Phosphate binders as a cause of hypothyroidism in dialysis patients: practical indications from a review of the literature

Although fatigue is common in dialysis patients, polypharmacy is seldom listed among its causes. In this report, we describe a dialysis patient who developed severe fatigue due to pharmacological interaction between two commonly prescribed drugs, phosphate binders and levothyroxine.

A 65-year old woman, on dialysis for 17 years, complained of fatigue (weight 54 Kg, height 1.55 m, BMI: 23 Kg/m2; malnutrition inflammation index: 10; Charlson index 9). She had been treated with lithium for about 20 years. A heavy smoker, she was obese and diabetic when young, but stopped treatment after weight loss. She had undergone thyroidectomy for papillary carcinoma, left hemicolectomy for colon adenocarcinoma, left quadrantectomy followed by radiotherapy for ductal mammary adenocarcinoma, subtotal parathyroidectomy for tertiary hyperparathyroidism. At the time of this report, she was on thrice-weekly hemodiafiltration (Daugirdas 2 Kt/V: 1.6–1.8). Her recent treatment included spironolactone, amlodipine, perindopril, valproate, lamotrigine, levothyroxine, vitamin D, calcium carbonate, sodium polystyrene and sevelamer. After she questioned her doctor about whether her fatigue might be the result of a drug interaction, levothyroxine interference was identified (TSH, previously normal, increased to 13.07 mU/L, after increasing sevelamer dose, and normalized after change of drug schedule).

Literature review: only 5 relevant papers on levothyroxine and phosphate binders on dialysis were found on Pubmed and EMBASE (out of 351 titles retrieved). Information was therefore inferred from studies in normal volunteers or in other diseases.

Our case differs from other reports on lower TSH at diagnosis, underlining the need for awareness of the importance of early diagnosis. Integrating the scant literature on dialysis patients with data available in the general population, some working conclusions can be reached: while all phosphate binders potentially interfere with levothyroxine absorption, interference seems to be highest for sevelamer; interference is limited but not excluded by increasing the intervals between drugs; morning fast is usually indicated but, when clashing with the timing of other drugs, a bedtime dose and liquid preparations may be indicated. In the absence of an agreed control schedule, our case supports close monitoring of TSH (1–3 months if unstable, twice-yearly in stable patients).