Endocrine: GH disorders and hypothyroidism Flashcards
What is pituitary dwarfism caused by?
Hyposomatotropism (lack of growth hormone production)
What is thought to cause congenital hyposomatotropism?
Primary failure of complete differentiation of the craniopharyngeal ectoderm of Rathke’s pouch into a functioning anterior pitutary
What are potential causes of acquired hyposomatotropism?
Trauma, iatrogenic removal (hypophysectomy), neoplasia of the pituitary, infection/inflammatory
The initial post-natal growth period (1-2 months) is mostly determined by what?
Mostly genetically determined - so hyposomatotropism often isn’t visible until after 1-2 months of age
If isolated growth hormone deficiency is present (all other pituitary hormones are normal), the patient will have what physical appearance?
Proportionate dwarfism - the short stature is proportional throughout the body
Apart from dwarfism, what are other physical exam findings with hyposomatotropism?
- Prolonged retention of deciduous teeth
- Hair coat is dry and dull with potential retention of secondary hairs and lack of guard hairs
- Bilateral corneal edema from a reduction in corneal endothelial cell density has been described
How is hyposomatotropism typically diagnosed and why?
Measurement of IGF-1
- Hepatic IGF-1 secretion is primarily induced by GH
- Unlike GH, its secretion is not pulsatile and the results reflect GH concentrations over the prior 24 hours
What other systemic diseases may affect IGF-1 levels and should be ruled out before interpretation?
- Liver dysfunction (PSS)
- Renal disease
- DM
How is feline hyposomatotropism treated?
- No feline GH products, can use human or porcine, but there is some concern for antibody production. Also increases risk of DM and is expensive
- Treat other concurrent pituitary hormone deficiencies
It is recommended that all cats with newly diagnosed DM be screened for what disease?
Hypersomatotropism - in a recent study, 25% of diabetics had acromegaly
If serum IGF-1 is not supportive of hypersomatotropism, but the clinical picture suggests it, when should you repeat IGF-1 testing?
In 2 months or if the patient develops insulin resistance over time
What causes feline hypersomatotropism?
Neoplastic transformation of the somatotrophs (acidophils) in the anterior pituitary - most are adenomas with rare carcinomas described
What environmental contaminant has been linked to the development of hypersomatotropism in cats?
Organohalogenated contaminants (OHC) from flame retardant material, PCBs, etc. Increased in cats with HS but it’s unknown if its a cause or consequence of the disease
What are the clinical signs of feline hypersomatotropism?
- DM with insulin resistance
- PU/PD
- Polyphagia
- Weight GAIN despite suboptimal diabetic control
- Upper respiratory stridor (50%) from tissue swelling/narrowed nasopharynx
- Increased width of the head
- Broad facial features
- Prognathia inferior (protrusion of the lower jaw)
- Clubbed paws
- Abdominal enlargement with organomegaly
- Heart murmur and CHF
- CNS signs - circling, blindness, seizures
A serum IGF-1 > 1000mg/dL has a PPV of what for feline hypersomatotropism?
95%
What is a caveat of IGF-1 testing in new diabetics?
Hepatic IGF-1 synthesis is dependent on adequate concentrations of portal insulin - can be deficient in new diabetics, resulting in false negative IGF-1 results in 9% of cats
What surgical approach is used in a hypophysectomy in cats?
Transsphenoidal - through the soft palate and nasopharynx
What percent of cats enter diabetic remission within 2 months of surgery?
85%, remainder have good glycemic control with traditional insulin dosages
What is the peri- and post-operative mortality of hypophysectomy?
~10%
After a hypophysectomy, what medications are needed?
Hydrocortisone and levothyroxine for life, DDAVP can be temporary in most cats
What is the mechanism of action of pasireotide?
Multi-receptor somatostatin analogue
What hormone stimulates GH production? What inhibits it?
- Stimulatory: hypothalamic GH-releasing hormone (GHRH) or gherlin produced by the stomach
- Inhibitory: hypothalamic somatostatin
In dogs, what other tissue secretes GH?
Mammary ductular epithelium - GH concentrations in dogs do not decrease after hypophysectomy, likely due to mammary secretion
What reproductive hormone can increase the mammary secretion of GH in dogs?
Progesterone
What are the rapid (catabolic) effects of GH?
Insulin antagonism => lipolysis, gluconeogenesis, restricted glucose transport across cell membranes, hyperglycemia
What are the slow (anabolic) effects of GH?
Mediated by IGF-1 => stimulates protein synthesis, chondrogenesis, and growth
What is a major factor in the final body size of different dog breeds?
IGF-1 single nucleotide polymorphism