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The Endocrine Glands in the Dog: From the Cell to HormoneHelena Vala1, 2, Joao Rodrigo Mesquita2, Fernando Esteves2, Carla Santos2, Rita Cruz2, Cristina Mega2 and Carmen Nobrega2[1] Center for Studies in Education, and Health Technologies.
Tumors that grow from the pituitary gland can affect the whole body by interfering with normal hormone levels. The pituitary gland is a small, bean-shaped organ that sits at the base of the brain, behind the bridge of the nose (Fig.
Thyroid-stimulating hormone: causes the thyroid gland to make other hormones that control growth, temperature, and heart rate.
Luteinizing hormone and follicle-stimulating hormone: control the menstrual cycle in women and sperm production in men. Functional tumors secrete abnormal levels of hormones and interfere with the normal hormone regulation process. Symptoms of a pituitary tumor vary depending on its size and hormone secretion function; many are asymptomatic. Non-secreting tumors have few symptoms and are difficult to recognize until they grow quite large.
If you have symptoms that suggest a pituitary tumor, your physician will work with a team of specialists to confirm the diagnosis. First, the doctor will obtain your personal and family medical history and perform a physical examination. Magnetic Resonance Imaging (MRI) scan uses a magnetic field and radiofrequency waves to give a detailed view of the soft tissues of the brain. Endocrine evaluation measures hormone levels in the blood or urine to detect abnormal levels caused by pituitary tumors.
A visual field acuity test is performed by a neuro-ophthalmologist to detect vision loss and missing areas in the field of view.
Treatment options vary, depending on the type, grade, size, and location of the tumor, and your age and general health. The production of growth hormone can be controlled with the drugs octreotide (Sandostatin) or pegvisomant (Somavert), which are used in conjunction with surgical removal. To control the production of ACTH, drugs such as mitotane (Lysodren), ketoconazole (Nizoral), and aminoglutethimide (Cytadren) may be prescribed.
Surgical removal of a pituitary tumor may be performed as a minimally invasive endoscopic transsphenoidal, traditional transsphenoidal, or a craniotomy approach.
External beam radiation is delivered from outside the body by a machine that aims high-energy rays (x-rays, gamma rays) at the tumor. If you have more questions, please contact Mayfield Brain & Spine at 800-325-7787 or 513-221-1100.
Our pituitary team includes neurosurgeons, otolaryngologists (ear, nose, and throat surgeon), endocrinologists, ophthalmologists, pathologists, and radiologists. Advances in technology give Mayfield's neurosurgeons unprecedented access to brain tumors. Click here for information about clinical trials conducted by our doctors at local Cincinnati hospitals or call 1-800-325-7787. ThyroidCanine thyroid gland is located at cervical ventral region, lateral and ventral to the 5th-8th tracheal rings (Figure 7), being composed by two separate lobes, occasionally connected by an isthmus [17, 18].
Adrenal glandsThe adrenal glands are paired organs located against the roof of the abdomen near the thoracolumbar junction, in a position immediately prior to the kidneys and close to their cranial poles (Figure 16).
Clinical significance Endocrine diseases, associated to altered functions of endocrine glands, are frequently seen in veterinary practice. Molecular and genetic study of the role of hormones receptors, and enzymes in regulation of reproduction, lipid metabolism, and other human physiological functions. Follicle-Stimulating Hormone and Luteinizing Hormone Mediate the Androgenic Pathway in Leydig Cells of an Evolutionary Advanced Teleost.
G proteins and autocrine signaling differentially regulate gonadotropin subunit expression in the pituitary gonadotrope. Thyroxine-induced expression of pyroglutamyl peptidase II and inhibition of TSH release precedes suppression of TRH mRNA and requires type 2 deiodinase. Secretory cells of the supraoptic nucleus have central as well as neurohypophysial projections.
Physiology of the pancreatic ?-cell and glucagon secretion: role in glucose homeostasis and diabetes. Pituitary adenoma is the most common cause of hyperpituitarism that usually results in inappropriate secretion of one hormone.
The most reliable morphologic feature on light microscopy is the monomorphic appearance of tumor cells. Adenoma cells are small to medium-sized containing moderate to abundant amounts of finely granular cytoplasm and round to oval nuclei showing finely-stippled chromatin and indistinct to small nucleoli. One of the best and most reliable histopathologic features is the lack of reticulin network within tumor and compression of reticulin fibers around the tumor in normal pituitary tissue. It secretes hormones that control sexual development, promote bone and muscle growth, respond to stress, and fight disease.
Cortisol helps control the use of sugar, protein, and fats in the body and helps the body deal with stress.
Tumors of the pituitary gland occur in 15% of adults and are classified as functional or nonfunctional.
These tumors behave according to their cell of origin and are named for the specific hormone they produce.
Instead, they grow until their size and mass effect cause headache, vision loss, nausea, vomiting, or fatigue. The most common pituitary tumor, a prolactinoma, causes an overproduction of the hormone that helps control sexual function. Most commonly found in men, these pituitary tumors are larger and may grow toward the third ventricle of the brain. Some researchers believe they occur when a cell in the pituitary gland becomes abnormal or mutates. This team may include a neurosurgeon, otolaryngologist (ear, nose, and throat surgeon), endocrinologist, ophthalmologist, radiologist, and pathologist. In addition to checking your general health, the doctor performs a neurological exam to check mental status and memory, cranial nerve function (sight, hearing, smell, tongue, and facial movement), muscle strength, coordination, reflexes, and response to pain.
This test measures both central vision (how much is seen when looking straight ahead) and peripheral vision (how much is seen in all other directions while staring straight ahead).
Medication, surgery, and radiation either alone or in combination, are used to treat pituitary tumors and return hormone levels to normal. This technique is performed through an incision made under the upper lip (sublabial) along with removal of the nasal septum to access the tumor. Craniotomy approach to a pituitary macroadenoma that extends down into the sphenoid sinus and up into the third ventricle. Radiation works by damaging the DNA inside cells making them unable to divide and reproduce. The two main technologies are the Leksell Gamma Knife and linear accelerator systems such as the BrainLab Novalis.
A facemask is used to precisely localize the tumor and accurately reposition the patient for each treatment session. Small, slow-growing tumors that produce few symptoms may be observed with routine MRI scans until their growth or symptoms necessitate surgery.
For information about the University of Cincinnati Neuroscience Institutea€™s Brain Tumor Center, call 866-941-8264. Our affiliation with the University of Cincinnati Brain Tumor Center and the Precision Radiotherapy Center provides patients with care from a multidisciplinary team of doctors. Norberto Andaluz, discusses Management Options for Pituitary Tumors in this webinar produced in conjunction with the Pituitary Network Association.
Agrarian School of Viseu, Polytechnic Institute of Viseu, Viseu, Portugal[2] Agrarian Superior School of Viseu, Polytechnic Institute of Viseu.
In the dog there are four parathyroid glands, one external and one internal per each thyroid gland [17, 19, 20].External parathyroid glands are capsulated and may be found in varied positions, according to the species, which means that they can be placed between a cranial location to the thyroid gland and the entrance of the chest. The endocrine glands described may be targeted by several conditions summarized in table 7. Two histologic forms of primary hypothyroidism predominate in the dog: lymphocytic thyroiditis and idiopathic atrophy. About 75% of patients present with sign and symptoms related to mass effect of the enlarging pituitary or functional excess of a pituitary hormone. The cytoplasm can be eosinophilic, basophilic, acidophilic, or chromophobe recapitulating normal pituitary cell types. You may purchase original high-resolution image without Pathpedia logo using our automated system that grants single-user and multi-user, non-royalty-based, licenses. The gland has a larger anterior lobe (adenohypophysis) and a smaller posterior lobe (neurohypophysis).
A cross-section of the pituitary gland (green) shows its relationship to the optic chiasm above, the sphenoid sinus below, and the cavernous sinuses on each side. A healthy pituitary gland releases secretions into the bloodstream and provides feedback to the hypothalamus.
For example, a prolactin-secreting pituitary tumor (prolactinoma) arises from prolactin-producing cells.
Based on size, pituitary tumors can be either microadenomas (less than 10mm) or macroadenomas (larger than 10mm). Of hormonally active adenomas, about 50% secrete prolactin, 20% secrete growth hormone, 20% secrete adrenocorticotropic hormone, and 10% secrete multiple hormones. In women, the tumor can cause menstruation to stop (amenorrhea) or inappropriate production of milk by the breasts (galactorrhea).


Hyperthyroidism can accelerate the body's metabolism, causing sudden weight loss, irregular heartbeat, and nervousness or irritability.
They can also impair hormone secretion from the pituitary gland, which can cause fatigue, weakness, loss of body hair, and pale skin.Pituitary apoplexy.
Multiple endocrine neoplasia type 1 (MEN 1) is a rare condition with simultaneous tumors of the pituitary, pancreas and parathyroid glands. It is important to seek treatment at a center that offers the full range of options including surgery, radiation, and endocrine therapy.
Prolactinomas can be controlled with the drugs cabergoline (Dostinex) or bromocriptine (Parlodel), which reduce the size of the tumor while maintaining normal prolactin levels. For growth hormone-producing and ACTH-producing tumors, surgery is the treatment of choice to reverse the endocrine problems.
The endoscopic technique is replacing the traditional microscopic approach as it reduces the trauma to the nasal tissues and the recovery time for the patient.
The goal of radiation therapy is to maximize the dose to abnormal tumor cells and minimize exposure to normal healthy cells. Too much prolactin causes abnormal milk production in the breasts, lack of menstruation, infertility, and decreased sex drive.
This information is not intended to replace the medical advice of your health care provider.
Normal pituitary consists of a mixture of different cell types encased in reticulin meshwork but pituitary adenoma is characterized by a monomorphic expansion of usually one cell type with lack of reticulin network among neoplastic cells.
Examples of single-user license include conferences, seminars, presentations, and one-time teaching courses. The hypothalamus then regulates pituitary hormone levels, depending on the needs of the body. Both of these conditions affect the kidneysa€™ ability to regulate the balance of water and electrolytes.
Large tumors can press on the optic nerves and invade the cavernous sinuses, which house the carotid arteries and the nerves involved in eye movement. In men, prolactinomas may cause enlarged breasts (gynecomastia), erectile dysfunction or impotence, infertility, decrease in body hair, and low sex drive. A neurosurgeon, ENT surgeon, endocrinologist and radiation oncologist work as a team to treat pituitary tumors.
Expanded endoscopic transsphenoidal surgery involves opening more bone into the anterior skull base. Because a single radiosurgery dose is more damaging than multiple fractionated doses, the target area must be precisely located and completely immobilized with a head frame or facemask. Benign tumors, whose cells divide slowly, may take several months to a year to show an effect.
You and your doctor can weigh the risk of symptoms developing versus the risk of treatment intervention. IntroductionThe animal body represents one of the more complex and perfect systems of nature. They may be absent in some species or may be found included within the thyroid or close to them. The slender right lobe runs within the mesoduodenum and the thicker but shorter left lobe extends over the caudal surface of the stomach towards the spleen, within the greater omentum (Figure 13) [4, 17].
The cortex is yellowish and radially striated, while the medulla is more uniform and darker [17]. Doberman Pinschers and Golden Retrievers are the two breeds most frequently described [42].
The growth pattern can be diffuse, trabecular (as in this case), pseudo-acinar or pseudo-papillary. This tumor is arranged in pseudo-acinar formations with a central lumen-like space (arrowhead). Examples of multi-user license include books, book chapters, educational material, and other publications with multiple copies. Treatment options aim to remove the tumor or control its growth and restore normal hormone function.
Tumor growth may compress the normal pituitary gland, compromising its function and manifesting symptoms of decreased pituitary function. Other symptoms include excess sweating, high blood pressure, heart disease, diabetes, and arthritis. Cushinga€™s can also cause diabetes, menstrual irregularities, excessive hair growth, bruising, hypertension, and bone fractures from calcium depletion. Symptoms include sudden onset of a severe headache and vision changes, including vision loss, double vision, or drooping of an eyelid. An MRI scan of a pituitary macroadenoma (orange line) that has expanded upward to compress the optic chiasm.
This enables the surgeon to safely expose very large tumors that extend beyond the boundaries of the transsphenoidal approach. Despite its complexity and its functionality, which is incredibly effective, the control of its basic functions is performed by only two systems: the nervous system and endocrine system. Bar = 100 µm.The parenchyma of the pars distalis is composed by chromophilic cells, acidophilic or basophilic, arranged in cords, nests or follicles (Figure 4) and by small, round endocrine cells, without evident granules - chromophobe cells which means that they have low tinctorial affinity, also known as principal cells, reserve cells or C cells [4]. Bar = 25 µm.The follicle is, therefore, the structural and secretory unit of the thyroid gland, whose center is filled with a colloidal secretion (Figure 9), comprising the hormones triiodothyronine (T3) and thyroxine (T4) [4]. In the dog, internal parathyroid glands are within the thyroid capsule, in the caudal and medial aspects of the thyroid [19, 20].The parenchyma of parathyroid glands is composed of secretory cells, named chief or principal cells, arranged in cords, clusters, chains or rosettes (Figure 11, Figure 12). Both regions, cortex and medulla, correspond to areas specialized in producing different hormones [4, 32, 34]:The cortex consists of polyhedral secretory cells, arranged into two layered thick cords, which originate radially from the medullar zone [4, 33]. Clinical signs associated with hypothyroidism are varied, and behavioural changes are associated with a reduced metabolic rate, dermatological signs, cardiovascular and neuromuscular abnormalities. Tumor necrosis is generally not present unless infarction develops because of rapid growth. The pituitary gland is bordered on either side by the cavernous sinuses and below by the sphenoid sinus. Pituitary apoplexy requires emergency treatment, usually with corticosteroids and often surgery. It provides the surgeon with direct visualization of compressed structures, such as the optic nerves or anterior cerebral arteries. The nervous system is associated with electrical and chemical signals that are transmitted at high speed, resulting in rapid organic activities. Chromophilic cells secrete somatotropic hormone (also known as somatotropin - STH or growth hormone - GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), luteinizing hormone (LH) (which is also called interstitial cell-stimulating hormone or ICSH in males), thyrotropin or thyroid-stimulating hormone (TSH), melanocyte-stimulating hormone (MSH) and lipotropines [4]. In between the follicles, in a parafollicular position, cells with a pale cytoplasm, and a basal nucleus can be found - parafollicular cells or C cells which produce calcitonin [4, 16, 18]. In some species, such as cattle and humans, it is also composed by oxyphilic cells, organized in small clusters which have yet no known functions [4]. The later is produced in the islets of Langerhans, which are randomly scattered in the exocrine parenchyma (Figure 14) [10, 17, 24].
Next, the neurosurgeon removes the tumor by passing long instruments through the nostril while watching the monitor. The endocrine system acts through the synthesis and release of chemical messengers and is responsible for several functions of the organism, in a slower, but more durable way.Endocrinology is the science that studies the internal secretions produced by endocrine glands.
Somatotropin promotes epiphyseal growth [6] and protein production, whereas prolactin leads to mammary gland development and milk secretion. In dogs, this type of cells were only found in senile animals [21] and were also described in canine parathyroid adenoma [22].
Pancreatic islets are aggregates of endocrine cells required for blood glucose control and diabetes prevention after birth, consisting of polygonal shaped cells, with pale eosinophilic cytoplasm and coarse heterochromatin. The outer zone is the zona glomerulosa, a thin region that in dogs and cats is composed by cells arranged in an arched or arcuate pattern, therefore also named as zona arcuata (Figure 17) [32, 35, 36].The zona glomerulosa produces mineralocorticoids, particularly the steroid hormone aldosterone [32, 37], which is responsible for increasing sodium retention and water reabsortion in the distal tubules of the kidneys and sodium reabsorption in intestine. The internal carotid arteries and the nerves that control eye movement lie on the sides of the pituitary.
Craniopharyngiomas typically grow from the pituitary stalk upward into the third ventricle and cause symptoms similar to pituitary adenomas. Surgery is usually carried out with the aid of computer image guidance (an anatomical navigation system akin to a GPS). Endocrine glands are distributed throughout the body and secrete chemical messengers – hormones, in response to an internal or external stimulus. ACTH acts on the adrenal gland cortex, resulting in an increased release of adrenocortical hormones [7].
Cells are arranged in cords or clusters separated by sinusoids and are subdivided in the following subtypes (Figure 15) [4, 24, 25]:? cells, located peripherally and representing 10-20% of islet cells, secrete glucagon, a hyperglycaemic hormone, as well as cholecystokinin, gastric inhibitory protein and ACTH-endorphin [4, 10, 24, 26]. Aldosterone also maintains blood concentration and stimulates potassium excretion by the kidneys, thereby, indirectly regulating extracellular fluid volume.
Seborrhoea, bilateral and symmetrical alopecia, and pyoderma are also common dermatological symptoms. The goal is to precisely expose the tumor and to avoid nearby carotid arteries or optic nerves.
A small bone flap above the eye (supraorbital craniotomy) is cut and removed to access the brain (Fig.
These hormones are released directly into the bloodstream – endocrine mechanism, in contrast to exocrine glands, which use a ductal system to release their secretions in locations that lead, ultimately, to the exterior of the body – exocrine mechanism. ? cells, located in the centre of the islets, are more abundant, representing 60-80% of the islets of Langerhans, and secrete insulin, a hypoglycaemic hormone [4, 10, 24]. A decrease of mineralocorticoids, by loss of this zone or its functional ability, gives rise to water outlet of the blood to the tissues and may result in death, due to retention of high levels of potassium with excess loss of sodium, chloride and water [32]. These signs can be accompanied by bradycardia, low voltage ECG complexes and weakness [40, 41, 43, 44].Diabetes mellitusDiabetes mellitus is the result of any situation that affects insulin production, insulin transport or the sensitivity of target tissues to insulin [45].


When pituitary tumors grow they can compress the above-mentioned structures and cause symptoms. Hormones are transported through the bloodstream to target organs, where they will exert a physiological control, even in low concentrations, coordinating a multiplicity of organic functions and maintaining homeostasis. Many factors are known to contribute to the development of diabetes and its complications [46, 47]. The main endocrine glands in the animal body include pituitary gland, thyroid, parathyroid, pancreas, adrenal (Figure 1), and gonads (ovaries and testes). This hormone is also capable of reducing intestinal motility and secretion of digestive juices.
These include genetics, diet, sedentary lifestyle, perinatal factors, age, obesity and inflammatory causes [47, 48]. These cells represent about 5-40% of the islets [10, 24].Besides the above-mentioned cell types, the endocrine pancreas also contain some minor types of cells, that represent around 5% of the total pancreatic cells. Canine diabetes mellitus is generally classified as insulin dependent or non-insulin dependent based on the need for insulin treatment [40, 48]. A craniotomy is required for large tumors that have invaded nearby tissues and cannot be removed through a transsphenoidal approach. Gonadotropes or gonadotropic cells which secrete gonadotropins LH and FSH (basophilic) [13]. This hormone, together with calcitonin and vitamin D, is involved in the regulation of calcium homeostasis. Bar = 50 µm.The zona fasciculata is the middle and thickest zone (corresponding to more than 70% of the cortex) and is composed of parallel columns of secretory cells, one to two cells thick, separated by prominent capillaries. Most diabetic dogs are thought to have a disease like human type I diabetes mellitus and are insulin dependent [40, 49, 50]. Hypothalamic-pituitary axisThe hypothalamus, located at the base of the ventral diencephalon is limited rostrally by the optic chiasm, caudally by the mammillary processes, laterally by the temporal lobes and dorsally by the thalamus. It is released in response to low blood calcium level [23] due to it’s ability to enhance the mobilization of calcium ions from the small intestine and from bone resorption, and also by increasing the simultaneous absorption of calcium and excretion of phosphate from distal convoluted tubules of kidneys [10] (Table 4). The cells are cuboidal or polyhedral, containing vesicular nucleus, frequently binucleated) and foamy cytoplasm (intracellular lipid droplets) (Figure 18).
Unlike human type I diabetes mellitus, which occurs mainly in young human patients, in dogs it is more likely to occur later in life [40, 45, 48].
The chromophobe cells are also arranged in clusters or cords and their low tinctorial affinity probably indicates that these cells may correspond to depleted cells of any of the above types described or a state of partial degranulation.
Dogs do not appear to progress from obesity-induced insulin resistance to type 2 diabetes mellitus, probably because pancreatic beta cells in dogs are either not sensitive to toxicity due mild hyperglycemia or lack other components of the pathophysiology of beta cell failure in type 2 diabetes mellitus [51]. Although not considered a real endocrine gland, the hypothalamus coordinates all pituitary activity by the release of a number of peptides and amines that control the secretion of hormones in the pituitary gland (also named hypophysis). However, some of the chromophobe cells may also be undifferentiated, nonsecretory cells [4, 15]. Glucocorticoids have several functions, including protein catabolism and stimulation of the hepatic gluconeogenesis from amino acids [10, 37].
Certain breeds, including Australian Terrier, Keeshounds, Alaskan Malamutes, Finnish Spitzes, Standard and Miniature Schnauzers, Miniature Poodles, and English Springer Spaniels, seem to be at increased risk to develop diabetes. Bar = 25 µm.Insulin and glucagon are pancreatic hormones that play pivotal roles in regulating glucose homeostasis and metabolism, which have opposite effects on glycaemia as well as on the metabolism of nutrients [24, 26, 28].
Others, such as Boxers, German Shepherd dogs, Cocker Spaniels and Collies seemed to be at decreased risk [40, 52].
So, the actions of the two hormones combined contribute to the control of blood glucose.Glucagon secretion by ?-cells is highly regulated by multiple factors, being the most important the glucose and insulin levels.
Exercise intolerance or decreased activity, ketonic breath, recurrent infections (urinary tract, conjunctivitis), cataracts and hepatomegaly can also be present [45].
Bar = 25 µm.The pars tuberalis is composed by cuboidal weakly basophilic cells, arranged in cords, nests or follicles and its function is not yet well established [4]. Low glucose levels activate specific channels in the brain and in pancreatic ?-cells to generate action potentials of sodium and calcium currents, leading to glucagon secretion.
Bar = 25 µm.The zona reticularis is also composed of polyhedral cells, whose arrangement consists in freely anastomosing cords (Figure 19) [32].
Also, somatostatin inhibits glucagon secretion by inhibiting adenylate cyclase and cAMP production [26]. These cells contain less lipid content but have densely granular cytoplasm for which they are called “compact cells” [34]. Spontaneous hyperadrenocorticism is associated with inappropriate secretion of ACTH by the pituitary (pituitary-dependent hyperadrenocorticism) or with a primary adrenal disorder (adrenal-dependent hyperadrenocorticism) [40, 53, 54].
Insulin has several physiologic actions that include stimulation of cellular glucose and potassium uptake [29].
Over 80% of dogs with spontaneous hyperdarenocorticism suffer from pituitary dependent hypercorticism, resulting in an over secretion of ACTH [53, 54].
Glucose-induced insulin secretion from pancreatic ?-cells depends on mitochondrial activation, amongst other factors, like ATP, glutamate and others [30].
These hormones are produced in the hypothalamus, transported through the hypothalamic-pituitary axis and stored in the neurohypophysis, until a stimulus induces their release [4, 16] (Table 2).ADH has several effects on the body, particularly in terms of water saving and in increasing blood pressure. Incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide-1 (GLP-1), secreted by cells of the gastrointestinal tract in response to meal ingestion, exert important glucorregulatory effects, including the glucose-dependent potentiation of insulin secretion by pancreatic ?-cells [31].Table 5 summarizes hormones of the pancreas and their functions.
Oxytocin stimulates contraction of the myoepithelial cells of the mammary gland, causing the ejection of milk. Adrenal-dependent hyperadrenocorticism represent the remaining 20% of spontaneous hyperadrenocorticism and is generally associated with unilateral (or occasionally bilateral) adrenal tumours.
It also binds to the smooth muscle cells of the uterus, promoting uterine contractions during parturition [10] (Table 2). Dogs showing pituitary-dependent hyperadrenocorticism exhibit a mean age of 7-9 years old, and those with adrenal-dependent hyperadrenocorticism, a mean age of 11-12 years old. There are some breeds that are most frequently associated with hyperadrenocorticism, but any breed can develop it. The medulla consists of large columnar or polyhedral secretory cells, randomly distributed, with rich blood supply (Figure 20). The cells have large, vesicular nucleus, basophilic cytoplasm with fine positive chromaffin granules, due to the presence of catecholamines such as epinephrine and norepinephrine, which after exposure to oxidizing agents, such as chromate, yield a brown reaction by the formation of colored polymers [4, 31, 33].
This can arise from a destruction of more than 90% of both adrenal cortices, causing inability to produce corticosteroids (Primary hypoadrenocorticism or Addison’s disease), or from a deficiency in ACTH production by the pituitary (Secondary hypoadrenocorticism) [56, 57]. Besides different pathophysiology, primary and secondary hypoadrenocorticism also exhibit different clinical signs. In adults, there are 3 types of adrenal medullary cells (1): epinephrine cells (66–75%), norepinephrine cells (25–33%) and small granule-containing cells (SGC, 1-4%).
It is often associated with idiopathic adrenocortical atrophy, or with some therapeutic or surgical procedures, like mitotane treatment for hyperadrenocorticism or bilateral adrenalectomy. The adrenal SGC cells of dogs vary from cells with a few granules and a high nucleo-cytoplasmic ratio to cells filled with many granules and a large mass of cytoplasm. This condition generally affects young and middle age dogs with a median age of 4 years [57].
Most of the chromaffin granules of these cells are small, ranging from 100 to 200 nm in diameter [39]. Great Danes, Portuguese Water Dogs, Rottweilers, Standard Poodles, West Highland White Terrier and Soft-coated Wheaten Terriers are the breeds in greater risk to develop hypoadrenocorticism [56].
The medullary cells produce other peptides in addition to epinephrine and norepinephrine, such as met-enkephalin, substance P, neurotensin, neuropeptide Y, and chromogranin A.
The adrenal medulla contains also presynaptic sympathetic ganglion cells, randomly scattered [4, 32]. The first step in the synthesis of epinephrine is the enzymatic conversion of tyrosine to dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase. The animal can be in a hypovolaemic shock, and generally is found in a state of collapse, or collapses when stressed. Weak pulse, bradycardia, abdominal pain, vomiting, diarrhoea, dehydration and hypothermia can also be present.
Norepinephrine then leaves the granule to be converted into epinephrine in the cytosol by phenylethanolamine-N-methyltransferase (PNMT), and epinephrine re-enters the granule for storage in the cell. Animals with chronic hypoadrecocorticism may present anorexia, vomiting, lethargy, depression and weakness [57].8. The activity of PNMT is induced by the high local concentration of glucocorticoids in sinusoidal blood from the adrenal cortex [10, 32]. ConclusionsMalfunction of endocrine glands leads to severe multivariate syndromes, requiring a specialized medical approach and appropriate nursing care. Acute stress, hypoglycemia or other similar situations, result both in catecholamine secretion and in transsynaptic induction of catecholamine biosynthetic enzymes, including tyrosine hydroxylase.
For this reason, professionals engaged in clinical veterinary practice need to know animal organic structures and how they function as a whole, including the role of the endocrine system, its glands and their hormones. Other environmental influences, including growth factors, extracellular matrix, and a variety of hormonal signals that generate cyclic AMP, also may regulate the function of chromaffin cells [32].
This systematic approach to endocrine disorders promotes not only a trained professional but a professional with technical and scientific knowledge, enabled with the exact notion of the involved etiopathogenic mechanisms and capable of making a diagnostic and therapeutical difference.
In table 6, we can see a summary of some of the hormones produced by adrenal glands and their functions.
This concerted attitude would certainly contribute to improve veterinary medical care to a level of excellence in the care of animal patients.NaN.
AcknowledgementsThis work was supported by Portuguese Foundation for Science and Technology and Center for Studies in Education, Technologies and Health.



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