07- Drugs for pituitary, thyroid and adrenal disorders Flashcards
What are the “master glands”?
Hypothalamus and the pituitary
Why kind of relationship does the posterior pituitary have with the hypothalamus?
A neuronal relationship
What do the hypothalamus and the pituitary do?
Regulate the function of numerous endocrine glands, control major physiological processes in the body
What does the hypothalamus do?
Secretes hormones that regulate the function of the anterior pituitary
Can GnRH or GH be used clinically?
Limited use clinically
In what way is it easier to deal with clinical issues?
Easier to deal with the root issue as opposed to the activity of the glands upstream
Where do pituitary disorders arise from?
- Tumors
- Injury
- Radiation therapy
- Infection
- Infarction
- Hemorrhage
- Congenital defects
What is growth hormone? What is it also known as?
Somatotropin, anterior pituitary hormone stimulating growth and metabolism, its important throughout the lifespan
What is antidiuretic hormone?
Hormone that acts on the kidneys to increase water re-absorption, released because of increased osmolality
Where is ADH stored?
Stored and released by the posterior pituitary
What kind of drug would we give if someone isn’t making enough growth hormone?
Growth hormone agonist
What kind of drug would we give if someone is making too much growth hormone?
Growth hormone antagonist
What does growth hormone (somatotropin) deficiency result in?
- Short stature in children
- Dyslipidemia
- Decreased muscle mass
- Central adiposity
- Decreased bone density
- Increased cardiovascular mortality
What is the greatest increase we would see with administration of somatropinin in the height of a child without fused bone plates?
15 cm
What is the difference between somatotropin and somatropin?
Somatotropin = endogenous ligand/hormone Somatropin = agonist drug
What does somatropin do?
- Increases height in patients with short stature (associated with genetic disease) and in adults as a replacement therapy
- Increases protein synthesis and lean muscle mass, bone density, lipid mobilization from fat stores, improved lipid profile
What happens when there is too much growth hormone?
Causes acromegaly
What physical appearance changes occur with hypersecretion of GH?
- Very tall
- Broad nose
- Broad forehead
- Large hands
- Bones get thicker and larger
- Enlarged heart, feet, tongue, lips
What symptoms occur with hypersecretion of GH?
- Headaches
- Visual disturbances
- Fatigue
- Excessive sweating
Why do patients with acromegaly experience headaches?
The bones become thicker, it causes increased intracranial pressure which leads to the bad headaches
What happens to patients with acromegaly when they are given a GH agonist?
Will only see changes in soft tissue but not in bone
What are the growth hormone antagonists?
- Octreotide
- Pegvisomant
What is octreotide?
- Pharmacologically related to somatostatin (growth hormone inhibiting hormone produced by the hypothalamus)
- Demonstrates a prolonged duration of action compared to GHIH
- Signals the pituitary to produce less GH, mild efficacy, blocks GH from receptor
What is pegvisomant?
- Growth hormone receptor antagonist acts at target tissues
- More effective than GHIH drugs
- Good at reversal of soft tissue damage, more efficient than octreotide
What does under-production of anti-diuretic hormone cause?
Diabetes insipidus
What occurs with decreased levels of ADH?
- Kidneys reabsorb fluid, this causes dilute urine
- Patient is very thirsty
What is ADH also known as?
Vasopressin, acts like ADH but is also a potent vasoconstrictor
What is desmopressin?
- Has a prolonged action, increases dosage interval
- Does not exhibit changes on blood pressure
- Works closely and specifically with the kidney
In what situation would we give vasopressin?
Acute hypotensive crisis, ex. copious blood loss
The follicular cells of the thyroid produce what?
T3 (triiodothyronine) and T4 (thyroxine)
Thyrotropin is produced by what organ?
Hypothalamus
What does TRH act on?
The anterior pituitary to produce thyroid stimulating hormone
What do thyroid hormones do to the body?
Regulate the basal metabolic rate and impact the function of almost all major organ systems
Thyroid hormones comes mostly in what form?
T4, T3 is the active form. T4 needs to be converted so that we can use it
How do positive and negative feedback loops work in the thyroid gland?
- TRH by the hypothalamus, anterior pituitary makes TSH and TH is made in the thyroid
- Thyroid increases, binds at the hypothalamus and pituitary, hypothalamus makes less TRH, less TSH from the pituitary
- Thyroid hormone decreases and the mechanism starts all over again
Too much thyroid causes what?
Thyroid storm
Too little thyroid causes what?
Myxedema coma
What are signs and symptoms of thyroid storm?
- Tachycardia
- Hyperthermia
- Tachypnea
- Hypercalcemia
- Hyperglycemia
- Metabolic acidosis
- Cardiovascular collapse, cardiogenic shock, hypovolemia, arrythmia’s
- Depressed LOC
- Emotional liability
- Psychosis
- Tremors, restlessness
What are signs and symptoms of myxedema coma?
- Bradycardia
- Hypothermia
- Hypoventilation
- Hyponatremia
- Hypoglycemia
- Respiratory and metabolic acidosis
- Cardiovascular collapse, decreased vascular tone
- Depressed LOC
- Seizures, coma
- Hyporeflexia
What is primary hypothyroidism?
- Exposed to a virus, immune system creates antibodies which attack the thyroid
- Low serum T4 and elevated TSH, increased antithyroid antibody, body tries to compensate and wake up the thyroid
- Hashimoto’s thyroiditis
What is secondary/tertiary hypothyroidism?
- Not getting hypothalamus/pituitary symptoms
- Low TSH from anterior pituitary gland or TRH from the hypothalamus
- Drug induced hypothyroidism (ex. lithium)
What is maternal hypothyroidism associated with?
Low IQ in children, monitor TSH levels in the first trimester of pregnancy
What are the key features of throtoxicosis?
- Warm, moist skin
- Sweating, heat intolerance
- Tachycardia, increased stroke volume, cardiac output, and pulse pressure
- Dyspnea
- Increased appetite
- Nervousness, hyperkinesia, tremor
- Weakness, increased deep tendon reflexes
- Menstrual irregularity
- Decreased fertility
- Weight loss
- Exopthalmos (Graves disease)
What are the key features of hypothyroidism?
- Pale, cool, puffy skin
- Sensation of being cold
- Bradycardia, decreased stroke volume, cardiac output and pulse pressure
- Pleural effusions
- Reduced appetite
- Lethargy, general slowing of mental processes
- Stiffness, decreased tendon reflexes
- Infertility, decreased libido, impotence, oligospermia
- Weight gain
What is levothyroxine (synthroid)?
- Synthetic form of thyroxine (T4) administered once daily PO
- reverses the effects of hypothyroidism
- Increased metabolism, weight loss, improved tolerance to environmental temperature, increased activity levels, increased pulse rate
Why is synthroid considered a high alert medication?
Too much of the drug can cause a hyperthyroid state
Why does the patient need to be aware of the syptoms of hyperthyroidism?
They need to be careful of this, it can cause a thyroid storm and other issues
What is primary hyperthyroidism?
- Graves disease
- Virus, produces antibodies which bind to receptors on thyroid and thyroid stimulating receptor, decreases TSH and increases TH
- TSH levels will be low despite high thyroid hormone levels
What is secondary hyperthyroidism?
Pituitary is not functioning properly or there is an adenoma, this increases T4 production and release
What is the solution for secondary hyperthyroidism?
- Surgical removal is sometimes the only option
- Surgery is necessary in cases of adenoma or when pharmacological therapy is no longer effective
What is propylthiouracil and methimazole?
- Indirect antagonist, takes several weeks to work
- Inhibits the synthesis of T3 and T4, disrupts conversion of T4 to T3 in target tissues
- PO administration
- Regular monitoring of serum TSH levels
- Monitor so we don’t enter a hypothyroid state
What is sodium iodide?
- Radioactive, ablation of the thyroid
- Used when drug does not work or if there is cancer
Remove 3/4 of it, and whatever is left should be making enough thyroid (even if it is hyperactive) - Single exposure usually sufficient, commonly used in cases of thyroid cancer
What does the adrenal gland produce?
- Glucocorticoids and mineralcorticoids
What are glucocorticoids?
- Ex. cortisol
- Important effects on metabolism, catabolism, immune responses and inflammation
- Increases blood glucose levels, increases the breakdown of lipids and proteins, supresses the immune system and inflammatory responses, increases vascular smooth muscle sensitivity to NE and angiotensin II, affect mood and CNS excitability, decreased bone density, bronchodilation
What are mineralcorticoids?
Ex. Aldosterone
- Regulates plasma volume by promoting sodium reabsorption and potassium excretion by the kidney
What is adrenal deficiency?
Hyposecretion of cortisol and mineralcorticoids
What is primary adrenal insufficiency?
- Antibodies destroy the adrenals
- High ACTH, low cortisol, low aldosterone
What is secondary adrenal insufficiency?
- Inadequate secretion of ACTH from anterior pituitary OR
- Chronic, long-term glucocorticoid therapy leading to adrenal atrophy
What are symptoms of adrenal insufficiency?
- Hypoglycemia
- Fatigue
- Muscle weakness
- Hypotension
- Anorexia
- Diarrhea
- Dehydration
- Decreased plasma sodium levels
What does it mean if the symptoms happen acutely with medication errors?
Significant risk of death
Why should we withdraw high dose, systemic, chronic glucocorticoid therapy slowly?
To allow recovery of normal adrenal function, the adrenals develop tolerance to the hormone
Ex. Patient has normal adrenals but has lupus, we give them glucocorticoids to suppress immune response, adrenals see lots of cortisol and being to atrophy. If we abruptly stop the therapy, the patient has no circulating cortisol and can become very ill. Can cause death.
What are other conditions that glucocorticoids can be prescribed for?
- Arthritis
- Allergies
- Asthma
- Lupus
- IBD, Crohn’s disease
- Post-transplant rejection
- Cancers
- Skin disorders (rashes, eczema, etc)
How must we administer glucocorticoids?
Must always give the lowest dose, for the shortest amount of time in the most direct route
Pharmacology of corticosteroids
- Exert dose, duration and route dependent adverse effects
- Well absorbed and distributed, highly bound to plasma proteins
- Metabolized by the liver, excreted by the kidneys
- Crosses the placenta, enters breast milk
- Immune supression, myopathy, osteoporosis, mod changes, edema, hypertension, hyperglycemia, fluid retention, hyperlipidemia, F&E imbalances
What are causes of cushing’s syndrome?
- Metabolic disorder caused by excess excretion of adrenocorticoid steroids, most commonly due to increased amounts of ACTH
- Prolonged, high dose, systemic glucocorticoid therapy
What is the presentation of cushing’s syndrome?
- Adrenal atrophy, osteoporosis
- Increased risk of infection/decreased wound healing
- Redistribution of body fat to face, shoulders, trunk and abdomen
- Mood and personality changes
- Buffalo hump, central adiposity
What is the treatment for cushing’s syndrome?
- Surgery if associated with adrenal or ectopic tumor
- Slow and gradual reduction in glucocorticoid/corticosteroid dose
how often is synthroid given and by which method?
once a day by mouth
