Endocrine Pathology

Pathogenic Mechanisms of Endocrine Disease
1. 1) Primary Gland Hypofunction
  1. Destruction of secretory cells by a disease process (e.g. immune mediated or other inflammatory injury in thyroids, parathyroids or adrenal cortex)
  2. Failure of Gland development (Hypoplasia or agenesis)
  3. Biochemical defect in synthetic pathway of the hormone (usually genetic aberrations & not commonly identifed in vet species)
2. 2) Secondary Gland Hypofunction
  1. Destruction of glandular tissue or pituitary leading to failure of secretion of trophic hormone
    1. => Hypofunction of target organ
      1. Ex. Endochronologically inactive pituitary neoplasms interefere w/ secretion & release of ACTH, TSH & FSH
        => Clinically detectable hypofunction of adrenal cortex, thyroid follicular cells & gonads => Ensuing atrophy
3. 3) Primary Gland Hyperfunction
  1. One of the Most Common
  2. Hyperplasia/neoplasia of endocrine cells is involved
    1. The primary source synthesises & secretes hormone autonomously at a rate in excess of the ability of the body to utilise & degrade th ehormone
4. 4) Secondary Gland Hyperfunction
  1. Lesion in one gland causes excessive trophic hormone secretion which results in long-term hypersecretion in a target organ
    1. Ex. Canine ACTH-secreting pituitary tumor => Adrenal cortical hyperplasia/hypertrophy & Hypercorticolism (Canine Cushing's Syndrome)
5. 5) Hypersecretion of Hormones or Hormone-like factors by non-endocrine tumors
  1. Ex. Adenocarcinoma of the anal sac apocrine glands in Dogs
    1. Produces parathyroid hormone-related peptide (PTHRP) => pseudo-hyperparathyroidism => Hypercalcaemia
  2. Ex. Some canine lymphomas (lymphosarcomas) may also exhibit a similar effect (i.e. the tumor secretes or is associated w/ a factor which induces hypercalcaemia)
6. 6) Failure of Target cell response
  1. May be a failure of the cell surface receptor mechanism
  2. Lack of a 2nd intracellular messenger (e.g. cAMP) response
  3. Ex. Diabetes mellitus (Insulin resistance in Obesity - receptor loss in connective tissue cells, which then fail to react to insulin)
7. 7) Endocrine Hyperactivity 2ndary to disease in other organs
  1. Disease in one organ results in hyperfunction of an endocrine gland
  2. Ex. 2ndary hyperparathyroidism associated w/ chronic renal failure
    1. Retention of phosphorous & alterations in Vit. D metabolism lead to hypercalcaemia, w/ resultant hyperparathyroidism & skeletal demineralization
8. 8) Abnormal Hormone Degradation
  1. Decreased degradation: Can manifest as Hypersecretion
  2. Increased degradation: May relate to chronic drug administration
9. 9) Iatrogenic Causes
  1. Long term administration of hormones may lead to direct or indirect effects
  2. Ex. Corticosteroid excess -> Cortisol -> muscle weakness, calcinosis cutis, hair loss & adrenal cortical atrophy
Pituitary Gland
1. Pituitary Cysts
  1. Pituitary Dwarfism (Juvenile panhypopituitarism)
    1. Most common in German Shepards
    2. Most cases: Due to failure of the oropharnygeal ectoderm to differentiate into pars distalis
      1. Associated w/ development of a pituitary cyst
        Signs become apparent at 2 months of age: Retention of puppy coat progressing to bilaterally symmetrical alopecia & hyperpigmented skin
2. Neoplasia (Pituitary)
  1. ACTH secreting adenomas
    1. Most common in the Dog
    2. Leads to syndrome of cortisol excess (Cushing's syndrome)
  2. Pars intermedia neoplasia (Horse)
    1. Although some tumors are endochrinologically active, many of the features in equine disease are associated w/ the compression effect on the hypothalamus by the pituitary neoplasm
    2. Affects: seasonal shedding of hair, appetite, body temperature
  3. Non-functional pituitary neoplasms
    1. Combination of atrophy of surrounding pituitary & local extension into the brain can cause a range of problemms
      1. => Weakness, collapse, blindness
  4. Pituitary carcinoma
    1. Rare
    2. Usually endochronologically inactive
Adrenal Gland
1. Hypofunction
  1. Hypoadrenocorticism (Addison's Disease)
    1. Can occur due to bilateral idiopathic atrophy (immune mediated)
      1. Inflammation
        Bilateral Haemorrhage (sepsis related)
    2. Mineralocorticoid insufficiency
      1. Alterations in Na, K, Cl levels
        Can result in bradycardia (Hyperkalaemia)
    3. Glucocorticoid insufficiency
      1. Hypoglycaemia
2. Hyperfunction
  1. Canine Cushing's Disease
    1. Most common cause: functional corticotroph pituitary gland adenoma => Bilateral adrenal gland hyperplasia
    2. Note: Severity of the syndrome bears no relation to the size of the neoplasia
    3. Less common cause (10-15% cases): Functional adrenal gland neoplasia
    4. Pathogenesis: Gluconeogenesis , protein catabolism, lipolysis & anti-inflammatory effects due to glucocorticoids
      1. => Weakening of muscles (trembling, lordosis, pendulous abdomen, atrophy of temporal muscles)
        => Hepatomegaly (Due to steroid hepatopathy - increased deposits of lipid & glycogen)
        => Skin lesions (Atrophy of epidermis & adnexae, cutaneous calcification -30% cases - Ca is deposited along dermal connective tissue fibres & can penetrate the already atrophied skin)
        => Calcification in lungs, muscle & stomach
        => Increased appetite (Direct effect of cortisol &/or destruction of appetite centre in hypothalamus)
3. Adrenal Hyperplasia
  1. Nodular hyperplasia of Cortex (Common)
    1. Usually multiple & bilateral (Dog, Cat, Horse)
  2. Diffuse Hyperplasia
    1. Seen w/ functional tumors of pituitary gland
4. Adrenal Neoplasia
  1. Cortical adenomas
    1. Often incidental finding
    2. May arise in glands w/ existing nodular hyperplasia
  2. Cortical Carcinomas
    1. Less common than adenoma
    2. Can be bilateral
      1. If functional, these tumors will result in marked atrophy of the contralateral gland
        Clinical signs: as described for Cushing's disease + the potential for invasion of major vessels & distant metastases
    3. Cattle & Dogs > Other species
  3. Medullary phaeochromocytoma
    1. Cattle & Dogs > other species
    2. Can be large & invade locally to caudal vena cava plus distant metastases
      1. Some may be functional w/ signs relating to adrenaline/noradrenaline excess => Tachycardia, Cardiac hypertrophy
Endocrine Pancreas
1. Diabetes Mellitus
  1. Aetiology
    1. Relative or absolute lack of Insulin from pancreatic Beta cells (i.e. hypofunction)
      1. Destruction of islet cells secondary to pancreatitis
        The exocrine pancreas initially is inflamed, the rxn spreads to & involves the islets of Langerhans
        Condition can be chronic & relapsing, with gradual replacement of pancreatic tissue by fibrosis
      2. Amyloid Deposition in Islets of Langerhan(Cats)
        Note: Older Cats often have scattered amyloid deposits in islets w/o signs of diabetes mellitus
      3. Idiopathic Pancreatic Atrophy
      4. Hypoplasia
  2. Pathology
    1. Reduced availability of Insulin -> Hyperglycaemia
      1. Weight loss & weakness
        Reduced resistance to infection (Leukocyte function is impaired)
        Hepatic fatty change (can lead to cirrhosis in some cases)
        Cataracts -> bilateral lens opacity (due to sorbitol pathway metabolism of glucose by the lens)
        Renal glomerular sclerosis (Deposits of glycoprotein in the glomeruli)
  3. Common in Dogs (esp. Females)
2. Endocrine Pancreatic Neoplasia
  1. Insulinoma
    1. Neoplasia of pancreatic Beta cells
    2. Carcinomas are more common than adenomas
      1. Usually functionally active -> Marked systemic effects
        Functional tumors => Hypoglycaemia
        Over time, hypoglycaemia => Neuronal necrosis
        More common in duodenal limb of pancreas
        Weakness, ataxia, altered temperament (which can progress to seizures & collapse)
  2. Gastrinoma
    1. Uncommon compared to insulinoma
    2. Gastrin causes hypersecretion of gastric acid -> Ulceration of gastrointestinal mucosa
      1. Vomiting, diarrhoea & weight loss
        Invade pancreas, then spread to lymph nodes & liver
  3. Glucagonoma
    1. Rare
    2. Glucagon induces hyperglycaemia
Thyroid Gland
1. Develomental Disorders
  1. Accessory thyroid tissue
    1. Common
    2. Remnants of embryological development of thyroid gland
      1. Usually in mediastinum, often in heart base area
  2. Thyroglossal Duct Cysts
    1. In ventral cervical region, fluctuant cysts
      1. Can become neoplastic
2. Hypothyroidism
  1. Imp. in Dog (Uncommon in other species)
  2. Idiopathic follicular atrophy
    1. Slowly progressive replacement of the gland by adipose tissue
  3. Lymphocytic thyroiditis
    1. Lymphocytic infiltration into the gland as a consequence of autoantibody formation
  4. Extrathyroidal Effects of Hypothyroidism
    1. Reduced BMR
    2. Skin
      1. Bilaterally symmetrical alopecia (esp. tail & neck area)
      2. Hyperkeratosis & Hyperpigmentation
      3. Myxoedema can lead to thickening of the skin (due to dermal accumulation of glycosaminoglycans & hyaluronic acid)
    3. Reproductive system
      1. Reduced sperm count, reduced/absent oestrus
    4. Metabolic alterations
      1. Marked increase in cholesterol levels, which in turn can lead to enlarged liver, atherosclerosis & glomerular & corneal lipidosis
3. Hyperthyroidism
  1. Common in Cats
    1. Even w/ functional thyroid neoplasia in Dogs, it is uncommon to see hyperthyroidism since they are more able to excrete excess thyroid hormones
  2. Polyuria, Polydypsia, Polyphagia
    1. Weight loss
      1. Hyperexcitability
        Heat intolerance
        Cardiac alterations (Hypertrophic cardiomyopathy, Tachycardia, Dysrhythmia)
4. Thyroid Gland Hyperplasia
  1. Goitre
    1. Non-neoplastic, non-inflammatory enlargement of the thyroid gland
    2. Diffuse goitre occurs in animals w/ an iodine deficient diet
  2. Nodular Hyperplasia
    1. Multiple small nodules within the gland
    2. Usually functional in the Cat (rarely functional in other species)
5. Thyroid Gland Neoplasia
  1. Follicular adenoma
    1. Discrete capsule & usually solitary (compare to nodular hyperplasia)
    2. More common in Cats
  2. Follicular Carcinoma
    1. Locally invasive & often metastasize
    2. Can arise in extrathyroidal tissue
    3. More common in Dogs
  3. C-cell Neoplasia
    1. Most common in Bulls
      1. Thought to relate to high Ca2+ diet causing stimulation of the thyroid C-cells
    2. May be found in association with phaeochromocytomas & pituitary adenomas (multiple endocrine neoplasia - MEN)
Parathyroid Glands
1. Hyperparathyroidism
  1. Primary Hyperparathyroidism
    1. Chief cell neoplasia
    2. Adenoma more common than carcinoma
    3. Most common in Dogs
    4. Often functional tumors (Increased levels of PTH) => Bone resorption & hypercalcaemia
      1. May cause pathological fractures of the bones
  2. Secondary Hyperparathyroidism
    1. Renal secondary hyperparathyroidism
    2. Nutritional secondary hyperparathyroidism (Low Ca2+ &/or high P)
  3. Pseudohyperparathyroidism
    1. Humoral hypercalcaemia of malignancy (e.g. apocrine adenocarcinoma of anal sac, lymphosarcoma, metastatic neoplasia to the bone)
2. Hypoparathyroidism
  1. Most common in small breed Dogs
  2. Usually caused by lymphocytic thyroiditis
    1. Clinical Signs (relate to consequences of progressive decline in serum Ca2+): Neuromuscular excitability
  3. Note: Potential to remove parathyroid glands during surgery
Chemoreceptor Organs
1. Present at several sites (including carotid & aortic bodies) in many areas of the body -> Heart base tumors are most frequent
2. Aortic body Adenoma & carcinoma
  1. Most common in Dogs (brachycephalic breeds)
  2. Adenomas are more common than carcinomas (most often seen as a mass of or multiple nodules around the base of the heart)
    1. Carcinomas can invade the pulmonary artery or atria (although distant metastases are uncommon)
      1. They are non-functional, but can cause problems due to their space occupying effect
  3. In addition to aortic body tumors, ectopic thyroid tissue can cause tumor formation in the region of the base of the heart
3. Carotid body adenoma & carcinoma
  1. Arise near bifurcation of common carotid artery
    1. Due to proximity to the artery and nerves -> excision/biopsy can be difficult
      1. Carotid body tumors tend to be more malignant then aortic body
4. Multicentric tumors of chemoreceptor tissue occur (esp. in brachycephalic breeds)

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Endocrine Pathology

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	Created by melian.yates about 11 years ago