Lecture 27: Hyperthyroidism

• Steps of thyroid hormone

  1. Trapping of iodide: Iodide pump co-transports Na and I into the thyroid cell

  2. Oxidation of iodide of iodine by thyroperoxidase (TP)

  3. Exocytosis of thyroglobulin or thyroxine-binding globulin (TBG)

  4. Iodination of thyroglobulin

  5. Coupling of 2 DIT molecules to form T4. T3 is formed by condensation of MIT and DIT

  6. Endocytosis of thyroglobulin

  7. Hydrolysis of thyroglobulin

  8. Release of T3 and T4

  9. Deiodination of MIT and DIT

  10. Recycling of iodide

  11. Conversion of T4 to T3 by 5'-monodeiondinase in peripheral tissue
• Compounds (progoitrin, goitrin, thiocynates) inhibit uptake or organic binding of iodine, reduce secretion of thyroid hormones and cause enlarged thyroid gland


  Goitrogens
• HPT axis


  1.Hypothalamus secretes TRH

  2. Anterior Pituitary Gland (thyrotrophs) secrete TSH following TRH stimulation

  3. Thyroid gland (follicular cells) secrete T4 and T3
• Genomic actions of T3/T4


  1. In specific tissues,such as brain, transporters such as monocarboxylate transporter-8 transport T4 and t3 into cell

  2. Inside the cell T4 can be converted to rT3 by deiodinase-3 or to T3 by deoidinases-1 and 2

  3. In the absence of T3, Thyroid Hormone Receptor (TR) heterodimerizes with RXR and binds to thyroid receptor element and then to a compressor, repressing gene expression

  4. T3 binding to the ligand-binding domain results of TR causes disruption of corepressor binding, and promotion of coactivator binding, which then leads to recruitment of polymerase III and initiation of gene transcription
• Non-genomic actions of T3/T4


  bind to integrin avB3 on cell membrane and induce intracellular signaling pathways
• Physiological effects of thyroid hormones

  1) BMR: T3 and T4 increase BMR, lipolysis, glycolysis, and conversion of cholesterol into bile salts

  2) Growth and development: T3 and T4 stimulate maturation of nervous system and nerve conduction velocity, bone growth, and GH secretion

  3) Reproduction: T3 and T4 stimulate sex hormone secretion

  4) Heart and muscle: T3 and T4 maintain the receptors for epinephrine/norepinephrine

  5) Skin: T3 and T4 maintain skin integrity

  6) Amphibians: T3 and T4 control metamorphosis
• What is seen with feline hyperthyroidism?

  Excessive production and secretion of T3 and T4
• Is feline hyperthyroidism usually bilateral or unilateral?

  65% bilateral and 30% unilateral
• Signalment of feline hyperthyroidism

  -Older cats (4-20 years old)
• CS of feline hyperthyroidism

  -Weight loss/muscle wasting

  -Polyphagia

  -Restlessness, hyperactive

  -Hair coat changes

  -PU/PD

  -Vomiting, diarrhea

  -Lethargy, weakness, anorexia
• PE findings with feline hyperthyroidism

  -Palpable thyroid

  -Tachycardia

  -Thin

  -Unkempt hair coat

  -Heart murmur

  -Hyeractive, aggressive
• CBC findings with feline hyperthyroidism

  Generally unremarkable, possible increased Hct
• Serum chemistry findings with feline hyperthyroidism

  -Increased ALT, ALKP, AST

  -Increased BUN and creatine

  -Increased phosphorus
• UA findings with feline hyperthyroidism

  -USG generally acceptable

  -Watch for proteinuria
• What concurrent issues can occur with feline hyperthyroidism?

  -Cardiomyopathy

  -CKD

  -UTI

  -Hypertension

  -GI issues
• What is the most commonly used diagnostic method for hyperthyroidism?

  Baseline serum T4
• What is the most consistent and reliable diagnostic method for hyperthyroidism?

  fT4
• What test is used to distinguish euthyroid from mildly hyperthyroid?

  T3 suppression test
• What is the oral drug of choice for hyperthyroidism?

  Methimazole, can also use carbimazole or propylthiouracil
• What do you need to check when putting animals on methimazole?

  T4, kidney values, UA
• What is the target of oral hyperthyroid treatment?

  Get T3 in lower half of reference range
• How effective I-131?


  90% effective with first dose
• Why thyroidectomy not typically the first choice?

  CKD
• At what baseline serum T4 is considered likely for hyperthyroidism?

  >4.0 ug/dL
• Complications of throidectomy in cats


  -Transient or permenant hypoparathyroidism causing hypocalcemia

  -Laryngeal paralysis

  -Horner syndrome

  -Hypothyroidism

  -Exacerbation of current renal insufficiency
• What is the most common form of hypothyroidism?

  Primary hypothyroidism (problem with gland)
• Causes of primary hypothyroidism

  -Lymphocytic thyroiditis

  -Idiopathic atrophy
• Causes of secondary hypothyroidism

  -Pituitary thyrotroph dysfunction

  -Pituitary thyrotroph damage (neoplasia, glucocorticoids)

  -Pituitary hypoplasia (dwarfism)
• Causes of tertiary hypothyroidism

  Very rare; neoplasia only recognized cause
• What are congenital causes of primary hypothyroidism

  -Iodine deficiency

  -Thyroid hypoplasia/aplasia/dysgenesis

  -Cretinism
• Signalment of hypothyroidism


  Variable age, breed, degree/duration of issues
• CS of hypothyroidism


  -Endocrine alopecia

  -Gross skin and hair

  -Weight gain

  -Lethargy

  -Dull mentation

  
• Similarities between hypothyroidism with other endocrinopathies

  -Dermatologic issues

  -Weight issues

  -Lethargy

  -Immune system issues

  -Some clin path abnormalities
• Differences between hypothyroidism with other endocrinopathies

  -No PU/PD

  -Decreased appetite

  -Cold intolerant

  -Myxedema coma
• Hypothyroidism in puppies 1-3 months of age

  Cretinism
• What does autoimmune polyendocrine syndrome?

  DM, hypoadrenocorticism, hypothyroidism
• CBC findings with hypothyroidism

  -Normocytic, normochromic, nonregenerative mild anemia

  -Target cells increase cholesterol in RBC membrane
• Chemistry findings with hypothyroidism

  -Hypercholesterolemia

  -Hypertriglycerdiemia (lipemia)

  -Elevated ALKP, ALT, AST, CK
• UA findings with hypothyroidism

  Typically unremarkable
• Major players in hypothyroidism

  T4, fT4, TT4, TSH