Thyroid Flashcards
The alpha subunit of TSH is identical to that of ___, ____, ____
LH, FSH, hCG
What action does TSH have at the thyroid
stimulates iodine uptake
thyroid hormone production and release
upregulate TPO
What substances can inhibit thyroid hormone production?
glucocorticoids, somatostatin, dopamine
Describe embryonic development and migration of the thyroid gland
HPT axis develops by 11 weeks
thyroid starts to function by 18 weeks
migrates via thyroglossal duct from base of tongue to neck
The thyroid gland takes up iodide via ______ under TSH stimulation
Na/I symporter
Iodine is ______ and then incorporated into thyroglobulin tyrosyl residues by TPO
oxidized/organified
What is the Jod-Basedow phenomenon
in setting of longstanding iodine deficiency, patients exposed to high doses of iodine become hyperthyroid
What is the Wolff- Chaikoff effect
in setting of longstanding high levels of iodine, organification is transiently blocked to protect from hyperthyroidism
decrease in iodine transport allows for escape and normal thyroid hormone synthesis
Under what conditions is TBG increased
hyperestrogenic states- pregnancy, estrogen therapy
Under what conditions is TBG decreased
steroids, glucocorticoids, protein malnutrition, cirrhosis, nephrotic syndrome
What is the action of 5’MDIs
conversion of T4 to T3 in peripheral tissue
an upregulation of thyroid activity
stimulated by TSH
What is the action of 5- MDIs
removes inner iodine, converting T4 to rT3 (inactive)
a downregulation of thyroid activity
Thyroid hormone is critical for neurogenesis and _______ in the brain
myelination
What is the effect of thyroid hormone on carbohydrate metabolism?
Stimulates glucose absorption, increases gluconeogenesis and glycogenolysis.
What is the effect of thyroid hormone on lipid metabolism?
Increases hepatic LDL cholesterol receptors, increases lipolysis
stimulates metabolism of cholesterol to bile acids- hypercholesterolemia in hypothyroid state
What is the effect of thyroid hormone on cardiac function?
stimulates cardiac contractility, increases O2 consumption, enhanced sensitivity of tissue to catecholamines
What is the effect of thyroid hormone on bone turnover?
stimulates both bone formation and resorption, but resorption prevails in hyperthyroid state
What is the effect of thyroid hormone on the gut?
stimulates gut motility
What lab findings are expected in central hypothyroidism
- low T4
- TSH is low or inappropriately normal
What lab findings are expected in primary hypothyroidism
- elevated TSH
- normal or low T4
- normal or low T3; remains normal until late in course of hypothyroidism
What lab findings are expected in hyperthyroidism/ thyrotoxicosis
low TSH
normal or high T3/ T4
What lab findings are expected in central hyperthyroidism
high T3/T4
TSH is high or inappropriately normal
TSI is the causative agent in _______
Graves disease
bind TSH receptor, mimic action of TSH
Anti-TPO is the causative agent in __________
Hashimoto’s thyroiditis
antibody against enzyme that oxidizes and organifies iodide
List symptoms of hyperthyroidism
Nervousness, agitation, irritability
Palpitations, tachycardia, atrial fibrillation, exertional dyspnea
Heat intolerance, increased perspiration, dehydration
Tremor
Weight loss or gain
Hyperdefecation
Muscle weakness, fatigue
Menstrual disturbance and infertility
Insomnia
Orbitopathy and dermopathy (seen exclusively in Graves’ disease)
Lid lag, stare
List causes of high uptake thyrotoxicosis
Graves disease
toxic multinodular and solitary hyperfunctioning nodules
TSH secreting pituitary adenoma
selective pituitary thyroid hormone resistance
What antibodies are characteristic of Graves disease
TSI
What are the most common extra-thyroid manifestations of Graves disease
orbitopathy- diplopia, eye irritation, proptosis
associated with smoking
dermopathy- less common
Toxic multinodular and solitary hyperfunctioning nodules are more common in _____ patients
older
vs Graves, more common in younger
Why does hyperemesis gravidum present as high uptake thyrotoxicosis
cross reactivity of hCG at TSH receptor
What are causes of low uptake thyrotoxicosis
subacute thyroiditis silent thyroiditis post partum thyroiditis struma ovarii factitious hyperthyroidism
Subacute thyroiditis is usually preceded by ______
upper respiratory infection
What symptom can distinguish subacute vs silent thyroiditis
thyroid gland tenderness in subacute but not silent
What is the mechanism of increased thyroid hormone in subacute thyroiditis
increased release (but NOT production) of thyroid hormone
What is the prognosis of subacute thyroiditis
self-limited condition
may pass through hypothyroid phase prior to recovery
treat symptomatically
______ thyroiditis may have an autoimmune component, usually resolves completely, and the thyroid gland is not tender
post-partum
What is struma ovarii
ovarian tumor with thyroidal elements that autonomously produce thyroid hormone
What drugs are used to treat hyperthyroidism
PTU
Methimazole
What is the mechanism of action of PTU/ methimazole
Inhibit iodination of tyrosyl groups in thyroglobulin and coupling to form T3 and T4.
Why is there delay in onset of action of PTU/ methimazole?
no effect on stored thyroglobulin- must deplete thyroglobulin stores before peripheral thyroid hormone levels begin to decline
Why does PTU act faster than methimaxole
additional activity of inhibiting conversion of T4 to T3 peripherally
What therapy is appropriate for treatment of hyperthyroidism in pregnancy?
PTU is the treatment of choice in the first trimester
During the remainder of pregnancy (and at all other times), methimazole is felt to be safer due to the lower risk of hepatoxicity
What are adverse effects of PTU and methimazole
agranulocytosis
hepatic toxicity
urticaria, rash
vasculitis, arthralgias
What is used to ablate thyroid in Graves, thyroid cancer?
radioactive I-131
What are signs of thyroid storm?
thyrotoxicosis, fever, mental status changes
How is thyroid storm treated?
PTU, beta blocker, glucocorticoids (block T4–> T3)
What antibodies are characteristic of Hashimoto’s thyroiditis?
anti-TPO
What is the drug of choice for hormone replacement in hypothyroidism?
levothyroxine- consistent potency, long duration
In what settings is liothyronine used?
myxedema coma- faster onset
impaired T4–> T3 conversion due to 5’ deiodinase defect
How is TSH used to evaluate the effectiveness of a thyroid hormone replacement dose?
High TSH = dose is too low. Low TSH = dose is too high.
What is myxedema coma?
Defined as severe hypothyroidism associated with mental status changes and hypothermia.
Can have associated respiratory failure, hypotension, bradycardia, and hyponatremia
How is myxedema coma treated?
levothyroxine, possibly liothyronine, glucocorticoids, supportive care
TSH may be _____ during the recovery phase from illness, but usually returns to normal within a few months
elevated- not indicative of hypothyroidism
What are some medical reasons for decreased conversion of T4 to T3
caloric restriction
major systemic illness
drugs- PTU, glucocorticoids, propranolol, amiodarone
In illness, rT3 is increased due to _____ 5’MDI activity
decreased
Give a differential diagnosis for thyroid nodules
Adenoma (functioning or nonfunctioning) Cysts (simple, complex) Colloid nodules Developmental abnormalities Granulomatous disease Abscess Carcinoma
What features make malignancy more likely in a patient presenting with a thyroid nodule
Age 60
Positive family history, especially for medullary CA or MEN2
Rapid enlargement of the nodule
Hoarseness, dysphagia
History of head/neck irradiation, especially for papillary CA
A cold nodule in the setting of Graves’ disease
Firm or hard or fixed nodule
Cervical lymphadenopathy
Vocal cord paralysis
Describe workup of a thyroid nodule
- if TSH is normal or high- do FNA
- if TSH is low, do radionuclide imaging
FNA cannot distinguish between ______ and ______
follicular adenoma and follicular carcinoma- need to see tissue architecture to distinguish between these two
What type of thyroid cancer is suspected if:
- complex branching papillae with fibrovascular cores associated wiht folicles
- cells are cuboidal, nuclei are overlapping
- nuclear clearing (orphan annie eye cells)
- longitudinal nuclear grooves
- psammoma bodies
papillary thyroid cancer
Metastases in papillary thyroid cancer occur via:
lymphatics
How is papillary thyroid cancer treated?
thyroidectomy +/- radio ablation
What gene mutations are associated with papillary thyroid cancer?
RET, BRAF, NTRK
What is the prognosis for papillary thyroid cancer
excellent
What type of thyroid cancer is suspected if:
- follicular differentiation
- invasion of adjacent thyroid parenchyma
- capsule forms
follicular
Follicular thyroid cancer secretes _____
thyroglobulin- used as a tumor marker
Follicular thyroid cancer metastasizes:
hematogenously
How is follicular thyroid cancer diagnosed?
cannot dx by FNA, need a full tissue specimen to assess architecture, invasion of capsule
What type of thyroid cancer is suspected if:
- firm rapidly growing mass
- de-differentiated cells that do not secrete thyroglobulin
- spindle or squamoid cells
- cells are pleiomorphic
anaplastic
What mutation is associated with anaplastic cancer
BRAF
_______ is a malignancy of the C cells of they thyroid gland
medulary
What type of thyroid cancer is suspected if:
- polygonal, plasmacystoid, or spindle cells
- cells have granular cytoplasm and uniform round nuclei
- amyloid deposits
medullary
Medullary cancers secrete _____
calcitonin
List the features of MEN1
Parathyroid hyperplasia
Pancreatic islet cell tumors (gastrin, insulin, glucagon, somatostatin, VIP, pancreatic
polypeptide)
Pituitary adenoma
chromosome 11; MENIN gene, loss of tumor suppression
List the features of MEN2a
Parathyroid hyperplasia
Thyroid - medullary carcinoma of the thyroid (defining feature of MEN2)
Adrenal - pheochromocytoma
chromosome 10, RET oncogene activation in MEN 2a and 2b
List the features of MEN2b
Medullary CA of the thyroid Pheochromocytoma NOT parathyroid Marfanoid habitus Mucosal neuromas - usually present before other manifestations arise.
