thyroid disorders Flashcards
negative feedback loop for thyroid
- hypothalamus detect low circulating TH -> release TRH -> TRH instruct pituitary gland to release TSH -> TSH instruct thyroid gland to secrete TH
- hypothalamus detect elevated TH -> stop releaseing TRH
types of antibodies for autoimmunity test
1) ATgA: thyroglobulin antibodied
2) TPO: thyroperoxidase antibodies
3) TRAb: thyrottrppin receptor IgG Ab
indication for screening thyroid disorder
1) autoimmune disease
2) 1st degree relative
3) psychiatric disorder
4) amiodarone/lithium
5) Hx of head, neck radiation for malignancies
6) S&S of hypo/hyperthyroidism
7) new onset AF
possible causes of primary hypothyroidism
1) iodine deficiency
2) Hashimoto disease
- +ve ATgA & TPO antibodies
- disproportionately affect women
3) Iatrogenic
- thyroid resection
- radioiodine ablative therapy for hyperthyroidism
causes of secondary hypothyroidism
1) central hypothyroidism
- hypothalamus X TRH, pituitary gland X TSH
2) drug induced
- amiodarone, lithium
causes of tertiary hypothyroidism
hypothalamus X producing TRH
S&S hypothyroidism
- cold intolerance, dry skin, course hair
- lethargy, fatigue, weakness
- weight gain
- bradycardia, hypotension
- slow reflexes
- periorbital swelling
- menstrual disturbances
- goiter
clinical manifestations of hypothyroidism
- increase cholesterol, LDL, TG
- increase atherosclerosis & MI risk
- increase CPK
- increase miscarriage risk
- impaired fetal cognitive development
lab test for hypothyroidism
1) primary
- increase TSH, decrease T4
- +ve TPO, ATgA (autoimmune)
2) central
- decrease TSH, decrease T4
hypothyroidism - levothyroxine - dosage
1) initial
- young healthy adult: 1.4 mcg/kg/day
- 50-60 yo + X cardiac issue: 50 mcg daily
- CVD: 12.5-15mcg/day
2) titration
- increase/decrease 12.5-25mcg/day increment or 10-15% weekly dose
hypothyroidism - levothyroxine - dosing instruction
1) 30-60 mins before bfast or 4 hrs after dinner
2) food decrease absorption, can only take water, 2 hrs apart from divalent supplement & antacid
hypothyroidism - levothyroxine - PK
1) absorption
- oral, absorbed duodenum & jejunum
2) distribution
- highly plasma protein bound
3) metabolism
- liver (glucuronidation, sulphation, deiodination)
4) elimination
- kidneys, metabolite urine & faeces
hypothyroidism - levothyroxine - AE
1) reduced appetite
2) anxiety, trouble sleeping
3) Diarrhoea
4) hair loss
5) rare & serious
- heart issue (arrhythmia, high GP, pain, failure)
- seizure
- myxoedema
** reduce blood flow to GI -> affect gut absorption of oral levothyroxine
hypothyroidism - levothyroxine - monitoring
- target TSH 0.4 - 4 mIU/L
- 4 - 8 wks assess response after initiate/change therapy
- if normal FT4 but elevated TSH = non adherence
- monitor FT4 instead of TSH if central hypothyroidism
- thyroid function test (tFT)
** 6 - 12 month for non pregnant after euthyroid state
hypothyroidism - levothyroxine - CI
heart problem, epilepsy, hyperthyroidism
hypothyroidism - liothyronine - what is it
synthetic T3
hypothyroidism - liothyronine - indications
1) myxoedema coma
2) if T4 X work
3) combine w T4 if normalised TSH but still complain of hypothyroidism symptoms
4) need drug to wear off quickly (pre thyroid surgery)
hypothyroidism - liothyronine - dose
- normal: 25mcg
- elderly/CVD: 5mcg
effect of maternal hypothyroidism in pregnancy
- miscarriage, spontaneous abortion
- congenital defect, impaired cognitive development
transfer of TH from mother to child
maternal TH provide fetus up to 12 wks before fetus develop 1 thyroid gland
effect of pregnancy on dosage for hypothyroidism
increase dose by 30-50% to maintain euthyroid status
monitoring target for TSH for pregnancy and hypothyroidism
1) 1st trimester: < 2.5 mIU/L
2) 2nd trimester: < 3.0 mIU/L
3) 3rd trimester < 3.5 mIU/L
definition of subclinical hypothyroidism
1) elevated TSH w normal T4
2) result of early hashimoto disease
risks involved in subclinical hypothyroidism
- TSH > 7.0 mIU/L in older adult = greater risk of HF
- TSH > 10 mIU/L = greater risk of coronary heard disease
when to consider treating subclinical hypothyroidism
1) TSH > 10 mIU/L
2) TSH 4.5 - 10 mIU/L
- symptoms of hypothyroidism
- TPO Ab present
- history of cardiovascular disease, HF, HF risk factor
subclinical hypothyroidism treatment
initial dose 25-75mcg
causes of hyperthyroidism
1) Toxic diffuse goiter
- TSI stimulate TH production, not under -ve feedback loop
2) pituitary adenomas
3) toxic adenoma (hot nodule): secrete T3
4) toxic multi-nodular goiter (Plummer’s disease)
- multiple nodules that secrete T3
5) drug induced: amiodarone, lithium
6) subacute thyroiditis
- infection, drug induced, early Hashimoto
- released of stored hormone in follicle
S&S of hyperthyroidism
(THYROIDISME)
- tremor
- heart rate up
- yawning
- restlessness
- oligiomenorrhoea/amenorrhoea
- irritability
- diarrhoea
- intolerance to heat
- sweating
- muscle wasting & weight loss
- exophthalmos in Graves
diagnosis of hyperthyroidism
- S&S
- elevated free T4 serum concentration
- suppressed TSH concentration (except TSH-secreting adenomas)
- readioactive iodine uptake (RAIU) for better aetiology
** uptake elevated if gland actively secreting TH (Graves, TSH-secreting adenoma, toxic adenoma, multi nodular goiter)
** uptake suppressed in disorders caused by thyroiditis/cancer - presence of TRAb, ATgA, TPO
- biopsy
treatment options for hyperthyroidism
1) surgery resection
2) radioactive iodine (RAI) ablative therapy
3) thyroidectomy
4) antithyroid pharmacotherapy
surgery resection for hyperthyroidism
can cause hypothyroidism
radioactive iodine (RAI) for hyperthyroidism
- also result in hypothyroidism
- first line if X CI for Graves
- concentrate in thyroid tissue -> destroy overactive thyroid cells
- X pregnancy
thyroidectomy for hyperthyroidism
can also cause hypothyroidism
indication for hyperthyroidism pharmacotherapy
1) awaiting ablative therapy/surgery
- deplete stored hormone
- minimise risk of post-ablation hyperthyroidism caused by thyroiditis
2) X ablative/surgical candidates or failed to normalise thyroid
3) mild disease, small goiter, low or -ve antibody titres, women
4) limited life expectancy
pharmacotherapy options for hyperthyroidism
1) thionamide `
2) iodide
3) non selective beta blocker
MOA of thionamides
act as substrate for TPO -> inhibit thyroid peroxidase -> inhibit thyroid hormone synthesis -> reduce thyroid hormone output -> reduce S&S of thyrotoxicosis
dosing for thionamides
1) Carbimazole (more for Graves)
- initial: 15-60mg daily in 2-3 divided doses
- euthyroid: 5 - 15 mg once daily
2) PTU
- initial: 50-150mg oral 3 times daily
- euthyroid: reduce to 50mg 2-3 times daily
thioamides AE
1) Rash, joint pain, N, jaundice
2) hypothyroidism
- monitor thyroid size & serum TSH
- titrate dose (reduce) once thyroid size reduce + TSH normalise
3) hepatotox
4) rash (SJS)
5) agranulocytosis early in therapy (3 months)
6) fever
efficacy/monitoring for thioamide
- slow onset, max effect 4-6 month (stop production but X remove stored hromone)
- monthly dose titration
MOA of iodides
- inhibit release of stored TH
- minimal effect on hormone synthesis
- decrease vascularity and size of gland
iodides indication for hyperthyroidism
1) before surgery (7-10 days) to shrink gland
2) after ablative therapy (3-7 days) to inhibit thyroiditis-mediated release of stored TH
3) thyroid storm
non selective beta blockers
- propanolol
- MOA: block hyperthyroid manifestation by beta-adrenergic receptor, high dose block T4 -> T3 conversion
- indication
1) Symptomatic relief
2) bridge therapy for thioamide therapy to kick in or before ablation/surgery
3) Treatment of thyroiditis (self limiting)
pregnancy and hyperthyroidism
- symptoms: failure to gain weight despite good appetite, tachycardia
- fetal loss if untreated but thioamide risk of embryopathy
- treatment (lowest possible dose)
** T4 at uper limit
** 1st trimester: PTU
** 2nd and 3rd: carbimazole cuz PTU high hepatotox
definition of subclinical hyperthyroidism
- low/undetectable TSH w normal T4
risk of subclinical hyperthyroidism
- elevated risk of AF in pt > 60 yo
- elevated risk of bone fracture in postmenopausal women
- conflicting data about mortality risk
treatment of subclinical hyperthyroidism
- similar to over hyperthyroidism except oral therapy alternative to ablative therapy in young pt
- compelling if TSH < 0.1 mIU/L
- beta blocker (Esp AF)
drugs and thyroid problem
1) Amiodarone
- iodine in chemical structure
- affect iodine uptake/secretion/production -> thyroiditis
- hypo & hyper
2) lithium
- hypo: inhibit thyroid hormone secretion & release -> signal increase in TSH & possible goiter development
- hyper: thyroiditis
3) interferon alfa
- thyroiditis: hyper -> hypo
