Pharmacology of the Endocrine System: Drugs for Pituitary, Thyroid, and Adrenal Disorders

hypothalamus and pituitary gland

- regulate the function of numerous endocrine glands

- hypothalamus releases hormones that regulate the function of the anterior pituitary

- the hypothalamus controls the posterior pituitary through neuronal signalling

pituitary endocrine disorders

result of tumor formation, congenital defect, surgery, radiation, infection, hemorrhage, hypoxia, other injury

Growth hormone

somatotropin

- ant pituitary hormone that stimulates growth and metabolism

Antidiuretic hormone

ADH/vasopressin

- stored and released by post pituitary in response to increased serum osmolality, ADH acts on kidneys to increase water resorption

Growth hormone deficiency

- results in short stature (in kids bc they aren't fully grown yet), decrease muscle mass, central adiposity, decreased bone density, dyslipidemia, increased CV mortality

Somatropin

- agonist drug for growth hormone receptors

- increases protein synth and lean muscle mass, bone density, lipid mobilization from fat stores, improved lipid profile

- can induce up to 6in of height increase in pediatric cases of growth hormone deficiency

Acromegaly

- enlargement of the extremities

- caused by excessive secretion of growth hormone

- usually associated with pituitary adenomas

- headache, visual disturbances (Inc. ICP)

- enlarged heart, hands, feet, tongue, skull, nose, lips, deep voice, sleep disorders

- fatigue, excessive sweating, arthritis

treatment for acromegaly

- usually with surgery to remove the adenoma, medication and/or radiation therapy

- the ability to reverse changes depends on when we begin to treat the acromegaly

Growth hormone antagonists

- Octreotide (related to growth hormone inhibiting hormone, inhibits secretion of GH and reduces tumor size)

- Pegvisomant (GH receptor antagonist, blocks binding of somatotropin at GH receptors in target tissues)

Octreotide

- related to GH inhibiting hormone --> inhibits secretion of GH and reduces tumor size

Pegvisomant

- GH receptor antagonist

- blocks binding of GH at the target tissues

Deficiency of ADH causes which condition

- diabetes insipidus, a rare condition resulting in dilute urine and constant thirst

Desmopressin

- agonist drug

- SC, IV, PO, prolonged duration of action

- does not exert same BP effects as vasopressin, more just affects the kidneys to retain water

- must monitor the BP, weight, fluid intake, urine output to make sure we're giving the pt the right amount of drug

Thyroid gland feedback loop

- Hypothalamus releases TRH

- Ant. Pituitary releases TSH

- Thyroid gland releases T3 and T4 (thyroid hormone)

- 90% T4

why is T4 converted to T3?

- T3 is more biologically active than T4

what do thyroid hormones do?

regulate the basal metabolic rate and impact the function of almost all major organ systems

hypothyroidism

- insufficiency of the thyroid gland

what is primary hypothyroidism?

an abnormality of the thyroid gland itself

what is secondary hypothyroidism?

the pituitary gland is not releasing TSH as it should

Hashimoto's thyroiditis

an autoimmune disease where the immune system attack the thyroid, destroying it

what is tertiary hypothyroidism?

the hypothalamus doesn't secrete TRH

why id hypothyroidism in pregnancy dangerous?

- gestational hypothyroidism is associated with a low IQ in children, and we want to avoid that so we screen early and start to supplement thyroid hormone if we need to in early pregnancy

drug that can cause hypothyroidism

lithium

in someone with Primary hypothyroidism, what will their lab values show?

- low T4

- high TSH

- high antithyroid antibodies

secondary hypothyroidism lab values

- low TSH from ant. pituitary

tertiary hypothyroidism lab values

- low TRH from hypothalamus

clinical features of hypothyroidism

- pale, cool, puffy skin

- sensation of being cold (slow metabolism)

- bradycardia

- pleural effusion, hypoventilation, CO2 retention

- reduced appetite

- lethargy, slowing of mental processes

- stiffness

- infertility, decreased libido, impotence

- weight gain

clinical features of hyperthyroidism

- warm, moist skin

- sweating, heat intolerance

- tachycardia, increased CO, PP, SV

- dyspnea

- increased appetite

- nervousness, shaking, tremor

- weakness

- menstrual irregularity, decreased fertility

- weight loss

- exophthalmos (bulging eyes)

Levothyroxine (synthroid)

- thyroid hormone

- admin once daily PO

- reverses effects of hypothyroidism

- monitoring TSH levels required

- narrow therapeutic index

what happens if you give too much levothyroxine?

you can induce hyperthyroidism

adverse effects of Synthroid

- sweating

- insomnia

- rapid pulse

- dyspnea

- irritability

- fever

- weight loss

- drug-drug interactions

drug-drug interactions of Synthroid

Absorption

- colestipol

- calcium or aluminum containing antacids

- iron supplements

Metabolism (faster)

- dilantin

- tegretol

- rifampin

- phenobarbital

Synthroid increases effects of:

- warfarin

hyperthyroidism

overactivity of the thyroid gland

primary hyperthyroidism

- dysfunction of the thyroid gland itself, increased secretion of Thyroid hormone

- Grave's disease --> autoimmune disease

Grave's disease

- autoimmune disorder

- body develops antibodies (thyroid stimming immunoglobulins) that activate TSH receptors

Primary hyperthyroidism lab values

- low TSH, despite high thyroid hormone levels

- anterior pituitary not telling thyroid to make T4 anymore, the stimming antibodies do that

Secondary hyperthyroidism

- issues with the anterior pituitary, increased TSH leads to increased thyroid hormone release

- an overdrive of the typical system

Methimazole and Propylthiouracil (PTU)

- thioamides that inhibit the synth of thyroid hormone

- PTU disrupts the conversion of T4 into T3 --> faster onset

- PO admin, regular monitoring of TSH

- therapeutic effect of methimazole can take 3-4 weeks to happen, but it is more convenient in dosing and has no risk for hepatotoxicity or leukopenia like PTU

Radioactive Iodine

- single dose to permanently destroy follicular cells in overactive thyroid gland, commonly used in cancer

pros to methimazole over PTU

- more convenient dosing with methimazole (once daily instead of 4x daily)

- risk of hepatotoxicity and/or leukopenia with PTU

other medications used in the treatment of hyperthyroidism symptoms

- beta adrenergic antagonists

- calcium channel blockers

these usually help control BP, HR, help with tremor, anxiety, palpitations, etc.

hormones from the adrenal gland

- glucocorticoids (mostly cortisol)

- mineralocorticoids (mostly aldosterone)

glucocorticoids

- mostly cortisol

- anti-inflamm, immunosuppressant, inc. lipolysis and protein synth in the liver, protein breakdown everywhere else

- increased blood glucose

- mood and CNS excitability

- decrease bone density

- bronchodilation

mineralocorticoids

- aldosterone

- regulate plasma volume by conserving sodium and water and promoting potassium excretion by the kidney

Primary adrenal insufficiency (+labs)

- Addison's disease

- hyposecretion of corticosteroids due to autoimmune destruction of the adrenal glands

- high ACTH, low cortisol and aldost.

Secondary adrenal insufficiency (+labs)

- issue with the pituitary signalling

- inadequate ACTH from the pituitary OR chronic, long-term corticosteroid therapy leading to adrenal atrophy

symptoms of adrenal insufficiency

hypoglycemia, fatigue, muscle weakness, hypotension, anorexia, diarrhea, dehydration, decreased plasma sodium levels

discontinuation of corticosteroid therapy

slow, you have to wean off of it to allow the adrenals to recover and be able to function again

acute adrenal insufficiency treatment

- IV hydrocortisone/dexamethasone to prevent hypovolemic shock and death

- mineralocorticoid replacement with fludrocortisone may also be necessary

corticosteroid therapy indicated in:

- arthritis

- allergies

- asthma

- lupus

- IBD/Crohn's

- post transplant rejection

- cancers

- skin disorders like eczema

dosage of corticosteroids

you want to always use the lowest possible dose you can and use local routes of administration to minimize adverse effect potential with steroid medication

pharmacokinetics of corticosteroid drugs

- well absorbed and distributed

- highly bound to plasma proteins

- metabolized by the liver, excreted by kidneys

- crosses placenta, enters breast milk

adverse effects of steroid drugs with large, systemic doses

- osteoporosis

- mood changes

- edema

- HTN

- fluid retention

- hyperglycemia

- hyperlipidemia

- F/E imbalances

- myopathies

cushing's syndrome vs cushing's disease

DISEASE = caused specifically by the pituitary increased ACTH secretion

Syndrome = healthcare induced --> prolonged, high dose corticosteroid/glucocorticoid therapy

treatment of Cushing's

- surgery if associated with an adrenal or ectopic tumor (DISEASE)

- slow and gradual reduction in glucocorticoid/corticosteroid dose (for SYNDROME that we induce)

presentation of Cushing's disease/syndrome

- redistribution of body fat to face, shoulders, trunk, extremities

- increased risk of infection, decreased wound healing

- mood and personality changes --> steroid grumpiness

- adrenal atrophy and osteoporosis