23 – Adrenal Gland and Endocrine Pancreas

Question 1

Adrenal gland

Answer 1

• Cortex manufactures glucocorticoids, mineralocorticoids and androgens

Question 2

What does aldosterone do?

Answer 2

• Promotes K and H excretion AND Na and Cl retention
• Important for maintenance of ECF volume

Question 3

What is the secretion of aldosterone regulated by?

Answer 3

• Ang II
• Plasma K+ concentration
• ACTH (permissive effect)

Question 4

Primary hypoadrenocorticism (Addison’s disease)

Answer 4

• 90% have (bilateral) immune-mediated destruction of all layers of the adrenal cortex
  o Inadequate secretion of BOTH mineralocorticoids (aldosterone) and glucocorticoids (cortisol)
• 10% are ‘atypical”=only have glucocorticoid deficiency
  o Normal serum electrolytes at presentation
  o Some will progress to mineralocorticoid deficiency as well

Question 5

Secondary hypoadrenocorticism (Addison’s disease)

Answer 5

• Decreased pituitary release of ACTH
• Decreased GLUCOCORTICOIDS only
• Pituitary lesion OR prolonged exogenous steroid administration and subsequent rapid withdrawal (iatrogenic)
  o Pituitary decreases ACTH it produces and will eventually result in adrenal gland atrophy

Question 6

What is the common presentation of primary hypoadrenocorticism?

Answer 6

• Young to middle-aged dogs, rarely horses and cats
• Continuum of severity and chronicity
• Often display waxing/waning non-specific signs (secondary to lack of cortisol)
  o Episodic vomiting, diarrhea, melena, lethargy, dehydration, weight loss
• May have acute exacerbation: “Addisonian crisis”

Question 7

What might happen in an “Addisonian crisis”?

Answer 7

• Acute circulatory collapse
• Weakness
• Hypotension
• Severe electrolyte disturbances
• Dehydration
• Bradycardia

Question 8

What are the common changes seen with primary (typical) hypoadrenocorticism?

Answer 8

• Mild non-regenerative anemia
• **Lack of stress lymphopenia (in a sick dog)
  o +/- eosinophilia
• Hyperkalemia/hyponatremia (Na:K <23:1): NOT pathognomonic
• Azotemia and other changes related to hypovolemia
  o USG commonly <1.030
  o Often MIMICS renal failure

Question 9

Hyperkalemia/hyponatremia: is NOT pathognomonic, what are other situations?

Answer 9

• Renal failure
• Whip worm infection
• Pregnancy
• Some body cavity effusion

Question 10

What are the occasional changes you may see with primary (typical) hypoadrenocorticism?

Answer 10

• Hypoglycemia (20%)
• Hypercalcemia (30%)
• Hypocholesterolemia
• Hypoalbuminemia (20%)
• Elevated urea > creatinine

Question 11

How come lack of aldosterone mimic renal failure? (primary typical hypoadrenocorticism)

Answer 11

• Results in Na/Cl wasting
  o Losing more Na in urine
• Water follows Na, patient becomes progressively hypovolemic
• Start to accumulate lactic and renal acids
• May develop pre-renal azotemia and a high anion gap metabolic acidosis
• *chronic hyponatremia can lead to loss of corticomedullary gradient

Question 12

What does chronic hyponatremia lead to? (primary typical hypoadrenocorticism)

Answer 12

• Loss of corticomedullary gradient
  o Unable to concentration urine (USG <1.030)
  o Combination of azotemia and inappropriate USG may suggest primary renal disease at presentation
  o Should respond quickly to IV fluid therapy

Question 13

What are the lab abnormalities seen with primary (atypical) hypoadrenocorticism?

Answer 13

• **lack of STRESS leukogram in an obviously sick patient
• Eosinophilia
• Hypoglycemia
• Hypocholesterolemia
• (maybe hypercalcemia)

Question 14

It is easy to miss primary (atypical) hypoadrenocorticism, when should you suspect Addison’s?

Answer 14

• Profound weakness despite aggressive fluid therapy
• Not getting better despite appropriate therapy
• Dogs with chronic GI signs or another disorder that appear sicker than they should be

Question 15

What is the gold standard for diagnosing hypoadrenocorticism?

Answer 15

• ACTH stim
  o Post ACTH stim (1hr) cortisol <55mmol/L = SUPPORTIVE
  o Baseline cortisol is often low as well

Question 16

Some clinicians use basal cortisol alone as a ‘screening’ test for diagnosing hypoadrenocorticism. What is it ‘useful’ for?

Answer 16

• Can be used to RULE OUT hypoadrenocorticism
• NOT sufficient to diagnose hypoadrenocorticism
  o Cortisol levels fluctuate throughout the day
  o Does NOT measure adrenal reserve
  o Need to follow up with an ACTH stim to confirm the disease

Question 17

Type I DM

Answer 17

• Lack of insulin
• Hypoplasia or destruction of pancreatic beta-cells
• More common in dogs

Question 18

Type 2 DM

Answer 18

• Insulin resistance
• Decreased insulin production and poor tissue response
• Linked to lifestyle and obesity
• More common in CATS

Question 19

What are the common lab abnormalities with DM?

Answer 19

• Hypercholesterolemia and hypertriglyceridemia (lipemic plasma/serum)
• Elevations in hepatic enzymes (hepatic lipidosis)
• Fasting hyperglycemia and glucosuria
• Hyponatremia/hypochloremia (osmotic diuresis)
• May or may NOT see decreased serum K

Question 20

Why might you want to monitor K with the start of insulin therapy (with DM)?

Answer 20

• Look for evidence of weakness and collapse
• *insulin drives K levels into cells
  o Can lead to dangerous hypokalemia

Question 21

What are some complications that can happen with DM?

Answer 21

• Diabetic ketoacidosis
• UTI
• Diabetic hyperosmolar hyperglycemic state (HHS)

Question 22

Diabetic ketoacidosis

Answer 22

• Accumulation of ketone bodies formed from oxidation of FFAs
• Results in KETONURIA and KETONEMIA
• See positive urine dipstick +/- elevated anion gap (high AG metabolic acidosis)

Question 23

UTI (w/DM)

Answer 23

• May be ‘occult’ (not accompanied by pyuria)
• E. coli most commonly isolated

Question 24

Diabetic hyperosmolar hyperglycemic state (HSS)

Answer 24

• **Severe hyperglycemia (BG>34mmol/L), hyperosmolarity (>350mOsm/kg) and dehydration with the ABSENCE of significant KETOSIS (no high AG metabolic acidosis)
• May see neurological signs related to cerebral dehydration secondary to severe hyperosmolality (stupor, coma, ataxia, seizures)
• Poor prognosis, 65% mortality rate at initial hospitalization, 12% long term survival
• Aggressive rehydration may cause cerebral edema/herniation
• Many animals have serous concurrent disease

Question 25

How do you diagnosis DM?

Answer 25

- Persistent fasting hyperglycemia and glucosuria - Renal threshold - Serum fructosamine

Question 26

Persistent fasting hyperglycemia and glucosuria values

Answer 26

- DM: BC often >17mmol/L (can be lower) - Stress: BC usually <17mmol o Cats stress hyperglycemia up to 22-28mmol/L o Spillover glucosuria possible with stress if BG exceeds renal threshold

Question 27

What are the renal threshold values for glucose (and diagnosing DM)?

Answer 27

- Dog and horse: >10mmol/L - Cat: >15mmol/L - Cattle: ?5.6mmol/L

Question 28

Serum fructosamine

Answer 28

- Formed when glucose combines with protein - With persistent hyperglycemia, increased protein glycosylation occurs, resulting in increased serum fructosamine o Rough estimate of average BG over past 2-3 weeks

Question 29

When can you use serum fructosamine?

Answer 29

- Confirm diagnosis of DM - Monitor therapy in treated diabetes o Fructosamine decreases with improved glycemic control

Question 30

What is the most common cause of hypoglycemia on a chem panel?

Answer 30

- Delayed serum separation from cells (artefact) o RE-check BG to confirm persistence

Question 31

What are other common causes of hypoglycemia?

Answer 31

- Toxin ingestion (xylitol) - Sepsis and endotoxemia - Hepatic failure - Hypoadrenocorticism - Juvenile hypoglycemia - IF NO OTHER OVER CAUSE: possible insulinoma?

Question 32

Insulinoma

Answer 32

- Functional tumour of insulin-producing B-cell - See overproduction of insulin and resultant hypoglycemia - Most are malignant and metastasize

Question 33

How do you diagnosis insulinoma?

Answer 33

- BG <3.3mmol/L - Serum insulin=INAPROPRIATELY HIGH - Fructosamine, imaging, cytology and histopathology may also be helpful