Thyroid Pathophysiology

Hypothalamic-Pituitary-Thyroid Axis
This is a negative feedback system. TRH produced in the paraventricular nuclei of the
hypothalamus stimulates release of TSH from the pituitary.
TSH stimulates thyrocytes to pump in iodine. Then there is organification of iodine by thyroid
peroxidase. This forms T3 and T! "hich is stored as colloid. T secretion ## T3 secretion.
$ost T3 is formed peripherally! by deiodination of T. T3 is far more active! T is a prohormone.
%onversion of T to T3 is inhibited by starvation! illness! drugs &amiodarone! contrast dyes'.
$ore than (() of T3 and T in blood is bound to Thyroid Binding Globulin (TBG) and albumin.
*nly free hormone is active.
++%hanges in the level of binding proteins such as T,- alters total T3 and T4 but not free hormone.
T3 acts at nuclear receptors to stimulate %H*/fat metabolism! glycogenolysis! thermogenesis!
protein synthesis! myocardial contractility! oxygen delivery! digestion! and sympathetic
activity. 0t is critical for normal gro"th and metabolism.
Assessing Thyroid Function
The most common hormone measurements are free T4 and TSH.
These have an inverse loglinear relationship! in "hich TSH varies logarithmically "ith T.
**Therefore, the TSH level is the most sensitive index of thyroid function.
**o! TSH suggests hyperthyroidism. High TSH suggests primary hypothyroidism.
1l"ays rely on the TSH levels above other lab results.
1lso! do not evaluate thyroid function during acute illnesses! "hich may artifactually suppress TSH.
&Raymond removed images of TRH/TSH/T3/T regulation.'
Hypothyroidism
This is a deficiency of thyroid hormone! "hich is almost al!ays due to thyroid gland dysfunction
(primary hypothyroidism). Rarely! it can be caused by central &secondary' hypothyroidism.
Signs of hypothyroidism include2
33cold intolerance 33bradycardia! hypo3reflexia
33fatigue! lethargy 33anemia
33decreased metabolism! "eight gain 33constipation! hypoosmolar hyponatremia
33brittle nails! dry skin 33amenorhhea! galactorrhea
33myxedema 33myalgia! arthralgia
1utoimmune &Hashimoto4s' Thyroiditis
**The most common cause of hypothyroidism is autoimmune "Hashimoto#s$ thyroiditis.
*ther causes include iodine deficiency and iatrogenic &post3surgical/radiation/drug therapies'.
1utoimmune thyroiditis involves lymphocytic infiltration of the thyroid "ith production of
antithyroid pero"idase &anti3T5*' and antithyroglobulin &anti3T-' antibodies.
1utoimmune thyroiditis is associated "ith other autoimmune conditions including 6$7 and vitiligo.
0t has a marked female predominance.
-alactorrhea and amenorrhea occur because lo" levels of T3/T fail to inhibit the hypothalamus!
"hich secretes high levels of TRH. This stimulates the pituitary to release lots of prolactin.
*ther causes of primary hypothyroidism
7. 6rug3mediated inhibition of thyroid hormone production &5T8! lithium! amiodarone'.
9. 5eripheral thyroid hormone resistance &Refetoff4s Syndrome'! caused by defective T3 receptors.
6iagnosis of Hypothyroidism
++%n primary hypothyroidism "&''($, TSH levels will be elevated, and free T4 will be low!
1utoimmune thyroiditis is confirmed if there are anti3T5* or anti3T- antibodies present.
&Raymond removed images of drug3mediate hypothyroidism and TSH levels in primary
hypothyroidism vs thyrotoxicosis.'
Hyperthyroidism ) Thyrotoxicosis
Thyrotoxicosis is an excess of thyroid hormone.
Hyperthyroidism is an excess of thyroid hormone caused by overactive thyroid tissue.
Hyperthyroidism is almost al"ays &#(()' a primary thyroid problem.
Signs of hyperthyroidism include2
33heat intolerance! insomnia 33anxiety! irritability! tremor! hyper3reflexia
33increased metabolism! "eight loss 33hyperdefecation
33palpitations! tachyarrythmias 33hypercalcemia! hypercalciuria
33"arm moist skin! s"eating 33gynecomastia
-raves4 6isease
**The most common cause of hyperthyroidism is *raves# +isease.
-raves4 6isease is an autoimmune disease in "hich thyroid stimulating immuglobulins (TS#s)
bind and activate the TSH receptor on thyrocytes.
-raves4 6isease occurs mostly in 7:33: yo females.
Some particular signs of -raves4 6isease include2
7. -raves4 ophthalmopathy &proptosis! extraocular muscle fibrosis! retroorbital fat/edema'
9. 5retibial myxedema &non3pitting edema'
3. Thyroid achropachy &clubbing of the digits'
1ll of these signs are caused directly by the TS#s$ not the e"cess thyroid hormones. So these signs
are seen in Graves% &isease but not thyroto"icosis. 1lso! removing the thyroid gland to
correct the hormone imbalance !ill not correct Graves% ophthalmopathy or my"edema.
*ther causes of primary hyperthyroidism
7. To"ic 'denoma! a single large autonomously functioning hyperplastic thyroid nodule.
9. To"ic (ultinodular Goiter! a gro"th of multiple autonomously functioning hyperplastic nodules.
3. Subacute thyroiditis! often preceded by a viral illness and causing e")uisite thyroid gland pain
that radiates to the ;a" and ears. *adionuclide upta+e is very lo!.
. ,ymphocytic ('utoimmune) thyroiditis! "hich may have a period of hyperthyroidism follo"ed by
hypothyroidism. This oftens occurs postpartum. *adionuclide upta+e is very lo!.
6iagnosis of hyperthyroidism
**%n primary hyperthyroidism "&''($, TSH levels will be low, and free T4 will be elevated.
0f there is hyperthyroidism but no signs of -raves4 6isease! use radionuclide testing.
Radionuclide Testing2
33high radionuclide uptake < high thyroid activity < hyperthyroidism
33lo" radionuclide uptake < lo" thyroid activity < non3hyperthyroid thyrotoxicosis
&thyroiditis$ or pharmacologic-dietary inta+e of thyroid hormone'