Transdermal carbimazole for the treatment of feline hyperthyroidism

Orally administered antithyroid drugs are frequently used to treat hyperthyroidism in cats; however, the non-cooperative behaviour of some cats may make it difficult to administer tablets. The aim of this study was to develop a carbimazole ointment for application to the inner pinna of the ear and to test its effectiveness in 13 cats with hyperthyroidism. Laboratory investigations were performed before, and 4, 8, and 12 weeks after start of the treatment. Laboratory data for 9 cats were available at the end of the observation period. The starting dose of carbimazole ointment was 5 mg once daily. If no complications occurred, the dose was increased to 5 mg twice daily from the 6th day onwards. Further dose adjustments were mainly based on the plasma thyroxine (T4) concentration. The median plasma T4 concentration at the end of the observation period (24 nmol/l) was significantly lower than that before treatment (152 nmol/l). The dosage of carbimazole needed to achieve euthyroidism ranged from 4 to 17 mg twice daily. Treatment with carbimazole ointment resulted in disappearance of signs of hyperthyroidism; plasma concentrations of urea and creatinine increased significantly. The results of this study indicate that twice daily administration of carbimazole ointment to the inner pinna of the ear is an effective treatment for hyperthyroidism in cats. This provides the veterinarian with a new and promising treatment option. Because carbimazole ointment has not been registered, according to European law it can only be used for the treatment of hyperthyroidism in cats if other licensed medications have been tried and if there is a therapeutic need.     

Diagnosis of Spontaneous Canine Hyperadrenocorticism: 2012 ACVIM Consensus Statement (Small Animal)

This report offers a consensus opinion on the diagnosis of spontaneous canine hyperadrenocorticism. The possibility that a patient has hyperadrenocorticism is based on the history and physical examination. Endocrine tests should be performed only when clinical signs consistent with HAC are present. None of the biochemical screening or differentiating tests for hyperadrenocorticism are perfect. Imaging can also play a role. Awareness of hyperadrenocorticism has heightened over time. Thus, case presentation is more subtle. Due to the changes in manifestations as well as test technology the Panel believes that references ranges should be reestablished. The role of cortisol precursors and sex hormones in causing a syndrome of occult hyperadrenocorticism remains unclear.     

Short- and long-term follow-up of glomerular and tubular renal markers of kidney function in hyperthyroid cats after treatment with radioiodine

Hyperthyroidism can mask co-existing chronic kidney disease (CKD). Previous studies showed that post-treatment renal azotemia can be predicted by pre-treatment assessment of glomerular filtration rate (GFR). We hypothesized that treatment of hyperthyroidism may have different effects on glomerular and tubular function and these changes might be predicted by additional pre-treatment variables than GFR.     

Adenohypophyseal Function in Dogs with Primary Hypothyroidism and Nonthyroidal Illness

Background: A recent study of dogs with induced primary hypothyroidism (PH) demonstrated that thyroid hormone deficiency leads to loss of thyrotropin (TSH) hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement with large vacuolated "thyroid deficiency" cells that double-stained for growth hormone (GH) and TSH, indicative of transdifferentiation of somatotropes to thyrosomatropes.
Hypothesis: Similar functional changes in adenohypophyseal function occur in dogs with spontaneous PH as do in dogs with induced PH, but not in dogs with nonthyroidal illness (NTI).
Animals: Fourteen dogs with spontaneous PH and 13 dogs with NTI.
Methods: Adenohypophyseal function was investigated by combined intravenous administration of 4 hypophysiotropic releasing hormones (4RH test), followed by measurement of plasma concentrations of ACTH, GH, luteinizing hormone (LH), prolactin (PRL), and TSH. In the PH dogs this test was repeated after 4 and 12 weeks of thyroxine treatment.
Results: In 6 PH dogs, the basal TSH concentration was within the reference range. In the PH dogs, the TSH concentrations did not increase with the 4RH test. However, TSH concentrations increased significantly in the NTI dogs. Basal and stimulated GH and PRL concentrations indicated reversible hypersomatotropism and hyperprolactinemia in the PH dogs, but not in the NTI dogs. Basal and stimulated LH and ACTH concentrations did not differ between groups.
Conclusions and Clinical Importance: Dogs with spontaneous PH hypersecrete GH but have little or no TSH hypersecretion. Development of hyperprolactinemia (and possible galactorrhea) in dogs with PH seems to occur only in sexually intact bitches. In this group of dogs with NTI, basal and stimulated plasma adenohypophyseal hormone concentrations were not altered.     

Hypercortisolism affects glomerular and tubular function in dogs

Renal function was assessed in 25 dogs with Cushing's syndrome and in 12 healthy controls. Routine renal parameters and glomerular filtration rate (GFR) were measured and urinary biomarkers such as urinary albumin (uALB), urinary immunoglobulin G (uIgG), and urinary retinol-binding protein (uRBP) were assessed by ELISA. Urinary N-acetyl-β-D-glucosaminidase activity (uNAG) was determined colorimetrically. All urinary markers were indexed to urinary creatinine concentration (c). Plasma exo- (Cl(exo)) and endo-iohexol (Cl(endo)) clearance were used to measure GFR. Based on a Mann-Whitney U test, urea and Cl(exo) did not differ, sCr was significantly lower, and UPC, uALB/c, uIgG/c, uRBP/c, uNAG/c and Cl(endo) were higher in the dogs with Cushing's syndrome when compared with controls. The findings indicate that glomerular and tubular function are both altered in dogs with Cushing's syndrome. Further longitudinal studies will be required to elucidate the pathogenesis of the changes in GFR.     

Anoestrus in the Dog: a Fascinating Story

In the bitch, progression from early to late anoestrus is characterized by a higher amplitude and a larger number of gonadotrophin-releasing hormone (GnRH) pulses generated by the hypothalamus, an increase in the sensitivity of the pituitary to GnRH, and an increase in ovarian responsiveness to gonadotrophins. An increase in basal plasma follicle-stimulating hormone (FSH) concentration is a critical event required for initiation of folliculogenesis. A period of increased luteinizing hormone pulsatility has been reported shortly before the onset of pro-oestrus. Apart from these changes in the hypothalamic-pituitary-ovarian axis, there is also involvement of dopaminergic influences in the initiation of a new follicular phase in the bitch. Administration of the dopamine-agonists bromocriptine and cabergoline shortens the anoestrus and is associated with a decrease in the plasma prolactin concentration, suggesting that the shortened anoestrus is the result of suppression of prolactin secretion. Yet, the anoestrus is not shortened in bitches treated with metergoline, a drug, which in a low dosage lowers the plasma prolactin concentration via a serotonin-antagonistic pathway. In addition, under physiological conditions low plasma prolactin concentrations are found during the entire anoestrus. Furthermore, a low dosage of bromocriptine, insufficient to cause a decrease in the plasma prolactin concentration, prematurely induces folliculogenesis. These observations indicate that not the decrease in the plasma prolactin concentration, but another dopamine-agonistic influence plays a critical role in the transition to a new follicular phase. The dopamine-agonist induced shortening of the anoestrus is associated with a rapid rise in the basal plasma FSH concentration, similar to what is observed during the physiological late anoestrus. This observation underlines the importance of an increase in the circulating plasma FSH concentration in the initiation of folliculogenesis in the bitch.     

Induction of pancreatic differentiation by signals from blood vessels

Blood vessels supply developing organs with metabolic sustenance. Here, we demonstrate a role for blood vessels as a source of developmental signals during pancreatic organogenesis. In vitro experiments with embryonic mouse tissues demonstrate that blood vessel endothelium induces insulin expression in isolated endoderm. Removal of the dorsal aorta in Xenopus laevis embryos results in the failure of insulin expression in vivo. Furthermore, using transgenic mice, we show that ectopic vascularization in the posterior foregut leads to ectopic insulin expression and islet hyperplasia. These results indicate that vessels not only provide metabolic sustenance, but also provide inductive signals for organ development.     

Selection in runner beans (Phaseolus coccineus L.) with special reference to the use of tuberous roots

Summary It is recommended to improve runner beans by incorporating resistance to halo blight, and particularly by incorporating the stringless and tender-podded characters and by increasing the uniformity of the pods. In selection in this cross-pollinated crop, notably for the above pod characters, use can be made of the possibility to maintain the plants asexually by means of the tuberous roots.     

Molecular markers of prognosis in canine cortisol‐secreting adrenocortical tumours

Hypercortisolism is caused by a cortisol‐secreting adrenocortical tumour (ACT) in approximately 15%‐20% of cases in dogs. Little is known about which molecular markers are associated with malignant behaviour of canine ACTs. The objective of this study was to identify molecular markers of prognosis, which could be useful to refine prognostic prediction and to identify potential treatment targets. Cortisol‐secreting ACTs were included from 40 dogs, of which follow‐up information was available. The ACTs were classified as low risk of recurrence tumours (LRT; n = 14) or moderate‐high risk of recurrence tumours (MHRT; n = 26), based on the novel histopathological Utrecht score. Normal adrenals (NAs) were included from 11 healthy dogs as reference material. The mRNA expression of 14 candidate genes was analysed in the 40 ACTs and in 11 NAs with quantitative RT‐PCR. The genes' expression levels were statistically compared between NAs, LRTs and MHRTs. Univariate and multivariate analyses were performed to determine the association of the genes' expression levels with survival. Seven genes were differentially expressed between NAs and ACTs, of which pituitary tumour‐transforming gene‐1 (PTTG1) and topoisomerase II alpha (TOP2A) were also differentially expressed between LRTs and MHRTs. In survival analyses, high expression levels of Steroidogenic factor‐1 (SF‐1), PTTG1 and TOP2A were significantly associated with poor survival. In conclusion, we have identified several genes that are part of the molecular signature of malignancy in canine ACTs. These findings can be used to refine prognostic prediction, but also offer insights for future studies on druggable targets.