Endocrinology Part 2 (Thyroid and Parathyroid) Flashcards
Thyroid is butterfly-shaped due to?
bilobed structure
type of T3 that is biologically inactive
rT3 (reverse T3)
Location of iodine in T3
3, 5, 3’
Location of iodine in T4
3, 5, 3’, 5’
generation test that detects very minute amount of TSH
3rd gen
Due to parathyroid gland location, it is considered as?
smallest endocrine gland
Butterfly-shaped glands found in the lower anterior neck
thyroid gland
Tissue that connects 2 lobes of thyroid gland
isthmus
specific location of butterfly-shaped glands
lower anterior neck
functions of thyroid gland
Controls biosynthesis and release of TH from thyroglobulin
Regulates carbohydrates, proteins and lipid metabolism
Acts on CNS (by brain maturation and dev’t)
Stimulates the heart
Physical growth and development
Controls basal body temperature
how thyroid gland act on CNS
by brain maturation and development
body temp when there is ↑ TH
↑ body temp
oxygen consumption when ↑ TH
↑ O2 consumption / demand
(more cells consume O2)
hollow spheres of thyroid gland
colloid follicles
what type of tissue is follicle cells?
squamous epithelial cells, cuboidal cells
aka cuboidal cells
thyroid follicular cells
located within spherical structure
colloids
content of follicle cells, a gel-like matrix
colloids
has thyroglobulin within it
colloids
follicle cells are important for ______ synthesis
T3 and T4 synthesis
major component of thyroid colloids
thyroglobulin
important substance for TH synthesis
thyroglobulin
composition of thyroglobulin
2 tyrosine backbone
Each tyrosine backbone has 1 iodine binding site
how many iodine binding site is in each thyroglobulin
2
structures responsible for calcitonin production
parafollicular C cells
2 biologically active hormones
Triiodothyronine (T3)
Tetraiodothyronine/Thyroxine (T4)
more biologically active TH
Triiodothyronine (T3)
T3 pre-hormone
Tetraiodothyronine/Thyroxine (T4)
less biologically active (requires deiodination to become more biologically active)
Tetraiodothyronine/Thyroxine (T4)
enumerate steps for TH synthesis
- Iodide uptake
- Iodide → Iodine (oxidized)
- Iodine Uptake
- Iodination of tyrosine (thyroglobulin)
- Coupling reaction of iodinated tyrosine
what is acquired from diet that is necessary for TH synthesis
iodide
Iodide (I2) from diet will enter?
follicular cells (within follicular cells is colloid; colloid has thyroglobulin)
site of oxidation from iodide to iodine
colloid
process where iodine attaches to the tyrosine backbone of thyroglobulin
iodination of tyrosine (thyroglobulin)
1 iodine attached to thyroglobulin
monoiodothyronine
2 iodine attached to thyroglobulin
diiodothyronine
process of combination of two thyroglobulin with iodine
Coupling reaction of iodinated tyrosine
monoiodothyronine + diiodothyronine
triiodothyronine
diiodothyronine + diiodothyronine
tetraiodothyronine
important substance for TH synthesis
Iodine
Iodine deficiency indicates?
TH deficiency
removes 1 iodine atom from OUTER tyrosyl ring of T4 to produce T3 (biologically active form)
Monodeiodination
enzyme for the removal of 1 iodine atom from outer tyrosyl ring of T4 to produce T3
monodeiodinase
Combination of 2 thyroglobulin will form?
2 rings
Removal of iodine from outer ring produces?
Removal of iodine from inner ring produces?
T3
rT3 (reverse T3)
biologically inactive TH
rT3 (reverse T3)
regulation of TH follows this axis
hypothalamic pituitary thyroidal axis
secretes thyrotropin-releasing hormone (TRH)
hypothalamus
secretes thyroid-stimulating hormone (TSH)
pituitary gland
gland that produce TH (T3 & T4)
thyroid gland
after production of TH by thyroid gland? what is the next process?
TH (T3 & T4) acts on peripheral tissues with specific receptors
affected gland if a TH disorder is PRIMARY
thyroid
affected gland if a TH disorder is SECONDARY
pituitary
affected gland if a TH disorder is TERTIARY
hypothalamus
TH disorder classification if there is:
↑ TH
N/↓ TRH, TSH
primary hyperthyroidism
TH disorder classification if there is:
↓ TH
N/↑ TRH, TSH
primary hypothyroidism
TH disorder classification if there is:
↑ TSH, TH
N/↓ TRH
secondary hyperthyroidism
TH disorder classification if there is:
↓ TSH, TH
N/↑ TRH
secondary hypothyroidism
TH disorder classification if there is:
↑ TRH, TSH, TH
tertiary hyperthyroidism
TH disorder classification if there is:
↓ TRH, TSH, TH
tertiary hypothyroidism
hormone levels in primary hyperthyroidism
↑ TH
N/↓ TRH, TSH
hormone levels in primary hypothyroidism
↓ TH
N/↑ TRH, TSH
hormone levels in secondary hyperthyroidism
↑ TSH, TH
N/↓ TRH
hormone levels in secondary hypothyroidism
↓ TSH, TH
N/↑ TRH
hormone levels in tertiary hyperthyroidism
↑ TRH, TSH, TH
hormone levels in tertiary hypothyroidism
↓ TRH, TSH, TH
chemical name of T3
3, 5, 3’-triiodothyronine
Accounts for 20% of total TH synthesized
TRIIODOTHYRONINE (T3)
have the most active hormonal activity
TRIIODOTHYRONINE (T3)
Functions of T3
- Metabolic rate of every cell of the body
- Encourages cellular differentiation
- Tissue growth and development
- ↑ oxygen consumption
- Calorie and Vitamin/Mineral metabolism
- Indicator of hyperthyroidism recovery
- Involve brain maturation
- Cause ↑ heat production
Indicator of hyperthyroidism recovery
TRIIODOTHYRONINE (T3)
TH of heat intolerant individuals
increased (in cases of hyperthyroidism)
Reference Ranges of T3
Adult: 60-160 ug/dL
Children (1-14 y.o): 105 – 245 ng/dL
reason why there is increased values of T3 in children
T3 & T4 involvement in tissue growth and dev’t
chemical name of T4
3, 5, 3’, 5’ tetraiodothyronine
Accounts for 80% of total TH synthesized
TETRAIODOTHYRONINE (T4)
T/F
↑ T4 ↑TSH (vice versa)
F
↑ T4 inhibit TSH
Reference Ranges of T4
Adult: 5.5 – 12.5 ug/dL
Neonates: 11.8 – 22.6 ug/dL
Different Forms of Iodine in the Body
tyrosine
thyroxine (T4)
triiodothyronine (T3)
reverse T3 [inactive]
THYROID BINDING PROTEINS
Thyroxine Binding Globulin
Thyroxine Binding Prealbumin
Albumin
major transporter for T3
Thyroxine Binding Globulin
bind 70-75% of T4
Thyroxine Binding Globulin
binds 15-20% of T4
Thyroxine Binding Prealbumin
T3 transport protein
Albumin
bind 10% of T4
Albumin
T/F
TH can be free or bound
T
percentage of protein-bound TH and free TH
99.9% – protein-bound TH
0.1% – free (unbound) TH
percentage of free T4 (FT4)
0.04%
percentage of free T3 (FT3)
0.4%
thyroid binding protein levels if ↑ estrogen
↑ TBP (allows free TH to bind, ↑ bound TH)
total TH refers to
T3 & T4
Most useful test for assessing thyroid function
Thyroid Stimulating Hormone/Thyrotropin (TSH)
Used to differentiate primary hypothyroidism from secondary hypothyroidism
Thyroid Stimulating Hormone/Thyrotropin (TSH)
Used to monitor and adjust thyroid hormone replacement therapy (3rd Gen)
Thyroid Stimulating Hormone/Thyrotropin (TSH)
generation test with 0.1 mU/L detection limit
Second Generation
generation test with 0.01 mU/L detection limit (more sensitive)
Third Generation
generation test for research purposes only (not for diagnosis)
Fourth Generation
what are measured in Serum T3 and T4
o Total T3 and T4
o Free T3 and T4 (FT3, FT4)
methods for Serum T3 and T4
o Radioimmunoassay
o Chemiluminometric assay
o Immunometric technique
Measures relationship between TSH & TRH secretions
Thyrotropin-Releasing Hormone (TRH)
Used to confirm euthyroid Grave’s disease (type of hyperthyroidism)
Thyrotropin-Releasing Hormone (TRH)
Thyrotropin-Releasing Hormone (TRH) is increased during? decreased during?
Increased: primary hypothyroidism
Decreased: hyperthyroidism
Glycoprotein synthesized and secreted only by thyroid follicular cells
Thyroglobulin
Proof of presence of thyroid tissues / thyroid follicular cells
Thyroglobulin
Ideal tumor marker for thyroid cancer patients
Thyroglobulin
Post-operative marker of thyroid cancer
Thyroglobulin
Surgical removal of thyroid gland (2 lobes removed) leading to NO TGB in circulation
Bilateral thyroidectomy
methods for thyroglobulin
Immunoassays
Measures remaining free binding sites
T3 Resin Uptake
Analyzes the capacity of TBG to bind TH
T3 Resin Uptake
Indirect measurement of the number of free binding sites on the TBG molecules
T3 Resin Uptake
thyroid binding site when ↓ TH (not saturated)
↑
thyroid binding site when ↑ TH (saturated)
↓
Indirectly assesses conc. of circulating FT4
Free Thyroxine Index (FT4I)
a test that is not measured; requires computation
Free Thyroxine Index (FT4I)
formula for Free Thyroxine Index
FT41 = total T4 x T3 resin uptake
test that utilizes antibodies for screening
Thyroid Antibody Screen
antibodies used in Thyroid Antibody Screen
Anti-TSH receptor (TSH receptor antibody)
Antithyroglobulin
Anti-thyroid peroxidase (anti-TPO)
antibody associated with Grave’s disease
Anti-TSH receptor (TSH receptor antibody)
antibody associated with some if not all autoimmune hypothyroidism
Antithyroglobulin
antibody associated with Hashimoto’s thyroiditis
Anti-thyroid peroxidase (anti-TPO)
Measures pituitary TSH stores
TRH Stimulation Test
Conclusive test for hyperthyroidism
TRH Stimulation Test
process of TRH Stimulation Test
o Collect blood
o Inject 500 ug TRH (intravenous) – stimulate pituitary gland to secrete TSH
o Collect blood
o RESULT:
* Normal: ↑ TSH
* Hyperthyroidism: no ↑ (same level)
intravenous TRH injected during stimulation test will stimulate this gland? what is the hormone secreted by that gland?
pituitary gland
TSH
reason why hyperthyroidism has no increase (same level) during TRH stimulation test
pituitary is not stimulated by TRH injection (ex: if secondary), pituitary gland is already producing its own TSH regardless of TRH stimulation; same rate of production
Measures thyroid gland ability to trap iodine
Radioactive Iodine Uptake (RAIU)
Test where thyroid gland absorbs/uptake radioactive iodine
Radioactive Iodine Uptake (RAIU)
Uptake of iodine by thyroid gland is stimulated by
TSH
↑ iodine uptake signifies?
metabolically active gland (produces TH)
↓ iodine uptake signifies?
metabolically inactive gland (no TH production)
type of nodules with ↑ RAIU
Hot nodules
type of nodule found in thyroid gland
hot nodules
type of nodule that takes up large amt. of injected radioactive iodine
hot nodules
type of nodule that is less likely cancerous
hot nodules
type of nodules with ↓ / No RAIU
Cold/Indeterminate/Intermediate
type of nodules that is cancerous
Cold/Indeterminate/Intermediate
↑ RAIU, undetectable TSH indicates?
autonomous thyroid gland activity; takes iodine even TSH absence
used for thyroid anatomy assessment
Thyroid Ultrasound
used for characterization of palpable abnormalities
Thyroid Ultrasound
during thyroid ultrasound, thyroid nodule size that can be seen
Thyroid nodules (<1cm) - NORMAL
Most accurate tool in thyroid nodule evaluation
Thyroid needle biopsy/fine needle aspiration biopsy (FNAB)
First test to be performed for thyroid abnormalities
Thyroid needle biopsy/fine needle aspiration biopsy (FNAB)
used for identification and treatment of thyroid malignancy
Thyroid needle biopsy/fine needle aspiration biopsy (FNAB)
FNAB is assisted by either of these 2 methods
Nodule palpation
Ultrasound
TH deficiency
HYPOTHYROIDISM
hypothyroidism usually refer to this disorder classification
primary hypothyroidism
Hypothyroidism symptoms
o Thyroid gland enlargement/goiter
o Fatigue
o Impairment of mental process
o Loss of appetite
o Myxedema (↓ cardiac output)
o Cold intolerance
o Weight gain
Thyroid gland enlargement/goiter in hypothyroidism is due to?
↑ TSH (stimulates cell growth)
Impairment of mental process in hypothyroidism is due to?
slowed down CNS activity
Loss of appetite in hypothyroidism is due to?
multiple organ defect
How is TH associated with Myxedema (↓ cardiac output) in hypothyroidism?
TH regulates heart rate
mechanism of having cold intolerance in hypothyroidism
↓ TH : ↓ body temp
mechanism of weight gain in hypothyroidism
Slow macromolecule metabolism
Inadequate secretion of TH by thyroid gland
Primary Hypothyroidism
causes of Primary Hypothyroidism
o Lack of dietary iodine
o Thyroid tissue destruction (inability to produce TH)
o Autoantibodies
Laboratory Results of primary hypothyroidism
Decreased: T3, T4, FT3, FT4, FT41, T3 uptake
Increased: TSH, TRH
conditions associated with primary hypothyroidism
Hashimoto’s Thyroiditis
Congenital Hypothyroidism/Cretinism
Myxedema (low cardiac output)
aka Hashimoto’s Thyroiditis
Chronic Lymphocytic Thyroiditis
(massive infiltration of thyroid gland by lymphocytes)
Most common form of primary hypothyroidism; autoantibodies bind to cell membrane causing cell lysis and inflammatory reactions
Hashimoto’s Thyroiditis
manifestation of Hashimoto’s Thyroiditis
goiter
Laboratory Results of Hashimoto’s Thyroiditis
Decreased: T3, T4, FT3, FT4, FT41, T3 uptake
Increased: TSH, TRH
Anti-TPO positive
aka Congenital Hypothyroidism
Cretinism
Defect in development or function of thyroid gland
Congenital Hypothyroidism/Cretinism
symptoms of Congenital Hypothyroidism/Cretinism
Retarded physical and mental development
most common feature of Congenital Hypothyroidism/Cretinism
dwarfism
result if congenital hypothyroidism/cretinism is left untreated within 3 months
Irreversible neurologic & mental deficiency
Laboratory results of congenital hypothyroidism/cretinism
Decreased: T3, T4
Increased: TSH
Peculiar nonpitting swelling [no indentation after pressure] of skin
Myxedema (low cardiac output)
Sever form of myxedema
Myxedema coma
Clinical features of myxedema
o Puffy face
o Weight gain, slow speech, eyebrows thinned, dry and yellow skin, anemia
Decrease TSH production leading to ↓ serum levels of TH
Secondary Hypothyroidism
Laboratory results of Secondary Hypothyroidism
Decreased: T3, T4, FT3, FT4, FT41, T3 uptake, TSH
Increased: TRH
lack of TRH production (caused by hypothalamic failure)
Tertiary Hypothyroidism
Laboratory results of tertiary hypothyroidism
all TH Decreased: T3, T4, FT3, FT4, FT41, T3 uptake, TSH, TRH
Asymptomatic form of hypothyroidism
Subclinical Hypothyroidism
Lab results of Subclinical Hypothyroidism
Normal: FT3, FT4
Slightly increased: TSH
aka HYPERTHYROIDISM
THYROTOXICOSIS
T/F
↑ TH is NOT toxic to all cells
F
↑ TH = toxic to all cells
Caused by excessive TH in circulation
HYPERTHYROIDISM / THYROTOXICOSIS
Causes overactive cells
HYPERTHYROIDISM / THYROTOXICOSIS
symptoms of hyperthyroidism / thyrotoxicosis
o Weight loss
o Loss of muscle mass
o Hyperactivity yet quick fatigability
o Insomnia
o Increased sweating
o Nervousness
o Palpitations
o Goiter
o Exophthalmia (bulging of eyes)
weight loss during hyperthyroidism is due to
Rapid macromolecule metabolism
hyperactivity yet quick fatigability during hyperthyroidism is due to
↑ O2 demand
insomnia during hyperthyroidism is due to
↑ CNS activity
increased sweating during hyperthyroidism is due to
↑ body temp
nervousness during hyperthyroidism is due to
↑ CNS activity
palpitations during hyperthyroidism is due to
↑ cardiac output
goiter during hyperthyroidism is due to
↑ TH
T/F
Both hypothyroidism and hyperthyroidism manifest goiter
T
hyperthyroidism: due to ↑ TH
hypothyroidism: due to ↑ TSH
Dangerously HIGH TH levels leading to STROKE
Thyroid Storm
Dangerously HIGH TH levels leads to STROKE due to
↑ CNS output
↑ Body temperature
↑ Cardiac output
Group of syndromes caused by ↑ free TH in circulation
Thyrotoxicosis
FT3 level in T3 Thyrotoxicosis / Plummer’s Disease
↑
aka T3 Thyrotoxicosis
Plummer’s Disease
FT4 level in T3 Thyrotoxicosis / Plummer’s Disease
N
TSH level in T3 Thyrotoxicosis / Plummer’s Disease
↓
FT3 level in T4 Thyrotoxicosis
N/↓
FT4 level in T4 Thyrotoxicosis
↑
TSH level in T4 Thyrotoxicosis
↓
a primary hyperthyroidism; autoimmune disorder
Grave’s Disease
Prevalence of Grave’s dse
5-6x more in female than male
Clinical features of Grave’s dse
Exophthalmos (bulging of eye)
Pretibial myxedema
Laboratory Results of Grave’s dse
Increased: T3, T4, FT41, T3 uptake
Normal/Decreased: TSH
Anti-TSH receptor positive
condition where thyroid turns into woody or stony-hard mass (calcification of thyroid gland)
Reidel’s Thyroiditis
hyperthyroidism with no clinical symptoms
Subclinical Hyperthyroidism
Lab result of Subclinical Hyperthyroidism
Normal: FT3, FT4
Decreased: TSH
aka De Quervain Thyroiditis
Subacute granulomatous thyroiditis
Subacute nonsuppurative thyroiditis
results to painful/inflammed TH gland
De Quervain Thyroiditis/
Subacute granulomatous thyroiditis/
Subacute nonsuppurative thyroiditis
Lab result of De Quervain Thyroiditis
↑ ESR & thyroglobulin
Anti-TPO negative
Produced by parafollicular C cells of thyroid gland
CALCITONIN
Participated in calcium homeostasis by responding to hypercalcemia
CALCITONIN
Indirectly regulate phosphate by stimulating renal reabsorption of phosphorus (↑ PO4-)
CALCITONIN
Calcitonin is (hypercalcemic, hypocalcemic) and (hyperphosphatemic, hypophosphatemic)
hypocalcemic, hyperphosphatemic
actions of calcitonin as hypocalcemic agent
o Stimulates renal excretion of Ca2+
o Depresses release of Ca2+ from bone (↓ bone resorption)
o Inhibits bone-dissolving activity of osteoclasts (bone macrophage)
LABORATORY ANALYSES OF CALCITONIN
Serum Calcitonin
Pentagastrin Stimulation Test
Serum Calcitonin analysis is a marker for
Medullary thyroid carcinoma (MTC)
required period and repetition of serum calcitonin measurement
before & 6 mos after thyroid surgery
test used for MTC diagnosis
Pentagastrin Stimulation Test
Smallest endocrine gland
PARATHYROID GLAND
Bilaterally located in the posterior portion of thyroid gland
PARATHYROID GLAND
T/F
Most people have 4 PTH gland, some 2 or 8
T
Modulation of parathyroid gland
Free-Standing Endocrine Gland System
(regulation influenced by substance it regulates)
Regulates Blood Calcium and phosphate (sensitive to Ca2+, PO4- level changes; immediate production)
PTH
PTH metabolism of both calcium and phosphorus is done by these (2)
kidney
bone
PTH is (hypercalcemic, hypocalcemic) and (hyperphosphatemic, hypophosphatemic)
hypercalcemic, hypophosphatemic
Stimulates conversion of Vit D activated Vit D3
PTH
how PTH act as hypercalcemic agent
In Bone: ↑ bone resorption of Ca2+ into plasma
In Kidney: ↑ renal reabsorption of Ca2+
it stimulates bone resorption
osteoclast (bone macrophage)
LABORATORY ANALYSES OF PTH
PTH C-TERMINAL ANALYSIS
PTH N-TERMINAL ANALYSIS
Examines intact/whole PTH molecule
PTH C-TERMINAL ANALYSIS
Lab analysis specific for detecting hyperparathyroidism
PTH C-TERMINAL ANALYSIS
Measures both the whole (intact) PTH molecule and amino-terminal fragments in the serum
PTH N-TERMINAL ANALYSIS
Inability to maintain Ca2+ in blood without Ca2+ supplementation
~ ↓ PTH, ↓ Ca2+
HYPOPARATHYROIDISM
feature of hypoparathyroidism? how to assess?
tetany
Chvostek’s sign – facial contraction (tap)
Trousseau’s sign – carpal spasm
causes of hypoparathyroidism
Post-surgical cases: accidental injury to parathyroid gland
Autoimmune parathyroid destruction
condition with ↓ PTH (hyposecretion due to parathyroid gland defect)
Primary Hypoparathyroidism
condition with ↓ serum Ca2+, ↑ Phosphorus
Idiopathic Hypoparathyroidism
condition having lack of responsiveness of PTH by renal system (kidney) – ↓ PTH
Pseudohypoparathyroidism
All classifications of HYPERPARATHYROIDISM are always accompanied by
phosphaturia, presence of PO4- crystals in urine
Most common cause of hypercalcemia
Primary hyperparathyroidism
This condition occur due to parathyroid adenoma
Primary hyperparathyroidism
Lab result of Primary hyperparathyroidism
Increased: PTH, Ionized Ca2+
*Ca2+ also increased since it is hypercalcemic
Develops in response to hypocalcemia
Secondary hyperparathyroidism
causes of Secondary hyperparathyroidism
Vitamin D deficiency
Chronic renal failure
Lab result of Secondary hyperparathyroidism
Increased: PTH
Decreased: Ionized Ca2+
Occurs with secondary hyperthyroidism
Tertiary hyperparathyroidism
condition with Ca2+ phosphates precipitate (crystals) in soft tissues
Tertiary hyperparathyroidism
Lab Result of Tertiary hyperparathyroidism
Phosphates level: N/↑