Congenital diseases

• What is pituitary dwarfism?

  Congenital growth hormone difficiency.
• What are the causes of pituitary dwarfism?

  Abnormal development of the pituitary gland:

  • Hormone-producing cells fail to differentiate during gestation.

  Inherited disease (simple autosomal recessive):

  • German shepherd most commonly affected.
  • Rare in cats

  Other pituitary hormones may be affected: thyroid stimulating hormone, prolactin, gonadotropins.
• What is the presentation of pituitary dwarfism?

  Animal may appear normal until about 2 months old:

  • Stunted growth, delayed dentition.
  • Puppy coat (primary guard hairs don’t develop), bilateral symmetric alopecia.
  • Abnormal reproductive development (Cryptorchidism, anoestrus).
• What is the prognosis for pituitary dwarfism

  Affected dogs will have a shortended life span:

  • Prognosis is guarded with treatment, poor witrout GH (important for the development of kidneys) these dogs go into renal failure.
• Diagnostics for pituitary dwarfism - biochemistry

  Elevated Creatinine:

  • GH deficiency impacts renal development.
  • TSH deficiency reduces glomerular filtration rate.
• Diagnostics for pituitary dwarfism - thyroid hormone

  Low thyroxine

  Low TSH
• Diagnostics for pituitary dwarfism - growth hormone/insulin like growth factor-1

  Low (but can be low normal in animals):

  • IGF-1 - indirect evaluation of GH
• Diagnostics for pituitary dwarfism - GH stimulation test

  Requires a GH stimulant (plasma GH should increase after 20-30 min):

  • GH-releasing-hormone
  • Alpha-Adrenergic drugs (clonidine, xylazine)
  • Human ghrelin.

  Try to trigger release of GH, if you don’t get one then this is diagnostic.
• What is the treatment for pituitary dwarfism?

  There are problems with the treatment, which is supplemental GH.

  There are no effective treatment for cats.

  The treatment is for dogs is feline GH but this can cause several problems - diabetes, and animals may require support to treat thyroid disease.
• What is congenital hypothyroidism?

  Congenital thyroxine deficiency

  Primary = abnormality of the thyroid glands.

  • Dysmorphogenesis - anatomical
  • Dyshormonogenesis - abnormality in hormone synthesis (fox terriers, rat terriers)

  Secondary = abnormality of the pituitary

  Tertiary = abnormality of the hypothalamus
• How does congenital hypothyroidism present?

  Disproportionate dwarfism

  • Wide skull
  • Macroglossia (tongue to large for mouth)
  • Delayed dentition.

  Signs of adult hypothyroidism - chunky, heat seeking behaviour.

  Affected dogs at risk of osteoarthritis due to epiphyses dysgenesis (joint abnormalities)
• Diagnosing congenital hypothyroidism

  Biochemistry:

  • Hypercholesterolaemia

  Haemotology:

  • Non-regenerative

  Thyroid hormones:

  • Low T4
  • Interference of non-thyroidal illness.
  • Age-related interference
  • High TSH
  • Will be low if CCH - thyrotropin-releasing hormone (TRH) functional test.
• What is the treatment for congenital hypothyroidism?

  Problem = insufficient thyroxine

  • Levothyroxine
  • Prognosis guarded
  • Contrast with good prognosis for acquired
  • Age of diagnosis may limit growth.
• What do the pancreas Islet cells produce?

  Insulin.

  They are an endocrine cell
• What do the pancreas Acinar cells produce?

  Digestive enzymes e.g. trypsin.

  They are exocrine cells
• What is Exocrine pancreatic insufficiency (EPI)

  Exocrine pancreatic hormone deficiency (e.g. trypsin)

  Dogs:

  • Most commonly pancreatic acinar atrophy (PAA)
  • Believed to be auto-immune
  • Complex heritability
  • May have concurrent DM.
  • Cats:
  • Most commonly chronic pancreatitis, can be failed to be recognised.

  Other causes are possible in both species:

  • Acinar aplasia or hypoplasia, pancreatic duct obstruction (neoplasia)
• What is juvenile diabetes mellitus?

  Diabetes mellitus (DM) diagnosed <6 month of age.

  Uncommon

  Variable aetiologies:

  • Congenital islet cell atrophy, aplasia or hypoplasia.
  • Not usually autoimmune
  • Insulin receptor defects possible but not reported.
• How does juvenile diabetes mellitus present?

  Stunted growth, other hallmarks of Dm including cataracts.
• How to diagnose juvenile diabetes mellitus?

  Fasting hyperglycaemia, glucosuria, fructosamine, glucose curves.
• How to treat juvenile diabetes mellitus?

  Treatable with insulin therapy possibly but challenging:

  • The dose is hard to work out as the animal keeps growing and changing and the dose is based on weight and metabolism.
• What is a Porto-systemic shunt?

  Structural defect: foetal vascular structure fails to close during gestation (or forms during development).
• What is Cirrhosis?

  The liver suffers from poor portal perfusion (e.g. fibrotic disease), which is compensated by an increase in hepatic arterial perfusion to maintain blood supply. This hypertension pushes the blood back into the portal system and leads to acquired PSSs as blood takes the path of lest resistance through collateral vessels.
• What are the different number of shunts you can get?

  Single:

  • E.g. Persistent ductus venosus.

  Multiple:

  • e.g. Cirrhosis, portal hypertension.
• What are the locations you can get with portal shunts?

  Intra = most common congenital PSS of large dogs.

  Extra = Most common congenital disease of cats and small dogs.
• What is the presentation of PSS

  Neurological signs - hepatic encephalopathy

  • Depression, head pressing, blindness, ataxia, seizure (may occur soon after a meal).

  Gastrointestinal signs:

  • Hypersalivation, vomiting, diarrhoea.

  Urinary signs (ammonium biurate crystalluria)

  • Dysuria, pollakuria, haematuria, stranguria

  Stunted growth
• Why do you get ascites with PSS?

  Much more liKelly in acquired due to portal hypertension. The liver suffers from poor portal perfusion (e.g. in fibrotic disease), which is compensated for by an increase in hepatic arterial perfusion to maintain bloody supply. The hypertension pushes blood back into the portal system and leads to acquired PSS as blood takes path of least resistance through the collateral vessels.
• Diagnosing PSS - Haematology

  Leukocytosis

  Microcytic anaemia
• Diagnosing 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**, hypocholesterolaemia**, low urea.

  Hyperammonaemia

  • Dynamic testing: Ammonia tolerance test.
• Diagnosing PSS - urinalysis

  Low USG

  Ammonium biurate crystalluria
• Diagnosing PSS - imaging

  Radiography: may see microhepatica, renomegaly

  Ultrasound: May be challenging, especially extrahpetic shunts.

  Computed tomography: CT angiography

  Scintigraphy: Technetium circulated more rapidly to heart and lungs, not used often.
• Treatment of PSS - surgery

  Close the structure (ideal for congenital).

  • Ligation: may be abrupt, risk of complications.
  • Constriction: Gradual - ameroid constrictor, thromogenic coil.
• Treatment of PSS - medical management

  Not all can be closed (complexity, finances)

  • Lactulose - acidifies colonic contents, trapping ammonia
  • Antibiosis (e.g. amoxicillin) - reduces colonic bacteria that produce ammonia, long term treatment.
  • Protein-restricted diet - reduce ammonia production.
• What is VRA?

  Structural defect: foetal vasculature fails to close

  Six embryonic paired aortic arches surround the foregut (eventually becomes oesophagus and trachea)

  • Arches either involute or persist to become adult structures.
  • Embryonic foregut eco ems the oesophagus and trachea

  Fourth right aortic arch can persist (abnormally) and lead to compression of the oesophagus.
• What is the presentation of VRA?

  Regurgitation:

  • Soon after weaning as this is when solid food is introduced.
  • Regurgitation is a young animal is suspect, timing especially so. No muscle control, can lead to aspiration pneumonia.
• Diagnosing VRA

  Radiography: Leftward deviation of the trachea.

  Barium study: Oesophageal dilation.

  CT angiography: surgical planning.
• Treatment of VRA

  Surgical closure - no other treatment

  Prognosis can be good if carried out before development of chronic oesophageal dilation or other complications.
• What is congenital renal disease?

  Structural abnormalities of the kidneys

  • Developmental abnormalities:
  • Dysplasia/Hypoplasia
  • Aplasia/Agenesis
  • Renal fusion
  • Some types of cystic disease may be congenital
• Congenital disease - Dysplasia

  Kidneys fail to develop normally

  • Kidneys hypoplastic with subnormal cortex.
  • Unilateral cases usually develop hypertrophy of contralateral kidney.
  • Histologic abnormalities e.g. immature glomeruli-chronic renal failure may be identified between 6 months to 2 years old.
  • Rare in cats.
• Congenital renal disease - Aplasia/Agenesis

  Kidney and ureter fail to develop.

  • Unilateral cases may have same-sided reproductive abnormality
  • Bilateral = death
  • Other kidney function may function normally (incidental finding).

  renal fusion:

  • Kidneys fuse during development
  • Horseshoe kidney - kidneys fuse together at the cranial poll.
  • Function are normal.