Hyperthyroidism ILE 5

why does thyrotoxicosis occur?

tissues are exposed to excessive levels or T3, T4, or both

what is thyrotoxicosis?

having symptoms of excess thyroid hormones

what is hyperthyroidism?

-a type of thyrotoxicosis

-overproduction of TH by thyroid gland

what are some signs of hyperthyroidism?

-fatigue

-bulging eyes

-warm, moist palms

-weight loss

-nervousness

-irritability

-heat intolerance

-palpitations

what is a thyroid storm?

extreme thyrotoxicity with:

-tachycardia

-heart failure

-psychosis

-hyperpyrexia

-coma

what is hyperpyrexia?

extreme elevation in temperature (above 106 degrees F)

what does pathognomonic mean?

characteristic of a specific disease

what are the pathognomonic symptoms of Graves' disease?

-exophthalmos

-pretibial myxedema

what are the TSH levels USUALLY in hyperthyroidism?

low

what are the free and total T4 and/or T3 serum concentrations in hyperthyroidism?

elevated

what are the MAIN tests used to diagnose hyperthyroidism?

-RAIU

-TSAbs

what does RAIU stand for?

radioactive iodine uptake

what iodine isotype is used for RAIU?

123 I

what does a elevated RAIU tell us?

hormone is being overproduced (Graves)

what does a suppressed RAIU tell us?

non-thyroid gland cause of hyperthyroidism (ex. thyroiditis)

what does TSAbs stand for?

thyroid-stimulating antibodies

if a patient has TSAbs, what does that indicate?

Graves

specifically, what does RAIU tell us about hyperthyroidism?

helps us differentiate types of hyperthyroidism

evaluate the possible diagnoses for the following results:

-elevated TSH

-elevated free T4 and total T3 levels

suspect a TSH-secreting pituitary adenoma

what do you do if a pt has:

-low TSH

-elevated or normal free T4 and total T3 levels

obtain RAIU and scan of the thyroid gland

evaluate the possible diagnoses for the following results:

-low TSH

-elevated or normal free T4 and total T3 levels

-low uptake via RAIU

-thyroiditis

-ectopic thyroid hormone

-exogenous thyroid hormone

evaluate the possible diagnoses for the following results:

-low TSH

-elevated or normal free T4 and total T3 levels

-high uptake via RAIU

-homogenous radioactive iodine distribution

Graves disease

evaluate the possible diagnoses for the following results:

-low TSH

-elevated or normal free T4 and total T3 levels

-high uptake via RAIU

-nodular radioactive iodine distribution

-multiple areas of accumulation

toxic multinodular goiter

evaluate the possible diagnoses for the following results:

-low TSH

-elevated or normal free T4 and total T3 levels

-low uptake via RAIU

-nodular radioactive iodine distribution

-a single area of accumulation

toxic adenoma

what is endogenous hyperthyroidism?

thyroid gland is actively overproducing T4 and/or T3

what does TMNG stand for?

toxic multinodular goiter

what are "cold" nodules?

areas where no thyroid hormones are being produced

what are "toxic" nodules?

areas where excess thyroid hormone is being secreted

what is the most common cause of hyperthyroidism?

Graves disease

what is the second most common cause of hyperthyroidism?

nodules

what are examples of inflammatory thyroid disease?

-subacute thyroiditis

-painless/post-partum thyroid

what are examples of ectopic thyroid disease?

-struma ovarii

-follicular cancer

what are examples of exogenous sources of thyroid hormone?

-medications

-food

what is subacute thyroiditis?

a transient disease caused by viral invasion of the thyroid

what causes subacute thyroiditis?

thyroid dumps thyroid hormones due to infection or an immune response

what are the results of RAIU in transient thyroiditis?

below normal because the gland is inactive

what is the treatment for transient thyroiditis?

-beta blockers

-anti-inflammatories (NSAIDs, corticosteroids)

what occurs in ectopic hyperthyroidism?

-high plasma T3/T4 levels produced by the tumor

-suppresses the hypothalamus and pituitary

-reduces TSU and RAIU

what is the treatment for ectopic hyperthyroidism?

-surgery

-possibly radiation after tumor removal

what is thyrotoxicosis factitia?

excessive intake of thyroxine causing thyrotoxicosis

what is the treatment for thyrotoxicosis factitia?

-stop TH abuse

-reduce thyroid drug dose

what is plummer disease?

TMNG

graves disease:

A) antibodies activate gland

B) antibodies destroy gland

A) antibodies activate gland

what is another word for "hot nodules"?

toxic adenoma

what is another word for toxic adenoma?

hot nodules

what causes toxic adenomas?

gain-of-function somatic mutations of the TSH receptor OR the GSalpha protein (uncommon)

what is T3 thyrotoxicosis?

elevation of T3 in patients with autonomously functioning nodules even with normal T4 level

what does "gain-of-function mutation" mean?

receptor turned on all the time

which thyroid hormone is the "active thyroid hormone"?

T3

what does a "hot" or "warm" thyroid nodule that does NOT suppress the rest of the gland lead to?

hyperthyroidism

what does a "hot" or "warm" thyroid nodule that DOES suppress the rest of the gland lead to?

euthyroidism

what do you do when you find a "cold" thyroid nodule via RAIU?

perform a thyroid ultrasound to determine if "hollow" or "solid"

what is a cold and hollow thyroid nodule referred to as?

cysts

what is a cold and solid thyroid nodule referred to as?

benign adenoma

what do you do if a thyroid nodule is cancerous or suspicious?

perform surgery

what are the treatment options for a toxic adenoma?

-surgical resection

-RAIA

-percutaneous ethanol injection/ablation

what does RAIA stand for?

radioactive iodine ablation

what isotype does RAIA use?

131

what does 131 I do?

kills the thyroid gland

why is percutaneous ethanol injection/ablation not a good treatment option for toxic adenoma?

may be associated w/ pain and damage to surrounding extrathyroidal tissues

are thionamide drugs recommended to treat toxic adenomas? explain.

-not recommended

-these drugs do NOT halt proliferative process in the nodule

what are multinodular goiters also called?

MNG

what does MNG stand for?

multinodular goiters

what are MNGs?

-thyroid follicles with autonomous function coexisting with normal or even nonfunctioning follicles

-"lumpy, bumpy goiter"

what causes MNG?

-diffuse hyperplasia caused by goitrogenic stimuli, leading to mutations and clonal expansion of benign neoplasms

-activating such as TSH receptor mutations

-inhibitory such as ras mutations

what is toxic MNG?

a sufficient mass of autonomous follicles producing elevated levels of T4/T3 with s/s of thyrotoxicosis

what are the s/s of MNG?

typical of hyperthyroidism

how do you diagnose MNG?

-typical labs

-thyroid RAIU scan (hot and cold areas)

how do you treat MNG?

-RAIA

or

-surgery

or

-percutaneous injection of 95% ethanol

in what population of people is surgery used to treat MNG?

-younger pts

-pts with large goiters

what is the jod-basedow effect?

-hyperthyroidism in pts w/ an otherwise non-toxic MNG following administration of iodine (contrast dyes)

-aka pt with MNG is fine until they have iodine

what occurs with TSH-secreting pituitary adenomas?

they release active hormone that is unresponsive to normal feedback control

what do pts with TSH-secreting pituitary adenomas present with?

-normal s/s of hyperthyroidism

-amennorhea/galactorrhea (prolactin secreted)

-signs of acromegaly (growth hormone secreted)

what else might TSH-secreting pituitary adenomas secrete?

may co-secrete prolactin or growth hormone

what is amennorhea?

absence of menstruation

what is galactorrhea?

milk production from the breast unrelated to pregnancy or lactation

what other defects may occur due to TSH-secreting pituitary adenomas that does not deal with hormones secreted?

visual field defects due to impingement of optic chiasm by tumor

what can aid in diagnosis of TSH-secreting pituitary adenomas besides the usual labs for hyperthyroidism?

-labs for excess growth hormone

-labs for excess prolactin

-visual field defects

are TSH-secreting pituitary adenomas usually malignant?

no

what LABS can be done to diagnose pituitary TSH-induced hyperthyroidism?

-elevated TSH, TSH alpha subunits

-lack of TSH response to TRH stimulation

-elevated free T4/T3

-diffuse thyroid gland enlargement (TSH)

-peripheral hyper-metabolism (high T4/T3)

what IMAGING can be done to diagnose pituitary TSH-induced hyperthyroidism?

-MRI cannot detect small tumors since the pituitary is already small

-up to 10% of normal individuals may have incidental pituitary tumors or other benign focal lesions on imaging

what is the treatment for pituitary TSH-induced hyperthyroidism?

-transsphenoidal pituitary surgery***

-pituitary gland irradiation

-dopamine agonists and octreotide

what is the TREATMENT OF CHOICE for pituitary TSH-induced hyperthyroidism?

transsphenoidal pituitary surgery (for all TSH-secreting adenomas)

what is done after a patient receives transsphenoidal pituitary surgery for TSH-secreting adenomas?

pituitary gland irradiation

why is pituitary gland irradiation given following transsphenoidal pituitary surgery for TSH-secreting adenomas?

to prevent tumor recurrence

under what circumstances are dopamine agonists and octreotide used to treat TSH-secreting adenomas?

used to treat tumors, but especially those that co-secrete prolactin

what are CRTH and GRTH?

thyroid hormone receptor mutations

what does GRTH stand for?

generalized RTH

what does PRTH stand for?

pituitary RTH

what is PRTH also called?

CRTH

what is CRTH also called?

PRTH

what is CRTH (or PRTH)?

mutations in the hypothalamic/pituitary-specific TR beta2 receptors

what does CRTH/PRTH result in?

-dec sensitivity to elevated T3 in plasma

-results in loss of NEGATIVE feedback and inc plasma T3

-peripheral TR beta 1 receptors remain sensitive to T4/T3 resulting in hyperthyroidism

what is GRTH?

mutations associated with generalized RTH that impair both TR beta 2 and TR beta 1 receptor function proportionally

what occurs in patients with GRTH?

-TR beta 2 receptors in pituitary can sense rising T3 levels in advance of TR beta 1

-prevents thyrotoxicity

what are examples of resistance to thyroid hormone syndromes?

-CRTH/PRTH

-GRTH

what is the treatment for CRTH?

-drugs that suppress TSH secretion

-beta-blockers

what are examples of drugs that can suppress TSH secretion?

-glucocorticoids

-dopaminergic drugs

-somatostatin analogs

-thyroid hormone analogs with reduced metabolic activity (TRIAC)

what is an example of a glucocorticoid?

dexamethasone

what is an example of a dopaminergic drug?

pramipexole