Chapter 37: thyroid and parathyroid agents Thyroid and parathyroid glands regulate calcium homeostasis.

s. The thyroid gland produces two hormones with the use of iodine (from diet): tetraiodothyronine or levothyroxine (T4) and triiodothyronine or liothyronine (T3). When needed, thyroid hormone is broken down in t3 and t4 in thyroid cells and, released into circulation (carried on plasma proteins) The thyroid hormone production is regulated by pituitary (anterior) hormone called TSH. TSH is regulated by TRH (made by hypothalamus). High levels of TSH cause increase production of thyroid hormones (in thyroid gland). Increase levels of thyroid hormones cause negative feedback message to be send to decreased levels of TSH and TRH. A drop in TSH and TRH cause decrease in the production of thyroid hormone. The same mechanism works in the opposite way when there is a decrease in blood serum levels of thyroid hormone. This mechanism is called feedback loop. The function of thyroid hormone is to regulate metabolism .The thyroid hormone affects body temperature, oxygen consumption, cardiac output, blood volume, enzyme activity, growth and development and, metabolism of carbohydrates, fats and proteins. Thyroid gland produces another hormone called calcitonin which affects calcium levels and balance the effects or parathormone (parathyroid hormone). The release of calcitonin is regulated locally at cellar level (*). The released calcitonin blocks bone reabsorption, bone growth. Thyroid dysfunction involves hypothyroidism and hyperthyroidism. Hypothyroidism is a condition related to low levels of thyroid hormone. Can you name any causes of hypothyroidism? The causes could be: absence of thyroid gland, not enough iodine in the diet, tumor or autoimmune disorders, lack of TSH or lack of TRH (tumor of disorder of hypothalamus). Can you name any symptoms of hypothyroidism? Symptoms: obesity, goiter or enlargement or thyroid gland (thyroid overactive). Children who are born without thyroid gland or non-functioning thyroid gland are diagnosed with a condition called cretinism. Due to this they have poor growth and development, and mental retardation Severe hypothyroidism is called myxedema. This can develop due to autoimmune disease (hashimotos disease), viral infection, over treatment of antithyroid drugs or removal of thyroid gland. Signs and symptoms include decreased metabolism, lethargy, hypoactive reflex, hypotension, bradycardia, pale or coarse skin, loss of hair, intolerance of cold, thickening of tongue or vocal cords, decreased appetite, decreased sexual function or even sterility. Treatment: replacement thyroid hormone therapy Naturopathy advice on hypothyroidism: avoid food such as eating raw cabbage, cauliflower and broccoli. They are known as goitrogens because they inhibit uptake of iodine and elemental basis of thyroid hormones Hyperthyroidism is a condition that involves excessive amounts of thyroid hormones to be produced. Graves disease is the most common form of hyperthyroidism. Signs and symptoms include overactive metabolism, increase body temperature, tachycardia, palpitations,

hypertension, and flushing, thin skin, intolerance of heat, weight loss, amenorrhea and goiter. Treatment: removal of parts or all of thyroid gland and monitor metabolism with the use of replacement thyroid hormone therapy. Replacement thyroid hormone is used when there are low or absent thyroid hormone levels in the system and to suppress overproduction of TSH. The prototype drug is called Levothyroxine which is a synthetic salt of T3. It has rapid onset and long duration. This drug is known to cause greater incidence if cardiac side effects. Thyroid replacement hormones cause increase on metabolism, which leads to increase oxygen consumption, respiration, heart rate, growth and maturation, and metabolism of fats, proteins and carbohydrates. This therapy is used in hypothyroid condition, myxedema coma, suppression of TSH in order to treat and prevent goiter and thyroid cancer. These drugs are also used with anithyroid drugs to treat thyroid toxicity, goiter and over stimulation of thyroid during pregnancy. These drugs are will absorbed in GI and primarily eliminated in bile, these drugs do not cross placenta, do not cause harm to fetus but can enter in breast mils in small amounts. These drugs should not be used single handily for thyroidtoxicosis, any know allergy to the drug, during acute MI. Caution should be used during lactation of a person having an hypoadrenal condition. Side effects include skin reaction, hair loss, cardiac stimulation, anxiety, sleepiness, headache, difficulty swallowing and symptoms of hyperthyroidism when the dose is being regulated. Antithyroid agents block thyroid production and treat hyperthyroidism. These include thioamides and iodide solutions. Propylthiouracil (PTU) is the prototype drug under thioamides. This drug is known to have several GI effects. These drugs are well absorbed in the GI and concentrate in thyroid gland. PTU is known to have lower incidence of crossing placenta and entering breast milk. PTU is the best option during pregnancy but caution should be used. Side effects with thyroid suppression include: drowsiness, lethargy, bradycardia, nausea, skin rash. PTU- nausea, vomiting and GI effects. An increased risk of bleeding exists if PTU is used with oral anticoagulants.* High doses of iodine blocks thyroid function. Iodine solutions are used to treat hyperthyroidism. Radioactive iodine is used ad diagnostic agent or to destroy thyroid tissue (30+ years). Potassium iodide and sodium idodide are some of the examples which have rapid onset. The effects are short lived but they might cause further thyroid enlargement or dysfunction. Not used often for these reasons. These iodine solutions are used for suppression of thyroid gland before surgery, treatment for acute thyroidtoxicosis (until thyoamide takes effect), or during radiation therapy. These drugs are rapidly absorbed in GI, widely distributed and excreted in urine. This drug is known to cross placenta, enter breast milk, is rated pregnancy category X and should only be given in pregnancy if benefits outweigh the risks. The most common side effect is hypothyroidism and the patient is started on replacement thyroid therapy to maintain homeostasis. Other effects include iodism, staining of teeth, skin rash and goiter. Parathyroid hormone has functions such as release of calcium from the bones, increase intestinal absorption of calcium, increased calcium resorption from kidneys and stimulation of kidney cells to produce calcitriol (active form of vitamin D).

Decrease serum calcium cause PTH to be stimulated and vice versa. The absence of PTH is called hypoparathyroidism (rare). Treatment of hypothyroidism includes calcium and vitamin D to increase serum calcium levels. hyperparathyroidism is when excessive PTH is produced. Hypocalcemia occurs when there are low levels of PTH present or calcium deficiency. Vitamin D stimulates calcium and phosphate absorption from intestines to restore serum calcium levels. Furthermore, vitamin D regulates mineral resorption from bones and reasorption of phosphate from renal tubules. Calcitriol (form of vitamin D) is the prototype drug under hypocalcemic agents. It is used for the management of hypocalcemia in patients with chronic renal dialysis and hypoparathyroidism. The drug is metabolized in the liver and excreted in urine. Antihypocalcemic agents should not be used in patients who have allergy to vitamin D, hypercalcemia, vitamin D toxicity and pregnancy. Caution should be used during lactation and history of kidney stones. Side effects include weakness, headache, nausea, vomiting, dry mouth, constipation, muscle pain, bone pain and metallic taste. Antihypercalcemic agents: Used to treat excess of PTH and high serum calcium. These include biophosphates and calcitonin. They affect only the serum levels of calcium. Biophosphates: These drugs slow or block bone resorption which will help lower serum calcium levels. They do no inhibit normal bone formation and mineralization. Used to treat Pagets disease and post menopausal osteoporosis. The prototype of this drug type is alendronate which is also used to treat osteoporosis in men. These drugs are well absorbed from small intestines, do not undergo metabolism and excreted in urine. It should be used with caution with people who have renal dysfunction. It should be only given in pregnancy if benefits of mother outweigh the babys, but it should be used with extreme caution. Alendronate should not be used in nursing mother. Research has shown fetal abnormalities when tested on animals. Serious esophageal erosion is known to occur with this drug and should not be given to a person who cannot stand upright for at least 30 minutes. Other adverse effects include headache, nausea, diarrhea, increased or recurrent bone pain (patients with Pagets disease). Calcitonins: These are hormones released by thyroid gland in order to balance the effects of PTH these are available in synthetic form of human or salmon calcitonin. The function of these hormones is to inhibit bone resorption, lower serum calcium levels and, increase the excretion of phosphate, calcium and sodium from kidney. Salmon calcitonin has more wide uses for example; it is also used for emergency treatment of hypercalcemia. Human calcitonin can be only given by injection where as salmon calcitonin can also be given in the form of nasal spray. These drugs are metabolized in kidneys and excreted in urine. These are known to cross placenta and research has shown fetal abnormalities by studies done on animals. Therefore this drug should be given to mother only if the benefit outweighs risks. These drugs should not be given to mothers who are breast feeding mothers and salmon allergy (salmon calcitonin). Caution is used if patient has renal dysfunction or pernicious anemia. Side effects include flushing of face and hands, skin rash, nausea, vomiting, inflammation at the site of injection and urinary frequency.