Double-peaked Acetaminophen Concentration Secondary to Intestinal Trauma.

BackgroundReduced gastrointestinal motility can alter the toxicokinetics of acetaminophen poisoning. We report a case of altered acetaminophen toxicokinetics due to delayed gastrointestinal absorption, likely secondary to intestinal trauma/surgery.  Case ReportA 37-year-old woman ingested an unknown amount of acetaminophen and ethanol then stabbed herself in the abdomen. The initial acetaminophen was 1,285.9 µmol/L and the time of ingestion was not known. Intravenous acetylcysteine protocol was started. She developed an ileus post-surgery for the stab wounds. At 31 hours post-presentation, the acetaminophen returned undetectable, and the transaminases were normal. After the resolution of the ileus, repeated acetaminophen peaked at 363.3 µmol/L 52 hours post-admission. At 76 hours post-admission, the acetaminophen was undetectable, and transaminases and coagulation parameters were normal. ConclusionsReduction in gastrointestinal motility secondary to trauma and/or surgery must be considered when determining when to initiate or discontinue treatment as well as how long to monitor acetaminophen concentrations.

Sub-inhibitory concentrations of penicillin G induce biofilm formation by field isolates of Actinobacillus pleuropneumoniae.

Actinobacillus pleuropneumoniae is a Gram-negative bacterium and causative agent of porcine pleuropneumonia. This is a highly contagious disease that causes important economic losses to the swine industry worldwide. Penicillins are extensively used in swine production and these antibiotics are associated with high systemic clearance and low oral bioavailability. This may expose A. pleuropneumoniae to sub-inhibitory concentrations of penicillin G when the antibiotic is administered orally. Our goal was to evaluate the effect of sub-minimum inhibitory concentration (MIC) of penicillin G on the biofilm formation of A. pleuropneumoniae. Biofilm production of 13 field isolates from serotypes 1, 5a, 7 and 15 was tested in the presence of sub-MIC of penicillin G using a polystyrene microtiter plate assay. Using microscopy techniques and enzymatic digestion, biofilm architecture and composition were also characterized after exposure to sub-MIC of penicillin G. Sub-MIC of penicillin G significantly induced biofilm formation of nine isolates. The penicillin G-induced biofilms contained more poly-N-acetyl-D-glucosamine (PGA), extracellular DNA and proteins when compared to control biofilms grown without penicillin G. Additionally, penicillin G-induced biofilms were sensitive to DNase which was not observed with the untreated controls. Furthermore, sub-MIC of penicillin G up-regulated the expression of pgaA, which encodes a protein involved in PGA synthesis, and the genes encoding the envelope-stress sensing two-component regulatory system CpxRA. In conclusion, sub-MICs of penicillin G significantly induce biofilm formation and this is likely the result of a cell envelope stress sensed by the CpxRA system resulting in an increased production of PGA and other matrix components.

Autoimmune lymphocytic thyroiditis in dogs.

Primary diseases of the thyroid gland, especially lymphocytic thyroiditis and idiopathic follicular atrophy, were the most common lesions associated with clinical hypothyroidism in pet dogs. Lymphocytic thyroiditis resembled naturally occurring lymphocytic thyroiditis in the Obese-strain of White Leghorn chickens and Hashimoto's thyroiditis in man. The morphology of the thyroid lesion and frequent occurrence of circulating thyroglobulin autoantibodies suggested that lymphocytic thyroiditis was immune-mediated in pet dogs. Thyroid lesions similar to naturally occurring autoimmune thyroiditis in experimental dogs were induced by a local thyroidal graft-versus-host reaction. The lesions observed in the thyroid lobe which was not injected with immunocompetent cells appeared to develop from the formation of thyroid antibodies in the gland by migrating host lymphocytes. Autoimmune lymphocytic thyroiditis occurred secondary to an unrelated immune response occurring in target tissue.

Flavobacterium meningosepticum peptide:N-glycosidase: influence of ionic strength on enzymatic activity.

Flavobacterium meningosepticum peptide:N-glycosidase-mediated deglycosylation of N-linked glycan strands of glycoproteins has been found to be strongly influenced by the ionic strength of the assay medium. By use of a modification of a previously published assay procedure for quantitative analysis of glycan release we have been able to improve reproducibility and thus to compare the extent of deglycosylation achieved under a variety of conditions of ionic strength. We have observed that enzyme activity is adversely affected by high ionic strength buffers such as those recommended for deglycosylation of various glycoproteins and recommend the use of low ionic strength buffers for routine use.

Induced lymphocytic thyroiditis in dogs: effect of intrathyroidal injection of thyroid autoantibodies.

Multifocal infiltrations of lymphocytes and macrophages were present in the thyroid glands of dogs 1 month after an intrathyroidal injection (0.5 ml) of canine serum containing thyroglobulin autoantibodies. The development of thyroiditis was associated with a gradual increase in the incorporation of tritiated thymidine by the peripheral blood mononuclear cells. There was no alteration in circulating thyroid hormone values or thyroglobulin autoantibody titer for 1 month. Control dogs given a similar volume of canine serum without thyroglobulin antibodies did not have an inflammatory reaction in the thyroid gland, and the phytomitogen responses of lymphocytes did not change, compared with base-line values. An intrathyroidal injection of canine thyroglobulin autoantibodies induced lesions similar to naturally occurring lymphocytic thyroiditis in dogs, indicating that thyroid autoantibodies have an important role in the pathogenesis of immune-mediated thyroiditis.

Lymphocytic thyroiditis in dogs; induction with a local graft-versus-host reaction.

Fifty million allogeneic canine lymphocytes were injected in the left lobe of the thyroid gland of 10 dogs. The left lobe of the gland was surgically removed at 1 and 4 weeks after injection. The intrathyroidal injection of immunocompetent cells resulted in local graft vs host reaction within the thyroid gland. Multifocal infiltration of lymphocytes, plasma cells, and macrophages associated with scattered, isolated, or small groups of degenerated follicular cells were present in the follicular wall and colloid on day 7. Thyroidal lesions at 1 month after injection were characterized by extensive destruction of follicular cells, disseminated foci of mononuclear cell infiltration, and electrondense deposits between follicular cells and the basement membrane. The contralateral (noninjected) lobe of the thyroid gland at 4 weeks after injection was infiltrated by lymphocytes, macrophages, and many plasma cells. The inflammatory lesions were associated with multifocal areas of degeneration of follicular cells and focal electron-dense thickenings of the basement membrane. The noninjected lobe, following hemithyroidectomy at 1 week after injection of the thyroid gland undergoing graft-vs-host reaction, either had a focal infiltration of polymorphonuclear leukocytes, lymphocytes, macrophages, and mast cells or had no significant lesions.

Extrahepatic biliary carcinoma in sloth bears.

Extrahepatic biliary carcinoma was found in each of 5 adult sloth bears that died between 1970 and 1984 while on exhibit in Ohio zoos. The tumor was characterized by numerous mucin-producing neoplastic glands scattered throughout abundant fibrous stroma. The cause of the tumor was not determined.

Pathophysiology of excessive iron storage in mynah birds.

Hepatic iron overload was diagnosed in young and adult Rothschild's mynah birds. By light microscopic evaluation, it was determined that there was progressive accumulation of iron pigment with age in the hepatocytes. The Kupffer's cells of the liver, the reticuloendothelial cells of the spleen, and the phagocytic cells in the small intestine were negative for Prussian blue (iron) pigments. These observations suggested that diet had only a minor influence on the iron distribution in the mynah birds. This was confirmed by comparing iron distribution in the liver and spleen of mynah birds with that in other exotic birds receiving the same diet as the mynah birds. The syndrome of excessive iron overload in the mynah birds shared most of the important histopathologic characteristics with idiopathic (hereditary) hemochromatosis in human beings.

Dominantly inherited spastic paraplegia and multifocal palmoplantar hyperkeratosis.

We have extended the study of a previously published kindred with spastic paraplegia and palmoplantar hyperkeratosis from 2 to 18 persons. Present evidence suggests that both neural and cutaneous manifestations are due to a single mutant gene, inherited as an autosomal dominant. Nerve conduction and EMG examination provide evidence for mild lower motor and primary sensory neuron (axon) involvement but these techniques are not useful for early detection. The disorder is a unique genetic disease which stands apart from other mostly recessively inherited varieties of neuroichthyosis.

Four-hour acetaminophen concentration estimation after ingested dose based on pharmacokinetic models.

INTRODUCTION: The United Kingdom has recently changed the indications for N-acetylcysteine treatment for acetaminophen intoxication. Any ingestion over 75 mg/kg is now referred to the hospital. A model based on pharmacokinetic parameters was developed to predict 4-h acetaminophen concentration for this and other ingested doses. METHODOLOGY: EMBASE and Medline were searched to obtain values for volume of distribution, absorption, and elimination constants and bioavailability for acetaminophen. Four-hour concentrations were calculated for ingestion doses currently recommended for hospital referral in different countries. Calculated plasma concentrations at 4 h for several doses were plotted against the Rumack-Matthew and the United Kingdom treatment lines. RESULTS: Six articles were used for the calculations (4 adult and 2 pediatric). In order to achieve a 4-h acetaminophen concentration of 100 mg/L, doses (mg/kg ± 99.9CI) of 180.5 ± 43.2 for adults and 396.1 ± 115.5 for children were calculated. DISCUSSION: A dose of 75 mg/kg would likely yield a 4-h acetaminophen concentrations well below 100 mg/L. Medical toxicologists and poison information specialists are left without evidence-based guidance for which patients or which ingestion history would now warrant referral to hospital for acetaminophen concentration measurement. Larger toxicokinetic studies in acetaminophen overdose are needed to define ingestion dose for referral to hospital.

An Internet snapshot study to compare the international availability of the novel psychoactive substance methiopropamine.

CONTEXT: With the increased use of novel psychoactive substances, there is an increasing availability of these substances from Internet-based suppliers. Methiopropamine, first reported in 2011, is a recreational drug available over the Internet. The aim of this study was to investigate availability and cost of methiopropamine in three different countries: the UK, France, and Canada. METHODS: Using the European Monitoring Centre for Drugs and Drug Addiction Internet snapshot methodology, this study, conducted in June 2013, was undertaken in two different languages: in English (the UK and Canada) and in French (France and Canada), using three Internet searching engines: " google.co.uk ", " google.fr " and " google.ca ". RESULTS: A total of 62 sites were found, most of them were found from the English searches. 45% of the suppliers seemed to originate from the UK. The prices of methiopropamine were comparable between suppliers, no matter which search engine or language was used. The cost of a unit of methiopropamine was inversely related to the purchased quantity, going from 19.49 ± 0.15 GBP per gram for a purchase amount of 500 mg to 3.54 ± 0.13 GBP per gram for a purchase amount of 1 kg. DISCUSSION: The results of the present study demonstrate that the sale of methiopropamine has the potential to reach users across the world. It also appears to support that snapshot studies could be used for toxicovigilance across different countries, by studying the Internet market of novel psychoactive substances. CONCLUSION: To date, snapshot studies, used to monitor the Internet novel psychoactive substances market, have only been undertaken in Europe. We have shown that the flexibility of this methodology enables comparison of the online activity of drug sellers between different countries and continents and that, at least for methiopropamine, the UK is the predominant source for Internet supply.

Extracorporeal treatment for acetaminophen poisoning: recommendations from the EXTRIP workgroup.

BACKGROUND: The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments (ECTR) in poisoning and the results are presented here for acetaminophen (APAP). METHODS: After a systematic review of the literature, a subgroup selected and reviewed the articles and summarized clinical and toxicokinetic data in order to propose structured voting statements following a pre-determined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. Following discussion, a second vote determined the final recommendations. RESULTS: Twenty-four articles (1 randomized controlled trial, 1 observational study, 2 pharmacokinetic studies, and 20 case reports or case series) were identified, yielding an overall very low quality of evidence for all recommendations. Clinical data on 135 patients and toxicokinetic data on 54 patients were analyzed. Twenty-three fatalities were reviewed. The workgroup agreed that N-acetylcysteine (NAC) is the mainstay of treatment, and that ECTR is not warranted in most cases of APAP poisoning. However, given that APAP is dialyzable, the workgroup agreed that ECTR is suggested in patients with excessively large overdoses who display features of mitochondrial dysfunction. This is reflected by early development of altered mental status and severe metabolic acidosis prior to the onset of hepatic failure. Specific recommendations for ECTR include an APAP concentration over 1000 mg/L if NAC is not administered (1D), signs of mitochondrial dysfunction and an APAP concentration over 700 mg/L (4630 mmol/L) if NAC is not administered (1D) and signs of mitochondrial dysfunction and an APAP concentration over 900 mg/L (5960 mmol/L) if NAC is administered (1D). Intermittent hemodialysis (HD) is the preferred ECTR modality in APAP poisoning (1D). CONCLUSION: APAP is amenable to extracorporeal removal. Due to the efficacy of NAC, ECTR is reserved for rare situations when the efficacy of NAC has not been definitively demonstrated.

Treatment for calcium channel blocker poisoning: a systematic review.

CONTEXT: Calcium channel blocker poisoning is a common and sometimes life-threatening ingestion. OBJECTIVE: To evaluate the reported effects of treatments for calcium channel blocker poisoning. The primary outcomes of interest were mortality and hemodynamic parameters. The secondary outcomes included length of stay in hospital, length of stay in intensive care unit, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. METHODS: Medline/Ovid, PubMed, EMBASE, Cochrane Library, TOXLINE, International pharmaceutical abstracts, Google Scholar, and the gray literature up to December 31, 2013 were searched without time restriction to identify all types of studies that examined effects of various treatments for calcium channel blocker poisoning for the outcomes of interest. The search strategy included the following Keywords: [calcium channel blockers OR calcium channel antagonist OR calcium channel blocking agent OR (amlodipine or bencyclane or bepridil or cinnarizine or felodipine or fendiline or flunarizine or gallopamil or isradipine or lidoflazine or mibefradil or nicardipine or nifedipine or nimodipine or nisoldipine or nitrendipine or prenylamine or verapamil or diltiazem)] AND [overdose OR medication errors OR poisoning OR intoxication OR toxicity OR adverse effect]. Two reviewers independently selected studies and a group of reviewers abstracted all relevant data using a pilot-tested form. A second group analyzed the risk of bias and overall quality using the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) checklist and the Thomas tool for observational studies, the Institute of Health Economics tool for Quality of Case Series, the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines, and the modified NRCNA (National Research Council for the National Academies) list for animal studies. Qualitative synthesis was used to summarize the evidence. Of 15,577 citations identified in the initial search, 216 were selected for analysis, including 117 case reports. The kappa on the quality analysis tools was greater than 0.80 for all study types. RESULTS: The only observational study in humans examined high-dose insulin and extracorporeal life support. The risk of bias across studies was high for all interventions and moderate to high for extracorporeal life support. High-dose insulin. High-dose insulin (bolus of 1 unit/kg followed by an infusion of 0.5-2.0 units/kg/h) was associated with improved hemodynamic parameters and lower mortality, at the risks of hypoglycemia and hypokalemia (low quality of evidence). Extracorporeal life support. Extracorporeal life support was associated with improved survival in patients with severe shock or cardiac arrest at the cost of limb ischemia, thrombosis, and bleeding (low quality of evidence). Calcium, dopamine, and norepinephrine. These agents improved hemodynamic parameters and survival without documented severe side effects (very low quality of evidence). 4-Aminopyridine. Use of 4-aminopyridine was associated with improved hemodynamic parameters and survival in animal studies, at the risk of seizures. Lipid emulsion therapy. Lipid emulsion was associated with improved hemodynamic parameters and survival in animal models of intravenous verapamil poisoning, but not in models of oral verapamil poisoning. Other studies. Studies on decontamination, atropine, glucagon, pacemakers, levosimendan, and plasma exchange reported variable results, and the methodologies used limit their interpretation. No trial was documented in humans poisoned with calcium channel blockers for Bay K8644, CGP 28932, digoxin, cyclodextrin, liposomes, bicarbonate, carnitine, fructose 1,6-diphosphate, PK 11195, or triiodothyronine. Case reports were only found for charcoal hemoperfusion, dialysis, intra-aortic balloon pump, Impella device and methylene blue. CONCLUSIONS: The treatment for calcium channel blocker poisoning is supported by low-quality evidence drawn from a heterogeneous and heavily biased literature. High-dose insulin and extracorporeal life support were the interventions supported by the strongest evidence, although the evidence is of low quality.

Treating acetaminophen overdose: thresholds, costs and uncertainties.

The United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA) modified the indications for N-acetylcysteine therapy of acetaminophen (paracetamol) overdose in September 2012. The new treatment threshold line was lowered to 100 mg/L (662 µmol/L) for a 4 hours acetaminophen concentration from the previous 200 mg/L (1325 µmol/L). This decision has the potential to substantially increase overall costs associated with acetaminophen overdose with unclear benefits from a marginal increase in patients protected from hepatotoxicity, fulminant hepatic failure, death, or transplant. Changing the treatment threshold for acetaminophen overdose also implies that ingestion amounts previously thought not to require acetaminophen concentration measurements would need to be revised. As a result, more individuals will be sent to hospitals in order that everyone with a predicted 4 hours concentration above the 100 mg/L line will have concentrations measured and potentially be treated with N-acetylcysteine. Before others consider adopting this new treatment guideline, formal cost-effectiveness analyses need to be performed to define the appropriate thresholds for referral and treatment.

Acceptor hydroxyl group mapping for human milk alpha 1-3 and alpha 1-3/4 fucosyltransferases.

Two different fucosyltransferases (Fuc-Ts) have been isolated from human milk, an alpha 1-3 Fuc-T and an alpha 1-3/4 Fuc-T, for mapping of their acceptor binding sites. Kinetic studies employing a series of monodeoxygenated and modified Gal beta 1-->4Glc-NAc beta OR and Gal beta 1-->3GlcNAc beta OR acceptor substrates showed that modifications are tolerated at every hydroxyl group in these substrates except for 6-OH of galactose and 3- or 4-OH of N-acetylglucosamine. Deoxygenation at these positions rendered these compounds inactive as both substrates and inhibitors. These essential hydroxyl groups, which are required for recognition of the substrates, are identical to the key polar groups that have previously been reported for cloned FucTs III, IV and V.

HTLV-I/II infection in a high viral endemic area of Zaire, Central Africa: comparative evaluation of serology, PCR, and significance of indeterminate western blot pattern.

The frequency of indeterminate Western blot (WB) seroreactivities against HTLV-I "gag encoded proteins" only, and the use of low specific diagnostic WB criteria led to the overestimation of HTLV-I seroprevalence in initial studies in intertropical Africa and Papua New Guinea. In order to clarify the meaning of such seroreactivity, 98 blood samples of individuals from a high HTLV-I endemic area in Zaire, Central Africa were studied by a WB assay containing HTLV-I disrupted virions enriched with a gp 21 recombinant protein and a synthetic peptide from the gp 46 region (MTA-1), and by the polymerase chain reaction (PCR) with 3 primers pairs and 4 different HTLV-I and or HTLV-II-specific probes. These 98 samples were taken mainly from patients with neurological diseases and from their relatives. Using stringent WB criteria, 28 sera (29%) were considered as HTLV-I-positive, 3 as negative and 67 (68%) as indeterminate. A large proportion of these indeterminate sera would have been considered as HTLV-I-positive samples according to previous low specific WB diagnostic criteria. After PCR, 35 samples (36%) were considered as positive for the presence of HTLV-I proviral DNA. Out of the 67 WB seroindeterminate, 10 (15%) were found HTLV-I-positive by PCR. These 10 individuals exhibited in WB multiple band reactivity with p19 and/or p24 (7 cases of both) associated in 6 cases with rgp 21, but never with MTA-1. No samples were found PCR-positive for HTLV-II despite the findings of 11 sera suggestive of HTLV-II by WB.(ABSTRACT TRUNCATED AT 250 WORDS)

Histologic and ultrastructural evaluation of thyroid lesions associated with hypothyroidism in dogs.

Thyroid lesions in 16 pet dogs with hypothyroidism were evaluated by light and electron microscopy. Lymphocytic thyroiditis, found in seven dogs, was characterized by diffuse infiltration of the thyroid gland by lymphocytes, plasma cells and macrophages with formation of some lymphoid nodules and destruction of follicles, progressing to replacement of most of the thyroid by fibrous connective tissue. The basement membrane around follicles was thick and had electron-dense deposits. The morphology of the thyroid lesions and the presence of circulating thyroglobulin autoantibodies suggested that lymphocytic thyroiditis was immune-mediated. Idiopathic follicular atrophy, found in nine dogs, was characterized by loss of thyroid parenchyma and replacement by adipose connective tissue. Degeneration of individual follicular cells was present in the early stage, with exfoliation into the colloid and interfollicular area. Most of the thyroid gland consisted of adipose connective tissue with either interspersed small follicles or individual follicular cells that had dilated rough endoplasmic reticulum, large Golgi apparatus, and intracytoplasmic microfollicles in the advanced stage. Follicular atrophy was a degenerative lesion of follicular cells of unknown cause, not associated with inflammatory destruction in the thyroid gland.

Neuropathy associated with monoclonal gammopathies of undetermined significance.

Monoclonal proteins (IgM, IgG, and IgA) in the serum or urine of patients with neuropathy may provide a marker for amyloidosis, myeloma, lymphoma, leukemia, Waldenström's macroglobulinemia, or monoclonal gammopathy of undetermined significance (MGUS). The clinical characteristics, course, and electromyographic features among neuropathies associated with monoclonal IgM (IgM-MGUS, 31 patients), monoclonal IgG (IgG-MGUS, 24 patients), and monoclonal IgA (IgA-MGUS, 10 patients) evaluated between 1980 and 1986 were compared. Four statistically significant differences set IgM-MGUS neuropathies apart from IgG-MGUS and IgA-MGUS neuropathies: (1) higher frequency of sensory loss and ataxia, (2) higher frequency of nerve conduction abnormality--10 attributes were significantly worse (none were significantly better), (3) higher frequency of dispersion of the compound muscle action potential, and (4) higher frequency of IgM-MGUS in the MGUS neuropathy cohort than is characteristic of MGUS without neuropathy seen at our institution or than is encountered in epidemiological surveys. These differences were not thought to be due to selection or severity biases. Neither the amount of IgM nor the estimated size of the monoclonal peak was associated with severity of neuropathy. The type and severity of IgM-MGUS neuropathies with anti-myelin-associated glycoprotein antibodies were not significantly different from those without anti-myelin-associated glycoprotein antibodies. A simple relationship between the presence and amount of IgM-MGUS or anti-myelin-associated glycoprotein antibodies and neuropathy cannot be assumed.

Expression of the ras-related rap genes in human tumors.

The expression of the recently described rap genes, closely related in the effector region to the ras proto-oncogenes, was examined by Northern blot analysis in 41 primary human tumors. The structural and in vitro biological properties of the rap gene products suggest their possible antagonistic action in the same effector pathway as the ras proteins. In order to determine whether a deregulation in the rap transcription levels could be involved per se in the multistep carcinogenic process, we chose to analyze tumors for which the ras mutation rate was previously reported to be extremely rare or unknown, i.e., non-Hodgkin's lymphomas, certain types of carcinoma, sarcomas, germinal neoplasms of the testes and various tumors of the nervous system. A severe decrease in the expression of the rap1A gene was shown in the fibrosarcomas and the adenocarcinoma of the salivary gland studied, as compared to their normal counterparts, whereas no rap2 expression was found in the polyadenylated RNA of sarcoma samples.

Biochemical and immunological investigations on hypothyroidism in dogs.

Circulating antibody titers (1:20 to 1:2560) against thyroglobulin were demonstrated in 48% of pet dogs with hypothyroidism by the chromic chloride passive hemagglutination test. Four of six dogs with acanthosis nigricans (1:20) and one of six male dogs with hyperestrogenism (1:40) had low titers of antibody against thyroglobulin whereas clinically normal pet dogs and dogs with other selected endocrinopathies (hypoadrenocorticism, cortisol-excess, diabetes mellitus) or obesity were consistently negative. Circulating immune complexes evaluated by the mastocytoma cell-assay were present in the sera of 20% of pet dogs with hypothyroidism but were absent in clinically normal dogs. Although variations in dose significantly altered the quantitative response of the thyroid gland to thyrotropin the qualitative pattern of response was similar for T3 but not T4 in clinically normal laboratory beagles. The peak increases for serum triiodothyronine and thyroxine were observed either at eight (0.1 and 0.2 I.U bTSH/5 lbs) or 12 (1.0 I.U. bTYSH/5 lbs) hours postthyrotropin. Dogs with naturally occurring hypothyroidism had a decreased serum T3 and T4 at baseline and eight hours postthyrotropin (1.0 I.U. bTSH/5 lbs) compared to clinically normal pet dogs, laboratory beagles and dogs with other clinical endocrinopathies. The consistent lack of a significant increase of serum T3 and T4 in response to thyrotropin was necessary for the separation of certain hypothyroid from euthyroid pet dogs in which the baseline level of thyroid hormones were equivocal.