Endocrinology Lecture 21 PDF

Endocrine Testing Endocrine System Assays Produce and secrete hormones into bloodstream Adrenal glands Thyroid gland Parathyroid gland Pituitary Testing can involve measurement of resting hormones or response to stimulation/suppression ADRENOCORTICAL FUNCTION TESTING ...

Endocrine Testing Endocrine System Assays Produce and secrete hormones into bloodstream Adrenal glands Thyroid gland Parathyroid gland Pituitary Testing can involve measurement of resting hormones or response to stimulation/suppression ADRENOCORTICAL FUNCTION TESTING  Adrenal Axis Review Adrenal Glands Cortex- secrete Mineralocorticoid s, glucocorticoids, & sex hormones Medulla- secrete catecholamines (epinephrine/nore pin-ephrine) & dopamine) Mineralocorticoid Regulation (RAAS) Juxtaglomerular apparatus secretes renin in response to decreased renal perfusion Renin converts angiotensinogen to angiotensin I (AI) AI is converted to angiotensinogen II (AII) bye ACE AII binds to adrenal cortex to stimulate aldosterone secretion. Aldosterone decreases Na excretion from the kidney, water follows Na thus aldosterone serves to conserve H2O causing ↑ ECF an ↑ BP K+ is excreted from the kidney in response to aldosterone's Na retention effects (maintain electrolyte imbalance)  Glucocorticoid Regulation Starts with hypothalamus Corticotropin-releasing factor (CRF) is secreted by the hypothalamus under periods of stress CRF triggers anterior pituitary to secrete adrenocorticotropic hormone (ACTH) Cortisol is the major hormone released in animals. It feeds back to inhibit both CRF and ACTH release. Completes a balanced system  Adrenal Diseases Hyperadrenocorticism (aka Cushing’s Disease)- excessive cortisol release Hypoadrenocorticism ( aka. Addison disease) Typical: decrease in all Hyperaldosteronism Pheochromocytoma  Cushing’s Disease (Hyperadrenocorticism) Overproduction of cortisol Classified base on location of abnormality Pituitary Dependent Hyperadrenocorticism (PDH) Pituitary tumor secretes ACTH resulting in excess cortisol secretion Most common form Adrenal Tumor (AT) Less common 50/50 malignant vs benign Tumor itself secretes excessive cortisol Iatrogenic Due to excess exogenous steroid administration Will have ACTH stim that appears like an Addisonian Ectopic ACTH Secretion Rare in dogs, more common in humans ACTH is secreted from some place beside pituitary or adrenal cortex  Hyperadrenocorticism Clinical Signs PU/PD Polyphagia Truncal obesity/abdominal enlargement Panting Muscle weakness/wasting secondary to catabolic state  Addison’s Disease (Hypoadrenocorticism) Primary adrenocortical failure Failure of adrenal gland to respond to ACTH or to produce aldosterone and cortisol (typical hypoadrenocorticism) Atypical Addisonian’s still able to produce mineralocorticoids Life threatening Lack of mineralocorticoids hyponatremia, hyperkalemia, reduced ECF (hypovolemia, hypotension, reduced cardiac output) Lack of glucocorticoids Anorexia, vomiting, lethargy, ADR, diarrhea Signalment Young to middle aged dogs, females > males WHWT, SPOO, PWDG, ROT Clinical signs may wax/wane over period of time until animal presents in crisis. Na/K useful for screening (should be > 27) Other things can alter this (GI parasites, vomiting, etc) May be normal in atypical hypoadrenocorticism  Adrenocortical function tests ACTH Stimulation Test Dexamethasone Suppression Test Low-dose (LDDST) High-dose (HDDST) Urine- Cortisol Creatinine Ratio  ACTH Stimulation Test Used in animals with suspected hypoadrenocorticism (Addison) or hyperadrenocorticism (Cushing) Evaluates the degree of adrenal gland response to administration of exogenous ACTH Degree of response proportional to gland size and development Non-iatrogenic cushingoid animals will have an enlarged amt of glucocoid secreting tissue Distinguishes between iatrogenic and spontaneous hyperadrenocorticism Test of choice for diagnosing hypoadrenocorticism  Dexamethasone Suppression Tests Evaluates the suppression or lack there of following an injection of dexamethasone Under normal conditions exogenous steroids would suppress CRH & ACTH secretion Suppression is altered win animals with Cushing’s disease Cortisol levels are evaluated prior to injection, and 4hr & 8hr post injection Pattern of suppression/escape helps classify location of disease Dogs with HAC will have 8hr cortisol levels >1.4mcg/DL Confirms Cushing’s disease and can Urine Cortisol Creatinine Ratio Performed on urine sample Determines ratio of urine cortisol to urine creatinine Ratio normally low but will become elevated as the result of excess glucocorticoid release Any stress can cause this to occur Used only to confirm that an animal does NOT have Cushing’s disease Not used to diagnose hyperadrenocorticism  Sensitivity/Specificity of Screening Tests for HAC Sensitivity ability of a test to correctly identify those with the disease (true positive rate) Specificity ability of the test to correctly identify those without the disease (true negative rate).  Sensitivity/Specificity of Screening Tests for HAC ACTH is less Sensitive but more Specific than LDDST ACTH Stim is more likely to mistakenly diagnose some dogs that have HAC as being normal (false negative)but those that are identified as having HAC are more likely to have a correct diagnosis LDDST is more sensitive but less specific that ACTH LDDST is more likely to diagnose a normal dog as having HAC (false positive) More dogs that truly are Cushingoid will be diagnosed with LDDST than with ACTH Stim UCCR Sensitive but not specific Thus helpful for ruling OUT HAC  Case Study: Charlie 10 yr MN Cocker Spaniel PC: severe PU/PD 3 month duration PE: unremarkable Diagnostics CBC- NSF Chem- Alkp 900 UA- SpG 1.005 UC- e.coli (treated with no change in PU/PD status) ACTH stimulation test a resting cortisol of 2.7 1-hour post cortisol results 14.8 mcg/dL, respectively. These results were considered normal for the laboratory. Can Charlie still have hyperadrenocorticism?  Charlie LDDST resting cortisol - 5.1 mcg/dL (reference range, 1.4–5 mcg/dL) 4-hour post LDDS - 1.2mcg/dL 9 8-hour post LDDS= 4.6 mcg/dL The elevated 8-hour cortisol (reference range, < 1.4 mcg/dL), in combination with greater than 50% suppression in cortisol concentrations seen at 4 hours, was diagnostic of PDH.  Case Study: Yeti 18 month-old female spayed Irish Terrier 2 day history of decreased activity, depression, and anorexia Similar episode 2 months ago which resolved with supportive care PE: laterally recumbent and lethargic Injected mm, hyperemic, tacky CRT >3sec Temp- 95.1F, HR=48, RR- 16BPM BP- too low to measure  Yeti’s BW Results CBC HCT: 68% WBC 9.7k (WNL) Neuts WNL, Lymph Low N Plt WNL Chem ↑Phos 23; ↓Na 128; ↑K 10.5; ↓CL 95 ↑BUN 201/ ↑Creat 6.9  ER Treatment Aggressive IVF to address hypovolemic shock Dextrose, Insulin, and IV calcium gluconate Treat hyperkalemia (dextrose/insulin) Myocardium protectant(Calcium gluconate) K lower resting action potential and prevents repolarization of muscle cells Calcium stabilizes membrane potential and thus acts as a cardioprotectant IV Dexamethasone ACTH Stim: both pre and post cortisol < 1ug/dl = Addisonian  Long-term Treatment PO Pred (glucocorticoid support) Percorten Injections (mineralocorticoid support) THYROID TESTING  Thyroid Assays Thyroid hormone influences metabolic rate, growth, and differentiation of all body cells. Thyroid glands are governed by adrenal cortices. Thyrotropin-releasing factor (TRF) triggers release of thyrotropin or thyroid-stimulating hormone (TSH). TSH enhances thyroid growth, function, and thyroxine release. Thyroxine (T3 or T4) completes the cycle by inhibiting TRF and TSH.  Thyroid Assays Thyroid disease Hypothyroidism Primarily dogs, horses, ruminants, and swine. Hyperthyroidism cats Cause—dietary iodine deficiency or excess, primary gland disease Thyroid assays Total T4 Free T4 TSH Drugs may decrease T4 levels.  Total T4 Measurement of Total thyroxine (free and bound) Increased T4 diagnostic for Hyperthyroidism Small % of cats with hyperthyrodisim may have T4 WNL useful screening test for hypothyroidism. sensitivity 89% to 100% If the T4 concentration is well within reference range, it is very likely the dog is euthyroid and further thyroid testing is not required Free T4 (fT4) and thyroid-stimulating hormone (TSH) are evaluated only if the T4 concentration is low T4 concentration below reference range is not diagnostic for hypothyroidism Euthyroid Sick Syndrome a condition in which nonthyroidal illness suppresses the concentration of circulating thyroid hormones  Free T4 & TSH fT4 less likely to be affected by concurrent illness TSH  Hypothyroidism Most commonly due to idiopathic thyroid gland atrophy or immune-mediated lymphocytic thyroiditis Less common-abnormal thyroid-stimulating hormone (TSH) production, or abnormal thyroid gland development Signs related to decreased metabolic rate Lethargy or dull mentation Inactivity or unwillingness to exercise Weight gain Cold intolerance or heat seeking Dermatologic changes Symmetric, nonpruritic hair loss Post-clipping alopecia Dry, dull hair coat Scaling Hyperpigmentation Recurrent pyoderma or otitis externa  Hypothyroidism Diagnosis Total T4- low Free T4- Low TSH- High/normal  Hyperthyroidism Increase in T4 concentrations Most common thyroid disorder of cats occurs to adenoma (non-malignant tumor of the thyroid gland) Clinical signs Weight loss and poor hair coat Aggressive or “cranky” behavior Periodic vomiting Polyuria and polydipsia Increased appetite, activity, restlessness, and heart rate Occasionally, difficulty breathing, weakness, and depression Secondary hypertension and cardiomyopathies are of concern.