Endocrine & Metabolic Emergencies Flashcards
What are endogenous steroids synthesized from?
Cholesterol
What are two examples of hydrophilic compounds (water soluble)?
Peptides and catecholamines
What are two examples of lipophilic compounds (lipid soluble)?
- Steroids and thyroid hormones
- Circulate in blood bound to plasma proteins
- This binding greatly slows their clearance from plasma
What is the hypothalamic pituitary axis?
- A major neuroendocrine system
- Main stress response
- Relationship and interaction between hypothalamus, pituitary gland, and target organs
How does the HPA exert its effect?
In response to corticotropin releasing hormone (CTRH) from the hypothalamus, the anterior pituitary gland secretes adrenocorticotropic hormone (ACTH), which acts on the cortex of the adrenal gland to secrete cortisol to the body
What is the hypothalamus? (In relation to the HPA)
- The coordinating center of much of the endocrine system
- It consolidates signals from the body and then delivers precise signals to the pituitary gland
What hormones are secreted by the anterior portion of the pituitary gland? (adenohypophysis)
- TSH: thyroid stimulating hormone
- ACTH: adrenocorticoptropic hormone
- LH: luteinizing hormone
- GH: growth hormone
- Prolactin
- FSH: follicle stimulating hormone
What hormones are secreted by the posterior portion of the pituitary gland? (neurohypophysis)
- ADH
- Oxytocin
What part of the pancreas secretes insulin?
The beta cells of the islets of Langerhans
What are the acinar cells?
The functional unit of the exocrine pancreas that synthesizes, stores, and secretes digestive enzymes
What are the 4 cell types in the pancreas and what do they secrete?
- Alpha = glucagon
- Beta = secrete insulin
- Delta = somatostatin
- F = pancreatic polypeptide
What population of veterinary patients are most likely to develop DM?
- Dogs 4-14 years old
- Females are twice as likely
- Male neutered cats >6y
Describe Type 1 DM
- Primary insulin dependent
- Destruction of beta cells
- Require insulin for life
- Almost all dogs and 50-70% of cats develop Type 1
Describe Type 2 DM
- Non insulin dependent DM (NIDDM)
- Uncommon in dogs
- Results from insulin resistance, dysfunctioning beta cells, and increased hepatic gluconeogenesis
Does Type 2 DM progress to ketoacidotic states?
No
Can NIDDM cats progress to IDDM?
Yes
What is secondary diabetes?
- Development of carbohydrate intolerance secondary to concurrent insulin resistant disease
- Pregnancy, Cushings
What diet should be promoted for DM?
- Diet high in carbs with fiber
- Fiber helps promote weight loss and slows absorption of glucose from GIT, which helps reduce the post prandial flux of glucose
- High protein diet for cats
What does the fructosamine test indicate?
- Fructosamine is formed by glycosylation (the reaction in which a carb is attached to another molecule to form a glycoconjugate) of serum proteins such as albumin
- Evaluates BG over a matter of weeks
- Normal 225-360 umol/L
- > 500 suggests inadequate control of DM
What is the Somogyi phenomenon?
- Characterized by episodes of hypoglycemia, followed by rebound hyperglycemia
- Indicates that the insulin dose is too high
- Suspect if clinical signs of DM are present with fructosamine levels <400
What are the 3 types of ketones?
- Beta-hydroxybutyrate
- Acetoacetate
- Acetate
How do ketones form?
- Normally, fatty acids are released from adipose tissue, oxidized by liver, and formed into triglycerides via ‘beta oxidation’
- Without insulin, the fatty acids are converted to ketones
How do ketones cause an osmotic diuresis?
Ketones and glucose begin spilling into the urine; the secretion of ketones drags along positively charged ions (Na, K), which causes increased loss of fluid and salt
Why is lipemia sometimes seen in DKA?
Because of the increase in free fatty acids, because without insulin, the lipoprotein lipase is not activated
Why does hyponatremia occur in DKA?
An increase in osmoles within circulation draws fluid into the vascular space, resulting in dilution of Na
Do glucose and ketones improve with IVFT alone?
- Glucose: yes
- Ketones: no. Insulin required
Why does hypophosphatemia occur in DKA?
Phos shifts into the ICS like K
Why is dextrose administered to DKA patients?
It is vital to achieve metabolic breakdown of ketone bodies and resolve acidosis
How long does ketone resolution take?
~3 days
At what pH should NaHCO3 administration cease?
7.2
Why do glucose levels need to be lowered slowly?
- The brain produces neurogenic osmoles in an effort to maintain adequate hydration in a hyperosmolar environment
- It takes time for these idiogenic osmoles to be removed from the brain
- Rapid changes in serum glucose cause marked reductions in osmolality of blood which can lead to the brain becoming hyperosmolar, causing cerebral edema
Why does hypoglycemia cause CNS depression?
The nervous tissue relies on glucose as its primary energy source
Why is hypoglycemia seen in neoplasia?
- Some tumors produce biologically active insulin like proteins
- Large tumor burdens consume a disproportionately large amount of glucose to sustain aberrant metabolic needs
Why can polycythemia cause hypoglycemia?
Overuse of glucose to support the metabolic needs of the RBCs
What is Fanconi syndrome?
A form of renal tubular acidosis in which the proximal renal tubules do not properly reabsorb electrolytes and nutrients back into the body
What is an insulinoma?
- The most common tumor causing hypoglycemia in the dog
- A type of apudoma (endocrine tumor) that produces excessive amounts of hormones
What blood test can confirm an insulinoma?
- Serum insulin test taken at time of hypoglycemia
- Insulin level will be high
Is end stage hepatic insufficiency a common cause of hypoglycemia?
No, it is an uncommon cause as glucose homeostasis is one of the last functions to be lost
Why does Addison’s cause hypoglycemia?
- Absence of cortisol
- Cortisol causes increased insulin action and decreased gluconeogensis
What is hyperosmolar hyperglycemic state? (HHS)
- Profound hyperglycemia (>600) along with hyperosmolarity (>350) and dehydration without the presence of ketoacidosis
- Pt is in a continuous state of osmotic diuresis and polyuria, leading to a loss of free water and a state of hyperosmolarity
What is the base substrate used to synthesize steroid hormones?
Cholesterol
What is CushinG’s?
An excess of cortisol either from the pituitary gland or the adrenal CORtex causing an excess of GlucoCORticoids (medication = hydroCORtisone)
What is cortisol?
Glucocorticoid hormone produced by the CORTEX of the adrenal gland
What is aldosterone?
Mineralcorticoid hormone produced by the MEDULLA of the adrenal gland
What is the most common cause of Cushing’s?
A tumor on the pituitary
What population of veterinary patients are most likely to develop Cushing’s?
Dogs >6y
What biochemical changes can be seen in Cushing’s?
- Elevated ALKP, ALT, Chol
- Lipemia
- Low USG due to effects of glucocorticoids in GFR and renal response to ADH
Adrenal dependent Cushing’s dogs should have ___ circulating ACTH
Minimal
Pituitary dependent Cushing’s dogs should have ___ circulating ACTH
Excessive
How does Trilostane help treat Cushing’s?
It inhibits an enzyme necessary for the synthesis of cortisol
What is Addison’s?
- A deficiency in the production of mineralcorticoids (aldosterone) or glucocorticoids (cortisol), or both
- Generally the result of bilateral adrenal atrophy with fibrosis that can be idiopathic or immune mediated
What medication can cause iatrogenic Addison’s?
Mitotane, a cytotoxic agent used to treat Cushing’s
What is one possible cause of iatrogenic secondary Addison’s?
Sudden withdrawal of exogenous high dose or long term therapy
What is secondary hypoadrenocorticism?
- Decreased production of ACTH by the pituitary gland
- Causes glucocorticoid deficiency only
How much of the adrenocorticol cells must be lost before clinical signs appear?
85-90%
What is atypical hypoadrenocorticism?
Inadequate secretion of only glucocorticoids
What is an Addisonian crisis?
A lack of aldosterone, resulting in Na, Cl, and free water loss in urine, with retention of K+, H+, and Ca. Severe electrolyte imbalances and dehydration contribute to shock and cardiac abnormalities
Who is most likely to develop Addison’s?
- Young to middle aged females
- Appears to be inherited in standard poodles and leonburgers
What Na:K ratio is seen with Addison’s?
<27:1
What lab changes are seen with Addison’s?
- Low Na:K ratio
- Prerenal azotemia
- Low USG due to increased Na losses
- Hypercalcemia due to decreased Ca excretion
- Hypoglycemia due to decreased hepatic gluconeogeneis
- Normal WBC (no stress response)
- Hyperkalemia
- Hypoalbuminemia
Why is megaesophagus sometimes seen in Addison’s?
- Secondary to electrolyte imbalances and cortisol deficiency
- Lytes can cause altered membrane potentials, resulting in decreased neuromuscular function
How long are cortisol levels stable in plasma or serum at room temp?
5 days
What steroid does not cross react with the cortisol assay of the stim test?
Dex SP
What is a pheochromocytoma?
- A neuroendocrine tumor that forms from the chromaffin cells (which produces the catecholamines epinephrine and norepinephrine) of the adrenal medulla
- Has a high potential to invade the caudal vena cava
- Can potentially release life threatening levels of catecholamines
- Signs can be intermittent
- Rarely metastasizes
What medications can be included in the treatment of pheos?
- Phenoxybenzamine (x 2 weeks prior to sx)
- Atenolol, propranolol
What is critical illness related corticosteroid insufficiency?
Failure of the adrenals to secrete adequate cortisol during severe illness
How can CIRCI be treated?
Replace physiologic glucocorticoids with hydrocortisone
What does hyperthyroidism entail?
- Excessive concentration of thyroxine (T4) and triiodothyronine (T3)
- Middle to older age cats
- Most cats = bilateral lobe, functional thyroid adenoma
- Dogs = thyroid carcinoma
- Stress leukogram can be seen as a response to the stress of thyroid hormone excess
How does radioactive iodine treat hyperthyroidism?
- Radioiodine is concentrated in the thyroid gland after administration, primarily in the hyperplastic or neoplastic cells
- There, it releases the radiation at the hyperfunctioning cells, destroying them
- Normal thyroid and parathyroid tissue remain minimally affected
What oral meds can be used to treat hyperthyroidism?
- Methimazole and propylthiouracil
- Absorbed and concentrated in the thyroid
- Inhibit further formation of thyroid hormones but do not block release of stored thyroid hormones
What is myxedema coma?
- A life threatening condition that results from chronic, severe, hypothyroidism
- Decreased mental status, hypothermia
- Hypothyroid patients exhibit multiple physiologic alterations to compensate for the deficiency of thyroid hormone. Factors like infection can overwhelm these homeostatic mechanisms and can lead to myxedema coma
What medication is used to treat hypothyroidism?
Levothyroxine
What is hypoparathyroidism?
- Deficiency of PTH which results in hyperphosphatemia, hypocalcemia, and impaired vitamin D production
What is hyperparathyroidism?
- A common cause of hypercalcemia
- Rare in cats and uncommon in dogs
- Can be due to hyperplasia, adenomas, or carcinomas
- Treatment is surgical removal of affected tissue
