Do Not Forget Nephrotic Syndrome as a Cause of Increased Requirement of Levothyroxine Replacement Therapy

Abstract

Nephrotic syndrome increases <smlcap>L</smlcap>-thyroxine requirements because of urinary loss of free and protein-bound thyroid hormones. We report 2 hypothyroid patients referred to us because of high serum TSH, even though the <smlcap>L</smlcap>-thyroxine daily dose was maintained at appropriate levels or was increased. The cause of nephrotic syndrome was multiple myeloma in one patient and diabetic glomerulosclerosis in the other patient. As part of the periodic controls for diabetes, urinalysis was requested only in the second patient so that proteinuria could be detected. However, as in the first patient, facial puffiness and body weight increase were initially attributed to hypothyroidism, which was poorly compensated by <smlcap>L</smlcap>-thyroxine therapy. In the first patient, the pitting nature of the pedal edema was missed at the initial examination. An endocrinologist consulted over the phone by the practitioner hypothesized some causes of intestinal malabsorption of <smlcap>L</smlcap>-thyroxine. This diagnosis would have been accepted had the patient continued taking a known sequestrant of <smlcap>L</smlcap>-thyroxine, i.e. calcium carbonate. The diagnostic workup of patients with increasing requirements of <smlcap>L</smlcap>-thyroxine replacement therapy should not be concentrated on the digestive system alone. Careful history taking and physical examination need to be thorough. Endocrinologists should not forget nephrotic syndrome that, in turn, can be secondary to serious diseases.

Liquid and softgel capsules of l-thyroxine results lower serum thyrotropin levels more than tablet formulations in hypothyroid patients

“…In line with previous studies by our group [5], [8], [9], [10], [11], [12], [13], [14], [15], [33], to form the final cohort of 43 patients described here (not co-ingesting [n = 23; 18 women and 5 men] or co-ingesting [n = 20; 16 women and 4 men] medications that interfere with the intestinal absorption of L-T4), we requested to maintain the daily dose of L-T4 and the same local laboratory for measurement of serum TSH. This daily dose of L-T4 was 96 and 107 µg in the 23 and 20 patients, respectively.…”

“…Categorical variables are presented as proportions (%), and their differences handled by the two-tailed χ 2 or Fisher’s exact test. Per previous studies by our group [5], [8], [9], [10], [11], [12], [13], [14], [15], [33], proportions were % TSH levels considered to be target levels, viz. ≤2.50 mU/L or ≤ 4.12 mU/L.…”

“…As the Italian group who started and continue testing the possible benefit of the novel formulations of L-T4 compared to the classic tablet formulation in real-life settings [5], [8], [9], [10], [11], [12], [13], [14], [15], [33], a number of hypothyroid patients are referred to us for undertreated primary hypothyroidism while under tablet L-T4 or for beginning replacement therapy if other physicians plan to prescribe medications known to impair the intestinal absorption of L-T4 or to otherwise affect TSH levels (e.g., corticosteroids, carbamazepine). Upon explanation of a summary of the literature on the novel formulations [see Introduction] and discussion with the patients, either type of patients is left free to choose between the oral solution and the softgel capsule L-T4.…”

Increased Requirement of Replacement Doses of Levothyroxine Caused by Liver Cirrhosis

“…The second patient permits to add the chronic liver disease setting to the other settings ( 5 , 6 , 18 , 26 , 27 , 49 – 63 ) in which novel formulations of L-T4, because of their more favorable pharmacokinetics profile, perform better than the classic tablet formulation in achieving target levels of TSH ( 64 ). From a gastroenterological perspective, settings of interest are the correction of the impaired tablet L-T4 absorption caused by food and beverages, anti-ulcerants ( 26 , 27 ), esophageal dysmotility ( 15 ), gastritis ( 58 , 59 ), enteral feeding ( 63 ), and bariatric surgery ( 54 , 55 ).…”

Thyroxine replacement: a clinical endocrinologist’s viewpoint

“…87 Patients with nephritis have increased thyroxine requirements due to urinary losses of free and protein-bound thyroid hormones. 88 Screening for these disorders should be considered even in asymptomatic LT4 users with unexplained high serum TSH concentration, since they may be clinically silent or masked by features of hypothyroidism.…”