Endocrine Path Flashcards
How do thyroid and steroid hormones differ from other endocrine?
Lipid soluble so act on intracellular receptor cf. PGs, catecholamines etc. Which act on membrane receptors and exert actions quickly
How may endocrine diseases be classified?
> 1* hypo function > 2* hypo function - lack of stimulation > 1* hyper function > 2* hyper function - excessive stimulation > other dz - failure target cell response - endocrine dz 2* to other organ dz - failure foetal endocrine function - iatrogenic syndrome of hormone excess (external administration)
Causes of 1* hypo function and eg. Of effects?
- destruction of cells (abscess, granulomatous, immune mediated)
- embreyonic tissue fails to form secreting tissue (cysts in the pituitary -> lack of stimulating hormones)
- can cause lack of general growth and of specific tissue eg. gonads (2* hypofunction)
- defective synthesis eg. some lambs cannot make thyroglobulin -> congenital dyshormonogenic goitre d/t defect in mRNA processing
Causes of 2* hypo function
- abnormal (or lack of) production of tropic hormones
- hypofunction of target endocrine organ
- eg. Inactive pituitary –> hypo function adrenal and thyroids, hypoplasia/atrophy of the gonads
Causes of 1* hyper function. Eg?
- commonly tumour secreting excessive hormones
- hyperthyroid cats (pathogenesis differs to human Graves, hypofunction of thyroid -> ^TSH -> ^ gland size -> autonomous activity cf. Graves autoAb against TSH-R)
Causes of 2* hyper function
- excessive secretion of a trophic hormone -> inappropriate stimulation of target endocrine organ
- eg. ACTH secreting pituitary adenomas -> hyper trophy and hyperplasia of adrenal cortex (Cushings, ^ cortisol; aldosterone less of a problem as controlled by RAAS)
Where is the Hypothalamus ? Function?
- basal diecephalon below the thalamus
- autonomic function (apetite, heart rate)
- important neuroendocrine also (secretes hormones)
How are the hypothalamus and pituitary linked?
> anterior
- vascular portal system via pars tuberalis
- no direct neuronal connection to hypothalamus
posterior
- neuronal fibres from paraventricular (PVN) and supraoptic (SON) nuclei of hypothalamus pass directly to posterior pituitary
- OT and ADH stored here prior to secretion
Functions of the anterior pituitary?
- Master gland
- controls other endocrine organs (gonads, thyroid, adrenal cortex etc.)
Where is the anterior pituitary situated?
- sella turcica base of skull
- 5 cell types of the anterior pituitary
- gonadotroph
- lactotroph
- somatotroph
- corticotroph
- thyrotroph
anterior pituitary : Three Types of cells in the pars distlais and how they can be identified histologically. How many types of cells in pars intermedia?
~ pars distlais ~ > acidophils - lactotrophs - somatotrophs > basophils - thyrotrophs - gonadotrophs > chromophobes - corticotrophs (or baso) ~ pars intermedialis ~ - 2 types in dog - 1 makes ACTH
Which hormones are secreted from the anterior and posterior pituitary
> ## anteriorposterior
5 main pathologies of the pituitary gland
- Cysts
- esp dogs - Adenoma
- pars intermedia, functioning
- dog and horse - Adenoma
- pars distalis
- ACTH secreting - Adenoma
- pars distalis non functioning - Other pituitary tumours
- including craniopharyngioma
Pathology of pituitary cysts
- d/t failure of differentiation of oropharyngeal ectoderm into hormone secreting cells of pars distalis
- may compress pars nervosa and stalk of hypophysis -> especially affects the dog
- esp GSDs, Spitz, Toy Pinschers
- inherited in GSDs
Effects of pituitary cysts
- d/t v trophic hormones > dwarfism - noticable @ 2mo - v growth, retention of puppy coat -> bilateral alopecia and progressive hyperpigmentation - delayed closure of epiphyseal plates in long bones - delayed permenant dentiition - hypoplasia thyroid and adrenals - infantile gneitalia - life span short if severely affected
Which animals are affected by pituitary adenoma of the pars intermedia
- horses mainly (less common dogs)
- older animals
Pituitary adenoma dogs
- usually -> mod enlargemetn of gland, well demarcated from surrounding tissue
- may be hormonally active/inactive (if active -> ACTH production and Cushings
- larger tumours may obliterate gland causing hypopituitarism: seen mainly as diabetes insipidus
Details of pars intermedia pituitary adenoma in the horse
- tumour often large size but not always in Cushings
- may compress pars nervosa and overlying thalamus
- adenomas are multinodular, yellow/brown/white and firm
- plasma cortisol levels normal/slightly raised d/t diffferent metablism of precursor (Pro-OMC)
> in pars intermedia (produces mainly MSH, CLIP, B-endorphin)
> in pars distalis (produces ACTH - excess cortisol)
Why is size of pituitary adenoma of pars intermedia not necessary related to ACTH levels?
- depends which molecules are produced - not necessarily lots of ACTH produced
- cf. pars distalis where lots of ACTH -> lots of cortisol produced
Where do ACTH secreting adenomas in the dog arise from? Common? Breed pdf?
- arises from pars distalis or pars intermedia
- more commonly causes Cushings in the dog (cf. horse where may not necessarily become cushingoid)
- not uncommon in older dogs
- Boxer, boston terrier, daschaund over-represented
What is seen pathologically with pituitary adenoma in the dog?
- excess secretion ACTH -> bilateral enlargement adrenal cortex and Cushings
- adrenals yellowish/orange colored nodules, variable size, compress corticomedullary junction
- similar nodules in fat surrounding gland
- micro: nests/groups chromatophobe cells
- fine connective tissue stroma
- no secretory granules in light microscopy
> IHC ACTH staining in cells
> electron microscopy shows granules containing hormone
What causes the effects on the animals of Pituitary adenoma ?
- excess GCs from hyperplastic adrenal cortices
- gluconeogenesis, lipolysis, protein catabolism, anti-inflam options
Effects on the animal of pituitary adenoma
- gradual enlargement abdo
- muscle wasting (head and legs)
- enlarged liver
- bilateral alopecia , thin skin with mineralisation, hyperpigmentation
- fat pads neck and shoulders
- poor wound healing
What is the pars nervosa and what does it produce? How do these act?
- posterior pituitary
- OT and ADH (not produced here, produced in nerve cell bodies within hypothalamic nuclei, just secreted post pit)
- circulate at very low levels
- half life ~5mins
- acts though G-protein linked plasma membrane receptors
Outline pathology of central diabetes insipidus
- inadequate prouction/release of ADH
- d/t obliteration/compression pars nervosa by cyst or tumour
- compression of hypothalamus can also cause neuronal dysfunction and inadequate production ADH
- PUPD, hypotonic urine
- dx by water deprivation test and respnse to exogenous ADH
What is the adrenal gland comprised of? Which sections secrete what?
> medulla
- catecholamines (adrenaline, noradrenaline)
cortex
- steroids
( zona glomerulosa outside: MC aldosterone)
( zona fasiculata middle: GCs cortisol)
(zona reticularis inner: adrenal androgens small amount)
What is the cortex divided into
- See previous
Which species produces oestrogen in the adrenal?
Ferrets only species
Main actions of GCs
- eg. cortisol
- dealing with stress (physical or emotional), starvation or infection
Main actions of MCs?
- eg. adosterone
- essential for life
- regulated by RAAS and plasma levels of sodium/potassium
- conservation body sodium by stim resorption sodium in kidney in exchange for potassium
General pathological changes of the adrenal gland
- accessory adrenocortical tissue seen in dogs, rodents, rabbits
- mineralisation: calcification of adrenals in adult cats and monkeys
- amyloidosis old rats, mice and monkeys
- adrenalitis (abscesses and other disseminated dz eg. toxoplasmosis and TB)
Causes of hyperadrenocorticism (Cushings)
> excess GCs (dogs and horses)
- adrenal gland tumour
- ^ ACTH
- ^ CRH
- exogenous corticosteroid tx
Most common endocrine disorder of dogs is? Clinical signs? Breed pdf?
> Canine Cushings Syndrome
- esp poodles, boxers and dachshunds
- 80% cases caused by pituitary tumour
- pot bellied abdomen may look preg d/t hepatomegaly and abdo muscle weakness
- PUPD (excess GC antagonises ADH-R -> nephrogenic DI)
- muscle wastage over head, shoulders, thighs and pelvis
- polyphagia
comonest cause of Canine Cushings
- pituitary tumour
How do GCs affect kidney function?
- antagonise ADH-R -> nephrogenic DI
Adrenocorical hyperplasia types
> nodular hyperplasia
- yellowish spherical nodules (1-2cm) in cortex
- older dogs, cats and horses (similar found in spleen, liver and pancreas)
- micro: resemble zona glomerulosa
diffuse hyperplasia
- usually casued by ACTH secreting pit tumours, can be idiopathic
- cortices uniformly enlarged
- excess cortisol produced -> Cushings
- micro: hypertrophy and hyperplasia of zona fasciculaa and reticularis
- cells vacuolated (rich in lipids)
Path and histo of adrenocorticol adenoma. Ddx?
> seen old dogs occasionally
- appears as single pale yellow/red nodule
- partially/completely encapsulated
- adjacent parenchyma compressed
- sometimes bilateral
micro:
- well diff cells resembling zona fasiculata/reticularis
- vacuolated and divided by fibrovascular stroma
- capsule divides from normal adrenocortical tissue
ddx nodular hyperplasia: difficult, but adenoma more encapsulated, compressive and solitary
Hypoadrenocorticism common?
> deficiency of GC and MC
- relatively common and under diagnosed
Causes of Addisons - pathophysiology?
- destruction of adrenals
- idiopathic bilateral adrenocortical atrophy (1/10 normal thicknesss)
- all 3 layers of cortex affected
- young adults mainly affected
- autoimmune or inflam disease
> effects mainly d/t lack of MC (aldosterone) -> PUPD
Effects of Addisons
- ^ excretion Na Cl and Water -> Haemoconcentration and dehydration
- ^ blood K+ -> bradycardia and cardiac arrest
- generalised tissue underperfusion -> VD+
- v GC increases suscpetibility to stressful situations
Histo changes with Hypoadrenocorticism
- medulla increases in size , cortex decreases in size
How does cushings differ in horses and dogs?
Dogs hair loss, horses curly coat
Other slides on thyroid look
