Do not forget nephrotic syndrome as a cause of increased requirement of levothyroxine replacement therapy
Open accessAbstract
Nephrotic syndrome increases L-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 L-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 L-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 L-thyroxine. This diagnosis would have been accepted had the patient continued taking a known sequestrant of L-thyroxine, i.e. calcium carbonate. The diagnostic workup of patients with increasing requirements of L-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.
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Conditions increasing the serum TBG concentration (eg, elevated estrogen levels) or enhancing the renal clearance of serum proteins (eg, nephrotic syndrome) can reduce the bioavailability of LT4.
“Conditions increasing the serum TBG concentration (eg, elevated estrogen levels) or enhancing the renal clearance of serum proteins (eg, nephrotic syndrome) can reduce the bioavailability of LT4 (34–36).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [35]
In patients with nephrotic syndrome, T4-bound albumin and free T4 (FT4) are excreted into the urine, and TSH levels are elevated despite a dose increase.
“In patients with nephrotic syndrome, T4-bound albumin and free T4 (FT4) are excreted into the urine, and TSH levels are elevated despite a dose increase (35, 36).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [35]
Liquid solutions also alleviate the malabsorption induced by some nongastrointestinal disorders, such as nephrotic syndrome and pregnancy.
“Surprisingly, liquid solutions also alleviate the malabsorption induced by some nongastrointestinal disorders, such as nephrotic syndrome (35, 36) and pregnancy (61).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [35]
Nephrotic syndrome with marked proteinuria may increase the renal excretion of T4 bound to transport proteins like TBG, and hence the LT4 requirement would increase in this context.
“With regard to the specific modulation of T4 excretion by pathophysiological variables, the occurrence of nephrotic syndrome with marked proteinuria may increase the renal excretion of T4 bound to transport proteins like TBG. Hence, the LT4 requirement would increase in this context [ 118 , 119 ].”
From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [118]
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References 29 · Cited by 37
Research works printed but not linked: 4
- De Luca F, Gemelli M, Pandullo E, Barberio G, Benvenga S, Trimarchi F: Changes in thy- roid function tests in infantile nephrotic syn- drome. Horm Metab Res 1983; 15: 258-259.
- Trouillier S, Delèvaux I, Rancé N, André M, Voinchet H, Aumaître O: Nephrotic syn- drome: don't forget to search for hypothy- roidism (in French). Rev Med Interne 2008; 29: 139-144.
- Hatron PY, Wemeau JL, Guillemin R, Raviart B, Vanhille P, Devulder B: Thyroid function in the nephrotic syndrome (in French). Rev Med Interne 1984; 5: 35-42.
- Kacer M, Whyte DA, Boydstun I, Wilson TA: Congenital nephrotic syndrome and persis- tent hypothyroidism after bilateral nephrec- tomy. J Pediatr Endocrinol Metab 2008; 21: 597-601.
- Authors
- Benvenga, S., Vita, R., Di Bari, F., Fallahi, P., & Antonelli, A.
- Affiliations
- University of Messina (IT)
- 1Department of Clinical and Experimental Medicine, Italy
- University of Pisa (IT)
- Venue
- European Thyroid Journal
- Publisher
- Bioscientifica
- Published
- 2015-05-28
- Volume
- 4
- Issue
- 2
- Pages
- 138-142
- ISSN
- 2235-0640 (ISSN-L)
- 2235-0802
- PMC
- PMC4521056
- OpenAlex
- W1791276930
- Cited by
- 37
- References
- 29
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 7 · 2022: 6 · 2021: 9 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 4
- FWCI
- 2.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Thyroid Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Surgery › Medical Case Reports and Studies
- Keywords
- nephrotic syndrome, hypothyroidism, multiple myeloma, diabetic glomerulosclerosis, proteinuria, pedal edema, calcium carbonate, thyroid hormone replacement
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