Causes of treatment-refractory hypothyroidism and suggested investigations4–7
| Cause of hypothyroidism | Suggested investigations |
|---|---|
| Decreased bioavalability | |
| Poor adherence to drug therapy | Patient report, clinical impression or frequency of prescription refills at pharmacy |
| Absorption of oral levothyroxine | |
| Maldigestion related to hypochlorhydria | |
| Proton-pump inhibitor therapy | Medication history |
| Autoimmune atrophic gastritis | Antiparietal cell antibodies |
| Gastric infection with Helicobacter pylori | Carbon-14 urea breath test, esophagogastroduodenoscopy |
| Intestinal malabsorption of l-thyroxine | |
| Luminal factors (e.g., food, coffee and medications) | Diet and medication history (including herbal and over-the-counter medications) |
| Intramural factors (e.g., short bowel syndrome, lactose intolerance, gluten enteropathy, inflammatory bowel disease, infiltrative enteropathy, infection with Giardia | Transglutaminase antibodies |
| Esophagogastroduodenoscopy with jejunal biopsy | |
| Hydrogen breath test for lactose intolerance | |
| Culture and microscopy of stool for ova and parasites | |
| Increased need for levothyroxine | |
| Weight gain | Increase > 5%–10% from baseline |
| Pregnancy | Serum β-hCG for women of reproductive age |
| Increased metabolism of thyroxine | Medication history |
| Other factors that can alter serum levels of TSH | |
| Addison disease | ACTH stimulation test |
| Altered regulation of the hypothalamic–pituitary–thyroid axis | Liothyronine TSH suppression test |
| TSH heterophile antibodies | Use a different immunoassay |
Note: ACTH = adrenocorticotropic hormone, hCG = human chorionic gonadotropin, TSH = thyroid-stimulating hormone.