Growth Hormone Flashcards
Cell types in adenohypophysis
Corticotrophs
Somatotrophs
Gondaotrophs
Lactotrophs
Thyrotrophs
Positive and negative input on GH release
positive:
GHRH
Grehlin (synergistic with GHRH)
Thyroid hormone
Negative
Somatostatin
Progesterone
Cortisol
Rapid and indirect effects of GH
Direct/Rapid - GH receptor
- increased gluconeogenesis, increased lipolysis
- Protein synthesis
- Epiphyseal growth
- production of IGF1 by liver (if suffient nutrients and insulin in portal blood)
Indirect - slower, mediated by IGF1 from liver and other tissues
- protein synthesis
- Insulin effects –> inhibits gluconeogenesis and glycogenolysis and lipid lysis
- Epiphyseal growth
Causes of canine hypersomatotropism (4)
Increased endogenous progesterone (luteal dioestrus)
Exogenous progesterone increasing mammary tissue GH release
Rarely pituitary adenoma
hypoTH can also increase GH
Causes of feline hypersomatotropism
Neoplastic transformation of somatotrophs (adenoma) - unclear if overproduce other pituitary hormones.
Systemic effects of hypersomatotropism
DOGS:
Pretty much one of the only causes of Type 2 DM in dogs - why dioestrus DM occurs in some bitches and not others is not well understood (thought to be B cell dysfunction concurrently in this subset)
- oropharyngeal mucosal hypertrophy → snore, exercise intolerance
- Articular cartilage proliferation
- Abdominal enlargement
- Enlargement of paws
CATS
- Insulin resistance: enhanced hepatic gluconeogenesis and reduced peripheral glucose utilisation → DM if there is concurrent B cell dysfunction
The increase in IGF1 insulin agonism is not sufficient to overcome antagonistic effects of GH
- Phenotypic: thickened oropharyngeal tissue causing stridor, broad facial features, prognathia inferior, clubbed paws, abdominal organomegaly
- Degenerative arthropathy: chondrocyte proliferation disrupting joint congruity
- Cardiomegaly: hypertrophic phenotype
- Evidence of CNS signs due to expansion of mass
- Rarely have concurrent pituitary HAC
- Renal dysfunction: not reported as often as in past (12% cf 50%)
- hyperproteinaemia
Diagnosis of hypersomatotropism in dogs and cats
DOGS: measuure progesterone (if >2 this is likely the cause and coming from mammary tissue)
Dioestrus assoc - 3-5weeks after oestrus
Discontinue progesterones
If a source of exogenous progesterone not found:
Check for mammary tumour
Check for exogenous source of P4
Check for hypothyroidism
GH - single measurement is not enough due to pulsatile release. Labile in sample.
Glucose tolerance test: GH does not change in acromegaly and high basal insulin.
IGF1 - may be more available and less labile in sample.
→ ref ranges are based on dog size.
CATS:
Should be routinely evaluated in newly diagnosed DM cats - reports of HS having concurrent DM in up to 100% of cases.
Poorly controlled, older, diabetic patient that is gaining weight.
Also consider in cats with HCM - recent report of 6% prevalence of IGF1 > 1000
IGF-1- PPV of 95% if >1000 in diabetic patient.
800-1000 considered grey zone
More stable in blood and directly reflects GH levels (over 24h), can be lower in early disease → retest in 2 months if strong suspicion.
- May be reduced by severe systemic disease, starvation, lack of insulin.
Non-medicalTx options for hypersomatotropism in cats and adv/disadv
Surgery -
Removes tumour Normalisation of IGF-1 and cure of HS in >90% of cats Approximately 70% DM remission rate
HCM reported to resolve
JVIM 2021 - treated 68 cats with HS and DM; 58 survived to discharge. 55/58 surviving cats had improved diabetic control, 41/58 entered diabetic remission
Another 25 cat study same year reported only 1 death and 22/24 diabetic remission
Surgery is more effective than medical management or RT at controlling endocrine related signs associated with a FPA and can also address neurologic signs associated with the mass effect
BUT - Limited availability Costly
Associated mortality (<10%)
Long-term hormonal replacement required-
DDAVP, levothyroxine and hydrocortisone PO
RT - Improved DM control common, with 30%–40% diabetic remission rate (68% in JVIm 2018)
Might shrink tumour, and thus improve any neurologic signs
Less likely to cause concurrent hypoxia or hypoTH - JVIM 2018 study.
JVIM 2018 - stereotactic radiation, better than previous reports of non-stereotactic
BT - weeks to months for improvement to become apparent IGF-1 and mitogenic effects of GH do not normalise
Relapse common Limited availability Costly
Medical Tx options for hypersomatotropism in cats
Cabergoline D2 receptor agonist inhibits GH release
JFMS 2021 - 3 cats entered diabetic remission with treatment of 2-3 months
JFMS 2022 - 23 cat, reduced IGF in 35% (normal in 26%) . Insulin dose and resistance index improved. 8/23 (35%) achieved remission
Hypoglycemia in 3 cats
AEs are rare
Pasireotide - somatostatin analogue
Improved DM control common, with diabetic remission rates of approximately 20%–25%
Generally well-tolerated
JVIM 2017 - reduced insulin resistance and dose required. Diarrhoea common AE
Insulin only - Does not treat the pituitary tumour or mitogenic effects of GH (eg, acromegalic changes) DM control often poor with severe ongoing DM signs Large insulin doses potentially required, which is costly Large insulin dosage makes hypoglycemic episodes possible when pulsatile GH secretion is low
Diagnosis of pituitary dwarfism
Rule out: PSS, nutritional, parasites, EPI, congenital hypoTH
GSD - genetic test available.
Endocrine Testing: post-stimulation GH measurement
→ stimulation can be with clonidine, GHRH, xylazine
→ normally 2x increase with stimulation
GHRH stimulation seems to be most reliable and least likely to cause side effects
IGF1 - could be used as a surrogate marker but can be lowered due to other disease so is not a definitive diagnosis.
TSH - low levels are not definitive, need TRH stimulation test to confirm Dx (and can be normal in some cases with isolated GH deficiency)
Cause of pituitary dwarfism
failure of organogenesis which may cause isolated or combined pituitary hormone deficiency.
Dwarfism is GH deficiency and is the most obvious
→ Autosomal recessive inheritance in GSD (combined GH, TSH, prolactin deficiency, normal ACTH) degree of failure is variable
Similar syndrome described in a small number of cats with symptoms developing at 1-2 months of age.
Symptoms of pituitary dwarfism
Poorcoat, retention of guard hairs
Wolf-like
Undersized
Delayed growth plate closure
Truncal alopecia, hyperpigmentation
Lethargy, inactivity and dull from 2-3y, due to TSH deficiency and or cyst enlargement
