RESUMO
BACKGROUND: Pituitary pars intermedia dysfunction (PPID) is a prevalent, age-related chronic disorder in equids. Diagnosis of PPID can be challenging because of its broad spectrum of clinical presentations and disparate published diagnostic criteria, and there are limited available treatment options. OBJECTIVES: To develop evidence-based primary care guidelines for the diagnosis and treatment of equine PPID based on the available literature. STUDY DESIGN: Evidence-based clinical guideline using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. METHODS: Research questions were proposed by a panel of veterinarians and developed into PICO or another structured format. VetSRev and Veterinary Evidence were searched for evidence summaries, and systematic searches of the NCBI PubMed and CAB Direct databases were conducted using keyword searches in July 2022 and updated in January 2023. The evidence was evaluated using the GRADE framework. RESULTS AND RECOMMENDATIONS: The research questions were categorised into four areas: (A) Case selection for diagnostic testing, pre-test probability and diagnostic test accuracy, (B) interpretation of test results, (C) pharmacological treatments and other treatment/management options and (D) monitoring treated cases. Relevant veterinary publications were identified and assessed using the GRADE criteria. The results were developed into recommendations: (A) Case selection for diagnostic testing and diagnostic test accuracy: (i) The prevalence of PPID in equids aged ≥15 years is between 21% and 27%; (ii) hypertrichosis or delayed/incomplete hair coat shedding provides a high index of clinical suspicion for PPID; (iii) the combination of clinical signs and age informs the index of clinical suspicion prior to diagnostic testing; (iv) estimated pre-test probability of PPID should be considered in interpretation of diagnostic test results; (v) pre-test probability of PPID is low in equids aged <10 years; (vi) both pre-test probability of disease and season of testing have strong influence on the ability to diagnose PPID using basal adrenocorticotropic hormone (ACTH) or ACTH after thyrotropin-releasing hormone (TRH) stimulation. The overall diagnostic accuracy of basal ACTH concentrations for diagnosing PPID ranged between 88% and 92% in the autumn and 70% and 86% in the non-autumn, depending on the pre-test probability. Based on a single study, the overall diagnostic accuracy of ACTH concentrations in response to TRH after 30 minutes for diagnosing PPID ranged between 92% and 98% in the autumn and 90% and 94% in the non-autumn, depending on the pre-test probability. Thus, it should be remembered that the risk of a false positive result increases in situations where there is a low pre-test probability, which could mean that treatment is initiated for PPID without checking for a more likely alternative diagnosis. This could compromise horse welfare due to the commencement of lifelong therapy and/or failing to identify and treat an alternative potentially life-threatening condition. (B) Interpretation of diagnostic tests: (i) There is a significant effect of breed on plasma ACTH concentration, particularly in the autumn with markedly higher ACTH concentrations in some but not all 'thrifty' breeds; (ii) basal and/or post-TRH ACTH concentrations may also be affected by latitude/location, diet/feeding, coat colour, critical illness and trailer transport; (iii) mild pain is unlikely to have a large effect on basal ACTH, but caution may be required for more severe pain; (iv) determining diagnostic thresholds that allow for all possible contributory factors is not practical; therefore, the use of equivocal ranges is supported; (v) dynamic insulin testing and TRH stimulation testing may be combined, but TRH stimulation testing should not immediately follow an oral sugar test; (vi) equids with PPID and hyperinsulinaemia appear to be at higher risk of laminitis, but ACTH is not an independent predictor of laminitis risk. (C) Pharmacologic treatments and other treatment/management options: (i) Pergolide improves most clinical signs associated with PPID in the majority of affected animals; (ii) Pergolide treatment lowers basal ACTH concentrations and improves the ACTH response to TRH in many animals, but measures of insulin dysregulation (ID) are not altered in most cases; (iii) chasteberry has no effect on ACTH concentrations and there is no benefit to adding chasteberry to pergolide therapy; (iv) combination of cyproheptadine with pergolide is not superior to pergolide alone; (v) there is no evidence that pergolide has adverse cardiac effects in horses; (vi) Pergolide does not affect insulin sensitivity. (D) Monitoring pergolide-treated cases: (i) Hormone assays provide a crude indication of pituitary control in response to pergolide therapy, however it is unknown whether monitoring of ACTH concentrations and titrating of pergolide doses accordingly is associated with improved endocrinological or clinical outcome; (ii) it is unknown whether monitoring the ACTH response to TRH or clinical signs is associated with an improved outcome; (iii) there is very weak evidence to suggest that increasing pergolide dose in autumn months may be beneficial; (iv) there is little advantage in waiting for more than a month to perform follow-up endocrine testing following initiation of pergolide therapy; there may be merit in performing repeat tests sooner; (v) timing of sampling in relation to pergolide dosing does not confound measurement of ACTH concentration; (vi) there is no evidence that making changes after interpretation of ACTH concentrations measured at certain times of the year is associated with improved outcomes; (vii) evidence is very limited, however, compliance with PPID treatment appears to be poor and it is unclear whether this influences clinical outcome; (viii) evidence is very limited, but horses with clinical signs of PPID are likely to shed more nematode eggs than horses without clinical signs of PPID; it is unclear whether this results in an increased risk of parasitic disease or whether there is a need for more frequent assessment of faecal worm egg counts. MAIN LIMITATIONS: Limited relevant publications in the veterinary scientific literature. CONCLUSIONS: These findings should be used to inform decision-making in equine primary care practice.
Assuntos
Doenças dos Cavalos , Doenças da Hipófise , Adeno-Hipófise Parte Intermédia , Cavalos , Animais , Pergolida/uso terapêutico , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/terapia , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/terapia , Doenças da Hipófise/veterinária , Hormônio Adrenocorticotrópico , Insulina , Dor/tratamento farmacológico , Dor/veterinária , Atenção Primária à SaúdeRESUMO
Background: Hyperinsulinemia associated with pituitary pars intermedia dysfunction (PPID) and/or equine metabolic syndrome is well documented to put horses at high risk of laminitis. While dietary control of simple sugars and starch is the most effective therapy to control hyperinsulinemia, some horses fail to respond. Case Descriptions: Ten horses with hyperinsulinemia refractory to diet control, metformin, levothyroxine, and pergolide (if diagnosed with PPID) were treated with sodium-glucose cotransporter-2 inhibitor canagliflozin (Invokana®). Nine horses were hyperglycemic (>5.5 mmol/l) or had a history of hyperglycemia. Before instituting therapy, renal function was assessed by determining serum creatinine and blood urea nitrogen concentrations. Canagliflozin was administered orally once a day, with food. Dipstick urinalysis was performed every 2 weeks to confirm glucosuria and screen for proteinuria. Owners were also instructed regarding clinical signs consistent with urinary tract infection. All horses responded with a substantial decrease in serum insulin concentrations to normal or near normal values. Laminitis pain resolved in all cases, with regression of fat deposits. Owner satisfaction with outcomes was 100%. Conclusion: Once daily administration of the SGLT2 inhibitor canagliflozin corrected hyperglycemia, reduced insulin to normal or near normal levels, and was 100% effective in reversing or reducing abnormal fat pads and eliminating laminitis pain in horses with refractory hyperinsulinemia and laminitis. The core aspects of therapy-diet control, exercise when possible, and adequate treatment of PPID-must also be maintained if using canagliflozin. Canagliflozin should be reserved for refractory cases. Further controlled trials to investigate canagliflozin pharmacokinetics, pharmacodynamics, efficacy, and safety are needed.
Assuntos
Diabetes Mellitus Tipo 2 , Doenças dos Cavalos , Hiperglicemia , Hiperinsulinismo , Metformina , Doenças da Hipófise , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Canagliflozina/uso terapêutico , Creatinina/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/veterinária , Glucose/metabolismo , Glucose/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Cavalos , Hiperglicemia/complicações , Hiperglicemia/veterinária , Hiperinsulinismo/complicações , Hiperinsulinismo/tratamento farmacológico , Hiperinsulinismo/veterinária , Insulina , Metformina/uso terapêutico , Monossacarídeos/uso terapêutico , Dor/complicações , Dor/veterinária , Pergolida/uso terapêutico , Doenças da Hipófise/complicações , Doenças da Hipófise/veterinária , Sódio/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Amido/uso terapêutico , TiroxinaRESUMO
Thyrotropin releasing hormone (TRH) stimulation testing is often used to support a diagnosis of pituitary pars intermedia dysfunction (PPID) in horses although it is unclear whether or not repeat TRH stimulation testing post-treatment is a valid means of assessing response to medical therapy. Laboratory submissions from 64 suspected equine PPID cases were examined including the initial pre-treatment TRH stimulation test and a follow up test within 100 days of starting medical therapy with pergolide. In a subset of cases, further follow-up tests were examined beyond 100 days of starting treatment. Results from tests conducted between 1 July and 30 November were excluded. Significant improvements were seen in both the baseline and TRH-stimulated adrenocorticotrophic hormone (ACTH) concentrations within 100 days with no further improvements seen in the subset of cases examined thereafter. Although 88% (n = 56/64) of all cases showed a decreased response to TRH post-treatment, only 24% (n = 9/38) of horses with positive pre-treatment TRH stimulation tests normalised following treatment, with a further 34% (n = 13/38) improving into an equivocal test outcome category. Most commonly (42%; n = 16/38), horses with positive pre-treatment TRH stimulation tests remained positive following treatment, although 75% (n = 12/16) of these showed a numerically lower post-treatment response to TRH. These results will help inform practitioners of expected changes in TRH stimulation test results when assessing response of horses with PPID to medical therapy with pergolide.
Assuntos
Doenças dos Cavalos , Doenças da Hipófise , Hormônio Adrenocorticotrópico/farmacologia , Animais , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/tratamento farmacológico , Cavalos , Pergolida/farmacologia , Pergolida/uso terapêutico , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/tratamento farmacológico , Doenças da Hipófise/veterinária , Hormônio Liberador de Tireotropina/farmacologia , Hormônio Liberador de Tireotropina/uso terapêuticoRESUMO
Pituitary pars intermedia dysfunction (PPID) is a common endocrine disorder of aged horses, with muscle atrophy as one of the clinical signs. We sought to compare muscle mass and regulation of skeletal muscle proteolysis between horses with PPID and muscle atrophy to older horses without PPID, and to assess the impact of treatment with pergolide (dopaminergic agonist) on PPID horses. We hypothesized that PPID-associated muscle atrophy is a result of increased proteolysis, and that markers of muscle atrophy and proteolysis would improve over time with pergolide treatment. Markers of muscle atrophy, adiposity, insulin regulation, skeletal muscle composition, and proteolysis (muscle atrophy F- box/atrogin 1 [MAFbx1], muscle RING finger 1 [MuRF1], Bcl2/adenovirus EIV 19kD interacting protein 3 [Bnip3], and microtubule-associated light chain 3 [LC3]) were compared between PPID and control horses. PPID horses were treated for 12 weeks with either pergolide or placebo. Dose of pergolide was adjusted based upon monthly measurement of adrenocorticotropin, and markers of muscle atrophy, adiposity, insulin regulation, skeletal muscle composition, and proteolysis were compared after 12 weeks of treatment. Horses with PPID exhibited increased transcript abundance of MuRF1 (P= 0.04) compared to control. However, no difference was observed in transcript abundance of markers of proteolysis with treatment (P ≥ 0.25). Pergolide treated horses lost weight (P = 0.02) and improved fasting insulin (P = 0.02), while placebo treated horses gained weight and rump fat thickness (P = 0.02). Findings from this study suggest that treatment with pergolide may promote weight loss and improve insulin regulation in horses with PPID, but does not impact muscle mass or markers of muscle proteolysis.
Assuntos
Doenças dos Cavalos , Doenças da Hipófise , Adeno-Hipófise Parte Intermédia , Animais , Doenças dos Cavalos/metabolismo , Cavalos , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/patologia , Atrofia Muscular/veterinária , Pergolida/uso terapêutico , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia/metabolismoRESUMO
Pituitary neuroendocrine tumors (PitNET) are commonly benign tumors accounting for 10-25% of intracranial tumors. Prolactin-secreting adenomas represent the most predominant type of all PitNET and for this subtype of tumors, the medical therapy relies on the use of dopamine agonists (DAs). DAs yield an excellent therapeutic response in reducing tumor size and hormonal secretion targeting the dopamine receptor type 2 (D2DR) whose higher expression in prolactin-secreting adenomas compared to other PitNET is now well established. Moreover, although DAs therapy does not represent the first-line therapy for other PitNET, off-label use of DAs is considered in PitNET expressing D2DR. Nevertheless, DAs primary or secondary resistance, occurring in a subset of patients, may involve several molecular mechanisms, presently not fully elucidated. Dopamine receptors (DRs) expression is a prerequisite for a proper DA function in PitNET and several molecular events may negatively modify DR membrane expression, through the DRs down-regulation and intracellular trafficking, and DR signal transduction pathway. The current mini-review will summarise the presently known molecular events that underpin the unsuccessful therapy with DAs.
Assuntos
Adenoma/tratamento farmacológico , Agonistas de Dopamina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hipofisárias/tratamento farmacológico , Receptores de Dopamina D2/metabolismo , Adenoma Hipofisário Secretor de ACT/tratamento farmacológico , Adenoma Hipofisário Secretor de ACT/metabolismo , Adenoma/metabolismo , Aminoquinolinas/uso terapêutico , Bromocriptina/uso terapêutico , Cabergolina/uso terapêutico , Filaminas/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Humanos , Lisurida/uso terapêutico , MicroRNAs/metabolismo , Pergolida/uso terapêutico , Neoplasias Hipofisárias/metabolismo , Prolactinoma/tratamento farmacológico , Prolactinoma/metabolismo , Receptores de Dopamina D2/agonistas , beta-Arrestinas/metabolismoRESUMO
It remains unclear how pituitary pars intermedia dysfunction (PPID) and pergolide treatment (Prascend [pergolide tablets]) affect endocrine and immune function in horses. To evaluate these effects, blood was collected regularly from 28 university-owned horses (10 Non-PPID, 9 PPID control [PC], and 9 PPID treatment [PT]) over approximately 15 mo. Pergolide treatment was initiated after Day 0 collections. Analyses included ACTH, insulin, total cortisol, free cortisol, complete blood counts, plasma myeloperoxidase, and cytokine/receptor gene expression in basal whole blood and in vitro stimulations (PMA/ionomycin, heat-inactivated Rhodococcus equi, and heat-inactivated Escherichia coli) of whole blood and peripheral blood mononuclear cells (PBMCs). The results were analyzed using a linear mixed model (SAS 9.4) with significance set at P < 0.05. Significant group (P = 0.0014) and group-by-time (P = 0.0004) effects were observed in resting ACTH such that PT horses differed from Non-PPID horses only at Day 0. PT horses had significantly lower changes in ACTH responses to thyrotropin-releasing hormone stimulation tests than PC horses at non-fall time points only, mid-late February 2018 (P = 0.016) and early April 2018 (P = 0.0172). When PT and PC horses did not differ, they were combined before comparison to Non-PPID horses. No significant group or group-by-time effects were seen in resting insulin, total cortisol, or free cortisol; however, significant time effects were observed in these measures. PPID horses had lower absolute lymphocyte (P = 0.028) and red blood cell (P = 0.0203) counts than Non-PPID horses. In unstimulated whole blood, PPID horses had increased IL-8 expression compared with Non-PPID horses (P = 0.0102). In addition, PPID horses had decreased interferon γ production from PBMCs after stimulation with R. equi (P = 0.0063) and E. coli (P = 0.0057) and showed increased transforming growth factor ß expression after E. coli stimulation (P = 0.0399). The main limitations of this study were a limited sample size and an inability to truly randomize the PPID horses into treatment groups. Resting ACTH is likely the best choice for determining successful responses to pergolide. Neither PPID nor pergolide appears to influence insulin, total cortisol, and free cortisol. As measured, systemic immune function was altered in PPID horses, and it is likely that these horses are indeed at increased risk of opportunistic infection. Despite reducing ACTH, pergolide treatment did not appear to influence immune function.
Assuntos
Doenças dos Cavalos/tratamento farmacológico , Pergolida/uso terapêutico , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia/metabolismo , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/metabolismo , Animais , Relação Dose-Resposta a Droga , Feminino , Doenças dos Cavalos/sangue , Cavalos , Hipertricose/tratamento farmacológico , Hipertricose/etiologia , Hipertricose/veterinária , Masculino , Pergolida/administração & dosagem , Doenças da Hipófise/complicações , Doenças da Hipófise/tratamento farmacológicoRESUMO
Pergolide, a dopamine agonist, is commonly administered to manage pituitary pars intermedia dysfunction (PPID), a progressive neurodegenerative disease prevalent in aged horses. However, available evidence regarding pergolide's efficacy in improving clinical and endocrine parameters is limited. The aim of this systematic review was to assess published literature and evaluate evidence regarding whether pergolide treatment results in improvement of clinical signs and/or adrenocorticotrophic hormone (ACTH) concentration compared to no treatment or other unlicensed treatments. Systematic searches of electronic databases were undertaken in April 2019, repeated in August and October 2019, and updated in July 2020. English language publications published prior to these dates were included. Screening, data extraction and quality assessment of publications was undertaken individually by the authors using predefined criteria and subsequently cross-checked. Modified critically appraised topic data collection forms were used to extract data. Due to marked between-study variations, meta-analysis was not undertaken. After removal of duplicate records; 612 publications were identified, of which 129 abstracts were screened for eligibility and 28 publications met criteria for inclusion in the review. Most studies were descriptive case series, cohort studies or non-randomised, uncontrolled field trials. Despite marked variation in study populations, case selection, diagnostic protocols, pergolide dose, follow-up period and outcome measures, in the vast majority of the included studies, pergolide was reported to provide overall clinical improvement in >75% of cases. However, reported improvements in individual clinical signs varied widely. A reduction in plasma ACTH concentrations was reported in 44-74% of cases, while normalisation to within reported reference intervals occurred in 28-74% of cases.
Assuntos
Doenças dos Cavalos/tratamento farmacológico , Pergolida/uso terapêutico , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia/efeitos dos fármacos , Hormônio Adrenocorticotrópico/sangue , Animais , Cavalos , Pergolida/administração & dosagem , Doenças da Hipófise/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Pituitary pars intermedia dysfunction (PPID) develops slowly in aged horses as degeneration of hypothalamic dopaminergic neurons leads to proliferation of pars intermedia (PI) melanotropes through hyperplasia and adenoma formation. Dopamine (DA) concentrations and tyrosine hydroxylase (TH) immunoreactivity are markedly reduced in PI tissue of PPID-affected equids and treatment with the DA receptor agonist pergolide results in notable clinical improvement. Thus, we hypothesized that pergolide treatment of PPID-affected horses would result in greater DA and TH levels in PI tissue collected from PPID-affected horses versus untreated PPID-affected horses. To test this hypothesis, pituitary glands were removed from 18 horses: four untreated PPID-affected horses, four aged and four young horses without signs of PPID, and six PPID-affected horses that had been treated with pergolide at 2 µg/kg orally once daily for 6 months. DA concentrations and TH expression levels in PI tissues were determined by high performance liquid chromatography with electrochemical detection and Western blot analyses, respectively. RESULTS: DA and TH levels were lowest in PI collected from untreated PPID-affected horses while levels in the pergolide treated horses were similar to those of aged horses without signs of PPID. CONCLUSIONS: These findings provide evidence of restoration of DA and TH levels following treatment with pergolide. Equine PPID is a potential animal model of dopaminergic neurodegeneration, which could provide insight into human neurodegenerative diseases.
Assuntos
Agonistas de Dopamina/uso terapêutico , Dopamina/metabolismo , Doenças dos Cavalos/tratamento farmacológico , Pergolida/uso terapêutico , Doenças da Hipófise/veterinária , Tirosina 3-Mono-Oxigenase/metabolismo , Envelhecimento , Animais , Cavalos , Doenças da Hipófise/tratamento farmacológico , Adeno-Hipófise Parte Intermédia/efeitos dos fármacos , Adeno-Hipófise Parte Intermédia/patologiaRESUMO
Purpose: Neurotrophic keratopathy is a degenerative disease that may be improved by nerve growth factor (NGF). Our aim was to investigate the use of pergolide, a dopamine (D1 and D2) receptor agonist known to increase the synthesis and release of NGF for regeneration of damaged corneal nerve fibers. Methods: Pergolide function was evaluated by measuring axon length and NGF levels by enzyme-linked immunosorbent assay in cultured chicken dorsal root ganglion (DRG) cells with serial doses of pergolide (10, 25, 50, 150, and 300 µg/ml) and with different concentrations of a D1 antagonist. Pergolide function was further evaluated by cornea nerve fiber density and wound healing in a cornea scratch mouse model. Results: Pergolide increased DRG axon length significantly at a dose between 50 and 300 µg/ml. Different concentrations of D1 antagonist (12, 24, 48, and 96 µg/ml) inhibited DRG axon length growth with pergolide (300 µg/ml). Pergolide (50 µg/ml) upregulated NGF expression in DRG cells at both 24 hours and 48 hours. Pergolide improved cornea nerve fiber density at both 1 week and 2 weeks. Pergolide also improved cornea wound healing. Conclusions: We demonstrated that pergolide can act to promote an increase in NGF which promotes corneal nerve regeneration and would therefore improve corneal sensation and visual acuity in eyes with peripheral neurotrophic keratopathy.
Assuntos
Lesões da Córnea/tratamento farmacológico , Agonistas de Dopamina/uso terapêutico , Fibras Nervosas/efeitos dos fármacos , Pergolida/uso terapêutico , Animais , Axônios/efeitos dos fármacos , Galinhas , Agonistas de Dopamina/farmacologia , Gânglios Espinais/efeitos dos fármacos , Camundongos , Regeneração Nervosa , Pergolida/farmacologia , Cicatrização/fisiologiaRESUMO
Published information on the pharmacokinetic and pharmacodynamic properties of pergolide is limited. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of oral pergolide in horses with pituitary pars intermedia dysfunction (PPID). The study design was a nonrandomized clinical trial. Six horses with PPID diagnosed by thyrotropin-releasing hormone (TRH) stimulation tests received pergolide at 4 µg/kg for 18 d. Plasma samples for determination of pergolide and ACTH concentration were collected 0.5 h before and 2 and 12 h after each administration of pergolide. Maximum plasma concentrations after the first oral dose of pergolide (0.104-0.684 ng/mL; median 0.261 ng/mL; interquartile range [IQR] 0.184-0.416 ng/mL) were not significantly different to the maximum steady-state concentration at day 18 (0.197-0.628 ng/mL; median 0.274; IQR 0.232-0.458 ng/mL). Chronic administration was not associated with drug accumulation (R = 1.09) and pergolide concentration reached steady state within 3 d. Throughout, concentrations of pergolide fluctuated considerably, with median plasma peak concentrations more than four times higher than median trough concentrations. Plasma ACTH concentration reduced significantly within 12 h of administration with further reductions occurring up to 10 d after the initiation of treatment. Although there were parallel fluctuations in the concentrations of pergolide and ACTH, timing of ACTH measurement in relation to the administration of pergolide did not have a significant effect. Alterations in the response to TRH were identified at 8 d with no further change being identified at 18 d. A small number of horses were studied. Oral pergolide results in significant suppression of pars intermedia activity within hours. Pergolide and ACTH concentrations fluctuated in tandem although correlation was poor. Fluctuations in pergolide concentration were consistent with a terminal elimination half-life of less than 12 h. To reduce the level of fluctuation of ACTH, twice-daily dosing of pergolide may be more appropriate.
Assuntos
Doenças dos Cavalos/tratamento farmacológico , Pergolida/farmacocinética , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia/efeitos dos fármacos , Administração Oral , Hormônio Adrenocorticotrópico/sangue , Animais , Área Sob a Curva , Cavalos , Pergolida/administração & dosagem , Pergolida/sangue , Pergolida/uso terapêutico , Doenças da Hipófise/tratamento farmacológico , Hormônio Liberador de Tireotropina/administração & dosagem , Hormônio Liberador de Tireotropina/farmacologiaRESUMO
OBJECTIVE AND AIM: The nutritional status of 36 patients with equine pituitary pars intermedia dysfunction (PPID) under pergolide treatment was investigated. ANIMALS, MATERIALS AND METHODS: The body condi tion score (BCS) and feeding were determined at the beginning of the study and after 60 and 120 days. Sampled blood for control of pergolid therapy were used for insulin and glucose measurement. A standardized questionnaire regarding the symptoms of the disease, including hypertrichosis and weight change, was completed by the owners. RESULTS: The mean BCS (scale of 1 = cachexia to 9 = grossly obese) was 3.1 ± 0.8 (large horses 2.7 ± 0.8, ponies 3.5 ± 0.8). The mean energy requirement of the large horses was estimated to be 74 ± 10 MJ of metabolizable energy, but the intake amounted only to 65 ± 15 MJ. There was a significant correlation between the BCS and the estimated energy intake in percent of requirements in the large horses. The energy requirements of the ponies were generally met. The patients were fed a mean of 2.0 ± 0.7 meals of roughage per day (total roughage intake per day 0.2-2.1 kg/100 kg body weight) and a maximum of one meal of concentrates. Sixteen ponies and one large horse did not receive any concentrates, whereas five ponies and 14 horses were fed concentrates (mean amount for ponies 0.15 kg and for large horses 0.8 kg). The requirements for zinc, copper, selenium and vitamins A and E were not met in the majority of patients. Blood glucose levels were within the reference range in all samples, but insulin levels were elevated in seven animals at least at one sampling point. The serious underweight of some of the patients was not recognized as a problem by some of the owners. CONCLUSION AND PRACTICAL RELEVANCE: Owners of PPID patients need more guidance on body condition scoring, amount of feed, number of meals, and logistics of feeding to avoid malnutrition of their animals.
Assuntos
Síndrome de Cushing/veterinária , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/fisiopatologia , Pergolida/uso terapêutico , Animais , Peso Corporal , Síndrome de Cushing/tratamento farmacológico , Síndrome de Cushing/fisiopatologia , Ingestão de Energia , Cavalos , Avaliação NutricionalRESUMO
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.
Assuntos
Doenças dos Cavalos , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia , Hormônio Adrenocorticotrópico/sangue , Animais , Austrália/epidemiologia , Agonistas de Dopamina/uso terapêutico , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/epidemiologia , Doenças dos Cavalos/fisiopatologia , Cavalos , Nova Zelândia/epidemiologia , Pergolida/uso terapêutico , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/tratamento farmacológico , Doenças da Hipófise/epidemiologia , Adeno-Hipófise Parte Intermédia/fisiopatologia , Guias de Prática Clínica como Assunto , Fatores de Risco , Sociedades CientíficasRESUMO
INTRODUCTION: Impulse control behaviors (ICBs) are impulsive-compulsive behaviors often associated with dopamine replacement therapy in Parkinson's disease (PD). Although remission can occur in ICB, only four reports on the ratio of remission and the persistence of ICB have been published, and the associated factors with ICB remission or persistence have been little known. Therefore, we conducted a longitudinal assessment of the remission, persistence, and development of ICB and those associated factors in patients with PD. METHODS: We retrospectively investigated a PD database at Aomori Prefectural Central Hospital, Japan. One hundred and forty-eight patients with PD who could be followed up for 2 years were enrolled. ICB was assessed using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease. Motor severity (Hoehn and Yahr scale and United Parkinson's Disease Rating Scale), cognitive function (Mini-Mental State Examination), and other clinical variables (sex, age, onset age, disease duration, olfactory dysfunction, and dyskinesia) and medications used to treat PD were assessed. Univariate analyses were performed. RESULTS: Seven patients were excluded because of the exclusion criteria, and 141 patients were analyzed. Thirty patients (21.3%) had ICB at baseline, and these patients also had significantly higher use of pergolide. The ICB remission rate was 60%, the ICB persistence ratio was 40%, and the ICB development ratio was 12.6% over 2 years. Statistically, younger age and pergolide use were associated with ICB persistence. Being male, having dyskinesia, and rotigotine, entacapone, zonisamide, and istradefylline use were associated with ICB development. CONCLUSION: This study suggests that younger age and pergolide use may be the new associated factors with ICB persistence and that entacapone, zonisamide, and istradefylline use may be associated with the development of ICB. Drug profiles and medication practices in Japan may explain the association of these factors with ICB.
Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta/complicações , Comportamento Impulsivo/efeitos dos fármacos , Doença de Parkinson/complicações , Antagonistas do Receptor A2 de Adenosina/farmacologia , Antagonistas do Receptor A2 de Adenosina/uso terapêutico , Fatores Etários , Idoso , Antiparkinsonianos/farmacologia , Antiparkinsonianos/uso terapêutico , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Estudos de Casos e Controles , Catecóis/farmacologia , Catecóis/uso terapêutico , Estudos de Coortes , Transtornos Disruptivos, de Controle do Impulso e da Conduta/fisiopatologia , Agonistas de Dopamina/farmacologia , Agonistas de Dopamina/uso terapêutico , Feminino , Humanos , Japão , Estudos Longitudinais , Masculino , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Pergolida/farmacologia , Pergolida/uso terapêutico , Purinas/farmacologia , Purinas/uso terapêutico , Estudos Retrospectivos , Inquéritos e Questionários , Zonisamida/farmacologia , Zonisamida/uso terapêuticoRESUMO
Pituitary pars intermedia dysfunction (PPID) has been associated with diminished immune response in aged horses. This prospective study hypothesised that this may result in increased strongyle egg shedding in affected animals and that horses treated with pergolide would have reduced fecal egg counts (eggs per gram, EPG) compared to placebo-treated animals. Adrenocorticotropic hormone (ACTH) concentrations and EPG were tested in 48 horses. There were no significant differences in baseline EPG between horses with pre-clinical PPID and healthy controls. There was no significant difference in EPG between horses with PPID after treatment with pergolide and placebo-treated animals. Using EPG as a marker of immune function, these results did not support a proposed decrease in immune function in horses with pre-clinical PPID.
Assuntos
Doenças dos Cavalos/imunologia , Contagem de Ovos de Parasitas , Pergolida/uso terapêutico , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia , Strongyloidea , Hormônio Adrenocorticotrópico/sangue , Animais , Fezes/parasitologia , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/parasitologia , Cavalos , Pergolida/efeitos adversos , Doenças da Hipófise/tratamento farmacológico , Doenças da Hipófise/imunologia , Estudos Prospectivos , Infecções Equinas por Strongyloidea/complicaçõesRESUMO
BACKGROUND: Mycetoma is a chronic, proliferative lesion of cutaneous/subcutaneous tissue characterized by draining tracts and granules in the discharge caused by actinomycetes (actinomycetoma) or filamentous fungi (eumycotic mycetoma). OBJECTIVES: This case report describes the unusual finding of a cutaneous mycetoma of the lateral wing of the right nostril in a gelding. ANIMAL: A 16-year-old Fjord gelding with suspected pituitary pars intermedia dysfunction (PPID) was presented for evaluation of a nonpainful, firm and raised mass involving the lateral wing of the right nostril and the lip. METHODS AND RESULTS: Cytological examination of the mass showed marked pyogranulomatous inflammation and histopathological examination revealed a fungal mycetoma. Fungal culture identified the causative organism as Aspergillus terreus, which is not known for its propensity to cause either dermal granulomas or mycetoma in domestic animals. Further investigation, including a TRH stimulation test, led to a diagnosis of PPID (Cushing's disease), which may have led to immunosuppression of the animal and increased susceptibility to infection. CONCLUSIONS AND CLINICAL IMPORTANCE: The horse was treated medically with pergolide for the PPID and oral potassium iodide for the fungal infection, with good therapeutic response and no relapse after five months. Surgical debridement or excision was not performed. To the best of the authors' knowledge, this is the first case report of a cutaneous mycetoma caused by A. terreus in a horse.
Assuntos
Aspergilose/veterinária , Aspergillus , Doenças dos Cavalos/microbiologia , Doenças Labiais/veterinária , Micetoma/veterinária , Doenças Nasais/veterinária , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia , Animais , Antifúngicos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Cavalos , Doenças Labiais/microbiologia , Masculino , Micetoma/microbiologia , Doenças Nasais/microbiologia , Pergolida/uso terapêutico , Iodeto de Potássio/uso terapêuticoRESUMO
Equine endocrine disease is commonly encountered by equine practitioners. Pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS) predominate. The most logical therapeutic approach in PPID uses dopamine agonists; pergolide mesylate is the most common. Bromocryptine and cabergoline are alternative drugs with similar actions. Drugs from other classes have a poor evidence basis, although cyproheptadine and trilostane might be considered. EMS requires management changes as the primary approach; reasonable justification for use of drugs such as levothyroxine and metformin may apply. Therapeutic options exist in rare cases of diabetes mellitus, diabetes insipidus, hyperthyroidism, and critical illness-related corticosteroid insufficiency.
Assuntos
Doenças do Sistema Endócrino/veterinária , Doenças dos Cavalos/tratamento farmacológico , Animais , Agonistas de Dopamina/uso terapêutico , Doenças do Sistema Endócrino/tratamento farmacológico , Cavalos , Pergolida/uso terapêuticoRESUMO
The objective of this study was to gain an understanding of the pharmacokinetic and pharmacodynamic properties of pergolide in horses with PPID after of long-term oral administration. Six horses with confirmed PPID were treated with pergolide (Prascend® ) at 1 mg/horse po q24 h for 2 months, followed by 2 mg/horse po q24 h for 4 months. Following the last dose, plasma samples were collected for measurement of pergolide using an LC/MS/MS method and ACTH measurement using a chemiluminescent immunoassay. Noncompartmental and compartmental pharmacokinetic analyses were performed, as well as pharmacodynamic assessment of the effect of plasma pergolide concentrations on plasma ACTH concentrations. Pergolide effectively decreased plasma ACTH concentration in aged horses with PPID, with similar pharmacokinetic properties as reported in young horses, including an approximate terminal half-life of 24 h. Plasma ACTH concentration increased by 50% in 3/6 horses at 2 days and 6/6 horses 10 days after discontinuing drug administration. Pergolide was quantified in all horses at 2 days and in none at 10 days after last dose. In summary, after discontinuing pergolide treatment, plasma ACTH concentration increased while pergolide was still quantifiable in some horses. Once-daily dosing of pergolide is likely appropriate in most horses with PPID for regulating the plasma ACTH concentration.
Assuntos
Doenças dos Cavalos/tratamento farmacológico , Pergolida/farmacocinética , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia/patologia , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/metabolismo , Animais , Área Sob a Curva , Meia-Vida , Cavalos , Pergolida/administração & dosagem , Pergolida/uso terapêutico , Doenças da Hipófise/tratamento farmacológicoRESUMO
The adenosine A2A receptor antagonist, istradefylline improves motor function in patients with advanced Parkinson's disease (PD) optimally treated with a combination of L-DOPA and a dopamine agonist without increasing the risk of troublesome dyskinesia. However, the effects of istradefylline on motor function when administered in combination with low dose of L-DOPA and dopamine agonists as occurs in early PD are unknown. We investigated whether istradefylline enhances the combined anti-parkinsonian effects of a suboptimal dose of L-DOPA and a threshold dose of either the non-ergot dopamine agonist, ropinirole or the ergot dopamine agonist, pergolide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmoset. Threshold doses of ropinirole (0.025-0.075 mg/kg p.o.) and pergolide (0.01 mg/kg p.o.) produced a weak anti-parkinsonian effect. Co-administration of a suboptimal dose of L-DOPA (2.5mg/kg p.o.) with threshold doses of the dopamine agonists enhanced their anti-parkinsonian effect that led to increased 'ON' time without dyskinesia appearing. Administering istradefylline (10mg/kg p.o.) with the threshold doses of dopamine agonists and the suboptimal dose of L-DOPA in a triple combination caused a further enhancement of the anti-parkinsonian response but dyskinesia was still absent. In early PD, dopamine agonists are often used as first-line monotherapy, but efficacy is usually lost within a few years, at which time L-DOPA is added but with the risk of dyskinesia appearance. These results show that istradefylline is effective in improving motor function in combination with low dose dopaminergic drug treatment without provoking dyskinesia.
Assuntos
Antagonistas do Receptor A2 de Adenosina/uso terapêutico , Antiparkinsonianos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Levodopa/uso terapêutico , Intoxicação por MPTP/tratamento farmacológico , Purinas/uso terapêutico , Animais , Comportamento Animal/efeitos dos fármacos , Callithrix , Quimioterapia Combinada , Feminino , Indóis/uso terapêutico , Intoxicação por MPTP/induzido quimicamente , Masculino , Atividade Motora/efeitos dos fármacos , Pergolida/uso terapêuticoRESUMO
BACKGROUND: Paired measurement of ACTH concentration may be more reliable than a single measurement. HYPOTHESIS/OBJECTIVES: To determine whether the mean of 2 measurements of ACTH concentration is more reliable in assessing pituitary pars intermedia dysfunction (PPID) than a single measurement. ANIMALS: Paired ACTH measurements were performed on (1) 148 occasions from 124 horses being investigated for PPID, (2) 90 occasions from 76 horses with PPID that were receiving treatment with pergolide, and (3) 63 occasions from 50 horses in which there was no clinical suspicion of PPID. Histologic examination of the pars intermedia was performed in 67 of the untreated horses. METHODS: Outcome of testing using single and the mean of paired samples was compared directly and both methods were compared against histology, which was considered the gold standard. RESULTS: Paired ACTH measurement altered binary classification as healthy or diseased in 6 of 211 cases, all off which had equivocal initial ACTH concentrations between 20 and 39 pg/mL. Using histology as the gold standard, optimal sensitivity and specificity for diagnosing PPID were 69.4 and 80.9%, respectively, for a single measurement and 72.2 and 76.2%, respectively, for paired measurements. The area under the receiver operating characteristic curve was 0.72 and 0.73 for single and paired measurements compared with histopathologic diagnosis, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Paired measurement of ACTH concentration offers no advantage over a single measurement.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Doenças dos Cavalos/diagnóstico , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia/patologia , Animais , Agonistas de Dopamina/uso terapêutico , Feminino , Doenças dos Cavalos/sangue , Doenças dos Cavalos/tratamento farmacológico , Cavalos , Masculino , Pergolida/uso terapêutico , Doenças da Hipófise/sangue , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/tratamento farmacológicoRESUMO
BACKGROUND: Punding is a stereotypical behavior characterized by an intense fascination with repetitive handling and examining of mechanical devices or arranging common objects. This condition, which is different from both obsessive-compulsive disorder and mania, is still underestimated in patients with Parkinson's disease and may have deleterious social consequences on patients and their families. CASE REPORT: We report the case of severe punding in a 23-year-old parkinsonian woman, who presented, a few days following a rise in the dose of pergolide up to 2,5 mg/(d), frequent and daily unusual repetitive behavior, characterized by ceaseless sewing, disassembly and reassembly of phones, and coloring of drawings. These behaviors were associated with a common peak of dose dyskinesia and were responsible for a considerable reduction in duration of sleep with negative impact on the quality of life of her parents. These symptoms significantly improved immediately after switching pergolide to an equivalent dose of ropinirole (12 mg/(d). DISCUSSION: Punding has only recently come to the attention of physicians through the first report in a parkinsonian patient, triggered by dopaminergic replacement therapy. The phenomenon was thought to be related to excessive dopaminergic stimulation of the limbic and associative pathways. The current mainstay of treatment is the reduction in the dose of dopaminergic medication or changing the presumed responsible drug, often a dopaminergic agonist. In this article, the authors review the epidemiology, pathophysiology and management of this curious phenomenon.