N.V. Gómez

Diurnal ACTH and plasma cortisol variations in healthy dogs and in those with pituitary-dependent Cushing's syndrome before and after treatment with retinoic acid.

Daytime variations in ACTH and plasma cortisol were studied in healthy dogs and in dogs with pituitary-dependent hypercortisolism (PDH), before and after treatment with retinoic acid. In control dogs ACTH showed a higher concentration at 8.00 AM and between 2.00 and 6.00 PM, with the lowest concentration registered at 10.00 AM (p<0.05 vs. 8.00 AM and 2.00 PM and p<0.01 vs. 4.00 PM). Cortisol did not show significant differences. In dogs with PDH, ACTH was lower at 8.00 AM (ACTH: p<0.01 vs. 2.00 and 4.00 PM; and p<0.05 vs. 6.00 PM). The lowest cortisol concentration was registered at 8.00 AM and 8.00 PM and the highest at 4.00 PM (p<0.05 vs. 8.00 AM and p<0.01 vs. 8.00 PM). After treatment, the lowest ACTH concentration was registered at 10.00 AM (p<0.01 vs. 2.00 and 4.00 PM). To conclude, the adrenal is desensitized in PDH possibly showing negative in diagnostic tests.

Evaluation of Different Antiretroviral Drug Protocols on Naturally Infected Feline Immunodeficiency Virus (FIV) Cats in the late Phase of the Asymptomatic Stage of Infection

The aim of this study was to evaluate the efficacy of the antiretrovirals: Zidovudine (ZDV) alone; ZDV + Recombinant Human Interferon-α (rHuIFN-α); ZDV + Lamivudine (3TC) and ZDV + valproic acid (Valp) on naturally feline immunodeficiency virus (FIV)-infected cats, in the late phase of the asymptomatic stage of infection. The follow-up was performed over one year, through clinical evaluation and the determination of viral loads and CD4+/CD8+ ratios. Neurological signs were studied by visual and auditory evoked potentials (VEP, AEP) and the responses were abnormal in 80% of the FIV-infected cats. After one year, an improvement in VEP and AEP was observed in the ZDV + Valp group and a worsening in the group receiving ZDV + rHuIFN-α. The CD4+/CD8+ ratio showed a significant increase (both intra and inter-groups) only in ZDV and ZDV + 3TC, between their pre-treatment and one year values, as well as among the other groups. Viral load only showed a significant decrease in ZDV and ZDV + 3TC groups, when comparing the values at one year of treatment vs. pre-treatment values and when the different groups were compared. In addition, the viral load decrease was significantly more pronounced in the ZDV + 3TC vs. ZDV group. We conclude that ZDV and ZDV + 3TC produce significant reductions in viral load and stimulate a recovery of the CD4+/CD8+ ratio, compared with the other protocols. It is clear that the addition of 3TC resulted in a greater reduction in viral load than use of ZDV as a single drug. Therefore, the combination ZDV + 3TC could be more effective than the sole use of ZDV.

Interleukin-6 and insulin incrase and nitric oxide and adiponectin decrease in blind dogs with pituitary-dependent hyperadrenocorticism.

In this study, two populations of dogs with pituitary dependent hypercortisolism (PDH) were compared over a 2-year period. One group had normal vision (Group A, n=27) and one group was blind (Group B, n=20). Group B was characterised by the rapid appearance of the clinical signs of PDH that precede blindness. We found increases in pre-adrenocorticotropic hormone cortisol (P=0.002), IL-6 (P=0.0001), insulin, and insulin sensitivity (detected with the Homeostatic Model Assessment, P<0.0001) in Group B but not in Group A. The nitric oxide (NO) and the total adiponectin concentrations decreased (P=0.0001 and P=0.02, respectively) in Group B versus Group A. The IL-6 and insulin concentrations and the HOMA-A index were positively correlated with the cortisol concentration and were negatively correlated with the NO concentration. With the exception of adiponectin, the other variables were associated with blindness. We concluded that blindness in PDH is a haemodynamic event associated with metabolic changes, with the increase in the IL-6 concentration and the decrease in the NO concentration affecting the retinal vasculature and producing a high risk of vision loss.

Low dose of insulin detemir controls glycaemia, insulinemia and prevents diabetes mellitus progression in the dog with pituitary-dependent hyperadrenocorticism.

Diabetes is often associated with pituitary-dependent hyperadrenocorticism (PDH). Hypercortisolism causes insulin resistance and affects β-cell function. The purpose of this study was to test if daily administration of a long-acting insulin analogue during the first month of anti-PDH treatment can prevent progress to diabetes in these animals. Twenty-six PDH dogs were divided into three groups: one group with glycaemia <5.83 mmol/L and two groups with glycaemia >5.83 mmol/L and <9.35 mmol/L, one of which received insulin detemir during 4 months. Dogs with glycaemia <5.83 mmol/L and those with glycaemia >5.83 mmol/L which received insulin did not develop diabetes. In the non-insulin group, 6/7 dogs developed diabetes after the third month. There is a 13-fold higher risk of diabetes in dogs with glycaemia >5.83 mmol/L and no insulin treatment. Administering insulin detemir to dogs with PDH and glycaemia >5.83 mmol/L could prevent progression to diabetes.

Blindness in dogs with pituitary dependent hyperadrenocorticism: Relationship with glucose, cortisol and triglyceride concentration and with ophthalmic blood flow

Pituitary dependent hyperadrenocorticism (PDH) shows a high morbidity and blindness is one of its complications. Compression of the optic chiasm (OC) by the hypophysis adenoma is one of the causes. Another cause could be due to vascular and metabolic alterations of the PDH. Out of a total of 70 dogs with confirmed diagnosis of PDH, 12/70 showed blindness. In only 2/12 the OC was compromised. Electroretinography in dogs without the OC being compromised showed altered A and B wave patterns. Ophthalmological Doppler showed an alteration of the blood flow only in blind dogs without OC compression. Cortisol concentrations (Co), triglycerides (Tg) and glycaemia (G) were greater in 10 dogs with non-compressive blindness vs. dogs with conserved vision. Loss of vision correlated with the increase in these variables. Blindness in dogs with PDH would be related to changes in retinal blood flow, associated to higher Co, Tg and G concentrations.

Immune–endocrine interactions in treated and untreated cats naturally infected with FIV

Feline immunodeficiency virus (FIV) is a lentivirus that causes a progressive disruption of immune function in cats. The neuroendocrine and immune systems communicate bidirectionally, mediated by cytokines such as tumour necrosis factor-α (TNF), several interleukins (IL-1, IL-6, IL-10), and through signals induced by the ratio of IL-10 to IL-12. FIV can affect both pituitary adrenal and thyroid axis function. Twenty FIV-infected cats in similar stages of the disease were evaluated for six months. A cross-sectional study in which the twenty cats were divided into two groups was performed. Ten were treated with Zidovudine (ZDV: 5mg/kg/d, PO, q12h, for six months) and 10 were untreated. Plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, T4, FT4, T3, IL-10, IL-12 and viral load (VL) were evaluated after six months. ACTH was found in significantly lower concentrations (p<0.0001) in the treated group whereas cortisol did not show significant differences between the two groups. Both T4 and FT4 had high values in untreated individuals (p<0.001) compared with Zidovudine treated cats. T3 did not show significant differences between the two groups. Both IL-10 and IL-12 were found in significantly higher concentrations in ZDV treated cats (p<0.001). By contrast, the IL10/IL-12 ratio values were significantly lower in untreated cats. Viral load was significantly lower in the treated cats after six months of therapy, compared with values detected pre-treatment (p<0.002). Untreated cats showed a significant increase of VL (p<0.04) compared with the values at the beginning of the study. In treated cats, VL showed lower numbers of viral copies than in untreated cats (p<0.01). In summary, Zidovudine treatment appeared to contribute to the normalization of both the adrenal and thyroid axes. This effect could be attributed to the decrease observed in VL, resulting in a change in cytokine patterns.

Plasma ACTH, α-MSH and cortisol variations in the dog during the oestrous cycle in different photoperiods

The hypothalamic-pituitary-adrenal axis (HPA) is a complex system regulated by multiple factors. Sexual dimorphism of this axis has been described in different species under physiological conditions and it has been proposed that sexual hormones could have an effect on it. There are only a few reports about sex-linked variations in HPA axis hormones in the dog. Thus, studying the impact of sexual hormones on the HPA axis would broaden the knowledge about its function in this species. Therefore, the objective of this study was to determine whether there are variations in HPA plasma hormones (ACTH, alfa-melanocyte-stimulating hormone (α-MSH) and cortisol) according to the sex and photoperiod (positive or negative photoperiod were considered when the duration of the light hours of the day was more than 12 or less than 12, respectively) under basal conditions (like anoestrus) and throughout the oestrous cycle in the female dog. The population under study consisted of 11 intact female and 14 intact male dogs. Under basal conditions neither ACTH nor α-MSH concentrations showed differ - ences between sexes and different photoperiods. Cortisol showed greater values in the negative photoperiod than in the positive, both in females and males ( P = 0.03 and P = 0.015, respectively). Throughout the oestrous cycle, all the studied hormones showed variations ( P < 0.0001). The greatest concentrations of ACTH were observed at proestrus, while α-MSH and cortisol showed their greatest concentrations at oestrus. The three hormones decreased in diestrus . ACTH and cortisol concentrations were higher in the negative photoperiod ( P = 0.04 and P < 0.0001, respectively), while α-MSH concentrations were higher in the positive photoperiod ( P = 0.012). In the group of females oestradiol and progesterone correlated with ACTH ( r = 0.75, P < 0.0001; r = 0.34, P < 0.01, respectively), α-MSH (r = 0.49, P < 0.0001; r = 0.52, P < 0.0001, respectively) and cortisol ( r = 0.33, P < 0.01; r = 0.5, P < 0.0001, respectively). These results show that in females, HPA axis hormones vary during the oestrous cycle in relation to oestradiol and progesterone fluctuations. The ACTH, α-MSH and cortisol concentrations also showed differences between photoperiods in females, but only cortisol did so in males. These findings suggest that sexual hormones could have an effect on the HPA axis. Further research needs to be done to fully understand this interaction and the mechanisms involved.