THYROID AND PARATHYROID Flashcards
What are the signs of Hyperthyroidism
weight loss, sweating, palpitations, heat intolerance, diarrhoea, rapid heart rate. Long term; thyroid toxicosis
What are the signs of Hypothyroidism
weight gain, bradycardia, constipation, lethargy, cold intolerance. Long term; myxoedema coma
What is the primary TSH- thyroid stimulating hormone
problem w thyroid gland; opposite directions
What is the secondary TSH- thyroid stimulating hormone
problem w the hypothalamus; same directions
What is the Causes of Hyperthyroidism
- Graves’ disease (autoimmune disorder; ↑ T3 and T4), toxic multinodular goitre (enlarged or swollen thyroid gland producing lots of T3 and T4) and toxic adenoma (Tumour).
- Biomarker: Presence of thyroid stimulating immunoglobulin are antibody specific to Graves’ Disease
Hyperthyroidism: Agreed Principle
No surgery and radioactive iodine while a patient is grossly thyrotoxic (having high levels of T3 and T4) due to risk of precipitating a thyroid ‘storm; extremely high levels of T3 & T4.
Treatment guideline of Hyperthyroidism: Grave’s disease
Use antithyroid drug long term
Treatment guideline of Hyperthyroidism: If there is relapse after anti thyroid drug or surgery not possible
Use radioactive iodine (use when above C/I)
Treatment guideline of Hyperthyroidism: If patient has Grave disease and is unwilling or unable to have radioactive tx
Use thyroidectomy
What to do before surgery and radioactive iodine tx:
Use antithyroid drug for short term to prevent thyrotoxicosis. *Anti-thyroid drugs should be ceased 1 week before tx and recommenced 1 week after tx
Hyperthyroidism: If they have symptoms of hyperthyroidism such as palpitation, anxiety, tremor and sweating
use beta blocker
Hyperthyroidism: If they have severe exophthalmos (protrusion of the eyes) in Graves’ disease
use Corticosteroids (prednisolone
Anti-Thyroid Drug: What is the initial dose and maintenance dose for Propylthiouracil (PTU)
Initially: 200-400mg ddd for 3-4 wks
Maintenance: 25-300mg ddd
Anti-Thyroid Drug: What is the initial dose and maintenance dose for Carbimazole
Initially: 10-45mg ddd for 3-4 wks
Maintenance: 2.5-40mg daily in single or dd
Anti-Thyroid Drug: Monitoring
- Agranulocytosis -
o S & S: sore throat, fever, mouth ulcers
o FBC
Block Replace Regimen in Hyperthyroidism:
Combine……. and …… therapy
Antithyroid and levothyroxine Therapy
Block Replace Regimen in Hyperthyroidism: What treatment of high dose antithyroid drug
(carbimazole 20-40 mg d; PTU 200-400 mg ddd)
Block Replace Regimen in Hyperthyroidism: What treatment of levothyroxine
Begin levothyroxine 100-150 mcg when T4 is in normal range (at about 6 wks) while continuing high dose antithyroid drugs
Block Replace Regimen in Hyperthyroidism: Monitor
o Follow-up every 3 months to confirm biochemical euthyroidism
o T4 4 times a year
o Check thyroid levels
Hyperthyroidism: what are examples of beta blockers used?
Not for long term use
Eg. Propranolol 10-40mg 3-4 times daily; Atenolol 50-100 mg d.
Hyperthyroidism: Radioactive Iodine: C/I
C/I in individual < 15 yo, pregnancy and breastfeeding women
Hyperthyroidism: Radioactive Iodine: How long to taper off antithyroid drugs after radioactive iodine tx
2–4 months
Thyroidectomy: What rendered with anti-thyroid drugs prior to surgery to avoid Thyroid storm
euthyroid
What is the tx for Thyroid Storm
Propylthiouracil, IV hydrocortisone, IV fluid, propranolol
What are the symptoms relating to Thyroid Eye Disease
Artificial tears, Dust protection, Corticosteroid, Surgery, Smoking cessation if applicable
Hypothyroidism: Cause
Hashimoto’s disease (immune cell attack thyroid cell resulting in hypothyroidism) and thyroid ablation (radioactive iodine, surgery, and drugs)
Hypothyroidism Tx: What is used to restore well-being and return TSH to normal range
an adequate dose of levothyroxine
Hypothyroidism Tx: Before commencing levothyroxine in secondary hypothyroidism, what must be excluded
Hypothalamus and pituitary disorder must be excluded to avoid precipitating an Addisonian crisis (if in doubt give glucocorticoid replacement)
Thyroxine replacement in hypothyroidism: 1st line
Levothyroxine (thyroxine)
Thyroxine replacement in hypothyroidism: Levothyroxine Adult dose
50-200mcg daily dependent on TSH
~1.6 mcg/kg ideal body weight
Thyroxine replacement in hypothyroidism: Levothyroxine dose - Elderly, especially those with IHD
25-50mcg daily, increasing by 25mcg daily every 6-8 weeks
If symptoms of cardiac ischemia occur/worsen, dose increases should be avoided
Thyroxine replacement in hypothyroidism: Monitoring
Thyroid function tests are done every four to six weeks until euthyroidism is achieved
What is Myxoedema coma
Severe hypothyroidism with physiological decompensation
Myxoedema coma Treatment
Must be treated aggressively with Liothyronine (T3) + hydrocortisone
Myxoedema coma Monitoring
Monitor urea, electrolytes and haemotoglical indices, arrhythmia, body temperature
Thioureylenes/Thionamides: MOA
Inhibition of thyroid peroxidase (enzyme found in thyroid gland to produce thyroid hormone) with reduction in thyroid hormone production and storage
Inhibit iodination of tyrosine. Tyrosine is precursor to thyroid hormones.
PTU also inhibits conversion of T4 to T3 (more active form)
Thioureylenes/Thionamides: Side Effects
GI upset in first 8 weeks
Hypothyroidism
Agranulocytosis (rare)
Rashes
Thioureylenes/Thionamides: Drug Interactions
Anticoagulants (warfarin & phenindione) can ix with PTU and can cause ↑ risk of bleeding
Amiodarone, iodinated glycerol, lithium ↓ effects of anti-thyroid drugs
Anion Inhibitors (Iodine, Iodide) MOA: Ix short term short-term to render patient euthyroid before surgery in graves disease
High doses of iodine - suppress the action of TSH and TRH (negative feedback) symptoms subside within 1-2 days
Inhibit iodination of tyrosine. Tyrosine is precursor to thyroid hormones.
Inhibition of conversion of T4 to T3
Inhibition of thyroid hormone secretion/release
Reduce size and vascularity of gland
Anion Inhibitors (Iodine, Iodide) Side Effects
Allergic reactions: laryngitis, bronchitis, rashes
Chronic use: depression & impotence
Anion Inhibitors: C/I
Pregnancy - risk of neonatal hypothyroidism
Breastfeeding - risk of infant hypothyroidism.
Radioactive iodine MOA
Accumulates in thyroid tissue
Beta radiation emitted selectively destroys thyroid follicle cells
Radioactive iodine C/I
Pregnancy - risk of neonatal hypothyroidism
Breastfeeding - risk of infant hypothyroidism
L-Thyroxine (levo-thyroxine T4) Indication
hypothyrodisim
L-Thyroxine (levo-thyroxine T4) MOA
Thyroxine is converted to T3 in vivo
Has pharmacological properties of endogenous T4
L-Thyroxine (levo-thyroxine T4) Drug Interaction
Digoxin: Thyroxine reduces digoxin concentration
Cholestyramine, sucralfate, ferrous sulphate, aluminium hydroxide, calcium carbonate: Reduced gut absorption of T4
Oral anticoagulants (warfarin etc.): Thyroxine causes Increased clotting factor elimination Increased anticoagulant effect – increased risk of bleeding
Oral contraceptives containing oestrogens: Increased metabolism and elimination of thyroxine, hence increased dose of L-Thyroxine may be needed
Liothyronine (tri-iodothyronine T3) MOA
Has chemical and pharmacological properties of endogenous T3
Liothyronine (tri-iodothyronine T3) C/I
Not recommended in pregnancy and in children because of preferential use of T4 by the brain
Hyperparathyroidism Pathophysiology
Regulation of PTH is determined by serum calcium level
Dec calcium level will activate parathyroid gland to release PTH which will send signal to kidney, bone and intestine. In kidney, there will be inc calcium reabsorption by dec excretion of calcium thru urine. Mobilise calcium from the bone.
Once there is enough serum calcium, it will send negative feedback to parathyroid gland to dec synthesis of PTH
For hyperparathyroidism, there is: high PTH level, high serum calcium and high calcium/creatinine ratio
Primary Hyperparathyroidism cause
disorder of parathyroid gland
Secondary Hyperparathyroidism cause
renal failure; dec calcium reabsorption; unable to activate vitamin D; vitamin D enhances calcium absorption. The increase in PTH hormone in renal Fx is due to chronic hypocalcaemia as a result of the inability of the kidney to activate vitamin D to absorb calcium (negative feedback causing high PTH).
Tx of primary hyperparathyroidism: Parathyroidectomy
Indicated for patients with primary & asymptomatic hyperparathyroidism patient with the following:
persistent serum calcium > 2.85mmol/L
eGFR < 60 mL per minute per 1.73 m2
Bone mineral density T-score of less than −2.5 at any one of three sites (i.e., hip, spine, or wrist) and/or any previous fragility fracture
Age < 50 years
Tx of primary hyperparathyroidism: Cinacalcet
Initially 30mg bd; up to 90mg tds to qid
Monitoring:
monitor calcium and parathyroid hormone concentrations closely and reduce dose if necessary.
Tx of secondary hyperparathyroidism:
Cinacalcet + calcitriol
Protein restriction
Calcium supplement
Vitamin D supplement; calcitriol
Cinacalcet + calcitriol
Cinacalcet: Initially 30mg od; up to 180mg od + Calcitriol: 0.5-1 microg d
only used in pts w end-stage renal disease receiving dialysis; Elevated PTH (due to low calcium) will lead to hypercalcaemia and inc risk of osteoporosis. Hence use of cinacalcet with calcitriol is used to achieve calcium homeostasis. Cinacalcet is to Tx the initial high calcium (sensitises receptors on pt gland); cause negative feedback of PTH (lowers PTH). Calcitriol is to Tx the initial low calcium from the renal disease.
HYPOPARATHYROIDISM
