Endocrine diseases of Ungulates

Introduction

In order to survive, animals must constantly adapt to changes in the environment and it is the endocrine system that works to bring about these adaptations. In general, the endocrine system brings about longer-term adaptations by sending out chemical messengers called hormones into the intracellular fluid or the bloodstream. The endocrine system is very influential and relates to most, if not all the other principle systems of the body. It is accountable for the production of hormones as well as the regulation and monitoring of them as well. These hormones function as chemical messengers throughout the body. Through disparate mechanisms, they are able to generate specific responses in target cells or organs.

The hormones secreted by the endocrine system come from a variable range of different places. Amidst those culpable for hormone production are the glands as well as a few organs as well. The primary glands associated mostly with hormone production are the adrenal, pituitary, thyroid, parathyroid and the thymus. The organs, which also perform a substantial role are the kidneys, pancreas, gonads, heart and alternative parts of the digestive tract. The hormones which are regarded of greatest importance for maintenance of the body in ungulates and averting disease are;

• Growth hormone GH

• Luteinizing hormone LH

• Follicle stimulating hormone FSH

• Thyroid stimulating hormone TSH

• Adrenocorticotrophic hormone ACTH

• Anti-diuretic hormone ADH

• Adrenaline

• Noradrenaline

• Aldosterone

• Cortisol

• Insulin

• Glucagon

• Testosterone

• Oestrogen

It is these hormones in which enable the endocrine system in ungulates to promote growth, development, reproduction and behaviour among other traits too. Any deviation away from the regulatory level of these hormones listed above in ungulates will result in specific hormonal diseases to the animal in question.

Hypothyroidism

Hypothyroidism is an endocrine disease associated with the thyroid gland. The thyroid gland is located on the ventral side of the trachea on both sides just caudal to the larynx and vary in appearance amongst ungulates. In the horse and cow it consists of two lobes, which are connected by an isthmus. In the horse, each lobe appears more oval in shape in comparison to the cow which takes up a rectangular appearance. In the pig, the thyroid gland is an unpaired compact organ with a granular like presence.

The main two hormones relating to the thyroid gland are thyroxine (T4) and triiodothyronine (T3). They are produced by follicular cells before being released into the bloodstream. Hypothyroidism is also referred to as ‘goitre’ and a deficiency in these hormones will result in this endocrine disease, causing the overall well-being of the animal to deteriorate, such examples being, their decreased metabolism of lipids, carbohydrates and proteins, their desire and willingness to exercise and their overall growth.

Triiodothyronine is mainly derived from thyroxine, although both hormones are dependant on the presence of iodine in the diet of the animal to ensure adequate secretion.(Bragulla,2009).The secretion of thyroid hormones is coordinated by the negative feedback control in response to the hypothalamic-pituitary thyroid axis. In the pituitary, thyrotropin releasing hormone (TRH) attaches to thyrotrophic cells which stimulates the secretion of the thyroid stimulating hormone (TSH) thus, causing thyroid hormone synthesis and secretion.

In cattle, hypothyroidism is the most prevalent thyroid disease as a result of insufficient thyroglobin synthesis and secretion. However, on saying this, in the modern era this endocrine disorder is still quite rare owing to the fact that modern animal feeds encompass sufficient levels of iodine(Vetbook,2012).An animal suffering with hypothyroidism will have a large visual lump on its neck in the region of the larynx, which can vary in size and can be as small as a marble in some cases and may be initially difficult to observe. The majority of hypothyroidism cases are due to an iodine inadequacy, and its more prevalent in young/newborn calves than adult animals.(Jackson,2017).These young animals born with hypothyroidism are medically known as ‘congenital goitre’. There are few reasons why the pregnant cow/horse/sheep may be suffering from iodine deficiency.

Depending on the time of year, the amount of rainfall will vary in a region. High rainfall will ensure good growth and fertile lands with lush grass available throughout this period. This can be a negative problem for the animal as it is less likely to consume forage from surface soils which would contain a range of nutritional minerals including iodine. We can be of the opinion that hypothyroidism is more likely to occur if there is an endless supply of quality grass with a low stocking density. In some regions present across the world, sandy soils are most common (African plains) and pregnant animals here are much more susceptible to develop an iodine deficiency in contrast to those grazing on textured soils. Goitrogens are compounds present in brassica crops, which can further impede iodine availability. Sheep are more inclined to consume this type of vegetation. Iodine lacking newborn lambs are unable to adapt to harsh wet conditions in juxtaposition to iodine sufficient lambs, therefore, even a slight lack of iodine in lambs which could go easily unnoticed could be a major cause of mortality(Tasmanian Government,2014)

In severe equine cases, foals in particular with hypothyroidism, can be referred to as ‘dysmature’. The shortage of iodine can develop brittle bones, flexor and extensor tendons may become ruptured, and joint problems may be encountered which in turn leaves them unable to stand properly as well as having coats disorders. As well as all of this, the mare can have a prolonged gestation, risking death for both mother and young at the time of parturition.(R.Singh,2013)

Fortunately, certain methods and measures can be taken to inhibit or prolong the onset of hypothyroidism, by ensuring iodine is available and is part of the diet. One method is dosing the pregnant mother with iodine 4-5 months into pregnancy. A further approach would be the use of mineral licks to provide iodine consumption, although this measure may not always be reliable as its hard to know in a herd if the animals affected has consumed the lick or may be put off by the taste of the lick. On top of these, an additional procedure which entails the farmer painting the teats of the cow, ewe and mare with iodine, will allow the young animal to obtain traces of iodine whilst suckling.(Tasmanian Government,2014)

Cystic Ovarian Disease

Cystic ovarian disease is another example of an endocrine disease effecting ungulates. It effects sheep and horses but it is most prominent in a lactating cow.(partnersinreproduction,2003).This disease is most common in the first two months after parturition, and is a huge cause of reproductive failure in cattle. In the dairy cow, these ovarian cysts can be greater than 25mm in diameter and last for more than 10 days without a functional corpus luteum present.(Ahmad Ljaz,1987).The word ‘cystic’ is believed by many authors to refer to the inability of the ovarian follicle to ovulate. These cysts are said are said to occur when the hypothalamus and pituitary gland, under the influence of oestradiol, fail to release an adequate supply of luteinizing hormone (LH).(Vanholder,2006)

There can be two types of this cystic ovarian disease: Follicular Ovarian Disease; this disease has a negative impact on regular endocrine events of the oestrous cycle, with the presence of a thin-walled, fluid-like cavity known as a ‘cyst’. The alternative disease is known as a luteal cyst, the only noticeable difference being is that they appear thicker walled than the follicular cysts. Observable endocrine changes happen and ‘short inter-oestrous intervals’ occur as well as peculiar heat behaviour changes in the lactating cow.(Statham,2018).It is said that 65 to 80% of cows effected with ovarian cysts will retrieve normal ovary cycles within 30days following treatment.(Ahmad Ljaz,1987)

Treatments with intramuscular injections of corticosteroids were once used, however, the wound healing and anti-inflammatory effect of the mineralocorticoids and glucocorticoids proved not to have a very successful rate.(Edwards,2018).Treatments employing FSH were also used which would provoke follicular growth, enhancing ovulation, however, the cysts continued to grow after reaching the expected ovulatory size thus assisting with the development of the follicular cyst, instead of its elimination.(Palmar,2004).Multiple follicles may form cysts as a result of the inability of ovulation to occur at oestrous, It was found that the main reason for this failed ovulation was insufficient release of GnRH, by the positive feedback of follicular oestrogen on the hypothalamus in order to generate an LH surge.(Statham,2018).Gonadotrophin releasing hormone (GnRH) has been discovered to be the best treatment for ovarian cysts re-establishing the ovarian cycle within 30days. Subsequently treating the cow with this hormone, oestrous will develop within 18-23days, however the administration of PGf2 alpha on top of the GnRH will speed up the signs of oestrous dramatically. Approximately 9 days after GnRH is given to the cow an injection of PGf2 alpha will almost degenerate the ovarian cyst with the cow presenting oestrous within a couple of days.(Ahmad Ljaz,1987)

It is important not to confuse a developing cyst with a regressing corpus luteum. The corpus luteum has a large central cavity, which when palpated may resemble an ovarian cyst. Nonetheless the presence or absence of this corpus luteum has no implication on the diagnosis of cystic ovarian disease. During rectal palpation it is possible for the rupture of cysts to occur, however it is recommended to avoid this at all costs as it risks trauma and haemorrhage in the animal. As mentioned already, this endocrine disease can be quite frequent after parturition in ungulates. Uncommon post-parturition conditions such as ketosis, lameness and the inability of the female to pass the fetal membranes will double the likeliness of cystic ovarian disease to develop. Therefore measures taken to diminish other unnecessary post-parturition problems will decrease cystic ovarian disease development.(Palmar,2004)

PPID

Pituitary pars intermedia dysfunction (PPID) or equine cushings disease is an endocrine disease affecting the pituitary gland of horses. It manifests itself as a pituitary adenoma that results in erratic cortisol and insulin levels.(Ramaekers,2003).It is most often found in older horses usually over the age of 15, the average age is 19, and ponies are most often affected. It can develop in younger horses too but is rare, up to 30% of older horses have the condition and the risk of developing the disease increase directly with age.(Rendle,2018)

The pituitary gland is a small gland at the base of the brain, and releases its products, in response to signals from nerves that originate in another area of the brain called the hypothalamus, damage to these nerves causes the pituitary to enlarge and produce excessive amounts of hormones. The pituitary gland is divided into two lobes posterior and anterior. The anterior is separated into pars intermedius, pars distalis and pars tuberalis. The pars intermedia contains melanotrophs that process POMC to produce mainly beta endorphin, melanocyte stimulation hormone (MSH) and corticotrophil like intermedia peptide. Under 2% of the hormones produced is ACTH and hormone production from the pars intermedia is regulated solely by dopamine and serotonin from the hypothalamus.(Menzies, magonlinelibrary)

Clinical signs

Horses can develop one or multiple clinical signs.(Menzies,magonlinelibrary).Hirsutism is the name for excessive hair growth or abnormal retention of the hair coat in the summer and PPID is the only disease where this occurs.(Rendle,2018).Hirsutism is the most common clinical sign, its seen in 55% - 80% of cases. The mechanism underlying this unknown extra plasma cortisol or melatonin and pressure on the hypothalamic thermoregulatory centre by an enlarged pituitary gland have been suspected.(Menzies, magonlinelibrary).

Abnormal fat deposition and insulin resistance may develop in up to 60 % of horses with PPID.(Rendle,2018). Fat pads can be seen around the eyes, along the crest of the neck and above the tail.(Menzies, magonlinelibrary).

Laminitis is the inflammation of the laminea, making it difficult for the horse to walk.Loss of muscle mass normally observed over the back and hind quarters and the horse will have a potbellied appearance.(Graves,2007).Weight loss is seen in up to 90% of cases. The metabolic effects of cortisol are thought to be the case.(Menzies,magonlinelibrary)

Increased drinking (polydipsia) and urination(polyuria) may be seen in up to a third of horses, increased sweating(hyperhidrosis)Seizures, weakness, blindness and collapse may be seen in advanced cases.Infertility of mares.(Rendle,2018)

Abnormal mammary gland development.Chronic infections due to immunosuppression.(Graves,2007)

It is challenging to get an exact diagnosis of PPID because of the pituitary gland and the resultant blood and external changes can vary between animals. In addition, pituitary function varies with season in horses. In advanced cases hirsutism which is marked may be used for diagnosis but other clinical signs are not reliable. Changes in routine blood samples are not specific for diagnosis of PPID, but may show signs the disease is present. Some of these signs may be high white cell count, evidence of secondary infection, high glucose concentration and an increased level of liver enzymes. In saying this however, these changes may have other explanations. For definitive diagnosis of PPID, this would require measurement of hormones in the blood. Cortisol levels used to be used as an indictator of PPID because cortisol is released from the adrenal glands in response to increased hormone production from the pituitary but horses with PPID may have normal levels of cortisol and normal horses have higher levels.

Another indicator is high insulin levels in horses. Insulin levels can rise up to 60% in horses with PPID, although, these levels may also be high if for example the horse has Equine Metabolic Syndrome (EMS) or has just recently been fed, so then further tests would be required. In horses with PPID, melanotropes produce an abnormally high level of adrenocorticotrophic hormone (ACTH). Horses have seasonal changes in ACTH levels so this should also be accounted for in the test.

The dexamethasone suppression test has been commonly viewed as the best test but it is not reliable to detect early cases of the disease. In order to take the test, a blood sample is taken to measure natural cortisol levels and then repeating the test the next day again, to observe any additional change in the blood sample. If on analysis of the results there was no change, then this would determine that the horse had PPID.

Furthermore, the thyrotropin releasing hormone (TRH) stimulation test assesses the pituitary glands response to the application of TRH. In horses with PPID the pituitary gland has an exaggerated response to TRH with increased levels of ACTH and cortisol.(Rendle,2018).Post mortem examination usually reveals an enlarged pituitary gland. Tumours are composed of large columnar or polyhedral cells with heterochromatic nuclei. The adrenal glands will be enlarged and have many sites of infections.(Wiki Vet,2012)

For effective treatment of PPID, pregolide is available. It stimulates dopamine receptors in the brain, replacing the activity of the damaged nerve supply to the pituitary gland.(Rendle,2018).Other common allopathic drug for PPID is parlodel, a dopamine antagonist and cyprohepatidine, a serotonin blocker.(Ramaekers,2003).PPID is a natural degenerative condition therefore there is nothing that can be done to prevent it.(Rendle,2018)

Decline of the hypothalamic periventricular dopaminergic neurons results in disinhibition of the endocrine cells of the pars intermedial (PI); the melanotropes. As a result, the PI enlarges, compressing the other lobes. The dis inhibited melanotropes overproduce pro-opiomelanocortin peptides, including alpha melanocyte stimulating hormone, B-endorphin, corticotrophin-like intermediate lobe peptide and adrenocorticotrophin.The excess in pars intermedia hormones and perhaps with a deficiency in other pituitary hormones results in pituitary pars intermedia dysfunction.(McFarlane,2014)

Conclusion

In conclusion as discussed above it is my view that hormones play an integral part in the functioning and well being of animals.In circumstances where there is a hormonal deficiency Ungulates are found to present themselves with a number of diseases such as the ones discussed above. Hypothyroidism, Cystic Ovarian Disease & PPID are three diseases relating to three separate Endocrine glands in the body that can effect the lives of Ungulates. The hormonal changes that occur in each of these diseases shows the importance of maintaining the Endocrine System throughout the animals life. I would therefore submit that the points discussed above highlight the complexitys of the Endocrine System of Ungulates.

References

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D.McFarlane, 2014. Pathophysiology and clinical features of pituitary pars intermedia dysfunction. onlinelibrary.wiley., 26(11), p. 1.

Edwards, S. H., 2018. Corticosteroids. MSD manual Veterinary Manual.

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Statham, J., 2018. Follicular cystic ovary disease in cattle. MSD manual Veterinary manual.

Tasmanian Government, 2014. www.tas.gov.au. [Online] Available at: http://dpipwe.tas.gov.au/biosecurity-tasmania/animal-biosecurity/animal-health/sheep/goitre-and-iodine-deficiency [Accessed 28 04 2018].

Vanholder, T., 2006. Aetiology and Pathogenesis of cystic ovarian follicles in dairy cattle. Reproductive Nutrition Development, 46(Reprod. Nutr.Dev), pp. 105-119.

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EndocrineUngulates (last edited 2018-04-29 15:24:40 by 3390E)