Thyroid Endocrinology Flashcards
Obj: How are the different thyroid hormones regulated?
- mostly by level of Thyroid stimulating hormone from the anterior pituitary
- which is controlled by Thyrotropin releasing hormone (TRH) from the hypothalamus
Obj: What are all the tests for thyroid function?
What do they test for?
- Total T4
- sensitive screening test - negative rules out hypothyroidism
- Free T4
- Screening for hypothyroidism - low fT4 strongly suggestive
- Total T3
- screening test for euthyroidism - poor
- Basal TSH conc.
- screening for hypothyroidism - need confirmation
- low cTSH is consistent with hypothyroidism if TT4/fT4 decreased
- Antithyroglobulin Antibodies
- Autoantibodies form when thyrocyte destruction exposes intracellular thyroglobulin to immune system
- Positive TgAA titer does not reflect/predict abnormal thyroid function
- Anti-T3 and Anti-T4 antibodies
- can interfere with some hormone assays
- not necessarily indicative of hypothyroidism
What is the difference between T3 and T4?
- T4:
- produced exclusively in the thyroid
- T3:
- 20% from thyroid
- Most produced in peripheral tissues by enzymatic de-iodination of T4
- 3-5x mor potent than T4
What are the affects of thyroid hormone on the Heart?
- Chronotropic and Inotropic effect
- Increases # of B-adrenergic receptors
- enhances responses to circulating catecholamines
- increase proportion of a-myosin heavy chain
What are the effects of thyroid hormone on adipose tissue?
- Catabolic
- Stimulates lipolysis
What are the effects of Thyroid Hormone on muscles?
- Catabolic
- Increase protein breakdown
What are the effects of Thyroid Hormone on Bone?
- Developmental
- Promote normal growth and development
What are the effects of Thyroid hormone on the nervous system?
- Developmental
- Promote normal brain development
What are the effects of Thyroid hormone on the gut?
- Metabolic
- increase rate of carbohydrate absorption
What are the effects of thyroid hormone on lipoproteins?
- Metabolic
- stimulate formation of LDL receptors
What other effects do thyroid hormones have on the body?
- Calorigenic
- Stimulate oxygen consumption by metabolically active tissues
- except: testes uterus, lymph nodes, spleen, anterior pituitary
- Increase metabolic rate
What is a Total T4 (TT4) test?
Pros/Cons?
- Common screening test
- serum sample, randomly timed
- Non-thyroidal illness and drugs can suppress TT4 ( = misdiagnosis_
- Anti-T4 autoantibodies can interfere with assay ( = Misdiagnosis)
What is a Free T4 (FT4) test?
Pros/Cons?
- May be used as screening test
- Serum sample, randomly timed
- More specific than TT4 ( Fewer false positives)
- Non-thyroidal illness can suppress FT4 - but less effect than on TT4
- Anti-T4 antibodies do not interfere with assay
What is a Basal Serum TSH level test?
Pros/Cons?
- Serum sample, randomly timed
- Measured by immunoassay
- Species-specific assay needed (cTSH = canine TSH)
- Poor screening test when used alone
- Cannot be used as sole diagnostic test
- More reliable when TT4 and/or FT4 levels also support the diagnosis
How can the results of TSH and T4 tests be interpreted?
- TSH⇣ & T4⇡ = Hyperthyroidism
- TSH⇡ & T4⇣ = Primary Hypothyroidism
- TSH⇣ & T4⇣ = Secondary Hypothyroidism
What are thyroid Stimulation tests?
Pathways of Thyroid hormone metabolism
What is Autoimmune thyroid disease?
- Mediated by autoantibodies against various thyroid proteins
- Follicular proteins serve as autoantigens
- Antigen-antibody complexes promote inflammation and tissue damage
What are the anti-thyroid antibodies in dogs?
- Anti-thyroglobulin
- Anti-T4
- Anti-T3
What does the presence of Anti-thyroid antibodies in dogs mean?
- Clinical relevance isn’t clear
- may indicate onset of autoimmunity
- Not useful for dx
What is Hypothyroidism?
- Diminished production and secretion of thyroxine (T4) and triiodothyronine (T3)
What are the different types of Hypothyroidism?
- Primary Disease - Thyroid is abnormal (No/Low T4 production)
- Secondary Disease - Pituitary is abnormal (No/Low TSH production)
- Tertiary Disease - Hypothalamus is abnormal (No/Low TRH production)
Obj: what are the typical features of canine Hypothyroidism?
Obj: what are the laboratory methods for Hypothyroidism diagnosis?
Obj: what are the difficulties associated with definitive diagnosis of Hypothyroidism?
Obj: what are the treatment options for Hypothyroidism?
Obj: what are the causes and features of feline hypothyroidism?
What are the possible Pathogenesis of Hypothyroidism?
- Lymphocytic thyroiditis
- immune-mediated pathology/genetic influence
- Presence of anti-thyroglobulin antibodies
- Idiopathic follicular atrophy
- end point of thyroiditis or distinct disorder
- Other Causes:
- Adverse drug reaction
- Neoplastic destruction of thyroid gland
- Iodine deficiency
What is Cretinism?
- Congenital Hypothyroidism
What are causes for Iatrogenic hypothyroidism?
- Thyroidectomy
- Radioiodine therapy (usually cats)
- Radiation therapy (oncologic tx)
What is the epidemiology of canine primary hypothyroidism?
- Most commonly misdiagnosed canine endocrinopathy
- Incidence rates vary from 1:150 to 1:500
- Diagnoses most frequently made in dogs at 4-10yo
What breeds have increased risk of primary hypothyroidism?
- Beagle
- Golden Retriever
- Great Dane
- Irish Setter
- Doberman Pincher
- OE Sheep
What is the common hx of dogs with Hypothyroidism?
- Depressed mentation
- Inactivity
- Cold intolerance
- Weight gain
- Infertility - females
What organ systems are commonly affected in hypothyroidism?
- BCS
- Skin and coat
- Ocular
- Cardiac
- Neruomuscular
What are the dermatologic signs of Hypothyroidism?
- Alopecia/slow hair regrowth
- Dry skin with scaling
- Dull brittle hair
- Seborrhea
- Pyoderma
-
Myxedema - thick nonpitting edema of the skin
- pushing your finger in will not leave an indent
What are ocular abnormalities common with Hypothyroidism?
- Lipid accumulation - Cornea, aqueous humor, retinal vessels
What cardiac abnormalities are common with Hypothyroidism?
- Myocardial depression
- Sinus bradycardia
- weak apical beat
- Decreased fractional shortening
- Low voltage QRS complexes
- Sever DCM in Great Danes
What neuromuscular abnormalities are common with Hypothyroidism?
- Weakness (may be profound)
- Knuckling/hyporeflexia
- Slow, stiff gait
What reproductive abnormalities are common with hypothyroidism?
- Female infertility
What causes the “tragic” expression of hypothyroid patients
- Myxedema
- non-pitting edema
- Head, face, neck
What is a Myxedema crisis?
- Severe acute hypothyroidism
- Cerebral (CNS) signs
- Altered mentation
- Seizures, circling, head tilt
- Coma occurs infrequently
What CBC results are characteristic of Hypothyroidism?
- normocytic
- Normochromic
- Non-regenerative anemia
What abnormalities are common on the chemistry panel of hyperthyroidic patients?
- No changes are diagnostic or pathonomonic
- Lipid abnormalities:
- Hypercholesterolemia (65 - 75%)
- Hypertriglyceridemia
- Other:
- Elevated ALT, ALP
- Electrolyte disturbances
- Creatine kinase
How is Canine Hypothyroidism clinically diagnosed?
- Appropriate clinical signs
- Absence of other significant disease
- supportive lab results
- Screen with total T4
- Confirm with FT4 and TSH
What conditions/results may make hypothyroidism diagnosis difficult?
- Presence of factors that affect thyroid function:
- Breed factors - sight hounds have lower TT4
- Non-thyroidal illness (“sick-euthyroid”) lowers thyroid hormone levels but not TSH
- Diabetes mellitus, HaAC, Addison’s
- Inflammatory disorders, organ failure
- Sx, Starvation
- Drugs:
- corticosteroids
- Sulfa drugs - true hypothyroidism (reversible)
- Borderline or unexpected laboratory results
- low or normal TSh
- Borderline thyroid hormone levels when high likelihood Hypothyroidism
- May elect a therapeutic trial with T4 suppleentation
- need high confidence level and monitoring
What are the treatment options for Hypothyroidism?
- Hormone replacement:
- Synthetic L-thyroxine (T4) - preferred
- ThyroTabs is only approved veterinary formulation
- variable absorption due to poor oral availability
- BID dosing preferred for tablet preparations
What is the treatment for a Myxedema crisis?
- IV L-thyroxine - 5ug/kg (0.005mg/kg) IV q 12 h during crisis
What therapeutic monitoring should be done with hyperthyroidic patients
- Measure serum TT4 2-3 weeks after initiating treatment
- Peak serum T4 preferred - obtain serum sample 4-6hr post dosing
- Desired TT4 level: high normal or just above normal reference range
- Peak serum T4 preferred - obtain serum sample 4-6hr post dosing
- T3 levels unreliable, no noeed to follow cTSH
How long does treatment response take for hypothyroidism
- Clinical response usually begins within one week
- Up to 6-8 weeks needed for full clinical response
What to consider when the treatment for hypothyroidism fails?
- Incorrect diagnosis
- Poor owner compliance
- Poorly controlled concurrent conditions
- Pharmacologic considerations
- Inactivated product
- Inappropriate dose
- Inappropriate frequency
- poor bioavalability
- T3 more available than T4
Obj: Know typical features of feline Hyperthyroidism
- Polyphagia
- Weight loss
- Hypertension
- increased defecation size and frequency
- mild erythrocytosis
- stress leukogram
- Azotemia
Obj: Know laboratory methods for HT diagnosis
- TT4
- T3 suppression test
Obj: Understand the clinical relationship between Hyperthyroidism and masked renal disease in cats
- Increase in renal blood flow secondary to hyperthyroidism increases the glomerular filtration rate and decreases serum creatinine
- Urea and creatinine values may be misleading
- affected by BCS, Thyroid hormone, CKD and hydration
- Low USG is found in HT cats w/ or w/out CKD
- Urea and creatinine values may be misleading
Obj: Know the advantages and disadvantages of the three major Hyperthyroidism treatment options
- Medical Management
- Pros - cost spread out, no hospital stay
- Cons - Lifelong therapy and monitoring, Adverse effects
- Radioactive Iodine
- Pros - >95% cure rate
- Cons - patient selection crucial, must be stable, have concurrent illnesses controlled, can acclimate to hospital environment, lump sum Cost
- Dietary Therapy
- Pros: non-invasive (cats hard to medicate/hospitalize)
- Cons: Lifelong diet, SOLE diet
Obj: understand patient selection for each treatment option for hyperthyroidism
- Medical Management
- financial concerns
- debilitated patient
- Radioactive Iodine
- stable well established HT
- concurrent illnesses addressed
- patient can acclimate to hospital
- Dietary Therapy
- Stable enough to permit chronic dietary therapy
- concurrent illnesses addressed
- Surgery
- No ectopic thyroid tissue
- Unilateral thyroid disease
- other options limited
What causes Hyperthyroidim?
- Excess thyroxine (T4) and triiodothyronine (T3)
What kind of Endocrinopathy is Feline Hyperthyroidism?
- Primary endocrinopathy
- Arises from an autonomous change in thyroid gland
- Independent of hypothalamus (TRH) or pituitary (TSH) regulation
What are the different changes in the thyroid gland that result in hyperthyroidism?
- Benign Thyroid Tumors:
- multinodular adenomatous goiter (most common)
- both thyroid lobes involved
- Adenoma - single mass
- multinodular adenomatous goiter (most common)
- Malignant thyroid tumors
- thyroid carcinoma
What is the rate of the different tumors causing feline hyperthyroidism?
- Multinodular adenomatous goiter - 70-75%
- Adenoma - <30%
- Thyroid carcinoma 1-3%
What is the pathogenesis of feline hyperthyroidism?
- Unknown, some theories
- Environmental influences - polybrominated diphenyl ethers (endocrine disruptors)
- lifestyle influences - indoor only
- Nutritional influences - canned food, certain flavors
What are the common signalment of feline hyperthyroid patients?
- Middle-age and older
- less than 5% <10yo
- No breed predilections
- No sex predilections
What are the common signs of Feline hyperthyroidism?
Other signs?
- Weight loss
- polyphagia
- Other:
- unkempt hair coat
- PU/PD
- Vomiting
- Hyperactivity
- Diarrhea
- Heat intolerance
- Behavior changes
What are some major complications of Feline hyperthyroidsim?
- Cardiac failure/disease
- Thyroid ‘storm’ - acute release of thyroid hormones during events that illicit stress
- panting / open mouth breathing
- tachycardic
What does a physical exam of a cat with hyperthyroidism look like?
- Thyroid nodule (goiter) - usually present
- Abnormal BCS
- Fractious / hyperactivity / behavioral abnormalities
- Abnormal heart sounds
- tachycardia
- murmur
- Arrhythmia (gallop, VPC)
- Overgrown nails, sunken eyes
- Systolic hypertension
What laboratory abnormalities are common with feline hyperthyroidism?
- CBC - unremarkable / non-specific changes
- Chemistry - no pathognomonic changes
- Hyperglycemia - could be stress response
- Azotemia - variable changes in BUN and creatinine
- Symmetric dimethylarginine (SDMA) - may be elevated
- Elevated ALT /ALP, occasional mild increase in bilirubin
- ~80% of cases
- Usually NOT due to primary liver disease
- Urinalysis - non-specific changes
- specific gravity varies (1.009 - 1.055+)
What are the different interpretations for TT4, Free T4 and TSH tests for Hyperthyroidism
What is ‘Masked’ chronic kidney disease
- Abnormal kidney anatomy
- abdominal palpation / imaging findings
- Abnormal kidney function
- signs of CKD
- Urea and creatinine values may be misleading
- affected by BCS, thyroid hormone, CKD, and hydration
- Reduced urine concentration (low USG)
- in HT cats w/ or w/out CKD
- SDMA - dx usefulness unclear
- Abnormalities persist after euthyroidism restored
- changes consistent with CKD do NOT resolve or worsen after treatment for Hyperthyroidism
What cardiac changes can occur in feline hyperthyroidism?
- HT cats may develop a reversible hypertrophic cardiomyopathy
- all cardiac changes resolve after effective anti-thyroid treatment
- Imaging & echocardiogram are indicated when HT cat has cardiac signs
- Cardiac drugs may be needed
- cardiac conditions should be controlled before definitive treatment
What are the cardiac signs of Thyrotoxicosis?
- Tachycardia / Arrhythmia
- Murmur
- Respiratory Distress
- Tachypnea or panting
- Muffled heart sounds
What are the treatment options of Hyperthyroidism in cats?
- Medical management
- Radioactive Iodine
- best option for most patients
- Dietary Therapy
- select situations
- Surgical Thyroidectomy
- not routinely recommended
What is the medical management option for Feline Hyperthyroidism?
Methimazole
How does Methimazole work for Feline Hyperthyroidism?
- Drug concentrates in thyroid gland
- Prevents thyroid hormone production
- Initial dose is 2.5mg BID - adjust on T4 level and response
- oral and transdermal formulations
- LIFE LONG therapy and Monitoring
What are the possible side effects of methimazole?
- GI (inappetence, vomiting) - common
- Facial pruritis - common
- Hepatotoxicity
- Immune-mediated hemolytic anemia
- Agranulocytosis
- Thrombocytopenia
What occurs following methimazole withdrawal
- adverse reactions typically resolve
- Hyperthyroidism returns
How does Radioactive Iodine (131I) work for Hyperthyroidism
- Thyroid is the only organ that accumulates iodine
-
131I targets overactive thyroid tissue
- Emits beta radiation
- >95% cure rate w/ single dose
Why would Radioactive Iodine treatment fail?
- Thyroid carcinoma 2-3%
- Low 131I dose
What is the ideal patient for Radioactive Iodine treatment of hyperthyroidism?
- Stable, well established Hyperthyroidism
- methimazole trial may help evaluate patient
- Concurrent illness addressed
- cardiac thyrotoxicosis, hypertension
- Patient can acclimate to hospital environment
- isolation ~7 days; hospitalized ~10 days
- state and local rules govern isolation
- isolation ~7 days; hospitalized ~10 days
When is surgical thyroidectomy a reasonable option?
- NO ectopic thyroid tissue
- Unilateral thyroid disease
- other options limited
What are the advantages / disadvantages of thyroidectomy?
- Advantages:
- may be curative
- minimal oral medications
- Disadvantages:
- invasive
- Risk of anesthesia
- Hypoparathyroidism
- Hypothyroidism
How does a restricted iodine diet work for hyperthyroidism?
- Hill’s Science Diet Y/D
- Formulation has severely restriced iodine content (≤0.3ppm)
- must be fed as sole diet
- Thyroid levels fall by 3 wks and are normal by 8 wks in most cases
- Treatment failure may occur if cat gets other food / supplements
What is the ideal patient for a restricted iodine diet for hyperthyroidism
- Stable enough to permit chronic dietary therapy
- Concurrent illness is addressed
What is the prognosis of feline hyperthyroidism?
- Curable disease
- Depends on:
- physical condition at dx
- simulatneous diseases present
- Benign vs malignant tumor
- Treatment options available
What is a “thyroid storm’?
- Crisis caused by acute release of thyroid hormone
- can occur as acute exacerbation of hyperthyroidism
- Induced by stress/anxiety
What is the goal of emergency treatment of a hyperthyroid storm? what are the options for treatment
- Immediately prevent thyroid hormone release or action
- Stable iodines:
- Potassium iodide
- Potassium iodate - 25 mg/cat q8h
- Iopanoic acid - 100mg/cat BID -
- block T4 ⇢ T3 conversion
- block T3 at receptor
- Inhibit thyroid hormone synthesis
- Beta adrenergic blockers
- Propanolol - 5 mg q8h or 0.02 mg/kg IV over 1-min
- inhibits conversion
- Atenolol - 1 mg/kg q 12-24 h
- Esmolol (B1 agent) IV 0.5 mg/kg then CRI
- Propanolol - 5 mg q8h or 0.02 mg/kg IV over 1-min
What is Iatrogenic Hypothyroidism? How can it be caught?
- Usually 131I overtreatment
- May be clinical - usually subclinical
- ~30 days post treatment - measure TT4, FT4, TSH, serum chemistry
- Overt hypothyroidism - TT4 OR FT4 is low AND TSH is high
- requires T4 supplementation
- Subclinical hypothyroidism - TT4 OR FT4 in the lower ⅓ of the reference range AND TSH is high
- cat is mildly hypothyroid
- Supplementation can be withheld unless NEW azotemia has developed
- Overt hypothyroidism - TT4 OR FT4 is low AND TSH is high
- ~3 and 6 months post treatment:
- if TT4 OR FT4 is low AND TSH is high, OR the cat has developed NEW azotemia - T4 supplementation required
- If values meet criteria for subclinical hypothyroidism - continue to monitor
What is a Methimazole trial?
- Purpose = evaluate effect of hyperthyroidism on renal function
- Do a trial if concerned that CKD will worsen with anti-thyroid treatment
- Protocol:
- administer methimazole until euthyroidism is restored (1-2 weeks)
- Asses renal values and clinical condition
- If no clinical signs of CKD, No indication of azotemia
- THEN - patient should be a good candidate for 131I therapy
- Successful trial does NOT predict absence of CKD with certainty