Thyroid Disorders

Introduction 

Thyroid abnormalities affect women more than men, around 5 % of the population suffers from this disorder of the endocrine gland. This condition has a diverse manifestation because of the thyroid gland’s involvement in cellular differentiation and proliferation in virtually all nucleated cells of the body.

Thyroid Physiology

Thyroid gland consists of two lobes and secretes two active hormones, T3 and T4.

thyroid-disease-1

T3- Tetra-iodothyronine ( T4, Thyroxine ) and Tri-iodothyronine. The TRH (tripeptide thyrotrophin-releasing hormone regulates TSH and TSH, in turn, regulates T3 and T4. Therefore low secretion of T3 and T4 can stimulate the release of TSH and can stimulate TRH too.

The follicular cells are the production site for T3 and T4.  The mechanism is a bit complex but we have tried to make it simpler.

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Iodine is transferred and using iodinase enzyme forms Monoiodotyrosinase (MIT) and Di-Iodotyrosine (DIT), subsequently forming T4, the coupling of two DIT residues forms T4 and T3 is formed by coupling a DIT and an MIT residue.

Hormones are stored in follicular cells until the release into circulation. Thyroglobulin is reabsorbed into follicular cells, hydrolyzed and its amino acids, iodine are reused.

Laboratory Tests and Investigations

1. Ultrasonography– increases the chances of detecting thyroid disorder, especially the nodular ones, which can especially not be detected by physical examinations. Usually, 10-MHz instruments, spatial resolution and high-quality imaging can detect nodular cysts greater than 3mm. Ultrasound is also used for detecting thyroid cancer, which can include the possibility of cervical lymph nodes.

  1. Hypothyroidism
  • Symptoms such as fatigue, impaired memory, constipation, cold intolerance, changes to skin or hair
  • Physical examination- coarse features, dry skin, hypothermia, bradycardia, delayed relaxation of reflexes.
  • TSH alone is good for screening primary hypothyroidism, other tests such as free tiiodothyronine (fT3),
  • Free thyroxine, antithyroid peroxidases (anti-TPO) antibodies test
  1. Hyperthyroidism

Thyrotoxicosis is a condition when excessive thyroid hormones rise up, subclinical hyperthyroidism can give rise to atrial fibrillation due to its effect on metabolism and heart rate (TSH is suppressed while thyroid hormone levels are normal ). Treatment is necessary when the patient’s age is more and the frial or if he/she has osteoporosis.

Some causes of Thyrotoxicosis can be,

Grave’s disease- Due to thyroid stimulating immunoglobulins activating the TSH, antibodies for thyroid receptor is usually elevated.

Subacute thyroiditis- Scanning of the gland is low

Toxic Nodule- On scanning the gland, it will show as a hot area

  1. TSH, ft3, ft4
  2. Thyroid receptor antibodies (TRAb) if the diagnosis is not clear
  3. Thyroid scan (scintigraphy), contraindicated in pregnancy cases
  4. Radioactive iodine uptake

 

Non Pharmacological Therapy 

Surgery is an option where Grave’s disease is confirmed. Surgery is a part of management in cases of ectopic production of the hormone. Ectopic means when a fetus is developed outside the uterus.

To make the patient euthyroid (normal) is tried so that further complications can be avoided.

 

Pharmacological Therapy

Methimazole and Propylthiouracil are two drugs used to counter thyrotoxicosis, although evidence suggests that it might not work on every patient, therefore thyrodectomy may be important.

The reason why these drugs are administered before the surgery is that it will reduce the vascularity of the gland and chances of bleeding will reduce. Lugol’s solution is also given before the surgery to prepare the patients. Radioactive  Iodine can reduce the symptoms in 2 to 7 days.

Adverse effects include – agranulocytosis ( decrease in the number of white blood cells ) , this is a serious condition. Symptoms like hay fever, sore throat, skin rash, headache can occur due to decrease in the number of neutrophils, basophils, and eosinophils.

  • exfoliative deratitis
  • granulocytopenia
  • aplastic anemia
  • hypoprothrombinemia

Iodism can also occur if the level if iodine is not thought of. It can give the patient metallic taste in the mouth and throat, sore teeth and gums.

  • soreness of parotid glands, burning of mouth
  • symptoms of heat and cold
  • gastrointestinal upset
  • difficulty in breathing ( requires immediate medical attention)

Radioactive Iodine 

  • swelling of neck
  • sore throat
  • nausea
  • cough
  • pain
  • bone marrow depression
  • leukopenia
  • thrombocytopenia
  • tachycardia

Contraindications 

During pregnancy and lactation methimazole and propylthiouracil are contraindiacted.

Radioactive Iodine comes under Category X

Dosing

Thyroid Hormone– 1.6 μg/kg/day average adult dosing

LT4 – Levothyroxine– alone is considered treatment of choice for replacement of thyroxine hormone where deficiency is observed, dosing adjustment is done every 4-6 weeks, if needed, in the older patients if doses are increased it can raise the risk of fracture.

LT3- Triiodothyronine- is a short term management for patients undergoing cancer withdrawal of L-T4 when recombinant  TSH is not an option.

Methimazole–  10-30 mg daily po in 2-3 divided doses, higher doses are sometimes needed. If the patient has thyroid storm- upto 40 mg BID

Propylthiouracil – Initially 50-100 mg thrice po in most cases, dose to be adjusted in renal failure. Thyroid storm, doses upto 1200 mg daily in divided doses.

 

Hypothyroidsm  and  Pregnancy 

Women who already have thyroid levels as low , should increase the dose to two tablets a day after a positive test of pregnancy. TSH levels are low during first trimester which is because of high HCG levels, the test should be repeated and measured again to know the levels.

During pregnancy thyroid binding globulins can increase during pregnancy hence the dose of Levothyroxine will increase  to maintain TSH levels. TSH has to be monitored for better control.

TSH should be between < 4 mU/L, and should it  exceed 10 mU/L, therapy can be initiated.

If the patient is on iron supplements, it can interfere with levothyroxine requirements, therefore a time gap of 6 hrs has to be there.

Patient has to be told and educated about supplementation of Levothyroxine during pregnancy, it is needed both for the mother and for the fetal development.

Referral to endocrinologist is recommended if despite the treatments the TSH doesn’t return to normal.

Therapeutic Tips

  • Consistent dosing of medication is neccessary
  • Myxedema coma is a medical emergency which relates to dropping down of hypothyroidism too low, symptoms of hypotension and low level of consciousness are observed. 300-400 μg iv initially is recommended and thereafter 100 μg iv daily with concomitant corticosteroids such as 100 mg Q8H iv.

 

Hyperthyroidism during Pregnancy 

Grave’s disease giving rise to high levels of Thyroxine is most likely in pregnancy.

Near the upper limits of normal range should be the target area of fT3 and fT4. Untreated or under treatment could lead to fetal loss.

Methimazole has more tendency to cause fetal abnormalities in pregnancy than Propylthiouracil therefore its best to avoid it. Mehtimazole is considered an option after the first trimester and if propylthiouracil is contraindicated only then methimazole should be an option.

PropylthiouracilHepatatoxicity – major adverse effect.

Stopping the drug therapy may be needed and iodine might be the drug for treating first trimester hyperthyroidism.

Careful monitoring is recommended, since during pregnancy the thyroid levels can change and the condition can improve, or remission is observed. TSH might remain low, its not always the best guide. Free levels of T3, T4 every 6-8 weeks, should be checked.

Thyrotropin Receptor Auto Antibodies (TRAB) titre check should be done after 18-22 weeks. If the level is low , fetus risk is low, and if it’s high , fetal risk is more. Consultation of neonatologist should be preferred in cases which seem complex.

Other tests- Complete Blood Count, Liver Function Test ( ALT/AST), test for neutropenia if pharyngitis is suspected. Hepatic abnormalities can happen in the first 120 days of treatment. Consult the physician if any symptoms of jaundice or rash is observed.

Neutropenia is also common with anti-thyroid drugs in first 90 days of treatment. Prior to treatment nutrophil count should be done.

 

A table of different causes of Hypo and Hyperthyroidism is given below.

Hyperthyroidism 

 

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Hypothyroidism

hypothyroidism

 

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