Clinical Thyroidology® for the Public

Summaries for the Public from recent articles in Clinical Thyroidology
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New formulations of levothyroxine may benefit select patients

CTFP October 2021

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Hypothyroidism (underactive thyroid) is very common and affects >5% of the general population at some point in their life. The treatment of hypothyroidism requires thyroid hormone replacement, usually in the form of levothyroxine. Levothyroxine most commonly comes in the form of a tablet. Levothyroxine tablets contain thyroid hormone compressed into a tablet composed of lactose monohydrate, cornstarch, carboxymethyl starch, gelatin, and dyes, among other components. Before thyroid hormone is absorbed, it must be released from the tablet, which can be facilitated by crushing the tablets. In contrast, levothyroxine in liquid form is already in liquid. In gel from, the outer gelatin shell is readily dissolved in the stomach, allowing levothyroxine to remain in solution.

Missing doses and failing to take levothyroxine as recommended are common reasons for difficulty in treating hypothyroidism. However, erratic absorption of levothyroxine in the gut can make treatment of hypothyroidism difficult. This can be seen in patients with celiac disease or taking levothyroxine at the same time as certain foods or medications, such as calcium or iron that block the absorption of levothyroxine. This study was conducted to identify whether levothyroxine in liquid or gel forms provide a better intestinal absorption and more stable thyroid hormone levels in patients.

Nagy EV et al 2021 New formulations of levothyroxine in the treatment of hypothyroidism: Trick or treat? Thyroid 31:193–201. PMID: 33003978.

The authors reviewed the published research and reviewed papers in medical journals to summarize data on the absorption differences between levothyroxine tablets with gel or liquid forms of the hormone. These studies used a standard levothyroxine absorption test. Study subjects were given a single dose of 600 mcg of Levothyroxine in each form (tablet, liquid and gel) and serum FT4, and TSH levels were determined at several time points after administration. Overall, there was no difference in FT4 levels between the different forms at any time point. However, the level of TSH was lower after liquid form.

This study suggests that there is minimal difference between the absorption of levothyroxine in tablet, gel or liquid forms. The authors concluded that more study is needed to confirm these findings. However, they also suggest that selected patients may benefit from taking them, including those who take medications interfering with absorption of levothyroxine or those that have allergies to the dyes or other components in the tables.

— Shirin Haddady, MD MPH


Hypothyroidism: a condition where the thyroid gland is underactive and doesn’t produce enough thyroid hormone. Treatment requires taking thyroid hormone pills.

Thyroid hormone therapy: patients with hypothyroidism are most often treated with Levothyroxine in order to return their thyroid hormone levels to normal. Replacement therapy means the goal is a TSH in the normal range and is the usual therapy. Suppressive therapy means that the goal is a TSH below the normal range and is used in thyroid cancer patients to prevent growth of any remaining cancer cells.

Levothyroxine (T4): the major hormone produced by the thyroid gland and available in pill form as Synthroid™, Levoxyl™, Tirosint™ and generic preparations

Celiac disease: an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward.

TSH: thyroid stimulating hormone — produced by the pituitary gland that regulates thyroid function; also, the best screening test to determine if the thyroid is functioning normally.