Pathology of the Endocrine System 2 Flashcards
-Adrenal cortical and medullary hyperfunction - causes and consequences -Thyroid and parathyroid hypofunction- causes and consequences -Thyroid hyperfunction- causes and consequences.
ADRENAL CORTICAL HYPERFUNCTION
Most commonly seen due to functional neoplasms within the adrenal cortex- adenomas (benign glandular epithelial), adenocarcinomas (malignant).
Unilateral or bilateral.
PRIMARY HYPERADRENOCORTICISM- caused by the adrenal glands themselves.
Causes the clinical condition Cushing’s syndrome (see also pituitary hyperfunction)
Aldosterone, cortisol and androgens will be affected.
Aldosterone is the MOST concerning, as it will cause interruptions with fluid balance.
Androgens are of concern in breeding animals.
The pituitary will atrophy due to decreased ACTH production (negative feedback)
The contralateral adrenal will atrophy.
OVERPRODUCTION OF CORTISOL
From the zona fasciculata of the adrenal cortex, in hyperadrenocorticism.
-GLUCONEOGENIC
-LIPOLYTIC
-PROTEIN CATABOLIC (causes thin, flabby abdominal wall)
-ANTI-INFLAMMATORY
Disease is insidious and slowly progressive. Symptoms can take a long time to notice.
Eventually leads to Cushing’s syndrome.
CONSEQUENCES OF ADRENAL CORTICAL HYPERFUNCTION
Increased cortisol
-> non-pruritic, bilaterally symmetrical alopecia, PU/PD, immune suppression (leading to secondary infection), altered metabolism.
Altered metabolism leads to: increased protein catabolism -> muscle wasting; polyphagia; increased glycogen metabolism in liver -> vacuolar hepatopathy.
CUSHING’S SYNDROME
Can be caused by:
- Anterior pituitary neoplasia- PITUITARY DEPENDENT hyperadrenocorticism (PDH).
- Adrenal cortical neoplasia- ADRENAL DEPENDENT hyperadrenocorticism (ADH)
- IATROGENIC Cushing’s- caused by endogenous steroid therapy acting in lieu of the adrenal cortex. eg. chronic steroid therapy in cats- give drug every other day to try and minimise the effects of endogenous steroids and allow the adrenals time to regulate.
Animals present similarly for all three forms (pituitary, adrenal, iatrogenic). Routine serum biochemistry is similar- require advanced serum biochemistry to differentiate forms. eg. ACTH stimulation test, dexamethasone suppression test (low dose/high dose).
CANINE CUSHING’S SYNDROME
PITUITARY DEPENDENT: Pituitary neoplasia increases ACTH production. This causes bilateral stimulation of the adrenals- increased cortisol seen from BOTH glands in 85% of cases.
INCREASED ACTH, INCREASED CORTISOL
ADRENAL DEPENDENT: Adrenal neoplasia on one gland causes increased cortisol from the affected gland. This exerts negative feedback on the pituitary, so less ACTH is produced (low ACTH).
The contralateral (unaffected) gland will atrophy.
LOW ACTH, INCREASED CORTISOL
ADRENAL MEDULLA HYPERFUNCTION
HYPOfunction is rare.
HYPERfunction is associated with functional neoplasia- PHEOCHROMOCYTOMA.
“If there is hyperfunction, there is probably a tumour”
CATECHOLAMINES (adrenaline, noradrenaline) are affected.
The clinical effect depends on the extent of the medullary hyperfunction.
PHEOCHROMOCYTOMA
Most common adrenal medullary tumour in cattle, dogs and other species.
These tumours are INFREQUENTLY functional.
If functional, they release catecholamines- this causes TACHYCARDIA, OEDEMA and CARDIAC HYPERTROPHY.
THYROID GLAND
CRUCIAL for metabolism.
Hypothalamus produced TRH, which stimulates the anterior pituitary to produce TSH.
TSH stimulates the thyroid gland to produce T3 and T4, which enter the circulation and act at distant target cells.
THYROID HYPOFUNCTION
Hypothyroidism.
Common in DOGS, usually primary.
Causes:
-Idiopathic follicular atrophy- spontaneous.
-Lymphocytic thyroiditis (immune mediated)- lymphocytes invade thyroid, causing inflammation and secondary damage to thyroid cells. Common in dogs.
-Secondary to decreased TSH release from pituitary.
-Goitre- dietary or toxic.
HYPOTHYROIDISM IN DOGS
Important disease in adult dogs.
Lesions- thyroid atrophy or lymphocytic thyroiditis.
Results in low basal metabolic rate, low T3, T4 levels, high serum cholesterol.
METABOLIC FINDINGS- Lethargy, weight gain (obesity), exercise intolerance.
DERMATOLOGICAL FINDINGS- hair thinning, poor coat quality, hyperpigmentation, pyoderma (bacterial infection of skin)
HYPOTHYROIDISM IN DOGS- PATHOLOGY
PRIMARY- small, pale thyroid.
SECONDARY- hyperkeratosis (thickened stratum corneum)
-hyperpigmentation (black basal layer, pigmentary incontinence)
-Myxoedema
-Atherosclerosis- fatty plaques/mineralisation in blood vessel walls. CLASSIC sign of hypothyroidism.
GOITRE
Special kind of thyroid dysfunction. Causes:
-IODINE DEFICIENCY
-IODINE TOXICITY (overdose)
-GOITROGENIC PLANTS.
Results in too little T3/T4 synthesis and BILATERAL ENLARGEMENT of thyroid glands.
Bilateral enlargement occurs due to imbalance between TSH from pituitary and T3/T4 from thyroids. Decreased T3/T4 production stimulates the hypothalamus- TRH stimulates increased TSH from pituitary. This stimulates the thyroid, causing hypertrophy, but not enough T3/T4 production still occurs, because there is too little iodine.
MECHANISMS FOR DEVELOPMENT OF GOITRE
- Dietary iodine deficiency (can be maternal deficiency, resulting in goitre in foetus- treat mother once foetal goitre is discovered- may be when stillbirth occurs)
- Block of iodine uptake
- Enzyme defect
- > hypothyroidism- seen in horse/pig/sheep/cow
- > goitre formation.
- > stillbirth/weak newborn animal with ENLARGED THYROID GLANDS.
DIETARY IODINE DEFICIENCY
Seen in foetuses when dam is deficient, because the foetus will be affected first. Treat mother once foetal goitre is discovered.
Can also be seen in adult animals.
Treat with iodised salt.
HYPOTHYROIDISM- BLOCK OF IODINE UPTAKE
GOITROGENS interferes with the synthesis of thyroid hormone.
These substances are found in Brassica plants- rape, kale etc.
Signs will be seen in offspring first- LIMIT feeding from Brassica family during pregnancy.
Can be seen with excess iodide in the diet- pregnant mares fed on dried seaweed.
Often fatal in neonates, but in older animals treatment can shrink the goitre.
HYPOTHYROIDISM: ENZYME DEFECT
DYSHORMOGENESIS- impaired thryoglobulin biosynthesis- due to enzyme defect.
Seen in sheep, goats and cattle.
Causes massive enlargement of thyroids. Circulating T3/T4 levels are low.
THYROID HYPERFUNCTION
Hyperthyroidism. Common in CATS.
Bilateral or unilateral.
Often due to FUNCTIONAL NEOPLASMS- adenoma (benign) or carcinoma (malignant).
Can also be due to benign hyperplasia.
PRIMARY HYPERPARATHYROIDISM
THYROID is affected. eg. multinodular hyperplasia, thyroid neoplasia (tumour).
- > feline hyperthyroidism- increased T3/T4 levels.
- > increased metabolic rate, cardiac hypertrophy (dilated atrium, thickened ventricles), sudden death.
SECONDARY HYPERARATHYROIDISM
PITUITARY is affected- produces excess TSH. Very rare.
- > feline hyperthyroidism- increased T3/T4 levels.
- > increased metabolic rate, cardiac hypertrophy(dilated atrium, thickened ventricles), sudden death.
NODULAR THYROID HYPERPLASIA
Causes primary hyperthyroidism. Common in older cats.
Contralateral thyroid is often hypoplastic.
Increased metabolic rate -> emaciation.
Cardiac hypertrophy
Sudden death
PARATHYROID GLANDS
The PARATHYROID glands play a central role in CALCIUM HOMEOSTASIS.
Hypocalcaemia stimulates parathyroid glands to release PTH (parathyroid hormone)
This acts systemically:
BONE- increased remodelling by osteoclasts releases calcium and phosphate in to circulation.
GUT- increased Ca absorption from gut.
KIDNEY- increased activation of vitamin D, promotion of calcium reabsorption.
High serum Ca levels inhibit PTH release.
PARATHYROID HYPOFUNCTION
RARE.
Seen if the parathyroid is removed- can occur accidentally with (bilateral) thyroidectomy- TRUE hypoparathyroidism.
No parathyroid means no reaction to low blood Ca- true hypoparathyroidism is potentially life threatening.
HYPOPARATHYROIDISM CAUSES HYPOCALCAEMIA
Initially, bone resorption maintains calcium, but this rapidly decreases over time.
Renal tubular absorption of phosphorous increases.
-> HYPOCALCAEMIA, HYPERPHOSPHATAEMIA.
Hypercalciuria is seen early on (losing Ca in urine because there is no PTH stimulation to promote resorption), hypocalciuria is seen later.
Hypophosphaturia is seen due to increased renal tubular absorption of phosphate.
Hypocalcaemic animals present clinically as nervous, restless, ataxic and weak with intermittent tremors of different muscle groups due to increased neuromuscular excitability. May progress to generalised tetany and convulsive seizures.
CAUSES OF HYPOCALCAEMIA
- Decreased PTH concentration- primary hypoparathyroidism, pseudohypoparathyroidism (decreased PTH receptor responsiveness)
- Inadequate mobilisation of Ca from bone or absorption in intestine- hypovitaminosis D (chronic renal failure)- decreased gut Ca absorption. Milk fever- massive Ca requirement in late pregnancy/early lactation.
- Other mechanisms- acute pancreatitis in dogs, urinary tract obstruction.
RICKETS
Lack of dietary Vitamin D- Ca/P/vitamin D IMBALANCE
- > RELATIVE hypocalcaemia (if P is high)/absolute hypocalcaemia
- > enlarged parathyroids (stimulated by TSH)
- > increased PTH synthesis and action
- > bone resorption and abnormalities of the growth plate.
- > long bone abnormalities, costochondral junction ‘nuggets’ due to relative hypocalcaemia.
CHELATION BY OXALATES
Leads to hypocalcaemia.
eg. Ethylene glycol poisoning (antifreeze)- CALCIUM OXALATE crystal formation- decreases circulating Ca.
-> crystals excreted in urine -> HYPOCALCAEMIA.
Crystals also damage the kidney -> renal tubular necrosis -> decreased reabsorption -> HYPOCALCAEMIA.
MALABSORPTION- PROTEIN LOSING ENTEROPATHY
PLE can cause hypocalcaemia.
Malabsorption due to gut damage leads to protein loss -> hypoalbuminaemia -> hypocalcaemia, as a percentage of Ca is bound to albumin- less albumin means less Ca.
Malabsorption of Ca from the damaged gut also occurs.
ACUTE PANCREATITIS
-> glucagon release -> stimulates THYROCALCITONIN release -> HYPOCALCAEMIA.
Usually mild, subclinical.
Thyrocalcitonin is the opposite of PTH- it is normally released when circulating Ca levels are too high.
