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Veterinary Medicine > Endocrine > Flashcards

Endocrine Flashcards

1
Q

Catecholines

A 
Derived from tyrosine 
Noradrenaline, adrenaline, dopamin
Insoluble - do not enter cells
Exert their actions by binding to plasma membrane receptors
Rapid onset
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2
Q

Thyroid hormones

A 
Derived from tyrosine
Thyroxine (T4) and tri-iodothyronin (T3)
Lipid soluble and so can enter cells
Receptors are located within cell nucleus
Slow onset
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3
Q

Indoleamines

A

Derived from tryptophan
Serotonin, melatonin
Bind to plasma membrane receptors
Exert actions rapidly

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4
Q

Hypothalamus

A

Basal part of diencephalon
Appetite, HR, body temp, sexual appetite, stress response
Vascular link between median eminence and anterior pituitary

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5
Q

Somatostatin

A

Hypothalamus and delta cells of the endocrine pancrease
Potent inhibitor of GH secretion
Potential therapeutic to treat GH tumours

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6
Q

Thyrotrophin releasing hormone

A

Key regulator of TSH production in the pituitary

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7
Q

Dopamine

A

Catecholamine

Tonic inhibitor of prolactin secretion of pituitary

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8
Q

Corticotrophin releasing hormone

A

Key regulator of stress response

CRH mutations results in impaired stress response and front lobe epilepsy

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9
Q

Anterior posterior

A

Master gland
Controls function of numerous other glands
Situated in bony cavity at the base of the skull

5 cell types: gonadotroph, lactotroph, somatotroph, corticotroph, thyrotroph

Secretes: FSH, LH, GH, TSH, ACTH, PRL

Regulated by hypothalmic factors

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10
Q

Growth hormone

A

In response to GHRH and Ghrelin, inhibited by somatosytation
Effects on liver and muscle are mediated by the release of insulin-like growth factor

Acromegaly: GH-secreting tumour causing inappropriate growth, giantism and diabetes

GH insensitivity/deficiency: dwarfism, short stature, Laron’s syndrome

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11
Q

Thyroid stimulating hormone

A

Released in response to TRH stimulator and acts at thyroid gland to regulate the production of T4/T3 - regulate growth and metabolism

Thyrotropinomas: secrete high levels of TSH, treated by SST analogues, surgery and irradiation

TSH production is regulated by T4/T3 feedback at TRH neurons and at thyrotrophs

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12
Q

Prolactin

A

Secreted in response to TRH, oestradiol and VIP/PACAP and tonic inhibition by dopamine
Regulate lactation in oestradiol-primed mammary glands

Prolactinomas: cane be large - surgery

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13
Q

Adrenocorticotrophin hormone (ACTH)

A

Secreted from corticotrophs in response to CRH
Key regulator in stress response - regulates glucocorticoid production

Corticotrophinomas: Cushing’s syndrome - excessive glucocorticoid syndrome - surgery

Tpit mutations lead to ACTH deficiency - low glucocorticoids, weight loss, anorexia, low bp

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14
Q

Adrenal cortex

A

Paired gland, on top or near kidneys

Cortex: 80-90% gland volume
Medulla: 10-20%, highly vascularised

Zona glomerulosa: lies under capsule, 5-10% of cortex, cells are small and round, few lipid droplets, aldosterone

Zona fasciculata: 60-75% of the cortex, ZF cells are bigger than ZG, contains numbers of lipid droplets, cortisol

Zona reticularis: 20-30% of the cortex, intermediate size, relatively few lipid droplets, adrenal androgens

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15
Q

Actions of ACTH

A

Acute:

  • Deplete ascorbic acid
  • Stimulate steroid synthesis
  • Increase blood flow to gland

Chronic:

  • Increase adrenal weight
  • Increase both cell number and size
  • Induce synthesis of enzymes involved in steroid synthesis undos a consequence increase steroid synthesis
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16
Q

Transport of corticosteroids

A

In plasma bound vesicles to protein
Normal circulating volume: >90% of glucocorticoid are bound to transcortin or corticosteroid binding globulin (CBG)
Protein bound steroids - not biologically active
Aldosterone is not normally bound to specific proteins

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17
Q

Actions of glucocorticoids

A

Specific glucocorticoid receptor (GR)
Affects carbohydrate, lipid and protein metabolism
- Anabolic actions in the liver and catabolic actions in muscle and fat cells
- Protein breakdown and lipolysis (fat and muscle cells)
- Glycogenesis and gluconeogenesis (liver cells)
- Protein synthesis (liver cells)

Inhibit growth (young), anti-inflammatory, immunosuppressive, protection against stress, negative feedback on ACTH release

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18
Q

Clinical disorder of the adrenal cortex

A

Rare - usually female, middle aged - old dogs
Excessive quantities of glucocorticoids
Excessive secretion of cortisol may be due to increased secretion of ACTH
Cortisol excess due to hypersecretion of pituitary or extra pituitary-dependent hyperadrenocorticism (90%) or adrenal tumours (10%)

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19
Q

Actions of mineralocorticoids

A

Via specific mineralocorticoid receptors
Increase the reabsorption of Na in the kidney
Na ions are exchanged H and K ions leading to decreased Na and increased K excretion - increased acidity
No feedback effects on pituitary ACTH release

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20
Q

Aldosterone - excess primary hyperaldosteronism

Conn’s syndrome

A

Autonomous secretion of aldosterone due to presence of single adrenal adenomas in the zona glomerulosa
High levels of aldosterone:
- Hypertension - increase water and Na retention
- Hyperkalemia - muscle weakness, cardiac arrhythmias

21
Q

Aldosterone - excess secondary hyperaldosteronism

A

Increased aldosterone secretion in response to increased levels of angiotensin II due to increased renin secretion from juxtoglomerular cells
Physiological reflex designed to conserve sodium in cases such as haemorrhage, salt and water depletion

22
Q

ACTH stimulation test

A

Normal response: 2-3 fold increase over the pre-ACTH level of cortisol

Pituitary-dependent hyperadrenocorticism: exaggerated response (>660mmol/L)

Adrenal tumours: may hyper-respond or have very high resting cortisol levels with little or no change after ACTH

Addison’s: lack of response

23
Q

Low dose dexamethasone suppression test

A

Normal response is a decrease in cortisol levels to

24
Q

Steroids as treatment

A

Replacement for adrenal insufficiency
Anti-inflammatory therapy
Immunosuppressive therapy
Shock treatment

S/E: adrenal gland atrophy, hyperadrenocorticism, iatrogenic Cushing’s, PU/PD (ADH actions), polyphagia (anti-insulin effects), hepatomegaly (glycogen deposition in liver), fat deposition in abdomen, skeletal muscle weakness (muscle protein breakdown), thin skin and hair loss (effects on hair cycle and collagen synthesis)

25
Q

Thyroid anatomy

A

Two lobes joined by an isthmus
12 weeks of gestation: synthesises and secretes thyroid hormones under influence of foetal hypothalamic/pituitary axis - normal growth and development
HIghly vascularised, sympathetic and parasympathetic innervation

Functional unit: follicle - single layer of cuboidal cells surround clear mucus-like fluid (colloid)

  • Elongate upon stimulation
  • Growth and development of follicle is independent of TSH initially

Also contain larger epithelial cells know as clear cells - synthesise and secrete calcitonin - a hormone which regulates plasma

26
Q

Thyroid hormones

A

Tri-iodothyronine - T3
- Smaller amounts secreted but provides almost all thyroid hormone activity in target tissues
Thyroxine (tetraiodothyronine) - T4
- Converted to T3 in target tissues
Unique hormones: incorporate iodine into an organic structure made from tyrosine

27
Q

Thyroid hormone transport

A

Transport: thyroxine-binding globulin (TBG), thyroxine-binding pre-albumin (TBPA), albumin
Free hormone fraction - responsible for activity

28
Q

Thyroid hormone receptors

A

Alpha 1 and 2 expressed mainly in the brain (lower levels in the kidneys, skeletal muscle, lungs, heart and liver)

Beta1 - kidneys, liver, brain, heart and thyroid
Beta2 - brain, retina and inner ear
Beta3 - kidney, liver and lungs

29
Q

Metabolic action of thyroid hormone

A

Calorigenesis: increased energy production and consumption, increased BMR

Intermediate metabolism: Increased hepatic gluconeogenesis/glycognelysis, increase lipolysis

CVS effects: Increased cardiac muscle contractility, increased slow Ca2+ channels, increased beta adrenergic receptors (and in skeletal muscle, adipose tissue - increased sensitivity to catecholamines)

30
Q

Thyroid hormone metabolism

A

Liver, kidney, brain and muscle - deiodination enzyme

15-20% of T4 and 100% of T3 forms conjugates and excreted in faeces and urine

31
Q

Hypothyroidism

A

Signs:
Weight gain, scaly skin, seborrhoea, hyperpigmentation, alopecia, increased cholesterol in the blood, lipid accumulation in the liver, bradycardia

Causes:

  • Idiopathic atrophy - larger dog breeds
  • Immune mediated thyroiditis - binding of autoantibodes to thyroglobulin
  • Less common: bilateral non-functional thyroid tumours, sever iodine deficiency, destructive lesions in the pituitary gland
32
Q

Hyperthyroidism

A

Hyperplasia, adenomas, autoimmune response (Grave’s disease)

Signs: weight loaa, sweating, tremor, goitre, agitated and nervous, fast HR, atrial fibrillation

Most common endocrine condition in old cats (usually benign thyroid adenoma): weight loss, V/D, rapid HR, PD

Other causes:

  • Genetic enzymatic defect: can’t produce T3 or T4 e.g. congenital dyshormogenetic goitre in certain breeds of sheep
  • Iodine deficiency: foals, pigs, lambs, goats
  • Iodine excess: interferes with one or more steps in thyroxine synthesis, dried seaweed
  • Goitregenic substances: interfere with T3/T4 synthesis
33
Q

Drugs that act on the pituitary to affect TSH secretion

A

Protilerin: synthetic TRH - stimulates TSH release (and prolactin and FSH) - diagnosis of thyroid dysfunction

Thyroxin and tri-iodothyronine (T3 and T4): inhibit secretion and synthesis by negative feedback, used for diagnostic testing of thyroid gland function

34
Q

Drugs that influence thyroid hormone secretion or secretion

A

Thyrotrophin (TSH): increase metabolic activity of the gland - increase T3/T4, not licensed

Radioisotopes of iodide: selective radiation therapy of hyperactive tissue - treatment of hyperthyroidism

Anti-thyroid drugs:

  • Perchlorate and thiocyanate: compete with organic iodide for uptake by pump
  • Thioureylenes (methimazole, carbimazole, propylthiouracil) - orally active, potent inhibitors of throidal perioxidase/TG, block iodine incorporation into tyrosol
  • Inorganic iodide: large amounts over a brief period (10d) reduce size/vascularity of gland, management of hyperthyroidism in cats (prior to/instead of surgery)
35
Q

Drugs with mimic or inhibit thyroid hormone action

A

(MIMIC) Thyroid hormone replacement therapy synthetic prep:

  • Dose adjusted according to clinical response or base on serum (T4)
  • Care should be taken in animals with concurrent heart disease

(INHIBIT) Propanolol:

  • To functionally antagonise some of the CVS actions of excessive thyroid hormones - increase number of beta receptors in myocardium
  • Used in cats with hyperthyroidism - slows HR, decreases myocardial O2 demand and is anti-dysrhythmic
36
Q

Pancrease anatomy

A

Right side of abdomen - attached to caudal surface of stomach and cranial flexure of duodenum
Site within greater omentum and mesoduodenum
Right and left lobes

Exocrine (99%) and endocrine segments - 1.5g of patches spread out among exocrine area

37
Q

Islets of Langherhans

A

Endocrine cells of the pancreas

  • Alpha cells secreting glucagon (5-30%): raise blood sugar, breaks down glycagon in liver, also affected by symp NS, adrenaline/noradrenaline
  • Beta cells secreting insulins (60-80%): lower blood sugar, stimulate skeletal muscle fibre to take up blood glucose and convert it to glycogen, insulin binds to insulin receptors imbedded in plasma membrane, also produce IGF2 (mainly and some IGF1)
  • Delta cells secreting somatostatin (
38
Q

Insulin secretion

A

NS, retina, erythrocytes and germinal epithelium of gonads require glucose
Excess glucose - negative osmotic effects
Insulin secreted when there is high blood glucose - enhance acutely by blood fatty acids, amino acids, ketones

Increlin hormones:

  • GI hormone - cause increase in the amount of insulin released from beta cells
  • Slow rate of absorption of nutrients by reducing gastric emptying
  • Reduce glucagon release from alpha cells

Autonomic NS
GH, glucagon and glucocorticoids may increase insulin secretion chronically

39
Q

Acromegaly

Hypersomatotrophism

A

Growth hormone - elevated levels of IGF1
Cats: nearly always pituitary tumour
Dogs: increased GH secretion for mammary tissue
Juveniles: increase length of long bones

Treat:

  • Dogs: remove progesterone influence
  • Cats: consider dopamine agonists, local irridation, somatostatin analogues
40
Q

Dwarfism

Hyposomatotrophism

A

Congenital malformation of the pituitary adenohypophysis (cystic Rathke’s pouch) or possible malformations in trophic hormone producing cell lines
Reduced secretion of GH and possibly also TSH
Occasionally, reduced gondaotrophin secretion may also be present

Small stature, immature hair coat, 6-8w, persistent oestrous, normal life expectancy

No treatment need, consider progestin therapy

41
Q

Diabetes insipidis

A

Reduced vasopressin (ADH) secretion from the posterior pituitary
Occasionally secondary to an expanding mass lesion of congenital abnormality but usually idiopathic
Lack of ADH means collecting tubules remain impermeable to water, consequently urine is persistently and very hyposthenuric

PU >200ml/kg/24h, obvious PD
USG

42
Q

Parathyroid hormone related peptide

A

PTH like factor that is secreted by some neoplastic cells and is an important cause of the hypercalcaemia associated with malignancy

43
Q

Hypercalcaemia

A

PU/PD, anorexia, dehydration, weakness/lethargy, vomiting
Facial pruritis, oral discomfort, cardiac arrhythmias, seizures/twitching, acte renal failure and death

Primary hyperparathyroidism: signs often attributed to old age

High calcium interferes with kidney’s ability to concentrate urine so patients may be dehydrated with a pre-renal azotaemia but with a low USG

Transient inconsequential: hypoadrenocorticism, haemoconcentration, hyperproteinaemia

Pathologic: malignancy (especially lymphoma, anal sac adenocarcinoma), primary hyperparathyroidism (Keeshunds, parathyroid adenoma - u/s), renal failure, hypervitaminosis D (some rat poisons, psoriasis cream), granulomatous disease (fungal infections, lungworm), toxic (vitamin D analogues), skeletal lesions, idiopathic (cats)

Treat specific disease, when undiagnosed can lower serum calcium temporarily:

  • Diuresis with 0.9% NaCl
  • Bisphosphonates therapy e.g. palmidronate
  • Calcitonin
  • Furosemide
  • Peritoneal dialysis
  • Glucocorticoids - last resort
44
Q

Hypocalcaemia

A

Concurrent low albumin
Common problem in farm: milk fever

Muscle tremors/cramps, stuff gait, behavioural change, panting, hyperthermia tachycardia, hypotension, death

Small animals: chronic renal failure, eclampsia. acute pancreatitis, iatrogenic, ethylene glycol toxicity, intestinal malabsorption, primary hypoparathyroidism

10% calcium gluconate, oral calcium supplementation, supplement with vitamin D metabolite:

  • Ergocalciferol (cheap but long half life)
  • Dihydrotachysterol (middle ground)
  • Calctriol (most expensive, shortest half life)
45
Q

Pituitary adenoma

A

Produce ACTH

May obliturate the gland and cause hypopituitarism - diabetes insipidus

Can also cause Cushing’s in horses but not in all cases

46
Q

Addison’s

A

Hypoadrenocorticism - common and underdiagnosed

  • Destruction of adrenal glands
  • Idiopathic bilateral adrenocortical atrophy
  1. Increased excretion of Na and Cl
  2. Increased K in the blood
  3. Generalised tissue underperfusion
  4. Reduction of glucocorticoids
47
Q

Canine diabetes mellitus

A

Normal insulin sensitivity, esp winter, esp 7-12y, severe loss of Islets, rapid onset 3-5w
Tibetan terrier, Cairn terrier, Samoyed
Less likely: Boxer, GSD

48
Q

Hyperthyroidism treatment

A

Inexpensive: carbimazole, methimazole 100-200/year
Middle: unilateral thyroidectomy 500
Expensive: bilateral thyroidectomy 750-1000
Tops: thyroid irradiation 1700-2000

49
Q

Hypothyroidism

A

Congenital or acquired
Lethargic, disinterested, 30% overweight, may be exercise tolerant and have muscle or joint pain, alopecia, hyperpigmentation with thickened skin, infertility, neuro problems

Mild non-regenerative anaemia, elevated serum cholesterol, elevated serum CK, protein uria

Treat: thyroxine

Veterinary Medicine (15 decks)

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