Congenital disorders Flashcards
What can congenital dz be due to?
Due to developmental failure during gestation
Which may be a result of:
- inherited disorder
- nutritional deficiency or excess in gestation
- dz in gestation
Pituitary dwarfism - what is it?
= hyposomatotropism
Congenital growth hormone (GH) deficiency
Abnormal development of the pituitary gland
- hormone-producing cells fail to differentiate during gestation
Inherited dz (simples autosomal recessive)
- German shepherds most commonly affected
- KC scheme for Tibetan terriers introduced 2021
- rare in cats
Other pituitary hormones may be affected: thyroid stimulating hormone (TSH), prolactin, gonadotropins
- adrenocorticotropin hormone (ACTH) unaffected?
Pituitary dwarfism - presentation
Animal may appear normal until about 2m/o
- stunted growth, delayed dentition
- puppy coat (primary ‘guard’ hairs don’t develop), bilateral symmetric alopecia
- abnormal reproductive development (cryptorchidism, anoestrus)
Affected dogs will have shortened lifespan
- prognosis guarded with tx, poor without
‘Stunted growth’: Differentials
GI
- malnutrition (including parasitism)
- malabsorption dz
Endocrine
- pituitary dwarfism
- congenital hypothyroidism
- juvenile DM
- EPI
- hypoadrenocorticism
Hepatic
- portosystemic shunt
- other liver dz
Iatrogenic
- glucocorticoids
Renal
- aplasia, dysplasia
- other renal dz
Metabolic
- storage dz (lysosomal, glycogen)
Skeletal
- skeletal dysplasia ‘dwarfism’
Pituitary dwarfism - diagnostic options
- biochemistry
- thyroid hormones
- growth hormone / insulin-like growth factor 1 (IGF1)
- GH stimulation test
- advanced imaging
- genetic testing
Pituitary dwarfism - diagnostics - biochemistry
Elevated creatinine
- GH deficiency impacts renal development
- TSH deficiency reduces GFR
Pituitary dwarfism - diagnostics - thyroid hormones
- low thyroxine (T4)
- low TSH
Pituitary dwarfism - diagnostics - growth hormone / insulin like growth factor-1 (IGF-1)
Low (but can be low in normal animals)
- IGF-1: indirect evaluation of GH
Pituitary dwarfism - diagnostics - GH stimulation test
Definitive for GH deficiency
Requires a GH stimulant (plasma GH should increase after 20-30mins)
- GH-releasing hormone
- alpha-adrenergic drugs (clonidine, xylazine)
- human ghrelin
Pituitary dwarfism - diagnostics - advanced imaging
May reveal cyst (thought to be secondary)
- may be found incidentally in brachycephalic
Pituitary dwarfism - diagnostics - genetic testing
- GSD
- Tibetan terriers
Pituitary dwarfism - tx
Problem = insufficient GH, solution = supplement GH?
Cats: ideal tx unknown
Growth hormone
- porcine GH
- difficult to acquire
- canine GH not available
- DM risk: monitor GH, IGF-1, glucose
Progestagens
- medroxyprogesterone
- stimulates GH in mammary glands (ineffective in cats)
- risk of DM, mammary tumours, acromegaly, CEH
– spay females prior to tx
Supplement thyroxin (levothyroxine)
Prognosis still guarded even with tx
- progressive pituitary dysfunction and renal dz, cyst enlargement
Congenital hypothyroidism - what is it?
Congenital thyroxine deficiency
Primary = abnormality of the thyroid glands
- dysmorphogenesis - anatomical abnormality
- dyshormonogenesis - abnormality in hormone synthesis (fox terriers, rat terriers)
Secondary = abnormality of the pituitary
Tertiary = abnormality of the hypothalamus
Secondary & tertiary = ‘central’ CH (CCH), rare (<5% of cases)
Rare in both dogs and cats
- potentially misclassified as ‘fading puppy’
Congenital hypothyroidism - presentation
Disproportionate dwarfism
- wide skull
- macroglossia (tongue too large for mouth)
- delayed dentition
Signs of adult hypothyroidism
Affected dogs at risk of OA due to epiphyseal dysgenesis (joint abnormalities)
Only 3.6% of dogs diagnosed
Congenital hypothyroidism - diagnostics
Biochemistry
- hypercholesterolaemia
Haematology
- Non-regenerative anaemia
Thyroid hormones
- definitive: low T4 with high TSH
Low T4
- interference of non-thyroidal illness
- age-related interference (4.5x higher in healthy puppies up to 3mo)
High TSH
- will be low if CCH: thyrotropin-releasing hormone (TRH) functional test
Thyroid scintigraphy
- diagnostic
- decreased or absent radionuclide uptake
Congenital hypothyroidism - tx
Problem = insufficient thyroxin
Levothyroxin
Prognosis guarded
- contrast with good prognosis for acquired?
- age of diagnosis may limit additional growth
What does aplasia mean?
- failure to develop
What does hypoplasia mean?
- incomplete or under-development
What does atrophy mean?
- something may have developed, but now its deteriorating e.g. autoimmune dz
Pancreas - islet cells vs acinar cells
Islet cells
- produce insulin
- endocrine
Acinar cells
- produce digestive enzymes
- exocrine
EPI - what is it?
- exocrine pancreatic hormone deficiency (e.g. trypsin)
EPI in dogs
- most commonly pancreatic acinar atrophy (PAA)
- believed to be autoimmune
- complex heritability
- may have concurrent DM
EPI in cats
- most commonly chronic pancreatitis
Juvenile diabetes mellitus - what is it?
= insulin deficiency (usually absolute)
- DM diagnosed <6m/o
- uncommon
Variable aetiology
- congenital islet cell atrophy, aplasia or hypoplasia
- not usually auto-immune
- insulin receptor defects possible but not reported
- Keeshond’s may have heritable dz
Juvenile diabetes mellitus - presentation
- stunted growth
- other hallmarks of DM including cataracts
Juvenile diabetes mellitus - diagnostics
- fasting hyperglycaemia
- glucosuria
- fructosamine
- glucose curves
Juvenile diabetes mellitus - tx
Treatable with insulin therapy possibly but challenging
Porto-caval & portosystemic shunt (PSS) - what is it?
Structural defect: foetal vascular structure fails to close (or forms during development)
Porto-caval & portosystemic shunt (PSS) - types of shunt
When the shunt develops: congenital vs acquired
- congenital: usually single, persistent foetal structure
- acquired: usually multiple/complex, cirrhosis, portal hypertension
Number of shunts: single vs multiple/complex
- single e.g. persistent ductus venosus
- multiple e.g. cirrhosis, portal hypertension
Location: intra vs extra hepatic
- intra = most common congenital PSS of large dogs
- extra = most common congenital PSS of cats and small dogs
Porto-caval & portosystemic shunt (PSS) - presentation
Neurological signs - hepatic encephalopathy (HE)
- depression
- head pressing
- blindness
- ataxia
- seizure (may occur soon after a meal)
GI signs
- hypersalivation
- d+
- v+
Urinary signs
- ammonium bitrate crystalluria
- dysuria
- pollakiuria
- haematuria
- stranguria
Stunted growth
Acquired shunts:
- ascites
Porto-caval & portosystemic shunt (PSS) - haematology
- leukocytosis
- microcytic anaemia
Porto-caval & portosystemic shunt (PSS) - biochemistry
Increased bile acid (fasting in some cases, postprandial in all)
- highly suspect in young animal with signs of HE
Increased ALT, ALP
- ALP may be age-related (rather than cholestasis)
Other hepatic markers:
- hypoglycaemia
- hypoalbuminaemia (may be normal in cats)
- low urea
Hyperammoniaemia
- dynamic testing: Ammonia tolerance test
Porto-caval & portosystemic shunt (PSS) - urinalysis
- low USG
- ammonium biurate crystalluria
Porto-caval & portosystemic shunt (PSS) - imaging
Diagnostic
Radiography: may see micro hepatic, renomegaly
US: may be challenging, esp extra hepatic shunts
CT angiography
Scintigraphy: technetium circulates more rapidly to heart and lungs
Porto-caval & portosystemic shunt (PSS) - tx
Problem = persistent/abnormal vascular structure
Surgery - close the structure
- ideal for single congenital
- ligation: may be abrupt, risk of complications
- constriction: gradual - aneroid constrictor, thrombogenic coil
Medical management
- not all can be closed (complexity, finances)
- lactulose: acidifies colonic contents, trapping ammonia
- antibiotics (e.g. amoxicillin): reduces colonic bacteria that produce ammonia
- protein restricted diet: reduce ammonia production
Vascular ring anomaly: persistent right aortic arch (PRAA) - what is it?
Structural defect: foetal vasculature fails to close
6 embryonic paired aortic arches surround the foregut
- arches either involute or persist to become adult structures
- embryonic foregut becomes oesophagus and trachea
4th right aortic arch can persist (abnormally) and lead to compression of the oesophagus.
PRAA is the most common of up to 9 types of VRA identified.
Vascular ring anomaly: persistent right aortic arch (PRAA) - presentation
Regurgitation
- soon after weaning
More common in dogs than in cats
- may be heritable e.g. GSDs
Vascular ring anomaly: persistent right aortic arch (PRAA) - diagnostics
Radiography
- leftward deviation of trachea
Barium study
- oesophageal dilation
CT angiography
- surgical planning
Vascular ring anomaly: persistent right aortic arch (PRAA) - tx
- surgical closure
- prognosis can be good if carried out before development of chronic oesophageal dilation or other complications (aspiration pneumonia)
Congenital renal dz - what is it?
Structural anomalies of the kidneys
Developmental abnormalities
- dysplasia/hypoplasia
- aplasia/agenesis
- renal fusion
Some types of cystic dz (e.g. polycystic kidney dz [PKD] may be congenital)
- autosomal dominant heredity in Persian & DLH cats
Congenital renal dz - dysplasia
= kidney(s) fail to develop normally
- kidney(s) hypoplastic with subnormal cortex
- unilateral cases usually develop hypertrophy of contralateral kidney
- histologic abnormalities e.g. immature glomeruli: CRF may be identified between 6m-2y/o
- rare in cats
Congenital renal dz - aplasia/agenesis
= kidney and ureter fail to develop
- unilateral cases may have same-sided reproductive abnormality
- bilateral = death
- other kidney may function normally (incidental finding)
Congenital renal dz - renal fusion
= kidneys fuse during development
- horseshoe kidney
- function often normal
