Endocrine JC038: I Am Losing Weight And Sweating All The Time: Causes Of Severe Weight Loss: Thyrotoxicosis, Hypothyroidism Flashcards
Physiology of the thyroid gland
Hypothalamus —> TRH (Thyrotropin-releasing hormone)
—> Pituitary —> TSH
—> Thyroid gland —> Thyroxine (T3, T4)
—> Blood (>99% protein bound)
—> Free T3, T4 (active hormone) inhibit Hypothalamus + Pituitary
***Synthesis and Secretion of Thyroid hormones (T3, T4)
Iodine: ingested as iodide in diet
Iodide trapping
—> via Na/I symporter (NIS)
—> oxidised to Iodine by **Thyroperoxidase with H2O2
—> Iodine react with **Tyrosine (in Thyroglobulin) (Organification: Synthesis of Thyroid hormone) (within Follicular cells)
—> T3, T4 (Iodothyronines: stored in colloid on **Thyroglobulin)
—> secreted into Follicular cells upon stimulation by TSH
—> colloid droplets fuse with lysosomes
—> T3, T4 **cleaved from Thyroglobulin by Protease in Follicular cells
—> T3, T4 released into circulation
Synthesis of T3, T4
Iodide
—(Peroxidase)—> Iodine free radical
—(Peroxidase, added to Tyrosine unit of Thyroglobulin)—> Monoiodotyrosine-Thyroglobulin (MIT-Thyroglobulin) —> DIT-Thyroglobulin
Via Intra/Inter-molecular coupling
DIT + DIT —> T4-Thyroglobulin (Thyroxine)
MIT + DIT —> T3-Thyroglubulin (Triiodothyronine)
- Active Uptake of Iodide from blood by ***NIS into Thyrocyte / Follicular cell (basolateral membrane) (向出)
- cotransport 2 Na ions + 1 Iodide ion
- Na gradient: Driving force (created by Na/K ATPase: Na pump back to blood) - Efflux of Iodide into follicular lumen via ***Pendrin (apical membrane) (向入)
- Iodide **oxidised to Iodine and rapidly organified by incorporation into selected tyrosyl residues of Thyroglobulin
—> **Organification
—> form mono-iodotyrosine (MIT) + di-iodotyrosine (DIT) on Thyroglobulin
—> **catalysed by Thyroid peroxidase (with presence of **H2O2) - Coupling reaction
- T4 formed from 2x DIT
- T3 formed from MIT + DIT
—> T3, T4 still attached to Thyroglobulin
—> stored in follicle as colloid (for ~2-3 months) - T3, T4 liberated from Thyroglobulin scaffold before secreted as free hormone in blood
—> require endocytosis of Iodinated Thyroglobulin from apical membrane (成舊野食翻落Follicular cell)
—> ***digestion by Lysosomes (remaining MIT, DIT on Thyroglobulin will be deiodinated intracellularly —> Iodide transported back to colloid via Pendrin for reuse)
—> free T3, T4
—> T4»_space;> T3 (40 fold in plasma conc) - Circulating thyroid hormones bind to carrier protein
- ***Thyroxine-binding globulin (~70%)
- Albumin (~15%)
- Transthyretin (~10%)
- unbound (0.05%)
—> ensure circulating reserve + delay metabolic clearance of hormone
—> only unbound hormone are bioavailable
—> clinical measurement: measure total T4 instead of unbound T4 (in absence of protein binding abnormality) + measure binding protein level
Changes in binding protein level:
1. ↑ binding protein —> ↓ free thyroid hormone —> stimulate TSH release
2. ↓ binding protein (chronic liver disease) —> ↑ free thyroid hormone —> suppress TSH release —> ↓ thyroid hormone synthesis and release
- Active biological half life
- T4: 7 days
- T3: 1 day
Thyroglobulin and Thyroperoxidase
Thyroglobulin: Backbone protein for making + storage of thyroid hormone
Thyroperoxidase (past: Thyroid microsomal enzyme): Enzyme for organification process for synthesis of thyroid hormone
Mechanism of Thyroxine action
T3 (active hormone, secreted by thyroid gland / peripheral tissue (liver) conversion)
—> Active cellular uptake
—> **Intracellular protein receptor (T3>T4)
—> Modulation of nuclear RNA
—> 1. **Protein synthesis
—> 2. **Mitochondrial oxidative phosphorylation (Metabolism of cells)
—> 3. **Enzyme synthesis
***Thyroid function test
- Serum free thyroid hormone fT3, fT4 level (Active hormone)
- measures unbound free circulating hormone level
- fT4: 0.02%
- fT3: 0.2%
- NOT measure total (bound hormone ∵ fluctuations in binding protein e.g. pregnancy, contraceptive —> causing ↑ total thyroid hormone) - Serum TSH
- Thyrotoxicosis: Suppressed
- **Secondary hypothyroidism (hypothalamic-pituitary failure): Low / Normal (∴ sometimes cannot tell whether a patient has hypothyroidism just by TSH)
- **Primary hypothyroidism: Elevated - Serum Total T4
- measurement of total T4 which is bound to plasma binding proteins (99.96%) (**Thyroid hormone-binding globulin TBG, **Thyroxine-binding prealbumin TBPA)
- affected by disease state which alters TBG level e.g. ↑ in pregnancy, ↓ in hypoalbuminaemia (chronic liver disease)
Screening for Thyroid Dysfunction
Serum TSH (may miss unusual patient with secondary hypothyroidism with normal TSH)
- sometimes must be coupled to T4 for interpretation
Thyroid function testing algorithm (SpC Medicine)
Low TSH
—> Increased fT4 —> Hyperthyroid
—> Normal fT4 —> Subclinical hyperthyroidism, T3 thyrotoxicosis, Non-thyroidal illness
—> Decreased fT4 —> Hypopituitarism, Drugs, Non-thyroidal illness
High TSH
—> Increased fT4 —> Pituitary tumour, Thyroid resistance
—> Normal fT4 —> Subclinical hypothyroidism
—> Decreased fT4 —> Hypothyroid
***Signs / Symptoms of Hyperthyroidism
Symptoms:
↑ Metabolism + ↑ Sympathetic discharge
1. **Weight loss
2. **Palpitation
3. Nervousness
4. Easy fatiguability
5. **Excessive sweating
6. **Heat intolerance
7. Hyperkinesia
8. **Diarrhoea
9. Hair loss
10. **Eye problem (if ***autoimmune thyroid disease)
Signs (記: 頸, 眼, 皮膚):
1. Goitre
- Thyrotoxic eye signs
- **Lid lag, retraction (ALL causes of hyperthyroidism)
Specific to Grave’s (self notes):
- **Periorbital edema
- **Exophthalmos (Proptosis)
- **Extraocular muscle involvement —> Limitation in rotation of eyeballs —> Diplopia (∵ infiltration of retroorbital tissue, ∵ inflammation of retroorbital eye muscles)
- **Corneal involvement e.g. Corneal erosion (∵ failure of covering of eyes)
- **Sight loss (∵ traction of optic nerve) - Skin (if autoimmune thyroid disease)
- Pretibial myxoedema (non-tender, thickening, swelling, redness, hairy, pigmentation (may confuse with cutaneous polyarteritis nodosa), stop above ankle)
- ***Thyroid acropachy (autoimmune involvement, infiltration of soft tissue around nail bed —> finger clubbing)
***Causes of Thyrotoxicosis
- ***Graves’ disease (most common)
- ***Toxic MNG (middle age / older)
- ***Toxic adenoma (benign tumour)
- ***Thyroiditis (release of pre-formed hormone into bloodstream)
- ***Pituitary hyperthyroidism (presence of TSH-secreting pituitary adenoma)
- Molar hyperthyroidism (∵ multiple pregnancy, hyperemesis gravidarum during 1st trimester, struma ovarii, molar pregnancy)
- Factitious (takes too much / overdose of thyroid hormone)
Graves’ disease
Autoimmune disease
- lymphocytes acting against self-antigen: TSH receptor
***Thyrotropin-receptor Ab (TRAb) (aka TSH-receptor Ab) stimulates TSH receptor on Thyroid gland —> stimulates Thyroid gland
1. Stimulates thyroid cell hyperplasia
2. Increase thyroid hormone release
—> Hyperthyroidism —> Suppress TSH release from pituitary
Epidemiology:
- M:F = 1:4.8
- Highest incidence: Reproductive age (20-50)
Clinical diagnosis:
1. **Diffusely enlarged thyroid gland (x nodular)
2. ↑ fT3, fT4 but ↓ TSH level
3. **Diffuse ↑ uptake on radioiodine scintillation scan
4. ***Positive TSH receptor Ab in blood
Clinical presentation:
1. Goitre
2. Hyperthyroidism symptoms
3. **Exophthalmos (70%)
4. **Pretibial myxoedema (a few %) (specific for Graves, can be present on for dorsum as well (SpC Medicine))
5. **Related autoimmune disease (a few % e.g. MG, insulin dependent DM)
6. Complications of hyperthyroidism
- **Thyroid storm (severe hyperthyroidism)
- **Thyrotoxic periodic paralysis associated with **hypokalaemia
- **AF
- **Heart failure
Radioisotope Thyroid Scan
Find out underlying cause for Hyperthyroidism
↑ Uptake:
1. Graves’ disease: **Diffuse uptake
2. MNG: **Heterogeneous uptake
3. Toxic adenoma: **Focal area of ↑ uptake with ↓ uptake in rest of gland
4. TSH-secreting pituitary adenoma: **Diffuse uptake (TSH: high / normal differentiate from Graves’: TSH suppressed)
↓ Uptake:
1. **Thyroiditis
2. **T4 overdose
3. Iatrogenic overuse of thyroid hormone
Clinical usefulness of TRAb
- Establish diagnosis of Graves’ disease
- usually not necessary as ~100% patients with active Graves’ are positive for TRAb
- level of Ab ↓ with Anti-thyroid drug treatment - ***Prognostic indicator of the outcome of Anti-thyroid drug treatment for Graves’
- positive TRAb at the end of therapy indicates higher chance of relapse —> should continue treatment
- negative TRAb more likely to have prolonged remission - Forecasting ***neonatal Graves’ in pregnant woman during 3rd trimester
- high level of TRAb associated with neonatal Graves’ due to transplacental passage of Ab
***Management of Graves’ disease
- Anti-thyroid drugs
- Thiouracil derivatives (**Thionamides): Carbimazole, Methimazole, Propylthiouracil (PTU) (PTU shorter t1/2)
—> duration: **12-18 months (treat until TRAb **negative)
—> +/- T4 supplement (Block and Replace)
—> major drawback: **>60% relapse
- ***Lithium
(—> made use of hypothyroidism SE: Nephrogenic DI (SpC Medicine))
—> block Na-I transporter
—> monitor carefully
—> only use if patient sensitive to Thiouracil derivatives
- Surgery
- Radioactive iodine therapy
- Ancillary drug therapy
- Sedatives
- **β-blockers
- **Iodide (Lugol’s solution)
Indications of Definitive treatment (RAI / Surgery) over Medical treatment (Metabolic round)
- Concomitant heart conditions (e.g. HF, AF) —> Relapse from medical treatment can cause decompensation of heart conditions
- GO (avoid RAI since can exacerbate GO)
- Thyrotoxic Periodic Paralysis (TPP)
Thiouracil derivatives
MOA:
1. Inhibit ***Thyroid hormone synthesis
- inhibit organification of iodide to iodine
- inhibit coupling of iodotyrosines
- Inhibit ***T4 to T3 conversion (PTU only)
- ***Immunosuppressive effect
- action on intrathyroid antigen-presenting cells —> ↓ Thyroid AutoAb level
Absorption of PTU / Methimazole (Carbimazole converted to Methimazole in body)
- unrestricted
- actively concentrated by thyroid gland within minutes
- long t1/2 esp. Methimazole (can be given as QD dose)
- **PTU shorter t1/2
- **Pregnancy / Breastfeeding: **PTU preferred ∵ cross placenta less than Methimazole
- both transferable into milk (Methimazole > PTU)
- **Teratogenic: Methimazole / Carbimazole»_space; PTU: Aplasia cutis, **Choanal atresia —> using lowest possible dose
- use PTU from pre-conception until end of **1st trimester —> switch to Methimazole/ Carbimazole (less ***liver SE) in 2nd trimester
SE:
1. Rash (5%)
-
**Agranulocytosis (0.1%)
- **Idiosyncratic (SpC Medicine)
- Genetic predisposition: HLA-B38:02:01
- occur suddenly
- reversible
- usually **first 2 months
- with age (>40)
- with high dose (∴ lowest possible dose)
- S/S: fever, sore throat —> quickly go to doctor to check WBC (may need G-CSF)
- not routinely check CBC, only if deranged LFT / infection (SpC Medicine) - Rare: **Cholestatic jaundice, **Hepatocellular toxicity, Acute arthralgia, ANCA induced vasculitis
Indications for Anti-thyroid drugs
- Children and adolescents
- Pregnant women
- Adults
- esp. mild-moderate gland size + disease activity
- preference of patient
Predictive patient characteristics of response to Anti-thyroid drugs
Higher recurrence:
1. Large goitre
2. Positive family history
3. Higher initial T3 / T3:T4 ratio
4. Shorter course of treatment
5. Failure of normalisation of TSH after 1 / 2 years
6. High TRAb level
Surgical treatment for Diffuse toxic goitre
Definitive treatment
Indication:
- Young age
- **Failed medical treatment
- **Relapse a few times
- SE of medications
- **Eye signs
- **Expecting pregnancy
- Refuse radioactive iodine
- ***Big goitre
- Bilateral subtotal thyroidectomy
- Unilateral total + contralateral subtotal lobectomy
- Near total thyroidectomy
**Pre-operative preparation:
1. **Anti-thyroid medications until **Euthyroid
- avoid precipitation of **thyroid storm during operation
2. **β-blockers for 2 weeks
(3. Old practice: **Lugol’s iodine 5 days before operation (↓ vascularity of thyroid —> may ***reduce blood loss during operation))
***Complications of Thyroid surgery
-
**Vocal cord dysfunction (unilateral / bilateral)
- **RLN (Infraglottic) / ***External branch of Superior laryngeal nerve (Supraglottic: Cricothyroid)
- transient / permanent - ***Hypoparathyroidism (∵ injury / removal of parathyroid gland)
- transient / permanent - Bleeding
- superficial / deep - ***Tracheomalacia (cartilage in trachea collapses especially during increased airflow)
- Wound complications
- Seroma
- Hypertrophic scar - ***Thyroid storm
- Others
**Post-op Monitoring:
1. Voice
2. **Ca level (6-12 hours after operation) (Hypoparathyroidism)
3. SOB, Compression sensation
4. ***HR, temperature (Thyroid storm)
5. Infection
6. Keloid scar
Radioactive Iodine
α-emission of 131-I mostly not absorbed
***β-emission of 131-I almost completely absorbed
MOA:
1. Induce ***necrosis of follicular cells
—> fibrosis
—> disappearance of colloid
- Non-destroyed cells have limited replication
- Affect thyroid autoimmunity
- destruction of radiosensitive intrathyroid T-suppression cells
- but could lead to radiation thyroiditis —> release of thyroid Ag into blood —> **surge of TRAb within first few weeks of radioactive iodine (may have **thyroid eye disease come rapidly)
Use:
- since late 1940
- gradual trend ↑ use
- ↓ age limit esp. in USA
Advantages:
1. **Low relapse rate (15% after 1 dose)
2. Simple + economical
3. No immediate complication (caution with severe cases e.g. **thyroid storm, thyroid eye disease)
Indications for 131-I
- Adults >30
- age limit arbitrary
- except if small gland / mild disease - ***Thyrotoxic heart disease
- Relapse after surgery
- CI to surgery
Preparation and precautions of 131-I therapy (From ERS15)
Similar preparation for both Hyperthyroidism and Differentiated thyroid cancer
1. Follow legislation, regulation on safe use of radioisotope therapy
- Facilities needed: Trained personnel, storage equipment, radiation protection, waste handling, monitoring, controlling, handling contaminants
- Discussion of treatment options, patient’s consent, instruct patient on post-therapy precaution, follow-up
- In hyperthyroidism, **Stop anti-thyroid medication 4-14 days before RAI
- Carbimazole: **4 days
- PTU: **14 days
—> allow ↑ TSH production from pituitary
—> **↑ Iodine uptake by residual thyroid tissue / tumour cells - ALL female: ***stop breastfeeding, practice contraception 4 weeks before RAI
- ***Low iodine diet for >= 2 weeks
- avoid seafood, dairy products, soy products, iodine containing medications
Complication and Precautions of 131-I
- Hypothyroidism
- transient / permanent - Fetal risk (***definite)
- transient radiation —> induced changes in gametes —> avoid pregnancy for 6-12 months
- cross placenta + concentrated by fetal thyroid (>12 week) —> CI in pregnancy - Excreted in milk
- ***NO breastfeeding - **↑ Risk of Thyroid eye disease developing after RAI —> **Avoid RAI in GO
- Precipitate **thyroid storm due to **radiation thyroiditis
NB:
- Thyroid carcinoma (NOT ↑ with RAI)
- Leukaemia (NOT ↑ with RAI)
- Transmissible genetic damage (NOT ↑ with RAI)
***Thyroid eye disease (TED)
Aka ***Graves’ ophthalmopathy (GO), Dysthyroid eye disease
Pathogenesis (postulated):
**Orbital fibroblast is the target cell
- a subpopulation has the ability to **differentiate into adipocytes
- ↑ TSH receptor expression on orbital fibroblast / adipocytes is a consequence of adipocyte differentiation —> ***Adipogenesis
What stimulates adipogenesis and TSH-R expression in GO orbit
- TRAb level **correlates with clinical score of GO
- **TRAb stimulate orbital adipocytes (↑ PPARγ, adiponectin, TSH-R gene expression)
- ***TSH also stimulates orbital adipogenesis in GO but not normal orbital preadipocytes (i.e. not in normal individual)
Classification (“NO SPECS”):
- Class 0: No S/S
- Class 1: Only signs, no symptoms (Lid lag, **Lid retraction, Stare)
- Class 2: Soft tissue involvement (signs + symptoms e.g. **periorbital edema)
- Class 3: **Proptosis
- Class 4: **EOM involvement
- Class 5: Corneal involvement (ulceration / scarring)
- Class 6: Sight loss (optic nerve compression / traction at apex of orbit by enlarged extraocular muscles)
To differentiate GO from other infiltrative eye disease:
- GO: insertion of eye muscle ***spared
Relationship of GO to Thyroid status
- patient may be **hyper / **hypo / **euthyroid
- 80% of patients with GO developed **eye signs first —> within 18 months of diagnosis of thyrotoxicosis
- Debatable whether ophthalmopathy should affect choice of treatment of hyperthyroidism
- **131-I is associated with higher incidence of ophthalmopathy vs Anti-thyroid drugs (poor control of post-RAI hypothyroidism / high level of TRAb post RAI?)
—> **Avoid RAI in patients with GO
Histology of TED
Extraocular muscles:
- **edema
- mononuclear cell infiltration
- **↑ mucopolysaccharides
- fibrosis
Retrobulbar fat:
- **lymphocyte infiltration
- **replaced by fibrous tissue
- collagen tissue with hyaluronic acid
Optic nerve:
- atrophy
- ***replaced by fibrous and fatty connective tissue
Treatment of GO
- Rapid control of thyroid dysfunction to euthyroid
- treatment of hyperthyroidism will ***NOT cure TED —> also need other treatments -
**Immunosuppressants for infiltrative ophthalmopathy
- **Steroid (IV / Oral methylprednisolone)
- ***Cyclosporin A (IV)
- Plasmapheresis
- IVIG
- TNFα inhibitor - ***IGF-1 receptor inhibitor
- ***Orbital irradiation
- Orbital decompression / Eye muscle operation
- thinning of **medial wall + **floor (X Lateral wall + Superior roof)
Thyrotoxic Periodic Paralysis (TPP)
- mainly in ***Asians, rare in Caucasians
- predominantly in ***male (25%, female 0.8%)
- occur in ***ALL causes of thyrotoxicosis (not just Graves’)
- Skeletal muscles involved
Mechanism:
1. Thyroid hormone —>↑ Na/K-ATPase activity
2. ↑ Adrenergic response —> ↑ Na/K-ATPase activity
3. ↑ **Hypokalaemia
—> ∵ **enhanced insulin response
—> ↑ Na/K-ATPase activity (esp. after carbohydrate load)
—> insulin drives K into cells
—> shifting from extracellular to intracellular compartment
- Occur ***ONLY during hyperthyroidism but not in euthyroid
- Genetic susceptibility: 17q24.3
Clinical presentation:
1. **Motor involvement mainly (seldom respiratory muscle)
2. Danger of cardiac **arrhythmia (∵ HypoK + paralysed muscle)
3. **Spontaneous recovery (accelerated by IV K infusion)
4. Attacks prevented by low salt diet, appropriate carbohydrate intake, **spironolactone, propranolol
Treatment (SpC Revision):
1. IV K infusion
2. Antithyroid drug
Hypothyroidism
Causes:
1. Autoimmune
- **Atrophic thyroiditis
- **Hashimoto’s thyroiditis (enlarged Goitre)
2. RAI therapy
3. Subtotal thyroidectomy
4. **Subacute thyroiditis
5. **Excessive iodide intake (e.g. seaweed) (Wolff–Chaikoff effect)
6. Congenital hypothyroidism
7. ***Iodine deficiency (may contribute transient hypothyroidism at birth)
8. Secondary hypothyroidism (hypothalamic-pituitary disorder)
Clinical patterns (depend on onset):
1. **Cretinism
2. Juvenile myxoedema
3. Adult myxoedema
4. **Myxoedema coma (most severe form)
Signs / Symptoms of Hypothyroidism
Symptoms:
Adults:
1. Easy fatiguability
2. Coldness
3. Weight gain
4. **Constipation
5. **Menstrual irregularities
6. Muscle cramps
7. **Chest pain (∵ **hypercholesterolaemia —> IHD)
Signs:
1. **Dry, coarse skin
2. **Hoarseness
3. Slow reflex (or failure of relaxation of jerk) (pathognomonic)
4. **Bradycardia
5. **Pallor
Children:
1. Retardation of growth
2. Mental retardation
Newborn:
1. **Cretinism
2. **Mental retardation
3. **Short stature
4. Puffy face, flat nose, short neck, thick lips
5. **Deaf mutism
6. **Protuberant abdomen
7. **Umbilical hernia
8. ***Jaundice
Painless thyroiditis
Other names depending on clinical presentation:
1. Lymphocytic thyroiditis
2. Atrophic thyroiditis (atrophic gland)
3. Hashimoto’s thyroiditis (enlarged thyroid with lymphocyte)
4. Post-partum thyroiditis
Variable prognosis depending on residual thyroid reserve
Hashimoto’s thyroiditis
- Autoimmune disease
- common cause of hypothyroidism
- Low T4, ***High TSH
- Presence of ***Anti-microsomal (Thyroid peroxidase) Ab
- Enlarged goitre due to **↑ fibrosis + **infiltration by lymphocytes
- common in middle-aged females
- may be associated with ***other autoimmune disease
Subacute thyroiditis
- Aka ***De Quervain’s thyroiditis, Giant Cell thyroiditis
- Preceding ***URTI (e.g. COVID-19)
- Giant cells + Lymphocyte infiltration of gland
—> **Granulomatous inflammation
—> Extravasation of colloid + Follicle destruction
—> Thyrotoxicosis —> **Hypothyroid —> Euthyroid - Acute pain, ***tender goitre
- Fever, **high WBC, **high ESR
- ***Resolves spontaneously
- Corticosteroid, NSAID in severe cases
Congenital hypothyroidism
- Local incidence 1:3000
- Neonatal ***cord blood TSH screening
- Suspicious if at ***2 weeks:
—> fT4 <12 pmol/L
—> TSH >7 mIU/L - Early treatment —> Preserve brain development
Causes:
1. **Athyreosis
2. **Dyshormonogenesis
3. Ectopic thyroid gland
4. Associated with other **congenital syndrome (Down’s, Trisomy 18 (Edward’s), Congenital heart disease)
5. **Hypothalamic-pituitary hypothyroidism
6. **Transient hypothyroidism
- Anti-thyroid drugs in mother with hyperthyroidism
- **TSH-blocking Ab in mother
- ***Neonatal iodine deficiency
- Premature delivery
Clinical features:
1. **Cretinism
2. **Mental retardation
3. **Short stature
4. Puffy face, flat nose, short neck, thick lips
5. **Deaf mutism
6. **Protuberant abdomen
7. **Umbilical hernia
8. ***Jaundice
Incidence of hypothyroidism
- Relates to environmental dietary iodine
- Higher incidence of autoimmune thyroiditis in iodine-replete countries
- HK: borderline iodine intake, incidence of autoimmune thyroiditis and hypothyroidism is low (1% vs 10% in Western countries)
Hypothyroidism and IHD
- Hyperlipidaemia —> prone to Coronary atherosclerosis
- Initiation of Thyroxine may ↑ CO —> further worsen IHD
- ∴ Treat Coronary atherosclerosis ***prior to T4 supplementation
- Thyroxine takes 4-6 weeks to equilibrate (no need to add thyroxine too quickly)
Myxoedematous Coma
- Medical emergency
- Severe hypothyroidism
Clinical presentation:
1. **Confusion coma
2. **Hypothermia
3. **Respiratory failure and Hypoxia
4. **Prone to infection
Treatment:
1. **IV Thyroxine (until cause of hypothyroidism found: Primary vs Secondary)
2. **IV Hydrocortisone may be necessary (∵ may have concurrent hypoadrenalism + thyroxine may accelerate metabolism of Cortisol in system)
SpC Medicine:
- Thyroid function affect 11-beta-hydroxysteroid dehydrogenase activity —> metabolism of Cortisol
(Anti-thyroid AutoAb)
(Classification:
1. Anti-TPO Ab (Thyroid peroxidase / Microsomal)
- Hashimoto’s
- Anti-Thyroglobulin Ab (ATA)
- Hashimoto’s - TSH receptor Ab (TRAb) (Stimulating vs Blocking)
- Graves’)
Anti-TPO Ab (SpC Medicine)
- Diagnosis of AITD (***Autoimmune thyroid disease)
- Risk factor of AITD
- Risk factor for thyroid dysfunction during Amiodarone therapy
- Risk factor for thyroid dysfunction during pregnancy + for post-partum thyroiditis
- Risk factor for hypothyroidism during IFN-alpha therapy
Anti-Thyroglobulin Ab (SpC Medicine)
- Thyroglobulin (Tg) is polymerised + degraded during process of thyroid hormone synthesis + release
In Non-neoplastic conditions:
- Not usually necessary / cost-effective to order both TPO-Ab and Tg-Ab ∵ TPO-Ab negative patients with detectable Tg-Ab rarely display thyroid dysfunction in iodide sufficient areas
In differentiated thyroid carcinoma:
- Tg-Ab should be measured prior to Tg analysis ∵ low levels of Tg-Ab can interfere with serum Tg measurement
TSH receptor AutoAb (TRAb)
- Heterogeneous, types of methods are classified according to their functional activity
- Lack of correlation between TRAb levels and clinical status largely because of the heterogeneity of Abs
—> Stimulating / Blocking Ab —> can co-exist within an individual + change over time
