The issue is whether hypothyroidism is caused by poor compliance in taking levothyroxine, antibodies interference with laboratory technologies, or by malabsorption of the medication. A variety of cases of hypothyroidism with very low serum thyroid hormones and very high levels of thyroid-stimulating hormone (TSH) has been repeatedly described. In most adults, an average dosage of 1.6 micrograms per kilogram of body weight per day should normalise serum TSH levels. Typically, 70-80% of an orally administrated dose of levothyroxine is absorbed by the gastrointestinal (GI) tract.

Case report

A 24-year-old female patient presented with hypothyroidism secondary to autoimmune thyroiditis. Despite being treated with up to 600 micrograms of levothyroxine sodium daily, she was persistently hypothyroid. She complained of general fatigue and weakness, and her blood tests consistently revealed low free T4 and T3 and high TSH. Levels were: 

• Free T4 12.2pmol (9-19)
• Free T3 4.2pmol/l (2.6-5.7)
• TSH 42.6mU/L (02-4). 

She was repeatedly questioned about her compliance with the prescribed medication, but she professed good compliance. She was admitted as per consultant advice with a view to further evaluation and management, including work-up to rule out malabsorption. 

Testing was normal for coeliac disease, full blood count (FBC), calcium, magnesium, folate and prothrombin. For a levothyroxine loading test, she was given 1,000 micrograms of levothyroxine in tablet form to be taken by herself the first day. On the second day, she was again given 1000 micrograms, and she was observed while taking the tablets and for 30 minutes afterwards. On both days, her TSH and free T4 and T3 were tested immediately and then four hours later. 

In light of the test results, it was concluded that the problem was poor compliance by the patient, who apparently had not actually been taking the medication, despite her insistence otherwise.

Discussion

Clinical and biochemical hypothyroidism that is resistant to treatment with oral levothyroxine is repeatedly described in the literature. Ain et al¹ described four patients and suggested that they may be either poorly compliant in taking their medication or malabsorbing it. All patients were found to have normal absorption of oral levothyroxine, and the authors suggested the term pseudomalabsorption of levothyroxine to describe factitious presentation.

Ogawa et al² described a 51-year-old female patient who showed persistent hypothyroidism with a high TSH level and clinical symptoms of hypothyroidism. When it appeared that the patient was able to absorb liquid levothyroxine, further investigation revealed that the patient had been deliberately inducing herself to vomit after taking the medication by tablet.

Payer et al³ described a 42-year-old female patient who suffered from autoimmune thyroiditis resulting in severe hypothyroidism. She was treated for several years with a dose of 150 micrograms levothyroxine daily with no improvement in her TSH level or clinical signs. Her TRH test was normal, and a thin-needle biopsy supported autoimmune thyroiditis. Despite being prescribed an increased dose of oral levothyroxine of 300 micrograms and later 500 micrograms, her clinical status and TSH level still did not improve. Malabsorption of thyroxine was suspected. 

However, giving her a large single oral dose (1,000 mcg) of levothyroxine caused a rapid decrease of her TSH level and an increase of total T4 level. Treatment with intravenous levothyroxine resulted in a decrease of the patient’s TSH level.

The authors’ patient was very similar to those reported by Ain et al,¹ Ogawa et al² and Payer et al.³ Initially, she was suspected to suffer from a GI disorder that resulted in thyroxine malabsorption, but direct observation proved otherwise. Her poor compliance was apparently due to a depressive type of psychiatric disorder, which is not uncommon in severe hypothyroidism. Although she did not admit poor compliance, it appears very likely that she took oral thyroxine very rarely, if ever. 

In the literature mentioned, it is suggested that latent psychiatric factors may result in pseudomalabsorption of levothyroxine – non-compliance with the intent to deceive. Hypothyroidism that does not respond to treatment with high-dose levothyroxine should be investigated in depth with direct observation and, if appropriate, persistent questioning.

References

1. Ain KB, Refetoff S, Fein HG, Weintraub BD. Pseudomalabsorption of levothyroxine. JAMA 1991; 266: 2118-2120
2. Ogawa D, Otsuka F, Mimura Y et al. Pseudomalabsorption of levothroxine. Endocrine J 2000; 47: 45-50
3. Payer J, Sladekova K, Kinova S et al. Autoimmune thyroiditis with severe hypothyroidism resistant to the treatment with high per oral doses of thyroxine.  Endocrine J 2000; 34: 189-193