Endo - Drugs used in Thyroid Disorders Flashcards
Which hormone is released by the hypothalamus and controls thyroid hormone secretion?
Thyrotropin-Releasing Hormone (TRH).
Which hormone is released by the pituitary gland and controls thyroid hormone secretion?
Thyroid Stimulating Hormone (TSH)
How are TRH and TSH secretions controlled?
Negative feedback by T4 and T3
What is thyroid peroxidase enzyme’s role in thyroid hormone biosynthesis?
- Oxidation of iodide
- Iodination of tyrosyl residues to form mono or di-iodo tyrosyl residues, also known as organification
What is the half life of T3 and T4?
T3 - about a day, T4 about a week
State 5 causes of hypothyroidism
Hashimoto thyroiditis, Iodine deficiency in food, drugs, pituitary failure, hypothalamic failure, congenital conditions
What would be expected of the TSH and T4 levels in a person with primary hypothyroidism?
High TSH, Low T4
What would be expected of the TSH and T4 levels in a person with subclinical hypothyroidism?
Higher than normal TSH, normal T4
Name 5 symptoms of hypothyroidism
Fatigue/lethargy
Mental slowness
Dry skin
Weight gain
Irregular menses
Hair loss
Cold intolerance
What drugs are commonly used to manage hypothyroidism?
Levothyroxine and Liothyronine
What precipitates myxedema coma and how would a patient with myxedema coma present?
Myxedema coma occurs as a result of long-standing, undiagnosed, or undertreated hypothyroidism and is usually precipitated by a systemic illness (infection, heart attack, etc.).
Primary signs and symptoms of myxedema coma are altered mental status andlow body temperature, hypoglycemia, low blood pressure.
How often do we monitor TSH levels after initiating levothyroxine treatment?
6 to 8 weeks
What could cause persistently elevated TSH levels after initiation of treatment?
Poor medication compliance, malabsorption, drud/food interactions, inadequate dosing,
How does cholestyramine (lipid lowering medication) interfere with levothyroxine absorption?
It binds to levothyroxine and interferes with its absorption from the the intestines into the blood stream.
How does estrogen interfere with levothyroxine absorption?
High estrogen promotes synthesis of thyroid binding globulin, which binds to levothyroxine and reduces its free concentration
How would you expect levothyroxine requirements to change as one ages?
Expect it to reduce, this may be due to age-related decreases in thyroxine degradation
How would you expect levothyroxine requirements to change during pregnancy?
Increase by about 30% - 50% early in pregnancy
How should levothyroxine be dosed in patients with ischemic disease and why?
Slow upward titration starting with a low dose till euthyroidism is achieved. As thyroid hormones have ionotropic and chronotropic effects they can precipitate acute coronary disease if started at a full dose in these patients.
Name 5 symptoms of hyperthyroidism
Increased motor activity, metabolism, increased heat production (flushed, warm moist skin),Increased appetite, weight loss with insufficient intake,
Increased heart rate, anxiety, nervousness
What would be expected of the TSH and T4 levels in a person with hyperthyroidism?
Low TSH, High T4
Name 3 classes of drugs that are used to downregulate thyroid hormone levels in patients suffering from hyperthyroidism
- Anti thyroid drugs - Thioamides (carbimazole, propylthiouracil, thiamazole)
- iodine (Lugol’s solution / Potassium iodide),
- Radioactive iodine therapy (I131)
What is the mechanism of action thioamides?
They inhibit thyroid peroxidase and interfere with iodination. They also inhibit coupling of iodotyrosyl residues. PTU, specifically inhibits deiodination of T4 to T3.
What are the advantages carbimazole has over PTU?
Less frequent dosing, and lesser hepatotoxicity.
PTU has a black box warning due to its hepatotoxic effect.
What are some important adverse effects of thioamides that we need to look out for?
Agranulocytosis, need to stop and do a FBC if any signs or symptoms of an infection is observed after carbimazole or PTU administration. Cholestatic jaundice (carbimazole) or liver failure (PTU)
What are anti-thyroid drugs commonly used to treat?
Graves’ disease, thyroid storm, overactive thyroid gland
Which of the thioamides is prescribed during the first trimester of a pregnancy?
PTU is preferred in the first trimester. Switch to carbimazole after first trimester
What is iodide used to treat?
Thyroid storm (an hour after anti thyroid drugs) It prevents the release of thyroid hormones.
In preparation for thyroidectomy, reduces size and vascularity of the gland,
Endemic goiter (iodine deficiency) as iodine replacement
How long does iodides take to have an onset of action?
24 to 48 hours
What are the signs and symptoms of iodism?
Metallic taste, gastrointestinal discomfort (diarrhoea, vomiting), lacrimation, severe headache, sore teeth and gums
Which radioactive iodine isotope is used for diagnosis of toxic nodular goiter and which is used in the treatment?
123I (diagnosis) and 131I (treatment)
How does radioactive iodine therapy work?
Radioactive iodine is rapidly and efficiently trapped by the thyroid sodium-iodide transporter, into the follicular cells, from which it is slowly liberated. Destructive β particles act almost exclusively on the follicular cells to destroy them , with little or no damage to surrounding tissue.
Does 123I emit beta rays?
No, only 131I. 131I emits goth beta and gamma rays
What advantage does radioactive iodine therapy have over thyroidectomy?
No hospitalisation, low cost, ease of administration (oral), low rate of complications.
What are the contraindications for radioactive iodine therapy?
Pregnancy, Extra caution in patients with active (moderate to severe Graves’ ophthalmopathy) as it may worsen the condition
Can radioactive iodine therapy be con-administered with thioamides?
No, must stop thioamides at least 3 days before. Been found to otherwise reduce effectiveness of RAI
How could beta blockers help in a thyroid storm?
Beta blockers limit the positive ionotropic and chronotropic effects of thyroid hormones, slightly decrease T4 conversion to T3.
What is the utility of glucocorticoids in thyroid disorders?
They are useful in a thyroid storm as they can reduce the conversion of T4 to T3. Used in Graves’ ophthalmopathy to reduce inflammation and swelling.
