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IC15 Thyroid disorders Flashcards

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1
Q

Physiologic functions regulated by TH

A

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

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2
Q

TSH
causes of change in levels

A

Primary causes of conditions → involves thyroid gland pathology
Secondary ⇒ glands work normally; other factors causes hyper/ hypothyroidism

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3
Q

TSH
primary hypothyroidism

Level & reasons

A

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

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4
Q

TSH
primary hyperthyroidism

Levels & reasons

A

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

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5
Q

TH: T3

how its derived, t1/2, protein binding

A

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

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6
Q

TH: T4

t1/2, FT4

A

t1/2 = 6-7 days; highly protein bound

FT4 → unbound & routinely ordered with TSH to evaluate thyroid status

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7
Q

elevated TBG & effects

A
  1. lower free T3 [FT3] & free T4 [FT4] levels due to more T3 & T4 binding to extra TBG
    (Due to pregnancy/ on oestrogen)
  2. TSH released will instruct thyroid glands to release more THs
  3. Hence levels of FT3 & FT4 return to normal ⇒ achieve new equilibrium
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8
Q

Antibodies for testing

non-specific & specific

A

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

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9
Q

screening
compelling indications

A
  • 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
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10
Q

screening
individuals recommended

A

paediatrics & pregnant women
thyroid hormones required for growth & development

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11
Q

hypothyroidism
causes: primary

A

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

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12
Q

hypothyroidism
causes: secondary

A

Central hypothyroidism
* hypothalamus unable to secrete TRH
* Pituitary unable to secrete TSH

Drug induced: amiodarone, lithium

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13
Q

hypothyroidism
signs & symptoms

CD, G, FWB, SCMP

A

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

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14
Q

clinical manifestations of hypothyroidism

increased risks

A

Total cholesterol, LDL & triglycerides
ASCVD & MI
Miscarriage
impaired fetal development

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15
Q

cases of concern in hypothyroidism

A

pregnancy
subclinical hypothyroidism

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16
Q

diagnosis of hypothtyroidism

primary & secondary (labs)

A

Primary hypothyroidism
↑TSH, ↓ T4
Positive antibodies (TPO, ATgA)
Central hypothyroidism (secondary)
↓TSH, ↓ T4

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17
Q

cases of concern in hypothyroidism
pregnancy

risks, maternal TH, women on levothyroxine

A

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

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18
Q

cases of concern in hypothyroidism
subclinical hypothyroidism

increases risks, when to start therapy

A

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

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19
Q

hypothyroidism drugs

Study These Flashcards
A
  1. Levothyroxine
  2. Liothyronine
20
Q

hypothyroidism drugs
levothyroxine

initial dosing & titration

Study These Flashcards
A

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

21
Q

hypothyroidism drugs
levothyroxine

when to take

Study These Flashcards
A

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

22
Q

hypothyroidism drugs
levothyroxine

monitoring, ideal TSH, euthyroid state

Study These Flashcards
A
  • 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

23
Q

hypothyroidism drugs
levothyroxine

AE

Study These Flashcards
A

Cardiac abnormalities → tachyarrhythmias, angina, MI
Risks of fractures
Signs of hyperthyroidism

24
Q

hypothyroidism drugs
liothyronine

indication

Study These Flashcards
A

if deiodination not working properly
if TH required in short time frame (ie surgery)
If patient in myxedema coma ⇒ drug is more potent

25
hypothyroidism drugs liothyronine | t1/2
t1/2 = 1-2.5 days Much shorter than T4; more difficult to achieve stable state
26
hypothyroidism drugs liothyronine | initial dosing
Young, healthy adult: 25 mcg elderly/ CVD patients: 5 mcg
27
hypothyroidism drugs liothyronine | AE
High incidence of hyperthyroid symptoms
28
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
29
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
30
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
31
hyperthyroidism causing elevated risks
AF in patients > 60 years Bone fracture in postmenopausal women
32
hyperthyroidism goals of therapy
Minimise/ eliminate symptoms; improve quality of life Minimise long-term damage to organs Normalise free T4 and TSH concentrations
33
hyperthyroidism non-pharmacological treatments
1. Surgical resection 2. Radioactive iodine (RAI) ablative therapy 3. Thyroidectomy
34
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)
34
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
34
hyperthyroidism types of pharmacological therapy
1. thionamides (carbimazole & PTU) 2. non-selective BB (propanolol) 3. iodine (lugol's solution)
35
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
35
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
35
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
35
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
36
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
36
hyperthyroidism propanolol | MOA
Blocks hyperthyroidism manifestations mediated by b-adrenergic receptors May block T4/ T3 conversion when used at high dose
37
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)
38
hyperthyroidism iodine solution | MOA
Inhibits release of stored THs Helps decrease vascularity & size of gland
39
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
40
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

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