Some equine endocrine disorders
Neki endokrini poremećaji u konja

Han van der Kolk, DVM, PhD, dipl ECEIM
Aeres University of Applied Sciences, Dronten, the Netherlands [h.van.der.kolk@aeres.nl]

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Equine Cushing’s disease

Hyperadrenocorticism might originate from a pituitary pars intermedia adenoma, adrenocortical neoplasia or ectopic ACTH production. Equine Cushing’s disease by definition should originate from a pituitary adenoma. To date, hyperadrenocorticism in horses has not been documented in association with ectopic ACTH production, whereas pituitary-independent hyperadrenocorticism has been described only once in a 12-year-old warmblood gelding (van der Kolk et al. 2001). Of note, hyperadrenocorticism medicamentosus (iatrogenic Cushing’s disease) in the horse is apparently rare and has only been reported with the administration of triamcinolone (Cohen and Carter 1992). As a consequence, hyperadrenocorticism in horses is almost exclusively caused by a pars intermedia adenoma of the pituitary gland. Pituitary pars intermedia adenomas usually occur in aged horses, although the youngest reported was 7 years. In diseased horses, the average age is about 20 years with mares affected more frequently with Cushing’s disease. Initially, diseased animals usually show a remarkable clinical sign, namely hypertrichosis [an excessively long and curly coat due to excessive hair growth]. Exceptionally, a change in hair colour to light (golden) brown can be noticed (Figure 1).

Another remarkable clinical sign is the bulging of supraorbital fat seen in 20-60% of horses with Cushing’s disease. Major sequelae of an adenoma of the pars intermedia of the pituitary gland are secondary diabetes mellitus (and concurrent weight loss) and laminitis. It should be realised that horses with Cushing’s disease usually are not suffering from polyuria and polydipsia unless in association with secondary diabetes mellitus or diabetes insipidus. Other complications include hyperhidrosis [excessive sweating], infertility, galactorrhoea, delayed wound healing, bilateral blindness, depression, and seizures. Pregnant mares with Cushing’s disease and secondary diabetes mellitus might give birth to (underweight) foals with a very poor prognosis if the diabetes mellitus is not treated during pregnancy. The diagnosis is best confirmed using assessment of the basal plasma ACTH concentration or performing an overnight dexamethasone suppression test. Horses with hyperadrenocorticism have been shown to have resting hyperinsulinaemia and reduced tissue sensitivity to insulin (Beech and Garcia 1985). In addition, by using the euglycaemic hyperinsulinaemic clamp technique [*] it has been shown that horses with Cushing’s disease have a low basal rate of glucose metabolism associated with increased insulin resistance (Klinkhamer et al. 2011). With respect to treatment, preference should be given to dopamine agonists like pergolide or bromocriptine. It is important to realize that horses with Cushing’s disease only are not polyuric and polydipsic and might initially be more or less obese and as such might resemble horses with Equine Metabolic Syndrome.

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Equine Metabolic Syndrome

Horses affected with Equine Metabolic Syndrome are characteristically obese associated with a “cresty” neck and tail head (Body Condition Score 7-9) and are aged between 8-18 years. Other clinical signs include abnormal oestrous cycling or a “swollen sheath”. The syndrome in horses has neither gender nor breed predilections.
The major sequela of Equine Metabolic Syndrome is laminitis. Unfortunately, it is difficult to reduce weight in affected horses by dietary restriction (“easy keepers”).
Horses with Equine Metabolic Syndrome have resting hyperinsulinaemia similar to horses with Cushing’s disease. In contrast to horses with Cushing’s disease the result of the dexamethasone suppression test is normal in horses affected with Equine Metabolic Syndrome. Remarkably, the euglycaemic hyperinsulinaemic clamp technique as gold standard for the sensitivity of tissues to insulin has not been applied to horses affected with Equine Metabolic Syndrome yet. Most effective preventive and treatment strategies are those associated with both increased physical activity and dietary-induced weight reduction.

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Disproportionate congenital short stature (or dwarfism) in the Friesian horse breed

In the equine species, dwarfism is especially mentioned in Friesians identified as disproportionate congenital short stature with an autosomal recessive trait (Kroon and van der Plank 1931). The most salient feature of its phenotype is the physeal growth retardation in the limbs and ribs (Figure 2).

Affected animals have approximately 25% shorter fore- and hindlimbs and approximately 50% reduced bodyweight. In case of congenital dwarfism in the Friesian horse breed, a dysplastic metaphysis of the distal metacarpus and metatarsus is usually radiographically evident (Back et al. 2008), whereas no abnormalities were detected in the function of the hypothalamic-pituitary growth axis (de Graaf-Roelfsema et al. 2009). A B4GALT7 mutation identified affects the moieties of proteoglycans of the extracellular matrix (Leegwater et al 2016) associated with tendon laxity. Treatment of affected animals is supportive.

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Hypertrophic osteopathy (or Marie’s disease)

The disorder is characterised by the symmetrical proliferation of vascular connective tissue and subperiosteal bone, which occurs on the distal long bones. The term hypertrophic osteopathy is preferable to hypertrophic osteoarthropathy, because in the equine species there is no articular involvement. However, the swellings can be most prominent at joints with intracapsular involvement although the articular surface itself usually is not affected. Hypertrophic osteopathy generally is found in association with intrathoracic lesions and primary or metastatic pulmonary neoplasms, but has been seen with lesions in other locations. Affected horses range in age from one to 21 years (mean 7.4±4.7sd years) with a slight male (64%) predilection. The disorder is more common in larger horse breeds. The cause of hypertrophic osteopathy is still unknown. Proposed mechanisms include hypoxia, hormonal dysfunction, pulmonary vascular shunting, and neural mechanisms via afferent parasympathetic pathway. The diagnosis must be made on the basis of clinical signs and typical radiographic changes with the metacarpal and metatarsal bones most commonly affected. However, lesions are also recorded in the radius, carpal bones, proximal and middle phalanges, tibia and tarsal bones. The mandible, maxilla and nasal bones can also be affected (Figure 3).

Blood biochemistry might reveal increased activity of alkaline phosphatase. Treatment must be directed against elimination of the underlying cause if possible.

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Renal secondary hyperparathyroidism

It should be mentioned here that renal secondary hyperparathyroidism is not a disease entitity in the equine species since renal failure in horses usually is not characterised by hyperphosphataemia and concurrent hypocalcaemia.

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Cushingova bolest u konja

Hiperadrenokorticizam može potjecati od adenoma pars intermedia hipofize, adrenokortikalne neoplazije ili ektopične proizvodnje ACTH. Cushingova bolest konja po definiciji bi trebala potjecati od adenoma hipofize. Do danas, hiperadrenokorticizam u konja nije dokumentiran u vezi s ektopičnom proizvodnjom ACTH, dok je hiperadrenokorticizam neovisan o hipofizi opisan samo jednom u 12-godišnjeg toplokrvnog kastrata (van der Kolk i sur. 2001). Valja napomenuti da je hiperadrenocorticism medicamentosus (jatrogena Cushingova bolest) u konja očito rijedak i zabilježen je samo kod primjene triamcinolona (Cohen i Carter 1992). Kao posljedica toga, hiperadrenokorticizam u konja je gotovo isključivo uzrokovan pars intermedia adenomom hipofize. Adenomi pars intermedia hipofize obično se javljaju u starijih konja, iako je najmlađi prijavljeni imao 7 godina. Kod oboljelih konja prosječna dob je oko 20 godina, a kobile su češće oboljele od Cushingove bolesti. U početku, bolesne životinje obično pokazuju značajan klinički znak, naime hipertrihoza [pretjerano duga i kovrčava dlaka zbog pretjeranog rasta dlake]. Iznimno se može primijetiti promjena boje dlake u svijetlo (zlatno) smeđu (Slika 1).

Još jedan značajan klinički znak je ispupčenje supraorbitalnog sala koje se vidi u 20-60% konja s Cushingovom bolešću. Glavne posljedice adenoma pars intermedia hipofize su sekundarni dijabetes melitus (i istodobni gubitak težine) i laminitis. Treba imati na umu da konji s Cushingovom bolešću obično ne pate od poliurije i polidipsije osim ako nisu povezani sa sekundarnim dijabetes melitusom ili dijabetes insipidusom. Ostale komplikacije uključuju hiperhidrozu [pretjerano znojenje], neplodnost, galaktoreju, odgođeno zacjeljivanje rana, bilateralnu sljepoću, depresiju i napadaje. Gravidne kobile s Cushingovom bolešću i sekundarnim dijabetesom melitusom mogu roditi ždrebad (premale težine) s vrlo lošom prognozom ako se dijabetes melitus ne liječi tijekom trudnoće. Dijagnoza se najbolje potvrđuje procjenom bazalne koncentracije ACTH u plazmi ili provođenjem testa supresije deksametazonom tijekom noći. Pokazalo se da konji s hiperadrenokorticizmom imaju hiperinzulinemiju u mirovanju i smanjenu osjetljivost tkiva na inzulin (Beech i Garcia 1985). Osim toga, korištenjem tehnike euglikemične hiperinzulinemijske stezaljke [*] pokazano je da konji s Cushingovom bolešću imaju nisku bazalnu stopu metabolizma glukoze povezanu s povećanom inzulinskom rezistencijom (Klinkhamer i sur. 2011.). Što se tiče liječenja, prednost treba dati agonistima dopamina poput pergolida ili bromokriptina. Važno je shvatiti da samo konji s Cushingovom bolešću nisu poliurični i polidipsični te da u početku mogu biti više ili manje pretili i kao takvi mogu nalikovati konjima s metaboličkim sindromom konja.

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Metabolički sindrom u konja

Konji oboljeli od metaboličkog sindroma konja karakteristično su pretili povezani s “grebenastim” vratom i glavom repa (Ocjena tjelesne kondicije 7-9) i stari su između 8 i 18 godina. Ostali klinički znakovi uključuju abnormalni estrusni ciklus ili “natečenu ovojnicu”. Sindrom kod konja nema sklonosti prema spolu niti prema pasmini.
Glavna posljedica Metaboličkog sindroma konja je laminitis. Nažalost, teško je smanjiti težinu oboljelih konja ograničenjem prehrane („laki čuvari”).
Konji s metaboličkim sindromom konja imaju hiperinzulinemiju u mirovanju sličnu konjima s Cushingovom bolešću. Za razliku od konja s Cushingovom bolešću, rezultat testa supresije deksametazonom je normalan kod konja s metaboličkim sindromom konja. Zanimljivo je da tehnika euglikemične hiperinzulinemijske stezaljke kao zlatni standard za osjetljivost tkiva na inzulin još nije primijenjena na konje s metaboličkim sindromom konja. Najučinkovitije strategije prevencije i liječenja su one povezane s povećanom tjelesnom aktivnošću i smanjenjem tjelesne težine izazvanim prehranom.

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Neproporcionalno kongenitalni nizak rast (ili patuljasti rast) kod frizijske pasmine konja

Kod konja, patuljasti rast posebno se spominje kod frizijaca identificiran kao nesrazmjerno kongenitalno nizak rast s autosomno recesivnim svojstvom (Kroon i van der Plank 1931). Najistaknutija značajka njegovog fenotipa je retardacija rasta tijela u udovima i rebrima (Slika 2).

Zaražene životinje imaju približno 25% kraće prednje i stražnje udove i približno 50% smanjenu tjelesnu težinu. U slučaju kongenitalnog patuljastog rasta u frizijske pasmine konja, displastična metafiza distalnog metakarpusa i metatarzusa obično je radiografski evidentna (Back i sur. 2008), dok nisu otkrivene abnormalnosti u funkciji hipotalamus-hipofizna os rasta (de Graaf-Roelfsema i sur. 2009). Identificirana mutacija B4GALT7 utječe na dijelove proteoglikana izvanstaničnog matriksa (Leegwater i sur. 2016.) povezane s opuštenošću tetive. Liječenje oboljelih životinja je suportivno.

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Hipertrofična osteopatija

Poremećaj je karakteriziran simetričnom proliferacijom vaskularnog vezivnog tkiva i subperiostalne kosti, koja se javlja na distalnim dugim kostima. Izraz hipertrofična osteopatija je bolji od hipertrofične osteoartropatije, jer kod konja nema zahvaćenosti zglobova. Međutim, otekline mogu biti najizraženije na zglobovima s intrakapsularnim zahvaćanjem iako sama zglobna površina obično nije zahvaćena. Hipertrofična osteopatija općenito se nalazi u kombinaciji s intratorakalnim lezijama i primarnim ili metastatskim plućnim neoplazmama, ali je viđena i s lezijama na drugim lokacijama. Zaraženi konji su u dobi od jedne do 21 godine (prosjek 7,4±4,7sd godina) s blagom predilekcijom za muškarce (64%). Poremećaj je češći kod većih pasmina konja. Uzrok hipertrofične osteopatije još uvijek nije poznat. Predloženi mehanizmi uključuju hipoksiju, hormonsku disfunkciju, plućno vaskularno ranžiranje i neuralne mehanizme preko aferentnog parasimpatičkog puta. Dijagnoza se mora postaviti na temelju kliničkih znakova i tipičnih radiografskih promjena pri čemu su najčešće zahvaćene metakarpalne i metatarzalne kosti. Međutim, lezije su također zabilježene u radijusu, karpalnim kostima, proksimalnim i srednjim falangama, tibiji i tarzalnim kostima. Mogu biti zahvaćene i mandibula, maksila i nosne kosti (Slika 3).

Biokemija krvi može otkriti povećanu aktivnost alkalne fosfataze. Liječenje mora biti usmjereno protiv uklanjanja temeljnog uzroka ako je moguće.

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Renalni sekundarni hiperparatireoidizam

Ovdje treba spomenuti da sekundarni bubrežni hiperparatireoidizam nije bolest kod konja budući da zatajenje bubrega u konja obično nije karakterizirano hiperfosfatemijom i istodobnom hipokalcijemijom.

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