldosterone concentrations. In most dogs, but not all dogs, plasma cACTH concentrations increased. Lack of correlation between the change in cACTH concentration and the change in cortisol concentration suggested that increased postoperative cortisol concentrations may have been attributable to ACTH-independent mechanisms, an early ACTH increase that caused a sustained cortisol release, or decreased cortisol clearance. Further studies are indicated to evaluate the effects of various anesthetic protocols and minimally invasive surgical techniques on the stress response.

Are Functional and Activity Limitations Becoming More Prevalent among 55 to 69-Year-Olds in the United States?

OBJECTIVES: This study examines changes in functional and activity limitations 1998-2012 for individuals 55-69. METHODS: Logistic models are used to estimate trends in limitations in vision, hearing, physical and cognitive functioning, IADLs, and ADLs. Additional models assess the extent to which trends are associated with and differ by education, smoking, and BMI. RESULTS: Changes in prevalence of limitations in vision, hearing, cognitive functioning, and ADLs are not statistically significant. Limitations in physical functioning declined by 0.37% per year. IADL limitations increased by 1.33% per year, but most of the increase occurred between 2008 and 2010/2012, and are associated with economic hardship during the Great Recession. Increases in education are especially beneficially associated with trends in limitations, but reductions in smoking also appear to be advantageous for some outcomes. Increases in BMI are associated with trends in physical functioning, IADL, and ADL limitation. DISCUSSION: For Americans 55-69, functional and activity limitations were largely unchanged 1998-2012. Our results suggest that if educational attainment had not increased, most functional and activity limitations potentially could have worsened substantially. Future change in educational attainment is not expected to be so positive. Continued monitoring of trends in activity limitations might well include greater focus on the explanatory roles of environmental factors, including economic circumstances.

Trends in disability and related chronic conditions among the forty-and-over population: 1997-2010.

BACKGROUND: Downward trends in activity limitations among the older U.S. population have recently plateaued, while activity limitation among the pre-retirement population has increased. OBJECTIVES: Update temporal trends in limitations in sensory and physical functions, instrumental activities of daily living (IADLs), and activities of daily living (ADLs) for the 40-64 and 65-and-over U.S. populations; assess the extent to which trends in education, smoking, and obesity could account for the trends in limitations; and examine trends in conditions cited as causes of limitations, their durations, and proportion of life spent with them. METHODS: Multivariate analysis of the 1997-2010 National Health Interview Survey. RESULTS: For the younger group, there have been increases in all limitations, except trouble hearing, which has declined. Increased obesity could account for the increases in vision, physical function, and IADL limitations. Musculoskeletal conditions, such as arthritis and back/neck problems, are frequently cited as causes of limitation, and there are growing roles for depression and nervous system conditions. For the 65-and-over group, there have been decreases in all limitations, except difficulty with physical functions, which is up. Increased education could account for the decline in ADL limitation, and increased obesity could account for increased difficulty with physical functions. Musculoskeletal conditions are also frequently cited as causes of limitation, but declines in heart- and vision-related limitations have been important. CONCLUSION: Trends should continue to be monitored closely for both groups, since younger people have not experienced the improvements of the older group, but are its future members.

Trends and inequalities in late-life health and functioning in England.

BACKGROUND: Recently, late-life disability rates have declined in several countries of the Organisation for Economic Co-operation, but no national-level trend analysis for England has been available. The authors provide such analysis, including measures both early and late in the disablement process, and the authors investigate the extent to which temporal trends are associated with population changes in socioeconomic position (SEP). METHODS: The authors fit logistic models of trends in self-reports and nurse measures of 16 health indicators, based on cross-sectional data from those aged 65 years and older from the 1992 to 2007 Health Survey for England. RESULTS: Overall, prevalence rates of limitations in seeing, hearing and usual activities declined (p<0.05); ever smoking, measured high blood pressure, high cholesterol, and high C reactive protein decreased (p<0.05); and the proportion with limitations in self-care activities remained stable. But obesity and limitations in walking 200 yards and climbing stairs increased (p<0.05). Increases over time in education and non-manual social class membership were associated with declines in smoking, C reactive protein and problems with usual activities. Had the changes in SEP not occurred, the increases in problems walking and climbing would have been greater. People with less education or of manual social classes experienced relatively worse trends for hearing, mobility functions and usual activities. The opposite was true for seeing. CONCLUSIONS: Recent trends in late-life health and functioning in England have been mixed. A better understanding of which specific activities pose challenges, how the environment in which activities are conducted influences functioning and the causes of relatively worse trends for some SEP groups is needed.

Trends in health of older adults in the United States: past, present, future.

The decline in late-life disability prevalence in the United States was one of the most important developments in the well-being of older Americans in the 1980s and 1990s, but there is no guarantee that it will continue into the future. We review the past literature on trends in disability and other health indicators and then estimate the most recent trends in biomarkers and limitations for both the population aged 65 and older and those aged 40 to 64, the future elderly. We then investigate the extent to which trends in education, smoking, and obesity can account for recent trends in limitations and discuss how these three factors might influence future prospects for late-life health. We find that improvements in the health of the older population generally have continued into the first decade of the twenty-first century. The recent increase in the proportion of the younger population needing help with activities of daily living is concerning, as is the doubling of obesity in the last few decades. However the increase in obesity has recently paused, and favorable trends in education and smoking are encouraging.

Why is late-life disability declining?

CONTEXT: Late-life disability has been declining in the United States since the 1980s. This study provides the first comprehensive investigation into the reasons for this trend. METHODS: The study draws on evidence from two sources: original data analyses and reviews of existing studies. The original analyses include trend models of data on the need for help with daily activities and self-reported causes of such limitations for the population aged seventy and older, based on the National Health Interview Surveys from 1982 to 2005. FINDINGS: Increases in the use of assistive and mainstream technologies likely have been important, as have declines in heart and circulatory conditions, vision, and musculoskeletal conditions as reported causes of disability. The timing of the improvements in these conditions corresponds to the expansion in medical procedures and pharmacologic treatment for cardiovascular disease, increases in cataract surgery, increases in knee and joint replacements, and expansion of medications for arthritic and rheumatic conditions. Greater educational attainment, declines in poverty, and declines in widowhood also appear to have contributed. Changes in smoking behavior, the population's racial/ethnic composition, the proportion of foreign born, and several specific conditions were eliminated as probable causes. CONCLUSIONS: The substantial reductions in old-age disability between the early 1980s and early 2000s are likely due to advances in medical care as well as changes in socioeconomic factors. More research is needed on the influence of health behaviors, the environment, and early- and midlife factors on trends in late-life disability.

Another look at aggregate changes in severe cognitive impairment: further investigation into the cumulative effects of three survey design issues.

OBJECTIVES: This study explored whether previously reported declines in severe cognitive impairment were robust to cumulative effects of potentially confounding survey design issues. METHODS: Using the 1993 Asset and Health Dynamics of the Oldest Old study (n = 7,443) and 1998 Health and Retirement Survey (HRS; n = 7,624) the proportion of persons ages 70 and older with severe cognitive impairment was calculated under various assumptions about item nonresponse, differential loss to follow-up, and the size and composition of the nursing home population. Impairment was measured for self-respondents using a modified version of the Telephone Interview Cognitive Screen; for proxy respondents ratings of memory and judgment were used. Chi-square tests were adjusted to account for complex survey designs. RESULTS: Ignoring loss to follow-up, excluding nursing home residents, and assigning a low score to those refusing subscales yielded a statistically significant decline in severe cognitive impairment from 5.8% in 1993 to 3.8% in 1998, or an average annual decline of 6.9%. When cumulative effects of survey design issues were considered and design effects incorporated into statistical tests, statistically significant declines persisted, albeit at a reduced average annual rate, ranging from 2.5% to 6.9% per year. DISCUSSION: Previously reported improvements in severe cognitive impairment appear to be robust to a variety of specifications. Replication with future waves of the HRS and other data is warranted.