Endocrine Disease Flashcards
When do cats typically present with congenital hyposomatotropism?
2 months of age. Initial postnatal growth genetically determined, second phase growth hormone dependent
What are the typical clinical findings of feline congenital hyposomatotropism?
Proportional dwarfism, retained deciduous teeth, dry and dull haircoat, general weakness and lethargy
What % of cats with DM have acromegaly?
26%
Is there a sex predisposition in acromegalic cats?
70% neutered male
What non-diabetic clinical signs are often reported in cats with acromegaly?
Polyphagia, respiratory stertor, snoring, prognathia inferior, enlarged distal limbs, organomegaly, heart murmur, CNS signs
How is acromegaly screened for, what is the PPV of this test?
IFG-1 >1000 = PPC 95%
When can a false negative IGF be seen in acromegalic cats?
9% untreated diabetic cats (IGF-1 production dependent on portal insulin)
Can IGF-I levels be used as a marker of treatment success in cats with Hypersomatotropism treated with surgery or radiation?
Surgery - yes
Radiation - no
What alternative markers of Hypersomatotropism in cats have been explored?
Serum type III pro collagen peptide - marker of collagen turnover, 5x higher in FeHS DM than DM
Ghrelin - lower in FeHS than controls but not diabetics. Increases post radiation
What % of FeHS cases experience diabetic remission following hypophysectomy?
85%
What medical management do cats need following hypophysectomy?
Hydrocortisone and T4 (life)
DDAVP - can be discontinued in most
What options for medical management of FeHS have been described?
Pasireotide - SST analogue - remission in 25% on long acting form
Cabergoline
What is the response to radiation treatment for FeHS?
Unpredictable
Describe GH secretion in dogs. What regulates it’s secretion?
From anterior pituitary, pulsatile
GHRH +
Somatostatin -
Ghrelin +
IGF directly inhibits and stimulates somatostatin release
From mammary - progestogen, non-pulsatile, not controlled by SS, GHRH or ghrelin
When is canine mammary GH production increased?
Dioestrus
What are the physiological effects of GH in dogs?
Rapid - insulin antagonism - ^lipolysis, gluconeogenesis, reduced glucose transport and hyperglycaemia
Slow - IGF growth factors - growth-promotion
What can cause excess GH in dogs?
Endogenous/exogenous progesterone
GH-producing mammary tumour
Hypothyroidism associated with increased GH and IGF-1
Pituitary somatotropin adenoma (RARE)
What are the clinical signs of GH hyper secretion in dogs?
Soft tissue swelling of head, neck, abdomen, snoring, stertor, joint issues (articular cartilage proliferation), PU, PP, increased organ size
How is CaHS diagnosed?
GHRH stimulation or SS suppression tests (GH)
IGF-1
What should be tested in a dog with GH excess, not receiving progestogens?
T4/TSH
How can dogs with somatotroph adenomas causing CaHS be treated medically?
Octreotide/lanreotide
What are the typical endocrine findings in GSD with pituitary dwarfism?
GH, TSH and prolactin deficiency
Normal ACTH
What mutation is associated with congenital pituitary dwarfism?
LHX3
What are the clinical manifestations of pituitary dwarfism in dogs?
Proportionate dwarfism, retained secondary hairs, lack of primary hairs, truncal alopecia, pointed muzzle, cryptorchidism/ovulation failure. Lethargy develops at 2-3 years due to secondary hypothyroidism
What are the findings on biochem for canine pituitary dwarfs?
High creatinine - GH needed for normal glomerular development
How is pituitary dwarfism diagnosed in dogs?
GHRH/clonidine/xylazine stimulation test. GH should increase 2-4x
Ghrelin suppression test can be used to exclude
What are the typical imaging findings in pituitary dwarfism in dogs?
Pituitary cysts +/- hypoplasia
How is canine pituitary dwarfism treated?
Porcine GH
Progestogens described
What is the prognosis for canine pituitary dwarfism?
Poor without treatment, guarded with
Loss of pituitary function, expansion of pituitary cysts renal failure
Describe vasopressin secretion?
AVP formed in the magnocellular neurons in the hypothalamus and transported to the posterior pituitary
What stimulates AVP release?
Increased plasma osmolality and Na content
Angiotensin II
What inhibits AVP release?
Baroreceptor stimulation
BNP
How does AVP act?
Binds V2 receptors, increase cAMP, activates protein-kinase A - causes expression of aquaporin 2
In addition to AVP release, what are the effects of AVP binding V2 receptors?
VWF release
TPA release
ANP release
NO synthesis
FVIII release
What are the most common causes of CDI in dogs and cats?
Dogs - neoplasia
Cats - trauma
What are the causes of NDI?
HAC, pyometra, hyperCa++, pyelonephritis, liver disease, primary
What % of dogs with CDI develop neuro signs within a year?
~40%
What treatment options are described for NDI?
Thiazide diuretics - decrease Na+ absorption, reduce delivery to distal tubules
Low Na diet
What are the actions of the V1a and V1b receptors?
V1a - vascular SM, glucogenolysis, platelet activation
V1b - stimulates ACTH, catecholamine and insulin secretion
How is glargine insulin modified to increase its duration of action?
Structure modified to make soluble at pH 4 and relatively insoluble at physiological pH
How is detemir insulin modified to increase its duration of action?
Structure modified so reversibly binds albumin
How does the potency of detemir in dogs differ from other species?
4x as potent
If spaying isn’t possible in a recently diagnosed FE diabetic what is an alternative?
Aglepristone
What is fructosamine?
Glycated protein formed by irreversible non-enzymatic reaction between glucose and plasma proteins
What non-diabetic factors can alter fructosamine?
Hypothyroidism and multiple myeloma associated with increase
Where is the calcium-sensing receptor found?
Parathyroid, kidneys, bone, cartilage
How is circulating calcium found?
50% ionised
40% protein bound
10% bound to anions
What factors can falsely alter TCa/iCa measurement?
Haemolysis, lipaemia increase TCa
Hypoproteinaemia decreases TCa
Storage - RBC produce lactic acid, pH decreases, iCa increases
Air exposure - CO2 lost, pH rises, iCa decreases
What 4 hormones regulate calcium?
PTH
PTHrP
Vit D
Calcitonin
How is PTH production regulated?
CaSR activated by hypercalcaemia and reduced PTH production
Describe the anatomy of the parathyroid glands
4 glands, cranial pair external, caudal internal
How does PTH act?
Increases Ca, decreases PO4 by action in bone, kidneys and GIT
How do vitamin D and phosphate affect PTH production?
^Vit D = v PTH
^PO4 = ^ PTH
What is PTHrP
Integral in the foetus, undetectable after birth
Same physiological effects as PTH
Causes humoral hypercalcaemia of malignancy
Describe vitamin D metabolism
Cholecalciferol, hydroxylated in the liver to produce 25-OH calciferol (calcidiol) - inactive and unregulated
Activated to 1,25-OH-vit D (calcitriol) in kidney
Increased by PTH
Suppressed by PO4
Can also be catabolised to 24-OH and excreted
What is calcitonin
Produced in thyroid gland C-cells
Reduces serum Ca
Limits post prandial hypercalcaemia
What breed is predisposed to PHPT?
Keeshonden
How does hypercalcaemia cause PUPD
Ca antagonises AVP
Ca inhibits tubular uptake of Na and Cl
What are the clinical signs of PHPT?
PUPD (mild), lethargy, urolithiasis, muscle wastage, weakness
In dogs with PHPT how is the risk of urolithiasis increased?
Increased renal excretion of Ca
Increased PO4 excretion
GI absorption of oxalate increased when calcium absorption increased
Therefore urine supersaturated with Ca, PO4 and oxalate
What medications can be used to lower serum calcium, what is their MOA?
Steroids - increase renal loss, decrease intestinal absorption, decrease bone resorption
Bisphosphanates - inhibit osteoclast activity and increase apoptosis
Calcitonin - inhibits osteoclast activity and inhibits renal reabsorption
Cinacalcet - calcimemetic - interacts with the CaSR directly
How do the post operative outcomes for ethanol ablation, heat ablation and surgery in PHPT compare?
Ethanol - 72-90%
Heat - 90%
Surgery - 94%
What oral vitamin D formulations are available. What is the active ingredient?
Calcitriol - 1,25-(OH)2
Alfacalcidol - needs 25-hydroxylation, rapid and unregulated - no significant difference in time to become effective
What should be monitored for on the ECG when administering IV calcium
ST elevation
QT shortening
Arryhmias
What are the clinical signs of PHPT in cats?
Vomiting, PUPD, weight loss, cervical mass
What are the effects of hypoparathyroidism?
vCa
^PO4
What is the most common cause of hypoparathyroidism
Idiopathic
Evidence to support IM aetiology
What are the predispositions to hypoparathyroidism?
Females, miniature Schnauzers, Poodles, GSD, Terriers
What are the clinical signs of hypoparathyroidism?
Seizures, muscle tremors, stiff gait, inappetence, vomiting, lethargy, tacchycarrythmias
What eye change is described with hypoparathyroidism?
Lenticular cataract formation
What routine blood testing changes are found in hypoparathyroidism?
v Ca
^ PO4
Elevated CK
What are the ddx for hypocalcaemia?
Hypomagnesemia
AKI
CKD
Pancreatitis
DM
Eclampsia
Malabsorption
Urinary obstruction
Phosphate-containing enema
What ECG changes are described with hypocalcaemia?
ST and QT prolongation
In what forms (and relative quantities) is thyroid hormone bound?
60% - thyroxine-binding globulin
17% - transthyretin
12% - albumin
11% - lipoprotein fractions
How does the potency of T3/T4 compare?
T3 3-5x more potent
How is T3 produced?
40% in thyroid
60% by peripheral outer ring monodeiodination of T4
How is T3/4 secretion regulated
TRH (hypothalamus)
TSH (anterior pituitary)
What is rT3
Reverse T3 - metabolically inactive
How do thyroid hormones work?
Modify gene expression
In which dog breeds have congenital thyroid dyshormogenesis been described?
Toy Fox and Rat terriers
What are the common histopathological findings in primary acquired hypothyroidism?
Lymphocytic thyroiditis
Thyroid atrophy