Friday, May 4, 2012

What are thyroid hormones?

Glands such as the thyroid secrete chemical messengers (hormones) into the bloodstream. These messengers circulate to specific target organs and induce a response. Such messengers produced and secreted by the thyroid gland are called as thyroid hormones. 

Levothyroxine or L-thyroxine is one such hormone and this hormone contains four iodine molecules leading to the name T4. The thyroid also produces triiodothyronine, T3, which is identical to thyroxine except that instead of four iodine molecules T3 contains only three iodine molecules and thus leading to the name T3. 

Thyroid hormones are the same regardless of the species; T4 is the same in frog, dog, pig, sheep, or cow as in humans. In man, eighty to ninety percent of the thyroid hormone produced and released is T4; the reminder is T3. 

The thyroid also secretes another hormone, calcitonin, in very low amounts, this is produced from the para-follicular (C-Cells) of the thyroid gland. The main function of "Calcitonin" is that it acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone (PTH) which is secreted from the four para-thyroid glands behind the thyroid gland.

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What is Thyroid Binding Protein (TBP)?

Thyroid hormones circulate bound to binding proteins (TBP) which lead act as a reservoir and lead to stable levels of thyroxine (T4). 

Facts about thyroid hormone values
  • 99.98% of T4 is bound to protein in circulation.
  • 99.8% of T3 is bound to protein in circulation.
  • The half life of T4 is 7-8 days, it means it takes this length of time for the levels of T4 to fall from its original value to one-half of its basal value.
  • The half life of T3 is about 1 day. 
  • Circulating levels of T4 are 10 times higher than that of T3.
  • Unbound T4 is called Free T4 (FT4) and is about 0.02% of T4.
  • Unbound T3 is called Free T3 (FT3) and is about 0.2% of T3.
  • Only the free hormones are metabolically active and free to bind to target tissue.
  • The TBP acts as a equilibrium control system. 
  • Normal levels of Serum T4 (Bound T4) range from 5ug/dL to 12ug/dL.
  • The reference levels depends on the type of assay but in general can be estimates as - Free T4 (unbound T4) is about 1000 times less than the Bound (T4).
  • Since it would take this long for the levels to fall, a change in dose of oral thyroxine dosage in patients ( thyronorm or eltroxine) would minimum require 4-6 weeks to reach a stable dose and therefore is required only after that. This is the main reason why - thyroid levels are tested only after 6 weeks of initiating a dose for evaluation of the doses effects in the patient.    
(note: this article should not be read in isolation and if more understanding about the thyroid function and the hormone production is required please go through the other articles in this blog. Dr Ajith Joy k)

Effects of Hyperthyroidism & Hypothyroidism



The Mechanics of Thyroid Hormone Secretion

The thyroid hormones T4 & T3 are secreted from the thyroid gland under the control of the hormone called TSH (Thyroid Stimulating Hormone) released from the anterior part of the pituitary gland situated just below the Hypothalamus in the brain. The TSH is in turn controlled by the hormone TRH (thyrotropin releasing hormone) secreted by the hypothalamus. When there is enough T4 & T3 in circulation a negative feedback is sent to the pituitary and the hypothalamus to stop the stimulus signal and thus the over production of these hormones are limited and controlled. The whole system works in a rhythm and so does the actions exerted by the thyroid hormones on the target tissue.
  
Hyperthyroidism: A situation where the thyroid gland starts functioning autonomously and continuously producing T4 & T3 in excess, beyond or irrespective of the control of the brain.

Hypothyroidism: A situation when the production of T4 & T3 hormones by the thyroid gland is subnormal, due to any reason. The reasons could be Thyroiditis, Iodine deficiency, surgical removal of the gland or destruction of the gland due to any cause. There could also be other reasons like birth defects in children or central hypothyroidism due to the lack of production of pituitary hormones like TSH or lack of effectiveness of produced hormones due to some defect.    

What ever the cause the effects of Hyperthyroidism & Hypothyroidism are as follows:
   Article compiled by Dr Ajith Joy K, email: joyajith@gmail.com  

History of Iodine deficiency in Goiter & Iodine as a treatment

"Jean-Francois Coindet a doctor in Geneva, introduced iodine into the treatment of goitre in the year 1820. This was eight years after the discovery of iodine in the year 1813."

This short factual sentence epitomises an important advance in medicine. It seemed to be of some interest to try to unravel how this breakthrough was conceptualised, prepared and implemented, and to review some of its early consequences. Iodine had only been discovered seven or eight years earlier, its role in thyroid physiology was completely unknown, and the cause of goitre was still conjectural, so it took imagination, intellectual courage and determination to complete such a study. 
Coindet guessed that iodine was the substance in burned sponge that had been found to be effective in the treatment of goiter for at least seven centuries.

Coindet first communicated the results of his iodine treatment for goitre to the Société Helvétique des Sciences Naturelles in Geneva on July 21, 1820. His work became widely known from the three articles (1820-1821) he published in his Bibliothèque Universelle (Geneva). The first and the second articles also appeared in the Annales de Chimie et de Physique (Paris), the journal in which the discovery and the characteristics of iodine had previously been published, and they were widely translated. 

Coindet used three different preparations, a solution of potassium iodide, an iodide-iodine solution somewhat different from the one that Lugol later defined, and an alcoholic (tincture) solution that Coindet later was to recommend as the safest and easiest to use. Twenty drops of these solutions contained approximately 50 mg (one “French grain”) of iodine. Coindet routinely prescribed 10 drops three times a day for the first week, and then 15 drops thrice a day for the second week and 20 drops three times a day subsequently. He only rarely prescribed higher doses. The recommended duration of treatment was 8-10 weeks. Results of the treatment were spectacular: softening and shrinking of goitres occurred after 8 days, and disappearance or a significant improvement in disfiguring or uncomfortable goitres occurred later in many cases. In addition, he observed iodine had a general stimulating effect on the appetite, the uterus (?), acted as an aphrodisiac, and he concluded that, used with competence, iodine would become one of the most potent medication brought to medicine by modern chemistry ! 

Following Coindet's enthusiastic report on the efficacy of iodine, a craze for taking iodine rapidly developed in Geneva and elsewhere. The general public and more than a few physicians regarded it as a nostrum, and rapidly, ill-effects from taking iodine were observed.

In February 1821, J-F Coindet published an article concerning precautions and justification of iodine treatments. He reported that he himself had treated 150 patients, in robust health, and had not observed serious complications in any of them. Because of the public uproar about the ill-effects seen with iodine, in January of 1821 he requested the physicians, surgeons and pharmacists in Geneva to convene at City Hall to officially confirm that in these patients no serious ill-effects of iodine had been observed. Impressed by the aggressive effect of iodine on goitres, and recognising its potential danger, Coindet insisted that the dose of iodine be closely controlled, that patients be followed weekly and that the treatment be short-term. He also would not give iodine to subjects who were frail or nervous. Indeed, most of the complications which raised the iodine controversy – and discredited its use – had not occurred in Coindet’s patients, although his description of one of his own patients resembled what we would now consider a typical case of relapsing iodine-induced thyroiditis. Coindet noted that in several patients who had been given iodine by others and who had developed iodine-induced hyperthyroidism — his description being so classical that M. Greer suggested Jod-Basedow should be renamed Jod-Coindet – the symptoms improved rapidly after he treated them essentially by withdrawing iodine.

In contrast to the controversy that lingered in Geneva, Coindet received wide recognition for his work abroad. A thoughtful review in the Edinburgh Medical and Surgical Journal in 1824 stated : “…The physicians and surgeons of France, of Italy, of Germany, and of England have, since the publication of Dr. Coindet’s memoirs in 1820 and 1821, been zealously occupied, in hospital or in private practice, in ascertaining the powers of iodine, and observing its effects; and though, perhaps, in some respects, it has been misapplied, and in others its virtues have been overrated, it cannot be doubted that it possesses strong claims to the attention of the bold and judicious practitioner”. In 1831, J-F Coindet was awarded a major prize by the Paris Academy of Sciences. 

Who truly discovered iodine?

Marine sponges and other marine species had been used since antiquity to treat goitre. In 1815 – a time when Jean-Charles Coindet was an active member – Andrew Fyfe reported to the Royal Society of Edinburgh that sponge contained iodine. However, Fyfe did not publish his findings in the Edinburgh Philosophical Journal until 1819. Coindet very carefully pointed out that he had an intuition that iodine could be the active anti-goitre substance contained in the ashes of marine sponge and seaweeds 6 months before the publication of Fyfe’s findings. However, it is not unlikely that his son Jean Charles had already told his father about Fyfe's findings in 1815.

Iodine was discovered in Paris in 1811 by B. Courtois, the son of a saltpeter manufacturer from Dijon. During the extraction of sodium and potassium from the ashes of seaweed, in the presence of an excess of concentrated sulphuric acid, he noticed the release of a violet vapour which condensed on cold surfaces to form brilliant crystalline plates (12). With the chemist C.B. Désormes, Courtois reported the discovery in 1813. In 1813, H. Davy, who had been admitted to France with a special passport from Napoléon (despite the Continental Blockade) was given some iodine crystal by Gay-Lussac. Davy, perhaps unsportingly, competed with Gay-Lussac to be the first to report that iodine was a new element. Later during the same visit to the Continent, Davy spent 3 months in Geneva in 1814, where the discovery of iodine was widely discussed.  

(The above history was in part extracted from the published details of History of modern thyroidology by the European thyroid association. Thanks to the authors of the article in making this information public and in detail.) 

Preparing for a 131 Iodine Whole Body Scan after Thyroidectomy for Cancer Thyroid


131 Iodine Whole body scan of a 28 year Female patient with papillary carcinoma of the thyroid gland after near total thyroidectomy. The faint blue - black color seen in the neck region signifies functioning residual thyroid tissue. The patient had a thyroglobulin value of 26 ng/ml and the patients TSH was 92uIU/ml

The 131 iodine whole body scan is usually performed after good preparation by administering a 2-3mCi of 131 iodine whole body capsule and the scan is acquired at 48 - 72 hours post administration. What you see above is the image of such a scan.  

What should be the preparation of such a patient be?

When a whole body iodine scintigraphy or scan is done for a patient after thyroidectomy (removal of the thyroid gland surgically) for thyroid cancer, it should be delayed for about 4 weeks from the time of surgery to allow endogenously secreted thyroid hormones to be metabolized and give time for the TSH (Thyroid Stimulating Hormone) secreted by the pituitary gland to rise to near 100 uIU/ml levels. 
  • The patient should not have been administered with iodine contrast for a CT contrast study prior to surgery, which is currently never used and is only employed when the primary presentation is with some systemic condition other than thyroid swelling or nodule. If used the patient should wait about 3 months before the 131 iodine whole body scan to be done. 
  • The other precaution is for the treating surgeon not to start the patient on Thyroid Hormone Supplements (Eltroxin or Thyronorm) immediately after surgery and to refer such patients to a nuclear medicine department for 131 iodine scan appointments preferably in the second week of surgery with the - discharge summary, thyroid biopsy slide & block, and the histopathology report. If a patient was started on thyroid medications then the patient has to stop these medication for about 4 weeks before the scan to allow - TSH hormone to rise to near 100 values. 
  • After an appointment is given for an iodine 131 Whole body scan the patient is advised as follows as part of the preparation for the scan.
  1. A low iodine containing diet is recommended for 2 weeks prior to the scan and continued until the therapy is over - if the therapy date is further from the date of the scan. Ideally a therapy to be scheduled on the same day as the scan is taken is ideal in reducing the post therapy stunning if any. This is generally seen in >5 mci doses of 131 Iodine being used for whole body scans, currently a standard dose of today's practice is to use is a 2-3mCi dose for a whole body iodine scan which negates this possibility. The best ablative results are obtained when the patient is ablated within 3 months post surgery. 
  2. The patient should avoid Iodized salt and sea salt during this period as in [preparation for scan and therapy. this is to prevent the non radioactive iodine from blocking the 131 radioactive iodine from visualizing residual thyroid tissue or metastasis in the whole body scan. 
  3. Numerous milk and dietary products are fortified with iodine and the patient should avoid any sort of fortified food - to be safer it is best to avoid these as part of preparation. 
  4. Patients may also avoid Eggs, Seafood, Kelp, Breads with iodated dough conditioners, red food dyes, and restaurant foods since the content of iodine in these foods are also difficult to quantify and may vary in huge quantities.
  5. The aim of this preparation is to successfully reduce urinary iodine to 50ug/day. A normal iodine excretion in urine would be 100 ug/day anything below 75ug/day would be considered as iodine deficiency. This means the patients iodine pool is depleted and when 131 iodine is administered to the patient it will or most likely pick up all the residual functioning thyroid tissue in the body. 
  6. Normal faint uptakes of iodine are seen in the slavery glands, oral or nasal mucosa, stomach, colon urinary bladder. The liver 5-10 days after the administration of  radioactive iodine shows uptake and this is because the radioactive hormones produces are metabolized in the liver. 
  • Dr Ajith Joy K, Consultant Nuclear Medicine Physician.        

Thursday, May 3, 2012

What is the Thyroid Gland

The thyroid derives its name from the Latin word meaning "Shield". It looks like an old shield but in its true state it looks more like a butterfly. The thyroid is located just in front of the wind pipe (trachea). The normal thyroid consists of 2 lobes the left and the right lobe, placed on either side of the wind pipe which is connected by a bridge of thyroid tissue called the isthmus. Sometimes there is an additional thyroid tissue in the form of a tail found jutting upwards on the mid-line from the isthmus this is called the pyramidal lobe. Each lobe is about 1.5 to 2 inches (4-5cm) tall, 0.6-0.8 inches (1.5-2 cm) wide and 0.8-1.2inches (2-3 cm) in thickness. The total weight of the adult thyroid gland ranges from 0.35-0.87 ounces (10-25gms) in weight. The thyroid gland is a very vascular organ and in general has a reddish brown color. If one were to look at the microscopic structure of the thyroid gland, it would look like tiny, hollow, micro-spheres called follicles. Each of these tiny ball like structures has a central core containing a proteineous material called colloid surrounded by an outer lining of epithelial (follicular) cells. Sparsely scattered among the follicles are para-follicular cells, or C-cells that comprise much less than 0.1% of the the total number of thyroid cells. 

The thyroid has 2 types of different cells and they have a different embryonic origins. The follicular cells develop from the endodermal pharyngeal pouch and the para-follicular (C-Cells) originate from the ectodermal neural crest tissue. This is the differentiation that leads to the clinically important distinctions in the types of thyroid cancers that are encountered. The well differentiated cancers of the thyroid gland called the papillary & follicular carcinoma of the thyroid gland (90% of all thyroid cancers) originate from the follicular cells. The medullary carcinoma of the thyroid originates from the par-follicular cells or the C-Cells of the thyroid gland and consists of about 5% of all thyroid carcinomas. The rarest types of thyroid cancers of the thyroid gland are, the anaplastic type (1%), lymphoma and other metastatic types.    

The thyroid functions as an endocrine organ or gland. That is the thyroid gland produces hormones and secretes them into the blood, where they circulate and later bind with specific target tissues. The thyroid secretes these hormones: L-thyroxine (T4), L-triiodothyronine (T3), and calcitonin. The follicular cells produce T4 & T3 and the para-follicular cells produce Calcitonin.   

Hypothyroidism: A disorder when the thyroid gland does not produce enough (or normal) levels of T4 & T3 as is required by the human body to function properly. Causes of hypothyroidism can be Thyroiditis (Hashimotos Thyroiditis, Lymphocytic Thyroiditis), Congenital Hypothyroidism, Post Partum (Pregnancy) Hypothyroidism, after thyroidectomy (thyroid surgery), or a simple Iodine deficiency Hypothyroid state. 

Hyperthyroidism: A condition when the thyroid gland produces excess thyroid hormones than what is required in normal conditions. Here the circulating T3 & T4 levels are much higher than what is required or normal. The gland generally is detached from the control of the brain and starts to function autonomously, and does not depend on the TSH (thyroid stimulating hormones) produced by the pituitary gland as the basis of T3 & T4 production. TSH levels in the circulation is normally suppressed and is in the range of 0.1 - 0.001 uIU/ml. 

Thyroid Cancer: A condition when the thyroid gland or a nodule or growth inside the gland starts to grow uncontrollably and becomes malignant and invades the sourrounding structures. Cancers originate from different cell types and are of the specified type as mentioned above.

Dr Ajith Joy k
Consultant Nuclear Medicine Physician
Thyroid Cancer Specialist
4A-4H Aster Square, Ulloor, Trivandrum,
 Kerala, India. PIN: 695011
joyajith@gmail.com, 
Clinic Number : +91 9633275251, 944777508

www.thyroclinic.com 
www.healthcafe.in
www.ceevees.org/kimsddnmrc