Thereisgrowinginterestinthepossiblehealththreatposedbyendocrine-disruptingchemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor , retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness. (Endocrine Reviews 30: 293–342, 2009)

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Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement

The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans-especially during development-may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the evidence for endocrine health-related actions of EDCs. Based on this much more complete understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability, these findings can be much better translated to human health. Armed with this information, researchers, physicians, and other healthcare providers can guide regulators and policymakers as they make responsible decisions.

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EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals

https://apps.who.int/iris/bitstream/10665/78102/1/WHO_HSE_PHE_IHE_2013.1_eng.pdf

State of the Science of Endocrine Disrupting Chemicals - 2012

The adult rat hippocampus contains primordial neural stem cells.

Now in a fully updated seventh edition, Plumb's Veterinary Drug Handbook remains the most complete source of drug information relevant for animals available. Providing referenced dosing recommendations in each monograph, this book offers doses for a wide range of species, including dogs, cats, exotic animals, and farm animals, in a single resource. The book also includes detail on key aspects for appropriate use of each drug, including pharmacology, pharmacokinetics, contraindications, adverse effects, safety during pregnancy or nursing, overdoses, drug interactions, monitoring, chemistry and stability, storage, compatibility, and available products. The seventh edition adds 22 new drug monographs, as well as updated dosages and information for existing drugs. A noteworthy feature is the Prescriber Highlights section found at the beginning of each monograph that allows readers a quick method of finding important information for that drug. This is the 8 1/2 x 11-inch desk size, offering enhanced readability and ease of use; Plumb's Veterinary Drug Handbook is also available in the convenient 5 by 8-inch pocket size and as a mobile version. Plumb's exhaustive one-volume coverage of drugs approved for veterinary species and non-approved (human) drugs that are used in veterinary practices today make this book an essential reference for veterinarians, veterinary technicians, veterinary pharmacologists, pharmacists with veterinary patients, animal research or zoological facilities, and libraries that serve these groups.

Plumb's Veterinary Drug Handbook

Knowledge of thyroid hormone and iodide metabolism is derived from a combination of in vivo and in vitro studies in a variety of mammalian species Each species provides a unique opportunity to investigate various aspects of normal or altered thyroid hormone physiology This article compares thyroid hormone and iodide metabolism in dogs, cats, and humans, with emphasis on similarities and differences as well as on areas in which data are not currently available

Thyroid hormone metabolism. A comparative evaluation.

Hyperthyroidism was diagnosed in 131 cats during a 3 1/2-year period. The cats ranged in age from 6 to 20 years; there was no breed or sex predilection. The most frequent clinical signs included weight loss, polyphagia, increased activity, polydipsia, polyuria, and vomiting. Common serum biochemical abnormalities included high values for alkaline phosphatase activity (75%), lactate dehydrogenase activity (66%), aspartate transaminase activity (66%), and alanine transaminase activity (54%). Electrocardiographic changes included tachycardia (greater than or equal to 240 beats/min) and increased R-wave amplitude in lead II (greater than or equal to 0.9 mV) in 66% and 29% of the 131 cats, respectively. Thoracic radiography in 82 cats revealed cardiomegaly in 40 (49%) of these cats; 16 cats with congestive heart failure also had pulmonary edema or pleural effusion. In 5 cats with markedly increased fecal volume, mean 48-hour fecal fat content was significantly greater than normal, with daily fat excretion 2 to 15 times the upper limit of normal. Base-line serum thyroxine concentrations were increased above normal range in all cats, whereas triiodothyronine concentrations were increased in 127 (97%) of the 131 cats. In 11 cats tested, mean thyroxine concentration did not increase significantly after thyroid-stimulating hormone administration. Mean 24-hour percentage of thyroid radioiodine uptake in 32 hyperthyroid cats was significantly higher (39.1%) than normal (9.2%). Thyroid scans, performed on 126 cats, showed enlargement and increased radionuclide accumulation in 1 thyroid lobe in 36 (29%) and both lobes in 90 (71%) of the cats.

Feline hyperthyroidism: pretreatment clinical and laboratory evaluation of 131 cases.

Obesity is a major health problem in cats and a risk factor for diabetes. It has been postulated that cats are always gluconeogenic and that the rise in obesity might be related to high dietary carbohydrates. We examined the effect of a high-carbohydrate/low-protein (HC) and a high-protein/low-carbohydrate (HP) diet on glucose and fat metabolism during euglycemic hyperinsulinemic clamp, adipocytokines, and fat distribution in 12 lean and 16 obese cats before and after weight loss. Feeding diet HP led to greater heat production in lean but not in obese cats. Regardless of diet, obese cats had markedly decreased glucose effectiveness and insulin resistance, but greater suppression of nonesterified fatty acids during the euglycemic hyperinsulinemic clamp was seen in obese cats on diet HC compared with lean cats on either diet or obese cats on diet HP. In contrast to humans, obese cats had abdominal fat equally distributed subcutaneously and intra-abdominally. Weight loss normalized insulin sensitivity; however, increased nonesterified fatty acid suppression was maintained and fat loss was less in cats on diet HC. Adiponectin was negatively and leptin positively correlated with fat mass. Lean cats and cats during weight loss, but not obese cats, adapted to the varying dietary carbohydrate/protein content with changes in substrate oxidation. We conclude that diet HP is beneficial through maintenance of normal insulin sensitivity of fat metabolism in obese cats, facilitating the loss of fat during weight loss, and increasing heat production in lean cats. These data also show that insulin sensitivity of glucose and fat metabolism can be differentially regulated in cats.

Insulin sensitivity, fat distribution, and adipocytokine response to different diets in lean and obese cats before and after weight loss

Neuromuscular signs in association with hypothyroidism are described in 29 dogs. Eleven dogs had lower motor neuron signs, 9 had peripheral vestibular deficits, 4 had megaesophagus, and 5 had laryngeal paralysis. Primarily older (mean = 9.5 years), large-breed dogs were affected, and there was no sex or breed predisposition. Duration of clinical signs before presentation ranged from 2 to 8 weeks (mean = 5 weeks). The diagnosis was based on (1) results of neurological examination (29 dogs); (2) electromyographic abnormalities (18 dogs), including fibrillation potentials (n = 18), positive sharp waves (n = 15), and complex repetitive discharges (n = 4); (3) high serum cholesterol concentration (10 dogs; mean = 335 mg/dL); (4) low response to thyroid-stimulating hormone (29 dogs; mean T4 prestimulation concentration = 0.8 micrograms/dL; mean T4 poststimulation = 1.2 microgram/dL); and (5) good response to thyroxine supplementation (26 dogs). Dogs with vestibular deficits had abnormal brainstem auditory-evoked responses (BAER), including increased latencies of P1-P6 and decreased amplitude of P4,5-N5. Seven other dogs had similar BAER abnormalities without manifesting clinical signs of vestibular involvement. Three dogs with vestibular signs had fibrillation potentials and positive sharp waves without exhibiting lower motor neuron signs. All dogs were supplemented with levothyroxine (0.02 mg/kg PO bid). The follow-up period ranged between 6 and 30 months (mean, 14 months). Serum T4 concentrations were measured at least 3 times for each dog every 2 months (mean T4 concentration = 2.6 micrograms/dL). All but 1 dog with lower motor neuron signs and 1 dog with vestibular signs recovered after 2 months (mean, 57 days).(ABSTRACT TRUNCATED AT 250 WORDS)

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1939-1676.1994.tb03245.x

Neurological Manifestations of Hypothyroidism: A Retrospective Study of 29 Dogs

Several drugs can affect thyroid function test results in humans and eventually lead to an erroneous evaluation of thyroid function. These medications can alter the synthesis, secretion, transport, or metabolism of thyroid hormones. Some drugs also directly inhibit the hypothalamic-pituitary-thyroid axis. The effects of drugs on thyroid function in dogs have long been underestimated and have most likely contributed to the overdiagnosis of hypothyroidism in this species. This manuscript 1st reviews pertinent thyroid physiology followed by an overview of drugs for which the effects on canine thyroid function have been studied. The effects of glucocorticoids, propranolol, sulfonamides, phenobarbital, potassium bromide, and nonsteroidal anti-inflammatory agents (NSAIDs) on canine thyroid function are summarized here. Knowledge of the potential effect of these medications on thyroid function should contribute to a more reliable interpretation of thyroid function test results in dogs.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1939-1676.2003.tb02467.x

Duncan C. Ferguson

Papers

Thyroid hormone metabolism. A comparative evaluation.

Feline hyperthyroidism: pretreatment clinical and laboratory evaluation of 131 cases.

Insulin sensitivity, fat distribution, and adipocytokine response to different diets in lean and obese cats before and after weight loss

Neurological Manifestations of Hypothyroidism: A Retrospective Study of 29 Dogs

Influence of Drugs on Thyroid Function in Dogs