When thyroid hormone replacement is ineffective?

Benvenga, Salvatore

doi:10.1097/med.0000000000000003

Cited by 63 publications

(80 citation statements)

References 82 publications

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“…Onset of hypothyroidism, or aggravation of preexisting hypothyroidism with subsequent increased requirements of the L -T4 dose, stems from the loss of both protein-unbound (free) and protein-bound thyroid hormones [4]. L -T4 replacement is augmented when nephrotic syndrome (and therefore proteinuria) is uncontrolled, whereas it decreases when proteinuria decreases [14,21,22].…”

Section: Discussionmentioning

confidence: 99%

“…Our careful history taking [4] disclosed that she had consistently taken the L -T4 tablet with plain water early in the morning on an empty stomach, 60-90 min prior to breakfast. Calcium carbonate and vitamin D 3 were taken, but only for approximately 1 year after thyroidectomy, 4-6 h after L -T4; thus, no supplements and no medications other than L -T4 were taken during the last 2 years prior to our observation.…”

Section: Case Reportsmentioning

confidence: 99%

“…It does so with just one sentence (‘patients with nephrotic syndrome who excrete large quantities of albumin may have increased thyroxine requirements due to binding of T4 to the excreted albumin') and two references [7,8]. Another article [4] devotes 12 lines and 9 references to nephrotic syndrome, plus a mention in two tables. The very recently released American guidelines [1] fail to mention the renal etiology; however, table 10 in these guidelines contains a subsection entitled ‘Increased clearance' [1].…”

Section: Introductionmentioning

confidence: 99%

“…A complete, detailed diagnostic workup for failure of serum TSH to be normalized is multidisciplinary, may require hospitalization and can be expensive [3,4]. …”

Section: Introductionmentioning

confidence: 99%

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

Benvenga¹,

Vita²,

Bari³

et al. 2015

Eur Thyroid J

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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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Section: Discussionmentioning

confidence: 99%

Section: Case Reportsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…A complete, detailed diagnostic workup for failure of serum TSH to be normalized is multidisciplinary, may require hospitalization and can be expensive [3,4]. …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Benvenga¹,

Vita²,

Bari³

et al. 2015

Eur Thyroid J

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“…Once the first serum TSH check is performed (mostly between 4 and 8 weeks after initiation of therapy), rechecks are performed every 6 months by half of the respondents, but every 3 months or less by approximately 10% of the respondents (8). Approximately 15–20% of patients taking l -T4 show persistently abnormal serum TSH levels (a condition called “refractory hypothyroidism”), and this problem is frequently addressed by increasing the daily dose of l -T4 (9, 10), with associated frequent requests of the above hormone assays. Ultimately, a thorough diagnostic work-up is necessary to disclose the cause of the problem (9).…”

Section: Introductionmentioning

confidence: 99%

Refractory Hypothyroidism Due to Improper Storage of Levothyroxine Tablets

2017

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ContextA not negligible part of hypothyroid patients on levothyroxine therapy do not normalize serum thyrotropin (TSH) concentrations. “Refractory hypothyroidism,” i.e., a condition characterized by persistently abnormal serum TSH levels despite adequate titration of l-T4 substitution therapy, requires biochemical and instrumental investigation, but no definite etiology is found in up to 15% of cases.ObjectiveTo report patients presenting with refractory hypothyroidism with proven improper storage of levothyroxine tablets.DesignPatients on l-T4 substitution therapy referred to three Italian outpatient Clinics of Endocrinology between January 2013 and December 2015 for refractory hypothyroidism were investigated for levothyroxine tablet exposure to humidity, light, and high temperature.ResultsWe report eight patients, accounting for approximately 1% of all hypothyroid patients and 5% of those with refractory hypothyroidism in our series. Careful anamnesis disclosed that these patients stored levothyroxine tablets inappropriately. Normalization of serum TSH concentrations was obtained in all cases by simply recommending to store the new levothyroxine tablets away from heat, light, and humidity.ConclusionRefractory hypothyroidism linked to improper storage of l-T4 tablets does exist and might be an underrecognized entity. In addition to proper modalities of ingestion of l-T4 tablets, patients need to be instructed on proper modalities of storage, as well.

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Managing Hypothyroidism: Increasing Levothyroxine Requirements

2022

A Case-Based Guide to Clinical Endocrinology

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When thyroid hormone replacement is ineffective?

Abstract: Most frequently, reasons for ineffectiveness are noncompliance, inappropriate administration of levothyroxine, gastrointestinal disorders, and drug interactions. The diagnostic work-up should include careful history to elucidate the potential reasons for the ineffective therapy.

Cited by 63 publications

References 82 publications

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

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

Refractory Hypothyroidism Due to Improper Storage of Levothyroxine Tablets

Managing Hypothyroidism: Increasing Levothyroxine Requirements

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