Endocrine Pathology

Endocrine Pathology

1. Pathogenic Mechanisms of Endocrine Disease

   • 1) Primary Gland Hypofunction
     • Destruction of secretory cells by a disease process (e.g. immune mediated or other inflammatory injury in thyroids, parathyroids or adrenal cortex)
     • Failure of Gland development (Hypoplasia or agenesis)
     • Biochemical defect in synthetic pathway of the hormone (usually genetic aberrations & not commonly identifed in vet species)
   • 2) Secondary Gland Hypofunction
     • Destruction of glandular tissue or pituitary leading to failure of secretion of trophic hormone
       • => Hypofunction of target organ
         • 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) Primary Gland Hyperfunction
     • One of the Most Common
     • Hyperplasia/neoplasia of endocrine cells is involved
       • The primary source synthesises & secretes hormone autonomously at a rate in excess of the ability of the body to utilise & degrade th ehormone
   • 4) Secondary Gland Hyperfunction
     • Lesion in one gland causes excessive trophic hormone secretion which results in long-term hypersecretion in a target organ
       • Ex. Canine ACTH-secreting pituitary tumor => Adrenal cortical hyperplasia/hypertrophy & Hypercorticolism (Canine Cushing's Syndrome)
   • 5) Hypersecretion of Hormones or Hormone-like factors by non-endocrine tumors
     • Ex. Adenocarcinoma of the anal sac apocrine glands in Dogs
       • Produces parathyroid hormone-related peptide (PTHRP) => pseudo-hyperparathyroidism => Hypercalcaemia
     • 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) Failure of Target cell response
     • May be a failure of the cell surface receptor mechanism
     • Lack of a 2nd intracellular messenger (e.g. cAMP) response
     • Ex. Diabetes mellitus (Insulin resistance in Obesity - receptor loss in connective tissue cells, which then fail to react to insulin)
   • 7) Endocrine Hyperactivity 2ndary to disease in other organs
     • Disease in one organ results in hyperfunction of an endocrine gland
     • Ex. 2ndary hyperparathyroidism associated w/ chronic renal failure
       • Retention of phosphorous & alterations in Vit. D metabolism lead to hypercalcaemia, w/ resultant hyperparathyroidism & skeletal demineralization
   • 8) Abnormal Hormone Degradation
     • Decreased degradation: Can manifest as Hypersecretion
     • Increased degradation: May relate to chronic drug administration
   • 9) Iatrogenic Causes
     • Long term administration of hormones may lead to direct or indirect effects
     • Ex. Corticosteroid excess -> Cortisol -> muscle weakness, calcinosis cutis, hair loss & adrenal cortical atrophy

2. Pituitary Gland

   • Pituitary Cysts
     • Pituitary Dwarfism (Juvenile panhypopituitarism)
       • Most common in German Shepards
       • Most cases: Due to failure of the oropharnygeal ectoderm to differentiate into pars distalis
         • 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
   • Neoplasia (Pituitary)
     • ACTH secreting adenomas
       • Most common in the Dog
       • Leads to syndrome of cortisol excess (Cushing's syndrome)
     • Pars intermedia neoplasia (Horse)
       • 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
       • Affects: seasonal shedding of hair, appetite, body temperature
     • Non-functional pituitary neoplasms
       • Combination of atrophy of surrounding pituitary & local extension into the brain can cause a range of problemms
         • => Weakness, collapse, blindness
     • Pituitary carcinoma
       • Rare
       • Usually endochronologically inactive

3. Adrenal Gland

   • Hypofunction
     • Hypoadrenocorticism (Addison's Disease)
       • Can occur due to bilateral idiopathic atrophy (immune mediated)
         • Inflammation
           • Bilateral Haemorrhage (sepsis related)
       • Mineralocorticoid insufficiency
         • Alterations in Na, K, Cl levels
           • Can result in bradycardia (Hyperkalaemia)
       • Glucocorticoid insufficiency
         • Hypoglycaemia
   • Hyperfunction
     • Canine Cushing's Disease
       • Most common cause: functional corticotroph pituitary gland adenoma => Bilateral adrenal gland hyperplasia
       • Note: Severity of the syndrome bears no relation to the size of the neoplasia
       • Less common cause (10-15% cases): Functional adrenal gland neoplasia
       • Pathogenesis: Gluconeogenesis , protein catabolism, lipolysis & anti-inflammatory effects due to glucocorticoids
         • => 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)
   • Adrenal Hyperplasia
     • Nodular hyperplasia of Cortex (Common)
       • Usually multiple & bilateral (Dog, Cat, Horse)
     • Diffuse Hyperplasia
       • Seen w/ functional tumors of pituitary gland
   • Adrenal Neoplasia
     • Cortical adenomas
       • Often incidental finding
       • May arise in glands w/ existing nodular hyperplasia
     • Cortical Carcinomas
       • Less common than adenoma
       • Can be bilateral
         • 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
       • Cattle & Dogs > Other species
     • Medullary phaeochromocytoma
       • Cattle & Dogs > other species
       • Can be large & invade locally to caudal vena cava plus distant metastases
         • Some may be functional w/ signs relating to adrenaline/noradrenaline excess => Tachycardia, Cardiac hypertrophy

4. Endocrine Pancreas

   • Diabetes Mellitus
     • Aetiology
       • Relative or absolute lack of Insulin from pancreatic Beta cells (i.e. hypofunction)
         • 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
         • Amyloid Deposition in Islets of Langerhan(Cats)
           • Note: Older Cats often have scattered amyloid deposits in islets w/o signs of diabetes mellitus
         • Idiopathic Pancreatic Atrophy
         • Hypoplasia
     • Pathology
       • Reduced availability of Insulin -> Hyperglycaemia
         • 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)
     • Common in Dogs (esp. Females)
   • Endocrine Pancreatic Neoplasia
     • Insulinoma
       • Neoplasia of pancreatic Beta cells
       • Carcinomas are more common than adenomas
         • 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)
     • Gastrinoma
       • Uncommon compared to insulinoma
       • Gastrin causes hypersecretion of gastric acid -> Ulceration of gastrointestinal mucosa
         • Vomiting, diarrhoea & weight loss
           • Invade pancreas, then spread to lymph nodes & liver
     • Glucagonoma
       • Rare
       • Glucagon induces hyperglycaemia

5. Thyroid Gland

   • Develomental Disorders
     • Accessory thyroid tissue
       • Common
       • Remnants of embryological development of thyroid gland
         • Usually in mediastinum, often in heart base area
     • Thyroglossal Duct Cysts
       • In ventral cervical region, fluctuant cysts
         • Can become neoplastic
   • Hypothyroidism
     • Imp. in Dog (Uncommon in other species)
     • Idiopathic follicular atrophy
       • Slowly progressive replacement of the gland by adipose tissue
     • Lymphocytic thyroiditis
       • Lymphocytic infiltration into the gland as a consequence of autoantibody formation
     • Extrathyroidal Effects of Hypothyroidism
       • Reduced BMR
       • Skin
         • Bilaterally symmetrical alopecia (esp. tail & neck area)
         • Hyperkeratosis & Hyperpigmentation
         • Myxoedema can lead to thickening of the skin (due to dermal accumulation of glycosaminoglycans & hyaluronic acid)
       • Reproductive system
         • Reduced sperm count, reduced/absent oestrus
       • Metabolic alterations
         • Marked increase in cholesterol levels, which in turn can lead to enlarged liver, atherosclerosis & glomerular & corneal lipidosis
   • Hyperthyroidism
     • Common in Cats
       • Even w/ functional thyroid neoplasia in Dogs, it is uncommon to see hyperthyroidism since they are more able to excrete excess thyroid hormones
     • Polyuria, Polydypsia, Polyphagia
       • Weight loss
         • Hyperexcitability
           • Heat intolerance
             • Cardiac alterations (Hypertrophic cardiomyopathy, Tachycardia, Dysrhythmia)
   • Thyroid Gland Hyperplasia
     • Goitre
       • Non-neoplastic, non-inflammatory enlargement of the thyroid gland
       • Diffuse goitre occurs in animals w/ an iodine deficient diet
     • Nodular Hyperplasia
       • Multiple small nodules within the gland
       • Usually functional in the Cat (rarely functional in other species)
   • Thyroid Gland Neoplasia
     • Follicular adenoma
       • Discrete capsule & usually solitary (compare to nodular hyperplasia)
       • More common in Cats
     • Follicular Carcinoma
       • Locally invasive & often metastasize
       • Can arise in extrathyroidal tissue
       • More common in Dogs
     • C-cell Neoplasia
       • Most common in Bulls
         • Thought to relate to high Ca2+ diet causing stimulation of the thyroid C-cells
       • May be found in association with phaeochromocytomas & pituitary adenomas (multiple endocrine neoplasia - MEN)

6. Parathyroid Glands

   • Hyperparathyroidism
     • Primary Hyperparathyroidism
       • Chief cell neoplasia
       • Adenoma more common than carcinoma
       • Most common in Dogs
       • Often functional tumors (Increased levels of PTH) => Bone resorption & hypercalcaemia
         • May cause pathological fractures of the bones
     • Secondary Hyperparathyroidism
       • Renal secondary hyperparathyroidism
       • Nutritional secondary hyperparathyroidism (Low Ca2+ &/or high P)
     • Pseudohyperparathyroidism
       • Humoral hypercalcaemia of malignancy (e.g. apocrine adenocarcinoma of anal sac, lymphosarcoma, metastatic neoplasia to the bone)
   • Hypoparathyroidism
     • Most common in small breed Dogs
     • Usually caused by lymphocytic thyroiditis
       • Clinical Signs (relate to consequences of progressive decline in serum Ca2+): Neuromuscular excitability
     • Note: Potential to remove parathyroid glands during surgery

7. Chemoreceptor Organs

   • Present at several sites (including carotid & aortic bodies) in many areas of the body -> Heart base tumors are most frequent
   • Aortic body Adenoma & carcinoma
     • Most common in Dogs (brachycephalic breeds)
     • Adenomas are more common than carcinomas (most often seen as a mass of or multiple nodules around the base of the heart)
       • Carcinomas can invade the pulmonary artery or atria (although distant metastases are uncommon)
         • They are non-functional, but can cause problems due to their space occupying effect
     • In addition to aortic body tumors, ectopic thyroid tissue can cause tumor formation in the region of the base of the heart
   • Carotid body adenoma & carcinoma
     • Arise near bifurcation of common carotid artery
       • Due to proximity to the artery and nerves -> excision/biopsy can be difficult
         • Carotid body tumors tend to be more malignant then aortic body
   • Multicentric tumors of chemoreceptor tissue occur (esp. in brachycephalic breeds)

Images and files in the map