Term
Which of the following things mediate the 5’deiodination that converts T4=>biologically active T3?
Adrenal glands
Thyroid gland (where all of T4 is produced)
Kidney
Type 3 Deiodinase
Pituitary
liver |
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Definition
Pituitary
liver
Thyroid gland (where all of T4 is produced)
Kidney
Types 1 and 2 deiodinases convert T4 to T3
D1 primarily in liver and kidney, supplies plasma T3
D2 in pituitary, brain, placenta, brown fat, muscle and thyroid; produces T3 for “local” use as well as plasma T3
Type 3 deiodinase (D3) removes an inner ring iodine
Converts T4 to reverse T3, and T3 to T2
D3 inactivates thyroid hormone |
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Term
| T/F: One of four mature Tg molecules contains ~3 T4’s, and 3 of 4 Tgs contain 1 T3 molecule. |
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Definition
F Each mature Tg molecule contains ~3 T4’s, but only 1 in 4 Tg’s contains a T3 molecule.
Colloid is largely composed of Tg, and is basically a storage depot of thyroid hormone. |
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Term
NIS is the ____ that allows the _____ to come into the thyroid cell. Thyroglobulin (Tg), a large glycoprotein, is synthesized within the thyroid cell and is iodinated with tyrosines by ______ that creates _______. These _______ combine to form ____ within the Tg protein.
Plasma iodide, thyroid peroxidase, mono-diiodotyrosines, T3/T4 |
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Definition
| transporter, Plasma iodide, thyroid peroxidase, mono-diiodotyrosines, T3/T4 |
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Term
| T/F: TSH plays a key in stimulating iodide trapping as well as thyroid hormone synthesis and secretion. |
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Definition
T In response to TSH, pseudopodia form and endocytose colloid.
In the cell, colloid droplets fuse with lysosomes and thyroid hormone is cleaved enzymatically from Tg.
T4 and T3 are released into the circulation.
TSH stimulates iodide trapping, as well as thyroid hormone synthesis and secretion. |
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Term
| You see a 17 year old girl with a height of 100 cm, mental retardation, myxedema and a TSH of 288 (normal 0.3-5.5). What features of of this disorder? |
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Definition
She could have a goiter
She has impaired thyroid gland function/T4 secretion
Had untreated fetal/neonatal hypothyroidism propelled by her mother’s hypoth
She had an iodine deficiency due to endemic food conditions
During fetal period – hypothyroid and not trated…
Should check tsh in preggoes! |
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Term
| Tell me about Thytrotropin Releasing Hormone |
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Definition
A tripeptide: pyroGlutamate-histidine-proline-amide
Synthesized from a 29 kDa precursor protein that contains 5 copies of TRH flanked by basic amino acids.
A specific protease cleaves the precursor to yield TRH. The intervening peptides also may have hormonal function. |
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Term
| with which three other hormones does TSH share an alpha subunit? |
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Definition
| FSH, LH, and CG: choriogonadotropin |
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Term
| T/F: TRH receptors are members of the large family of G-protein coupled receptors. The major second messenger is cAMP, although activation of phospholipase C also may be involved. |
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Definition
| F: TSH receptors are…on the thyroid follicular cell |
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Term
| T/F: Thyroglobulin noncovalently binds 10x more T3 than it does T4 |
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Definition
F ~99.97% of plasma T4 and 99.7% of T3 are non-covalently bound to proteins.
Thyroxine Binding Globulin (TBG) is the major binding protein for T4 and T3. TBG’s affinity for T4 is ~10-fold greater than for T3.
Do not confuse TBG with thyroglobulin, the precursor protein from which T4 and T3 derive. |
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Term
| A patient with liver cirrhosis comes in with some thyroid problems. Which three proteins that carry T4/T3 would you expect to be affected and what would thyroid levels be? |
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Definition
Transthyretin (T4), albumin (T3/T4), TBG – are all made in liver
conditions that alter TBG levels alter total T4 and T3, but do not alter free T4 and free T3.
Pregnancy (elevated estrogen)
Acute hepatitis
Chronic liver failure |
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Term
| T/F: T3 can bind specifically to DNA sequences (hormone response elements) generally located in the 5’ flanking regions of target genes leading to gene expression |
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Definition
| False: it must first bind to nuclear receptor proteins and T3 binds w/ 10fold greater affinity than T4. |
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Term
Which of the following do T3 Receptors bind to form heterodimers?
RXRs (retinoid x receptors), VDR, PPARs, steroid receptors RARs |
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Definition
| All except steroid receptors even though they are related to them… |
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Term
| What’s worse to have? Hypothyroidism or being genetically deficient of T3 receptors? |
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Definition
The former (hypothyroidism) b/c T3-occupied T3 receptors activate many genes and repress others (e.g. TRH, TSH)…Unliganded T3 receptors are not “neutral” - they repress genes that are activated by T3, and activate genes that are repressed by T3.
hypothyroidism causes greater abnormalities |
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Term
| Humans and rodents with hypothyroidism may also have low levels of which other hormone? |
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Definition
Humans and rodents with hypothyroidism have low growth hormone levels and do not grow as rapidly as normal.
The rat growth hormone gene contains a T3 response element. How T3 regulates human growth hormone is uncertain. |
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Term
Which level do we want to measure in looking at thyroid function…T3/T4?
What affect do chronic liver failure or pregnancy have on its levels? |
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Definition
T4 FREE not TOTAL!
Measure free T4, not total T4
Only free T4 is biologically active
Conditions that alter TBG alter total T4 but not free T4
Pregnancy raises total T4
Chronic liver failure lowers total T4
High in hyperthyroidism
Low in hypothyroidism |
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Term
| Serum Triiodothyronine (T3) levels in hypo/hyperth |
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Definition
High in hyperthyroidism
Low in hypothyroidism
But generally not worth measuring in hypothyroidism because T3 is less sensitive and less specific than the decrease in free T4
Not as influenced by changes in TBG as is T4, but measurement of free T3 is still preferable to total T3 |
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Term
| TSH levels low or hi...what does it mean? |
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Definition
TSH is HIGH in primary hypothyroidism; inappropriately “normal” or low in secondary and tertiary hypothyroidism
TSH is the most sensitive screening test for hyperthyroidism and primary hypothyroidism
TSH within the normal range excludes these diagnoses |
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Term
| Antithyroid antibodies such as Antimicrosomal antibodies against the antigen TPO or Antithyroglobulin antibodies are elev in hashimotos ____% of the time and Grave’s ____% so are not very helpful in making a diagnosis or guiding therapy…. |
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Definition
| Present in ~95% of Hashimoto’s and ~60% of Graves’ patients at the time of diagnosis |
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Term
| How can radioiodine uptake be used to identify the cause of hyperthyroidism and what can it be used for in treatment? |
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Definition
Used to evaluate the cause of hyperthyroidism
High if the thyroid is hyperfunctioning e.g. Graves’ disease
Low if thyroid hormone is leaking out of damaged thyroid cells (subacute thyroiditis) or the patient is taking excess exogenous thyroid hormone
Expressed as a NUMBER (e.g., 35%)
Used to calculate the dose of I-131 to treat hyperfunctioning thyroid tissue or cancer |
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Term
| Hot vs. Cold nodules seen in the thyroid scan? |
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Definition
Primary use is to determine whether palpated nodules are functional or non-functional.
“Hot” nodules concentrate the radionuclide and are essentially always benign.
“Cold” nodules are usually benign but are sometimes malignant. => NOT HYPERTHYROIDISM
The majority, perhaps 90%, of palpable nodules are cold. |
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Term
| A 35 year old working lady comes in with Nervousness, Diaphoresis, Heat intolerance, Palpitations; tachycardia, Insomnia, Weight loss, and Hyperdefecation.Describe the a) etiology of the disease, b) Genetic factors that may increase risk, c) if this patient were older >65yo what would she be at risk of? |
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Definition
Thyroid Stimulating Immunoglobulins (TSIs) bind to the TSH receptor and mimic the action of TSH.
Underlying defect probably lies with T lymphocytes, perhaps CD8 cells.
Increased risk of other autoimmune diseases.
MHC class II antigen HLA-DR3 increases risk ~3 fold
~50% concordance in monozygotic twins, ~5% concordance in dizygotic twins
Atrial fibrillation in older px |
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Term
| What two other findings are common and specific for Grave’s disease? You listen to her neck and you hear bruits and tell you attending that this Grave’s patient should have a carotid endarterectomy. What have you just done? |
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Definition
Graves’ ophthalmopathy
Graves’ dermopathy (pretibial myxedema)
You fucked up. Thyroid thrills or bruits
Increased thyroid blood flow causes turbulence |
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Term
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Definition
Gritty, dry eyes
Periorbital puffiness
Diplopia
Decreased vision |
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Term
| Graves’ Ophthalmopathy: Pathogenesis |
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Definition
Presumed autoimmune, likely due to shared antigens on thyroid and retroorbital tissue (possibly the TSH receptor).
Extraocular muscles enlarge with edema, glycosaminoglycan deposition, mononuclear cell infiltrate, and fibrosis. |
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Term
| T/F: Treating the hyperthyroidism of grave's disease gets good outcomes in treating the opthalmopathy. |
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Definition
F: Course independent of hyperthyroidism
Generally not influenced by treatment of hyperthyroidism
Therapy includes artificial tears, taping lids closed at night, glucocorticoids, orbital XRT, and decompression surgery but not during active disease! |
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Term
| You see Graves’ Dermopathy (Pretibial Myxedema). What's the reason for this? |
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Definition
Violaceous induration of pretibial skin
Glycosaminoglycan deposition
Rare, generally accompanied by eye disease
Usually asymptomatic
Therapy typically topical glucocorticoids |
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Term
Your sexually active, 25 yo patient presents with a low TSH, high free T4, decreased radioiodine uptake. What do you expect to find in this patient?
Thyroid stimulating antibodies present (could measure instead of RAIU)
Antithyroid (anti-TPO and Tg) antibodies often present
Painful post-infectious problem that radiates to the ears/jaw
Decreased levels of T3/T4 binding proteins |
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Definition
| #3 - subacute thyroiditis |
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Term
| The 35yo woman who came to see you receives a prescription for beta-blockers for palpitations. You prescribe her antithyroid drugs in the class of thionamides. What are 2 drugs and their mechanism of action? Which one is preferred for our patient and why? What are her outcomes? |
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Definition
Methimazole, Propylthiouracil (PTU)
Inhibit organification of iodine by TPO
PTU (high dose) inhibits type 1 deiodinase
PTU is preferred in severe hyperthyroidism such as thyroid storm. It is also preferred in hyperthyroidism during pregnancy. There have been cases of severe liver injury and death due to PTU (reported by FDA in 2009).
In typical hyperthyroidism PTU and methimazole are equally good but methimazole should be the first choice because of the liver injury and death due to PTU.
Do not influence the long term course of Graves’ disease.
~30% of Graves’ patients undergo spontaneous remission within ~1 year of diagnosis. Patients treated with antithyroid drugs are hoping to be in the lucky 30%. |
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Term
| Lupus-like syndrome, vasculitis, liver damage, agranulocytosis are rare complications of ________? what are common complications? |
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Definition
Antithyroid Drugs: Toxicity
Common (1-5%)
Rash, urticaria, fever, arthralgias |
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Term
| B-blockers used in grave's disease accomplish what? |
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Definition
Improve sympathetic overdrive type symptoms
Propranolol at high doses modestly inhibits T4 to T3 conversion (other b blockers don’t)
Do not lower serum T4 levels
Usual contraindications apply |
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Term
Your patient has asthma and Grave’s disease. Which medicines would you like to avoid?
Iodide, propanolol, methamazole, propylthioluracil |
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Definition
propanolol
Iodide notes: Rarely indicated
Rapidly lowers serum T4 and T3 by blocking thyroidal secretion
Can cause hyperthyroidism
Iodine can both cause and cure both hyperthyroidism and hypothyroidism!
Blocks radioiodine uptake |
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Term
Which of the following is false about radioiodine therapy vs. surgery?
I131 is safer and painless
Both require pretreatment with antithyroid drugs/b-blockers
The risk of complications such as hypoPTH or recurrent laryngeal nerve palsy is greater with surgery
I131 risks causing hypothyroidism during its slow treatment but surgery does not |
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Definition
| all but 2 are true. only surgery needs pretreatment |
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Term
What makes a nodule hotter than Jessica Alba?
Overproduction of thyroid hormone
Activating mutations of the TSH receptor
It happens in greater frequency than Grave’s
Positive TSI and anti-thyroid Abs
The smaller the size the more likely it is to produce TH |
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Definition
Adenomatous hot nodules are Less common cause of hyperthyroidism than Graves’ disease
In most patients, the nodule produces too little thyroid hormone to cause hyperthyroidism
Generally must be >2.5 cm to cause clinical hyperthyroidism (“toxic adenoma”)
Constitutively activating mutations of the TSH receptor are causative in many cases
Labs are similar to Graves’ disease except TSI and anti-thyroid Abs are negative. |
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Term
| Lab findings and treatment of Toxic Adenomas (hot nodules) |
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Definition
Labs are similar to Graves’ disease except TSI and anti-thyroid Abs are negative.
Spontaneous remissions are very rare.
Thionamides will lower T4 and T3, but will not lead to cure.
Therefore, preferred therapy is surgery or radioiodine.
The patient can be followed without therapy if she/he is euthyroid (normal TSH). |
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Term
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Definition
Thyroid has multiple nodules, some of which may be too small to palpate.
Some of the nodules function autonomously.
“Toxic” multinodular goiter signifies that the level of autonomous function is sufficient to cause hyperthyroidism. |
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Term
| An older woman presents with signs and symptoms of Grave’s disease. You palpate her neck and feel multiple nodules. What mutation causes this, the etiology, and what are good treatments and outcomes like. |
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Definition
Usually occurs in an older age group than Graves’ disease.
Generally the cause is not known, although some nodules have activating mutations of the TSH receptor.
Treat with radioiodine or surgery, as spontaneous remissions do not occur. |
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Term
| Phase of thyrotoxicity in subacute thyroiditis happens when? |
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Definition
A 30 y.o. woman had a respiratory illness a week ago, and now c/o rapid heart beat, sweating and neck pain, especially noting tenderness to touch.
This is typical of subacute thyroiditis.
Leakage of thyroid hormone from damaged thyroid cells, rather than increased synthesis, is the cause of thyroid hormone excess.
Therefore, the radioiodine uptake is low.
Resolves spontaneously after 2-3 months.
Thyrotoxic phase may be followed by a hypothyroid phase, also lasting 2-3 months. |
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Term
| A patient comes in with severe neck pain and you are puzzled b/c he has had a period of palpitations and heat intolerance but now no longer. What medicines can you use to treat each? |
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Definition
The thyrotoxic and/or hypothyroid phases may be asymptomatic.
If needed, use beta blockers to treat the thyrotoxic phase.
If needed, use levothyroxine to treat the hypothyroid phase.
If needed, use NSAIDs for neck pain.
This disease also is called subacute painful thyroiditis, De Quervain’s thyroiditis, subacute granulomatous thyroiditis, and giant cell thyroiditis. |
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Term
| His friend has had similar problems but no pain and comes in to you see you…What tests should you run on her? |
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Definition
Silent, or painless, subacute thyroiditis is similar in clinical course to painful subacute thyroiditis, except there is no neck pain.
Autoimmune etiology with lymphocytes infiltrating the thyroid.
Since a small, symmetric goiter is common, painless subacute thyroiditis must be distinguished from Graves’ disease by laboratory testing. |
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Term
| Non-thyroidal Illness Syndrome - etiology and labs |
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Definition
Also called the sick euthyroid syndrome.
Definition: decreased serum T3 (total and free) caused by non-thyroidal illness rather than thyroid dysfunction.
TSH usually is normal but can be low in severe cases.
T4 and free T4 usually are normal but can be low in very severe cases. |
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Term
| A patient comes in having been quite sick with a bacterial infection and on examination you find signs of hypothyroidism. You run his TSH but surprisingly you find that it’s normal.What’s going on and how do you go about treating it? |
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Definition
Non-thyroidal Illness Syndrome
Occurs with virtually any acute or chronic illness, e.g. infections, myocardial infarction, chronic renal failure, surgery, trauma.
Inhibition of 5’ deiodinase causes the low serum T3.
TSH secretion is “inappropriately” normal.
Underlying mechanisms are poorly understood. |
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Term
| T/F: it is important to treat the hypothyroidism course of the life-threatening sick euthyroid syndrome with thyroxine therapy. |
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Definition
F: Prognosis: Full recovery when the non-thyroidal illness resolves.
Therapy: It is currently felt that patients do not benefit from attempts to normalize serum T3 levels.
It is important to know of this syndrome so as not to confuse it with secondary hypothyroidism. |
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