Endocrine Thyroid Disease- Pharmacology Exam 3

In hypothyroidism BMR

slows down (loss of metabolism, HR, RR, BP, sweating, estrogen and progesterone, reflexes)

2 lobes of the thyroid gland

Right lobe: Right upper, right lower

Left lobe: upper, left lower

• All wrap around the trachea and are connected by an isthmus

Back of lobes of the thyroid gland contain

4 parathyroid glands→ need to be cautious of in a total thyroidectomy

Thyroid is the ____ endocrine gland in vertebrates

Largest

Functional unit of the thyroid

Thyroid follicle→ lined with follicular cells (thyrocytes) and occasional parafollicular cells that surround a lumen containing colloid

3 hormones secreted by thyroid gland

• T3- Triiodothyronine (active form of T4)

• T4- thyroxine (produced in higher quantities and transformed to T3 in the periphery)

• Peptide hormone→ Calcitonin (controls calcium homeostasis)

What do T3 and T4 do?

Influence BMR and protein synthesis, energy source, growth and development

TSH

Secreted from the anterior pituitary gland

• MOA: Regulates the secretion of thyroid hormone

TSH is regulated by

TRH (thyrotropin releasing hormone) that is produced by the hypothalamus

Follicular cell of thyroid patho

1. Iodine enter with NA (synporter)

2. Iodine separates and both get recycled

3. Iodine combines with TG (thyroglobulin) ORGANIFICATION→ Gets into the colloid space and can attach to 1 or 2 molecules of iodine

• Monoiodothyronine: 1 TG to 1 molecule of iodine

• Diiododthyronine: TG to 2 molecules of iodine

4. MIT+ DIT= T3, DIT+DIT= T4→ goes directly into bloodstream

• These bonds are covalent, and catalyzed by thyroid peroxidase

There is a ____ feedback mechanism in thyroid hormones

Negative

Grave’s disease feedback mechanism

1. TRH stimulates excessively TSH, TSH stimulates thyroid hormone

• T3, T4 high and the TSH high (anterior pituitary problem)

• T3, T4 high and TSH high and TRH high (hypothalamus problem)

2. Auto-ABY: increase stimulation of the thyroid gland to function more than it should

• Extremely increased T3 and T4, low TSH and low TRH because they want all of the production to stop (thyroid gland problem)

Hashimoto’s thyroiditis feedback mechanism

1. Destructive Auto-Aby: thyroid problem

• High TSH, low T3 and T4

2. Thyroidectomy (hypo functional gland): no source of thyroid hormone and not taking medication

3. Anterior Pituitary defect: not enough TSH

• T3 and T4 low, TSH low

4. Hypothalamus problem: not enough TRH

• T3 and T4 low, TSH low, TRH low

Hypothyroidism

Syndrome characterized by low circulating levels of T4 and T3

• S/S: reversible slowing down all functions that is REVERSIBLE

• Infants and children (Cretinism): growth and developmental delays and learning disabilities (irreversible)

Primary hypothyroidism

Thyroid problem

• High TSH, low T3 and T4

Secondary Hypothyroidism

Anterior pituitary problem

• T3 and T4 low, TSH low

Tertiary Hypothyroidism

Hypothalamus problem

• T3 and T4 low, TSH low, TRH low

Management of Hypothyroidism

Replace T3 or T4 or Thyroid extract products

• Infants and children require more T4 (levothyroxine) per kg than adults

  • Newborns: 6-10 ug/kg/day

  • Adults: 1.6 ug/kg/day

• DOSE IN THE MORNING ON EMPTY STOMACH

Myxedematous Coma

Decompensated hypothyroidism (extreme), rare and high mortality

• End state untreated hypothyroidism

• S/S: hypothermia, bradycardia, HoTN, hypoventilation→ coma and death

Sodium levothyroxine

Synthroid, Levothyroid→ management of hypothyroidism DOC

• MOA: synthetic T4 hormone, identical to the T4 secreted from the thyroid

  • want the peripheral receptors to turn it into T3 to protect normal physiologic function

• SE: Well tolerated at clinical dose→ titrate to response

• Coronary heart disease: extra challenge, must be very careful→ increase HR, BP, RR

Liothyronine

Cytomel→ management of hypothyroidism

• MOA: synthetic T3

• SE: well tolerated at clinical dose→ higher doses: cardiac arrhythmia, chest pain, palpitation, tachycardia, ataxia, fever, HA, insomnia, nervousness

Liotrix

Thyrolar→ management of hypothyroidism

• MOA: synthetic T4/T3 combination in the way that we normally secrete it

Stimulatory sympathomimetics

Increased risk of coronary artery spasm when these agents are used together

Hyperthyroidism types

• Grave’s Disease

• Toxic multinodular goiter (Plummer’s disease)

• Toxic adenoma→ single lesion/growth producing high amounts of T3/T4

• Subacute thyroiditis: inflammation of the thyroid can be classical or postpartum

S/S of hyperthyroidism

Excessive heat, increase sympathetic activity, hyperalgesia, protruding eyes (Grave’s exopthalmos), anxiety, gross tremor, decreased menstrual flow, irritability/nervousness, diarrhea, weight loss, increased appetite

Grave’s Disease

MCC of hyperthyroidism

• MOA: autoimmune disorder in which antibodies are produced by the immune system and stimulate the thyroid to make high T3/T4

Toxic multinodular goiter (Plummer’s Disease)

Occurs MC in elderly, especially those that have had a long standing goiter

Toxic adenoma

Single hyperfunctioning follicular thyroid adenoma

• benign monoclonal tumor that usually is larger than 2.5 cm

• nuclear scintigraphy scan shows only a single hot (hyperfunctioning) nodule

Non-pharmalogical management of hyperthyroidism

• Nutrition, hydration, rest (especially in the elderly)

• Subtotal/total thyroidectomy

Pharmacological management of hyperthyroidism

• Thioamines

• Thiocyanate

• Iodine (potassium iodide)

• Radioactive iodine

• Beta blockers

Thioamines (management of hyperthyroidism)

Methimazole (Tapazole), Propylthiouracil (PTU- Prophylthiour)→ indicated for hyperthyroid patients except with subacute thyroiditis

• MOA: decrease T4 and T3 production/synthesis and decreased conversion of T4 to T3

• SE: maculopapular pruritic rash ± fever, vasculitis, arthralgia, lupus like reaction

Thiocyanate (management of hyperthyroidism)

• MOA: potent inhibitor of iodide transport; detoxification product of cyanide and can easily be measured in body fluids.
  

Iodine (management of hyperthyroidism)

Potassium Iodide

• MOA: inhibits iodine dependent hormone release (T4/T3), decrease the size and vascularity of the hyperplasticity gland d/t great affinity for thyroglobulin molecule

  • Often given prior to surgery to shrink gland DOC (PO or IV)

• SE: exocrine gland swelling and tenderness

Radioactie Iodine (management of hyperthyroidism)

• MOA: taken up by thyroid and incorporate into storage follicles that destroys the cells (thyroid parenchyma)

• CI: subacute thyroiditis and during pregnancy

• Administered orally

Beta-Blockers (management of hyperthyroidism)

Adjuvant agent

• MOA: reduce the symptoms of hyperthyroidism (palpitations, tremor, sweating)

• Does not alter circulating T4 or T3

Perchlorate, Thiocynate, Pertechenate inhibit

Potent inhibitor of iodide syntransport with Na into the follicular cell

Thioamines and Iodides inhibit

Prevent formation of MIT and DIT (coupling and organification)

• enzyme thyroid peroxidase

PTU inhibits

Prevents peripheral conversion of T4 to T3