Thyroid gland

The thyroid gland consists of two bulky lateral lobes connected by a relatively thin
isthmus ,usually located below and anterior to the larynx .The thyroid is divided by
thin fibrous septae intolobules composed of about 20 to 40 evenly dispersed
follicles,lined by a cuboidal to low columnar epithelium ,and filled with Pas-positive
thyroglobulin.In response to hypothalamic factors,TSH (thyrotropin )is released by
thyrotrophs in the anterior pituitary into the circulation.The binding of TSH to its
receptor on the thyroid follicular epithelium results in conformational change and
activation of the receptor ,allowing it to associate with a G (S) protein.Activation of
the G protein eventually results in an increase in iintracellular cAMP levels , which
stimulates thyroid growth,and hormone synthesis and release via cAMP dependent
protein kinases.The dissociation of thyroid hormone synthesis and release from the
controlled influence of TSH-signalling pathways results in so-called thyroid
autonomy and hyperfunction.
Thyroid follicular epithelial cells convert thyroglobulin into thyroxine (T4) and lesser
amounts of triiodothyronine(T3).T4 and T3 are released into the systemic
circulation,where most of these peptides ae reversibly bound to circulating plasma
proteins ,such as thyroxine binding globulin and transthyretin,for transport to
peripheral tissues.The binding protiens serve to maintain the serum unbound
(free) T3 and T4 concentrations within narrow limits yet ensure that the hormones
are readily available to the tissues.In the periphery,the majority of free T4 is
deiodinated to T3;the latter binds to thyroid hormone nuclear receptors in target
cells with tenfold greater affinity than does T$ and has proportionately greater
activity.The interaction of thyroid hormone with its nuclear thyroid hormone
receptor (TR)results in the formation of a multiprotein hormone-receptor complex
that binds to tyroid hormone response elements(TREs)in target genes,regulating
their transcription.Thyroid hormone has diverse cellular effects, including upregulation of carbohydrate and lipid catabolism and stimulation of protein synthesis
in a wide range of cells.The net result of these processes is an increase in the basal
metabolic rate.One of the most important functions of thyroid hormone is its critical
role in brain development in the fetus and neonate.
The function of the thyroid gland can be inhibited by a variety of chemical
agents,collectively referred to as goitrogens.Because they suppress T3and T4
synthesis,the level of TSH increases,and subsequent hyperplastic enlargement of
the gland(goiter) follows.The antithyroid agent propylthiouracil inhibits the oxidation
of iodine and this blocks the production of the thyroid hormones,parenthetically
,prophyluracil also inhibits the peripheral deiodination of circulating T4 into T3,thus
ameliorating symptoms of thyroid hormone excess.Iodine when given to individuals
with thyroid hyperfunction,also blocks the release of thyroid hormones but through
different mechanism.Iodines in large doses inhibit proteolysis of
thyroglobulin.Thus,thyroid hormone is synthesized and incorporated within
increasing amounts of colloid,but it is not released into the blood.
The thyroid gland follicles also contain a population of parafollicular cells,or C
cells ,which synthesizes and secrete the hormone calcitonin.This hormone promotes

the absorption of calcium by the skeletal system and unhibits the reabsorpbtion of
bone by osteoclast.
Disease of the thyroid include conditions associated with excessive release of
thyroid hormones(hyperthyroidism),those associated with thyroid hormone
deficiency (hypothyroidism),and mass lesion of the thyroid.We first consider the
clinical consequences of distributed thyroid function ,then focus on the disorders
that generate these problems.
Hyperthyroidisme
Thyrotoxicosis is a hypermetabolic state caused by elevated circulating levels of
free T3 and T4.Because it is caused most commonly by hyperfunction of the thyroid
gland,it is often referred to as hyperthyroidism.However,in certain conditions the
oversupply is related to either excessive release of preformed thyroid hormone or to
an extrathyroidal source,rather than hyperfunction of the gland.Thus,strictly
speaking hyoerthyroidism is only one (albeit the most common)cause of
thyrotoxicosis.The terms primary and secondary hyperthyroidism are sometimes
used to designate hypertiroidism arising from and intrinsic thyroid abnormality and
the arising from the processes outside of the thyroid,such as TSh secreting
pituitary tumor.With this caveat ,we will follow the common practice of using the
terms thyrotoxixosis and hyperthyroidism interchangeably.The three most common
causes of thyrotoxicosis are also associated with hyperfunction of the gland and
include the following:
-Diffuse hyperplasia of the thyroid associated with Graves disease (accounts for
85% of cases).
-Hyperfunctional multinodular goiter
-hyperfuncitonal adenoma of the thyroid
The clinical manifestations of the hyperthyroidism are protean and include changes
referable to the hypermetabolic state induced by excess thyroid hormone and to
overactivity of the sympathethic nervous system(i.e, an increase in the betaadrenagic tone).
Excessive levels of throid hormone results in an increase nin the basal metabolic
rate.The skin of thyrotoxic patients tends to be soft ,warm and flushed because an
increase blood flow and peripheral vasodilation to increase heat loss.Heat
intolerance is common.Sweating is increased because of the higher levels of the
calorigenesis.Increased basal metabolic rate also results in characteristic weight
loss despite increased appetite.
Cardiac manifestation are among the earliest and most consistent features of
hyperthyroidism.Individuals with hyperthyroidism can have an increase in cardiac
output,due to both increased cardiac contractility and increased peripheral oxygen
requirements.Tachycardia,palpations and cardiomegaly are common.Arrhythmias
,particulary atrial fibrillation occur frequently and are more common in older
patients.Congestive heart failure may develop,particulary in elderly patients with

preexisiting cardiac disease.Myocardial changes ,such as foci of lymphocyctic and

eosinophilic infiltration,mild fibrosis in the interstitium,fatty changes in
myofibers,and an increase in size and number of mitochondria,have been
described.Some individuals with thyrotoxicosis develop reversible left ventricular
dysfunction and low output heart failure,so called thyrotoxic cardiomyopathy.
In the neuromuscular system ,overactivity of the sympathetic nervous system
produces tremor ,hyperactivity ,emotional lability,anxiety ,inability to
concentrate,and insomnia.Proc=ximal muscle weakness and decreased muscle
mass are common (thyroid myopathy).

Ocular changes often call attention to hyperthyroidism.A wide,staring gaze and lid
lag are present because of sympathetic overstimulation of the levator palpabrae
superiors.However ,true thyroid opthalmopathy associated with proptosis. Is seen
only in Graves disease.
In gastrointestinal system ,sympathetic hyperstimulation of the gut results in
hypermotility,malabsorption and diarrhea.
The skeletal system is also affected.Thyroid hormone stimulates bone
resorptiom,increasing porosity of the cortisol bone and reducing the volume of the
trabecular bone. The net effect is osteoporosis and an increased risk of fractures in
patients with chronic hyperthyroidism.
Other findings include atrophy of skeletal muscle ,with fatty infiltration and focal
interstitial lymphocytic infiltrates; minimal liver enlargement due to fatty changes in
the hepatocyctes ; and generalized lymphoid hyperplasia and lymphadenopathy in
patients with Graves disease.
Thyroid storm is used to designate the abrupt onset of severe hypertiroidism.This
condition occurs most commonly in patients with underlying Graves disease and
probably from an acute elevation in catecholamine levels,as might be encountered
during infection,surgery ,cessation of antithyroid medication,or any form of
stress.Patients are often febrile and present with tachycardia out of proportion to
the fever.Thyroid strom is a medical emergency;A significant number of untreated
patients die of cardiac arrhythimias.
Apathetic hyperthyroidism refers to thyrotoxicosis occurring In the elderly,in whom
advanced age and various co-morbidities may blunt the typical features of thyroid
hormone excess seen in younger patients. The diagnosis is thyrotoxicosis in these
individuals is often made during laboratory work up for unexplained weight loss or
worsening cardiovascular disease.
A diagnosis of hyperthyroidism is made using both clinical and laboratory
findings.the measurement of serum TSH concentration using sensitive TSh assays
provides the most useful single screening test for hyperthyroidism ,since its levels
are decreased even in the earliest stages,when the disease may still be subclinical.A
low TSH value is usually confirmed with the measurement of fee T4,which is

expectedly increased.In occasional patient, hyperthyroidism results predominantly

from an increased circulating levels of T3 (T3 toxicosis).In these cases,free T4
levels may be decreased,and direct measurement of the serum T3 may be useful.In
rare cases of pituitary-associated (secondary )hypethyroidism ,TSH levels are either
normal or raised.Determining TSsh levels after the injection of thyrotropin-releasing
hormone(TRH stimulation test ) is used in the evaluation of cases of suspected
hyperthyroidism with equivocal changes in the baseline serum TSH level.A normal
rise in TSH after administration of TRH excludes secondary hyperthyridisme.Once
the diagnosis of thyrotoxicosis has been confirmed by a combination of TSH assays
and free thyroid hormone levels,measurement of radioactive iodine uptake y the
thyroid gland may be valuable in determining the etiology .For example,there may
be diffusely increased uptake in the whole gland(Graves disease ).increased
uptake in a solitary nodule (toxic adenoma),or decreased uptake (thyroiditis).
The therapeutic options for hyperthyroidism include multiple medications ,each of
which has a different mechanism of action.Typically ,these include a beta-blocker to
control symptoms induced by increaded adregenic tone,a thinamide to block the
new hormone synthesis ,an iodine solution to block the release of thyroid
hormone ,and agents that inhibit peripheral conversion of T3 to T 4.Radioiodine
,which is incorporated into thyroid tissues ,resulting in ablation of thyroid function
ever a eriod of 6 to 18 weeks ,may also be used.