Predicting soil pH changes in response to application of urea and sheep urine.

Volatilization of NH3 following urea application or livestock urine deposition can result in significant loss of N to the environment. Urea hydrolysis to NH4 + results in an increase in pH, which in turn promotes transformation of NH4 + to NH3 . Accurately predicting changes in soil pH following urea (or urine) application will allow successful simulation of NH3 volatilization. The magnitude of the pH change depends on the soil's pH buffering capacity (pHBC). However, as actual pHBC values are not generally available, pHBC proxies (e.g., cation exchange capacity) have been used in modeling studies. In a 34-d laboratory incubation study, we measured soil pH and mineral N (NH4 + and NO3 - ) following a large application of urea (800 mg N kg-1 soil) to four soils with a range of pHBC values. In a second incubation, pH changes and mineral N dynamics were monitored in soil treated with sheep urine (773 mg N kg-1 soil) in the absence and presence of the nitrification inhibitor dicyandiamide. In both incubations, pH changes associated with urea hydrolysis and subsequent nitrification of NH4 + were predicted well using measured pHBC data. Our results confirmed that pHBC is base-type dependent (values greater when measured using KOH than NH4 OH). Soil pHBC is easily measured, and the use of a measured value (determined using NH4 OH) can improve model simulations of pH in the field and, potentially, lead to improved estimates of NH3 loss from animal-deposited urine patches and urea-treated soil.

Short-term biological variation of serum thyroid hormones concentrations in clinically healthy cats.

Thyroid disease is common in cats, but little is known about the biologic variability of serum thyroid hormone concentrations and its impact on diagnostic utility in either healthy cats or cats with thyroid disease. The purpose of this study was to determine the biological variation, index of individuality, and reference change values for thyroid hormones and thyroid-stimulating hormone (TSH) in clinically healthy cats. Serum samples for analysis of total thyroxine (T4), triiodothyronine (T3), free T4 by dialysis, and TSH were obtained weekly for 6 wk from 10 healthy cats, then frozen until single-batch analyzed. Data were evaluated for outliers, and we determined the CV within individual cats (CVI) and between individual cats (CVG) for each hormone and the variation between duplicates or analytical variation (CVA). The index of individuality and reference change values for each hormone were then calculated. Serum concentrations of total T4, free T4, T3, and TSH all showed greater variation between cats (CVG) than within cats (CVI). Total and free T4 had an intermediate index of individuality (1.1 and 1.2, respectively), suggesting that these hormones would be best evaluated by a combination of their population-based reference intervals and reference change values. Serum TSH concentrations had high index of individuality (1.8), suggesting this hormone would be best evaluated with reference change values rather than the population-based reference interval. Total T3 also had a high calculated index of individuality (1.8); however, T3 had high ratio of analytical variation (CVA) to within cat variation (CVI), so RCV could not be accurately calculated. This study demonstrates that clinically normal cats show considerable interindividual biological variation in serum thyroid hormone and TSH concentrations, whereas the intraindividual variability in hormone concentrations is much narrower. This suggests that for all serum thyroid hormones, but especially serum TSH and T3 concentrations, comparing individual cat's hormone results to a population-based reference interval may be misleading, especially in those with early or subclinical thyroid disease. Clinicians might improve the diagnosis of feline thyroid disease by establishing baseline concentrations of T4, free T4, T3, and TSH for individual cats (ideally when healthy) and applying reference change values to subsequent measurements.

Pituitary intermediate lobe in dog: two cell types and high bioactive adrenocorticotropin content.

The pituitary intermediate lobe of most species is cytologically monotonous, but that of the dog is composed of two immunocytochemically distinct cell types. The predominant A cells are typical pars intermedia cells: they stain immunocytochemically for alpha-melanotropin and, more weakly, for adrenocorticotropin and beta-lipotropin. The B cells are like the corticotrophs of the anterior lobe: they stain intensely for adrenocorticotropin and beta-lipotropin but not for alpha-melanotropin. The B cells may account for the high concentration of bioactive adrenocorticotropin measured in the canine pars intermedia, and may explain why in dogs adenomas causing Cushing's disease through hypersecretion of adrenocorticotropin can arise from the intermediate as well as the anterior pituitary lobe.

Evaluation of Serum Symmetric Dimethylarginine Concentration as a Marker for Masked Chronic Kidney Disease in Cats With Hyperthyroidism.

BACKGROUND: Hyperthyroidism can complicate (mask) the diagnosis of chronic kidney disease (CKD) because it increases glomerular filtration rate and decreases body muscle mass, both of which can lower serum creatinine concentrations. Currently, there is no clinical test that can reliably predict which hyperthyroid cats have concurrent azotemic CKD that will become apparent after treatment of the hyperthyroidism. OBJECTIVES: To investigate serum symmetric dimethylarginine (SDMA) concentration as a potential marker of masked azotemia in untreated hyperthyroid cats. ANIMALS: Two hundred and sixty-two hyperthyroid cats and 206 aged-matched, clinically normal cats. METHODS: Prospective study. We measured creatinine, urea nitrogen, SDMA, T4 , and TSH concentrations before and 1, 3, and 6 months after treatment with radioiodine (131 I) and classified 131 I-treated cats as azotemic or nonazotemic based on persistent, post-treatment creatinine concentrations >2.1 mg/dL. Groups were compared via nonparametric tests, and diagnostic accuracy was determined by receiver operating characteristic analysis and logistic regression. RESULTS: No hyperthyroid cats were azotemic before treatment, but 42 (16%) became azotemic when rechecked at 4-8 months (median, 6 months) after 131 I treatment; of these, 14 had high SDMA concentrations before treatment. As a diagnostic test for pre-azotemic (masked) CKD in untreated hyperthyroid cats, SDMA showed a sensitivity of 33.3% and specificity of 97.7%. CONCLUSIONS AND CLINICAL IMPORTANCE: Finding a high serum SDMA concentration in a hyperthyroid cat can help predict development of azotemia after treatment. The test has high diagnostic test specificity (few false-positive results) but relatively low sensitivity (fails to predict azotemia in most hyperthyroid cats).

Autonomy of growth and of iodine metabolism in hyperthyroid feline goiters transplanted onto nude mice.

Hyperthyroidism caused by nodular goiters is a common disease of aging cats. Growth and iodine metabolism were studied by autoradiography in normal and hyperfunctioning thyroid tissue obtained from cats injected with 125I before surgery, and in xenografts, grown in nude mice, after double-labeling with 131I and [3H]thymidine. Hyperthyroid cat goiters contain single or multiple hyperplastic nodules, consisting of highly cellular tissue with an iodine metabolism exceeding that of the surrounding normal tissue. Xenografts of hyperplastic hot tissue in thyroxine-treated nude mice retain their original histologic pattern and continue to accumulate radioiodine intensely. Autoradiographs assessed for [3H]thymidine incorporation reveal autonomously proliferating follicular cells within the hyperplastic foci but not within the normal tissue. Administration of sera from donor cats into host mice fails to stimulate the xenografts. Neither hyperfunction nor growth of toxic cat goiters depends on extrathyroidal stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells.

Natural killer cells and mast cells from gp49B null mutant mice are functional.

Immune responses are controlled by a combination of positive and negative cellular signals. Effector cells in the immune system express inhibitory receptors that serve to limit effector cell expansion and to protect the host from autoreactivity. gp49B is a receptor of unknown function that is expressed on activated mast cells and natural killer (NK) cells and whose cytoplasmic tail endows it with inhibitory potential. To gain insight into the function of gp49B in mice, we disrupted the gp49B gene by homologous recombination. gp49B(0) mice were born at expected ratios, were healthy and fertile, and displayed normal long-term survival rates. gp49B(0) mice showed no defect in NK or mast cell development. Furthermore, NK and mast cells from the gp49B(0) mice showed activation properties in vitro similar to those of cells isolated from wild-type mice. Therefore, gp49B is not critical for the development, expansion, and maturation of mast cells and NK cells in vivo. The healthy status of gp49B(0) mice makes them suitable for testing the role of gp49B in immune responses to infectious agents.

Serum thyroxine and thyroid-stimulating hormone concentration in hyperthyroid cats that develop azotaemia after radioiodine therapy.

OBJECTIVES: The objectives of this study were to determine which serum thyroid hormone test best identifies iatrogenic hypothyroidism in cats that develop azotaemia after radioiodine treatment and to determine which thyroid test best differentiates these azotaemic, hypothyroid cats from azotaemic, radioiodine-treated euthyroid cats, as well as from azotaemic cats with chronic kidney disease and no history of thyroid disease. MATERIALS AND METHODS: A total of 42 hyperthyroid cats that developed azotaemia (serum creatinine ê220 µmol/L) after radioiodine treatment had serum concentrations of thyroxine and free thyroxine by dialysis and thyroid--stimulating hormone measured at 3, 6 and 12 months. Iatrogenic hypothyroidism was confirmed (n=28) or excluded (n=14) on the basis of thyroid scintigraphy. A total of 14 cats with chronic kidney disease and 166 clinically normal cats underwent similar serum thyroid testing and scintigraphy. RESULTS: Concentrations of thyroxine and free thyroxine were lower and thyroid-stimulating hormone higher in hypothyroid cats than in all three groups of euthyroid cats (P<0·0001). Of the hypothyroid cats, thyroxine and free thyroxine concentrations were low in 15 (53·6%) and seven (25%), respectively. Low serum thyroxine and free thyroxine concentrations were also detected in seven (50%) and two (14·3%) of the cats with chronic kidney disease. Thyroid-stimulating hormone concentrations were elevated in all hypothyroid cats but remained within the reference interval in all three groups of euthyroid cats. Serum thyroid--stimulating hormone had a higher test sensitivity and specificity than either thyroxine or free thyroxine concentration. CLINICAL SIGNIFICANCE: The finding of high serum thyroid-stimulating hormone concentrations best identifies feline iatrogenic hypothyroidism and differentiates it from non-thyroidal illness syndrome in cats that develop azotaemia after treatment.

Thyroid Cysts in Cats: A Retrospective Study of 40 Cases.

BACKGROUND: Thyroid cysts are rare in cats and poorly documented. OBJECTIVES: To report distinguishing clinical features and treatment responses of cats with thyroid cysts. ANIMALS: Forty client-owned cats. METHODS: Retrospective review of medical records for cats with thyroid cysts confirmed by scintigraphy, ultrasound, magnetic resonance imaging, or necropsy at 4 referral centers between 2005 and 2016. Signalment, clinical findings, diagnostic testing, treatment, and outcome were recorded. RESULTS: Cats ranged in age from 8 to 20 years with no apparent breed or sex predilection. 37 of 40 (93%) cats were hyperthyroid (duration, 1-96 months). Clinical findings included palpable neck mass (40/40, 100%), weight loss (15/40, 38%), dysphagia (8/40, 20%), decreased appetite (5/40, 13%), and dyspnea (4/40, 10%). Cysts were classified as small (≤8 cm3 ) in 16 (40%) and large (>8 cm3 ) in 24 (60%) cats. Of 25 cats treated with radioiodine, hyperthyroidism resolved in 23 (92%), whereas thyroid cysts resolved in 12 (50%). Radioiodine treatment resolved small cysts in 8 of 13 (62%) cats and large cysts in 4 of 11 (36%) cats. Eight cats, including 2 euthyroid cats, underwent thyroid-cystectomy; 3 with bilateral thyroid involvement were euthanized postoperatively for hypocalcemia. Excised cystic thyroid masses were identified as cystadenoma (4) and carcinoma (4). CONCLUSIONS AND CLINICAL IMPORTANCE: Thyroid cysts are encountered in hyperthyroid and euthyroid cats with benign and malignant thyroid tumors. Radioiodine treatment alone inconsistently resolved thyroid cysts. Thyroid-cystectomy could be considered in cats with unilateral thyroid disease or when symptomatic cysts persist despite successful radioiodine treatment of hyperthyroidism.

Efficacy of Low-dose (2 millicurie) versus Standard-dose (4 millicurie) Radioiodine Treatment for Cats with Mild-to-Moderate Hyperthyroidism.

BACKGROUND: Radioiodine (131 I) is effective treatment for hyperthyroidism in cats, but optimal dose to restore euthyroidism without inducing hypothyroidism is unclear. Treatment-induced hypothyroidism can lead to azotemia and reduced duration of survival. OBJECTIVE: To compare efficacy and short-term outcomes of low-dose 131 I versus higher, standard-dose 131 I as treatment for hyperthyroidism. ANIMALS: A total of 189 client-owned cats undergoing 131 I treatment for mild-to-moderate hyperthyroidism (serum T4 ≥ 4.0 µg/dL and <13.0 µg/dL). METHODS: Prospective, nonrandomized, cohort study comparing treatment with either low-dose (2 mCi, n = 150) or standard-dose (4 mCi, n = 39) 131 I. Serum T4 , thyroid-stimulating hormone (TSH), and creatinine concentrations were measured after 1, 3, and 6 months to determine persistent hyperthyroidism, overt hypothyroidism (low T4 , high TSH), subclinical hypothyroidism (normal T4 , high TSH), and azotemia. RESULTS: There was no significant difference in prevalence of cats with persistent hyperthyroidism between standard- and low-dose treatment groups at 3 (0% versus 5.3%; P = .34) and 6 (0% versus 3.3%; P = .51) months. Overt (18% versus 1%; P = .0005) or subclinical (46% versus 21%; P = .004) hypothyroidism was more common in cats at 6 months after standard-dose 131 I. No difference in incidence of azotemia existed between groups, but cats treated with standard-dose 131 I had higher creatinine concentrations (P < .05) and higher percent rises in creatinine (P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Low-dose 131 I is safe and effective for cats with mild-to-moderate hyperthyroidism, as evidenced by a cure rate of >95% with reduced frequency of iatrogenic hypothyroidism and azotemia.

Evaluation of Body Weight, Body Condition, and Muscle Condition in Cats with Hyperthyroidism.

BACKGROUND: The contribution of fat loss versus muscle wasting to the loss of body weight seen in hyperthyroid cats is unknown. OBJECTIVES: To investigate body weight, body condition score (BCS), and muscle condition score (MCS) in hyperthyroid cats. ANIMALS: Four hundred sixty-two cats with untreated hyperthyroidism, 117 of which were reevaluated after treatment. METHODS: Prospective cross-sectional and before-after studies. Untreated hyperthyroid cats had body composition evaluated (body weight, BCS, and MCS). A subset of these cats were reevaluated 3-12 months after treatment when euthyroid. RESULTS: Pretreatment body weight (median, 4.36 kg; IQR, 3.5 to 5.2 kg) was lower than premorbid weight (5.45 kg; IQR, 4.6 to 6.4 kg, P < .0001) recorded 1-2 years before diagnosis. 154 (35.3%) cats were thin or emaciated; 357 (77.3%) had loss of muscle mass. Cats showed increases in body weight (median, 4.1 kg to 5.0 kg), BCS (median, 3/5 to 3.5/5), and MCS (2/3 to 3/3) after treatment (P < .001), but mild-to-moderate muscle wasting persisted in 45% of treated cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Most hyperthyroid cats lose body weight but maintain an ideal or overweight BCS, with only a third being underweight. As in human hyperthyroid patients, this weight loss is associated with muscle wasting, which affects >75% of hyperthyroid cats. Successful treatment leads to weight gain and increase of BCS in most cats, but almost half fail to regain normal muscle mass.

Evaluation of Serum Thyroid-Stimulating Hormone Concentration as a Diagnostic Test for Hyperthyroidism in Cats.

BACKGROUND: In humans, measurement of serum thyroid-stimulating hormone (TSH) concentration is commonly used as a first-line discriminatory test of thyroid function. Recent reports indicate that canine TSH (cTSH) assays can be used to measure feline TSH and results can help diagnose or exclude hyperthyroidism. OBJECTIVES: To investigate the usefulness of cTSH measurements as a diagnostic test for cats with hyperthyroidism. ANIMALS: Nine hundred and seventeen cats with untreated hyperthyroidism, 32 euthyroid cats suspected of having hyperthyroidism, and 131 clinically normal cats. METHODS: Prospective study. Cats referred to the Animal Endocrine Clinic for suspected hyperthyroidism were evaluated with serum T4, T3, free T4 (fT4), and TSH concentrations. Thyroid scintigraphy was used as the gold standard to confirm or exclude hyperthyroidism. RESULTS: Median serum TSH concentration in the hyperthyroid cats (<0.03 ng/mL) was significantly (P < .001) lower than concentrations in clinically normal cats (0.05 ng/mL) or euthyroid cats with suspected thyroid disease (0.06 ng/mL). Only 18 (2.0%) hyperthyroid cats had measurable TSH concentrations (≥0.03 ng/mL), whereas 114 (69.9%) of the 163 euthyroid cats had detectable concentrations. Combining serum TSH with T4 or fT4 concentrations lowered the test sensitivity of TSH from 98.0 to 97.0%, but markedly increased overall test specificity (from 69.9 to 98.8%). CONCLUSIONS AND CLINICAL IMPORTANCE: Serum TSH concentrations are suppressed in 98% of hyperthyroid cats, but concentrations are measurable in a few cats with mild-to-moderate hyperthyroidism. Measurement of serum TSH represents a highly sensitive but poorly specific test for diagnosis of hyperthyroidism and is best measured in combination with T4 and fT4.

Plasma immunoreactive proopiomelanocortin peptides and cortisol in normal dogs and dogs with Cushing's syndrome: diurnal rhythm and responses to various stimuli.

We have studied the diurnal rhythm of pars distalis and pars intermedia-type immunoreactive (IR)-POMC peptides and cortisol in 3 normal dogs and 1 dog with Cushing's syndrome and have documented the responses to a variety of agents in 42 dogs with Cushing's disease, 2 of which were known or presumed to have pars intermedia tumors and another of which had both pars distalis and pars intermedia adenomas, and in 20 dogs with adrenocortical adenomas causing Cushing's syndrome. The normal dogs did not have a diurnal plasma POMC peptide rhythm; the dog with Cushing's disease appeared to have a similar number of secretory episodes of increased amplitude. Plasma POMC peptides and cortisol in animals with Cushing's disease did not suppress normally with low dose dexamethasone. Five animals with Cushing's disease did suppress with high dose dexamethasone, the dog with dual adenomas suppressed only partially, and 1 dog with a pars intermedia adenoma did not suppress at all. The response to insulin-induced hypoglycemia was similar in normal dogs and 4 dogs with Cushing's disease, but 3 animals with adrenal tumors did not respond. The response to metyrapone was normal in 6 dogs with Cushing's disease and, surprisingly, in 1 with adrenal tumor. Arginine vasopressin stimulated POMC peptide secretion in normal and 6 Cushing's dogs, as well as alpha MSH, a pars intermedia-type POMC peptide, in a dog presumed to have a pars intermedia tumor. Ovine CRF stimulated pars distalis-type POMC peptide secretion in normal dogs and 17 dogs with Cushing's disease, but not in 15 dogs with adrenal tumor; IR-alpha MSH was unaffected. TRH appeared to stimulate IR-ACTH in normal animals, but not in those with Cushing's disease. Dopamine had no apparent effect in 2 normal and 1 Cushing's dogs. Initial plasma disappearance t1/2 values of IR-ACTH and lipotropin were 22-27 min. In summary, responses in normal and Cushing's dogs were generally what would be predicted from previous human and animal studies, but some of those in animals with pars intermedia tumors and even in normal dogs were different from what had been anticipated. Canine Cushing's syndrome provides an interesting model for an uncommon human disorder.

Plasma immunoreactive proopiomelanocortin peptides and cortisol in normal dogs and dogs with Addison's disease and Cushing's syndrome: basal concentrations.

We measured basal plasma concentrations of the immunoreactive (IR) proopiomelanocortin (POMC)-derived peptides ACTH, beta-lipotropin (beta LPH), beta-endorphin (beta END), and alpha MSH in 160 normal dogs, 32 dogs with Addison's disease, 42 dogs with adrenocortical tumors causing Cushing's syndrome, and 169 dogs with pituitary-dependent Cushing's disease. In normal dogs, plasma IR-POMC peptide levels were similar to those in man, except that IR-alpha MSH, a pars intermedia POMC product, was readily detected. In Addisonian dogs, plasma cortisol was decreased, and the IR-POMC peptides were increased, except for IR-alpha MSH, which was normal. In 7 Addisonian dogs given dexamethasone, elevated plasma IR-ACTH, beta LPH, and beta END levels fell dramatically. In dogs with Cushing's syndrome due to adrenal tumors, plasma IR-ACTH, beta LPH, and beta END were decreased, and cortisol was increased, but IR-alpha MSH was normal. Dogs with Cushing's disease due to pars distalis tumors had elevated plasma IR-ACTH, beta LPH, beta END, and cortisol, but normal IR-alpha MSH; their plasma cortisol was suppressed by dexamethasone. There appeared to be 2 types of pars intermedia tumors causing Cushing's disease: 1 dexamethasone nonsuppressible and with disproportionately high plasma IR-alpha MSH levels, the other relatively dexamethasone suppressible and with normal to slightly elevated IR-alpha MSH levels. These 2 pars intermedia tumor types may arise from 2 distinct normal canine pars intermedia cell types. Canine Cushing's disease may provide a useful model for variants of the disorder in man.

Outcomes in breast cancer patients relative to margin status after treatment with breast-conserving surgery and radiation therapy: the University of Pennsylvania experience.

PURPOSE: To evaluate the significance of final microscopic resection margin status on treatment outcomes in women with early breast cancer who are treated with breast-conserving surgery and definitive breast irradiation. METHODS AND MATERIALS: An analysis was performed of 1021 consecutive women with clinical Stage I or II invasive carcinoma of the breast treated with breast-conserving surgery and definitive breast irradiation. Complete gross excision of tumor was performed in all cases, and an axillary staging procedure was performed to determine pathologic axillary lymph node status. The 1021 patients were divided into four groups based on the final microscopic margin from the tumor excision or from the re-excision if performed. These four groups were: (a) 518 patients with negative margins; (b) 124 patients with focally positive margins; (c) 96 patients with focally close margins (< or = 2 mm); and (d) 283 patients with unknown margins. RESULTS: Local failure was not significantly different in patients with negative, focally positive, focally close or unknown final pathologic margins of resection at 8 years (8% vs. 10% vs. 17% vs. 16%, respectively, p = 0.21). The 8-year outcome also was not different among the four groups for overall survival (86% vs. 83% vs. 88% vs. 81%, respectively, p = 0.13), cause-specific survival (89% vs. 86% vs. 88% vs. 83%, respectively, p = 0.14), no evidence of disease survival (81% vs. 73% vs. 86% vs. 77%, respectively, p = 0.09), and freedom from distant metastases (85% vs. 75% vs. 86% vs. 79%, respectively, p = 0.08). CONCLUSION: These results demonstrate that selected patients with focally positive or focally close microscopic resection margins can be treated with breast-conserving surgery and definitive breast irradiation with 8-year local control rates and survival rates that are similar to those seen in breast-conservation patients with negative or unknown final resection margins.

Domestic cats show episodic variation in plasma concentrations of adrenocorticotropin, alpha-melanocyte-stimulating hormone (alpha-MSH), cortisol and thyroxine with circadian variation in plasma alpha-MSH concentrations.

Blood samples were collected from 31 healthy domestic cats to characterize possible episodic and/or circadian variation in plasma concentrations of adrenocorticotropin (ACTH), cortisol, thyroxine and alpha-melanocyte-stimulating hormone (alpha-MSH). Samples were collected with minimal disturbance through indwelling jugular cannulae at two frequencies: at 20-min intervals for 3 h for evaluation of episodic variation, and at 2-h intervals for 48 or 72 h to identify possible circadian changes. Episodic peaks in profiles of all hormones were found in the majority of cats. When data were compared across four bleed periods (each of 3 h duration), no differences were detected in average hormone concentrations or characteristics of episodic pulses. Correlation analyses showed a significant (p < 0.001) relationship between concentrations of ACTH and cortisol (r = 0.44) when these hormones were measured in the same plasma sample. A weaker but significant correlation (r = 0.13, p < 0.05) was also detected between concentrations of ACTH and alpha-MSH, suggesting that proopiomelanocortin peptide secretion from the pars distalis and pars intermedia occurs at least on occasion in synchrony. No differences in hormonal profiles were noted when comparing data across sexes. Data from the studies designed to evaluate circadian change (48 and 72-h bleed periods) indicated that, of the four hormones, only concentrations of alpha-MSH changed with a significant circadian periodicity. A significant circadian component of period length 24-25 h was detected in 37% (seven of 19) of cats examined. Concentrations of alpha-MSH were greatest coincident with or shortly after the onset of darkness. These findings indicate that pituitary-adrenocortical hormones are secreted episodically in domestic cats and that, in contrast to the patterns shown by ACTH and cortisol, secretion of the pars intermedia product alpha-MSH occurs with a circadian rhythm in about one-third of cats.

Biogenic Amine and Corticotrophin-Releasing Factor Concentrations in Hypothalamic Paraventricular Nucleus and Biogenic Amine Levels in the Median Eminence of Normal Dogs, Chronic Dexamethasone-Treated Dogs, and Dogs with Naturally-Occurring Pituitary-Dependent Hyperadrenocorticism (Canine Cushing's Disease).

Abstract We measured dopamine, norepinephrine, serotonin and epinephrine concentrations in the paraventricular nucleus and median eminence, and corticotrophin-releasing factor levels in the paraventricular nucleus. Tissue was isolated by micropunch technique from hypothalami of normal dogs, dogs treated for one week with dexamethasone (1 mg/kg/day) and dogs with spontaneous pituitary-dependent hyperadrenocorticism. Concentrations of corticotrophin-releasing factor and most of the neurotransmitters were found to be similar between our three groups of dogs. However, we found the mean dopamine concentration in the median eminence tissue to be significantly decreased in dogs with Cushing's disease and in steroid-treated dogs. Epinephrine levels were elevated in the hypothalamic paraventricular nucleus of steroid-treated dogs.

Increased serum D-lactate associated with diabetic ketoacidosis.

We hypothesized that serum D-lactate may be increased in vivo in diabetes mellitus as a result of increased glucose flux through the glyoxalase pathway and/or via hepatic ketone metabolism. Levels of D-lactate and related metabolic intermediates were measured in 30 cats with spontaneous diabetes mellitus and in one ketoacidotic nondiabetic cat. Serum D-lactate was significantly (P = .0051) elevated in cats with ketoacidosis (337.2 +/- 70.2 mumol/L) as compared with nonketoacidotic diabetic (140.3 +/- 58.8) and control (25.0 + 6.5) cats. Two nonketoacidotic cats also had high levels of D-lactate. There was a significant linear correlation (r = .684, P = .0001) between D-lactate and beta-hydroxybutyrate concentrations. Serum D-lactate did not correlate with serum glucose (r = .078, P = .6825), and in vitro erythrocyte D-lactate formation did not increase in the presence of hyperglycemia. These data suggest that hepatic ketone metabolism, rather than hyperglycemia, may be a major source of serum D-lactate in diabetics.

Autonomous growth and function of cultured thyroid follicles from cats with spontaneous hyperthyroidism.

Spontaneous feline hyperthyroidism is a unique experimental model of toxic nodular goiter. To determine whether feline toxic goiter is caused by extrathyroidal stimulating factors or by the intrinsic autonomy of follicular cells, primary cultures of enzymatically dissociated follicles from 15 hyperthyroid cat goiters and from 3 normal cat thyroid glands were embedded in collagen gels. Growth and function in chemically defined media were assessed by autoradiography after double labeling with 3H-thymidine and 131I-Na. Iodine organification in follicles from normal glands was TSH dependent, but intense radioiodine organification occurred in follicles from hyperfunctioning goiters even in the absence of TSH. Similarly, twice as many follicular cells of hyperfunctioning thyroid tissue, maintained without TSH in the medium, were labeled after exposure to 3H-thymidine than in follicles from normal glands. The results strongly suggest that intrinsic alterations of cell function lead to autonomy of follicular growth and function and subsequently to the development of hyperplastic nodules, causing thyrotoxicosis. The reason for the focal nature of the disease remains an unresolved challenge. Further investigation using this model may further understanding of the growth of autonomous endocrine tumors.

Beta cell and insulin antibodies in treated and untreated diabetic cats.

Beta cell and insulin antibodies are involved in the pathogenesis of diabetes in human patients. Beta cell antibodies have also been found in about 50% of newly diagnosed diabetic dogs. This study's objective was to examine these antibodies' role in feline diabetes. The serum of 26 newly diagnosed untreated diabetic cats, 29 cats on insulin therapy, 30 cats with diseases other than diabetes, and 30 healthy cats was examined for beta cell and insulin antibodies. For beta cell antibody testing, purified beta cells from a radiation-induced transplantable rat insulinoma were used. Serum from cats in which anti-beta cell antibodies were induced by injecting a purified beta cell suspension subcutaneously was used as a positive control. Following incubation with test sera, fluorescein-labeled anti-cat immunoglobulins were used to visualize binding between the beta cells and cat gamma globulins. Each serum was tested on two different tumor preparations. For the detection of insulin antibodies, a charcoal separation method was used. It was found that none of the healthy cats, none of the newly diagnosed, untreated diabetic cats and none of the cats with diseases other than diabetes had antibodies against beta cells or against endogenous insulin. Four diabetic cats (14%) that had been treated with different insulin preparations had insulin antibodies. It is concluded that immune-mediated processes are not causing diabetes in the cat. Further studies are needed to evaluate if antibodies directed against exogenous insulin alter the response of diabetic cats to insulin.

Lack of circulating thyroid stimulating immunoglobulins in cats with hyperthyroidism.

Although feline hyperthyroidism has become a commonly diagnosed disorder of older cats, the underlying etiology remains unknown. Pathological findings of adenomatous hyperplasia involving both thyroid lobes in most hyperthyroid cats suggests the possibility that feline hyperthyroidism may be similar to human Graves' disease, which results from high circulating levels of thyroid stimulating immunoglobulins (TSIs). To exclude high circulating levels of TSIs as the cause of feline hyperthyroidism, we measured intracellular concentrations of cyclic adenosine monophosphate (cAMP) in functioning rat thyroid cells (FRTL-5) incubated with IgG extracted from hyperthyroid cat serum. Since TSIs stimulate thyroid hormone secretion through activation of cAMP, their presence can be evidenced in vitro by generation of high cAMP concentrations in cultured thyroid cells. No significant difference was found in intracellular cAMP concentrations in FRTL-5 cells incubated with IgG from normal versus hyperthyroid cats. In contrast, IgG from a human patient with Graves' disease caused substantially more cAMP generation than either normal human IgG or IgG from the cats of this study. These results indicate that feline hyperthyroidism does not result from high circulating concentrations of TSI and, in that respect, is not analogous to Graves' disease.