THYROID DISEASE-III -THYROID DEFICIENCY TREATMENTS

HYPOTHYROIDSM-THYROID UNDER ACTIVITY

This is the inability of the thyroid to secrete sufficient quantity of hormone needed by the body.This is ranges from mild and clinically unimportant to moderate to severe.When the condition go to extreme it may result in life threatening myxedema coma.

Classifications

Primary  1.This is due to tissue damages or malfunctions of the gland by diseases,or destructive therapies such as over or toxic radiations by radio therapies,and mistaken surgeries.

2.Under development and under maturity of the gland by incompetence or congenial.e.g cretinism

Secondary This is a passive inactivity of the gland by not get enough or nil stimulation by TSH secretion from the pituitary gland.In this the gland is healthy but there may be some problem at the anterior pituitary- gland axis and thereby no secretion of the TSH from the pituitary gland.This may be due to some disease in pituitary gland.

Tertiary In this even if both thyroid and pituitary glands are healthy there may be some problem or defects at the hypothalamus pituitary axis so that there is no hypothalamus secretion of Thyrotropin Releasing Hormone (TRH), to stimulate anterior pituitary to release TSH to stimulate thyroid.

Causes

Hashimoto's thyroditis This is an autoimmune condition in which gland is ineffective as its hormones are inactivated by circulating lymphocyts.This condition is chronic and the gland is damaged by lymphocytes,a kind of WBCs as our body's own immunity.

Toxic treatments of Hyperthyroidsm This may be due to careless and toxic radio iodine treatment of hyperthyroidsm,partial removal of the gland,and over administrations of anti thyroid agents.

Surgical damages

Goiter 1)Endemic goiter this condition develops due to the insufficient or zero intake of dietary iodine supplements.This is common in the region where there are soils devoid of iodine contents.

2)Sporadic goiter This is due to the high intake of foods drugs especially herbal medicines containing a chemical known as Progoitrin which is inactive but will be hydrolysed and converted by our body to the active Goitrin.

Goitrin prevent the oxidation of iodine to iodide and blocking the uptake of iodide by the colloidal thyroglobulin to synthesize the hormone.

Vegetables like cabbage,cauliflower,mustard,spinach,brussels,sprouts,peanuts,horse radish and kale are found to be containing more progoitrin.

Drugs such as Propyl thiouracil,iodide,phenylbutazone,cobalt and lithium are said to be goitrogenic

3.Acute thyroiditis,nodules,nodular goiter and thyroid cancer are also said to contribute hypothyroidsm but to a lesser extend.

Symptoms 1)A the start,signs of lethergy,followed by fatigue,forgetfulness,cold like feelings,weight gain without any proper cause,and difficult tight motion.

2)If not properly attended at the beginning the disease will progress further leads to signs of myxedema will surface such as dry flaky inelastic skin,coarse hair,slowed speech and thought,hoarseness,puffy face,hands and feet.Eyelid loop,hearing loss,menorrhagia,impotence,decreased libido, finally losses all reflexes ends in coma.

TREATMENTS

Treatments are mainly based on replacement therapy by drugs

Desiccated thyroid preparations-Variant ratio preparations

In olden days the desiccated thyroid preparation were considered as drug of choice but slowly they lost its favour as more favourable synthetic safe and fast therapeutic agents such as synthetic levothyroxin preparations are available.

Eventhough the desicated thyroid preparation met the USP creteria they are not bioequivalent as their T-3 and T-4 contents are varying.The contents are variying according to their source of preparations.Porcine gland preparations were having higher T-3 to T-4 variations when compared with the preparations from ovine and bovine sources.
Fixed ratio preparations
These are synthetic preparations in order to minimize the variations of the ratio of T-4/T-3.and they almost mimic the glandular functions.In these preparations T-3 component are almost unnecessary because of its disadvantages like tremor,headache,palpitations and diarrhea.Hence preparations like Levothyroxin (Levothroid,Synthroid,and Levoxyl) contains only T-4 and hence the disadvantages of T-3 are nill.Eventhough these contains only T-4 after consumption the body would convert it to T-3 and get the glandular benefits with minimum side effects.Hence these preparations are the drugs of choice.
The average adult maintenance dose is 75 to 150 mic.gm/day for Levothroid and Synthroid.
The dose range is shown to be 1.5 to 1.7 or an average of 1.6 mic/kg/day.for otherwice healthy patients.
Elderly or longtime ill patients require 50 to 100 mic.gm/day as an average dose.
Thyroxin levels become normal within a few weeks and full recovery may be seen after 3 to 6 months.
Precautions and monitoring effects to the patients
1.Adult patient with a history of heart problems should begin with a low dosage like 25 mic.gm/day and gradually increase the dose after 3 to 4 weeks to 100 mic/gm/day. 
2.Patient should be watched for cardiac arrhythmias,palpitations,and anginal pain on initiating the therapy. 
3.Serum T-4,RT-3U,and TSH levels should be monitored.FTI should also to be monitored.
4.Sensitive TSH test should be observed 2 to 6 months after the last dosage is recommended .However the test continue to change for 1 year. Testing early may result into over treatment.
5.Long time Levothyroxine may precipitate hyperthyroidsm;even at the recommended constant dosage T-4 level may increase to induce thyrotoxicosis and hence monitor carefully.
6.Patients receiving replacement therapy with low TSH values may have lower bone mineral density since the excess hormone accumulation may have the effect on the bone resorption to the boneformation equillibrium to result in bone fracture.
7.Cholestyramine a bile acid cholesterol reducing drug may lower the bioavailability of thyroxine on co-administration.
Mixedema coma The most serious emergency situation of hypothyroidism claims high mortality rate.
Common in elderly patients and in patients with under estimated diagnoses.
Precipitating factors are alcohol,sedatives and narcotic uses;over use of anti thyroid agents;
Abrupt discontinuation of thyroid hormone therapy.
Infections;
Exposure to extreme cold temperatures;
Toxic radiations;
Thyroid surgery.
Symptoms
The patient will fall from lethargy to coma.
Hypothermia,and a fall in respiration follows.
Decrease in metabolic rate leads to fluid retension 
Decrease in sodium level.
Decrease in heart rate.
Treatments include rapid restoration of T-3 and T-4 levels to normal
Desiccated thyroid preparations can be tried with risk.More preferably the synthetic Liothyronine (Cytomel)is reseved for the treatments of Myxedema coma.
A loding dose of 400 to 500 mic.gm is given as an I.V. bolus.followed by a maitenance dose of 25 mic.gm is given orally every 6 hrs.
Treatment should be continued until improvement is noted.Then Levothyronine is discontinued followed by the Levothyroxine with the maitenance dose of 100 mic.gm/day.

THYROID DISEASES-II -FTI TESTS

FREE THYROID INDEX TEST-FTI

This is an estimation of free thyroid hormone most importantly T-4 which is the major contributor of the thyroid secretion but minor contributor of the effects of thyroid.

Usually the secretion of T-4 is more in hyperthyroidism and less in hypothyroidism as there may not be much change in the secretions of T-3.

Hence T-4 estimation which is freely circulating in the blood is very important index of assessing the patient's condition.Even though the effects of thyroid is mostly contributed by T-3 it is not important to asses it as a factor because most of the T-3 conversions from T-4 happens only in circulation and not within the thyroid gland

Also this not a separate test rather an estimation of T-4 level which is freely circulating in the blood by mathematical relationship between Resin Triiodothyronine Uptake(RT3U) and serum T-4 levels as follows

FTI = TT-4 x RT-3U/mean serum RT-3U

TT-4 = Total serum T-4;

FTI is higher in hyperthyroidism in which TBG the thyroxin binding globulin is less and vice versa
Alternatively thyroid functions can be assessed by TSH test.TSH the thyroid stimulating hormone is secreted by the pituitary gland according to the thyroid functions.
If pituitary secretes high TSH secretions which elevates the serum TSH level above the normal that means the thyroid gland is underacting which is known as Hypothyroidism.
But if the pituitary secretions of TSH is less which is reflected by the depression of serum TSH level then it means the thyroid gland is over acting which is known as Hyperthyroidism
The normal range of serum TSH level is 3.9 to 4.6 milliunits/Liter.(American Thyroid Association)

THYROID DISEASES-I

THYROID-A VIEW

The thyroid gland which is looking like a butter fly with  spreaded wings is situated in the anterior(front side)of the neck or throat just below the laryngeal prominence (Adam's Apple).It contains two lobes on either side spreaded like the wings of a butterfly.

Thyroid gland is one of the largest ductless gland (endocrine) in our body and it controls many important body functions such as rate of use of energy sources.protein synthesis and controls the body's responses to other hormones.

The thyroid gland synthesizes,stores and secretes hormones which are controlling and participating the processes like growth and protein anabolism.These hormones are as follows:-

1.Tetraiodo thyronine or thyroxine (T-4)-Less active-More stable-and Major secretion of the gland

2.Triiodo thyronine (T-3)-More active-Less stable-Minor secretion of the gland.

A portion of the thyroid gland is secreting a hormone known as calcitonin which is controlling calcium metabolism.

The sequences of thyroid secretion of hormones are as follows,

In our brain system there is a gland like a peanut known as thalamus.Below the thalamus a minute part of the brain is known as hypothalamus which is controlling all our endocrine systems including thyroid.

Hypothalamus secrets a hormone known as Thyrotropin Releasing Hormone(TRH) which inturn stimulates anterior pitutary gland to release Thyrotropic Hormone or Thyroid Stimulating Hormone(TSH) which inturn stimulate thyroid gland to secrete its hormones T-4 and T-3 which on free circulation will send the negative feed back signals to the anterior pitutary to stop to secret the TH.The process will continue like a cycle.Thus the amount of the free circulating hormones are maintained in a constant level.

Synthesis Thyroid hormones are synthesised by thyroid gland by combining tyrosine with the available iodine.

Iodine containg foods like sea foods are essential for the synthesis of thyroid hormones.The food release in the plasma iodide in an inorganic form.

Before synthesis starts a process of manipulating the iodide ion by a process known as the organification which involves the iodide oxidised by peroxidase and bound to tyrosyl residues within the thyroglobulin molecule as follows

1.The inorganic iodide from the plasma is trapped by the gland and the process is known as iodide pump

2.The inorganic iodide has to undergo the organification after thatTyrosine combines with iodide to form Mono Iodo Tyrosine(MIT)

3.MIT binds with another iodide ion to form Di Iodo Tyrosine(DIT)

4.Two DIT couples to form the stable T-4,the Thyroxin

5.One MIT and one DIT couples to form the unstable T-3 which is highly active

Hormone Transport
1.After the gland get stimulated by TSH (Thyrotropic Hormone or Thyroid Stimulating Hormone) from the anterior pituitary gland the T-3 and T-4 are cleaved from the thyroglobulin and released into the blood circulation.
2.In the blood the hormones are bound up with plasma proteins like thyroxine binding globulin (TBG),Prealbumin and Albumin in order to protect them from inactivation by early metabolic processes.These protein carriers help the hormones to reach the site of action very easily.
Metabolism Mostly occur at pituitary,liver,and kidney by conversion of 80% of T-4 into T-3.
The active T-3 is responsible for 99% of the thyroid activity in our body and its abnormal elevation and fall are the complete representations of thyroid dysfunctions.
T-3 is further degraded step by step by a process of deiodization finally converted to thyronine and excreted in feces and urine.
Functions of thyroid hormones
1.Growth
2.Delelopment of our body
3.Energy production by increasing the rae of basal metabolism.
4.Tissue sensitivity to hormones like adrenalin and there by affecting cardio vascular system like increasing heart rate,blood flow,cardiac out put,metabolic rates
5.Increasing the activity of nervous system.
6.Causing tremour.
7.Thyroid over activity may cause sleepiness and tired
8.Thyroid underactivity may cause somnambulance.
9.Affecting lipid meabolism.
Thyroid tests-A.Serum Total T-4 Test.
1.Radio immuno assays these tests more sensitive and rapid to assay total thyroxine T-4.which will indicate the total availability of hormone to the tissues.
Unless otherwice not affected by other factors like pregnancy kidney failure,or liver damage an elevated Total T-4(TT-4) may indicates Hyperthyroidism and a dippressed T-4 may indicate Hypothyroidism
Serum total T-3 Test
This sensitive and most specific test indicates measure of TT-3.
This test is more accurate and help early detection in hyperthyroidsm as the elevation of TT-3 is immediate and more quicker than TT-4.Many of the symptoms of hyperthyroidsm is due to the elevation of TT-3.
But on the contrary in hypothyroidism this test is not reliable as even though there is a fall in TT-3 but will stay at the normal level.In rare case the TT-3 may be low.These test may also mislead by those factors which affect the test result of TT-4.
Resin T-3 uptake(RT,U)
This test will clarify whether the abnormal T-4 levels are due to thyroid disorder or a disorder by protein uptake because it evaluate the binding capacity of TBG
This test read more accurate changes of the abnormal levels of the hormone in the blood.
Serum Thyrotropin(TSH) and Sensitive TSH Assays
a)Serum Assay This assay results are more reliable and sensitive as the hypothalamus - pituitary axis is more sensitive in responding even a minute variations of the circulating blood thyroid hormones to release or stop the TSH.This axis is very sensitive to indicate hypothyroidsm as a small dip in the blood hormone will receive a quick compensatory response from the hypothalamus - pituitary axis.
The TSH levels may be elevated even much before the TT levels are dipped and very useful and easy to detect Hypothyroidsm in advance.
This test is not reliable to asses Hyperthyroidsm as the hypothalamus-pituitary axis is varyingly responding to the elevated TT in plasma
Sesitive Assay This is an advanced technology using immunoradiometric methods instead of the old radioimmune assay and is very expensive.This is the most occurate method of detecting thyroid defects.
This is a very useful test to monitor paients receiving hormone replacement therapy to control hormone over exposures,since over exposure to thyroid hormones may precipitate unwanted elevation of liver enzymes,bone demineralizations and ECG effects.