Endocrine - pathology Flashcards
In endocrine disease, what tends to cause the clinical signs?
The FUNCTIONAL effects of the altered hormone levels
Rather than physical effects of endocrine gland lesions - lots less common
What are the two mechanisms of increasing functional effects of hormones?
Hyperfunction - excess production of hormone
New source of hormone
What is primary hyperfunction?
Hormone secretion occurs independent of a stimulus
From a pathological change in the endocrine gland eg. hyperplastic or neoplastic cells
Causes autonomous secretion of excess hormone
What is secondary hyperfunction?
When the stimulus causing hyperfunction is outside the primary gland - extrinsic cause
What are some examples of secondary hyperfunction?
Functional lesion is on an endocrine gland producing excess stimulatory hormone
Or excess stimulation from negative feedback loops eg. from hypercalcaemia
What are two examples of a new source of hormones increasing functional effects of hormones on the body?
Exogenous - glucocorticoid administration
Endogenous - anal sac apocrine gland carcinoma producing PTHrp
What are two mechanisms that cause decreased functional effects of hormones on the body?
Hypofunction - insufficient production of hormone
Lack of response to a hormone
What causes primary hypofunction?
Impaired ability or lack of ability to produce hormone
What are two causes of congenital primary hypofunction?
Genetic mutation causing biochemical defect in hormone synthesis or activation
Developmental anomaly
What are 5 causes of acquired primary hypofunction?
Destruction of functional cells from -
Infections
Immune mediated disease
Treatments eg. radiotherapy, drugs
Vascular disease - infarcts
Neoplastic disease
What are two causes of secondary hypofunction?
Reduced stimulatory signal between endocrine glands causing subnormal hormone secretion
Or lack of substrate for hormone synthesis eg. nutritional deficiency
What causes lack of response to a hormone from the target tissue?
Primary disease
Or another disease condition in the body causing dysfunction to the target tissue
What are the main endocrine glands in the body?
Pituitary gland
Thyroids
Parathyroids
Adrenals
Pancreas
What hormones are produced in the adrenal gland (cortex)?
Mineralocorticoids - aldosterone
Glucocorticoids - cortisol
Sex steroids
What disease is hyperadrenocorticism known as?
Cushings syndrome
What is the endocrine pathway of cortisol?
Hypothalamus releases CRH
Acts on pituitary to release ACTH
Act on adrenals to release cortisol
What causes primary hyperadrenocorticism?
Functional tumour in the adrenal cortex
What are the consequences of primary hyperadrenocorticism?
Increased cortisol production
Negative feedback on hypothalamus/pituitary - decreased CRH/ACTH
Bilateral adrenal cortex atrophy
What are adrenal cortical tumours most common in? What type of tumour is most common?
Dogs - cortical adenomas
What tumour of the adrenal cortex doesnt cause hyperadrenocorticism but is a common incidental finding in older dogs/cats/horses?
Adrenal cortical nodular hyperplasia
What is secondary hyperadrenocorticism?
A functional pituitary tumour producing excess ACTH
What are the consequences of pituitary dependent secondary hyperadrenocorticism?
Increased cortisol
Bilateral HYPERTROPHY of the adrenal cortices
What is more common - primary or secondary pituitary dependent hyperadrenocorticism?
Secondary more common - 85% of cases are pituitary-dependent
What can cause iatrogenic hyperadrenocorticism?
Glucocorticoid administration
What are the consequences of glucocorticoid administration?
Reduced CRH and ADH
Bilateral adrenal cortex atrophy
What are the similarities and differences in primary and secondary (pituitary dependent) hyperadrenocorticism?
Primary - adrenal cortical atrophy, decreased ACTH
Secondary - adrenal cortical hypertrophy, increased ACTH
What is the name for hypoadrenocorticism?
Addisons disease
What occurs in primary hypoadrenocorticism?
Bilateral adrenocortical atrophy/destruction
What are 4 causes of primary hypoadrenocorticism?
Idiopathic
Adrenal inflammation
Vascular disease
Metastatic tumour
What are the consequences of primary hypoadrenocorticism?
Reduced synthesis of mineralocorticoids - aldosterone
Leads to disturbances in potassium, sodium and chloride - hyperkalaemia and hyponatremia
What are some causes of secondary hypoadrenocorticism?
Pituitary disease - uncommon
Iatrogenic - withdrawal of glucocorticoid therapy
What tumour can you get in the adrenal medulla? (uncommon)
Pheochromocytoma
What hormones do pheochromocytomas affect?
Catecholamines - adrenaline and noradrenaline
Where can pheochromocytoma spread to?
Local invasion
Metastatic spread via vena cava
What does insulin do?
Stimulates uptake of glucose into the tissues
Suppresses hepatic glucose production - gluconeogenesis
Stimulates glucose absorption from the GI tract
What are the two main mechanisms for diabetes mellitus?
Pancreatic beta cell hypofunction - insufficient insulin production (type 1)
Insulin resistance - reduced response to insulin by target cells or antagonism of insulin (type 2)
What is type S diabetes mellitus?
Destruction of beta cells by exocrine pancreatic disease eg. pancreatitis
Antagonism of insulin by other hormones/drugs
What is type 2 diabetes mellitus?
Complex multifactorial disease
Involving inadequate insulin production AND resistance to insulin in tissues
What type of diabetes mellitus do dogs get?
Beta cell destruction - pancreatitis, pancreatic necrosis or immune mediated (type 1, type S)
Insulin antagonism (type S)
What are some hormones that can cause insulin antagonism?
Progesterone - dioestrus, pregnancy
Cortisol - hyperadrenocorticism, glucocorticoids
Growth hormone
What type of diabetes mellitus do cats get?
Reduced insulin production and insulin resistance - type 2
What are the risk factors for cats getting diabetes mellitus?
Age
Obesity
Male
Burmese breed
How does chronic hyperglycaemia cause diabetes mellitus (type 2)?
Chronic hyperglycaemia causes deterioration of beta cell function
Reduces insulin secretion
Initially reversible by progresses to irreversible injury
What can cause beta cell hyperfunction - excess insulin production?
Insulin secreting beta cell tumour - insulinoma
Are insulinomas benign or malignant?
Malignant - 90% of cases
High risk of metastasis
What is the normal hypothalamic-pituitary-thyroid axis?
Hypothalamus releases TRH
Pituitary releases TSH
Thyroid gland releases T3 and T4
What causes primary hyperthyroidism?
Functional nodular hyperplasia or neoplasia
In one or both thyroids
What are the consequences of primary hyperthyroidism?
Increased T3 and T4
Reduction in TRH/TSH
What tumours of the thyroid do cats get?
Multinodular hyperplasia
Follicular adenoma
What tumours of the thyroid do dogs get?
Carcinomas - 90%
Invasive and metastasise to lungs and lymph nodes
But rarely cause hyperthyroidism
How does thyroid neoplasia differ between dogs and cats?
Cats more likely be benign or hyperplastic, but cause hyperthyroidism
Dogs more likely to be malignant carcinoma, but not cause hyperthyroidism
What is primary hypothyroidism?
Destruction of thyroid follicular cells
Causing insufficient production of thyroid hormones
What are the main causes of primary hypothyroidism in dogs?
Lymphocytic thyroiditis - autoantibodies in inflammatory cell infiltrate causing degeneration of thyroid follicular cells
Idiopathic follicular atrophy
What are 2 less common causes of hypothyroidism in dogs?
Destruction of thyroid glands by neoplasms
Secondary hypothyroidism from pituitary lesion - insufficient release of TSH
What is the main species affected by hypothyroidism?
Dogs
What cells produce PTH?
Chief cells in the parathyroid gland
What are the methods of action of PTH?
Increases calcium reabsorption in bones, GI tract and kidneys
Decreases phosphorus reabsorption in the kidneys
Activates calcitriol (vitamin D) synthesis
What has suppressive regulatory action on PTH production?
Calcitriol
Increased blood Ca
What causes primary hyperparathyroidism?
Functional chief cell adenoma
Or nodular hyperplasia
What are the consequences of primary hyperparathyroidism on the parathyroid glands?
Atrophy - reduced PTH secretion from normal chief cells
What is humoral hypercalcaemia of malignancy?
Neoplasia producing parathyroid hormone related protein (PTHrp)
What are some tumours that produce PTHrp?
Anal sac apocrine gland carcinoma
Multiple myeloma
Lymphoma
What is renal secondary hyperparathyroidism?
Where renal disease causes hyperphosphataemia
This reduces calcitriol synthesis - less regulation on PTH
It also decreases blood calcium by reducing Ca uptake in GI tract
Increased PTH produced to compensate causes Ca resorption from bones
What is nutritional secondary hyperparathyroidism?
Dietary calcium:phosphate imbalance
And vitamin D deficiency
Increased PTH to compensate for low Ca - Ca resorption from bones
What bone condition occurs due to nutritional/renal secondary hyperparathyroidism?
Fibrous osteodystrophy - Ca resorption causes bone to be replaced with fibrous tissue
What animals are susceptible to nutritional secondary hyperparathyroidism?
Horses fed mostly grain and bran
Pig on unsupplemented rations
Dogs fed only meat or offal
To summarise what are the causes of hyperparathyroidism?
Primary - functional tumour/nodular hyperplasia
Secondary - chronic renal disease, nutritional imbalance
PTHrp - neoplastic disease
What is cushings called in horses?
Pituitary pars intermedia dysfunction (PPID)
What is pituitary pars intermedia dysfunction (PPID)?
Age related degeneration of the inhibitory dopaminergic neurones that regulate pars intermedia activity between the hypothalamus and the pituitary
Causing excess secretion of pars intermedia hormones and hyperplasia adenoma formation
Adenoma can compress pituitary and hypothalamus
What are the clinical manifestations of pituitary pars intermedia dysfunction (PPID)
Sweating
Fail to shed hair
Muscle weakness
Increased appetite
PUPD
Laminitis
Lethargy
What is diabetes insipidus?
Inability of the kidneys to concentrate urine due to loss of functional effects of ADH
What are the two mechanisms of diabetes insipidus?
Insufficient ADH production or release from hypothalamus/pituitary (central diabetes insipidus)
Renal tubules insensitive to ADH (nephrogenic diabetes insipidus)
What can cause central diabetes insipidus?
Injury/destruction of hypothalamus or pituitary - insufficient ADH production
eg. trauma, neoplasm, inflammatory disease
What can cause nephrogenic diabetes insipidus?
Primary - rare congenital diseases eg. mutation of ADH receptor
Secondary - diseases eg. pyometra, pyelonephritis, hyperadrenocorticism
What is acromegaly?
Growth hormone secretion by a functional pituitary tumour - usually adenoma
What species does acromegaly usually affect?
Cats
What are the consequences of acromegaly?
Broader face
Feet enlargement
Liver and kidney enlargement
Growth hormone has insulin antagonistic effects - can cause symptoms of diabetes mellitus
