Abstract：
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.
OBJECTIVE: To develop evidence-based primary care guidelines for the diagnosis and treatment of equine PPID based on the available literature.
METHODS: 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.
CONCLUSIONS: 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.
CONCLUSIONS: Limited relevant publications in the veterinary scientific literature.
CONCLUSIONS: These findings should be used to inform decision-making in equine primary care practice.
OBJECTIVE: To develop evidence-based primary care guidelines for the diagnosis and treatment of equine PPID based on the available literature.
METHODS: 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.
CONCLUSIONS: 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.
CONCLUSIONS: Limited relevant publications in the veterinary scientific literature.
CONCLUSIONS: These findings should be used to inform decision-making in equine primary care practice.
摘要：
背景：垂体中间功能障碍（PPID）是一种普遍存在的，与年龄相关的慢性疾病。PPID的诊断可能具有挑战性，因为其广泛的临床表现和不同的公开诊断标准。并且可用的治疗选择有限。
目的：根据现有文献制定马PPID诊断和治疗的循证初级护理指南。
方法：使用建议分级的循证临床指南，评估,发展和评价（等级）框架。
方法：研究问题由兽医小组提出，并发展成PICO或另一种结构化格式。搜索了VetSRev和兽医证据以获取证据摘要，2022年7月使用关键字搜索对NCBIPubMed和CABDirect数据库进行了系统搜索，并于2023年1月进行了更新。使用等级框架对证据进行了评估。
结论：研究问题分为四个方面：（A）诊断测试的病例选择，预测试概率和诊断测试准确性，(B)测试结果的解释，(C)药物治疗和其他治疗/管理选择,以及(D)监测治疗的病例。使用GRADE标准鉴定和评估相关的兽医出版物。结果发展为建议：（A）诊断测试和诊断测试准确性的病例选择：（i）年龄≥15岁的动物中PPID的患病率在21％至27％之间；（ii）多毛症或延迟/不完全的毛发脱落提供了对PPID的临床怀疑的高指数；（iii）临床体征和年龄的组合在诊断测试之前告知临床怀疑的指数，在PPID的基础测试中使用前，PPID的可能性<基础ACTH浓度用于诊断PPID的总体诊断准确性在秋季为88％至92％，在非秋季为70％和86％。取决于预测试概率。基于一项研究，30分钟后对TRH的ACTH浓度对诊断PPID的总体诊断准确性在秋季为92％至98％，在非秋季为90％和94％。取决于预测试概率。因此，应该记住，在预测试概率低的情况下，假阳性结果的风险会增加，这可能意味着在没有检查更可能的替代诊断的情况下开始对PPID进行治疗。由于终身治疗的开始和/或未能识别和治疗可能危及生命的替代疾病，这可能会损害马的福利。（b）诊断测试的解释：（i）品种对血浆ACTH浓度有显着影响，特别是在秋季，一些但不是所有的“节俭”品种的ACTH浓度明显较高；（ii）基础和/或TRH后ACTH浓度也可能受到纬度/位置的影响，饮食/喂养，外套颜色,危重病和拖车运输；（iii）轻度疼痛不太可能对基础ACTH产生大的影响，但是对于更严重的疼痛可能需要谨慎；（iv）确定允许所有可能的促成因素的诊断阈值是不切实际的；因此，支持使用模棱两可的范围；（v）动态胰岛素测试和TRH刺激测试可以组合，但口服糖试验后不应立即进行TRH刺激试验；(vi)与PPID相当，高胰岛素血症似乎发生椎板炎的风险较高，但ACTH不是椎板炎风险的独立预测因子。（C）药物治疗和其他治疗/管理选择：（i）培高利特改善了大多数受影响动物中与PPID相关的大多数临床症状；（ii）培高利特治疗降低了基础ACTH浓度，并改善了许多动物对TRH的ACTH反应，但是在大多数情况下，胰岛素失调（ID）的测量值没有改变；（iii）chasteberry对ACTH浓度没有影响，并且将chasteberry添加到培高利特治疗中没有益处；（iv）赛庚啶与培高利特的组合并不优于单独的培高利特；（v）没有证据表明培高利特对马有不良的心脏作用；（vi）培高利特不影响（D）监测培高利特治疗的病例：（i）激素测定提供了响应培高利特治疗的垂体控制的粗略指示，然而，尚不清楚ACTH浓度的监测和培高利特剂量的滴定是否与内分泌或临床结果的改善有关；(ii)尚不清楚ACTH对TRH的反应或临床体征的监测是否与结果的改善有关；(iii)有非常微弱的证据表明，在秋季月份增加培高利特剂量可能是有益的；(iv)在等待超过一个月的时间后，在进行补充试验时，可能没有证据表明表明在然而,对PPID治疗的依从性似乎较差，尚不清楚这是否会影响临床结果；（viii）证据非常有限，但是有PPID临床症状的马可能比没有PPID临床症状的马脱落更多的线虫卵;目前尚不清楚这是否会增加寄生虫病的风险,或者是否需要更频繁地评估粪便虫卵数量.
结论：限制兽医科学文献中的相关出版物。
结论：这些发现应用于马初级保健实践的决策。
目的：根据现有文献制定马PPID诊断和治疗的循证初级护理指南。
方法：使用建议分级的循证临床指南，评估,发展和评价（等级）框架。
方法：研究问题由兽医小组提出，并发展成PICO或另一种结构化格式。搜索了VetSRev和兽医证据以获取证据摘要，2022年7月使用关键字搜索对NCBIPubMed和CABDirect数据库进行了系统搜索，并于2023年1月进行了更新。使用等级框架对证据进行了评估。
结论：研究问题分为四个方面：（A）诊断测试的病例选择，预测试概率和诊断测试准确性，(B)测试结果的解释，(C)药物治疗和其他治疗/管理选择,以及(D)监测治疗的病例。使用GRADE标准鉴定和评估相关的兽医出版物。结果发展为建议：（A）诊断测试和诊断测试准确性的病例选择：（i）年龄≥15岁的动物中PPID的患病率在21％至27％之间；（ii）多毛症或延迟/不完全的毛发脱落提供了对PPID的临床怀疑的高指数；（iii）临床体征和年龄的组合在诊断测试之前告知临床怀疑的指数，在PPID的基础测试中使用前，PPID的可能性<基础ACTH浓度用于诊断PPID的总体诊断准确性在秋季为88％至92％，在非秋季为70％和86％。取决于预测试概率。基于一项研究，30分钟后对TRH的ACTH浓度对诊断PPID的总体诊断准确性在秋季为92％至98％，在非秋季为90％和94％。取决于预测试概率。因此，应该记住，在预测试概率低的情况下，假阳性结果的风险会增加，这可能意味着在没有检查更可能的替代诊断的情况下开始对PPID进行治疗。由于终身治疗的开始和/或未能识别和治疗可能危及生命的替代疾病，这可能会损害马的福利。（b）诊断测试的解释：（i）品种对血浆ACTH浓度有显着影响，特别是在秋季，一些但不是所有的“节俭”品种的ACTH浓度明显较高；（ii）基础和/或TRH后ACTH浓度也可能受到纬度/位置的影响，饮食/喂养，外套颜色,危重病和拖车运输；（iii）轻度疼痛不太可能对基础ACTH产生大的影响，但是对于更严重的疼痛可能需要谨慎；（iv）确定允许所有可能的促成因素的诊断阈值是不切实际的；因此，支持使用模棱两可的范围；（v）动态胰岛素测试和TRH刺激测试可以组合，但口服糖试验后不应立即进行TRH刺激试验；(vi)与PPID相当，高胰岛素血症似乎发生椎板炎的风险较高，但ACTH不是椎板炎风险的独立预测因子。（C）药物治疗和其他治疗/管理选择：（i）培高利特改善了大多数受影响动物中与PPID相关的大多数临床症状；（ii）培高利特治疗降低了基础ACTH浓度，并改善了许多动物对TRH的ACTH反应，但是在大多数情况下，胰岛素失调（ID）的测量值没有改变；（iii）chasteberry对ACTH浓度没有影响，并且将chasteberry添加到培高利特治疗中没有益处；（iv）赛庚啶与培高利特的组合并不优于单独的培高利特；（v）没有证据表明培高利特对马有不良的心脏作用；（vi）培高利特不影响（D）监测培高利特治疗的病例：（i）激素测定提供了响应培高利特治疗的垂体控制的粗略指示，然而，尚不清楚ACTH浓度的监测和培高利特剂量的滴定是否与内分泌或临床结果的改善有关；(ii)尚不清楚ACTH对TRH的反应或临床体征的监测是否与结果的改善有关；(iii)有非常微弱的证据表明，在秋季月份增加培高利特剂量可能是有益的；(iv)在等待超过一个月的时间后，在进行补充试验时，可能没有证据表明表明在然而,对PPID治疗的依从性似乎较差，尚不清楚这是否会影响临床结果；（viii）证据非常有限，但是有PPID临床症状的马可能比没有PPID临床症状的马脱落更多的线虫卵;目前尚不清楚这是否会增加寄生虫病的风险,或者是否需要更频繁地评估粪便虫卵数量.
结论：限制兽医科学文献中的相关出版物。
结论：这些发现应用于马初级保健实践的决策。
