Equine pituitary pars intermedia dysfunction: current understanding and recommendations from the Australian and New Zealand Equine Endocrine Group

The purpose of this article is to provide a review of the current knowledge and opinions about the epidemiology, clinical findings (including sequelae), diagnosis, treatment and monitoring of equine pituitary pars intermedia dysfunction, particularly in the Australian context. This information and the recommendations provided will assist practitioners in making informed decisions regarding the diagnosis and management of this disorder.     

Adenohypophyseal function in bitches treated with medroxyprogesterone acetate

The aim of this study was to investigate the effects of treatment with medroxyprogesterone acetate (MPA) on canine adenohypophyseal function. Five Beagle bitches were treated with MPA (10mg/kg, every 4 weeks) and their adenohypophyseal function was assessed in a combined adenohypophyseal function test. Four hypophysiotropic hormones (CRH, GHRH, GnRH, and TRH) were administered before and 2, 5, 8, and 11 months after the start of MPA treatment, and blood samples for determination of the plasma concentrations of ACTH, cortisol, GH, IGF-1, LH, FSH, prolactin, alpha-MSH, and TSH were collected at -15, 0, 5, 10, 20, 30, and 45 min after suprapituitary stimulation. MPA successfully prevented the occurrence of estrus, ovulation, and a subsequent luteal phase. MPA treatment did not affect basal and GnRH-induced plasma LH concentrations. The basal plasma FSH concentration was significantly higher at 2 months after the start of MPA treatment than before or at 5, 8, and 11 months after the start of treatment. The maximal FSH increment and the AUC for FSH after suprapituitary stimulation were significantly higher before treatment than at 5, 8, and 11 months of MPA treatment. Differences in mean basal plasma GH concentrations before and during treatment were not significant, but MPA treatment resulted in significantly elevated basal plasma IGF-1 concentrations at 8 and 11 months. MPA treatment did not affect basal and stimulated plasma ACTH concentrations, with the exception of a decreased AUC for ACTH at 11 months. In contrast, the maximal cortisol increment and the AUC for cortisol after suprapituitary stimulation were significantly lower during MPA treatment than prior to treatment. MPA treatment did not affect basal plasma concentrations of prolactin, TSH, and alpha-MSH, with the exception of slightly increased basal plasma TSH concentrations at 8 months of treatment. MPA treatment did not affect TRH-induced plasma concentrations of prolactin and TSH. In conclusion, the effects of chronic MPA treatment on adenohypophyseal function included increased FSH secretion, unaffected LH secretion, activation of the mammary GH-induced IGF-I secretion, slightly activated TSH secretion, suppression of the hypothalamic-pituitary-adrenocortical axis, and unaffected secretion of prolactin and alpha-MSH.     

Effect of tetracosactid on post partum cyclicity in cows after induction of parturition with PGF2 alpha

Parturition and retention of fetal membranes were induced with PGF2 alpha in 3 primiparous dairy cows. Starting on day 12 post partum (PP) the cows were treated with 500 micrograms i.m. of ACTH-analogue (tetracosactid) every 6 h for 6 times. Changes in plasma concentrations of cortisol, progesterone and 15-ketodihydro-PGF2 alpha were evaluated immediately after treatment. The effects on the resumption of ovarian activity were evaluated by clinical and ultrasound examinations and by progesterone and 15-ketodihydro-PGF2 alpha analyses for 56 days after parturition. Treatment was able to induce a statistically significant (p < 0.01) similar increase in cortisol and progesterone after both the 1st and the 6th injections, in all cows. No changes in 15-ketodihydro-PGF2 alpha concentrations were seen after any of the injections of ACTH-analogue. The first corpus luteum (CL) was seen on day 18 PP (cow A), and 28 (cow B) and in both cases it was followed by a normal ovarian cyclicity. No CL was observed during the whole period of study in cow C. Progesterone profiles confirmed these clinical and ultrasonographic findings. The steroid output, especially progesterone, induced by the ACTH-analogue might be a stimulus for the onset of ovarian cyclicity, since 2 of the 3 animals ovulated earlier than expected. These findings point to the fact that interference with the stress system might have a positive effect on ovarian cyclicity. The different pattern of response does however demand further studies.     

Failure to induce mucosal disease in cattle persistently infected with bovine viral diarrhea virus by treatment with adrenocorticotropic hormone

Recent research has shown that cattle that develop mucosal disease (MD) often, if not always, have been persistently infected with bovine viral diarrhea virus (BVDV) since birth. The purpose of the present study was to determine whether MD could be induced by immunosuppression of persistently BVDV-infected cattle. For that purpose, adrenocorticotropic hormone (ACTH) was injected intramuscularly, twice daily for 5 consecutive days in 4 persistently BVDV-infected cattle and in 3 control cattle. Before the ACTH treatment, the numbers of leukocytes, neutrophils and mononuclear cells (MNC) per litre of blood in BVDV-infected cattle were in the same range as in the controls. Similarly, the proportions of B cells, T cells, monocytes and Fcγ⁺ cells (cells with receptor for the Fc part of IgG) were the same in the 2 groups of animals. On the other hand, the proliferative response to mitogen stimulation of MNC obtained from the control animals was twice as high as the corresponding value of the persistently BVDV-infected cattle.In all animals, ACTH treatment caused increased Cortisol concentrations, leukocytosis, neutrophilia and decreased mitogen-induced lymphocyte stimulation. However, the MNC count and the proportions of B cells, T cells, Fcγ⁺ cells and monocytes remained unaltered. In spite of the immunosuppression, indicated by the decrease in mitogen-induced lymphocyte stimulation. ACTH treatment did not provoke any clinical signs of MD in the persistently BVDV-infected cattle.     

Lymphoma as a model for chronic illness: effects on adrenocortical function testing

Many dogs with chronic illness have serum biochemical abnormalities consistent with hyperadrenocorticism (HAC). Lymphoma (LSA) is a chronic disease of dogs. The purpose of this study was to evaluate adrenocortical screening test results in dogs with LSA to evaluate their specificity. Criteria for inclusion in the study included a diagnosis of LSA, an expected survival time of 16-56 weeks, no glucocorticoid treatment beyond 4 weeks after the initiation of chemotherapy, no evidence of HAC, and owner consent. Post-ACTH stimulation plasma cortisol concentrations (PACs), urine cortisol : creatinine (UC : Cr) ratios, and maximal left adrenal width measurements were performed at the time of LSA diagnosis before the initiation of chemotherapy and at 16, 24, 32, 40, and 52 weeks or until the loss of remission or the development of another disease. Ten dogs met the criteria for inclusion. Forty-two PACs were performed; 1 abnormal, 2 borderline, and 39 normal values were detected. Thirty-five maximal left adrenal width measurements were obtained; 0 abnormal, 5 borderline, and 30 normal measurements were detected. Thirty-six UC : Cr ratios were obtained, with 26 abnormal, 4 borderline, and 6 normal values detected and 9 of 10 dogs having at least 1 abnormal value. These data suggest that in dogs with LSA, the UC : Cr ratio frequently is abnormal and may not be a specific test for HAC, or it may be the most sensitive test for increases in cortisol secretion due to chronic illness. Maximal left adrenal width measurements and PACs were almost always normal and may be more specific for HAC or less sensitive for demonstrating chronic increases in cortisol secretion.     

Repeated administrations of adrenocorticotropic hormone during gestation in gilts: Effects on growth, behaviour and immune responses of their piglets

This study investigated whether repeated administrations of adrenocorticotropic hormone (ACTH) during mid or late gestation, a treatment which induces endogenous cortisol release, affect growth performance, early vitality, open-field behaviour and immune responses of neonatal pigs. Administrations of ACTH (100 IU per animal, Synacthen^® Depot) were given intramuscularly to gilts every second day either during mid (Day 49 until 75, Experiment 1) or late gestation (Day 85 until 107, Experiment 2). Control gilts received repeated injections of saline. The repeated ACTH stimulation of gilts during late gestation significantly reduced their daily weight gain during this period, but not when applied during mid gestation. Gestation length, number of born piglets and vitality measures of the newborn piglets, such as the rectal temperatures after birth and times elapsed between birth and first udder contact or milk uptake were not affected by the prenatal treatments. Administration of ACTH during late but not during mid gestation significantly increased the birth weights of piglets, and this difference in postnatal body weight was detectable until an age of 21 days. In addition, only the stimulation with ACTH during late gestation had an immunosuppressive effect on the lymphocyte proliferation of piglets 1 day after birth in response to the T-cell mitogen ConA and, in tendency, on the proliferation in response to the B-cell mitogen LPS. Twenty-four day old piglets from gilts treated during late gestation showed significantly more escape behaviour in an open-field than piglets from control litters. In conclusion, elevated maternal glucocorticoid levels during critical periods of prenatal development in pigs may affect prenatal growth, cell-mediated immunity and emotional reactivity in the neonatal piglets. The occurrence of these effects depends on the timing of increased maternal cortisol levels during gestation.     

Effects of delmadinone acetate on pituitary-adrenal function, glucose tolerance and growth hormone in male dogs

Objective To characterise the effects of delmadinone acetate on the pituitary-adrenal axis, glucose tolerance and growth hormone concentration in normal male dogs and dogs with benign prostatic hyperplasia.
Design A prospective study involving nine normal male dogs and seven with prostatic hyperplasia.
Procedure Delmadinone acetate was administered to six normal male dogs and seven dogs with benign prostatic hyperplasia at recommended dose rates (1.5 mg/kg subcuta-neously at 0, 1 and 4 weeks). Three normal controls received saline at the same intervals. Blood concentrations of ACTH, cortisol, glucose, insulin and growth hormone were measured over 50 days. Intravenous glucose tolerance and ACTH response tests were performed before and after treatment in the nine normal animals.
Results A substantial suppression of basal and 2 h post-ACTH plasma cortisol secretion was demonstrated after one dose in all dogs given delmadinone acetate. Individual responses after the second and third administration varied between recovery in adrenal responsiveness to continued suppression. Plasma ACTH concentration was also diminished after one treatment. No effects were evident on glucose tolerance or serum growth hormone concentrations.
Conclusion Delmadinone acetate causes adrenal suppression from inhibition of release of ACTH from the pituitary gland. Treated dogs may be at risk of developing signs of glucocorticoid insufficiency if subjected to stressful events during or after therapy. Neither glucose intolerance nor hyper-somatotropism seems likely in male dogs given delmadinone acetate at the recommended dose rate, but the potential for excessive growth hormone secretion in treated bitches remains undetermined.     

Plasma cortisol responses to three cortico-trophic preparations in normal dogs

Objective To compare cortisol responses to three corticotrophic preparations in normal dogs.
Animals Eight clinically normal dogs (four intact males, four intact females) of medium size.
Procedures Each dog received four treatments on four separate occasions in a duplicated Latin square pattern. Treatments were two adrenocorticotrophin (ACTH) preparations given intramuscularly at 2.2 U/kg, one of the ACTH preparations given intramuscularly at 1 U/kg and a synthetic polypeptide with ACTH-like activity (tetracosactrin, cosyntropin) given intravenously at 5 μg/kg. Plasma samples were taken for cortisol assay before and at 0.5, 1, 2 and 4 h after treatment.
Results Plasma cortisol concentrations were similar with the two ACTH preparations and at both dose rates. Tetracosactrin produced smaller mean peak cortisol concentrations, which tended to occur earlier than with ACTH, and smaller values for the area under the curve of plasma cortisol concentration from zero time to 4 h.
Conclusion The findings suggest that canine adrenal function can be tested adequately by giving ACTH intramuscularly at 1 U/kg and measuring plasma cortisol in samples taken at 0 and 2 h, or by giving tetracosactrin intravenously at 5 μg/kg and determining cortisol concentration at 0 and 1 h.     

A comparison of the adrenal cortical response to ACTH stimulation in Angora and non-Angora goats

The adrenal cortex is believed to be implicated in the high incidence of abortion in the Angora goat. Stimulation testing with adrenocorticotrophic hormone (ACTH) was used to assess the adrenal cortical function in 5 Angora does from herds with a history of abortion and 5 non-Angora does. An acute test involving a single intramuscular (i.m.) injection of 0.25 mg of synthetic ACTH was given during anoestrus, at mid-oestrus, on day 90 and on day 120 of gestation. Blood samples were collected from the jugular vein at 30 min intervals for 1 h before and 5 h after injection. Cortisol concentrations rose within 30 min and returned to baseline values within 3.5 h. Cortisol production was lower (p<0.01) in the pregnant state compared to the non-pregnant state in both groups. Production of cortisol was consistently lower (p<0.05) in the Angora does compared to the non-Angora does during anoestrus and pregnancy and marginally so at mid-oestrus. A chronic stimulation test involving once daily injections of 0.5 mg of a depot form of ACTH i.m. for 7 days commencing on day 90 of pregnancy was also conducted. Cortisol concentrations rose to reach a peak on the third day of treatment in both groups. The values then declined in the Angora does despite continued ACTH treatment, while those for the non-Angora does exhibited a second peak. During and following this treatment, two non-Angora does delivered live kids (day 95, day 120). Out of 7 Angora pregnancies, one Angora doe aborted two dead fetuses at day 116. No significant difference in the cortisol response in the acute test was detected between the animals that aborted and their respective cohorts, but the two non-Angora does that aborted had significantly lower cortisol concentrations during depot ACTH administration. Progesterone and oestradiol levels did not differ between Angora and non-Angora animals during pregnancy or on the test days. The results suggest that the steroidogenic response of the adrenal cortex to ACTH stimulation is significantly less in Angora does with a history of abortion than it is in non-Angora does and support the view that the Angora goat would make a more limited adrenal cortical response to a stressful occurrence during pregnancy.     

Endocrine stress response and abnormal development in carp (Cyprinus carpio) larvae after exposure of the embryos to PCB 126

To investigate whether PCB 126 exposure duringembryonic development induces an endocrine stressresponse in larval carp, eggs were exposed,containing 0.01% ethanol (vehicle-control), 10^-11,immediately after fertilization, for 48 h to water10^-10 or 10^-9 mol l^-1 PCB in 0.01% ethanol. Eggsincubated in water served as controls. After transferto PCB-free water, mortality, the incidence ofyolk-sac and pe-ricardial oedema, wet and dry weight,rate of skin pigmentation, and whole-body contents ofthe stress hormones ACTH, -MSH and cortisol weredetermined at 48, 96, 144, 168, 192 and 216 hpost-fertilization. Except for the dry weight, allparameters of animals exposed to 10^-10 and 10^-9 moll^-1 PCB increased in a concentration-related manner.However, these changes became evident only at 144 hpost-fertilization, i.e. after resorption of theyolk-sac. Swelling of the yolk sac and pericardiumoccurred, and whole-body ACTH, -MSH and cortisollevels increased. Although animals exposed to 10^-10and 10^-9 mol l^-1 PCB displayed stable but elevatedwhole-body ACTH and -MSH levels until 216 h,whole-body cortisol concentrations gradually decreasedfrom 168 h post-fertilization, and were significantlybelow control values at 216 h post-fertilization.Exposure of the carp embryos to 10^-11 mol l^-1 PCB only increased whole-body -MSH levels. Increased whole-body ACTH and cortisol levels indicate that PCBinduces a stress response in carp larvae, possiblymediated by a disturbed hydromineral balance (oedema).We further suggest that the PCB-stimulated bodypigmentation is mediated by a stimulation of -MSHsecretion.