Thyroid Gland Flashcards
Develops as an endodermal outgrowth or an evagination from the midline of the floor of the pharynx, between tuberculum impar and copula
Thyroid gland
The thickening becomes what duct
Thyroglossal duct
- wc elongates and later be bilobed
The duct becomes a solid cord and migrates down the neck passing thru the developing
Hyoid bone
Site of origin of the thyroglossal duct on the tongue remajns as a pit called the
Foramen cecum
Thyroid gland location
Below larynx on either side of and the anterior to trachea
Thyroid gland and relation to larynx, trachea, esophagus
Below larynx on either side
Anterior to trachea
Trachea lies inferior to larynx, esophagus is posterior to it
Surgical removal of thyroid may lead to injury of these organs
Thyroid gland and relation to parathyroid glands
Parathyroid glands - embedded posterior to thyroid gland, superior & inferior pole
Inadvertent removal during thyroidectomy causes hypoparathyroidism
Thyroid gland and relation to recurrent laryngeal nerve
These bilateral branches of the vagus nerve pass posteromedially along the groove between the esophagus and the trachea
Tumor invasion or injury results to hoarseness
Thyroid gland and relation to neck muscles & great vessels
Common carotid artery lies immediately lateral to the thyroid
Tumor invasion or injury may cause injury to any or all adjacent structures
Relation to lobes: ANTEROLATERALLY
The sternothyroid, superior belly of omohyoid, and anterior border of the sternocleidomastoid
Relation to lobes: POSTEROLATERALLY
Carotid sheath w the common carotid artery, the internal jugular vein, and vagus nerve
Relation to lobes: MEDIALLY
Larynx, trachea, pharynx and esophagus
Associated w these are cricothyroid muscle and its nerve supply, external laryngeal nerve
Between esophagus & trachea = recurrent laryngeal nerve
Rounded posterior border of each lobe is posterior to the superior and inferior parathyroid glands and the anastomosis between the superior and inferior thyroid arteries
Relations of the Isthmus
Anteriorly: the sternothyroids, sternohyoids, anterior jugular veins, fascia, and skin
Posteriorly: the second, third, and fourth rings of the trachea
The terminal branches of the superior thyroid arteries anastomose along its upper border
Thyroid gland is firmly attached to the laryngotracheal skeleton via the
Visceral or pretracheal fascia
When swallowing, what moves? Thyroid masses or brachial cysts and dermoid cyst
Thyroid masses
What lvl of the thyroid does the base lie?
4th and 5th tracheal ring
Others sources: attached to travhea from the midlvl of thyroid cartilage to the 5th and 6th travheal cartilage
Thyroid wt
Approx 15-20g
Some source: 16 +/- 6 g (10-22)
Each lobe is approx what thickness and length
2 to 2.5cm in thickness and width at its largest diameter and 4cm length
Thyroid lobes are connected by a narrow bridge of tissue called
Isthmus
A vascular organ surrounded by a sheath derived from the
pretracheal layer of deep fascia
- sheath attaches the gland to the larynx and trachea
Isthmus extends across the midline in front of the
2nd, 3rd or 4th tracheal rings
A pyrimidal lobe projects upward from the isthmus, usually to
the left of the midline
A fibrous or muscular band frequently connects the pyramidal lobe to the hyood bone; if it’s musculare it is referred to as
Levator glandulae thyroideae
Abnormalities in the pattern of thyroid dev, s/a persistence of this tract leads to a
thyroglossal duct cyst
Protrusion of tongue causes movement of thyroglossal duct cyst as opposed to
True thyroid masses (e.g goiter) wc move on deglutition
Fxnal unit of thyroid gland
Follicle (acinus) surrounded by a rich capillary plexus
The ht of the follicular epithelium varies w the degree of stimulation of
TSH
The ht of the follicular epithelium varies w the degree of stimulation of
TSH
Glandular epi veries w the degree of stimulation
Columnar: active
Flat: inactive
Lumen of the follicle filled w a clear, amber proteinaceous fluid called
Also a major constituent of thyroid mass
Colloid
Extend to colloid from the apical (adluminal) border, wc is the site od iodination rxn
Microvilli
Also occurs in the apical border
Initial phase of thyroid hormone secretion (i.e resorption of the colloid by endocytosis)
Parafollicular (C) cells secrete
Do not border on the follicular lumen
Calcitonin
Major constituent of colloid is the large glycoprotein that contains thyroid hormones within its molecule
Thyroglobulin
When the gland is inactive
The colloid is abundant
Follicles are large
Cells lining them are flat
When gland is active
Follicle are smol
Cells cuboid or columnar
Edge of colloid is scalloped, forming many smol “reabsorption lacunae”
Thyroid gland arteries
Superior thyroid artery
Inferior thyroid artery
Thyroidea ima
A branch of the external carotid artery
Descends to the upper pole of each lobe, accompanied by external laryngeal nerve
Superior thyroid artery
A branch of the thyrocervical trunk, ascends behind the gland to the lvl of the cricoid cartilage
It then turns medially and downward to reavh the posterior border of the gland
The recurrent laryngeal nerve crosses either in front or behind the artery or pass between its branches
Inferior thyroid artery
If present, may arise from the brachiocephalic artery or arch of aorta
Ascends in front of trachea to the isthmus
Thyroidea ima
Thyroid gland veins
Superior thyroid - drains into internal jugular vein
Middle thyroid - drains into internal jugular vein
Inferior thyroid - receives its tributaries from the isthmus and the lower poles of the gland
Veins of the two sides anastomose w one another as they descend in front of the trachea
They drain into the left brachiocephalic vein in the thorax
Inferior thyroid vein
Lymphatic drainage of thyroid gland
Mainly laterally into the deep cervical LN
Few descend to the paratracheal nodes
Thyroid innervation
Both adrenergic and cholinergic NS via fivers arising from the cervical ganglia and vagus nerve, respectively
Afferent fibers pass thru the laryngealnerves and regulate an
Active vasomotor system
One fxn of neurogenic stimuli is to
regulate blood flow of thyroid
Major secretory product of thyroid gland is
3,5,3’,5’ - tetraiodothyronine (thyroxine) T4
Other thyroid hormone
T3
3,5,3’-triiodothyronine
Molar activity
T3 to T4
3-5:1
Secretory ratio
T4 to T3
10-20:1
Plasma conc ratio
Free T4 to free T3
2:1
Most T3 in plasma is derived from the monodeiodination of T4 by action of
Monodeiodinase (5’-deiodinase)
- found in peripheral tissues
Biologically inactive thyronine formed by peripheral conversion catalyzed by 5-deiodinase
rT3
Each thyroglobulin molecule contains approximately how many tyrosine residues?
120
Thyroid accumulates what from the plasma?
Inorganic iodide
In the US, Daily dietary iodine intake is about
500ug
How much iodide is required per week to maintain euthyroidism?
1mg of iodide or 150ug/day
Thyroid gland stored enuff thyroid hormone to maintain a euthyroid state for how many months w/o hormone synthesis?
3 months
Throid gland contains how much iodide?
5-7mg iodide
2/3 of total iodide content in the colloid is in the form of
biologically inactive iodothyrosines
1/3 of the colloid iodide content is in form of
biologically active thyronines t3t4
Also formed in the peripheral tissues by deiodination of T4
T3
More active hoe
T3 ayt
The naturally occurring forms of T4 and its congeners with asymmetric C atom are the
L isomers
Has only smol fraction of the activity of D form
D-thyroxine
Smol amts of rT3 are also found in
Thyroid venouse bld
Thyroglobulin glycoprotein is made up of two subunitsand has a MW of
660,000
10% carbs by wt
123 tyrosine residues (4-8 lang incorporated)
3 fxns of thyroid cells
- Collect abd transport iodine
- Synthesize Tg, secrete it into the colloid
- Remove thyroid hormones from Tg and secrete to circ
The normal plasma iodine lvl
0.3ug/dL
How much iodine enter the thyroid at normal rates?
120ug/d
Thyoid secretes how much iodine in T3 and 4
80ug/d
How much iodine per day diffuses into the ECF?
40 micrograms
The secreted t3&4 are metabolized in the liver and other tissues, w the release of how much in the ECF
60ug/d
Net loss of iodine in the stool
20ug/d
Normal thyroid iodide to plasma iodide conc ratio
25-40:1
Biosynthetic steps that are stimulated by TSH
- Iodine uptake (Iodide Trapping)
- Oxidation of iodide; the role of thyroperoxidase
- Iodination of Tyrosine (Organification)
- Coupling (Condensation)
Luminal iodide to follicular cell iodide conc ratio
5:1
A useful therapeutic index of the fxnal statys of the thyroid gland
Radioactive iodide uptake by the thyroid gland
A 24-hr uptake normally ranges between
10-35% of the administered dose
In a nirmal gland, the iodide pump concentrates the iodide to abt
30x its conc in bld
Active iodide forms
Iodinum ion (I+)
A free radixal of iodine (IO3-)
Iodine (I2)
Denotes tge addition of iodide to the tyrosyl residues of thyroglobulin
Iodination of active iodide
Substrate for iodination
Thyroglobulin
Requires the fusion of two diiodotyrosine molecs
T4 synthesis
Requires the condensation of monoiodotyrosine with a diiodotyrosine
T3 synthesis
Also mediates the coupling rxn
Thyroid peroxidase
The release of hormones involves the following rxns
- Hydrolysis of Tg by thyroid protease and peptidases
- Secretion of iodothyronines
- Pseudopod extensions –> pinocytic vesicles
- 3/4 of iodinated tyrosine in the Tg never become thyroid hormones but remain MIT abd DIT
Freed from the Tg but they’re not secreted into the bld, instead their iodine is cleaved from them by a deiodinase enz (iodotyrosine deiodinase)
Iodinated tyrosines
99.95% of T4 is bound to
Plasma proteins
Binds about 75% of plasma T4
TBG (Thyroxine-binding globulin)
In normal indivs, less than half of the available binding sites on TBH are saturated with
T4
Binds abt 15-20% of the circulating T4
Thyroxine-binding prealbumin (TBPA or transthyretin)
Abt 9% of T4 is bound to
Albumin
Almost all (99.5%) of T3 is transported bound to
TBG
Very little T3 us bound to
Albumin
None is bound to
TBPA :
Thyroid hormone is metabolized by
Deiodination
Deamination
By conjugation w glucoronic acid
Is secreted via the bile duct into the intestine
Conjugate
Catalysing the formation of T3 and rT3 (inactive)
5’-deiodinase
In the liver, T4 & T3 are conjugated to form
Sulfates and glucoronides
The thyroid conjugates are
Hydrolyzed
Reabsorbed (enterohepatic circ)
Excreted in the stool
TSH secretion is infuenced by 4 factors:
- TRH secretion from the median eminence
- Bld lvl of unbound T4
- Bld lvl of unbound T3 generated by peripheral conversion of T4 to T3
- Peripheral conversion of T4 to T3 within the pituitary gland
A tripeptide synthesized by the parvicellular peptidergic neurons in the hypothalamus
TRH
Plays a major role in negative feedback in pituitary lvl
T3
High conc of intrathyroidal inorganic iodide lead to
Inhibition of thyroid release
High conc of organic iodide (thyroid hormone) lead to
Decrease in iodide uptake
cAMP synthesis
TSH receptors -activate-> adenylcyclase -to form-> cAMP -activate-> protein kinase —> PHOSPHORYLATION
It inhibits TSH secretion and the response to TRH
Somatostatin
Decrease the basal secretion of TSH
Dihydroxyphenylethylamine (dopamine)
Dopa
Bromocriptine
Cause competitive inhibition of iodide transport into the cell, that is, inhibition of iodide-trapping mechanism
Thiocyanate in high enuff conc
Deficiency of thyroid hormones leads to increased secretion of TSH by ant pit gland wc causes
Overgrowth of thyroid gland
Block of thyroid secretion can lead to the ions to block thyroid secretion can lead to the development of an enlarged thyroid gland wc is called
Goiter
Prevents formation of thyroid hormone from iodides and tyrosine
Propylthiouracil
Also methimazole and carbimazole
The mild abd transient inhibition of organic binding of iodide and hence of hormone synthesis is known as the
Wolff-Chalkoff effect
Vegetables of Brassicacae family, particularly rutabagas, cabbage and turnips, contain
Progoitrin
Attached to the DNA genetic strands or in proximity to them
Thyroid hormone receptors
Total membrane surface area of the mitochondria increases almost directly in proportion to the
Increased metabolic rate of the whole animal
Enz that becomes increased in response to thyroid hormone is
Na-K-ATPase
Thyroid hormone causes cell mem to be
Leaky to Na ions
- wc further activates the Na pump and further increase heat prodxn
Normal BMR for adult euthyroid males is
35-40kcal/m^2 body surface/hr
Normal BMR
6-10% lower in euthyroid females
Marked decrease in the myelination abd arborization of neurons in the brain
Hypothyroidism
What occurs if hypothyroidism it is untreated?
Mental retardation
Thyroid hormone is necessary for
Normal lactation
Thyroid hormone potentiates the glycogenolytic effevt of epinephrine, causing
Glycogen depletion
In physiologic amounts, thyroid hormones has a
Potent protein anabolic effect
In large doses, thyroid hormone has a
Protein catabolic effect
Increased thyroid hormone
decreases the concentrations of cholesterol, phospholipids, and triglycerides in the plasma, even though it increases the free fatty acids.
The large increase in circulating plasma cholesterol in prolonged hypothyroidism is often associated with
severe atherosclerosis
One of the mechanisms by which thyroid hormone decreases plasma cholesterol concentration is to
Increase significantly cholesterol secretion in the bile and consequent loss in the feces
A possible mechanism for the increased cholesterol secretion is that thyroid hormone induces increased numbers of
low-density lipoprotein
receptors on the liver cells, leading to rapid removal of low-density lipoproteins from the plasma by the liver and
subsequent secretion of cholesterol in these lipoproteins by the liver cells
relative vitamin deficiency can occur when
excess thyroid hormone is secreted
A greatly increased amount of thyroid hormone almost always
decreases body weight
mean arterial pressure usually remains normal. Because of
increased blood flow through the tissues between heartbeats, the pulse pressure is often increased, with the systolic pressure elevated 10 to 15 mm Hg in hyperthyroidism and the diastolic pressure reduced a corresponding amount.
lack of thyroid hormone can cause
constipation
diarrhea
Hyperthyroidism
lack of thyroid hormone
decreases rapidity of cerebration
extremely nervous and have many psychoneurotic tendencies, such as anxiety complexes, extreme worry, and paranoia
hyperthyroidism
makes the muscles react with vigor, but when the quantity of hormone becomes excessive, the muscles become weakened because of excess protein catabolism
hyperthyroidism
it causes the muscles to become sluggish, and they relax slowly after a contraction.
hypothyroidism
resting hand tremors, wt loss, palpitations, DoB, complaining of lack of sleep
hyperthyroidism
feeling of constant tiredness, but because of the excitable effects of thyroid hormone on the synapses, it is difficult to sleep
hyperthyroidism
extreme somnolence (Sleepiness, the state of feeling drowsy, ready to fall asleep) is characteristic of
hypothyroidism
is likely to cause loss of libido
lack of thyroid hormone
sometimes causes impotence
a great excess of the hormone
menorrhagia and polymenorrhea
amenorrhea
lack of thyroid hormone
the production of heat via the digestion of food, or by the action of hormones.
Calorigenesis
the basal metabolic rate falls to almost one-half normal
when no thyroid hormone is produced
Chronotropic effevt on heart
Increase number and affinity of B-adrenergic receptors
Inotropic effect on heart ❤️
Enhance responses to circulating catecholamines
Increase proportion to a-myosin heavy chain (w highger ATPase activity)
Effect of adipose and muscle
Catabolic
Metabolic effects of the gut
Increase rate of carbohydrate absorption
Metabolic effects og lipoprotein
Stimulate formation of LDL receptors
Stimulate O2 consumption by metabolically active tissues and inc metabolic rate
Tissue exceptions: testes, uterus, LN, spleen, ant pit
Calorigenic
Characterized by nervousness, wt loss, hyperphagia, heat tolerance, increased pulse p, fine tremor of outstretched fingers, warm soft skin, sweating, BMR +10 to as high as +100
Hyperthyroidism (thyrotoxicosis)
Hyperthyroidism most common cause is
Graves’ dse (exophthalmic goiter)
Autoimmune dse in wc circulating Ab formed against the TSH receptor activate the receptor, making glands hyperactive
Graves’ dse
Immunity that destroys the gland rather than stimulates it
Hypothyroidism
Hypothyroidism pt first have this
Thyroiditis - inflammation
Goitrous glands may secrete normal quantities of thyroid hormones, but more frequently, the secretion of hormone is depressed
Idiopathic nontoxic colloid goiter
Iodine is not pumped adequately into the thyroid cells
Deficient iodide-trapping mechanism
Iodides aren’t oxidized to the iodine state
Deficient peroxidase system
Final thyroid hormones cannot be formed
Deficient coupling of iodinated tyrosines in the thyroglobulin molecule
Prevents recovery of ipdine from the iodinated tyrosines that are not coupled to form the thyroid hormones thus leading to iodine deficiency
Enz deiodinase deficiency
Prevents recovery of ipdine from the iodinated tyrosines that are not coupled to form the thyroid hormones thus leading to iodine deficiency
Enz deiodinase deficiency
Are substance s that block the synthesis of thyroid hormone
They hav a propylthiouracil-type of antithyroid activity
TSH secretion is enhanced
Goitrogens
Goiterogenic agents include
Perchiorate, thiocyanate, pertechnetate
Thionamides (propylthiouracil and methimazole)
Iodide def
Excess iodide
Turnips, rutabagas, cabbages, veggies of fam Brassicacae
Monovalent anions that block iodide-trapping
Perchiorate, thiocyanate, pertechnetate
Block coupling of iodotyrosines
Thionamides (prophylthiouracil and methimazole)
Physiologic characteristics of hypothyroidism
Depressed growth of hair and scaliness of skin
Frog like husky voice
Edematous appearance throughout the body (myxedema)
Wc can result in peripheral vascular dse, deafness, coronary artery dse w consequent early death
D/t increase in quantity of blood CHOL bcs of altered fat and CHOL metabolism and diminished liver excretion of cholesterol in bile
Atherosclerosis
Hypothyroidism tx
Daily ingestion of tablet or more containing thyroxine to maintain a steady lvl if thyroid hormone activity
Conc of binding proteins in hyperthyroidism and hypothyroidism
Normal
Conc of binding proteins in Euthyroid: estrogens, methadone, heroin, major tranquilizers, clofibrate
High
Also high total plasma T4, T3 abd RT3
Normal: fT3 fT4 and frT3 also plasma TSH
Conc of binding proteins in Euthyroid: glucocorticoids, androgens, danazol, asparaginase
Low
Also low total plasma T4, T3 abd RT3
Normal: fT3 fT4 and frT3 also plasma TSH