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Thyroid Hormone Regulation +negative feedback

Hypothalamus release-> Thyrotropin Releasing Hormone (TRH) -> anterior pituitary
Anterior pituitary release ->Thyrotropin/Thyroid Stimulating Hormone (TSH) -> thyroid
Thyroid release -> T3 & T4
Negative Feedback -> T3 and T4 on anterior pituitary

T3 & T4

T3 is more potent, but T4 is excreted more from the thyroid
Both transported in plasma by thyroxine-binding globlin (TBG)
Half-life: 6 - 7 days due to binding (extends half-life)
T4 converted to T3 in cell -> T3 enters nucleus

Effects of Thyroid Hormones (3 main)

Development and growth:
-important for brain development
Calorigenic effect:
- increase oxygen consumption (makes you skinny)
Cardiac Effects:
-increases heartrate --mimics sympathetic N.S.

Hasimoto's thyroiditis

Most common form of hypothyroidism
Leads to:
-impairment of growth
-mental retardation (in children)
-weight gain
-cold intolerance

Infantile Cretinism

hypothyroidism in prenatal to 3 months old
-mental retardation, deaf, mute, dwarfism, poor thermoregulation

-can be prevented if detected early


advanced hypothyroidism in adults characterized by sluggishness, slow pulse, puffiness in the hands and face, and dry skin (myx = mucous)
Can lead to coma

Hypothyroidism Treatment (3 drugs)
-essentially hormone replacement

Levothyroxine (L-T4) - analogue of T4
- first-line therapy, long half-life (slow onset)
-dosage and adjustment: start low and go slow
Liothyronine (L-T3) - analogue of T3
- more potent and faster onset (4-8 hours)
Liotrix (Combination of L-T4 and L-T3)


-Increased metabolism (weight loss)
-skin is flushed
- Increased apetite
- tachycardia, hypertension and tremor

Graves' Disease

the most common form of hyperthyroidism; caused by an autoimmune defect that creates antibodies that stimulate the overproduction of thyroid hormones; exophthalmos (bulging eyes) is a featured characteristic
antithyroid drug therapy (radioactive iodide) and thyroidectemy.

Thyroid Storm

Crisis Alert!!!
Hypermetabolism and increased sympathetic signaling.
essentially all the symptoms of hyperthyroidism at once
treatment with antithyroid drugs and symptomatic use of beta-blockers. These go against the sympathetic signaling

Anti-thyroid drugs

Methimazole and Propylthiouracil
MOA: Inhibition of thyroid peroxidase to decrease organification- stops the formation of T3 and T4
-does not effect T3 and T4 that have already been made - so onset of action may be 3-4 weeks.
Toxicity: itchy rash, fever

Anti-thyroid drugs

Perchlorate (ClO4-)
Pertechnetate (TcO4-)
Thiocyanate (SCN-)
MOA: Competitive inhibition of I- uptake into the thyroid - inhibition of organification
Fast onset (2 days)

Anti-thyroid drugs
Radioactive iodine

MOA: emits beta particle radiation, slowly destroying the thyroid tissue

Type 1

aka - insulin-dependant diabetes mellitus (IDDM)
-Juvenille onset, due to destruction of beta cells (that produce insulin)
-Absence of insulin results in catabolism
Treat by giving insulin

Type 2

Tissue insensitivity to insulin
treatment: sulfonylureas (enhance insulin secretion), Glitinides (enhance insulin secretion), biguanides (sensitizes cells to insulin), thiazolidinedione (sensitizes cells to insulin)

Insulin effects

Liver: stimulates glycogen synthase activity, increases glucose uptake, inhibits glycogen phosphorylase, and inhibits gluconeogenesis
Muscle: promotes protein synthesis, and glycogen synthesis
Adipose Tissue: promotes triglyceride deposition, reduces circulating free fatty acids, and reduces intracellular lipolysis

Insulin Preparations
(regular, Neil Patrick Harris and lente)
all given parenterally

Crystallin zinc insuling (regular insulin)
-fast onset (minutes), fast duration of action (8-12 hours)
NPH insulin (neutral protamine Hagedorn)
-Onset (1-2 hrs) duration (18-24)
Combination Regular and NPH
-used to imitate regular insulin release (which has two phases: fast and slow release)
Lente: onset (2.5 hrs), duration (22 hrs)
ultralente: onset (4 hrs), duration (28 hrs)

Insulin analogues
all given parenterally

Insulin Lispro & Insulin Aspart:
Very fast onset (30-45 min) and very short duration of action (3-5 hrs). Good for taking before meals
Insulin Glargine:
for basal level of insulin - not for meals


MOA: Enhances insulin secretion
Tolbutamide: Short duration of action (safest)
Chlorpropamide: Longer duration of action (not as safe)
More potent
Glyburide, glipizide, glimepiride
Nausea and vomiting, flushing/alcohol intolerance, hypoglycemia


Repaglinide, nateglinide

MOA: Enhance insulin secretion - just like sulfonylureas
unlike sulfonylureas, short duration of action which decreases the chance of hypoglycemia


Metformin, butformin, phentformin
MOA: reduces gluconeogenesis from liver, decrease glucose absorption in gut, increased sensitivity of cells to insulin
First Line therapy for Type II diabetes
Does not cause hypoglycemia because it does not effect insulin itself

Thiazolidinedione derivatives

Rosiglitazone, pioglitazone
MOA: agonist of PPAR gamma
increases sensitivity to insulin, increase glucose uptake in muscle of fat tissue, reduces hepatic glucose output
ADR: cardiotoxicity, weight gain, heart problems in general

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