IC15 Thyroid disorders Flashcards
Physiologic functions regulated by TH
Main: Oxygen consumption by tissues, basal metabolic rate, lipid metabolism, uptake & utilisation of glucose
Others: Body temperature, CNS, sleep, cardiac & GI functions, muscle strength, breathing, menstrual cycle, skin dryness
TSH
causes of change in levels
Primary causes of conditions → involves thyroid gland pathology
Secondary ⇒ glands work normally; other factors causes hyper/ hypothyroidism
TSH
primary hypothyroidism
Level & reasons
Hypothalamus detect persistently low levels of THs & secretes TRH
TRH instructs pituitary to secrete TSH
* Elevation of TSH supposed to increase TH levels
* However, thyroid gland dysfunction does not allow for stimulation & secretion of THs
TSH continuously increase ⇒ elevated levels
TSH
primary hyperthyroidism
Levels & reasons
Hypothalamus detect persistently elevated levels of THs & no longer secretes TRH
No TRH to instruct pituitary to secrete TSH
* Drop in TSH supposed to decrease TH levels
* However, thyroid gland is functioning independently of TSH → not affected by low TSH
TRH not secreted due to high TH ⇒ TSH low levels
TH: T3
how its derived, t1/2, protein binding
derived from peripheral conversion of T4 by de-ionidination via deiodinases
t1/2 = 2 days; highly protein bound
Irregular, may not be representative of TH stores in body
TH: T4
t1/2, FT4
t1/2 = 6-7 days; highly protein bound
FT4 → unbound & routinely ordered with TSH to evaluate thyroid status
elevated TBG & effects
- lower free T3 [FT3] & free T4 [FT4] levels due to more T3 & T4 binding to extra TBG
(Due to pregnancy/ on oestrogen) - TSH released will instruct thyroid glands to release more THs
- Hence levels of FT3 & FT4 return to normal ⇒ achieve new equilibrium
Antibodies for testing
non-specific & specific
non-specific
ATgA: thyroglobulin Ab
TPO: thyroperoxidase Ab (significantly associated with hypothyroidism)
Diseases with (+) ATgA & TPO ⇒ 95% of Hashimoto; 60-70% of Graves’
Specific
TRAb: thyrotropin receptor IgG Ab
Confirmatory for graves’ disease but expensive
Ab continuously trigger receptors ⇒ TG continuously produce TH
screening
compelling indications
- Presence of autoimmune disease (eg. T1DM, cystic fibrosis)
- First-degree relative with autoimmune thyroid disease
- Psychiatric disorders:
Thyroid abnormalities can induce mood, anxiety, psychosis etc
Important to determine root causes of psychiatric conditions - Taking amiodarone (anti-arrhythmic) or lithium (psychiatric drug)
- Hx of head / neck radiation for malignancies
- Symptoms of hypothyroidism / hyperthyroidism
screening
individuals recommended
paediatrics & pregnant women
thyroid hormones required for growth & development
hypothyroidism
causes: primary
Iodine deficiency → most common
Hashimoto disease (chronic autoimmune thyroiditis)
Most common in areas with iodine sufficiency
(+) ATgA & TPO Ab → disproportionately affects women
Latrogenic: thyroid resection/ radioiodine ablative therapy for hyperthyroidism
Removing too much thyroid glands; lesser TH produced now
hypothyroidism
causes: secondary
Central hypothyroidism
* hypothalamus unable to secrete TRH
* Pituitary unable to secrete TSH
Drug induced: amiodarone, lithium
hypothyroidism
signs & symptoms
CD, G, FWB, SCMP
General: Slowing down of body functions
Cold intolerance, Dry skin
Fatigue, lethargy, weakness, Weight gain, Bradycardia
Slow reflexes, Coarse skin and hair, Menstrual disturbances (more frequent, more blood), Periorbital swelling [edema]
Goiter
clinical manifestations of hypothyroidism
increased risks
Total cholesterol, LDL & triglycerides
ASCVD & MI
Miscarriage
impaired fetal development
cases of concern in hypothyroidism
pregnancy
subclinical hypothyroidism
diagnosis of hypothtyroidism
primary & secondary (labs)
Primary hypothyroidism
↑TSH, ↓ T4
Positive antibodies (TPO, ATgA)
Central hypothyroidism (secondary)
↓TSH, ↓ T4
cases of concern in hypothyroidism
pregnancy
risks, maternal TH, women on levothyroxine
Effects:
* Miscarriage, spontaneous abortion
* Congenital defects, impaired cognitive development
* Maternal THs provide fetus with TH for up to 12 weeks
Fetus TH production only occurs after formation of own thyroid glands
Important for metabolism
Pregnant women on levothyroxine → may need 30-50% increase in pre-pregnant dose to maintain euthyroid status
Target TSH
1st tri: <2.5 mIU/ L
2nd tri: <3.0 mIU/ L
3rd tri: <3.5 mIU/ L
cases of concern in hypothyroidism
subclinical hypothyroidism
increases risks, when to start therapy
Elevated risk
TSH >7.0 mIU/L in older adults → heart failure
TSH >10 mIU/L → coronary heart disease
Considerations for treatment for 25-75 mcg OD:
* TSH >10 mIU/L
* TSH 4.5-10 mIU/L and
Symptoms of hypothyroidism
TPO Ab present
History of CVD, HF or risk factors
hypothyroidism drugs
- Levothyroxine
- Liothyronine
hypothyroidism drugs
levothyroxine
initial dosing & titration
Initial dosing
* Young, healthy adults: 1.6 mcg/ kg/ day
Usually just start at 100 mcg OD
* With CVD: 12.5-25 mcg OD & titrate up
Should be lower, if not may cause cardiac stress ⇒ start low & go slow
Titration
* Depends on response → control of symptoms, normalisation of TSH & TH
Takes weeks to reduce symptoms & improve physiologically
Can increase/ decrease in 12.5 - 25 mcg OD or in 10-15% of weekly dose
hypothyroidism drugs
levothyroxine
when to take
30-60 mins before breakfast OR 4 hours after dinner ⇒ on empty stomach
Note: Ca or Fe supplements & antacids ⇒ to space at least 2 hours apart
hypothyroidism drugs
levothyroxine
monitoring, ideal TSH, euthyroid state
- 4-8 weeks to assess response in TSH after initiating/ changing therapy
- General target TSH (younger adults): 0.4-4 mIU/ L
- For central hypothyroidism: use FT4 levels
- TSH target for older adults: higher TSH can still be WNL (>70 yo: up to 6.9 mIU/L)
- Symptomatic relief (in 2-3 weeks)
- Normalisation of FT4 with consistently increasing TSH → likely non-adherence
Euthyroid state: Thyroid function tests (TFT) → recommended semi annually - annually in non-pregnant adult patients
hypothyroidism drugs
levothyroxine
AE
Cardiac abnormalities → tachyarrhythmias, angina, MI
Risks of fractures
Signs of hyperthyroidism
hypothyroidism drugs
liothyronine
indication
if deiodination not working properly
if TH required in short time frame (ie surgery)
If patient in myxedema coma ⇒ drug is more potent
hypothyroidism drugs
liothyronine
t1/2
t1/2 = 1-2.5 days
Much shorter than T4; more difficult to achieve stable state
hypothyroidism drugs
liothyronine
initial dosing
Young, healthy adult: 25 mcg
elderly/ CVD patients: 5 mcg
hypothyroidism drugs
liothyronine
AE
High incidence of hyperthyroid symptoms
hyperthyroidism Causes
Graves disease (toxic diffuse goiter) → most common
* TSH receptor Ab [TRAb; aka TSI] mimic TSH binding ⇒ TSI subtype stimulates TH production
Pituitary adenomas: increased TSH ⇒ stimulates more TH
Toxic adenoma (hot nodule): Solitary functioning nodule that secrete T3
Toxic multinodular goiter (Plummer’s Disease): multiple nodules that secrete T3
Drug induced: amiodarone, lithium
Subacute thyroiditis: infections, drug induced, early Hashimoto’s disease
* Results in the release of stored hormone; large amounts at once
hyperthyroidism signs & symptoms
THYROIDISM E
Tremor
Heart rate up
Yawning (fatigability)
Restlessness
Oligomenorrhea & amenorrhea
* Menstrual disturbances; lighter/ more infrequent menstruation
Intolerance to heat
Diarrhoea
Irritability
Sweating
Muscle wasting & weight loss
Exophthalmos (protruding eyeballs) → in Graves disease
hyperthyroidism lab results
- Elevated free T4 serum concentrations
- Suppressed TSH concentrations (except in TSH-secreting adenomas)
- Radioactive iodine uptake (RAIU) → used for better etiology
Uptake elevated if gland is actively secreting TH: Graves disease, TSH-secreting adenoma, toxic adenoma, multinodular goiter
Requires more iodine for formation of more TH
Uptake suppressed in disorders caused by thyroiditis/ cancer - Presence of TRAb, ATgA, TPO
hyperthyroidism causing elevated risks
AF in patients > 60 years
Bone fracture in postmenopausal women
hyperthyroidism goals of therapy
Minimise/ eliminate symptoms; improve quality of life
Minimise long-term damage to organs
Normalise free T4 and TSH concentrations
hyperthyroidism non-pharmacological treatments
- Surgical resection
- Radioactive iodine (RAI) ablative therapy
- Thyroidectomy
hyperthyroidism
purpose of radioactive ablation
indication, c/i
First line option if no contraindications for Graves Disease
Destroys part of thyroid
Decreases signs of hyperthyroidism
Colourless, tasteless liquid in a capsule; concentrates in thyroid tissue
Destroys overactive thyroid cells
Pregnancy = absolute contraindication (can cross to fetus)
hyperthyroidism indication for pharmacological therapy
- Those waiting for ablative therapy/ surgical resection
Depletes stored hormones
Minimises risks of post-ablation hyperthyroidism caused by thyroiditis - Those cannot have ablative/ surgery/ failed to normalise thyroid
- Mild disease/ small goiter/ low or negative Ab titres/ women
- Limited life expectancy
hyperthyroidism types of pharmacological therapy
- thionamides (carbimazole & PTU)
- non-selective BB (propanolol)
- iodine (lugol’s solution)
hyperthyroidism therapy
thionamides (carbimazole & PTU)
MOA
Inhibits iodination & synthesis of TH by acting as substrate for TPO
PTU → also blocks T4/ T3 conversion in periphery at high doses
hyperthyroidism
thionamides (carbimazole & PTU)
dosing: initial & euthyroid
Carbimazole
Initial: 15-60 mg daily in 2-3 divided doses
Euthyroid: reduce to 5-15 mg OD
Once physiological function & symptoms improve, may be able to stop treatment → requires ~ 1 year
PTU
Initial: 50-150 mg PO TDS
Euthyroid: reduce to 50 mg BD-TDS
hyperthyroidism
thionamides (carbimazole & PTU)
AE
- Hepatotoxicity risk (boxed warning for PTU → carbimazole first line)
- Rash → risks for SJS
- Agranulocytosis early in therapy (usually within 3 months)
- Fever
hyperthyroidism
thionamides (carbimazole & PTU)
efficacy, remission rates, dose titration (&monitoring)
Maximal effect may take 4-6 months
* Due to TH being stored in TG that still can be released & cause high levels of TH
* Important to clear first, which takes time
Remission rates low
Monthly dosage titrations as needed (depending on symptoms and free T4 concentrations)
* TSH may remain suppressed for months after therapy begins
* Early in therapy, total T3 maybe better marker of efficacy than free T4
hyperthyroidism
thionamides (carbimazole & PTU): pregnancy
symptoms, importance & choice based on trimester
Symptoms:
* Failure to gain weight despite good appetite
* Tachycardia
Will have fetus loss if remain untreated → note that thioamides have risks of embryopathy
Important to use lowest possible dose & keep T4 at ULN
1st tri: use PTU, carbimazole ⇒ higher risks of congenital malformations
2nd & 3rd tri: use carbimazole, PTU ⇒ higher risks of hepatotoxicity
hyperthyroidism
propanolol
MOA
Blocks hyperthyroidism manifestations mediated by b-adrenergic receptors
May block T4/ T3 conversion when used at high dose
hyperthyroidism
propanolol
place in therapy
- Symptomatic relief (ie: tachycardia)
- Bridging therapy for thioamide effects to take place
- Before ablation/ surgery
- PRN for high risk patients → elderly with CVD, AF
- Treatment for thyroiditis (usually self-limiting)
hyperthyroidism
iodine solution
MOA
Inhibits release of stored THs
Helps decrease vascularity & size of gland
hyperthyroidism
iodine solution
place in therapy
Before surgery (7-10 days) ⇒ shrink gland
After ablative therapy (3-7 days) ⇒ inhibit thyroiditis-mediated release of stored TH
Thyroid storm
hyperthyroidism
iodine solution
efficacy duration, what to avoid
Limited efficacy after 7-14 days → TH release will resume
Do not use before ablative RAI
May reduce uptake of RAI
