endocrine - thyroid Flashcards
DIT plus DIT
Tetraiodithyronine or T4
Biosynthesis of T3 and T4
- Dietary iodide ingestion by follicular cells
- Active transport and uptake of iodide into colloid by thyroid gland
- Oxidation of I and iodination of Tg tyrosine residues
- Coupling of Iodotyrosine residues (MIT & DIT) to form T3 and T4
- Proteolytic of Tg with release of T3 and t4 into circulation
DIT plus MIT
Triiodothyronine T3
Indispensable component of thyroid hormone comprising 65% of T4 and 58% of T3’s weight.
Iodine
Required daily intake of iodine in 0-7y/o.
90 ug/d
Required daily intake of iodine in 7-12y/o.
120 ug/d
Required daily intake of iodine in teenager and adults
150 ug/d
Required daily intake of iodine in pregnant and lactating women
25o ug/d
Iodine intake not more than
1100 ug/d
Excess iodine
Wolff chaikoff effect
Jodbasedow phenomenon
Excess iodine with transient shut down of thyroid hormone production (normally).
When increasing doses of iodide inhibit organification and hormonogenesis of thyroid hormone.
Wolff chaikoff effect
In some pts with HAshimoto’s thyroiditis, they may stay hypothyroid because of inability to escape this effect
Wolff-chaikoff effect
Thyroid hyperfunction induced by excess iodine ingestion in pts with various thyroid disorder (grave’s disease)
Jod-basedow phenomenon
Dietary iodine reaches the circulation as
Iodide anion
Iodide active transport by thyroid Is mediated by this membrane protein
Sodium-iodide symporter or NIS
It functions as iodide concentrating mechanism that enables iodide to enter the thyroid for hormone biosynthesis
NIS
Iodide trapping by the aid of
NIS
Iodide must be first ___ to be able to iodinate tyro sly residues of Tg
Oxidized
Iodination of tyrosyl residues then forms monoiodotyrosine and diiodotyrosine which are then coupled to form either T3 or T4. Both reactions are catalyzed by
Thyroperoxidase
Thyroperoxidase Catalyzes oxidation steps involved in:
I- activation
Iodination of Tg tyrosyl residues
Coupling of iodotyrosyl residues
TPO uses ___ as the oxidant to activate I- to hypoiodate the iodination species
H2O2
To liberate t3 and t4, Tg is resorted into follicular cells in the form of ___ which fuse with lysosomes to form phagolysosome
colloid droplets
Primary secretory product of thyroid gland
T4
Thyroid secretes approximately how many grams of thyroxine daily
70-90 ug/d
Total daily production rate of t3
15-30 ug/d
T3 is derived from 2 processes
- 80% of circulating T3 comes from deiodination of T4 on peripheral cells
- 20% comes directly from thyroid secretion.
Pro hormone for T3
T4
T4 is biologically inactive in target tissues
True. Until converted to T3
T4 is converted to T3 by
5-deiodination of outer ring of T4
T3/T4 which is biologically active responsible for the majority of thyroid hormone effects
T3
Major extrathyroidal T4 conversion site for production of T3
Liver
Some occurs in kidney and other tissue
Normal disposition of T4
41% is converter to T3
38% is converter to rT3
21% is metabolized via other pathways (conjugation on liver and excretion in bile)
Normal circulating concentration of t4
4.5-11 ug/dl
Normal circulating concentration of t3
60-180 ng/dl
T3/4: Produced only in thyroid gland
T4
T3/4: 80% are from peripheral conversion
T3
Half life of t4
7 days
Half life of t3
One day
T3/4: only free hormones are active
T4
3-8x more potent
T3
More than 99% of circulating T3 and t4 is bound to plasma protein Carrier proteins which are
TBG 75%
Transthyretin TTR / thyroxine-binding prealbumin TBPA 10-15%
Albumin 7%
HDL 3%
Decrease or increase TBG effects on total serum T3 and T4 level and free T3 and T4.
Decrease or increase TBG will decrease/increase total serum T3 and T4 level.
While free T3 and T4 remain unchanged
Drugs that increase TBG
Oral contraceptives Methadone Clofibrate 5-fluorouracil Heroin Tamoxifen
Conditions that increase TBG
Pregnancy Infectious/chronic active hepatitis HIV infection Biliary cirrhosis Acute intermittent porphyria Genetic factors
Drugs that decrease serum t3 and t4 by decreasing TBG conc
Glucocorticoids Androgens L-asparaginase Mefenamic acid Furosemide
Drugs that decrease serum t3 and t4 by decreasing binding
Antiseizure medications
Salicylates
Decreased thyroid hormone concentration may lead to alteration of ___. May develop impairment of attention, slowed motor function, and poor memory
cognitive function.
Thyroid hormone influences cv hemodynamics by
Increase HR and decrease systemic vascular resistance thus increase CO = improve cardiac performance Elevate blood volume Local vasodilators Decrease diastolic blood pressure Cardiac chronotropy and inotropy
Thyroid hormone is critical for normal bone Growth and development
T3 regulates sk maturation at growth plate.
T3 participates in osteoblasts differentiation and proliferation and chondrocytes maturation loading to bone ossification.
Major regulator of mitochondrial activity
T3
Thyroid hormone is a major regulator of mitochondria activity
T3 induces early transcription and increases TFA expression.
T3 stimulates O2 consumption.
Thyroid hormone stimulates mitochondrial activity in most tissue
T3 increases basal metabolic rate, body heat production and O2 consumption.
Metabolic effects of T3
- Lipolysis- FA + glycerol
- expression of lipogenic enzymes
- cholesterol catabolism into BA
- Rapid removal of LDL from plasma
- Carbohydrate and protein catabolism
Thyroid hormone influences the female repro system
Hypothyroidism may be asso with menstrual disorder, infertility, risk of miscarriage and other complications of pregnancy.
AOG when fetus is completely dependent on maternal thyroid hormones
First 3 mos
AOG when fetal thyroid begins to conc iodine and synthesize Iodothyronines
10-12wks
AOG when fetal pituitary gland differentiates
10-12 wks
Thyroid hormones that appear in fetal serum
TSH
T4
Placental transfer without difficulty
Iodide
Thionamides
Thyroid ab
TRH
Some placental transfer
T3
T4
Little or no placental transfer
TSH
Increased thyroid hormone requirements during pregnancy
Increase free TH binding to TBG - marked fall in serum free T4 - if no compensatory increase in thyroid secretion leads to hypo.
Transplacental transfer of T4 - placental degradation of T4 - if no compensatory increase in thyroid secretion leads to hypo.
During first trimester, ___ is at its highest conc and can stimulate thyroid cells to produce new thyroid hormones.
B-HCG
There is transient low TSH during 1st trimester due to increased thyroid hormone production.
True
During pregnancy, there is an increased Renal iodine clearance, therefore..
Increased 24-hr RAIU
During pregnancy, there is an decreased plasma iodine and placental iodine transport to the fetus, therefore..
In deficient women, decreased T4, increases TSH then leads to goiter formation
During pregnancy, there is an increased O2 consumption, therefore..
Increased BMR
During 1st tri in pregnancy, there is an increased HCG, therefore
Increased free T4 and T3
Decreased basal TSH
During pregnancy, there is an increased serum TBG, therefore..
Increased total T3 and T4
During pregnancy, there is an increased plasma volume, therefore..
Increased T3 and T4 pool size
During pregnancy, there is an increased plasma type 3 deiodinase, therefore..
Accelerates rates of t3 and T4 degradation and production.
Refers to classic physiologic manifestations if excessive quantities of the thyroid hormones
Thyrotoxicosis
RAIU level in thyrotoxicosis
Decreased
Most common cause of thyrotoxicosis
Thyroiditis
Reserved for disorders that results from sustained overproduction of hormone by the thyroid gland itself
Hyperthyroidism
Most common cause of hyperthyroidism
Graves disease
Lab diagnosis for thyrotoxicosis and hyperthyroidism
Suppressed TSH <0.1 mU/L
Elevated T4
RAIU
Lab diagnosis to differentiate thyrotoxicosis and hyperthyroidism
RAIU
TSH level and RAIU level of: Graves disease Toxic multinodular goiter Toxic adenoma Gestational hyperthyroidism
Low TSH
High RAIU
TSH level and RAIU level of: Iodine induced hyperthyroidism Amiodarone- induced hyperthyroidism Struma ovarii Metastatic thyroid Ca Thyroiditis
Low TSH
Low RAIU
TSH level and RAIU level of:
TSH-secreting pituitary tumor
TH hormone resistance
Elevated or normal TSH
TSH level and free T4 level of:
Secondary or central hypothyroidism
Low TSH
Low T4
TSH level and T4 level of:
Sick euthyroid syndrome
Low TSH
Low T4
TSH level and T4 level of:
T3 thyrotoxicosis
Sub clinical hyperthyroidism
Low TSH
Normal T4
TSH level and T4 level of:
True hyperthyroidism
Low TSH
High T4
TSH level and T4 level of:
Graves disease
Low TSH
High T4
Graves disease is a syndrome characterized by
Hyperthyroidism
Ophthalmopathy
Dermopathy
Pretibial myxedema
Graves disease is an autoimmune disease with a strong familial disposition more common in male/female.
Female
Environmental triggers of graves disease
Stress
Tobacco use
Infection
Iodine exposure
Most frequent cause thyrotoxicosis in iodine-sufficient countries
Graves disease
Main ag in graves disease
TSHR
Circulating ab in graves disease
TRAbs
Dermopathy in graves disease
Plummer's nail Hyperpigmentation Hyperhidrosis Alopecia Acropachy (triad of digital clubbing, soft tissue swelling of hands and feet and periosteal new bone formation)
Signs and symptoms of hyperthyroidism
Freq bowel movement Bulging eyes Sudden paralysis Weigh loss / gain Tachycardia Heat intolerance Warm, moist palm Light period
Increase sweating
Insomnia
Nervousness, tremors
Goiter Hoarseness Infertility Irritability Dry/sore throat Dysphagia
Signs and symptoms in hypothyroidism
Constipation Puffy eyes Muscle weakness Weigh loss gain Bradycardia Cold intolerance Dry, patchy skin Heavy period
Hairloss Tiredness Forgetfulness Depression Elevated cholesterol
Goiter Hoarseness Infertility Irritability Dry/sore throat Dysphagia
Atrial fibrillation is characteristically manifested in what thyroid disorder
Graves disease
First line therapy for hyperthyroidism or graves disease
Radioactive iodine
Mechanism of action do radioactive iodine
Destroys the thyroid and stops the excess production of hormone
Indication for radioactive iodine treatment
Female planning a pregnancy in the future
Pts with increase ping surgical risk
Pts previously operated or externally irradiated neck
Pts with CI to ATD
Treatment of choice for recurrent hyperthyroidism after ATD therapy
RAI
RAI is used by elderly and cardiac pts
True.
RAI has no effect on fertility, no increased incidence of congenital malformation and no increased risk of cancer
True
RAI is contraindicated during
Lactation and pregnancy
Pregnancy must be postponed for at least ____ after RAI therapy
6 mos
RAI therapy or RAI ablation:
To destroy some thyroid tissue in graves disease or toxic nodules.
RAI therapy
RAI therapy or RAI ablation:
Low dose
RAI therapy
RAI therapy or RAI ablation:
With intention to destroy all thyroid remnant and metastasis in well diff Ca
RAI ablation
Indications for thyroidectomy
Planning for pregnancy (<4-6 mos) Thyroid malignancy Large goiter (>80gms) Low RAIU Coexisting hyperparathyroidism
Patients undergoing surgery (thyroidectomy) should be rendered
Euthyroid
What would be given in immediate preop period in thyroidectomy
Potassium iodide
To diminish vascularity to suppress the thyroid hormone production becoz patients undergoing surgery should be rendered euthyroid.
Potential complication of thyroidectomy
Hypoparathyroidism
Hypothyroidism
Vocal cord paralysis
Anti thyroid drugs
Methimazole
Propylthiouracil
Carbimazole
Thiamazole
PTU / MMI:
Blocks thyroid hormone production and secretion
Both
PTU / MMI:
Blocks peripheral conversion of T4 to T3
Porpylthiouracil
PTU / MMI:
Long half life
MMI
PTU / MMI:
More binding to albumin
PTU
PTU / MMI:
Less placental passage
PTU
PTU / MMI:
Lower conc in breast milk
PTU
PTU / MMI:
With peculiar toxicity - aplastic cutis embryopathy
MMI
Mechanism of action of ATDs
Inhibition of organification (iodine binding to Tg)
Inhibition of coupling of Iodothyronines
Inhibition of T4 to T 3 conversion (PTU)
Possible immunosuppressive effects (MMI)
ATD that is used in all patients
MMI
Except those in 1st tri in pregnancy, treatment for thyroid storm
Myxedema is due to
Accumulation of hyaluronic acid which alter the composition of the subs of the dermis and other tissue
Life threatening clinical condi in pts with long standing severe untreated hypothyroidism
Myxedema coma
Severe hypothyroidism in infancy with irreversible mental and growth retardation
Cretinism
TSH level, T3 or t4 level in subclinical hyperthyroidism
Low TSH
Normal t4 and t3
Asymptomatic
TSH level, T3 or t4 level in subclinical hypothyroidism
High TSH
Normal t4 and t3
Thyroxine therapy must be considered in subj (age) if TSH is ___ and/or TPO ab is (present/absent)
<65 yrs old if TSH >10mU/L and/or TPO ab is present
In cases wherein TSH <10mU/L and/or TPO ab is absent, thyroxine therapy still might be warranted in individual with high background for
Cv risk, pregnancy and infertility
Most common case of hypothyroidism in areas wherein dietary iodine is sufficient
HAshimoto’s thyroiditis
Pathologic feature of HAshimoto’s thyroiditis
Presence of both mononuclear cells and thyroid follicle destruction
Hallmark of classic HAshimoto’s disease
Goiter
Treatment of choice in HAshimoto’s disease and /or large goiter
Levothyroxine
Self limited anti-inflammatory disorder of thyroid and the most common cause of pain from thyroid origin
Subacute thyroiditis
Rare disorder of chronic sclerosing thyroiditis
Riedel’s thyroiditis