endocrine

• Primary gland hypofunction occurs due to:

  • Destruction of secretory cells by a disease process e.g. immune mediated or inflammatory injury
  • Failure of gland development (hypoplasia or agenesis)
  • Biochemical defect in the synthetic pathway of the hormone. This is usually genetic and not commonly identified in animals
• Secondary gland hypofunction occurs due to:

  • Destruction of the upstream primary glandular tissue so there is failure of a trophic hormone
  • Hypofunction of a downstream endocrine organ

  An endocrinologically inactive pituitary neoplasms (interferes with secretion) which can lead to target organ atrophy from lack of use.
• Primary gland hyperfunction often involves a hyperplasia or neoplasia of the involved endocrine cells. The primary source synthesises and secretes hormones autonomously in excess of the body’s ability to use the hormone. E.g.:

  • Adrenal cortical adenoma or carcinoma – releases cortisol causing hyperadrenocorticism
  • Pancreatic islet beta cell tumour – releases insulin causing hypoglycaemia
  • Adrenal medulla phaeochromocytoma – releases adrenaline causing hypertension
  • Thyroid follicular cell adenoma or hyperplasia – releases T4 and T3 causing hyperthyroidism
• Secondary gland hyperfunction means a lesion in a gland cases excessive trophic hormone secretion, causing long-term hypersecretion in a target organ. An example is canine ACTH-secreting pituitary tumour, resulting in adrenal cortical hyperplasia and hyperadrenocorticism (canine cushings )
• Non-endocrine tumours can cause hypersecretion of hormones or hormone-like factors e.g.:

  • Adenocarcinoma of the apocrine glands of the anal sac in dogs – causes production of parathyroid hormone-related peptide, inducing pseudohyperparathyroidism -> hypercalcaemia
  • Certain canine lymphomas may exhibit similar action, secreting or associated with production of a factor inducing hypercalcaemia.
• Failure of target cell response describes failure of the cell surface receptor or lack of a second intracellular messenger. An example is insulin resistance in obesity – receptors are lost in connective tissue cells so the body fails to react to insulin, causing diabetes mellitus.
• Endocrine hyperactivity can occur secondary to disease in other organs e.g. secondary hyperparathyroidism associated with chronic renal failure: phosphorus retention and vitamin D metabolism leads to hypocalcaemia, hyperparathyroidism and skeletal demineralisation.
• Abnormal hormone degradation can go either way: a decreased or increased rate:

  • Decreased degradation rate, e.g. due to atrophy or disease of the target organ (e.g. liver or kidneys)
  • Increased degradation rate e.g. chronic drug administration activating P450 mixed function oxidase enzymes (abnormally)
• Canine cushing’s syndrome due to excess steroid administration is an example of iatrogenic endocrine pathology.
• Adrenocorticotrophic hormone secreting adenomas of the pituitary gland are most common in the dog, causing hyperadrenocorticism (Cushing’s). these lesions appear expanded and pale grossly, with a histological loss of normal pituitary architecture. Produce excess ACTH
• Developmental pathologies of the pituitary gland include pituitary cysts causing loss of pituitary tissue, and pituitary dwarfism (generally associated with a cyst or is genetic)
• Pituitary pars intermedia dysfunction in horses is seen with hyperplasia or neoplasia of the pars intermedia -> equine cushings (producing excess ACTH and alpha melanostimulating hormone). Affects about 20% of horses over 15 years old. See changes in adipose metabolism and muscle atrophy with a curly coat. Often also see laminitis as a secondary metabolic syndrome. The pituitary gland is massively expanded, with the normally thin band of pars intermedia appearing very large on histology.
• Neoplasias of the pituitary gland include non-functional adenomas (atrophy of surrounding pituitary gland and compression or local extension into the brain), or the more rare pituitary carcinoma (non-secretory but locally invasive)
• Hypofunction of the adrenal gland is hypoadrenocorticism (addison’s disease) is caused by loss of the zona glomerulosa. Histologically, the adrenal cortex appears shrunken (should have a 3:1 ratio to the medulla). Can occur for several reasons:

  • Bilateral idiopathic atrophy of the adrenal cortex – this is often immune mediated, so inflammation or bilateral haemorrhage may be seen
  • Mineralocorticoid insufficiency – alterations in sodium, potassium and chloride levels. Presents as bradycardia and sometimes hyperkalaemia.
  • Glucocorticoid insufficiency – causes hypoglycaemia
• Hyperfunction of the adrenal gland is hyperadrenocorticism (hypercortisolism) – aka Cushing’s disease. This is a syndrome of cortical excess. The most common cause is a functional corticotroph pituitary adenoma in the dog, causing bilateral adrenal gland hyperplasia (but severity of syndrome bears no relation to the size of the primary tumour). A less common cause is a functional adrenal gland neoplasm, which involves effects on gluconeogenesis, protein catabolism, lipolysis and anti-inflammatory effects by glucocorticoids.
• Canine Cushing’s -> changes in gluconeogenesis, protein catabolism, lipolysis & anti-inflammatory effects. Also:

  • muscle weakening (lordosis, pendulous abdomen (pot belly), atrophy of temporal muscles) due to excessive protein catabolism and decreased protein synthesis
  • Hepatomegaly due to steroid hepatopathy – increased deposits of glycogen and lipid to the liver
  • Skin lesions where the epidermis atrophies, also cutaneous calcification
  • Calcification of the lungs, muscles and stomach wall
  • Increased appetite – a direct effect of cortisol, or the destruction of the hypothalamus appetite centre
• Adrenal hyperplasia comes in two forms:

  • Nodular hyperplasia of the cortex. This is common and often incidental, with multiple and bilateral nodules often seen in the dog, cat and horse. Very rarely functional
  • Diffuse hyperplasia, which often occurs in response to functional tumours of the pituitary gland. Results in hypersecretion of adrenal hormones
• The three most common types of adrenal neoplasia are adrenal cortical adenoma, adrenal cortical carcinoma and medullary phaeochromocytoma.
• Adrenal cortical adenomas are often incidental findings, which arise in adrenal glands with existing nodular hyperplasia
• Adrenal cortical carcinomas are less common ^ but if functional, will result in marked atrophy of the contralateral gland. Mostly seen in cattle and dogs. Clinical signs are hyperadrenocorticism and potential distant metastasis.
• Medullary phaeochromocytoma is most seen in cattle and dogs. These can get large and invade locally, spreading through the azygous vein to metastasise. May be functional with adrenaline or noradrenaline excess.
• Developmental disorders of the thyroid glands include:

  • Accessory thyroid tissue. Relatively common with remnants from embryological development in the mediastinum. Can become neoplastic.
  • Thyroglossal duct cysts – in ventral cervical region, forming cysts. Can become neoplastic
• Hyperthyroidism is common in cats, but is uncommon in the dog, even with a functional thyroid neoplasia as they can excrete excess thyroid hormones.

  Clinical signs are polyuria, polydipsia, weight loss despite good appetite, poor coat, hyperexcitability, heat intolerance and hypertrophic cardiomyopathy.
• Thyroid gland hyperplasia may present as goitre or nodular hyperplasia:

  • Goitre is non-neoplastic, non-inflammatory enlargement of the thyroid gland, occurring in animals with an iodine deficient diet.
  • Nodular hyperplasia is multiple small raised nodules, which are rarely functional in most species but are often functional in the cat
• Thyroid gland neoplasias include follicular adenoma, follicular carcinoma and c-cell neoplasia.

  • Thyroid follicular adenoma forms discrete, encapsulated, usually solitary lesions, common in the cat
  • Thyroid follicular carcinoma is most common in the dog but is rarely functional. Locally invasive with tendency to metastasise. Capable of arising in extra-thyroidal tissue
  • C-cell neoplasia affects the interstitial tissue cells which secrete calcitonin. Most common is bulls. These tumours are found in association with phaeochromocytomas and pituitary adenomas.
• Hypothyroidism (under function) is important in the dog, but not common in other species. Aetiology may be:

  • Idiopathic follicular atrophy, where follicles are progressively replaced by adipose tissue
  • Lymphocytic thyroiditis – autoimmune reaction, autoantibodies form and lymphocytes infiltrate the gland
• Hypothyroidism is associated with:

  • Reduced basal metabolic rate
  • Bilaterally symmetrical alopecia (hyperkeratosis, hyperpigmentation, myxoedema)
  • Reduced spermatozoa count in males, anoestrus in females
  • Increased cholesterol levels -> atherosclerosis (lipid deposits in vessels)
• Primary hyperparathyroidism occurs due to chief cell neoplasia, with adenoma more common than carcinoma – occurring most in the dog. Tumours are often functional, causing bone resorption and hypercalcaemia as more PTH is circulating. Can lead to pathological fractures. Grossly appear as enlarged parathyroid gland within atrophied thyroid gland
• Psuedohyperparathyroidism occurs due to hypercalcaemia of malignancy e.g. apocrine adenocarcinoma of the anal sac, lymphoma, or metastatic neoplasia to bones.
• Secondary hyperparathyroidism usually occurs due to renal disease or as a nutritional condition (low calcium and/or high phosphorus)
• Hypoparathyroidism is more common in small breed dogs than other species. It is usually caused by lymphocytic thyroiditis. Can also occur if the parathyroid glands are mistakenly removed in thyroidectomy, causing a progressive decrease in serum calcium concentration.
• Islets of Langerhans are composed of three cell types: alpha cells which produce glucagon, beta cells which produce insulin and delta cells which produce somatostatin.

  In diabetes mellitus there is a relative or complete lack of insulin produced from beta cells (hypofunction), especially in dogs. This could be due to:

  • Destruction of islet cells secondary to pancreatitis
  • Amyloid deposition in islets (esp cats)
  • Idiopathic pancreatic atrophy
  • Hypoplasia
• The pathogenesis and pathology of diabetes mellitus:

  Reduced availability of insulin leads to hyperglycaemia. This impairs the function of leucocytes, leading to reduced resistance to infection. There is resultant hepatic fatty changes and renal glomerular sclerosis by glycoprotein deposition. Cataracts may also form as the sorbitol pathway metabolises glucose in the lens.
• Diabetes insipidus is unrelated to the pancreas – it is a central (neurohyphyseal) disorder or a peripheral (nephrogenic) disorder:

  • Neurohyphyseal is production of inadequate ADH due to neoplasms, cysts, inflammatory lesions or trauma to the pituitary gland
  • Nephrogenic is an inability of renal epithelial cells to adequately respond to ADH. Either due to a congenital lack of receptors or blockage of ADH receptors by antibodies.
• An insulinoma is a neoplasia of pancreatic islet beta cells, most commonly carcinoma, but adenomas are possible. They are usually functionally active, overproducing insulin, leading to hypoglycaemia. Usually locally invasive but may also metastasise to panctreatic lymph nodes and distant sites.
• Other endocrine pancreatic neoplasias include:

  • Gastrinoma: a rare gastrin producing tumour which leads to hypersecretion of gastric acid, causing ulceration of GI mucosa
  • Glucagonoma: a rare tumour which produces glucagon, causing hyperglycaemia.
• Chemoreceptor organs are present at several sites, including the carotid and aortic bodies (as well as many other areas). ‘heart base’ tumours are the most common tumours of chemoreceptors, where multicentric tumours of chemoreceptor tissue occur – brachycephalic breeds are at particular risk.
• Heart base tumours (chemodectomas) are most commonly aortic body adenoma or carcinoma. Most common in dogs, with adenomas being more frequent. The mass forms around the base of the heart, with carcinomas capable of invading the atria and pulmonary artery. These are non-functional and metastasis is uncommon, but cause issues as they are space occupying.