Hypothyroidism with Dr. Francis Hall
The thyroid produces mainly (85%) thyroxine (T4) and some (15%) triiodothyronine (T3). Thyroxine is converted to triiodothyronine in certain tissues, including the liver, kidneys, gut and brain by the enzyme deiodinase 2 (DIO2). T3 is more biologically active than T4.
Thyroid-stimulating hormone (TSH) controls the amount of thyroid hormone produced by the thyroid through a negative feedback mechanism. TSH is produced by the anterior pituitary gland under the influence of Thyrotropin-releasing hormone (TRH) released from the hypothalamus. As the level of T4 rises in the blood, it has a negative feedback effect on both the hypothalamus and the anterior pituitary, resulting in a decrease in both TRH and TSH.
Symptoms of hypothyroidism
Thyroid hormone is essential for cellular metabolism and growth. The most common symptoms of hypothyroidism are:
- Cold intolerance
- Fatigue
- Lethargy
- Weight gain
- Constipation
- Dry skin
There are a number of scoring systems looking at the symptoms and signs of hypothyroidism, including those by Billewicz and Zulewski(1). The scoring systems are a useful teaching tool but have low sensitivity in diagnosing hypothyroidism.
In the newborn, untreated hypothyroidism can lead to cretinism, resulting in short stature, dysmorphic features and severe intellectual impairment. Fortunately, hypothyroidism is one of the diseases detected on the Guthrie test (heel prick) and early commencement of thyroxine results in preventing the development of cretinism. If untreated, hypothyroidism can result in coma and death.
Causes of Hypothyroidism
There are four types of hypothyroidism. Primary hypothyroidism occurs when the thyroid fails to make enough thyroid hormone. Secondary hypothyroidism is due to the anterior pituitary not making enough TSH and tertiary hypothyroidism is due to the hypothalamus not making enough TRH. Peripheral hypothyroidism is due to aberrant expression of deiodinase 3 leading to deactivation of thyroid hormones.
Hypothyroidism affects about 5% of the population (2). Some of the more common causes of primary hypothyroidism are:
- Hashimoto’s thyroiditis. This is an autoimmune thyroid condition. It is associated with thyroid peroxidase (TPO) antibodies in the blood. About 50% of people with Hashimoto’s thyroiditis eventually become hypothyroid; therefore, it is recommended to check the TSH and fT4 levels once a year in patients with Hashimoto’s thyroiditis.
- Latrogenica. Post total thyroidectomyb. Post hemi thyroidectomy (up to 20% in some studies)c. Post external beam radiotherapy to the neckd. Post radioactive iodinee. Lithium, amiodarone, tyrosine kinase inhibitors
- Post thyroiditis
- Severe iodine deficiency or iodine overload (Wolff-Chaikoff effect)
- Down syndrome and Turner syndrome
- Congenital absence of the thyroid.
In primary hypothyroidism we see an elevated TSH level and a decreased fT4 level. The standard treatment of hypothyroidism is thyroid hormone replacement therapy with levothyroxine.
Thyroxine
An endocrinologist once told me, “as a general rule of thumb, if the TSH level is between 5–10 mIU/L and the patient is asymptomatic consider simply repeating the TSH level in six months. If the TSH level is above 5 and the patient is symptomatic, start treating with thyroxine. If the TSH level is above 10, treat with thyroxine even if the patient is asymptomatic.”
The usual starting dose of thyroxine is 1.6 µg per kg per day. In the elderly and in patients with a cardiac history, start at a much lower dose (25 µg per day) and increase slowly. In obese patients, it is recommended that the dose of thyroxine is calculated on ideal body weight (the weight if the patient had a BMI of 25 kg/m2. Patients on thyroxine who become pregnant should increase their dose of thyroxine by 30%. In patients who have had a total thyroidectomy for either papillary or follicular thyroid cancer, the dose of thyroxine is titrated to the TSH according to the level of risk of cancer recurrence. In low-risk patients, aim for a TSH 0.5–2; in intermediate risk patients, aim for a TSH 0.1–0.5; and in high-risk patients aim for a TSH <0.1.3
There are four main commercial preparations of thyroxine tablets available in New Zealand:
- Eltroxin (Glaxo Smith Kline)
- Synthyroid (Abbott Laboratories)
- Levothyroxine (Mercury Pharma)
- Eutroxsig (approved by not funded)
Thyroxine tablets are taken 30–60 minutes before breakfast as some foods may interfere with the absorption of thyroxine from the stomach. After commencement of thyroxine or adjusting the dose of thyroxine, it takes 4–6 weeks for the TSH and fT4 levels to stabilise, so recheck the TSH and fT4 levels in 4–6 weeks. An important aspect of the treatment of hypothyroidism is to adjust the thyroxine dose so that the patient feels well and that the TSH and fT4 are both within the normal range. Recheck the TSH and fT4 levels annually.
Overtreatment (iatrogenic subclinical or overt hyperthyroidism) can cause atrial fibrillation and osteoporosis and should be avoided, especially in the elderly and postmenopausal women. Undertreatment (persistent low fT4) can result in an increased risk of cardiovascular disease.
A small proportion (5–10%) of patients on thyroxine with normal TSH and fT4 levels have persistent symptoms. One explanation for this is variations in the deiodinase 2 (DIO2), the enzyme that converts T4 to T3. These patients can be considered for combination therapy with both thyroxine (T4) and triiodothyronine (T3), although there is mixed evidence of support for this approach (4).
Triiodothyronine (T3)
Liothyronine (T3) may also be used to treat hypothyroidism. In healthy adults, the usual starting dose of T3 is 20 µg per day and is adjusted up to 80 µg per day depending on the measured TSH level. Note that 25 µg of T3 is roughly equivalent to 100 µg of T4. Because T3 works faster and has a shorter half-life than thyroxine, it may be easier on patients to start and stop T3. This is sometimes done when patients are going to have radioactive iodine.
Whole thyroid extract
This is obtained from pigs and contains both T4 and T3. The dose of T3 and T4 in whole thyroid extract is not standardised, so it may be difficult to get good control of hypothyroidism as judged by blood tests (TSH, fT4 and fT3). Dr Hall has no experience with whole thyroid extract.
Summary
Hypothyroidism is a common condition that is usually easy to diagnose (high TSH and low fT4), and in the majority of patients, it is easy to treat.
References:
- Kalra S, Khandelwal SK, Goyal A. Clinical scoring scales in thyroidology: A compendium. Indian J Endocrinol Metab. 2011 Jul;15(Suppl 2):S89-94. doi: 10.4103/2230-8210.83332.
- Layal Chaker, et al. Hypothyroidism. Lancet. 2017 September 23; 390(10101): 1550–1562. doi:10.1016/S0140-6736(17)30703-1
- Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016 Jan;26(1): 1-133. doi: 10.1089/thy.2015.0020.
- Jonklaas J, Bianco AC, Cappola AR, et al. Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document. Eur Thyroid J. 2021 Mar;10(1):10-38. doi: 10.1159/000512970.
