Table 2.

Factors that modulate the absorption of LT4. (↓ = decrease, ↑ = increase, ↔ = no change)

Factor	Category	Subcategory	Effect	Suggested clinical strategy	References
Ulcerative colitis	Pathophysiological	pathological	↑ in the LT4 dose required to achieve the target TSH level	Screen for ulcerative colitis	[49]
Coeliac disease	Pathophysiological	pathological	↑ in the LT4 dose required to achieve the target TSH level	Screen for coeliac disease	[50]
Bariatric surgery	Pathophysiological	pathological	↓ in BMI, ↓ in the LT4 dose but ↓ in LT4 absorption, ↑ in the time to serum T4 peak, ↑ in mean steady-state TSH levels	Monitor TSH and thyroid hormone levels periodically during weight loss and adjust as required	[56–60]
Autoimmune gastritis	Pathophysiological	pathological	↑ in the LT4 dose required to achieve the target TSH level	Screen for serum anti-parietal cell antibodies	[53]
Helicobacter pylori infection	Pathophysiological	pathological	↑ in the LT4 dose required to achieve the target TSH level	Screen for a Helicobacter pylori infection and eradicate if present. Consider a switch to a liquid LT4	[43, 52, 73]
Proton pump inhibitors (e.g. omeprazole, lansoprazole, esomeprazole, and pantoprazole)	Behavioral	medications	Effect subject to debate: ↑ in TSH levels reported in studies of omeprazole and lansoprazole but no significant effect or no consensus for esomeprazole and pantoprazole	Check for PPI treatment, check the TSH level, and increase the dose level of LT4 if TSH is elevated	[72–76]
Tyrosine kinase inhibitors (e.g. imatinib and sorafenib)	Behavioral	medications	↑ in TSH levels with imatinib ↓ in serum FT4 and FT3 with sorafenib, after adjustment for LT4 dose and bodyweight. ↓ in T3/T4 and T3/rT3, possibly due to an increase in DIO3 activity	Check for the use of tyrosine kinase inhibitors; if so, increase the LT4 dose level	[113, 115]
Alendronate	Behavioral	medications	↔ no significant effect or no consensus	An effervescent formulation of alendronate supplement is unlikely to interfere with concomitant LT4 treatment	[133]
Patiromer (potassium-binding resin)	Behavioral	medications	↓ in LT4 absorption	Delay patiromer administration by several hours in patients taking LT4	[69]
Ciprofloxacin (antibiotic)	Behavioral	medications	↓ in plasma T4	Check for concomitant use of ciprofloxacin; if so, increase the LT4 dose level	[71]
Rifampin (antibiotic)	Behavioral	medications	↑ in plasma T4	Check for concomitant use of rifampin; if so, decrease the LT4 dose level	[71, 117]
Simvastatin (statin)	Behavioral	medications	↔ no significant effect or no consensus	No action required because an interaction is unlikely	[134]
Colesevelam HCl (bile acid sequestrant)	Behavioral	medications	↓ in serum T4	Check for the use of the bile acid sequestrant colesevelam; if so, increase the LT4 dose level	[123]
Lanthanum carbonate (phosphate binder)	Behavioral	medications	↓ in serum T4	Check for the use of phosphate binders; if so, increase the LT4 dose level	[123]
Sevelamer hydrochloride (phosphate binder)	Behavioral	medications	↓ in serum T4	Check for the use of phosphate binders; if so, increase the LT4 dose level	[70]
Fluoxetine and sertraline (selective serotonin reuptake inhibitors)	Behavioral	medications	↓ in serum T3 and T4	Check for the use of the SSRIs (small effect); if so, increase the LT4 dose level	[129]
Famotidine (H2 antihistamine, antacid)	Behavioral	medications	↔ no significant effect or no consensus	No action required because an interaction is unlikely	[76]
Oral gonadotropin (infertility treatment)	Behavioral	medications	↔ no significant effect or no consensus	No action required because an interaction is unlikely	[139]
Calcium supplements	Behavioral	dietary supplements	↑ in TSH levels, ↓ in LT4 absorption	Calcium carbonate supplements should be taken 6 to 8 h after LT4. Also consider a switch to a liquid LT4 formulation in patients taking calcium carbonate supplements	[64–67]
Iron supplements	Behavioral	dietary supplements	↑ in TSH levels, ↑ in LT4 dose adjustments required to achieve the target TSH level	Screen for the use of iron or mineral calcium supplements	[39]
Food ingestion (breakfast)	Behavioral	foodstuffs	↔ no significant negative effect or no consensus for breakfast in general but some components of the meal (listed in the lines below, e.g. cow’s milk) have effects	Check that LT4 is taken at the same time of day, regardless of whether this is before or during breakfast. Check TSH levels more frequently in patients taking LT4 with food	[27–31]
Grapefruit juice	Behavioral	foodstuffs	↓ in T4 peak and AUC. ↔ for TSH levels	Monitor TSH levels	[82]
Coffee	Behavioral	foodstuffs	↔ no significant effect or no consensus	Consider a switch to a liquid formulation if the patient persists in drinking coffee at the same time as the LT4 dose	[77–79]
Cow’s milk	Behavioral	foodstuffs	↓ in LT4 absorption	Check that the patient is avoiding cow’s milk and similar substances at the time of the LT4 dose	[80]
Soy milk (formula)	Behavioral	foodstuffs	↑ in TSH and the time to TSH normalization	Check that the patient is avoiding milk and similar substances at the time of the LT4 dose	[81]
Dietary fibre (wholewheat and fiber-enriched bread)	Behavioral	foodstuffs	↑ in TSH levels and the LT4 dose requirement	Consider withdrawing dietary fiber	[68]
Curcumin extract	Behavioral	foodstuffs	↔ no significant effect or no consensus	A curcumin supplement is unlikely to interfere with LT4 treatment	[132]
Vitamin C	Behavioral	foodstuffs	↓ in TSH levels and ↑ in FT4 and TT3	Consider supplementation with vitamin C in patients with malabsorption	[141, 142]

LT4 levothyroxine, TSH thyroid-stimulating hormone, BMI body mass index, T4 thyroxine, FT3 free liothyronine, FT4 free thyroxine, rT3 reverse liothyronine, DIO3 type 3 deiodinase, AUC area under the curve