Thyroid Clin Med

Foramen cecum location of Thyroid cells before they migrate thru the thyroid duct to sit IN ANTERIOR NECK.
Thyroid duct cyst remnant cells of thyroid that didnt migrate.
Histology
Follicular cells surround the colloid.
Colloid contains TG that helps in scaffolding for the thyroid hormone
Parafollicular cells found between the follicular cells make calcitonin. ARE NOT however involved in production of
thyroid hormone
HPA Axis
Drop in thyroid hormone(+) Hypothalamus TRH(+) AP to release TSH (goes thru blood) to thyroid to produce
T3/T4
Negative Feedback: Too much T3/T4 will inhibit production at hypothalamus or at the AP
**TSH is more clinically relevant and measurable b/c it circulates thru the blood and thus can cause systemic
effects; Unlike TRH which does not circulate in the blood.***
Iodine
-Thyroid is the only place that requires Iodine for normal functioning
Thyroid synthesis within the Thyroid follicular cell
1. Iodine trapping symporter brings in I- into follicular cell; Simultaneously TG is being made in the follicular
cell from tyrosine residues.
2. Thyroid peroxidase (TPO)
a. Oxidation- catalyzes oxidation of I- I2;
b. Organification- binds tyrosine residues + I2 MIT + DIT is bound to the tyrosyl residues (TG with I
attached (MIT and DIT) ).
c. Coupling of iodotyrosine molecules put MIT + DIT = T3 (biologically active) or DIT + DIT= T4
i. ****Note: PTU/Tapizole inhibit this step to block production of T 3 and T4
3. Proteolysis Cleavage of T3/T4/MIT/DIT from TG. TG stays in the follicular cell along with left over MIT/DIT
for reuse.
4. Deiodination via 5iodinase into:
a. T3
b. T4
rT3- used to balance the mount of T3 that is in the blood5t is taken back into the follicular cell via
endocytosis
c. Exocytosed into the blood
Pathology to Thyroid synthesis
Both have same etiology: Excess iodine brought in thru symporter
Wolff Chaikoff effect
Normal Wolf-Chaikoff effect: excess iodine shuts down symporter for ~72 hours and then returns
to normal
Pathologic Wolff Chiakoff entity: inhibition of symporter never returns to normal. Ends in
hypothyroidism
a. Can be caused by Amiodarone [ stated by Barone not Haedel]
2. Jod Basedow effect- Sees iodine load and it just churns out thyroid hormone.
a. Autoimmune predisposition. Never have normal effect of the symporter to shut down. So excess Ijust results in hyperthyroidism b/c symporter doesnt exist.
3. ***Underlying thyroid problem (genetic predisposition, family hx) causing these pathologic problem***
Hormone Transport
Unbound vs Bound
Unbound =Free T3/T4
Bound= Hormone: Protein + T3/T4 **99% of thyroid hormone is bound ***
Total = Bound + Unbound
Total t3/t4= bound + unbound
1. Thyroid binding globulin: carrier protein transports T3 and T4
a. ***Made In the liver**
b. Acts in circulation
2. Transthyretin
3. Albumin
a. Dysalbuminemic familial hyperthyroxinems
i. Abnormal over production of circulating proteins (albumin or usually more TBG) . More
albumin attached to T3/T4
ii. If you measure a Total T3/T4 (Bound hormone to T3/T4)it would be high (due to increased
bound T3/T4)
iii. But T3/T4 have not increased , its just the protein that has increased. Patient is
Euthyroid.
iv. Clinically: Patient is Euthyroid b/c TSH/T3/T4 levels will be normal.

v.

b.

Not imp today b/c wouldnt pick up in TSH normally, normally measure unbound T4
(metabolically active)
T4 longer half life = 7 days
i. Give for hypothyroid b/c last longer in the blood
ii. Thus give Levothyroxine (Synthetic T3)

c.

T3 half life = 1 day

Hypothyroid
Problem in the thyroid gland- low levels of T3/T4
AP continually tries to stimulate thyroid but thyroid will not respond. Thus,
1. Increased TSH low T3/T4
Etiology
1. MCC: Hashimotos Autoimmune destruction of thyroid
i.
MC in women.

Note autoimmunity is common in women.

ii. Pathology: HurthelCells
2. Iodine deficiency decreased Iodine then cannot even make thyroid
3. Medications
i.
Lithium blocks cleavage
ii. PTU/Tapazone- blocks synthesis of T3/T4

Used to treat hyperthyroidism if give etoo much then you can induce
hypothyroidism
iii. Amiodarone

Made up of 35% iodide. High content

Body thinks you have excess I- so it can cause

o
Wolf Chiakoff induces hypothyroidism
o
Excess I- used for production of T3/T4

Causes hypothyroidism via Wolf chikoff effect causeses excess I-.

iv. Radioiodine treatment for hyperthyroidism

I-123 nuclear imaging of the thyroid

I-131 used to ablate thyroid cells via beta/gamma cells

Path class: Radioiodine treatment- give the person I-131 and they uptake it
has hyperthyroid/ Graves and if decreased uptake then have thyroiditis
(Hashimotis)

v. Surgery

Thyroidectomy remove thyroid thus no production of thyroid hormone

vi. Central

Problem at Hypothalamus do not make TRH so cannot make TSH/T3/T4

vii. Postpartum

During preganancy you have immune suppression

After pregnancy we have surge in autoimmunity to make up for lost time

and can induce destruction of thyroid.
viii. Subacute Granulomatous (DeQuervains thyroiditis)

Have viral infection (GIT,Viral, MC:URT)

o
Sx; pain in the neck, increased temperature, inflammation

Transient hyperthyroidism (Results from inflammatory destruction of thyroid

follicles will cause release of thyroid hormone)
o
Release of colloid as foreign body produces granulomatous
inflammation in the thyroid

Bx: giant cells (granulomas made up of macrophages

makes sense b/c have a viral infection)

Hypothyroidism presents later b/c when the increased levels of thyroid

hormones decreases you have an abnormal drop
ix. Reidels: rock hard, woody thyroid- caused by extensive fibrosis of thyroid
x. Thyroid hormone resistance
xi. Cessation of L-thyroxine: go off of your leveothyroxine (T4)- come off the meds and
become hypothyroidism
Symptoms
- THINK: Thyroid regulates metabolism
- Hypothyroidism: Decrease in thyroid hormones, thus decrease in metabolism.
What do you see w/ decreased metabolism?
1. Weight gain, cold intolerance, fatigue

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3.
4.
5.
6.
7.
8.
9.
10.

Constipation
Myalgia
Depression
Skin, hair, nail changes
Depression
Hyporeflexia
Bradycarida
Hypothermia
Myxedema thickening of skin and soft tissue
a. Myedema coma profound changes in metal status

Treatments for hypothyroidism

I.
Levothyroxine, T4
a. ATA/Endorince associated: Recommendation for this as replacement
i. T4 is readily is deiodinated by deiodinases to T3.
Levoxyl
Synthorid
o
MC used
Unithroid
Levothroid
II.
Triiodothyronin, T3
4. Cytomel
5. Dessicated Armour
i.
Pig / cow hormone hyoid thyroid gland; Problem: considerly more potentially
antigenic reactions.
ii. Not entirely T3, has some T3 in it.
Bunevicius, NEJM, Feb. 1999
1. Improved psychomotor sx w/ decrease in levothyroxine w/ added cytomel. (T4+T3)
2. Trend toward T3 helping psychomotor sx.
- Replacement therapy: Subclinical Hypohtyroidism
-subclinical relating to dz that is not severe enough to present w/ readily observable sx.
- Evaluate s/sx to see if really have hypothyroidism
- Look at Autoimmune markers [Also used to dx Autoimmunity at level of the thyroid, not necessarily
pathologic]
1. antimicrosomal Ab (antiperoxidase) - Hashimotos patinets
2. Antithyroglobulin Ab seen in 65% of Hashimotos
3. If seen give replacement therapy
-No s/sx but have TSH just educate, dont treat
EuThyroidal
-

Illness
Seen in hospitals due thru illness causing stress on your body.
Thyroid being the regulator of metabolism that it is, will try to conserve E to help fight off the illness.
This causes TRH TSH T3/T4
Free T3 will be low for many reasons
1. Downregulation at level of Hypothalamus to TRH
2. Downregulation of monoidoinase that converts T4T3
Upregulation of monoiodinase involved in T3rT3 = Elevated rT3
Gold standard to test for euthyroid illness: Elevated Rt3
Self limiting will no need to treat.

Replacement in Pregnancy
What happens in pregnancy?
1. Increase in TBG levels due to two mechanisms:
i.
estrogen (+) Liver to make more TBGTBG
ii. Carboxylation of TBG that leads to decrease in renal clearance

Sugar moiety sticks to the TBG and makes it a more bulky molecule that
the kidney cannot clear so you have less TBG excreted and more TBG
retained in your body
iii. OUTCOME OF INCREASED TBG: Thyroid gland will need to make more Thyroid
hormone to occupy the increased available receptor sites on the TBG.
2.
Increase in total T4 because we have TBG, which will increased Bound T4.
3. Normal pregnancy requires in Thyroid hormone production by a normal Thyroid gland, so
you will already get TH replacement for this.
i.
Pathologic: Thyroditis or Thyroidectomy pregnancy

TH replacement that you are already giving her due to her pregnancy
requirements will increase by 50%

4.
5.

Stable free T4 because these patients are not hyperthyroid to begin with the problem is TBG.
Low TH levels due to HCG during pregnancy
i.
HCG has similar structure to TSH. Since we increase HCG body thinks we have
enough TSH and it shuts down production of thyroid hormones, thus body is in
hypothyroid state.
ii. Therefore pregnant patient will require TH replacement to fix low thyroid levels.

Assessment of Replacement Therapy

Gold standard: Ultrasensitive TSH assay
1. Helps you identify if replacement therapy is working
If pt has pituitary/hypothalamus problem default use to: Free T4 to evaluate thyroid levels.
***Note: TSH undergoes a carboxylation also, where a sugar is bound to it. If it
is inappropriately bound it can make the TSH will not work properly in the body. TSH assay
doesnt look for the sugar moiety. So you can have adequate immunoassay activity (TSH looks
normal on the assay (b/c you are only measuring amount but do not have normal
bioactivity****
Cascade/reflex to free T4.
1. Get blood sample and run levels of TSH
i.
If TSH is normal: Get report of the measured levels of TSH
ii. If TSH is abnormal: the machine will automatically reflex and takes that same blood
and runs a free T4. (Benefit: Pt will not have to get restock bc you can resue the
same blood sample)
-

Pregnancy
1. Look at TSH + Free T4
i.
1st trimester TSH hard to interpret

4 molecules with similar appearances: LH, FSH, TSH, HCG

o
o

unit
Differ in unit; This confers functional/activity differences.

***This is why we run a HCG.*** IN PREGNANCY.

SAME

ii.

Weeks 10-12 When HCG is VERY HIGH:

Since similarity in HCG and TSH during pregnancy.

o
HCG can bind to TSH receptor and can fool the body into thinking
that there is high levels of TSH = Molecular mimicry

Looks like patient is hyperthyroid, when really they could

have low TSH.

So, free T4 becomes valuable.

Pituitary surgery: measure free T4 + total T3
1. TSH levels would not be accurate b/c some parts of pituitary may be removed, so measure
free T4 and possible total T3.
i.
Do not do free T3 b/c too expensive and take too long.
ii. Free T4 more readily available!!!
Thyroid cancer look at TSH (we want to induce suppression) + free T4 (want to make sure that the
low TSH isnt inducing more free T4 + TG (marker for disease recurrency)

Hyperthyroid
Definition: Excess T3/T4
T3/T4 = hyper so feedback is TSH
Etiology:
1. Graves Diseas
i.
MCC hyperthyroidism
ii. Pathogenesis: autoimmune disease: where Ab stimulates the TSHr. the TSHr
iii. Symptoms Triad:

Goiter,

Exopthalmus,

Pre-tibial myxedema
o
Due to deposition of GAGs
iv. Increase uptake of I-123 b/c the I- symporter is intact.
2. DeQuervains Thyroidtis
i.
Pain in neck caused by viral infection
ii. Pathogenesis: destruction of the follicular cells.
iii. Low I-123 uptake b/c there is destruction of the follicular cell so no uptake.
iv. Transient hyperthyroid hypothyroid
3. Hamburger toxicosis
i.
Pt took amour thyroid
ii. Neck meat used to make the meat for the burger had some

4.

Apathetic thyrotoxicos: Unusual presentation of hyperthyroidism in older patients, that looks

like they are hyperthyroidsm
i.
Appear depressed (which makes it weird, they should be bouncing off the walls in
hyperthyroidism presents as hypothyroid
Symptoms
1. Everything speeds up
i.
Tachy (RISK FOR A FIB)Weight loss heat intolerance
ii. Acropatchy
Treatment want to treat the symptoms
1. Betablockers want to slow the heart rate.
i.
MC: Propanolol
ii. Decrease conversion of T4T3
2. Thionamides
i.
PTU (Propythiouracil)
o
MOA: blocks the synthesis of T3/T4
o
Also blocks conversion T4T3
ii. Tapazole (Methimazole)

USE: MC: 1st line DOC for hyperthyroidism

MOA: Blocks the synthesis of T3/T4

iii. TEST QUESTION: S/E: Agranulocytosis (low WBC), drug induced hepatitis, cutaneous
eruption
3. Radioiodine treatment
1. I-123- nuclear imaging ( gamma)
2. I- 131 ablation
Surgery Thyroidectomy
1. Use KI (Lugols solution)- to temporarily immunosuppress the thyroid by inducing
Wolfchicoff syndrome, it overloads the thyroid w/ I- and shuts off the thyroid.
i.
Pharm: Decreased the vascularity of the gland and size so that it easier to
take out.
Pregnancy treatment
1. Pregnant with hyperthyroidism
2. PHARM: 1ST Trimester GIVE PTU, cannot give Methimazole b/c baby is at risk for cutis aplasia
i.
Further on in the pregnancy give Methimazole
Pharm: breastfeeding post partum- Methimazole is a better choice to avoid
liver side effects.

EVALUATION OF THRYOID NODULE

Goiter- enlarged thyroid gland, due to iodine deficiency
Nodule bump on the thyroid that can be benign or cancerous
Who is at risk?
Women : MC have nodules most are benign
Males with nodule are at higher risk for cancer.
Person exposed too radiation increased risk for thyroid nodules and risk for carcinoma
1. MCC thyroid cancer = paipillary cancer
Prognosis of thyroid cancer: Good b/c slow growing cancer
History

<20 years age or >60 (MC in elderly)

Males higher risk of cancer
Family hx (not heavy influence)
1. MEN2A/B linked to Medullary cancer and Ret Oncogene.

Differential Diagnosis
Colloid (adenomatous) nodules
Follicular adenomas
Malignant
Thyroid cysts
Physical examination
1-2cm can be palpated
o
Any nodule can be malignant each must be evaluated independently
Local, asymmetric adenopathy
o
MC thyroid cancer is papillary that spreads t/o the lymph nodes and can cause adenopathy.
o
This can be concerning for thyroid cancer.

Labs
-

TSH most sensitive for thyroid function

Serum calcitonin = carcinoma of parafollicular cells (which produces calcitonin)
1. This is sign for Medullary thyroid cancer
Radionucleotide imaging
1. I-123: to see imaging
a. Graves increased uptake
b. Dequervains- decreased uptake
2. ****This not tell you whether it is benign or malignant ***
Ultrasound
1. Benign
a. Multiple
b. Halo
c. Cystic
2. Margins
a. Smooth = benign
b. Irregular, asymmetric Malignancy
3. Calcification:
a. Rim of calclification= Benign
b. Stippling calcification= malignant
4. Tall vs wide
a. Tall cancer
b. Wide benign
5. Vascularity
a. Increased vascularity cancer
b. Decreased vascularity benign
Fine Needle Aspiration Biopsy
c. Adenoma Benign
i. Papillary MC- slowest growing and treatable
1. Pathogenesis: metastasis of lymphatics DOES NOT
d. Carcinomas
i. Papillary
ii. Follicular
1. MC in post 40 year old age group
2. Pathogenesis :Metastasis lymphatics or the Blood can go to the bone
iii. Medullary
iv. Anaplastic
e. Caveat: Follicular: Cannot distinguish adenoma vs carcinoma b/c cant tell whether it has
invaded the capsule.
f.
Most thyroid cancer have genetic mutations in DNA
i. Do testing abnormal RNA expression: benign bc the mutation is in RNA not DNA.
Treatment:
Cysts- generally benign you aspirate but most likely refill
Benign nodule L Thyroxine
1. Annual followup
2. US and re bx
Malignant
1. Surgery do bx
2. L- thyroxine suppression
i.
Cause the TSH to decrease.
Bethesda system for reporting cytopathology
#2 Hurthel cell, Hashimoto - benign
#6 is malignant- see Orphan Annie Eyes, nuclear inclusion and psamommma = Papillary carcinoma

MEN/PGA
History
Dr. Werner found a family that had multiple endocrine growths and peptic ulcers: All which had the symptoms of
Ca2+, Pituitary tumors, Kidney stones, Pancreatic tumors
Test question: Peptic ulcers and son with acromegaly, What is treatment? Calcitonin, GH, and cortisol free urinary
levels.

MEN (Multiple Endocrine Neoplasias)

Definition:: group of benign or malignant tumors in endocrine tissue that can be inherited
Tumor Types
1. Functional tumor secrete hormones
2. Nonfunctional tumor Do not secrete hormones
***Note: All MENs are Autosomal dominant***
Test: Know all the MEN syndromes and what tumors they have!!!
How to remember MEN syndromes?
MEN 1 = 3Ps
MEN 2a= 2Ps
MEN 2b = 1P
MEN 1 = 3 PS Pity-Para-Pan
Pituitary Adenoma
-rarely malignant
1. Functional
THINK: Adenoma of the ANTERIOR PITUITARY (thus, secretion of AP hormones)
o
Prolactin secreting leads to Prolactinoma
o
Labs: Order a Prolactin level
o
GH secreting Acromegaly
o
Order GH or IGF-1
o
ACTH secreting leads to Cushings
o
Order ACTH or Cortisol
o
LH/FSH secreting
o
TSH secreting
2. Non-functional
Parathyroid hyperplasia (hyperparathyroidism)
****MC feature of MEN 1 syndrome = distinguishes MEN1 from MEN2***
o
PTH important for calcium homeostasis
o
Stimulataes reabsorption of calcium in DT of kidneys
o
Stimulates activation of vit D
o
Primary Hyperparathyroidism: PTH Ca2+
o
Hyperparathyroidism 2* to MEN, causes a 4 gland hyperplasia
o
Presents to 2nd-4th decade of life
Pancreatic Tumor
o
Neuroendocrine Tumors [THINK of what gets secreted from the pancreas]
o
Gastrinoma

Malignant

Association with Zollinger-Ellison Syndrome

Severe peptic ulcer dz causesd via hypersecretion of gastric

acid

Tumor secretes gastrin causing hypergastrinemia, peptic ulcers and

diarrhea
o
Insulinoma

MC Sx: Obesity: due to overeating to prevent hypoglycemia

o
Glucagonoma
o
VIPoma
o
Somatostatinoma
o
Nonfunctional pancreatic tumor