Hyper/Hypothyroidism Flashcards
(40 cards)
sx of hyper thyroidism?
heat intolerance palpitations tachycardia irritable/nervousness loose stools tremor moist warm skin mm. wasting hyperreflexia neck enlargement clubbing of fingers pretibial myxedema
typical findings of Grave’s?
goiter, exopthalmos, pretibial myxedema
Labs: Decreased TSH
High free T4
High free T3
- Thyroglobulin Abs
- Thyroid peroxidase Abs
- TSH receptor antibodies act on the follicular cell (GPCR)*, fibroblast in the eye and pretibial skin.
Thyroid scan: shows increased uptake
what type of hypersensitivity is Grave’s?
Type II ( IgG antibody dependent cytotoxicity – antibodies to cell surface receptors or other cell surface components)
- complement mediated lysis (MAC);
- antibody dependent cytotoxic attack (K cells);
- alter cell surface receptor function by function toward activation or blockade (
which HLA seen in Grave’s?
HLA-DRB1, DR8
** Its a MHC class II cell surface receptor - stimulates TH2 cell response and production of antibodies from B cells
CD4 T cells (TH2) also stimulate TSH receptor antibodies (TSIs) (also ANA, anti-thyroperioxidase antibodies, and anti-thyroglobulin antibodies) that act on follicular cells to stimulate thyroid growth and secretion. They also cross-react with antigens in fibroblasts, adipocytes, etc.
** see TH1 response in Grave’s as well w/ pretibial myxedema and Graves orbitopathy
CD4 T cells (TH1) secret cytokines that stimulate effector cells (macrophages, cytotoxic T cells, NK cells, etc) against TSH receptors and fibroblast to produce glycosaminoglycans (GAG, hyaluronic acid).
cause of “staring”, lid lag, and strabismus seen in Graves? pretibial myxedema?
Fibroblast proliferation with GAG deposits, and lymphocyte infiltration in the muscles around the eyes produce proptosis and diplopia.
Pretibial myxedema:
The same thing can happen in the skin when the TSH receptors are attacked.
heart problems assoc. w/ grave’s?
Thyrotoxic cardiomyopathy: tachycardia induced cardiomyopathy,
AF, high output failure, and pulmonary hypertension.
Why is calcium elevated in hyperTH?
Increased T3 leads to increased bone turnover.
Which hormone is imp. to differentiate exogenous hyperTH from Grave’s?
elevated thyroglobulin indicates the thyroid is actively making thyroid
Causes for hypercalcemia?
SPERM DIF
Sarcoid (or any granulomatous disease)
Primary Hyperparathyroidism, Paget’s
Endocrine disease (Pheo, Addisons, HyperT)
Renal disease (diuretic phase of ARF, dialysis)
Malignancies (hypokalemic alkalosis), Milk Alkali
Drugs (Vit D, Vit A, lithium, thiazides)
Immobilization, Immune deficiency syndrome, inflammatory disorders
Familial hypocalcuric hypercalcemia
Treatment of Grave’s hyperTH?
1a. Antithyroid (thiourea) drugs:
- Block oxidation (TPO inhibition of I- to Io) , organification (iodination) and coupling– usually used up to four days before RAI to avoid RAI induced storm.
1. PTU* – OK in Pregnancy (1st trimester only). Blocks T4–>T3.
2. methimazole – less hepatic necrosis and drug of first choice.
Side effects of both: Agranulocytosis, Hepatitis,
1b. Iodine – (Iopanoic acid or Ipodate sodium) which block T4–>T3
(give after starting thiourea drugs) - works via peripheral inhibition of 5’ monodeiodination of T4. Wolff-Chaikoff effect – stops synthesis and release.
- RAI unless pregnant - may start with propranolol and anti-thyroid drugs (PTU qid or methimazole daily).
- Surgery
factors that can simulate primary hyperTH via creating low TSH?
Drugs: steroids, CCBs, dopamine, NSAIDS, opiates
elderly euthyroid
pregnancy/hCG secretion: hCG looks like T3/4, thus TSH is sometimes turned off during pregnancy
severe non-thyroidal illness = euthyroid sick syndrome
which drug can give you hyper/hypothyroidism/thyroiditis?
amiodarone : can activate autonomous thyroid nodules to become MNG
Type I amiodarone induced thyrotoxicosis – can be a Jod Basedow type with TMNG and no thyroid antibodies or an actual Graves type with antibodies.
Type II Amiodarone induced thyrotoxocosis - Thyroiditis
apathetic hyperthyroidism
apathy, w/l, angina, AF, CHF and less adrenergic symptoms
- found in functioning thyroid nodules or toxic multinodular goiters
- NOT an AI disease, thus won’t see an Abs developed - rather related to somatic mutations of the TSH receptor and cAMP cascade of inositol phosphate pathway
scan of TMNG?
decreased uptake of iodine
“Jod-Basedown phenomenon” - can be caused by amiodarone
causes of high RAIU other than Graves?
GAIT2
Graves
Adenoma (Plummers)
Inappropriate secretion of TSH (pituitary adenoma) -rare
Toxic Multinodular Goiter
Trophoblastic* (Embryonal carcinoma and Hydatiform mole - hCG – looks like TSH to the thyroid),
tx for AFTN/TMNG?
AFTN – RAI (Na 131I) or surgery (under age 40) or ATDs (usually given to avoid storm)
TMNG - RAI or Surgery or ATDs
For RAI treatment with low uptake – prime with PTU or recombinant TSH
subclinical hyperthyroidism
(usually d/t AFNs or MNGs)
see normal amount of T4, with very depressed TSH
Risks:
- AF/diastolic dysfunction
- osteoporosis
- dementia
tx:
- RAI or small dose ATD
what levels of TSH should just be tx w/ observation and beta blocker?
TSH Between 0.1- 0.3 mIU/L treat with observation and consider a beta blocker (blocks T4 –> T3), etc.
Thyrotoxic Crisis or Storm
caused by an acute illness, thyroid
surgery or RAI therapy in an inadequately treated thyrotoxicosis
patient.
Manifested by fever (>102F), tachycardia, tachypnea,
hypotension, vomiting, diarrhea, irritability, delirium, coma
and death. May have anemia, increased BUN, Ca, SGPT, and glucose.
Treatment: Thiourea ( methamizole 30 mg every 6 hours or
PTU 200 mg every 6 hours) with iodides (Ipodate or SSKI) started
1 hour after the thiourea. Also start metoprolol and hydrocortisone.
Thyrotoxic Periodic Paralysis
a condition featuring attacks of muscle weakness in the presence of hyperthyroidism Hypokalemia is usually present during attacks –> risk of arrhythmias
hx: oriental male, mm. pain/weakness, recurrent episodes, increased appetite, increased BP, increased HR, decreased reflexes, low potassium
cause:
- a channelopathy with muscle weakness (K+ being transferred into muscle cells from increased Na/K–ATPase activity with resultant hypopolarization and serum hypokalemia)
- occurring with a heavy meal* or post exercise in Asian men
- Thyroid hormone increases the ATPase activity as does catecholamines, insulin and testosterone, etc.
(often have underlying Grave’s) resulting in increased K+ in
- channelopathy involves L-Ca2+ channel along with K voltage gated channel
postpartum thyroiditis
sx:
- post-partum female
- shakiness, palpitations, heat intolerance
- non-tender thyroid
- fine tremor in hands
- wide pulse pressure
Labs:
- see elevated T4, low TSH
- TPO antibodies present
see DR3, DR5
precursor to hashimotos
RAI scan shows: very little uptake
causes of hyperTH assoc. w/ decreased RAIU?
- Drugs: Thyroxine (low serum TG level)
- Iodine: amiodarone type I
- Ectopic production
- Painful Thyroiditis:
- Subacute Granulomatous (deQuervain’s): HLA B-35, viral , high ESR
- suppurative (staph infection)
- amiodarone type II
- radiation / trauma - painless (silent) thyroiditis:
- Postpartum – DR3, DR5 (precursor to Hashimotos).
- Subacute or chronic autoimmune (lymphocytic) – diabetes, vitiligo, Downs or Turners syndrome.
- Riedel’s fibrosis (Normal or low uptake and function).
Note: Most cases of thyroiditis produce only a transient hyperthyroidism over a few months
transforming to hypothyroidism and then normal function or permanent hypothyroidism
subacute granulomatous thyroiditis
- painful thyroiditis
- (deQuervain’s): HLA B-35, viral , high ESR
myxedema/ hypothyroidism sx?
- dry brittle hair
- edema of face/eyelids
- coldness
- diminished perspiration
- slow pulse
- ascites
- mm. weakness
- slow reflexes
- deep voice
- enlarged heart
- numbness in hands/fingers
- Tinel’s sign
- jaundice
- diastolic HTN
- lethargy, memory impairement
- doughy skin = lymphedema w/ accumulation of GAGs in skin
- loss of lateral 1/3 of eyebrows (queen Anne’s sign)
