2/15: Thyroid and Parathyroid Hormones Flashcards
What hormone is the most potent in the thyroid gland?
T3 is more potent thatn T4
About 93% of the active hormones secreted by the thyroid gland is _________, while 7% is __________
Thyroxine (T4)
Triiodyhronine (T3)
What do thyroid hormones impact?
metabolism
and growth/development. They also
have permission action on
catecholamines
What does calcitonin do?
Decrease plasma calcium
Wha tis required for thyroid hormone synthesis?
Iodine (I2) so thyroid follicular cells actively transport iodide (I-) obtained from the diet
How does iodide exit the thyrocyte?
Across the apical membrane
to access the colloid,
where the initial
steps of thyroid
hormone synthesis
occur
What is pendrin?
A Cl-/I- exchanger
What is the Na+/I- symporter (NIS) capable of producing?
intracellular I- concentrations that are 20–40 times as great
as the concentration in plasma
Where are T3 and T4 produced?
In the colloid
What are T3 and T4 complexed with?
Thyroglobulin (Tg)
What are the steps of T3 and T4 secretion into blood?
- Colloid is internalized by endocytosis.
- The vesicles fuse with lysosomes in the cell.
- Proteases cleave T3 and T4 from TG.
- T3 and T4 diffuse out of the cell and into
capillaries
99% of T3 and T4 bind with what plasma proteins for transport?
Thyroxine-Binding Globulin (TBG), Transthyretin (TTR), Albumin
What are T3 and T4 half lifes?
- Due to the strength of its binding to the transport protein, T4 has a long
half-life (6-7 days). - T3 doesn’t bind as tightly so its half-life is only 2-3 days
How do target cells make active T3?
By using enzymes called Deiodinases/iodinases that remove an iodine from T4
How do individual target cells alter their exposure to T3?
By regulating their tissue deiodinase synthesis
What conditions inhibit deiodinase activity?
selenium deficiency,
burns, trauma, advanced cancer, cirrhosis, chronic kidney disease,
MI and febrile states, fasting, stress. Could show signs of hypothyroidism
Do T4 or T3 actions occur sooner?
T3 - with the maximum activity 2-3 days
*slower onset, but higher duration of action
What is the synthesis of new proteins important for?
- other systems
- growth
- CNS development
- Cardiovascular
- metabolism
Where is there negative feedback when secreting thyroid hormones?
Mainly at the level of the anterior pituitary gland
What is the main circulating form of thyroid hormone?
T4 -> responsible for most of the (-) feedback
What are the effects of thyroid hormone on metabolism?
- Stimulates oxygen consumption by most metabolically active tissues.
- Increased Basal Metabolic Rate (BMR)
- stimulates carbohydrate metabolism
- stimulates protein catabolism and synthesis
- stimulates fat metabolism
How does thyroid hormone stimulate carbohydrate metabolism?
– Causes uptake of glucose by cells
– Enhances glycolysis & gluconeogenesis
– Increases rate of CHO absorption from G.I. tract
How does thyroid hormone stimulate fat metabolism?
– Increases lipid mobilization & oxidation of fatty acids by cells
– Required to convert beta carotene to vitamin A (Hypothyroid patients have
yellowish skin)
– Decreases circulating cholesterol levels (Hypothyroidism associated with hyperlipidemia)
What do thyroid hormones do for our nervous system?
- Needed for normal development of
the NS - Impacts reflex time (i.e.
hypothyroidism can cause prolonged
reflex times) - Muscle tremors due to increased
reactivity of neuronal synapses - Feeling of tiredness but difficulty
sleeping - Anxiety, worry and paranoia
What do thyroid hormones do for our cardiovascular system?
- Increased expression of β-
adrenergic receptors - Increased blood flow, heart rate, and heart contractility
What do thyroid hormones do for our endocrine system?
- Activation of bone
formation causes a need
for increased PTH
secretion
What do thyroid hormones do for our gastrointestinal system?
- Increased appetite and
food intake - Increased rate of
secretion and motility of
the GI tract (i.e.
hypothyroidism can
produce constipation)
What is goiter?
Enlarged thyroid that DOES NOT indicate functional status
- seen in Hypothyroidism, Hyperthyroidism, Euthyroidism
What is goiter caused by?
Excessive amounts of TSH secretion
– High TSH stimulates thyroid to secrete large amounts of thyroglobulin colloid into follicles, resulting in gland enlargement
What is the most common form of hyperthyroidism?
Grave’s disease
What is grave’s disease?
An autoimmune disease where antibodies to
TSH receptor called thyroid-stimulating immunoglobulins (TSIs) stimulate the thyroid
gland to excess
What do high levels of thyroid hormone secretion caused by TSI do?
Suppress anterior pituitary TSH secretion (negative feedback)
What are hyperthyroidism symptoms?
Fine hair
Exopthalmos
Nervousness
Goiter
Tachycardia
Increased appetite
Weight loss
Fine tremor
Pretibial myxedema
Oligomenorrhea
Muscle wasting
Sweating, heat intolerance
What is treatment of hyperthyroidism?
- Radioactive I 131 thyroid ablation, or
Antithyroid Drugs (propylthiouracil or
methimazole).
– Surgery rarely indicated. - Propanolol (b blocker) given for adrenergic symptoms while awaiting
resolution. - L-thyroxine administered to prevent hypothyroidism in patients who have undergone ablation or surgery
What are oral symptoms of hyperthyroidism?
- Burning Mouth Syndrome
- Gum disease
- Excessive salivation
- Weakening of mandible
- Increased caries risk
What is thyroid storm (thyrotoxicosis)?
- Elevated Thyroid Hormone with stressful events (trauma, surgery,
severe emotional distress) or serious illness (DKA, MI, etc.). - Symptoms: fever, tachycardia, elevated BP, nausea, vomiting,
diarrhea, breathing problems, etc
What should you do with a patient with hyperthyroidism that wants to have dental care?
administration of epinephrine is contraindicated, and elective dental care should be deferred
What is hashimoto’s thyroiditis?
Autoimmune reaction against thyroid gland destroys gland
rather than stimulating it
What is the most common cause of hypothyroidism?
Hashimoto’s thyroiditis
What is the physiology of hashimoto’s thyroiditis?
- Most patients first exhibit autoimmune “thyroiditis,” thyroid inflammation
- Inflammation leads to fibrosis of thyroid resulting in decreased secretion of thyroid hormone
What is treatment for hashimoto’s thyroiditis?
L-thyroxine (T4)
In hypothyroid states, what is goiter and no goiter a result from?
Goiter: iodine deficiency
No goiter: TSH deficiency
Is hypothyroidism due to iodine deficiency a primary or secondary endocrine disorder?
Primary
What are TRH, TSH, and T3,T4 levels in hypothyroidism?
High TRH
High TSH
Low T3, T4
What are symptoms of hypothyroidism?
- coarse, dry, brittle hair
- loss of lateral eyebrows
- large tongue
- weight gain
- peripheral edema
- lethargy and impaired memory
- periorbital edema and puffy face
- deep coarse voice
- slow pulse
- gastric atrophy
- constipation
- muscle weakness
Who is myxedema seen in?
Severly hypothyroid patients
What is myxedema?
Increased quantities of
hyaluronic acid and
chondroitin sulfate bound
with protein plus water
accumulate in skin
What does cretinism result from?
– Congenital absence of thyroid gland
(congenital cretinism)
– Iodine deficient diet (endemic cretinism):
most common cause worldwide
What does cretinism cause?
Physical and mental retardation of nenonates
- thyroid hormones required for postnatal brain maturation
What is inhibited in cretinism?
Skeletal growth than tissue growth (obese, stocky and short with large protruding tongue)
What are oral manifestations of hypothyroidism?
- Macroglossia
- Dysgeusia
- Delayed tooth eruption
- Poor wound healing and increased risk of infection (due to
decreased activity of fibroblasts) - Increased periodontal disease
- Salivary gland enlargement
Where is most of the body’s phosphate stored?
In bones, the rest in cells, and EC fluid
What does low calcium result in?
Neuronal hyper-excitability (tetany)
*carpal spasm due to HYPOcalcemia
What does high calcium result in?
Neuronal depression
What are control points for calcium and phosphate?
- Absorption – via intestines
- Excretion – via urine (calcium and phosphate) and feces (calcium only)
- Temporary storage – via bones (hydroxyapatite)
20Ca10 (PO4)6 (OH)2
What 3 hormones regulate plasma calcium?
- Parathyroid hormone (PTH)
- Calcitriol (1,25-dihydroxycholecalciferol or vitamin D3)
- Calcitonin (from the parafollicular cells of the thyroid gland)
What does PTH do?
increase Plasma Calcium and decrease Phosphate
– Mobilizes calcium from bone
– Enhances renal reabsorption of calcium
– Increases intestinal absorption of calcium (indirectly)
What does calcitriol do?
Increase Plasma Calcium and Increase Phosphate
– Calcitriol is the primary hormone that enhances intestinal absorption of calcium and it also causes absorption of phosphate.
What does calcitonin do?
Decrease Plasma Calcium and Decrease Phosphate
- Bone formation is stimulated by Calcitonin, Insulin, GH, IGF-1, Estrogen and Testosterone
What does vitamin D3 and parathyroid hormone stimulate?
Bone matrix resorption and increase plasma calcium
What does calcitonin stimulate?
bone matrix deposition and inhibits osteoclasts
Decreases plasma calcium
How does parathyroid hormone work with bone resorption?
- Osteoblasts deposit hydroxyapatitie and secrete RANKL
- RANKL binds to RANK receptor, activating osteoclasts
- Osteoclasts break down HA, releasing calcium into blood
How does calcitonin hormone work with bone resorption?
- OPG prevents binding of RANKL to RANK
- When osteoclasts need to be blocked, apoptosis decreases number of active osteoclasts
When does osteoporosis occur?
When there is an imbalance between bone formation and resorption
What are risk factors for osteoporosis?
vitamin D deficiency (secondary hyperparathyroidism), inadequate calcium intake
(secondary hyperPTH), glucocorticoid medications, reduced physical activity, estrogen
deficiency (post-menopausal), cigarette smoking, alcohol
What is treatment for osteoporosis?
- Exercise (walking and weight-
bearing 3X per week) - Physical Therapy (postural exercises,
muscle strengthening) - Estrogen (replacement or receptor
agonists) - Calcium (carbonate or citrate)
- Vitamin D
- Bisphosphonates
What is PTH secreted by?
Chief cells
How do PTH increase plasma calcium?
By increasing intestinal absorption, decreasing renal excretion and increasing bone resorption
How does the PTH decrease plasma phosphate?
By increasing renal excretion
What happens when the PTH decreases ECF Ca2+ concentration?
Increases rate of PTH secretion hypertrophy of parathyroid gland
- pregnancy
- rickets
- lactation
What happens when the PTH increases ECF Ca2+ concentration?
↓ activity of parathyroid gland
↓ size of parathyroid gland
o increased vitamin D intake
o excess quantities of calcium in the diet
o bone resorption caused by factors other than PTH
What 3 ways does the PTH increase plasma calcium?
- Bone resorption
- Reabsorption of Calcium by
Renal Tubules which reduces
excretion - Converts 25-
hydroxycholecalciferol to
1,25-
dihydroxycholecalciferol
(Vitamin D/Calcitriol), which
causes intestinal calcium
absorption.
What way does the PTH decrease plasma phosphate?
Decreased reabsorption
by renal tubules leading to
increased urinary excretion
how long can vitamin D3 be stored in the liver?
For several months
What is the main effect of vitamin D3?
Absorption of Ca2+ and PO43-
What is calcitonin secreted by?
Parafollicular cells (C cells) of the thyroid gland
What is calcitonin released in response to?
Elevated free plasma Ca2+
What does calcitonin do?
Lowers plasma Ca2+ by decreasing activity of osteoclasts, thus decreasing bone resorption
What is not a main controller of Ca2+ in humans?
Calcitonin
What is primary hyperparathyroidism?
Excess PTH secretion due to a parathyroid gland tumor
What does extreme osteoclastic activity in bones cause?
Cystic bone disease (Osteitis fibrosa cystica)
– Hypercalcemia leads to polyuria
and calcuria
– Low phosphate due to increased
renal excretion
– Muscle weakness and easy
fatigability
– Osteoblastic activity also
increased leading to high
secretion of alkaline phosphatase
(ALP)
What is secondary hyperparathyroidism?
High PTH levels occur as compensation for hypocalcemia not due
to primary abnormality of parathyroid glands
What are causes of hypocalcemia?
- Vitamin D deficiency
- Chronic renal disease-cannot synthesize Vit D3
What does vitamin D defieciency lead to in children?
Rickets
What does vitamin D deficiency lead to in adults?
Osteomalacia and high PTH, which causes bone resorption
What is high PTH a risk factor for?
Osteoporosis and fractures
What does primary hypoparathyroidism result from?
Accidental surgical parathyroid gland removal
What does parathyroid gland removal cause?
Decreases plasma Ca levels from 10 to 6-7
What increases membrane Na+ permeability and what does this lead to?
Hypocalcemia; muscle spasms, and tetany
What does spasms of laryngeal muscles cause?
Obstructs respiration causing death unless appropriate treatment applied
