The Clinical Utility of Free Thyroxine in Oral Levothyroxine Absorption Testing

ObjectiveOriginal absorption studies for levothyroxine (LT₄) were validated using total thyroxine (TT₄) measurements. Free thyroxine (FT₄) has largely supplanted TT₄ in clinical practice. The objective of our study was to assess the clinical utility of FT₄ in oral LT₄ absorption testing.MethodsIn this retrospective electronic health record analysis, we recorded data of patients who underwent LT₄ oral absorption testing between November 2010 and January 2012 because of persistent hypothyroidism despite a greater than anticipated weight-based dose of LT₄. Patients included had primary hypothyroidism and an absorption test with assessment of both TT₄ and FT₄ measured at times 0, 30, 60, 90, 120, 180, 240, 300, and 360 minutes. The test was conducted with 1 mg (five 200-μg tablets) of Synthroid® after an overnight fast by a standard nonisotopic method.ResultsA total of 10 patients (3 men/7 women) underwent absorption testing. Prior to testing, the median daily LT₄ dose was 250 μg (range, 150 to 350 μg). Three patients were also on liothyronine (10, 20, or 50 μg daily). Based on the calculated amount absorbed, 1 patient demonstrated subnormal absorption, and 9 patients were normal. Median body mass index was 33 kg/m² (range, 21 to 50 kg/m²). Median calculated absorption was 105% (range, 3.7 to 195.6%). The correlation comparing FT₄ and TT₄ was 0.88 (95% confidence interval, 0.56 to 0.97, P < .001), a significant correlation.ConclusionFT₄ and TT₄ correlated highly, even in patients who were severely hypothyroid; FT₄ may be used interchangeably with TT₄ as a qualitative assessment of suspected malabsorption using an oral LT₄ absorption test. (Endocr Pract. 2014;20:925-929)     

Influence of Levothyroxine With Recombinant Human Thyroid-Stimulating Hormone on Urinary Iodine Excretion Before Radioactive Iodine Administration

ObjectiveStimulation with recombinant human thyroid-stimulating hormone (rhTSH) before radioactive iodine administration for patients with thyroid cancer may increase the body iodine pool in the presence of continued levothyroxine; however, the precise significance of its influence remains unclear.MethodsThis was a prospective observational study conducted between March 2017 and August 2020. We measured the 24-hour urinary iodine excretion and urinary iodine-to-creatinine ratio in patients with thyroid cancer stimulated by rhTSH or thyroid hormone withdrawal (THW) before radioactive iodine administration. Oral iodine intake was controlled by a 7-day self-managed low iodine diet, followed by a strict 3-day low iodine diet while in the hospital.ResultsOverall, 343 subjects were included (rhTSH: n = 181; THW: n = 162). The mean levothyroxine dose in the rhTSH group was 115.2 μg daily. The median 24-hour urinary iodine and urinary iodine-to-creatinine ratio in the rhTSH group (71.0 [interquartile range, 57.5-88.0] μg/day and 80.0 [59.0-97.5] μg/gCr, respectively) were significantly higher than those in the THW group (42.0 [30.0-59.0] μg/day and 39.0 [28.0-61.3] μg/gCr, respectively; both P < .001). After propensity score matching by age, sex, body weight, and renal function (rhTSH: n = 106; THW: n = 106), consistent results for both values were observed for both methods. The increase in urinary iodine with the rhTSH method was smaller than the expected value calculated from the amount of levothyroxine.ConclusionUrinary iodine excretion was significantly higher among patients with rhTSH stimulation than those with THW, indicating that the rhTSH method slightly increases the body iodine pool.     

Effect of Proton Pump Inhibitors on Serum Thyroid-Stimulating Hormone Level in Euthyroid Patients Treated with Levothyroxine for Hypothyroidism

ObjectiveTo examine retrospectively the effect of proton pump inhibitors (PPIs) on thyrotropin (thyroid-stimulating hormone or TSH) values in patients with hypothyroidism and normal TSH levels receiving levothyroxine (LT₄) replacement therapy.MethodsThe data collection was done by retrospective review of electronic medical records from the period of December 2002 to August 2005 from patients with hypothyroidism who were receiving at least 25 μg of LT₄ replacement daily at Queens Hospital Center. The first 92 patients meeting all inclusion and exclusion criteria were included in the study. The study group (N = 37) patient data were collected by selecting euthyroid patients who had received stable LT₄ replacement for at least 6 months and in whom PPI therapy (lansoprazole) was later initiated. TSH levels were collected before and at least 2 months after the PPI treatment was started. The control group (N = 55) patient data were collected by reviewing TSH levels among euthyroid patients with a history of hypothyroidism receiving stable LT₄ therapy and not receiving a PPI during the period of data collection. The statistical analysis was done by comparing the mean change in TSH level in each group with use of the Student t test.ResultsIn the study group, the mean change in the TSH level from before to at least 2 months after initiation of PPI therapy, 0.69 ± 1.9 μIU/mL, was statistically significant (P = 0.035). In the control group, the mean change in the TSH level during the study period, 0.11 ± 1.06 μIU/mL, was not statistically significant (P = 0.45).ConclusionTo our best knowledge, this is the first study in humans with hypothyroidism demonstrating the effect of PPIs on serum TSH levels. PPIs should be added to the list of medications affecting the level of thyroid hormone in patients with hypothyroidism treated with LT₄ replacement. Patients with hypothyroidism and normal TSH values during LT₄ replacement therapy may need additional thyroid function testing after treatment with PPIs and may need adjustment of their LT₄ dose. (Endocr Pract. 2007;13:345-349)     

Levothyroxine Dosing in Older Adults: Recommendations Derived From The Baltimore Longitudinal Study of Aging

ObjectiveAs thyroid hormone metabolism slows with advancing age, treatment dosing requirements change. Guidelines recommend titration from a low starting dose for older adults with hypothyroidism while providing weight-based estimates for younger populations. However, rapid replacement may be appropriate with acute onset of overt hypothyroidism. Therefore, a weight-based recommendation specific to older adults is needed.MethodsWe determined mean levothyroxine dose using actual and ideal body weight (IBW) ratios for the outcome of euthyroid on therapy relative to assay-specific and proposed age-specific ranges for independently living participants aged ≥65 years in the Baltimore Longitudinal Study of Aging. We examined risk factors to identify those at highest risk of overtreatment using regression analyses adjusted for potential covariables and clustering to account for multiple visits per individual.ResultsOne hundred eighty-five participants aged ≥65 years were on levothyroxine at 645 eligible visits. At euthyroid visits, participants were on an average dose of 1.09 μg/kg (1.35 μg/kg IBW), with 84% of euthyroid individuals on a dose of <1.6 μg/kg. Average euthyroid dose did not differ by sex using either actual body weight (ABW) or IBW. For obese individuals, mean euthyroid dose was lower if calculated using ABW (0.9 μg/kg vs 1.14 μg/kg; P < .01) but similar if calculated using IBW (1.42 vs 1.32 μg/kg IBW; P = .41) compared with those with a body mass index of <30.ConclusionThyroid hormone dose per body weight estimates for replacement in older adults (1.09 μg/kg ABW or 1.35 μg/kg IBW) are one-third lower than current weight-based dose recommendations for younger populations.     

Exacerbation of Underlying Hypothyroidism Caused by Proteinuria and Induction of Urinary Thyroxine Loss: Case Report and Subsequent Investigation

ObjectiveTo describe a patient with excess urinary thyroxine (T₄) excretion and worsening of preexisting hypothyroidism in the setting of nephrotic syndrome and to determine whether excess urinary T₄ excretion is present in other patients with proteinuria.MethodsWe present data regarding the patient’s initial presentation, diagnostic studies, and course of her illness. We suspected urinary T₄ loss to be the cause of her presentation and analyzed her urine sample for total T₄. We also analyzed differences in urinary T₄ excretion in 22 patients with proteinuria and 16 control patients without proteinuria. Relevant medical literature is reviewed.ResultsA 44-year-old woman presented with a 3-month history of increasing fluid retention, weight gain, and fatigue. She had long-standing hypothyroidism on a stable levothyroxine dosage, 125 mcg/d. She had gained 27 kg and had developed significant edema. She had a grossly elevated thyroid-stimulating hormone level of 91 mIU/L. Her condition worsened, and a urinary protein measurement was 14.06 g/24 h—diagnostic of nephrotic syndrome. The levothyroxine dosage was increased to 225 mcg/d. Urinary total T₄ concentration in a 24-hour sample was 59.0 μg/L (83.1 μg/24 h), indicating that a substantial fraction of her orally ingested T₄ was lost in urine. Urinary total T₄ excretion was significantly higher in patients with proteinuria (mean ± standard deviation, 18.0 ± 18.2 μg/L) vs control patients without proteinuria (mean, 3.8 ± 1.8 μg/L) (P = .0014).ConclusionIn the patient described, urinary T₄ loss due to proteinuria and nephrotic syndrome resulted in a severe exacerbation of underlying hypothyroidism. (Endocr Pract. 2008;14:97-103)     

Optimal Free Thyroxine Levels for Thyroid Hormone Replacement in Hypothyroidism

ObjectiveTo determine whether a difference exists in the free thyroxine level required to achieve a normal thyrotropin (thyroid-stimulating hormone or TSH) level between patients with primary hypothyroidism and euthyroid control subjects and compare the free thyroxine levels in patients with primary and secondary hypothyroidism receiving thyroid hormone replacement.MethodsWe retrospectively assessed TSH and free thyroxine values in 58 patients with primary hypothyroidism and 78 euthyroid control subjects for whom screening thyroid function tests had been performed. From the medical records, we also obtained free thyroxine values for 23 patients with central hypothyroidism receiving stable levothyroxine replacement therapy.ResultsThe mean free thyroxine level was significantly higher in patients with primary hypothyroidism than in euthyroid control subjects (1.36 ± 0.201 ng/dL versus 1.10 ± 0.155 ng/dL, respectively, P < .0001), whereas the corresponding mean TSH concentrations did not differ significantly (1.60 ± 1.183 mlU/L versus 1.73 ± 0.792 mlU/L, P = .46). The mean free thyroxine value was also significantly higher in the patients with central hypothyroidism in comparison with that in the euthyroid control subjects (1.31 ± 0.278 ng/dL versus 1.10 ± 0.155 ng/dL, respectively, P < .0001), and no significant difference was noted between the patients with primary and central hypothyroidism (1.36 ng/dL versus 1.31 ng/dL, P = .60).ConclusionPatients with hypothyroidism require a higher level of serum free thyroxine to achieve a normal TSH value in comparison with euthyroid control subjects. This finding suggests that patients with central hypothy-roidism should be treated to achieve free thyroxine levels in the upper part of the reference range. (Endocr Pract. 2008;14:550-555)     

Destructive Thyroiditis Followed by Hypothyroidism Associated with Infliximab Therapy

ObjectiveTo present the rare case of a patient who developed destructive thyroiditis accompanied by transient thyrotoxicosis resulting from infliximab therapy for the treatment of psoriasis.MethodsThe clinical presentation and management of a case with infliximab-associated thyroiditis is described with a brief review of the literature.ResultsA 57-year-old male who suffered from psoriasis was treated with infliximab therapy for 4 years. Thyroid function tests were normal before infliximab therapy. When the patient presented in our clinic, he had thyrotoxicosis and was using propylthiouracil. A 99m Technetiumpertechnetate thyroid scintigraphy scan showed no visualization of either thyroid lobe or decreased thyroid iodine uptake. Thyroid-stimulating hormone (TSH) receptor antibody, thyroid peroxidase antibody (anti-TPO Ab) and thyroglobulin antibody (anti-Tg Ab) were negative. Thyroid ultrasonography revealed a heterogeneous thyroid gland without nodules. After stopping propylthiouracil therapy, we advised monitoring of his thyroid function tests in the following weeks, and infliximab therapy for psoriasis was continued. Four weeks later, his thyroid function tests showed an elevated TSH level with normal levels of free triiodothyronine and thyroxine (FT3 and FT4, respectively), and levothyroxine treatment was administered to the patient. Thyroid function tests normalized after levothyroxine treatment. One year later, infliximab therapy was stopped because of clinical remission. Simultaneously, levothyroxine treatment was also stopped. His thyroid function tests were normal 6 weeks after the cessation of levothyroxine treatment.ConclusionTo our knowledge, the present report is the third infliximab-associated thyroid disorder case. Periodic follow-up of thyroid function tests is necessary during infliximab therapy. (Endocr Pract. 2014;20:e207-e210)     

Substitution of Liothyronine at a 1:5 Ratio for a Portion of Levothyroxine: Effect on Fatigue,Symptoms of Depression,and Working Memory Versus Treatment With Levothyroxine Alone

ObjectiveTo attempt to confirm a previous report of superior effectiveness of using two thyroid hormones rather than one hormone to treat hypothyroidism.MethodsThis trial attempted to replicate prior findings, which suggested that substituting 12.5 μg of liothyronine (LT₃) for 50 μg of levothyroxine (LT₄) might improve mood, cognition, and physical symptoms in patients with primary hypothyroidism. Additionally, this trial aimed to extend the previous findings to fatigue and to assess for differential effects in subjects with low fatigue and high fatigue at baseline. A randomized, double-blind, two-period, crossover design was used. At an endocrinology and diabetes clinic, 30 adult subjects with primary hypothyroidism stabilized on LT₄ were recruited. Patients randomly assigned to treatment sequence 1 received their standard LT₄ dose in one capsule and placebo in another. Patients assigned to sequence 2 received their usual LT₄ dose minus 50 μg in one capsule and 10 μg of LT₃ in the other. At the end of the first 6 weeks, subjects were crossed over to receive the other treatment. Carryover and treatment effects were assessed by t tests.ResultsOf the 30 enrolled study subjects, 27 completed the trial. The mean LT₄ dose was 121 ± 26 μg/day at baseline. No significant differences in fatigue and symptoms of depression were found between treatments. Measures of working memory were unchanged. During substitution treatment, the free thyroxine index was reduced by 0.7 (P < 0.001), total serum thyroxine was reduced by 3.0 μg/dL (P < 0.001), and total serum triiodothyronine was increased by 20.5 ng/dL (P = 0.004).ConclusionWith regard to the outcomes measured, substitution of LT₃ at a 1:5 ratio for a portion of baseline LT₄ yielded no better results than did treatment with the original dose of LT₄ alone. (Endocr Pract. 2005;11:223-233)     

Tyrosine Kinase Inhibitors and the Thyroid as Both an Unintended and an Intended Target

ObjectiveTo review the association of the tyrosine kinase inhibitor sunitinib with hypothyroidism as well as the mean time to onset, possible mechanisms, reversibility, and mean duration.MethodsWe performed a MEDLINE search of the English-language literature using a combination of words (“sunitinib,” “tyrosine kinase inhibitors,” “thyroid,” and “hypothyroidism”) to identify original studies and reviews on sunitinib and thyroid function.ResultsHypothyroidism was reported in 36% to 46% of patients who took sunitinib in prospective studies. A higher incidence (53% to 85%) was reported in studies containing both retrospective and prospective data. The mean time to onset of hypothyroidism after initiation of sunitinib therapy ranged from 12 to 50 weeks. The risk of development of hypothyroidism appears to increase with the increasing duration of sunitinib therapy, and the condition is likely reversible once therapy has been discontinued.ConclusionBaseline thyroid function tests should be performed before the initiation of sunitinib treatment. Because hypothyroidism can develop early in the course of therapy, thyroid function tests should be monitored frequently throughout the duration of treatment. Possible mechanisms for thyroid dysfunction include impaired thyroid hormone synthesis, a destructive thyroiditis preceding the development of hypothyroidism, and increased thyroid hormone clearance. If hypothyroidism is identified, levothyroxine therapy should be promptly initiated. (Endocr Pract. 2008;14:618-624)     

Diagnostic Confusion Attributable to Spurious Elevation of Both Total Thyroid Hormone and Thyroid Hormone Uptake Measurements in the Setting of Autoantibodies: Case Report and Review of Related Literature

ObjectiveTo review the effect of thyroid autoantibodies on thyroid function assays and to present a case in which thyroid autoantibodies resulted in spurious assay readings for both total thyroid hormone levels and thyroid hormone uptake measurements.MethodsWe present a detailed case, including serial laboratory data, and review the relevant literature.ResultsA 61-year-old man with a history of autoimmune disease presented for evaluation of abnormal results of thyroid function tests. The patient had been treated for hypothyroidism with levothyroxine and was noted to have an elevated total thyroxine (T₄) level in the setting of a low total triiodothyronine (T₃) value and a mildly elevated thyrotropin concentration. He had been referred for evaluation of a presumed deiodinase deficiency that impaired conversion of T₄ to T₃. During treatment with levothyroxine, these test results were confirmed, and the patient was also found to have an elevated T₄ uptake. These findings were initially thought to be due to an excess of transthyretin; however, more extensive testing revealed that the patient had an autoantibody to T₄ that interfered with the assays for both T₄ and T₄ uptake.ConclusionAutoantibodies to both T₃ and T₄ have been described. Such antibodies are not uncommon in patients with thyroid disease. On rare occasions, these antibodies may cause spurious assay readings and obscure the diagnosis. To our knowledge, this is the first report in which both the total T₄ level and the T₄ uptake were elevated because of the presence of autoantibodies. Thyroid hormone autoantibodies must be considered when clinicians encounter patients with unexplained abnormal results of thyroid function tests. (Endocr Pract. 2008; 14:738-742)     

Impact of Lifestyle Changes During Ramadan on Thyroid Function Tests in Hypothyroid Patients Taking Levothyroxine

Objective: The holy month of Ramadan poses a challenge for levothyroxine-treated patients due to altered eating habits and time restrictions. The aim of this study was to examine the impact of lifestyle changes during Ramadan on thyroid function tests in hypothyroid patients taking levothyroxine in the United Arab Emirates.Methods: Retrospective design whereby levothyroxine-treated hypothyroid patients who had thyroid function tests within 3 months pre-Ramadan and within 2 months post-Ramadan were included. We looked at adherence to levothyroxine, eating pattern, and levothyroxine administration in relation to meal times during Ramadan. Pre- and post-Ramadan thyroid function tests and the potential impact of independent variables using a random-intercept mixed effects linear model were examined.Results: A total of 112 patients (89 females) were recruited in the study, with a mean age ± standard error (SE) of 44.70 ± 1.36 years (range, 19.0 to 79.0 years). The mean thyroid-stimulating hormone (TSH) within 3 months before Ramadan was 1.809 ± 0.094 mIU/L (median, 41.5 days; interquartile range &lsqb;IQR], 25.0 to 73.0 days), while the mean TSH within 2 months post-Ramadan was higher at 3.072 ± 0.312 mIU/L (median, 27.5 days; IQR, 14.0 to 42.0 days). Post-Ramadan, 36 out of 112 patients had a plasma TSH outside of the normal reference range. The independent variable outcomes model showed that older patients and males were more likely to have an increased plasma TSH post-Ramadan. There was no relationship between the time of levothyroxine administration and change in TSH level.Conclusion: Levothyroxine-treated hypothyroid patients showed a significant increase in plasma TSH post-Ramadan, amounting to 2.525 standard deviations, with older patients and males more likely to be affected.Abbreviations: IQR = interquartile range; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Osteopetrosis and Congenital Hypothyroidism Complicated by Slipped Capital Femoral Epiphysis

ObjectiveTo describe a 13-year-old girl with unilateral slipped capital femoral epiphysis (SCFE), who presented with an acute onset limp during follow-up for congenital hypothyroidism and osteopetrosis.MethodsWe present a case report detailing the patient’s history as well as clinical, laboratory, and imaging findings and discuss the related literature.ResultsThe patient had been diagnosed elsewhere with congenital hypothyroidism, and levothyroxine therapy was initiated when she was 20 days of age; however, adherence to the treatment was irregular. Both her weight and her height were below the 5th percentile, her breast development and pubic hair were consistent with Tanner stage 1, and she had mental retardation and atypical facies. Her gait was antalgic; no muscle atrophy or shortness in the affected leg was present. On laboratory investigation, thyroid function tests were concordant with primary hypothyroidism. Her bone age was estimated as 8 years. Dual-energy x-ray absorptiometry revealed increased bone mineral density. Radiographic studies disclosed striking opacity of the bones of the pelvis and sclerosis at the skull base. Computed tomography of the affected left lower limb showed a fragmented appearance of the capital femoral epiphysis and thickening and irregularities of the physis line on the left, consistent with SCFE.ConclusionWe underscore the possible facilitator role of osteopetrosis in the pathogenesis of SCFE, suggest the need to consider SCFE in the differential diagnosis when a lower extremity abnormality is detected in patients with congenital hypothyroidism or delayed puberty (or both), and emphasize this association with osteopetrosis.(Endocr Pract. 2010;16:646-649)     

Postpartum Levothyroxine Adjustment and Its Impact Factors in Women With Hypothyroidism in Pregnancy

ObjectiveWomen with hypothyroidism need to increase exogenous thyroid hormone levels during pregnancy to reduce adverse outcomes. Few studies have reported the effect of gestational levothyroxine (LT4) variations on postpartum LT4 treatment.MethodsWomen were classified as having subclinical hypothyroidism (SCH) (n = 101), overt hypothyroidism (OH) caused by autoimmune thyroiditis (AIT-OH), OH following thyroidectomy for benign thyroid disease (BA-OH) (n = 66), and OH after surgery for papillary thyroid cancer (PTC-OH) (n = 46). Thyroid function was monitored, and LT4 therapy was adjusted accordingly.ResultsAfter delivery, all women with SCH stopped LT4 treatment, and 57.4% of them restarted LT4 treatment in the following 1 year, independently of the gestational LT4 variations. Among patients with OH, after adjusted by gestational body weight, 49.1% of them had LT4 doses less than the prepregnancy dose (baseline) in late pregnancy, leading to LT4 reduction in postpartum. The LT4 dose was reduced to approximately 50% baseline for women with AIT-OH and BA-OH and reduced by 27% for women with PTC-OH. The reduction reasons for AIT-OH and BA-OH were thyroid-stimulating hormone levels of <2.5 mU/L during pregnancy and postpartum thyrotoxicosis occurrence (39.4%), and for PTC-OH, the reason was thyroid-stimulating hormone overinhibition (<1.0 mU/L) before delivery.ConclusionFor patients with SCH, postpartum LT4 treatment could initially be suspended. For women with OH, if the LT4 dose in late pregnancy was less than baseline, a prepregnancy dose reduced by 50%, 50%, and 27% should be applied after delivery for women with AIT-OH, BA-OH, and PTC-OH, respectively.     

不同剂量左旋甲状腺素对妊娠合并甲减患者胎儿发育的影响

目的:探讨不同剂量左旋甲状腺素对妊娠合并甲减患者胎儿发育的影响。方法:选择2012年5月至2016年6月在我院诊治的妊娠合并甲减孕妇72例作为研究对象,根据随机数字表法抽签分为观察组与对照组各36例,两组都给予左旋甲状腺素治疗,对照组应用剂量为低剂量,观察组应用剂量为高剂量,两组均治疗观察3个月,对比两组的临床疗效、治疗前后游离三碘甲状腺原氨酸(FT3)、游离甲状腺激素(FT4)、血清促甲状腺激素(TSH)水平的变化及并发症的发生情况。结果:治疗后,观察组的总有效率[97.2%(35/36)]显著高于对照组[83.3%(30/36)](P0.05),两组TSH值显著低于治疗前(P0.05),FT3与FT4值均显著高于治疗前(P0.05),且观察组的FT3、FT4值均明显高于对照组(P0.05),而血清TSH值显著低于对照组(P0.05)。治疗期间,观察组的早产、产后出血、宫内窘迫、妊娠高血压等并发症发生率为11.1%,对照组为30.6%,观察组显著低于对照组(P0.05)。所有孕妇都顺利分娩,新生儿都存活,观察组新生儿的智力发育与精神运动发育评分都显著高于对照组(P0.05)。结论:高剂量左旋甲状腺素治疗妊娠合并甲减患者的临床效果明显高于低剂量左旋甲状腺素,其可有效促进甲状腺激素分泌平衡,减少妊娠并发症的发生,促进新生儿的发育。     

Evaluation of Treatment of Central Hypothyroidism Versus Primary Hypothyroidism in Relation to Levothyroxine Replacement Dose

Objective: The aim of this study was to evaluate levothyroxine (LT4) replacement daily doses in patients with central hypothyroidism (CeH) and compare them with those adequate for patients with primary hypothyroidism (P-HYPO).Methods: We included 53 patients with CeH and 57 with P-HYPO, matched by sex, age, weight, and body mass index, in the period of 1 year. At the time of inclusion, all presented a stable and adequate dose of LT4 for at least 3 months, considering as adequate the dose associated with normal thyroid-stimulating hormone (TSH) levels and free thyroxine (T4) in P-HYPO patients, and free T4 levels in CeH patients.Results: The absolute daily dose of LT4 differed significantly between the two groups, 103.0 ± 27.1 μg (CeH) and 89.3 ± 32.0 μg (P-HYPO) (P = .017), even after adjustment for age, gender, and free T4 (P = .04). The LT4 dose adjusted to weight was also higher after adjustment for age, gender and free T4 (P = .04), with an average of 1.3 ± 0.4 μg/kg (CeH) and 1.2 ± 0.4 μg/kg (P-HYPO). Sheehan syndrome patients had a lower absolute daily dose of LT4 (P = .001), and patients who underwent pituitary radiotherapy required higher doses (P = .008). There was no difference in the daily dose of LT4 according to other pituitary hormone deficiencies.Conclusion: The results reinforce the relevance of a careful individualization of LT4 replacement in CeH management and the need for new markers for proper LT4 replacement therapy in such cases.Abbreviations: BMI = body mass index; CeH = central hypothyroidism; GH = growth hormone; LT4 = levothyroxine; P-HYPO = primary hypothyroidism; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Graves’ Disease and Stiff-Person (Stiff-Man) Syndrome: Case Report and Literature Review

ObjectiveTo report an association between two autoimmune conditions, Graves’ disease and stiff-person (stiff-man) syndrome, and discuss the relevant literature.MethodsWe present a case of a 52-year-old white woman with stiff-person syndrome who also had Graves’ disease, discuss her management, and review the related literature. Pertinent published reports from 1950 through 2004 were researched with use of MEDLINE and PubMed, and cross-references to other articles were reviewed.ResultsA 52-year-old white woman presented with symptoms of hyperthyroidism due to Graves’ disease. Laboratory data were as follows: thyrotropin < 0.005 μIU/mL, thyroxine 11.1 μg/dL, free thyroxine index (FTI) 10.7, and triiodothyronine 170 ng/dL. Thyroid-stimulating immunoglobulins (TSI) and thyrotropin-binding inhibitory immunoglobulins (TBII) were positive at 1,986% and 82.5 U/L, respectively. The hyperthyroidism was treated with propranolol. She had a long-standing history of musculoskeletal complaints and was ultimately diagnosed with stiff-person syndrome. During her thyroid evaluation, she had severe neurologic deterioration that necessitated hospitalization and treatment with clonazepam, baclofen, intravenous immunoglobulin, and subsequently prednisone and azathioprine for appreciable symptomatic relief. The aggressive immunosuppression had a profound effect on her symptoms of hyperthyroidism, results of thyroid function tests, and thyrotropin receptor antibodies (TRABs). Thyrotropin was 0.52 μIU/mL, thyroxine was 6.9 μg/dL, and FTI was 5.7. The TSI decreased from 1,986% to 248%, and her TBII normalized from 82.5 U/L to < 5 U/L. She was clinically and biochemically euthyroid at last follow-up in May 2004.ConclusionThis case illustrates the association between TRAB-positive Graves’ disease and stiff-person syndrome and the improvement of Graves’ disease with immunosuppressive therapy. (Endocr Pract. 2005;11: 259-264)     

Tablet Levothyroxine (L-T4) Malabsorption Induced by Proton Pump Inhibitor; A Problem that was Solved by Switching to L-T4 in Soft Gel Capsule

ObjectiveTo report a patient in whom the impaired absorption of tablet levothyroxine (L-T4) due to a proton pump inhibitor (PPI) use was corrected by switching the patient to the soft gel capsule.MethodsA woman with Hashimoto’s thyroiditis-associated hypothyroidism (serum thyroid-stimulating hormone [TSH] 6.8-9.6 mU/L) had been treated with tablet L-T4 (100 μg/day). Because she used to take pantoprazole just before L-T4 in the morning, TSH failed to normalize (4.4-6.5 mU/L). Thus, the daily dose had been progressively increased to 125 and 150 μg/day, with serum TSH levels of 2.4 and 0.6 mU/L, respectively.ResultsWhile maintaining pantoprazole, we switched the tablet L-T4 (150 g/day) to a soft gel capsule (125 μg/ day; Tirosint® capsule, IBSA, Lugano, Switzerland) and after 2 months, to 100 μg/day. Serum TSH was lower than under the equivalent regimens with the tablet: 0.5 versus 2.4 mU/L (125 μg/day) and 2.4 versus 4.4 to 6.5 mU/L (100 μg/day). Upon switching back to the tablet (100 μg/day), serum TSH increased to 3.2 and 4.7 mU/L and then dropped to 2.7-3.0 mU/L when the dose was increased to 125 μg/day. We also acutely evaluated the intestinal absorption of L-T4 by administering 600 μg LT4 as a tablet or soft gel capsule while maintaining pantoprazole. Pharmacokinetic indices showed better and faster absorption for the soft gel capsule versus tablet (area under the curve [AUC]_0-4h = 16,240 vs. 10,960 nmol/L × 4 hours, maximum absorption [C_max] = 108 vs. 73 nmol/L, and time of maximum absorption [T_max] = 120 minutes vs. 180 minutes).ConclusionConfirming in vitro studies conducted by other authors, the soft gel capsule L-T4 is negligibly affected by changes in gastric pH compared to tablet L-T4. (Endocr Pract. 2014;20:e38-e41)     

Does Combination T4 And T3 Therapy Make Sense?

ObjectiveTo evaluate the existing evidence regarding the combined use of levothyroxine and liothyronine to treat hypothyroidism.MethodsEleven published randomized controlled trials evaluating the efficacy and safety of combined levo- thyroxine and liothyronine therapy for hypothyroidism were reviewed and summarized. Related basic and clinical research findings were also incorporated for perspective.ResultsAn initial randomized controlled trial reported symptomatic improvement in hypothyroid patients taking combined levothyroxine and liothyronine therapy compared with those taking levothyroxine therapy alone. Subsequently, multiple relatively small randomized controlled trials failed to demonstrate any subjective or objective benefit from combined levothyroxine and liothy- ronine therapy. A polymorphism (Thr92Ala) in the gene encoding the deiodinase 2 (D2) enzyme that converts thy- roxine to triiodothyronine in the brain was later identified in about 16% of hypothyroid persons. This polymorphism may impair brain deiodinase activity in the presence of low brain thyroxine levels. One randomized controlled trial found that patients with the D2 Thr92Ala polymorphism had more baseline symptoms than those with the wild type D2 and experienced significantly greater symptomatic improvement in response to combined levothyroxine and liothyronine therapy.ConclusionsMost hypothyroid patients experience rapid symptomatic relief after institution of levothyroxine replacement therapy, but persistent symptoms remain in some despite what appears to be adequate levothyroxine therapy with normalization of the serum thyrotropin level. A thorough investigation is warranted in these patients to detect and treat other responsible lifestyle issues, medical conditions, and endocrine conditions. A subset of hypo- thyroid patients has a polymorphism in the gene encoding the D2 enzyme that may prevent full resolution of symp- toms with levothyroxine therapy alone; these patients may benefit from combination levothyroxine and liothyronine therapy. (Endocr Pract. 2012;18:750-757)     

瘿瘤消散汤联合左甲腺素钠片治疗结节性甲状腺肿的疗效观察

目的:探讨瘿瘤消散汤联合左甲腺素钠片治疗结节性甲状腺肿的临床疗效。方法:选择2013年7月到2016年2月在我院门诊治疗的120例结节性甲状腺肿患者,随机分为对照组和试验组,各60例。对照组患者给予左甲腺素钠片治疗,试验组患者给予瘿瘤消散汤联合左甲腺素钠片治疗,两组患者均治疗6个月。评价并比较两组患者临床疗效。测量并比较两组患者治疗前后甲状腺结节最大横截面积和最大直径,检测并比较两组患者治疗前后血清促甲状腺激素(TSH)、促甲状腺素受体抗体(TRAb)、游离三碘甲状腺原氨酸(FT3)及游离甲状腺素(FT4)水平。结果:试验组患者的总有效率为86.67%,明显高于对照组的66.67%(P0.05)。治疗后,两组患者的甲状腺结节最大横截面积、最大直径均明显低于治疗前,并且试验组患者均明显低于对照组(P0.05)。治疗后,两组患者血清TSH、TRAb及FT3水平均明显低于治疗前,并且试验组患者均明显低于对照组,差异均具有统计学意义(P0.05);两组患者血清FT4水平治疗前后均无明显变化(P0.05)。结论:瘿瘤消散汤联合左甲腺素钠片治疗结节性甲状腺肿的临床疗效显著,能够明显缓解临床症状和体征,值得在临床上推广应用。