Canine Hyperadrenocortism (Cushing Disease) PDF

Canine Hyperadrenocortism (Cushing disease) Hyperadrenocortism Signs Ddx Diagnosis Therapies Prognosis In Cats -caused by -No sex  -Cannot use basal  Mitotane  Adrenal...

Canine Hyperadrenocortism (Cushing disease) Hyperadrenocortism Signs Ddx Diagnosis Therapies Prognosis In Cats -caused by -No sex  -Cannot use basal  Mitotane  Adrenal No known breed excessive predilection for Hypothyroidis cortisol as non-adrenal  Trilostane adenoma: or sex production of HAC but female m illness can cause a high  Ketoconazole good predilection cortisol in the body dogs  Acromegaly circulating cortisol level  I-Deprenyl  Adrenal  Middle age- -Spontaneous: have higher  Diabetes 1) History and clinical  Surgery dependent older cats Pituitary dependent risk for adrenal mellitus signs (adrenalectomy / HAC- with  Clinical signs, ( Macroadenoma tumours  2) CBC/ serum hypophysectomy) carcinoma history similar to involving the -Middle aged- Hepatopathies biochemistry  Other treatment: (50%) dogs anterior pituitary) old animals  Renal 3) Urinalysis Antibiotics for UTI poor prognosis  Diagnostic Adrenal dependent disease 4) Baseline cortisol  Small work similar to (85% benign Sign:  Neoplasia measurement Carcinoma: if dogs except: adenoma /  5) Screening tests not mets- fair  ALP- not Hyperplasia, 15%  Abdominal Sex-hormone UC:CR to good common in cats malignant tumours) distension dermatoses (screening test)  Large because cats do -Iatrogenic Polyuria, * 10% of dogs ACTH carcinoma: not (excessive polydipsia, with HAC Stimulation test poor- fair (but have exogenous polyphagia, have (differentiation can do very corticoid-induced glucocorticoids/ lethargy Diabetes test) well isoenzyme steroids)  Mellitus LDDST on mitotane)  LDDST: Hepatomegaly, (screening test)  Pituitary extremely Characteristic of pendulous macroadenom sensitive, require HDDST adrenal tumour: abdomen, a + neuro 10 times the (differentiation Variable sizes obesity signs- poor to dose of dogs, test)  If one gland is  Hair loss, grave 0.1mg/kg IV affected, comedones, Endogenous  Untreated Treatment: contralateral gland hyperpigmentati ACTH HAC- poor Mitotane (rarely will be atrophied on Skin atrophy, concentration prognosis effective) thin hair 6) Diagnostic imaging  Rarely bilateral coat Radiography,  Treated Treatment of tumours  Thin skin, CT scan, MRI PDH – good choice:  Metastasis to bruising, Abdominal prognosis adrenalectomy lungs and heart calcinosis cutis, ultrasonograph (10% can even and (adenocarcinoma) Trauma of the y (identification live supplementation  Invasion of site of adrenal up to 4 years) with tumours into vena causing mild tumour or – average 26 mineralocorticoid cava bleeding adrenal months s and  Can lead to vena  Testicular glucocorticoids. enlargement) caval thrombosis atrophy usually with  Muscle *0% with HAC malignant tumours weakness, are diabetics  muscle atrophy, Progesterone Histopathologically: atrophy of secreting adenoma or temporal tumours cause carcinoma muscle, trunc the same clnical and sign as cortisol hindlimb muscle secreting  facial nerve tumours palsy CLiniacal sign: Truncal obesity Pot bellied Some dogs may appearance, develop thin, pyoderma serborrheic (superficial, slow growing deep) haircoat, muscle weakness, skin fragility, CNS sign if macroadenoma Corticotropin-releasing hormone (CRH) is released by the paraventricular nucleus of the hypothalamus, and transported via the hypophyseal portal system to the anterior pituitary where it stimulates the release of adrenocorticotropic hormone (ACTH). Corticotrophs of the anterior pituitary releases ACTH, which stimulates the release of cortisol from the adrenals. Cortisol exerts negative feedback on the release of both ACTH and CRH.  ACTH excess is a feature of both Addison's disease (primary adrenocortical insufficiency)and ACTH dependent Cushing's syndrome  Cortisol exhibits diurnal variation, in which the plasma concentration of cortisollevels vary during a 24 hour period. History and C/S CBC and SBC Urinalysis Radiograph Abdominal Ultrasounography Most patients “Stress SG600nmol/L) only considered PDH presence of AT mg/kg) test or LDDST to confirm Sensitivity 57-83%,  Can never confirm PDH-high ACTH hyperadrenocorticism 4. Collect a basal specificity 59-93% adrenal tumours (>28pg/ml) sample for serum or  There is still 50% chance ADH-low ACTH plasma cortisol the dog has PDH or AT (90% of cats) muscle mass complications Can be production of thyroid animals thyroid carcinoma) increased Very active such as unilateral or hormones from the 9mV) cell abnormalities Echocardiography- (high thickness of the left PCV, MCV), ventricular gastrointestinal wall, increased upset. contractility HCM Most side effects Serum appear within the biochemistry panel first 4–6 weeks of often shows therapy and elevation of are less common several liver after 2 or 3 months enzymes. of treatment Thyroid Lifelong daily scintigraphy medication is required which is a MRI, disadvantage to Ultrasonography, owners whose cats CT scan resist pilling Definitive CBC and T4 levels diagnosis: feline need to be thyroid panel or rechecked regularly blood test for the remainder with elevated T4 of the cat’s life. levels Transdermal 2-10 % of cats will methimazole have normal T4 preparations, levels when available, can be useful for Feline thyroid uncooperative panel: cats. I Which includes T4, 2. Surgical T3, free T4 by removal of affected equilibrium dialysis thyroids and TSH. Most hyperthyroid This would be the cats have benign, most useful in well-encapsulated assessing a cat with tumors that are many health easily removed. problems. Surgery usually results in a cure, Diagnosis of feline but anesthesia can hyperthyroidism be requires the challenging in these demonstration of older patients persistently whose disease may elevated thyroid have affected their hormone hearts and other organs. concentrations (T4, Although surgery or T4 may seem costly, it plus fT4ed) often ends up being occurring less expensive than concurrently with years of oral one or more of the medication and typical regular clinical signs. bloodwork rechecks. but will end up hypothyroid and need to supply with T4 orally 3. Radioiodine therapy I-133 Best and most sophisticated treatment option Radioactive iodine, given by injection (SQ), becomes concentrated in the thyroid gland, where it irradiates and destroys the hyperfunctioning tissue. No anesthesia or surgery is required, and only one treatment is usually needed to achieve a cure. Cats may need to be kept at the treatment facility for 10 to 14 days until the level of radioactivity in their urine and feces decreases to an acceptable level. owners. Success rate of a single 131I treatment is very high – over 95% in most studies. T4 declines into the reference interval by 4–12 weeks post-treatment. Complete resolution of clinical signs of FHT may take several months. ❖Although 131I has a physical half-life of 8 days, the biological half-life is much shorter, generally 1.5–4 days. ❖131I emits both beta particles and gamma radiation. ❖The beta particles are responsible for the majority of tissue destruction, but are only locally destructive, traveling a maximum of 2 mm. ❖Therefore, no significant damage to adjacent parathyroid tissue or other cervical structures occurs. 4. Supportive treatment – y/d diet Diet with low amounts of iodine Helps keep thyroid hormone production low Sole diet therapy!  Not for growing kittens or pregnant TT4 fT4 T3 test TSH level Radiograph Ultrasounography Thyroid scintigraphy T4 is preferable to Free T4 (FT4) is the T3 (total T3 or TSH (Thyroid The enlarged Transverse Technetium99m T3 non-protein bound triiodothyronine) is Stimulating thyroid gland is ultrasonographic Pertechnetate Specificity : thyroxine present the active form Hormone) visualized as an image. Uptake in thyroid 98-100% in the blood. of thyroid measurement can ovoid, A diffusely glands is compared Sensitivity Measuring FT4 hormone. be used in welldefined, affected, mildly to uptake in 90% (all can help determine T3 levels are combination with soft tissue heterogeneous, salivary glands – hyperthyroid cats) if cats with usually elevated or the other thyroid opacity ventral to enlarged right should be equal 60% (mild high-normal or high-normal in tests mentioned. the third and thyroid gland in a Activity in the hyperthyroidism) borderline total T4 hyperthyroid cats. Hyperthyroid fourth cervical cat with normal thyroid It is also useful as levels are normal or Increase in T3 cats will generally vertebrae. hyperthyroidism. closely approximates a screening test for hyperthyroid. is usually not have low levels of The lesion is Use Doppler to activity in the salivary hypothyroidism FT4 ED levels can obvious TSH. creating a ventral visualize glands, with an and for monitoring be falsely elevated Hyperthyroid cats displacement of vascularization expected treatment with by showing clinical the trachea “brightness” ratio of methimazole. mishandling signs of 1:1. T4 concentrations specimens/samples hypothyroidism Hyperthyroid – can be affected by (e.g. warming, after Benign adenoma: non-thyroidal severe hemolysis, treatment with Thyroid glands illness, medications etc.), hence careful radioactive iodine exceed salivary and nutrition. handling is will generally have glands important. high TSH Functional thyroid FT4 levels. tumors: Patchy concentrations may Unfortunately, to irregular inconsistent also be affected by this day, no TSH pattern low assay has Thyroid scintigraphy protein states been made provides valuable caused by kidney available for feline information or liver disease, patients. neoplasia, etc, but The canine TSH regarding both fT4 is not being assay may be used thyroid anatomy and affected as much as for cats but does physiology and in TT4. not appear can play an integral The problem: fT4 sensitive enough role in the diagnosis, increases in animals to differentiate all staging, and with nonthyroidal hyperthyroid cats management of illness and may from thyroid disease. even be increased normal cats.  The “gold in standard” for normal animals, diagnosing mild potentially creating hyperthyroidism in false positive cats. diagnoses if this is  An invaluable tool the only for evaluating the measurement stage and extent performed. of thyroid tumours The method of (adenomas and measurement is carcinoma) in both also important for dogs and cats. the Indication: determination of hyperthyroid cats, the fT4 level, with thyroid tumours in the equilibrium dogs, cervical dialysis tumours of being considered as unknown tissue the gold standard. (fibrosarcoma, Use first TT4, if hemangiosarcoma), high post operative normal but evaluation( to suspicion high check for leftover – then measure tissue), detection of fT4 (ED) thyroid metastasis,  congenital thyroid dysfunction (ectopic thyroid, juvenile hyperthyroidism) Canine Hypothyroidism Hypothalamus, master regulator which will release thyrotropin releasing hormone which will act on pituitary gland, and pituitary gland will secrete thyroid stimulating hormone, which hv effect on the thyroid gland. Thyroid gland will then produce T4 and T3. The hormone will be majority in the tissue. If the body detect an elecvation, then will hv negative feedback mechanism, signal back to pituitary gland and hypothalamus, to stop TSH and TRH, to keep the body in homeostasis. Hypothyroidism Signalment C/S Diagnostic work up Treatment Prognosis In Cats Primary Middle aged  SYSTEMS 1. Blood tests: 1. DIET: reduced fat Prognosis:  CATS-VERY hyothyroidism is dogs (4-10 ) AFFECTED hypercholestrolemia, 2. Oral synthetic Excellent! RARE! common in dogs years (OVERALL): hypertriglyceridemia, levothyroxine Life commonly after (1:500), but rare in ▪ Age at ▪ Gastrointestinal gross lipaemia, ▪ -treatment of expectancy bilateral cats diagnosis ▪ Skin nonregenerative choice! normal. thyroidectomy  Definition: ▪ 46 % were 1 – ▪ Nervous anemia (50% of ▪ Synthetic Thyroxin or radioiodine ▪ Clinical condition 3 years of age ▪ Cardiovascular cases), mild (T4) preferable over therapy that results from ▪ 29% were 4 – ▪ Reproductive elevation of CK levels crude or generic  Unkempt inadequate 6 years of age ▪ Opthalmic  2. Basal serum products or T3 appearance ▪ Neuromuscular thyroid hormone production and  No sex concentrations: ▪ Starting dose:  Nonpruritic release of predilection / Clinical signs develop subnormal levels of T4 0.02mg/kg SID or seborrhea ▪* 2.5: 1 ratio slowly and are  Determination of 0.5mg/m3 per day  Pinnal alopecia tetraiodothyronine female to male progressive serum free T4 levels (given in  Lethargy (levothyroxine, T4) ▪ Castrated  Most common: by divided doses)  obesity ▪* males and lethargy, inactivity, equilibrium or direct ▪ Adjust dosage Ddx: diabetes, triiodothyronine spayed females dullness, dialysis is a sensitive based on T4 cushing, flea (T3) appear to weight gain, and measurement/ clinical allergy ▪ by the thyroid have higher risk excessive scaling, specific way to response glands. Breed hyperpigmentation, diagnose! (monitor from time to 2 types: predilection: cold intolerance, time) Acquired and Golden recurrent infections fT4 ▪ Once responds to Congenital Retrievers  Bilateral  Two assay therapy- can Most common  Doberman symmetrical truncal methods gradually reduce type: pinchers alopecia  A. Analogue dosage  Acquired  Dachshunds  Spares head and techniques Two veterinary primary: caused by  Shetland extremities Chemiluminescence : drugs: : sheepdogs  Non pruritic confers no Sodium ▪ Lymphocytic  Irish setters  Rat tail advantages over assay Levothyroxine thyroiditis (Familial  Airedales  Alopecia at of total T4 ▪ Thyforon® -Tablets : beagles, Great  Cocker friction areas  B. Equilibrium ▪ Thyro-Tabs® Danes) spaniels (ventrum, axilla) dialysis (DIRECT Canine -Tablets ▪ Idiopathic thyroid  Fox Terriers,  DIALYSIS) Retesting at 4-6 atrophy French Bulldog Hyperpigmentation ▪ Increased sensitivity hours post pill ▪ Neoplasia (TPO gene and increased and specificity over needs to be done to destruction of mutation) thickness total T4 determine if thyroid glands  Shih Tzu of the epidermis- Validated canine T4 levels are normal ▪ Dietary iodine (SCLA5 gene especially in friction assay is not available Daily: monitoring deficiency mutation areas in Malaysia. levels and Rare in cats and  Seborrhea- ▪ Changes in total T4 adjusting doses most commonly generalized, with illness and drugs frequently after bilateral multifocal or may not affect free initially daily for one localized T4. week then thyroidectomy  Dull, dry hair coat ▪ Equilibrium dialysis monthly, quarterly, 6 or radioiodine  Secondary assay is less affected monthly therapy pyoderma is by thyroid 3. Liothyronine common (superficial hormone therapy Uncommon in not deep). autoantibodies. ▪ Only indicated if at dogs and cats:  Dermal 3. Endogeneous least 2 different accumulation of Thyrotropin (TSH) brands of  Acquired mucopolysaccharides Concentrations levothyroxine fails! secondary: caused can lead to non ▪ Increased in most ▪ Initial dosage: 4-6 by : pitting dogs with primary ug/kg PO TID, final ▪ Pituitary edema (myxedema) / hypothyroidism BUT dosage dysfunction puffy face, in at least 25% of the depend on clinical ▪ Destruction of particularly in the dogs response thyroid tissue facial areas may have normal  Possible drug leading to reduced adult TSH! interactions TSH production onset of ▪ Measurement of ▪ Glucocorticoids, ▪ Glucocorticoid Demodicosis!! TSH should be used in androgen, phenytoin, can transiently  Ceruminous otitis conjunction with the furosemide- may suppress TSH externa may be seen thyroid tests enhance the effect of secretion by  Seborrhea sicca,   serum TSH levothyroxine pituitary flaky dry skin concentration, when ▪ Sucralfate and thyrotropes  Corneal lipid present in a dog aluminium hydroxie leading to low deposits with a T4 can inhibit GI T4.  Lipaemia retinitis concentration, has a absorption  Some sensitivity of 75% and  Precautions: Rare in both dog hypothyroid dogs a specificity between ▪ Reduce dose is given and cat: develop a 69% and 95% for the to dogs with  Primary generalized diagnosis concurrent congenital weakness of hypothyroidism. heart failure, DM, hypothyroidism:  Weight gain 4. TSH stimulation renal failure, liver ▪ thyroid agenesis  Neurological test disease or and dysgenesis, symptoms: hyperadrenocorticism iodine deficiency ▪ Seizures ▪ Genetic defect ▪ Laryngeal paralysis ▪ Used to be the gold Follow up: among Fox ▪ Megaesophagus standard for Prolonged use of Terriers: ▪ Horner’s syndrome diagnosing inappropriate high simple autosomal ▪ Proprioceptive hypothyroidism… dosage drugs recessive deficits ▪ Recombinant human can cause iatrogenic ▪ Disease seen in ▪ Hyporeflexia, ataxia TSH is available but hyperthyroidism Giant Schnauzers ▪ Head tilt/ facial expensive.  Clinical signs of  Secondary paralysis ▪ Dogs show little or thyrotoxicosis: congenital: ▪ General myopathy, no response in T4 panting, deficiency in stiffed or stilted gait levels with polyphagia, weight pituitary  Congenital: TSH stimulation test. loss, polyuria, anxiety, TSH production cretinism in German ▪ Not reliable! diarrhea Thyroid neoplasia Shepherd If there is more pdt  How to know if Mostly are  Dwarfism: broad of TT4, means treatment is euthyroid head with short neck pituitary gland got working?? and limbs problem; if no ▪ Mental alertness,  Delayed dental increase, then it will activity levels eruption be thyroid gland increase within 1-2 prob weeks of  Less common therapy signs: head tilt, 5. TRH stimulation ▪ Dermal signs resolve incoordination, testing over 1-4 months facial paralysis, ▪ Unreliable, results  If clinical response infertility in low increase in and normal T4 levels serum T4 is not ▪ Measurement of achievable after 3 TSH in response to months of therapy, TRH could then potentially be used to the diagnosis of differentiate primary hypothyrodism can from be secondary incorrect!! hypothyroidism 6. Radiography  Repeat serum T4 ▪ Not useful except levels every month. for in congenital hypothyroidism: ▪ epiphhyseal dysgenesis ▪ delayed ossification ▪ shortened vertebral bodies ▪ Megacolon is common in cats with hypothyroidism (congenital) 7. Histopathology ▪ Lymphocytic thyroiditis: infiltration of lymphocytes and plasma cells into thyroid parenchyma ▪ Thyroid atrophy: thyroid parenchyma atrophy and replaced by fibrous or adipose tissues ▪ Dermahistopathologic abnormalities, sebaceous gland atrophy, hyperkeratosis, follicular atrophy, epidermal hyperplasia, myxedema Euthyroid sick syndrome  Attributable to nonthyroidal illness or treatment with any of a variety of drugs such as phenobarbital.  Low T3 syndrome & Low T4 due to state of medical illness  Predictor of mortality in man and cats ▪ In dogs with epilepsy, treatment with anticonvulsant drugs can lead to subnormal plasma thyroid hormone concentrations despite normal thyroid function. Eg: hyperadrenocoticism, DM, Hypoadrenocortism, chronic renal failure, hepatic disease, intensive care Drug: steroid, pnenobarbital, sulfanomides, Carprofen, clomipramine