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QUESTIONS
- Explain how steroid hormones are able to effect action within cells.
- There are three zones of the adrenal cortex. Which layer is the outermost and which layer is responsible for aldosterone production? Which layers produce cortisol?
- What is the effect of corticosteroids on:
a) hepatic gluconeogenesis?
b) cellular uptake of glucose? - What is released into the hypothalamo-hypophyseal portal system to cause the release of ACTH by the adenohypophysis?
- Of dogs with Cushing�s disease, what percentage have pituitary dependent disease and what percentage have adrenal dependent disease?
- Of the dogs with pituitary dependent Cushing�s disease, what percent have microadenomas and what percentage have macroadenomas?
- How big does a pituitary tumor have to be to be classified as a macroadenoma?
- What is ectopic ACTH syndrome?
- Explain the rationale behind the ACTH stim test.
- Explain the rationale behind the low and high dose dexamethasone suppression tests.
- How should the urine cortisol:creatinine ratio fit into the diagnosis of Cushing�s disease?
- What percentage of adrenal tumors show calcification?
- What volume per pound is considered normal water consumption in determining whether a pet is polydypsic.
- What is �pseudomyotonia?�
- How do corticosteroids induce a �stress leukogram?�
- List the isozymes of alkaline phosphatase.
- In using Lysodren, what are the chief complications to beware of?
- What are the advantages and disadvantages of using Ketoconazole to treat Cushing�s disease?
- Describe a typical protocol for the initiation of and maintainance on lysodren therapy.
- What treatment options are available for pituitary macroadenoma?
- What treatment options are available for adrenal tumors?
ANSWERS
- The glucocorticoids exert their effects in responsive cells by getting absorbed into the cell & then binding w/an aporeceptor. They go together to the nucleus & influence transcription together.
- The zona glomerulosa is the outermost layer & it is also the layer responsible for aldosterone production. Zona fasciculata = the middle layer & the zona reticularis is the inner most. The innermost & middle layers produce cortisol.
- Glucocorticoids increase hepatic gluconeogenesis but inhibit peripheral glucose uptake.
- Corticotrophin-releasing hormone is the substance released into the hypothalamo-hypophyseal portal system.
- 85% have pituitary disease, 15% have adrenal dependent disease.
- Approximately 10% have macroadenomas.
- Macrotumors are > 1 cm across.
- Ectopic ACTH syndrome involves a tumor that secretes an ACTH-like substance. This phenomenon has not been documented in the dog but is usually due to lung tumors in humans.
- When ACTH is delivered, the adrenal gland will dump its stored cortisol. A Cushing�s adrenal has a lot to dump & will produce a higher cortisol level than a normal adrenal can.
- If you give a normal dog dexamethasone, the pituitary will cut ACTH production & 8 hours later, cortisol level will be suppressed. If the dog has cushing�s disease, either the pit. tumor will be unaffected by the dex & no suppression will result or the adrenal tumor will not be affected by the loss of ACTH & will not suppress.
In HDDS, there is so much dex being used that a pit. tumor actually will suppress.
- The urine cortisol:creatinine ratio is a screening test only. If it is normal, cushing�s is ruled out. If it is high, more testing is needed.
- Approximately 50% of adrenal tumors will calcify.
- A water consumption of 100 cc/kg (or 50cc/lb -1/5 cup per lb) would be considered polydipsia.
- Pseudomyotonia is a rare myopathy that occurs in Cushing�s disease is characterized by persistent muscle contraction after a voluntary effort ends. dogs have pelvic limb stiffness & bizarre EMGs.
- Increased PMNs & increased monocytes come from inducing demarginization & prevention of normal egress from the vasculature. The decrease in eosinophils comes from induced marrow sequestration. The decrease in lymphocytes comes from lysis.
- The isozymes of ALP are: placental, bone, steroid induced, liver.
- Chief problems w/lysodren = induction of Addison�s disease, temporary cortisol reductions leading to GI signs, or just reactions to the drug. It can even cause CNS signs as Opddd is related to DDT.
- The advantages of ketoconazole include the lack of necessary ACTH stims on a regular basis. If you get side effects from keto, you just stop the drug & wait for side effects to go away. Disadvantages = cost & that it must be given BID.
- Typical induction is 50 mg/kg divided BID for approx. 9 days. ACTH stim confirms the endpoint of induction. If ACTH is a flat line, the same dose is divided 2x per week. ACTH stims are due twice a year.
- Pituitary macroadenomas are treated with radiation. 70% will show improved neuro function. Of these 50% will show rapid improvement & the rest improvement didn�t show up until a month or two. Radiation may or may not control the Cushing�s disease, too.
- Treatment options for adrenal tumors include surgery or high doses of lysodren.
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