Endocrine System and Adrenocortical Testing

Endocrine Testing

• The endocrine system comprises glands that produce and secrete hormones into the bloodstream
• Glands include the pineal gland, hypothalamus, pituitary, thyroid, thymus, pancreas, adrenal, testes, and ovaries.
• Endocrine system assays measure resting hormones or hormone responses to stimulation/suppression.

Adrenocortical Function Testing

• Adrenal glands comprise a cortex and medulla
• Adrenal cortex secretes mineralocorticoids, glucocorticoids, and sex hormones
• Adrenal medulla secretes catecholamines (epinephrine/norepinephrine) and dopamine.

Mineralocorticoid Regulation (RAAS)

• The juxtaglomerular apparatus secretes renin in response to decreased renal perfusion
• Renin converts angiotensinogen to angiotensin I (AI)
• AI is converted to angiotensin II (AII) by ACE
• AII stimulates aldosterone secretion from the adrenal cortex
• Aldosterone conserves water and sodium, thus increasing ECF volume
• Potassium (K+) excretion increases in response to aldosterone's sodium retention

Glucocorticoid Regulation

• Hypothalamus secretes corticotropin-releasing factor (CRF) under stress
• CRF triggers the anterior pituitary to secrete adrenocorticotropic hormone (ACTH)
• ACTH stimulates the adrenal glands to release cortisol
• Cortisol feeds back to inhibit both CRF and ACTH release, maintaining a balanced system.

Adrenal Diseases

• Hyperadrenocorticism (Cushing's disease): excessive cortisol release.
• Hypoadrenocorticism (Addison's disease): decreased cortisol and often aldosterone production. This can be categorized as Typical Addison's (lack of all hormones) or Atypical.
• Other adrenal diseases include hyperaldosteronism, and pheochromocytoma.

Cushing's Disease (Hyperadrenocorticism)

• This condition is classified based on the location of the abnormality:
  • Pituitary Dependent Hyperadrenocorticism (PDH): Pituitary tumor secretes ACTH
  • Adrenal Tumor (AT): Adrenal tumor secreting cortisol
• Iatrogenic Cushing's can be caused by exogenous steroid administration.
• Ectopic ACTH secretion is rare, ACTH is secreted outside the pituitary and adrenal cortex

Hyperadrenocorticism Clinical Signs

• Polyuria/polydipsia (PU/PD)
• Polyphagia
• Truncal obesity/abdominal enlargement
• Panting
• Muscle weakness/wasting

Addison's Disease (Hypoadrenocorticism)

• Primary adrenocortical failure: failure of the adrenal glands to respond to ACTH or to produce cortisol and aldosterone
• Atypical Addison's: some mineralocorticoid production
• Life-threatening condition due to mineralocorticoid deficiency (hyponatremia, hyperkalemia, reduced ECF, hypovolemia, hypotension, and reduced cardiac output) and lack of glucocorticoids
• Clinical signs include anorexia, vomiting, lethargy, ADR, and diarrhea
• Signalment: frequently observed in young to middle-aged dogs, and more frequently in females
• Useful for screening; Na/K levels

Adrenocortical Function Tests

• ACTH Stimulation Test
• Dexamethasone Suppression Test (Low-dose LDDST, High-dose HDDST)
• Urine-Cortisol Creatinine Ratio

ACTH Stimulation Test

• Evaluates adrenal gland response to exogenous ACTH
• Degree of response proportional to gland size and development.
• Test of choice for diagnosing hypoadrenocorticism

Dexamethasone Suppression Tests

• Evaluates suppression/lack of following dexamethasone injection.
• Under normal conditions, exogenous steroids suppress CRH and ACTH secretion.
• Cortisol levels are monitored before and after injection (4 hours, 8 hours post-injection).
• Classifies the site of the disease.
• Confirms Cushing's disease and differentiates types.

Urine-Cortisol Creatinine Ratio

• Measures cortisol to creatinine ratio in urine.
• Normally low, elevated in excess glucocorticoid release.
• Only used to rule out Cushing's; not for diagnosis of hyperadrenocorticism
• Any stress can cause increase.

Sensitivity/Specificity of Screening Tests for HAC

• Sensitivity: ability of a test to correctly identify animals with the disease. (true positive rate)
• Specificity: ability of a test to correctly identify animals without the disease.(true negative rate)
• ACTH less sensitive but more specific than LDDS.
• LDDST is more sensitive, but less specific

Case Study: Charlie

• 10-year-old MN Cocker Spaniel
• History: severe PU/PD for 3 months, unremarkable PE
• Diagnostics: -CBC- normal -Chem- elevated alk phos
  • UA- sp gravity 1.005
  • UC- e-coli (no effect on PU/PD)
  • ACTH Stimulation Test - resting cortisol 2.7, 1-hour post 14.8.
• Could Charlie still have hyperadrenocorticism?

Case Study: Yeti

• 18-month-old female spayed Irish Terrier
• History: 2-day history of decreased activity, depression, anorexia
• PE: laterally recumbent, lethargic, injected mm, hyperemic tacky CRT >3sec, Temp 95.1F, HR=48, RR=16BPM, BP too low to measure.
• Diagnostics:
  • CBC- some abnormalities
  • Chem- elevated phosphorous, lowered sodium, elevated potassium, and lowered chloride; BUN and creatinine elevated

ER (Emergency Room) Treatment for Yeti

• Aggressive IVF to address hypovolemic shock
• Dextrose, insulin, and IV calcium gluconate (treat hyperkalemia)
• Myocardial protectant (calcium gluconate) preventing repolarization and thus acting as a cardioprotectant
• IV dexamethasone
• ACTH stim (both pre and post-cortisol < 1ug/dl = Addisonian)

Long-term Treatment for Yeti

• PO Pred (glucocorticoid support)
• Percorten injections (mineralocorticoid support)

Thyroid Testing

• Thyroid hormones regulate metabolic rate, growth, and cell differentiation
• Thyroid glands are controlled by the adrenal cortices.
• Thyrotropin-releasing factor (TRF) triggers thyrotropin or thyroid-stimulating hormone (TSH) release
• TSH enhances thyroid growth and thyroxine release.
• Thyroxine (T3 or T4) feeds back to inhibit TRF and TSH production.

Thyroid Disease

• Hypothyroidism: Primarily dogs, horses, ruminants, and swine; cats. Caused by dietary iodine deficiency. Primary gland disease.
• Hyperthyroidism: Primarily cats. Caused by dietary iodine excess. Primary gland disease.
• Thyroid Assays include measuring Total T4, Free T4, and TSH.

Total T4

• Measurement of total thyroxine (free and bound).
• Increased T4 is diagnostic for hyperthyroidism; small % of cats with hyperthyroidism may have normal T4.
• Useful for hypothyroidism screening; 89-100% sensitivity for hypo.
• If T4 in reference range, it’s likely euthyroid.

Free T4 & TSH

• fT4 is less likely to be affected by illness compared to total T4.
• TSH is useful for hypothyroid diagnostics.

Hypothyroidism

• Idiopathic thyroid gland atrophy or immune-mediated lymphocytic thyroiditis
• Less common: abnormal TSH production or abnormal thyroid gland development
• Signs reflect decreased metabolic rate, including lethargy, inactivity, weight gain, cold intolerance
• Dermatologic changes include symmetrical, non-pruritic hair loss, post-clipping alopecia, dry/dull coat, scaling, and hyperpigmentation, recurrent pyoderma, or otitis externa.
• Diagnosis includes decreased Total T4, Free T4, and elevated TSH levels

Hyperthyroidism

• Increased T4 concentrations, most common in cats, caused by thyroid adenoma.
• Clinical signs: weight loss, poor hair coat, aggression, increased appetite, polyuria, polydipsia, increased activity and restlessness, and occasionally panting, difficulty breathing, weakness, or depression.
• Secondary hypertension and cardiomyopathy of concern.

This quiz covers the essentials of the endocrine system, including the various glands and their hormone products. It also delves into adrenocortical functions, mineralocorticoid regulation, and the mechanisms of hormonal responses. Test your understanding of these critical concepts in endocrinology.