Hypothyroidism and Myxedema Coma Flashcards
Hypothyroidism results from inadequate production or action of thyroid hormone, either due to primary hypothyroidism or secondary hypothyroidism.
Overt hypothyroidism has a frank decrease in serum T4 and increased TSH
Subclinical hypothyroidism has normal T4 but elevated TSH
- They often present with few or no symptoms
- Subtle symptoms such as hypercholesterolaemia and cardiac abnormalities
Epidemiology of hypothyroidism
- Hypothyroidism: prevalence of 0.3 -0.4%
- Subclinical hypothyroidism: 4-8%
- Mean age of diagnosis: mid-50s
- More common in women (female to male ratio 3:1)
Postpartum hypothyroidism occurs in 5-10% of women
What are the causes of hypothyroidism?
- are commonest causes
A. Primary thyroid failure
1. Autoimmune (Hashimoto’s) thyroiditis*
2. Subacute (de Quervain’s) thyroiditis
3. Riedel’s thyroiditis - fibrosis
4. Postpartum thyroiditis (transient hypothyroidism)
5. Idiopathic atrophy
6. Previous RAI or thyroidectomy*
7. Iodine deficiency
8. Anti-thyroid drugs: amiodarone, lithium, TKI
9. Infiltrative conditions (systemic sclerosis, sarcoidosis, Riedel’s thyroiditis)
B. Secondary thyroid failure
1. Hypothalamic or pituitary disease
Clinical symptoms in hypothyroidism
- Fatigue
- Cold intolerance
- Depression
- Weight gain
- Weakness
- Joint aches
- Constipation or megacolon
- Dry skin and hair loss
- Menstrual irregularities - menorrhagia, irregular period
- Heart failure symptoms
Clinical signs in hypothyroidism
A. Inspection
1. Coarse hair
2. Periorbital swelling
3. Yellow skin
B. Vitals
1. Hypertension (diastolic)
2. Bradycardia
C. Goitre examination
1. Size may vary: small, normal or enlarged
2. Firm consistency
3. Tender or non-tender
D. Limb examination
1. Proximal myopathy
2. Reduced/absent deep tendon reflex with delayed relaxation
E. Complications
1. Toxic megacolon - distended abdomen, tenderness, absent bowel sounds
2. Cardiomegaly
3. Pericardial effusion - pericardial rub
4. Signs of congestive heart failure
Investigations of hypothyroidism
Blood
1. TFT: high TSH, low fT4
1A. tT3, fT3, T3RU, RT3 (if indicated)
2. NCNC anaemia or IDA (FBC, iron panel)
3. Hyponatraemia (RP)
4. Hypercholesterolaemia (lipid panel)
5. High CK
6. Thyroid autoantibodies: anti-TG, anti-TPO
How do you interpret serum total T4 (tT4) levels?
> 99% T4 is protein bound
Thus total T4 depends on amount of thyroid-binding proteins which varies greatly
Total T4 is interpreted with another T3RU to reflect amount of thyroid-hormone binding proteins
Thyroid panel in acutely ill patients
Non-thyroidal illness
Acute phase: reversible suppression of all TT4, FT4, TT3, FT3 and TSH levels
Recovery phase: TSH elevated
Other medications that suppress TSH: dopamine, glucocorticoids
Since TFT may be inaccurate in acutely ill patients, how do you diagnose hypothyroidism in the acutely ill?
- Presence of hypothyroidism clinical signs
- Bradycardia inappropriate, puffy face, dry skin, reduced DTR - Lab investigations of low T4, varying TSH level
(careful of diurnal variation of TSH highest at night) - Additional: RT3 - low in hypothyroidism
(RT3 is elevated in NTI)
Target TSH level for primary hypothyroidisim is 0.5 - 2 mU/L
(Ongoing controversy to allow autoantibody negative patients to have higher target < 2.5mU/L)
Subclinical hypothyroidism should be treated if TSH level is persistently >10mU/L
- Patients experience improved well-being and reduced lipid and cardiac abnormalities risks.
Management of hypothyroidism
- Levothyroxine (LT4)
- Young: full replacement 1.6 mcg/kg/day
- Elderly or cardiac disease: low 25-50mcg/day, increasing by 25mcg/day every 4-6 weeks until TSH reaches normal level
- Subclinical: 50-75% predicted full replacement - Liothyronine (LT3) - short half life, high potency (only for special cases)
- Combination T4/T3 therapy in select patients
(Studies on combi T4/T3 therapy no demonstrable benefit, despite that T4 replacement alone does not restore tissue levels of T4 and T3 to euthyroid levels)
When should we trial combination T4/T3 therapy?
How do we initiate combi therapy?
- Patients with low-normal TSH on LT4 still feeling “hypothyroid”
- After excluding: anaemia, B12 deficiency, sleep apnoea
Reduce LT4 by 12-25mcg
Add 5mcg of LT3
Monitor for symptom improvement
Adverse effects of excessive thyroid hormone replacement
- Acute complications: thyrotoxicosis
- Anxiety, tremors, palpitations, insomnia, etc
Chronic complications
2. AF
3. Osteoporosis and fractures
4. Premature mortality
Post-stress/operative complications of patients with hypothyroidism
Hypothyroidism planning for surgery
Post-stress/operative complications
1. Constipation and ileus
2. Toxic megacolon
3. Confusion, psychosis
4. Impaired immune and fever response to infection
Hypothyroidism planning for surgery
1. Ensure TSH normalised first
2. If intending for emergency surgery, can proceed without LT4 replacement and monitor for post-operative complications
- Post-op to replace LT4 at slow rate, monitor for heart failure
Hypothyroidism in pregnancy
Higher thyroxine requirement during pregnancy
Maternal iodine deficiency, hypothyroidism is associated with:
1. Fetal neurological deficit and mental restriction (neurological cretinism)
2. Neonatal hypothyroidism (myxoedematous cretinism)
3. Maternal pre-eclampsia
4. Placenta abruption
5. Pre-term delivery
6. LSCS
Postpartum thyroiditis
Occurs in women within one year of parturition
Typically progression:
- Mild subclinical hyperthyroidism at 3 months postpartum
- Hypothyroid phase at 6-9 months
Prognosis:
80% full recovery, 20% need long term thyroxine
If thyroxine started at 6 months, trial stopping at 12 months to see if condition recovers
Caveats:
Think of postpartum exacerbation of Graves’ disease as a differential
- will present with severe disease and persistent thyrotoxicosis
Subacute granulomatous (De Quervain’s) thyroiditis
Initial hyperthyroid phase with neck pain
Tender diffuse goitre
Elevated thyroid hormones
Hyperthyroidism subsides after 2-6 weeks to become hypothyroidism (depleted thyroid stores)
Eventual thyroid hormone levels return to normal when thyroid function is restored
Causes: viral or post-viral inflammatory process
Riedel’s thyroiditis
Rare chronic inflammatory condition of thyroid gland causing thyroid parenchyma fibrosis by dense fibrous tissue
Fibrosis may extend beyond thyroid capsule and affects other local structures (parathyroid gland, recurrent laryngeal nerve)
Myxedema coma
Life threatening exaggeration of hypothyroidism manifestation
What are the precipitating causes of myxedema coma?
A. Mandatory predisposing factor:
Underlying undiagnosed or inadequately treatment hypothyroidism
B. Superimposed precipitating events:
Medical
1. Infection (commonest)
2. Sudden withdrawal of thyroid medication
3. Exacerbation of illnesses (stroke, ADHF, MI, DKA, bleeding, PE, respiratory distress, etc)
4. CNS depressant medications
Surgical
1. Trauma
2. Undiagnosed hypothyroidism patient undergoing surgery
Evaluation of myxedema coma
_A. Hypothyroidism_
_B. Manifestations of myxedema coma_
1. Hypothermia
2. Bradycardia
3. Hypoventilation
4. Hypotension (usually variable BP)
5. Effusions - pleural, pericardia, peritoneal
6. Ileus
7. Acute urinary retention
8. Neurological dysfunction (stupor, seizure, coma)
9. Absent deep tendon reflex, or delayed relaxation
10. Hypothyroid skin and hair changes
_C. Precipitating cause_
- Sepsis, trauma, surgery, CVA, MI, stroke, DKA, etc
- Previous thyroidectomy scar
- Goitre is helpful finding, but often absent
Myxedema Coma Scoring System
- Hypothermia (up to 20 points)
- Cardiovascular and respiratory effects
- Bradycardia (up to 30 points)
- Hypotension (20 points)
- Cardiomegaly (15 points)
- Pulmonary oedema (15 points)
- Pericardial/pleural effusion (10 points)
- Respiratory failure - hypoxaemia, hypercarbia (up to 20 points)
- ECG changes - prolonged QT, low voltage, BBB, ST-T changes (10 points) - CNS disturbance (up to 30 points)
- GI disturbance (up to 20 points)
- Metabolic and renal disturbance (10 pts each)
- Hypoglycaemia, hyponatraemia, reduced eGFR - Precipitating events (10 points)
- < 24: unlikely myxedema coma
- 25-59: suggestive of myxedema coma
- > 60: likely myxedema coma
What is the normal total body pool of T4?
(Important to determine replacement in myxedema coma)
Total: 1000mcg
- 500mcg in thyroid
- 500mcg in rest of body
Laboratory abnormalities in myxedema coma
- Thyroid panel: T4 and T3 low, TSH significantly elevated
(does not correspond to severity) - Anaemia
- Hyponatraemia
- Hypoglycaemia
- Hypercholesterolaemia
- Elevated CK
- ABG - CO2 retention, hypoxaemia
- ECG: sinus bradycardia, heart block, low voltage, T wave flattening
Management of myxedema coma
General
1. HDU or ICU admission
2. Multidisciplinary team - Endocrine
3. Treat precipitating cause
Medical management
A. Rapid replacement of depleted thyroid hormone pool
Choice of:
1. IV levothyroxine 200-300mcg over 5 minutes for few days
1A. Then regular PO/IV levothyroxine 50-100mcg daily
2. Add IV tri-iodothyronine 5-10mcg Q6-12 hours (in profound heart failure or non-responsive to 1-2 days of LT4 therapy)
B. Glucocorticoid therapy
Stress dose for 2-3 days, choice of:
1. Hydrocortisone 200mcg daily
2. Methylprednisolone 50mg daily
3. Prednisolone 50mg daily
4. Dexamethasone 7.5mg daily
C. Supportive measures
1. IV fluid resuscitation
2. Oxygen support
3. Mechanical ventilation (if needed)
4. Passive rewarming in severe hypothermia
Prognosis of myxedema coma:
100% mortality if untreated
0-45% mortality with early treatment
