endocrine Flashcards
endocrine
– cells respond to
factors (hormones) produced
by distant cells
thyroid anatomy
-pared organ, bilateral, connected at bottom
-1/4 width of trachea
-lots of collagen
parathryoid: partially embedded in thyroid gland, parathyroid is ontop of the thyroid gland. esp. cats
hormone synthesis in thyroid follicular cells
-iodine is being brought across, T3 and T4 are brought back through and released.
-cell needs AA, Carbs, regular amount iodine which are needed to synthesize thyroglobulin.
-T3/T4 have a negative feedback look with the hypothalamus, if you have an adenoma it can disrupt this. have TRH hypothalamus–> TSH anterior pituitary–> T3/T4
effects of thyroid hormones
Effect on many tissues
Normal development (brain) and growth
Increase metabolic rate
Increase lipid metabolism (lipylysis)
Increase glucose metabolism (glycolysis, glucose absorption)
Heart: Rate, output, vasodilatation
Brain: Alter mental state
Reproductive system
-T3/T4 amps up metabolism
reverse T3
-useless T3 (biologically inactive) in the body, converts t4-> T3 in states of
-protein starvation**
-liver and kidney disease
-febrile illness
congenital thyroid anomaly
Aplasia or Hypoplasia: Rare
Accessory thyroid tissue or
ectopic thyroid tissue***
Common in dogs from the Larynx to diaphragm but 50 % around intrapericardial aorta around base of heart, can become neoplastic
Differential diagnosis aortic base
tumors
Thyroglossal duct cysts: Ventral neck midline cervical region dog, can become neoplastic
- Parathyroid cysts: Bilaterally along trachea in cat.
incidental seline changes of the thyroid
-minerlization, lipofuscinosis, copora amyloidosis,
-horses: thyroid cysts normal
hypothyroidism
One of the MOST COMMON endocrinopathies in DOGS, but is rare in cats and uncommon in other species.
Affected dogs are usually between 4 and 10 years of age.
Mid to large breeds»_space;» Toy and miniature breeds
No sex predilection
thyroid gland lesions with hypothyroidism
Small thyroid gland:
Gland is destroyed or was never there. So no functional thyrocytes
Thyroiditis
Idiopathic follicular atrophy
Agenesis
Big:
Gland is continuously stimulated (hyperplastic and hypertrophic thyrocytes) by TSH because hormones not produced
Iodine deficiency/excess
Goitrogenic compounds
Defect in biosynthesis of hormones
-goiter thyroid in neonate from pregnant mother with low iodine.
clinical signs of hypothyroidism
Metabolic changes:
- Weight gain
- Cold intolerance**
- Lethargy
Skin:**
-Bilateral symmetrical thinning of hair
coat
- Scaliness of coat
- Hyperpigmentation of skin
- Secondary pyoderma
- Myxedema
-hair follicles are the targets of T3/T4 hormones
Reproductive:
- Anestrus**, lack of libido
- Joint Pain
Hypercholesterolemia:
- Atherosclerosis
- Lipid infiltration in liver, kidney and
cornea
Anemia
common causes hypothyroidism
Lymphocytic thyroiditis: Inflammatory
Idiopathic thyroid atrophy: degenerative
-75% tissue lost before clinical signs
Goiters (rare) from:
Iodine deficiency
Iodine excess
Goitrogenic compounds
Genetic
lymphocytic thyroiditis
Seen mostly in dogs
may or may not develop clinical hypothyroidism.
-antibodies to Thyroglobulin, Thyroperoxidase, TSH receptor
Similar to Hashimoto’s disease of humans
Gross appearance:
Slightly enlarged, normal size or smaller, pale, micro: lymphocytes
idiopathic follicular atrophy
Idiopathic: arising spontaneously or from an obscure or unknown cause
Primary degenerative disease of the thyrocytes
Replacement of the gland by adipose tissue
Not associated with inflammation
Distinct from the follicular atrophy due to decrease in TSH stimulation.
Thyroid follicles undergo involution
hyperplasia= goiter thyroid
-most common sheep, goats at birth: abortion with slow growth rate, lethargy and abnormal mentation.
-non neoplastic, non inflammatory enlargement of the thyroid gland due to increased TSH secretion resulting from inadequate thyroxine synthesis and decreased T3/T4.
hyperplasia= Goiters path causes 4
The four major pathologic mechanisms include:
1.) Iodine deficient diet**
Feed deficiency less common – born dead or weak
Can be exacerbated by goitrogenic compounds
Begins as a hyperplastic goiter -> colloid goiter with correction of diet
Excess dietary iodine**
High intake leads to inhibition of thyroid peroxidase -> decreases the
organification of iodine -> decreased thyroixine
Goitrogenic compounds interfering with thyroxinogenesis: Brassica plants
Genetic enzyme defects in hormone synthesis
goiter thyroid 3 morphological causes
1.) Diffuse Hyperplastic Goiter:
More common in young animals born to dams on iodine deficient diet or excess iodide or dams fed goitrogenic substances.
2.) Colloid goiter:
Represents involutionary phase of hyperplastic goiter (recovery following correction of the problem in diffuse hyperplastic goiter).
3.) Congenital dyshormonogenetic goiter (inherited goiter):
Autosomal recessive disorder in some breeds of sheep, goats and cattle; rare in dogs and cats (more common in children).
Result of genetic impairment of thyroglobulin synthesis; T4 & T3 levels are low even though iodine uptake and turnover are increased.
-symmetrically enlagred at birth
thyroid hyperplasia/ musculoskeletal syndrome in horses
Hyperplastic goiters
Mandibular prognathia
Flexural deformity**
Ruptured tendons of the common
digital extensor muscles
Delayed ossification of carpal bones
hyperthyroidism
-most common endocrinopathie in CATS
DISCRETE ADENOMAS or HYPERPLASTIC NODULES seen grossly
Follicles (on histo) outside the adenomas or nodular hyperplasia may be atrophied (decreased TSH due to feedback)
Carcinomas are uncommon in cats
clinical signs/ lesions with hyperthyroidism
-metabolic changes: hyperactivity, PU/PP/PD **, weight loss
-skin: rough coat, cervical swelling, coughing and dyspenia due to enlarged gland.
-heart: left ventricular hypertrophy in cats if left untreated, can get to HCM
-tachycardia/ murmor
- 10-15% of cats present with overt
congestive heart failure (dyspnea,
muffled heart sounds, ascites
multifocal nodular hyperplasia of the thyroid
-idiopathic, incidental lesion in old animals exept CATS where it may be functional
follicular cell adenoma in thyroid
-more common and may be functional in cats
-also in horses(white) dogs
hyperthyroidism in dogs
-rare Occurs in middle aged and older dogs (7-15 years)
Clinical findings can be similar to cats with hyperthyroidism
Discrete Adenomas or hyperplastic nodules (not common)
THYROID CARCINOMAS
Follicular cell adenocarcinoma
May or may not be functional
Highly aggressive and invasive, may become fixed or invade lungs, thyroid vein, lymph nodes.
parafollicular cells
C cells are found between follicles or follicular cells and are derived
from neural crest cells.
Secretory granules contain calcitonin (CT), an emergency hormone, which protects against hypercalcemia by:
Inhibiting bone resorption
Diuresis of Ca2
parathyroid feedback
PTH and CT act in concert to keep [Ca2+] in the ECF within narrow
limits
PTH level is controlled by direct feedback control system based on [Ca2+ /P] in the blood
Protects against hypocalcemia by
increasing intestinal absorption of calcium (with Vit D3)
Stimulating bone resorption of calcium
Enhances renal tubular reabsorption of calcium
hypoparathyroidism causes
Lymphocytic parathyroiditis: Believed to be immune-mediated
Parturient Paresis (Milk Fever): Occurs in cows fed a high calcium diet before parturition
Other causes include:
Destruction of the parathyroids by neoplasms, accidental removal during thyroid
surgery or long-term hypercalcemia from ingestion of calcinogenic plants like Cestrum
diurnum.
hyperparathyroidism primary vs secondary
-primary:
- parathyroid adenomas usually in older dogs (single, encapsulated, functional tumors produce excess PTH will see atrophy of para gland
-secondary:
due to nutritional imbalances
-excess dietary P, N or low Ca and vitamin D3.
-bran diets in horses
-meat diets in cats/ dogs
renal: response to hypercalcemia and progressive hyperphosphatemia due to decreased GFR, low calcium
secondary will lead to prolonged hypocalemia –> hyperplasia of cheif cells –> bilateral enlargement of parathyroid gland
-excess PTH can lead to fibrous osteodystrophy from bone resorption, bones become swollen.
hypercalcemia of malignancy
Paraneoplastic syndrome:
-caused by secretion of PTH-related protein which mimics the action of PTH
- cause hypercalcemia and hypophosphatemia.
examples:
- Adenocarcinoma of apocrine glands of anal sac (mainly in dogs)
-Lymphosarcoma (in dogs and cats).
GNRH -> somatotrophin
-metabolic actions:
-AA transport into cells
-stimulation of protein synthesis
-cariltage growth
-lipid metabolism
-increased insulin resistance, leading to increased blood glucose
-release of somatotrophin stimulated by:
-sleep stages III and IV
-stress, exercise, fasting
pituitary congenital anomalys
Aplasia or Hypoplasia: Rare
Pituitary Cysts: Rathke’s pouch–> Benign if no changes to pituitary function!
German shepherds with pituitary dwarfism*
Stunted puppy growth (decreased somatotropin) leads to endocrine dystfunction due to lack of sygnals
Secondary hypothyroidism or Cushings
Diabetes insipidus if compresses neurohypophysis
diabetes insipidus
Hypophyseal form (= central diabetes insipidus)
seen with any lesion that interferes with ADH SYNTHESIS or secretion like damage to the pars nervosa or hypothalamus.
-administration of exo ADH will increase urine osmolarity only in hypophyseal form
Nephrogenic form:
hereditary defects in the ADH receptor or in the water channels in kidneys, cells dont respond to ADH
Both forms of diabetes insipidus result in:
PU/PD
urine of low osmolality even after water deprivation.
inflammation of the adrenal gland
Associated with meningitis or encephalitis can spread to hypo or pituitary
can have Neutrophils = Abscesses
-sporadic in ruminants and pigs
- Bacteria causes A. pyogenes
- Fungus (pyogranulomatous)
-animals will have neuro signs
Lymphoplasmacytic:
- Viral or protozoan
pituitary hyperplasia
Old sheep/ horses
Hyperlasia of the pars intermedia can be inactive or lead active and ACTH–> cushing disease
Adenoma vs. Hyperplasia hard to tell grossly
Size and number
Presence of a capsule
Compression of the adjacent tissue
pituitary hyperplasia and neoplasia
-may be functional: overproducing trophic hormone on organ
-or nonfenctional but destructive to adjacent structures ± metastatic.
* Adenomas and carcinomas are seen more commonly in middle age to older;
craniopharyngiomas seen more in young animal
corticotroph adenoma
Pars Distalis (intermedia)
-functional tumor
- secretes ACTH which leads to bilateral (symmetrical) hypertrophy/hyperplasia of zona fasciculata and zona reticularis (CORTEX)
leads to Too much CORTISOL
Cushing’s diseases
chromophobe adenoma
-invades tissues, removing pituitary and brain
-non functional
-usually in dogs
horses: pituitary pars intermedia dysfunction PPID
-horses and ponies over 15 years old
-Pituitary is large
-PI cells produce excess proopiomelanocortin (POMC)
derived peptide –> higher levels α-MSH, β-endorphin**
Modest elevations in:
Plasma cortisol
ACTH
Adrenal cortex hyperplasia
PPID horses clinical signs (equine cushings like) clinical signs
PU/PD/PP
Muscle atrophy, weakness
Laminitis
Hirsutism
Crested Neck – altered fat deposition
Flop sweats – hyperhidrosis
Hyperglycemia or hyper-insulinemia
craniopharyngioma
-seen in younger animals can be large and lead to dwarfism, diabetes insipidus
adenohypophysis and neurohypophysis destroyed (the entire pituitary gland is destroyed)
leads to Atrophy of thyroid and adrenal glands, hypoplastic adrenal cortex
- Thyroid appears normal size but is mostly Colloid, not active follicles.
adrenal secretions different zones
Adrenal cortex:
-Zona Glomerulosa: Mineralocorticoids (Aldosterone) Salt
-Zona Fasciculata: Glucocorticoids (Cortisol) Sugar, controlled by ACTH
-Zona Reticularis: Adrenal androgens Sex
Adrenal medulla:
Norepinephrine
Epinephrine
Dopamine
HPA axis
hypoadrenocorticism types
Primary Hypoadrenocorticism:
Bilateral idiopathic adrenal cortical atrophy
Destruction of all THREE CORTICAL LAYERS, often with infiltration of mononuclear inflammatory cells
Bilateral destruction of adrenal glands**
Secondary Hypoadrenocorticism:
Destructive pituitary lesions
Iatrogenic
MOST COMMON CAUSE
Following the sudden withdrawal of synthetic glucocorticoids treatment after prolonged usage when they are depended on these exo)
Atrophy of only the inner two zones
hypoadrenocorticism lesions
Lethargy,
Stress intolerance
Heart: bradycardia
-GI: V/ A/ D
SKIN: hyperpigmentation
Chemistry: hyponatremia & hyperkalemia**
hallmark of Addison’s.
Metabolic: Hypoglycemia, hemoconcentration which does not respond to ACTH administration
hyperadrenocortiiscm types
COMMON endocrinopathy in OLDER DOGS, less so in horses but rare in other animals.
Combined gluconeogenic, lipolytic, protein catabolic and immunosuppressive effects of corticosteroids
- Primary hyperadrenocorticism (10-15%): functional cortical neoplasm or hyperplasia
- Secondary hyperadrenocorticism (80%): PDH or idiopathic, pituitary depended**
- Iatrogenic hyperadrenocorticism (5-10%): medication
Primary Hypoadrenocorticism
- Bilateral idiopathic adrenal cortical atrophy
o Autoimmune hereditary?
o Occurs most frequently in young to middle-age female dogs
o Destruction of all three cortical layers**, often with infiltration of mononuclear
nflammatory cells
o Deficient production of all cortical hormones - Bilateral destruction of adrenal glands
o Due to inflammation, infarction, hemorrhage, tumor
secondary hypoadrenocorticism
Destructive pituitary lesions:
o Damage to the pituitary, including corticotrophs, results in deficiency of ACTH.
o Atrophy of only the inner two zones; mineralocorticoids are minimally affected
and generally no electrolyte imbalances
Iatrogenic**
o MOST COMMON CAUSE of secondary hypoadrenocorticism
o Following the sudden withdrawal of synthetic glucocorticoids treatment after prolonged usage
o Atrophy of only the inner two zones; mineralocorticoids are minimally affected
and generally no electrolyte imbalances
lesions of hyperadrenocorticism
Polyuria / polydipsia
Polyphagia
Hepatomegaly
Pendulous abdomen
Skin lesions
(90% of cases) DERMAL ATROPHY, alopecia
Dystrophic mineralization:Calcinosis Cutis
Bacterial infections
Clinical pathology tests:
hypercoagulability
Eosinopenia
Lymphopenia
corticotroph adenoma
-in pars distalis secretes ACTH
bilateral (symmetrical)
hypertrophy/hyperplasia of zona
fasciculata and zona reticularis (CORTEX)
Too much CORTISOL
Cushing’s disease
-usually small breed, brown belly, scaily skin, thin haircoat
iatrogenic cushings
-atrophy of the cotrex not hyperplasia
-from long term, daily use of large doses or corticosteroids
-decreased ACTH
phenochromatocytoma
-in adrenal medulla cells of dog, horses, cattle
Often large and encapsulated
may invade the vena cava ***and metastasize extensively.
Rarely functional, if so:
secrete epinephrine and/or norepinephrine
can cause tachycardia, edema and cardiac hypertrophy
BULLS: pheochromocytoma and C-cell neoplasia often develop concurrently.
Paraganglioma if outside the adrenal gland
main pancreatic outputs
EXOCRINE: ACINAR CELLS compose most of the pancreas (>90%) and
these make pancreatic enzymes that aid in digestion.
ENDOCRINE: Insulin (β cells) and Glucagon (α cells), along with delta
and PP cells
GLYCOGENESIS (the conversion of glucose to glycogen)
GLUCONEOGENESIS (the conversion of glycogen to glucose).
This is stimulated by GLUCAGON, CATECHOLAMINES and CORTISOL
hypoglycemia
A decrease in blood glucose = HYPOGLYCEMIA
Hypoglycemia can impair brain function, potentially causing seizures,
coma, and death, common in young animals.
-glucose is a very important energy substrate, particularly for the CNS which cannot use fat metabolism
glucose feedback loop
Increased blood glucose concentration: increased insulin secretion
Decreased blood glucose concentration–> increased secretions of:
Glucagon
Catecholamines
Somatotrophin
Cortisol
insulin response to HIGH GLUCOSE
glucagon response to LOW GLUCOSE
beta cells of the islet
-60-70%
- Increased Blood glucose -> insulin release, which leads to:
Increased GLYCOGENESIS
Increased GLYCOLYSIS
Increased GLUCOSE TRANSPOR
also AA transport, protein synthesis, LIPOLYSIS, LIPOGENESIS
alpha cells of the islet
-20%
Decreased Blood glucose -> Glucagon release, which leads to:
Increased HEPATIC GLYCOGENOLYSIS
-> Increased blood glucose
also: gluconeogenesis, increasing blood glucose, increased LIPOLYSIS
delta cells and PP cells in pancreases
Delta cells
~5% of the islet
Produce somatostatin which inhibits release of insulin, glucagon and gastro-intestinal peptides.
PP cells
~10% of the islet
Make pancreatic polypeptide inhibits intestinal motility & stimulates secretion of gastric/intestinal enzymes
type 1 diabetes mellitus
Also called insulin-dependent diabetes mellitus.
Destruction of beta cells with progressive loss of insulin secretion.
This is usually an abrupt presentation and insulin is required for life after diagnosis.
May present with KETOACIDOSIS.
In humans, this starts with lymphocytes infiltrating the islets and destroying the beta cells.
-not very common, most common one in dogs female over male
type 2 diabetes mellitus
-old cats 9-10 years +
Develops due to insufficient
insulin secretion relative to
metabolic demand
This is usually a gradual
presentation**
Insulin resistance AND/OR
Dysfunction of the beta cells
Insulin resistance: secondary to obesity or counter regulatory hormones like GH not functioning properly.
IAPP
- Produced by pancreatic β-cells***
- Called islet amyloid polypeptide (IAPP
or amylin) - It is co-processed, packaged and
released with insulin in response to
glycemia - Apoptosis in the islets can be seen with
toxic accumulations - Common in obese cats, but does not
necessarily mean they have diabetes
secondary diabetes mellitus
causes:
* Dogs and cats with chronic, relapsing pancreatitis, inflammation interferes with function.
* HIGH CORTISOL: from Dogs with Cushing’s or Chronic steroid therapy. cortisol raises blood sugar and inhibits insulin.
* Cats with growth hormone excess (GH secreting pituitary tumor).
* Glucagon (glucagonomas)
clinical signs of Diabetes mellitus
PU/PD/PP
Weight loss and weakness
Hepatic lipidosis may occur: requires that the cat be overweight and anorexic
Increased omental fat deposition and triglyceride formation
Cataracts (DOGS) – lens
becomes cloudy due to high
blood sugar
Blood vessels in the glomeruli
and retina are most susceptible
to damage from DM
peripheral demyelinating
neuropathies occasionally seen
Clinical pathology:
Hyperglycemia
Glycosuria
ketone bodies in urine
adrenal diabetes
-increased gluconeogenesis and decreased glucose use leads to secretion of insulin –> adrenal diabetes
steroid hepatopathy
-cortisol causes: decreased glucose USAGE by cells. INCREASED GLUCONEOGENESIS
-INCREASED gluconeogenesis and glycogenesis –> INCREASED GLYCOGEN STORAGE
pancreatic islet tumors ( insulinomas)
-beta cell neoplasms= insulinomas
Mostly seen in adult dogs & ferrets
Often functional and producing excess insulin
gross:
-single discrete tumor
Adenomas are encapsulated
Carcinomas are larger with features of malignancy and may metastasize
Clinical signs of functional tumors are related to severe hypoglycemia
often present clinically with seizures
CLINICAL diagnosis of an insulinoma is established by detecting high serum
insulin, low blood glucose and one or more nodules in the pancreas
(ultrasound) with biopsy.
pancreatic islet tumors
Glucagonomas
Rare, but have been reported in dogs
Produce excess glucagon
secondary diabetes mellitus
Gastrinomas
Rare, but have been reported in dogs and cats
Produce excess gastrin
Gastric ulcers
pancreatic nodular hyperplasia
This is an EXOCRINE hyperplasia
Multifocal and VERY COMMON
-if chronic has fibrinogen and is dense
chemodectoma
-aortic body adenoma
-tumor of chemoreceptors
-heart failure due to large space occupying mass in pericardium
-does not usually secrete hormones
-heart base tumor is differential diagnosis of a ectopic thyroid tumor.
ferret tumors
Lymphosarcoma
Any organ can be affected. (spleen and LN usually)
Ferrets may not have symptoms until full of tumors.
Adrenal tumors
Tumors excrete excessive ESTROGEN.
The most common symptoms of this disease is hair loss. bald, Pot belly
Insulinoma
Insulin-secreting tumor -> serious drops in blood glucose -> brain dysfunction
The most common symptoms of this disease are lethargy, going into trances
or experiencing hind end weakness.
ferret GI problems
Gastric ulcers:
Suspected to be caused by stress. Treated by acid reducers and bland
diet.
Inflammatory bowel disease:
Autoimmune disease causing lymphocytic enteritis.
Need to biopsy to distinguish from lymphoma
chordoma
