Discussion
Refractory hypothyroidism, a condition where the thyroid gland does not
respond adequately to treatment, can arise from a multitude of factors.
Non-pathological reasons include patient non-compliance, often due to
poor adherence to medication schedules, leading to reduced treatment
absorption
. Certain medications, such as proton-pump inhibitors (PPI), histamine
receptor blockers, and cholestyramine, along with conditions like
irritable bowel syndrome, lactose intolerance, and gastroesophageal
reflux disease, can interfere with gastrointestinal absorption.
Pregnancy also necessitates specific adjustments in medication dosage
across different trimesters. Pathologically, gastrointestinal disorders
like inflammatory bowel disease, H. pylori infection, and the effects of
gastric bypass surgery can contribute to the condition. Furthermore,
individual factors such as body mass, gender, and genetic variations
specifically in deiodinase D2 can influence the effectiveness of
levothyroxine therapy. It is essential to differentiate true
malabsorption from pseudo-malabsorption, which is linked to poor
treatment adherence. Idiopathic causes, where the reason remains
unknown, account for 10-20% of cases. Understanding these diverse
factors is crucial for the effective management of refractory
hypothyroidism. (3)(4).
The management of refractory hypothyroidism requires a meticulous and
structured approach. Confirming patient adherence to prescribed
treatment and proper medication administration techniques is crucial. A
thorough review of the patient’s medication history is essential to rule
out drug interactions that may affect thyroxine levels. Subsequently,
conducting tests to investigate potential thyroxine malabsorption is
advised, which may include assessing gastrointestinal function and
health. For women of childbearing age, a pregnancy test is imperative as
pregnancy can alter thyroid hormone levels. Finally, a thyroxine
absorption test should be performed to distinguish between
pseudo-malabsorption where the issue is not actual malabsorption but
perhaps non-compliance or interference, and true levothyroxine (LT4)
malabsorption (4).
Treatment in cases of refractory hypothyroidism is achieved by different
methods as proposed in different studies of soft gel and liquid LT4
showing potential in specific groups such as pediatric patients,
bariatric surgery patients, patients on PPI, and patients unwilling to
delay breakfast \RL (5). Parenteral administration is another
suggested treatment. This includes subcutaneous (SQ), intramuscular
(IM), and intravenous (IV) routes. Hays’ mathematical model \RL
(6)(7) is used to figure out the doses, and the rates of absorption are
twice as high with intramuscular and intravenous administration compared
to SQ administration. Moreover, intramuscular administration was
reported in multiple cases and favored due to the ability to safely
adjust the dose once or twice weekly, which proved to be an acceptable
alternative in cases of resistant hypothyroidism to achieve euthymic
state in reported patients \RL (7)(8)(9).
Only a limited number of studies in the outpatient setting reported the
IV administration of LT4. This was primarily due to its use in
hospitalized patients and patients with myxedema. However, given that
the IV dose is 75% of the enteral dose and can be administered weekly,
it serves as a great substitute for the oral form as evidenced in our
study to achieve an euthymic state. This method effectively addresses
pseudo-malabsorption and overcomes the factors associated with
levothyroxine malabsorption in the GI tract \RL (10)(11)(12)(13)