Lecture 4: Drugs for Pituitary, Thyroid and Adrenal Disorders

what does growth hormone defiency result in

• short stature

• decreased muscle mass and bone density

• central adiposity

• dyslipidemia (abnormal lipid levels in the blood)

• increased cardiovascular mortality

what is administered in growth hormone defiency

somatropin

acromegaly cause

associated with benign anterior pituitary tumours which causes excessive growth hormone production and secretion

acromegaly symptoms

• Enlarged heart, hands, feet, tongue, skulls, etc.

• Increased intracranial pressure because of skull -> headache, visual disturbances

• Fatigue, excessive sweating, arthritis

acromegaly drug treatment

antagonists drugs used when surgery or radiation therapy is inadequate

octreotide

growth hormone antagonist which inhibits secretion of growth hormone and reduces tumor size

pegvisomant

growth hormone receptor antagonist which blocks the binding of somatotropin (growth hormone) at the growth hormone receptor in target tissues

antidiuretic hormone defiency symptoms

diabetes insipidus where symptoms include dilute urine and constant thirst

desmopressin use and importance

• agonist drug that treats ADH deficiency

• does not vasoconstrict and increase BP like vasopressin does

• important in bleeding to restore fluid loss

production of T3 and T4 process

• hypothalamus produces TRH to stimulate ant pit to produce TSH

• TSH induces thyroid gland to produce T3 and T4

T3 vs T4

• T3 is much more potent than T4

• T3 is 10%, T4 is 90% released

• T4 is converted to T3 inside target tissues

primary hypothyroidism

• Immune system damages thyroid gland and cannot produce enough T3 and T4

• Autoimmune disease “Hashimoto’s thyroiditis”

who is especially at risk of hypothyroidism

women in menopause

T4, TSH, antithyroid antibody levels in primary hypothyroidism

categorized by low T4 because thyroid is unable to produce, elevated TSH because low T4 detected, increased antithyroid antibody

why is it important to monitor TSH levels in 1st trimester pregnancy

Gestational hypothyroidism is associated with lower IQ in children

hypothryoidism symptoms

• being cold

• bradycardia

• hypoventilation

• reduced appetite

• letheragy

• stiffness

• infertility

• weight gain

hypothyroidism treatment

• synthetic form of T4 called levothyroxine (synthroid) is given

• administered once daily PO

hypothyroidism monitoring after treatment and adverse effects

• TSH levels should be monitored because decreased levels can cause increased cardiovascular demand

• adverse effects can include sweating, insomnia, rapid pulse, irritability, weight loss, etc.

primary hyperthyroidism

• Autoimmune disorder called Grave’s disease

• The body develops antibodies that bind and activate the TSH receptor to produce more T4

• TSH levels will then drop, inhibited by high T4

secondary hyperthyroidism

Increased TSH secretion from anterior pituitary resulting in increased T4 production and release

hyperthyroidism symptoms

• heat intolerance

• tachycardia

• dyspnea

• increased appetite

• weight loss

• menstrual irregularity

treatment of hyperthyroidism medications

• Inhibits the synthesis of thyroid hormones (T3 and T4)

• PTU also disrupts conversion of T4 to T3 in target tissues

• Methimazole takes 3 to 4 weeks to induce effects but is preferred because PTU causes liver toxicity and white blood cell decrease

what drug is preferreded in pregnant females with hyperthyroidism

PTU is preferred because it is less likely to cross the placenta and harm do fetus

treatment of hyperthyroidism: radioactive iodine

• Single dose to destroy cells in thyroid gland

• Used in cases of thyroid cancer

treatment of hyperthyroidism: surgery

• Reduce thyroid size in patients with breathing or swallowing problems because of goiter

• Drug therapy used prior to surgery to reduce risk of thyrotoxicosis and decrease vascularity of the gland

how are external symptoms of hyperthyroidism treated (tremors, anxiety, palpitations, increased HR)

Beta adrenergic antagonists and calcium channel blockers are used

primary adrenal insufficiency

• Also called Addison’s disease

• Low secretion of corticosteroids due to autoimmune destruction of both adrenal glands

• Characterized by high ACTH, low cortisol, low aldosterone

secondary adrenal insufficiency

Inadequate secretion of ACTH from the anterior pituitary or chronic, long term corticosteroid therapy which leads to adrenal atrophy

symptoms of adrenal insuffiency (not acute)

• Hypoglycemia

• Fatigue

• Muscle weakness

• Hypotension

• Anorexia

• Diarrhea, dehydration

• Decreased plasma sodium levels

treatment of secondary adrenal insuffiency

• In cases of high dose, chronic corticosteroid therapy, the drug should be withdrawn slowly over the course of several months to allow recovery of normal adrenal function

how are corticosteroid drugs bound, metabolized and excreted

bound to plasma proteins, metabolized by liver and excreted by kidneys

what can sudden withdrawl of corticosteroid therapy lead to

acute adrenal insuffiency:

hypotension, lethargy, renal failure, nausea and vomiting, asthenia (lack of energy and strength)

treatment of acute adrenal insuffiency

IV hydrocortisone/dexamethasone to prevent hypovolemic shock and death

how to ensure corticoid therapy safety

the lowest effective dose and select local routes should be chosen to minimize adverse effects

cushing’s disease - what is it and how is it caused

Metabolic disorder caused by excess secretion of corticosteroids due to excess amounts of adrenocorticotropic hormone (ACTH) or most commonly caused by prolonged, high dose, corticosteroid drug therapy

symptoms of cushing’s disease

• Redistribution of body fat to face, shoulders, trunk, abdomen

• Increased risk of infection and decreased wound healing

• Mood and personality changes

• Hyperglycemia

• Adrenal atrophy and osteoporosis

treatment of cushing’s syndrome

• Surgery if there is a tumour

• Slow and gradual reduction in corticosteroid drug