Endocrine JC038: I Am Losing Weight And Sweating All The Time: Causes Of Severe Weight Loss: Thyrotoxicosis, Hypothyroidism

Question 1

Physiology of the thyroid gland

Answer 1

Hypothalamus —> TRH (Thyrotropin-releasing hormone)
—> Pituitary —> TSH
—> Thyroid gland —> Thyroxine (T3, T4)
—> Blood (>99% protein bound)
—> Free T3, T4 (active hormone) inhibit Hypothalamus + Pituitary

Question 2

***Synthesis and Secretion of Thyroid hormones (T3, T4)

Answer 2

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

Question 3

Synthesis of T3, T4

Answer 3

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)

1. 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)
2. Efflux of Iodide into follicular lumen via ***Pendrin (apical membrane) (向入)
3. 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)
4. 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)
5. 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&raquo_space;> T3 (40 fold in plasma conc)
6. 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

7. Active biological half life
   - T4: 7 days
   - T3: 1 day

Question 4

Thyroglobulin and Thyroperoxidase

Answer 4

Thyroglobulin: Backbone protein for making + storage of thyroid hormone
Thyroperoxidase (past: Thyroid microsomal enzyme): Enzyme for organification process for synthesis of thyroid hormone

Question 5

Mechanism of Thyroxine action

Answer 5

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

Question 6

***Thyroid function test

Answer 6

1. 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)
2. 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
3. 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)

Question 7

Screening for Thyroid Dysfunction

Answer 7

Serum TSH (may miss unusual patient with secondary hypothyroidism with normal TSH)
- sometimes must be coupled to T4 for interpretation

Question 8

Thyroid function testing algorithm (SpC Medicine)

Answer 8

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

Question 9

***Signs / Symptoms of Hyperthyroidism

Answer 9

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

2. 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)
3. 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)

Question 10

***Causes of Thyrotoxicosis

Answer 10

1. ***Graves’ disease (most common)
2. ***Toxic MNG (middle age / older)
3. ***Toxic adenoma (benign tumour)
4. ***Thyroiditis (release of pre-formed hormone into bloodstream)
5. ***Pituitary hyperthyroidism (presence of TSH-secreting pituitary adenoma)
6. Molar hyperthyroidism (∵ multiple pregnancy, hyperemesis gravidarum during 1st trimester, struma ovarii, molar pregnancy)
7. Factitious (takes too much / overdose of thyroid hormone)

Question 11

Graves’ disease

Answer 11

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

Question 12

Radioisotope Thyroid Scan

Answer 12

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

Question 13

Clinical usefulness of TRAb

Answer 13

1. 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
2. ***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
3. Forecasting ***neonatal Graves’ in pregnant woman during 3rd trimester
   - high level of TRAb associated with neonatal Graves’ due to transplacental passage of Ab

Question 14

***Management of Graves’ disease

Answer 14

1. 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

2. Surgery
3. Radioactive iodine therapy
4. Ancillary drug therapy
   - Sedatives
   - **β-blockers
   - **Iodide (Lugol’s solution)

Question 15

Indications of Definitive treatment (RAI / Surgery) over Medical treatment (Metabolic round)

Answer 15

1. Concomitant heart conditions (e.g. HF, AF) —> Relapse from medical treatment can cause decompensation of heart conditions
2. GO (avoid RAI since can exacerbate GO)
3. Thyrotoxic Periodic Paralysis (TPP)

Question 16

Thiouracil derivatives

Answer 16

MOA:
1. Inhibit ***Thyroid hormone synthesis
- inhibit organification of iodide to iodine
- inhibit coupling of iodotyrosines

2. Inhibit ***T4 to T3 conversion (PTU only)
3. ***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&raquo_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%)

2. **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)
3. Rare: **Cholestatic jaundice, **Hepatocellular toxicity, Acute arthralgia, ANCA induced vasculitis

Question 17

Indications for Anti-thyroid drugs

Answer 17

1. Children and adolescents
2. Pregnant women
3. Adults
   - esp. mild-moderate gland size + disease activity
   - preference of patient

Question 18

Predictive patient characteristics of response to Anti-thyroid drugs

Answer 18

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

Question 19

Surgical treatment for Diffuse toxic goitre

Answer 19

Definitive treatment

Indication:
- Young age
- **Failed medical treatment
- **Relapse a few times
- SE of medications
- **Eye signs
- **Expecting pregnancy
- Refuse radioactive iodine
- ***Big goitre

1. Bilateral subtotal thyroidectomy
2. Unilateral total + contralateral subtotal lobectomy
3. 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))

Question 20

***Complications of Thyroid surgery

Answer 20

1. **Vocal cord dysfunction (unilateral / bilateral)
   - **RLN (Infraglottic) / ***External branch of Superior laryngeal nerve (Supraglottic: Cricothyroid)
   - transient / permanent
2. ***Hypoparathyroidism (∵ injury / removal of parathyroid gland)
   - transient / permanent
3. Bleeding
   - superficial / deep
4. ***Tracheomalacia (cartilage in trachea collapses especially during increased airflow)
5. Wound complications
   - Seroma
   - Hypertrophic scar
6. ***Thyroid storm
7. 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

Question 21

Radioactive Iodine

Answer 21

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

2. Non-destroyed cells have limited replication
3. 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)

Question 22

Indications for 131-I

Answer 22

1. Adults >30
   - age limit arbitrary
   - except if small gland / mild disease
2. ***Thyrotoxic heart disease
3. Relapse after surgery
4. CI to surgery

Question 23

Preparation and precautions of 131-I therapy (From ERS15)

Answer 23

Similar preparation for both Hyperthyroidism and Differentiated thyroid cancer
1. Follow legislation, regulation on safe use of radioisotope therapy

2. Facilities needed: Trained personnel, storage equipment, radiation protection, waste handling, monitoring, controlling, handling contaminants
3. Discussion of treatment options, patient’s consent, instruct patient on post-therapy precaution, follow-up
4. 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
5. ALL female: ***stop breastfeeding, practice contraception 4 weeks before RAI
6. ***Low iodine diet for >= 2 weeks
   - avoid seafood, dairy products, soy products, iodine containing medications

Question 24

Complication and Precautions of 131-I

Answer 24

1. Hypothyroidism
   - transient / permanent
2. 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
3. Excreted in milk
   - ***NO breastfeeding
4. **↑ Risk of Thyroid eye disease developing after RAI —> **Avoid RAI in GO
5. Precipitate **thyroid storm due to **radiation thyroiditis

NB:
- Thyroid carcinoma (NOT ↑ with RAI)
- Leukaemia (NOT ↑ with RAI)
- Transmissible genetic damage (NOT ↑ with RAI)

Question 25

***Thyroid eye disease (TED)

Answer 25

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

Question 26

Histology of TED

Answer 26

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

Question 27

Treatment of GO

Answer 27

1. Rapid control of thyroid dysfunction to euthyroid
   - treatment of hyperthyroidism will ***NOT cure TED —> also need other treatments
2. **Immunosuppressants for infiltrative ophthalmopathy
   - **Steroid (IV / Oral methylprednisolone)
   - ***Cyclosporin A (IV)
   - Plasmapheresis
   - IVIG
   - TNFα inhibitor
3. ***IGF-1 receptor inhibitor
4. ***Orbital irradiation
5. Orbital decompression / Eye muscle operation
   - thinning of **medial wall + **floor (X Lateral wall + Superior roof)

Question 28

Thyrotoxic Periodic Paralysis (TPP)

Answer 28

• 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

Question 29

Hypothyroidism

Answer 29

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)

Question 30

Signs / Symptoms of Hypothyroidism

Answer 30

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

Question 31

Painless thyroiditis

Answer 31

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

Question 32

Hashimoto’s thyroiditis

Answer 32

• 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

Question 33

Subacute thyroiditis

Answer 33

• 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

Question 34

Congenital hypothyroidism

Answer 34

• 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

Question 35

Incidence of hypothyroidism

Answer 35

• 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)

Question 36

Hypothyroidism and IHD

Answer 36

• 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)

Question 37

Myxoedematous Coma

Answer 37

• 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

Question 38

(Anti-thyroid AutoAb)

Answer 38

(Classification:
1. Anti-TPO Ab (Thyroid peroxidase / Microsomal)
- Hashimoto’s

2. Anti-Thyroglobulin Ab (ATA)
   - Hashimoto’s
3. TSH receptor Ab (TRAb) (Stimulating vs Blocking)
   - Graves’)

Question 39

Anti-TPO Ab (SpC Medicine)

Answer 39

1. Diagnosis of AITD (***Autoimmune thyroid disease)
2. Risk factor of AITD
3. Risk factor for thyroid dysfunction during Amiodarone therapy
4. Risk factor for thyroid dysfunction during pregnancy + for post-partum thyroiditis
5. Risk factor for hypothyroidism during IFN-alpha therapy

Question 40

Anti-Thyroglobulin Ab (SpC Medicine)

Answer 40

• 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

Question 41

TSH receptor AutoAb (TRAb)

Answer 41

• 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