Veterinary researchers discover first US strains of hepatitis E virus from rabbits
Among the many challenges to health, infectious diseases stand out for their ability to have a profound impact on the human species. Great pandemics and local epidemics alike have influenced the course of wars, determined the fates of nations and empires, and affected the progress of civilization, making infections compelling actors in the drama of human history.For 200 years, the Journal has captured the backdrop to this human drama in thousands of articles about infectious diseases and about biomedical research and public health efforts to understand, treat, control, and prevent them.
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Cushing disease is a condition in which the pituitary gland releases excessive adrenocorticotropic hormone (ACTH) as a result of an adenoma arising from the ACTH-secreting cells in the anterior pituitary. ACTH-secreting pituitary adenomas lead to hypercortisolemia and cause significant morbidity and mortality. Pituitary-directed medications are mostly ineffective, and new treatment options are needed. As these tumors express EGFR, we tested whether EGFR might provide a therapeutic target for Cushing disease. Here, we show that in surgically resected human and canine corticotroph cultured tumors, blocking EGFR suppressed expression of proopiomelanocortin (POMC), the ACTH precursor. In mouse corticotroph EGFR transfectants, ACTH secretion was enhanced, and EGF increased Pomc promoter activity, an effect that was dependent on MAPK. Blocking EGFR activity with gefitinib, an EGFR tyrosine kinase inhibitor, attenuated Pomc expression, inhibited corticotroph tumor cell proliferation, and induced apoptosis. As predominantly nuclear EGFR expression was observed in canine and human corticotroph tumors, we preferentially targeted EGFR to mouse corticotroph cell nuclei, which resulted in higher Pomc expression and ACTH secretion, both of which were inhibited by gefitinib. In athymic nude mice, EGFR overexpression enhanced the growth of explanted ACTH-secreting tumors and further elevated serum corticosterone levels. Gefitinib treatment decreased both tumor size and corticosterone levels; it also reversed signs of hypercortisolemia, including elevated glucose levels and excess omental fat. These results indicate that inhibiting EGFR signaling may be a novel strategy for treating Cushing disease.
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Candidates play to the right on science
Rivals for the Republican nomination laud research but take a hard line on embryonic stem cells and climate.
BY SUSAN YOUNG
US presidential elections do not tend to revolve around science. But thanks to the latest twist in the race for the Republican candidacy, the unusual topic of mining the Moon looks set to be up for discussion. Lunar resources and the space pro- gramme in general are popular themes with former US House speaker Newt Gingrich. Following his decisive victory over the Republican frontrunner, former Massachusetts governor Mitt Romney, in the South Carolina primary on 21 January, Gingrich — whose fortunes have zigzagged during the campaign — is back in the media spotlight.
Romney and Gingrich now dominate an unsettled contest. Both are taking staunchly conservative positions on controversial sci- ence issues: they are against regulating carbon emissions and oppose embryonic stem-cell research. Yet both have held more moderate views in the past. And, with concern grow- ing about unemployment and international competition (see page 420), the state of US research and its role as an economic driver could have more resonance than usual in this year’s presidential race.
“The public supports science strongly,” says Mary Woolley, president of the medical-science advocacy group Research!America, based in Alexandria, Virginia. “They can connect the dots between science and better jobs for them- selves, their children, their grandchildren. They don’t want to be part of a country that’s not making progress in science at the level we used to.”
Last November, the group sent a list of research-oriented questions to all candidates, including US President Barack Obama, against whom the winner of the Republican contest will face off later this year. So far, only Gingrich and Obama have responded. In keeping with Republican ideology, Gingrich credits the US private sector as the key driver of technical innovation and success. But his tone is urgent. “We are on the cusp of an explosion of new science that will create new opportunities in health, agriculture, energy, and materials technology,” he writes. “We must move quickly and decisively so we will be the creators of this innovation, not just the recipients of it.” Now, with the race moving on to the Florida primary on 31 January, Gingrich has promised to deliver a visionary speech on the US space programme, in the tradition of Democratic president John F. Kennedy.
Yet, on stem cells, Gingrich leans firmly to the right, mindful that many social con- servatives in the United States equate research on human embryos with abortion. In 2009, Obama lifted a ban imposed by former Repub- lican president George W. Bush that limited federal funding for human embryonic stem- cell research to just a handful of existing cell lines. By contrast, Gingrich says he would “oppose at every turn any process of destroying embryos”.That could mean a freeze on the approval of new lines, or possibly an end to federal funding for such work altogether.
Romney’s history on the issue is more complex. As a candidate for governor in 2002, he voiced general support for stem-cell science. But, once in office, he vetoed a 2005 bill that allowed cloning to create human embryonic stem cells for research. Romney was overruled by the state’s legislature, but the following year his administration set down regulations that could have criminalized the work of scientists using human embryonic stem cells. However, no scientists were prosecuted under the regulations, and the bill was amended when the next governor took over.
The positions that Romney and Gingrich now espouse suggest that if either were to be
in the White House with a Congress similar to today’s, US stem-cell policy would take a hard right turn. “It would be very likely that there would be a reduction or elimination of fund- ing for embryonic stem-cell research”, says Alta Charo, a professor of law and bioethics at the University of Wisconsin–Madison.
this by conservative commentators. Gingrich now says he regrets the ad and, in recent weeks, has further distanced himself from his proactive former stance. After he was criticized on right- wing talk radio for involving Katharine Hayhoe, a climate scientist at Texas Tech University in Lubbock, in a book project on environment entrepreneurship, Gingrich said he would drop Hayhoe’s chapter from the book. Hayhoe supports the idea that human activity is driving climate change. “Any time a scientist stands up in a public forum and says climate change is real and we need to do something about it, there are immediate repercussions,” Hayhoe says.
Yet whoever becomes the Republican candidate — and whoever ultimately becomes president — these disputes may not mean much for the support of science as a whole. Since the cold war, both Republican and Democratic administrations have a steady record of support for basic science. And with the US electorate focused on the economy and unemployment, it seems likely that if science is discussed at all in this year’s campaign it will be in the context of jobs and competitiveness — issues on which all candidates, no matter what their ideology, see a need for action. ■
Nature 481, 421–423 (26 January 2012)
Pituitary, 4 November 2011
ACTH-secreting pituitary adenomas (Cushing’s disease, CD) are the most frequent cause of Cushing’s syndrome. To test whether the size of ACTH-secreting adenomas correlates with the degree of biochemical and clinical features of hypercortisolism, we retrospectively reviewed all newly diagnosed CD patients seen at our institution by two neuro-endocrinologists over a 10-year time period. We documented the number of clinical manifestations and baseline hormonal measurements. There were 37 microadenomas (μAs) and 16 macroadenomas (MAs). We sought to characterize the relationship between tumor size (μA vs. MA) and number of signs and symptoms of hypercortisolism and biochemical assessment of hypercortisolemia. There were no significant differences in mean age, BMI, or prevalence of hypertension and type 2 diabetes between the μA and MA groups. However, the MAs had fewer clinical manifestations of hypercortisolism (29.4% vs. 36.1%, P = 0.02) compared to μAs. There was a higher prevalence of easy bruisability and proximal muscle weakness in the μAs, but otherwise the prevalence of signs and symptoms were similar between groups. The MAs had a lower random serum cortisol (18.2 ± 2.4 vs. 25.9 ± 1.8 mcg/dl, P = 0.018), lower cortisol:ACTH ratio (0.25 ± 0.03 vs. 0.42 ± 0.05, P < 0.048), and lower cortisol:tumor diameter ratio (14.1 ± 2.2 vs. 56.8 ± 7.2, P < 0.0001) than the μAs. We conclude that tumor size does not directly correlate with the extent of hormonal activity in ACTH-secreting adenomas. Biochemical activity and clinical manifestations may be mild even in larger tumors, and therefore a high index of suspicion may be necessary to recognize hypercortisolism in pituitary MAs.
A study published in the journal Nature purports to prove the Geomyces destructans fungus is causing a deadly illness responsible for catastrophic die offs among multiple bat species in eastern North America.
The investigation led by the U.S. Geological Survey is offered as the first direct evidence that G destructans is behind white-nose syndrome in bats.
Since the disease was first reported in January 2007 in New York state, the white-nose syndrome outbreak has spread to hibernating bats in more than a dozen states and four Canadian provinces. Biologists estimate more than a million bats have died of white-nose syndrome, making it the worst wildlife health crisis in memory, according to the U.S. Fish and Wildlife Service.
"By identifying what causes WNS, this study will greatly enhance the ability of decision makers to develop management strategies to preserve vulnerable bat populations and the ecosystem services that they provide in the U.S. and Canada," said Anne Kinsinger, USGS associate director of ecosystems.
White-nose syndrome has been diagnosed in nine species of bats hibernating in eastern North America. Species known to be susceptible to the disease are the little brown bat (Myotis lucifugus), Indiana bat (M sodalis), northern long-eared bat (M septentrionalis), eastern small-footed bat (M leibii), tricolored bat (Perimyotis subflavus), and big brown bat (Eptesicus fuscus).
Insect-eating bats are estimated to save the U.S. agricultural industry nearly $4 billion annually in pest-control expenses. Earlier this year, the USFWS rolled out a national management plan addressing the threat posed by white-nose syndrome (see JAVMA, July 15, 2011, page 169).
More than 100 state and federal agencies, tribes, organizations, and individuals are trying to contain the disease outbreak, the first epizootic ever documented in bats. Over the past several years, the Department of the Interior has invested close to $11 million in the effort, including more than $3 million for ongoing research looking for methods to control or cure the disease.
Debate over the role of G destructans in the WNS outbreak stems in part from an assumption that fungal infections in mammals are typically associated with immune system dysfunction. Moreover, G destructans was recently found to commonly colonize the skin of bats in Europe, where no unusually high bat mortality incidents have been reported. These factors have fueled speculation that the fungus is an opportunistic pathogen and that North American bats are dying as a result of unidentified factors.
Researchers at the USGS National Wildlife Health Center in Madison, Wis., exposed captive, healthy little brown bats to pure cultures of G destructans while the animals were hibernating. All the bats subsequently developed white-nose syndrome. Researchers also demonstrated the fungus can spread through contact between individual bats.
"While our study confirmed that G destructans is spread bat to bat, it is also important to note that virtually all pathogens, especially spore-producing fungi, are spread by multiple routes," said USGS microbiologist and study author David Blehert, PhD.
The study was conducted by scientists from the USGS, University of Wisconsin-Madison, Wisconsin Veterinary Diagnostic Laboratory, University of Tennessee-Knoxville, New York Department of Environmental Conservation, USFWS, Wisconsin Department of Natural Resources, and Bucknell University.
The Nature article, "Experimental infection of bats with Geomyces destructans causes white-nose syndrome," was published online Oct. 26 at www.nature.com. More information about WNS is available on the websites of the USGS National Wildlife Health Center (www.nwhc.usgs.gov) and USFWS (www.fws.gov).
HoPe Veterinary Center of Los Angeles is holding their free monthly clinic day this Sunday, November 20 to serve the pets of the homeless community.
Every third Sunday of the month, a volunteer staff of doctors and support team members donate their time to provide routine health care, vaccines, flea treatment, microchipping and more advanced medical diagnostics and treatment. Patients and their caregivers can simply walk-in, no appointment is necessary. Refreshments, a sack lunch and donated dog food is given to each client.
Clients find HoPe through a word-of-mouth network and via information booths on the Third Street Promenade in Santa Monica and on the Venice Boardwalk. Other clients are “found” by staff of HoPe, like Joseph and Fergie (pictured).
Mao La Beet, HoPe’s director of marketing, took a personal interest in the pair after seeing them by the road. “This gigantic dog with a heart of gold has softened a man that I can tell has endured so much in his life,” said Mr. La Beet. After transporting them to the clinic twice, “Joseph was very happy to know that if the unfortunate occurrence happened and she became lost and ended up at a hospital or the shelter she would be identified as a HoPe patient and we could get her back to him,” he continued.
HoPe was started by Tina Owen, a board certified veterinary surgeon, after working with the late Dr. Leo Bustad, founder of the People-Pet Partnership and co-founder of the Delta Society. “Being exposed to these two organizations impacted me tremendously to be involved somehow in trying to help people live healthier and more fulfilled lives by keeping their animal companions healthy,” said Dr. Owen. “It is well documented that pets provide companionship and stability to the lives of people and in the case of the homeless their animal companion may be the only interaction they may have with a living being. It is our goal to keep their companions healthy and take away the stress when their friend is sick and they have no other place to turn.”
HoPe also offers trauma, hospitalization and emergency services through a local hospital. Since HoPe requires that patients are spayed or neutered, they also offer a free surgery day once a month.
HoPe, a 501(c)(3) non-profit corporation, is seeking donations to help raise funds for their emergency treatment services. All donations are tax deductible.
Sunday, November 20, 2011
8:00 a.m. - 2:00 p.m.
HoPe Veterinary Center
1827 Pontius Avenue
Los Angeles, California 90025
Photos courtesy of Rachel DeLeon
Type 2 diabetes mellitus is caused by a combination of genetic and environmental factors that result in decreased insulin function at sites of insulin action and a reduced ability of pancreatic beta cells to elevate insulin secretion in response to increased blood glucose levels. The variant genes that cause susceptibility to diabetes were virtually unknown until the advent of genomewide association studies. In 2007, one such study identified associations between type 2 diabetes and six different chromosomal loci.1 The company deCODE Genetics subsequently confirmed these associations and identified an association with variant CDKAL1.2 Subsequent studies increased the number of implicated loci to about 40. Unfortunately, this plethora of loci has not yielded a proportionate improvement in our understanding of disease mechanisms, partly because genomewide association studies often implicate genes (or nongenic regions) of unknown function, such as CDKAL1.
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Two veterinarians awarded Institute of Medicine membership
Dr Patricia Conrad
Dr Li-Huei Tsai
Two veterinarians were recently elected as members of the Institute of Medicine—one of the highest honors in the fields of health and medicine.
Drs. Patricia A. Conrad of the University of California-Davis and Li-Huei Tsai of the Massachusetts Institute of Technology were among 65 individuals granted IOM membership Oct. 17.
Fewer than 20 veterinarians are members of the IOM, which, as the health branch of the National Academy of Sciences, is a national resource for independent, scientifically informed analysis and recommendations on health issues.
Current IOM members elect new members through a highly selective process that recognizes individuals who have made major contributions to the advancement of the medical sciences, health care, and public health. IOM members volunteer for a variety of activities, including participation on national advisory committees.
"Each of these new members stands out as a professional whose research, knowledge, and skills have significantly advanced health and medicine, and their achievements are an inspiration," IOM President Harvey V. Fineberg said. "The Institute of Medicine is greatly enriched by the addition of our newly elected colleagues."
Dr. Conrad is widely recognized for her research on babesiosis and is credited with discovering two new species of babesial parasites infecting dogs and humans in the United States.
At the UC-Davis School of Veterinary Medicine, where Dr. Conrad is a professor in the Department of Pathology, Microbiology, and Immunology, she and her collaborators have helped improve the diagnosis and control of the parasite Neospora caninum, a common cause of abortion in dairy cattle.
In addition, Dr. Conrad is a co-director of the One Health Center of Expertise at the University of California Global Health Institute. There, she leads a team of researchers investigating the impact of fecal pathogen pollution in freshwater, marine, and terrestrial ecosystems on wildlife and human populations.
Dr. Conrad received a DVM degree from Colorado State University and a doctorate in tropical animal health and protozoology from the University of Edinburgh in Scotland.
As director of the MIT Picower Institute for Learning and Memory, Dr. Tsai studies the pathologic mechanisms underlying neurologic disorders affecting learning and memory.
Dr. Tsai has a DVM degree from Taiwan's National Chung Hsing University and a doctorate from the University of Texas Southwestern Medical Center. In 1994, she joined the faculty in the Department of Pathology at Harvard Medical School. Three years later, Dr. Tsai was named an investigator at Howard Hughes Medical Institute, one of the nation's largest private supporters of biomedical research, based in Chevy Chase, Md.
In 2006, Dr. Tsai was appointed professor in the Department of Brain and Cognitive Sciences at MIT, where she also joined the Picower Institute for Learning and Memory. Major research areas at the institute include neuropsychiatric disorders, autism, and Alzheimer's disease.
Veterinary researchers discover first US strains of hepatitis E virus from rabbits
Researchers in the Virginia-Maryland Regional College of Veterinary Medicine at Virginia Tech have identified the first strains of hepatitis E virus from farmed rabbits in the United States. It is unknown whether the virus can spread from rabbits to humans.
Caitlin Cossaboom of Salisbury, Md., a second-year student in the combined Doctor of Veterinary Medicine and Ph.D. program in the Department of Biomedical Sciences and Pathobiology, is the first author of a publication entitled "Hepatitis E Virus in Rabbits, Virginia, USA" in the November issue of Emerging Infectious Diseases, published by the U.S. Centers for Disease Control and Prevention.
"Although researchers found hepatitis E virus in rabbits in China in 2009, this is the first time the virus has been identified in rabbits in the United States or anywhere outside of China," Cossaboom said.
Dr. X.J. Meng, professor of biomedical sciences and pathobiology in the veterinary college, Cossaboom's graduate advisor, and senior author of the study, identified the first animal strains of hepatitis E virus — swine hepatitis E virus from pigs — in 1997. Following the landmark study on swine hepatitis E virus by Meng and his colleagues at the National Institutes of Health's National Institute of Allergy and Infectious Diseases, researchers began to consider hepatitis E virus a zoonotic virus.
"Since 1997, researchers have found hepatitis E virus in pigs essentially in every swine-producing country and shown that the virus from pigs can infect humans," said Meng, who added that his lab also identified avian hepatitis E virus from chickens in the United States and that other researchers later discovered strains of the virus in other animal species, including rats, mongoose, deer, and wild boars.
Hepatitis E is an acute hepatic disease caused by infection with an RNA virus that has a fecal-oral transmission route. The disease is mainly prevalent in developing countries, though sporadic cases have been reported in industrialized countries such as the United States. The mortality rate associated with hepatitis E virus infection in humans is generally less than 1 percent, but it can reach up to 28 percent in infected pregnant women.
The virus has at least four distinct genotypes. Genotypes 1 and 2 infect only humans and typically occur in developing countries with poor sanitation conditions. Meanwhile, genotypes 3 and 4 are zoonotic, can spread from animals to humans, and are found in both industrialized and developing countries.
"It is worth noting that the strains of the virus found in rabbits in the U.S. and China closely relate to genotype 3, a genotype that has been shown to transfer from animals to humans," Meng said. "The question is, 'Do the strains of hepatitis E virus in rabbits infect humans?' We don't know, but the possibility is there and more research is needed to address this potential concern."
Cossaboom and her colleagues collected fecal and serum samples from 85 rabbits from two farms in Virginia — one in Southwest Virginia and one in Eastern Virginia — and found that approximately 50 percent of the rabbits were exposed to the hepatitis E virus. Researchers were able to genetically identify four isolates of the virus from the two rabbit farms.
"For future research, we are particularly interested in the potential zoonotic infection of humans and food safety concerns," Cossaboom said.
She added that pigs can serve as "animal reservoirs" for genotypes 3 and 4 hepatitis E virus. In other words, the pigs can carry and shed the virus, and occasionally the virus may transmit to humans. "However, it is unknown if the virus from rabbits can infect across species or serve as a reservoir," Cossaboom said.
There are five known types of viral hepatitis: Hepatitis A transmits from person to person from ingesting contaminated food and water. Hepatitis B and C spread by blood-to-blood contact; the hepatitis C virus can also cause chronic infection and, in some cases, liver cancer. Hepatitis D occurs in individuals who already have hepatitis B. Although all of these viruses, including hepatitis E virus, target the liver, none of them are genetically related.
Dr. Laura Córdoba, a postdoctoral associate, and Barbara Dryman, a senior laboratory specialist, both in the Department of Biomedical Sciences and Pathobiology, also co-authored the paper.
Meng's lab studies the molecular mechanisms of viral replication and pathogenesis and develops vaccines against emerging, reemerging, and zoonotic viral diseases. The lab, located in the college's Center for Molecular Medicine and Infectious Disease, is considered one of the world's leading hepatitis E virus research centers.
The Virginia-Maryland Regional College of Veterinary Medicine is a two-state, three-campus professional school operated by the land-grant universities of Virginia Tech in Blacksburg and the University of Maryland at College Park. Its flagship facilities, based at Virginia Tech, include the Veterinary Teaching Hospital, which treats more than 40,000 animals annually. Other campuses include the Marion duPont Scott Equine Medical Center in Leesburg, Va., and the Avrum Gudelsky Veterinary Center at College Park, home of the Center for Public and Corporate Veterinary Medicine. The college annually enrolls approximately 500 Doctor of Veterinary Medicine and graduate students, is a leading biomedical and clinical research center, and provides professional continuing education services for veterinarians practicing throughout the two states. Virginia Tech, the most comprehensive university in Virginia, is dedicated to quality, innovation, and results to the commonwealth, the nation, and the world.
Subnormal levels of thyroid stimulating hormone (TSH) along with an elevation in free thyroxine is the primary method of diagnosing hyperthyroidism in humans. The role of TSH in the diagnosis of cats with this disease however is still an area of active research in veterinary medicine.
Previous studies have demonstrated that cats with a low TSH level may indeed have a form of subclinical hyperthyroidism which can ultimately become overt disease. Researchers at the Royal Veterinary College in London conducted a prospective, cohort study evaluating whether low TSH concentrations in a population of geriatric cats would eventually lead to a diagnosis of hyperthyroidism and what, if any, clinical signs developed. Results of this study were published in the most recent issue of the Journal of Veterinary Internal Medicine.
The population consisted of cats over 9 years of age that were presented for routine evaluation and with no apparent clinical problems or history of chronic illness or medications. Cats were excluded if a diagnosis of hyperthyroidism was made at the time of the initial visit or within 3 months of enrollment. The diagnosis of hyperthyroidism was based on a serum total T4 > 55nmol/L (range 19-55nmol/L), a serum total T4 >40nmol/L and free T4>40 pmol/L (range 19-40pmol/L) in a cat with concurrent illness and supportive symptoms of hyperthyroidism, or by T3 suppression test. A complete physical examination, systolic blood pressure measurement (by Doppler), thyroid/ TSH levels, PCV, urinalysis and baseline chemistry testing were obtained at the initial visit. Cats with no underlying health problems at the initial visit were re-evaluated every 6 months. Those with evidence of azotemia, urinary tract infections or hypertension were monitored as clinically necessary. All cats were followed for a minimum of 2.5 years and up to 4.5 years.
A total of 104 cats were enrolled. Thyroid status, TSH concentrations and baseline variables were re-evaluated between 9 and 14 months of enrollment (short-term follow-up endpoint)and again between 2.5 to 4.5 years post-enrollment (long-term follow-up endpoint). Age, breed, sex, history of weight loss, vomiting, diarrhea, polyphagia, polydipsia, skin disease, behavioral changes, presence of a goiter, blood pressure, heart rate, and presence of a murmur were evaluated for a possible association with the development of hyperthyroidism.
At the time of the short-term follow up, 85 cats remained in the study and, of these, 11 were diagnosed with hyperthyroidism. While baseline free T4 concentration were similar between the hyperthyroid and non-hyperthyroid groups, the baseline TSH levels were significantly lower (<0.03ng/ml) for those in the hyperthyroid group. Cats in this group were also more likely to have a goiter, a heart murmur, a history of vomiting and a higher alkaline phosphatase (ALKP) however, only a subnormal TSH level was determined to be predictive of the development of hyperthyroidism within 14 months. Of the cats with a subnormal TSH level at enrollment, 40% went on the develop hyperthyroidism. Only 1 cat with a detectable TSH level at the time of enrollment was diagnosed with hyperthyroidism at the short-term follow-up visit.
Long-term follow-up evaluation took place between 2.5 and 4.5 years following enrollment. An additional 6 cats were diagnosed with hyperthyroidism during this phase of the study for a total of 17 hyperthyroid cats. All of these cats also developed symptoms associated with hyperthyroidism (weight loss, tachycardia, vomiting, diarrhea, polyphagia). Thirteen of the 17 cats had undetectable TSH levels (<0.03ng/ml) at the baseline visit. For the 4 with detectable TSH levels at enrollment, all went on to demonstrate a decline in their TSH to <0.03ng/ml within 12 months with a subsequent diagnosis of hyperthyroidism within 6-28 months.
One of the limitations of using TSH concentrations in the evaluation of thyroid status in cats is the insensitivity of the assay at very low TSH levels. Almost one third of recruited cats had a TSH level < 0.03ng/ml at baseline and yet only 13/25 were diagnosed with hyperthyroidism during the study period. While development of a more sensitive assay will help determine the prognostic value of a single TSH level, results of this study still demonstrate that a single TSH level below 0.03ng/ml is a strong predictor for the development of hyperthyroidism. Furthermore, results suggest that a TSH level above 0.03ng/ml may serve as a marker to rule out hyperthyroidism in a geriatric feline.
Wakeling J, Elliott J, and Syme H. Evaluation of predictors for the diagnosis of hyperthyroidism in cats. J Vet Intern Med. 20