ETJ hypothyroidism collection

 

Although in principle, nothing might be easier than treating a patient with hypothyroidism, in practice there are several pitfalls and some recent new developments. This special topic collection brings together a series of exciting papers on different aspects of the management and complications of hypothyroidism.

 

Explore all European Thyroid Journal Special Collections

 

Hypothyroidism

You are looking at 1 - 10 of 12 items

Roberto Fiore Division of Endocrinology, Diabetes and Metabolism, University Hospital of Lausanne and University of Lausanne, Hôtel des Patients, Lausanne, Switzerland

Search for other papers by Roberto Fiore in
Google Scholar
PubMed
Close
,
Stefano La Rosa Unit of Pathology, Department of Medicine and Surgery, University of Insubria, Varese, Italy

Search for other papers by Stefano La Rosa in
Google Scholar
PubMed
Close
,
Silvia Uccella Unit of Pathology, Department of Medicine and Surgery, University of Insubria, Varese, Italy

Search for other papers by Silvia Uccella in
Google Scholar
PubMed
Close
,
Deborah Marchiori Unit of Pathology, Department of Medicine and Surgery, University of Insubria, Varese, Italy

Search for other papers by Deborah Marchiori in
Google Scholar
PubMed
Close
, and
Peter A Kopp Division of Endocrinology, Diabetes and Metabolism, University Hospital of Lausanne and University of Lausanne, Hôtel des Patients, Lausanne, Switzerland

Search for other papers by Peter A Kopp in
Google Scholar
PubMed
Close

Introduction

Consumptive hypothyroidism is a rare paraneoplastic condition most commonly associated with infantile hemangiomas. It is caused by overexpression of deiodinase type 3 (D3), which leads to preferential conversion of thyroxine to the metabolically inactive reverse triiodothyronine (rT3), paralleled by a decrease of the biologically active T3.

Case presentation

A 46-year-old male patient with previously normal thyroid function was diagnosed with a renal carcinoma with rhabdoid differentiation. He was treated with sunitinib, followed by the immune checkpoint inhibitors ipilimumab and nivolumab, and he developed primary hypothyroidism secondary to thyroiditis. Substitution with unusually high doses of levothyroxine as high as 4.3 µg/kg/day did not normalize his thyroid function. Poor compliance was refuted because there was no improvement after observed administration. He had no malabsorption. Although tyrosine kinase inhibitors can increase the expression of D3, this effect tends to be modest. Therefore, the suspicion of tumor-related consumptive hypothyroidism was raised and supported by low free T3 and elevated rT3 levels. The therapy could not be further modified because the patient opted for palliative care and passed away 12 days later.

Immunohistochemistry of the tumor from a sample obtained prior to systemic therapy documented abundant expression of D3, corroborating the diagnosis of consumptive hypothyroidism.

Conclusions

This observation extends the spectrum of malignancies overexpressing D3. Although rare, increased awareness of this paraneoplastic syndrome is key, if persistent hypothyroidism cannot be explained by compliance issues or malabsorption. Substitution with high doses of levothyroxine, and combination therapy with liothyronine, can correct hypothyroidism in these patients.

Open access
Maja Hjelm Lundgaard Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

Search for other papers by Maja Hjelm Lundgaard in
Google Scholar
PubMed
Close
,
Allan Carlé Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark

Search for other papers by Allan Carlé in
Google Scholar
PubMed
Close
,
Ulla Birgitte Christiansen Department of Gynaecology and Obstetrics, Aalborg University Hospital, Aalborg, Denmark

Search for other papers by Ulla Birgitte Christiansen in
Google Scholar
PubMed
Close
,
Anne Sørensen Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Gynaecology and Obstetrics, Aalborg University Hospital, Aalborg, Denmark

Search for other papers by Anne Sørensen in
Google Scholar
PubMed
Close
,
Søren Risom Kristensen Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

Search for other papers by Søren Risom Kristensen in
Google Scholar
PubMed
Close
, and
Stine Linding Andersen Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

Search for other papers by Stine Linding Andersen in
Google Scholar
PubMed
Close

Introduction

Thyroid disorders have been linked to abnormalities in the coagulation system, and a hypocoagulant state has been proposed in hypothyroidism. The assessment of thyroid function is, however, not routinely recommended as part of the assessment for coagulation disorders.

Case presentation

We present a 32-year-old woman who had no history of thyroid disease and who recently gave birth preterm because of severe preeclampsia and intrauterine growth restriction. Due to severe placental dysfunction, she underwent a routine biochemical assessment of the coagulation system 6 months postpartum, and a prolonged activated partial thromboplastin time (APTT) (43 s) was identified along with a low level of coagulation factor VIII (0.44 IU/mL), and a low level of von Willebrand factor (vWF) antigen (0.35 IU/mL), vWF activity (0.38 IU/mL) as well as reduced generation of thrombin. The assessment of thyroid function in the patient identified autoimmune, overt hypothyroidism with a thyroid-stimulating hormone (TSH) concentration of 139 mIU/L, low levels of the peripheral thyroid hormones (total thyroxine: 43 nmol/L, total triiodothyronine: 0.9 nmol/L), and high levels of thyroid peroxidase antibodies (296 U/mL) as well as thyroglobulin antibodies (927 U/mL).

Conclusion

In this case, prolonged APTT provided a diagnostic clue for the assessment of thyroid function in a young woman with a recent history of severe placental dysfunction. The identification of autoimmune, overt hypothyroidism emphasizes that measurement of TSH may be of clinical importance in cases of unexplained prolonged APTT or other biochemical signs of abnormalities in the coagulation system.

Established facts

  • Hypothyroidism has been associated with alterations of the coagulation system suggesting a hypocoagulant state.

  • At present, measurement of thyroid-stimulating hormone is not routinely recommended as part of the assessment for coagulation disorders.

Novel insights

  • In this case, biochemical assessment of the coagulation system was routinely performed following a pregnancy complicated by severe placental dysfunction.

  • Overt hypothyroidism of autoimmune origin was identified secondary to prolonged activated partial thromboplastin time (APTT) postpartum along with low levels of coagulation factor VIII, von Willebrand factor, and thrombin generation.

  • Measurement of thyroid-stimulating hormone may be considered in cases of unexplained prolonged APTT.

Open access
Aurore Geslot Department of Endocrinology and metabolic diseases, CHU Larrey, Toulouse, France

Search for other papers by Aurore Geslot in
Google Scholar
PubMed
Close
,
Frédérique Savagner Laboratory of Biochemistry, CHU Purpan, Toulouse, France

Search for other papers by Frédérique Savagner in
Google Scholar
PubMed
Close
, and
Philippe Caron Department of Endocrinology and metabolic diseases, CHU Larrey, Toulouse, France

Search for other papers by Philippe Caron in
Google Scholar
PubMed
Close

Introduction: Iodothyronine deiodinases are selenoproteins with the amino acid selenocysteine (Sec) introduced into the position of a TGA stop codon by a complex machinery involving tRNA<sup>[Ser]Sec</sup> when a cis-acting Sec-insertion sequence element is present in the 3′ end of the mRNA. Recently, a variant in the TRU-TCA1-1 gene encoding for tRNA<sup>[Ser]Sec</sup> was reported, which resulted in reduced expression of stress-related selenoproteins. The proband presented with multisystem symptoms, euthyroid hyperthyroxinemia, and selenium deficiency. Here, we describe 2 new members of a family harboring the same tRNA<sup>[Ser]Sec</sup> variant. Case Presentation: A 13-year-old patient was seen for Hashimoto’s disease with high FT3 (4.6 pg/mL, normal range 2–4.2 pg/mL) and normal FT4 and TSH concentrations. He had no clinical complaints. During a 6-year clinical and hormonal follow-up, the index patient was not treated, FT3 decreased, FT4 increased, and serum TSH stayed in the normal range resulting in a euthyroid hyperthyroxinemia. Reverse T3 concentration was significantly increased at the last visit (19 years and 4 months). At the last evaluation, the total selenium level was low (91 μg/L, normal range 95–125). DNA sequencing identified a germinal homozygous variant (C65G) in the TRU-TCA1-1 gene. During follow-up, no additional clinical symptom was observed in the absence of any treatment. The same germinal tRNA<sup>[Ser]Sec</sup> variant was identified at heterozygous state in his father, who had normal thyroid function tests except a moderately increased reverse T3 concentration, with increased total selenium (143 μg/L) level. In both patients, the expression of stress-related selenoprotein GPX3 was in the low-normal range (168 and 180 IU/L, respectively, normal range: 150–558 IU/L). We did not find any significant biological abnormalities evocative of other selenoprotein deficiencies. Discussion/Conclusion: We report on 2 members of a family with a variant in the TRU-TCA1-1 gene encoding for tRNA<sup>[Ser]Sec</sup>. Our study suggests that this tRNA<sup>[Ser]Sec</sup> variant is not exclusively causative of disruption in selenoprotein synthesis.

Free access
Samer El-Kaissi Department of Endocrinology, Medical Subspecialties Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

Search for other papers by Samer El-Kaissi in
Google Scholar
PubMed
Close
,
Laila AbdelWareth Department of Laboratory Medicine, National Reference Laboratory and Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

Search for other papers by Laila AbdelWareth in
Google Scholar
PubMed
Close
,
Ruba Dajani Department of Pharmacy, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

Search for other papers by Ruba Dajani in
Google Scholar
PubMed
Close
,
Terrence J. Lee-St. John Research Department, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

Search for other papers by Terrence J. Lee-St. John in
Google Scholar
PubMed
Close
,
Sherry Ann Santarina Research Department, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

Search for other papers by Sherry Ann Santarina in
Google Scholar
PubMed
Close
,
Fiona Makia Research Department, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

Search for other papers by Fiona Makia in
Google Scholar
PubMed
Close
,
Malak AlTakruri Department of Pharmacy, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

Search for other papers by Malak AlTakruri in
Google Scholar
PubMed
Close
,
AbedElRahman Kaskas Department of Patient Education, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

Search for other papers by AbedElRahman Kaskas in
Google Scholar
PubMed
Close
, and
Yahya Ahmed Department of Pharmacy, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

Search for other papers by Yahya Ahmed in
Google Scholar
PubMed
Close

Background and Aim: We have previously shown in a retrospective analysis that the plasma thyroid-stimulating hormone (TSH) rises significantly post-Ramadan in levothyroxine-treated hypothyroid patients, possibly as a result of lifestyle alterations and time restrictions during the nonfasting period from dusk until dawn. The aim of this study is to determine the best time to instruct patients to take levothyroxine during Ramadan so as to minimize changes in thyroid function tests during this period. Methods: In a randomized prospective design, hypothyroid patients taking levothyroxine were randomized to receive instructions to take levothyroxine at one of the following 3 times during Ramadan: (group 1) at dusk 30-min before Iftar meal, (group 2) 3 or more hours after Iftar meal, or (group 3) at dawn 30-min before Suhur meal. Thyroid function tests were performed within 3 months before Ramadan and within 6 weeks post-Ramadan. Data from patients with at least 1 blood test before or after Ramadan were analyzed using mixed-effects regression models. Results: Plasma TSH levels were available at one or more time points for 148 patients, group 1 (n = 50), group 2 (n = 46), and group 3 (n = 52). A statistically significant within-patient increase in plasma TSH was seen in patients at the 25th percentile pre-Ramadan in groups 2 and 3 (p values <0.001), but not in group 1. A statistically significant within-patient decrease in plasma TSH was found in patients at the 75th percentile in group 1 only. For patients at the 50th percentile pre-Ramadan, no statically significant within-patient changes were found, though descriptively, increases in plasma TSH were observed for groups 2 and 3, while a decrease was observed in group 1. Conclusions: Our data suggest that instructing patients to take levothyroxine at the time of breaking the fast 30 min before the Iftar meal minimizes unfavorable changes in plasma TSH post-Ramadan. In contrast, instructing patients to take levothyroxine 3 h post-Iftar or 30 min before Suhur led to a greater rise in post-Ramadan TSH.

Free access
Ladan Mehran Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Search for other papers by Ladan Mehran in
Google Scholar
PubMed
Close
,
Atieh Amouzegar Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Search for other papers by Atieh Amouzegar in
Google Scholar
PubMed
Close
,
Hengameh Abdi Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Search for other papers by Hengameh Abdi in
Google Scholar
PubMed
Close
,
Negar Delbari Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Search for other papers by Negar Delbari in
Google Scholar
PubMed
Close
,
Elham Madreseh Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

Search for other papers by Elham Madreseh in
Google Scholar
PubMed
Close
,
Maryam Tohidi Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Search for other papers by Maryam Tohidi in
Google Scholar
PubMed
Close
,
Mohammad Ali Mansournia Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

Search for other papers by Mohammad Ali Mansournia in
Google Scholar
PubMed
Close
, and
Fereidoun Azizi Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Search for other papers by Fereidoun Azizi in
Google Scholar
PubMed
Close

Background: Studies assessing thyroid hormones in metabolic syndrome (MetS) patients are contradictory. Also, the effect of MetS on thyroid function over time is not yet evaluated. This study investigated the prevalence and incidence of thyroid dysfunction (TD) as well as time trends of thyroid hormones in subjects with and without MetS, during a 10-year follow-up in Tehranian adult population. Methods: This is a prospective cohort study conducted in the framework of Tehran Thyroid Study on 5,786 subjects aged ≥20 years: 4,905 eligible participants entered the study after excluding those with corticosteroid or radioactive iodine use, pregnancy, thyrotropin (TSH) <0.1 and >10 mU/L, and missing data. Physical examinations were performed and serum concentrations of TSH, free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), fasting plasma glucose, insulin, and lipid profile were assessed at baseline and 3-year intervals during the follow-up. MetS was defined according to the Joint Interim Statement Definition. Results: At baseline, there were no difference in median serum concentrations of FT4 and TSH between MetS and non-MetS group after adjusting for age, sex, BMI, smoking, and TPOAb positivity. Although there was higher risk of overt (42%) and subclinical hypothyroidism (16%) in MetS compared with non-MetS subjects, no significant difference was observed in adjusted ORs for any TD between 2 groups. There were also no significant differences in time trends of TSH, FT4, TPOAb positivity, and incidence rates of TDs between MetS and non-MetS groups during 10 years, after adjustment for age, sex, BMI, smoking status, and TPOAb positivity. Conclusion: MetS is not associated with thyroid hypofunction considering other important confounders such as age, sex, smoking, BMI, and TPOAb positivity. There is also no difference in the trend of thyroid hormones and incidence of TD between MetS and non-MetS subjects during a 10-year follow-up.

Free access
Salman Razvi Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom

Search for other papers by Salman Razvi in
Google Scholar
PubMed
Close
,
Bronia Arnott Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom

Search for other papers by Bronia Arnott in
Google Scholar
PubMed
Close
,
Dawn Teare Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom

Search for other papers by Dawn Teare in
Google Scholar
PubMed
Close
,
Shaun Hiu Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom

Search for other papers by Shaun Hiu in
Google Scholar
PubMed
Close
,
Nicki O’Brien Department of Psychology, Northumbria University, Newcastle upon Tyne, United Kingdom

Search for other papers by Nicki O’Brien in
Google Scholar
PubMed
Close
, and
Simon H. Pearce Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom

Search for other papers by Simon H. Pearce in
Google Scholar
PubMed
Close

Background: International societies have recommended that levothyroxine should not routinely be prescribed in older individuals for the management of mild subclinical hypothyroidism (SCH). However, it is unknown whether clinicians managing people with SCH are either aware of or adhere to these guidelines. Methods: A web-based survey of members of several international thyroid associations and general practitioners in North-East England was conducted. Respondents were presented with a vignette of an 80-year-old gentleman with mild persistent SCH experiencing tiredness. Multivariable logistic regression analyses were performed to evaluate predictors of awareness of guidelines and responses to treatment. Results: The survey response rate was 21.9% (565/2,583). Only 7.6% of clinicians were unaware of guidelines regarding management of SCH in older people. Twenty percent of clinicians stated that they would treat the older patient with mild SCH, whereas 13% were unsure. Clinicians from North America were more likely to treat the older person with mild SCH than clinicians from elsewhere (OR 2.24 [1.25–3.98]). Likewise, non-endocrinologists were also more likely than endocrinologists to treat the older person with mild SCH (OR 3.26 [1.45–6.47]). Conclusion: The majority of clinicians are aware of guidelines regarding management of SCH in older individuals. However, a considerable proportion of clinicians would still treat an older person with non-specific symptoms and mild SCH. These guidelines need to be disseminated more widely and more research is required to understand barriers to adherence to international recommendations.

Free access
Tal Almagor Pediatric Endocrine Institute, Ha’Emek Medical Center, Afula, Israel
Pediatric Department B, Ha’Emek Medical Center, Afula, Israel
Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel

Search for other papers by Tal Almagor in
Google Scholar
PubMed
Close
,
Shoshana Rath Pediatric Endocrine Institute, Ha’Emek Medical Center, Afula, Israel

Search for other papers by Shoshana Rath in
Google Scholar
PubMed
Close
,
Dan Nachtigal Department of Otolaryngology, Head and Neck Surgery, Ha’Emek Medical Center, Afula, Israel

Search for other papers by Dan Nachtigal in
Google Scholar
PubMed
Close
,
Zohara Sharroni Department of Otolaryngology, Head and Neck Surgery, Ha’Emek Medical Center, Afula, Israel

Search for other papers by Zohara Sharroni in
Google Scholar
PubMed
Close
,
Ghadir Elias-Assad Pediatric Endocrine Institute, Ha’Emek Medical Center, Afula, Israel
Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel

Search for other papers by Ghadir Elias-Assad in
Google Scholar
PubMed
Close
,
Ora Hess Pediatric Endocrine Institute, Ha’Emek Medical Center, Afula, Israel

Search for other papers by Ora Hess in
Google Scholar
PubMed
Close
,
Gilad Havazelet Clalit Health Services, North District, Israel

Search for other papers by Gilad Havazelet in
Google Scholar
PubMed
Close
,
Yoav Zehavi Pediatric Department B, Ha’Emek Medical Center, Afula, Israel

Search for other papers by Yoav Zehavi in
Google Scholar
PubMed
Close
,
Ronen Spiegel Pediatric Department B, Ha’Emek Medical Center, Afula, Israel
Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel

Search for other papers by Ronen Spiegel in
Google Scholar
PubMed
Close
,
Dani Bercovich Faculty of Medical Science, Tel Hai Academic College Upper Galilee, Tel Hai, Israel
GGA – Galil Genetic Analysis Laboratory Ltd., Kazerin, Israel

Search for other papers by Dani Bercovich in
Google Scholar
PubMed
Close
,
Shlomo Almashanu The National Newborn Screening Program, Ministry of Health, Tel-HaShomer, Israel

Search for other papers by Shlomo Almashanu in
Google Scholar
PubMed
Close
, and
Yardena Tenenbaum-Rakover Pediatric Endocrine Institute, Ha’Emek Medical Center, Afula, Israel
Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel

Search for other papers by Yardena Tenenbaum-Rakover in
Google Scholar
PubMed
Close

Background: An association between hearing impairment (HI) and congenital hypothyroidism (CH) has been reported previously. However, in general, studies were retrospective and had small sample sizes, and the results were variable and inconclusive. The aim of our study was to assess the prevalence of HI among patients with CH and to examine factors potentially predictive of HI including severity of CH, etiology of CH, and timing of treatment initiation. Methods: Audiometry was undertaken prospectively in 66 patients aged 3–21 years diagnosed with primary CH and 49 healthy matched controls. All patients with HI underwent examination by an otolaryngologist, and in patients with sensorineural loss, brainstem evoked response audiometry was performed. A next-generation sequencing (NGS) panel for genes involved in deafness was performed in patients with sensorineural HI to exclude additional genetic etiologies. Results: HI was found in 19 patients (28.7%). Among them, 5 (7.6%) had moderate to severe bilateral sensorineural impairment and 14 (21.2%) had mild conductive HI. Conductive HI was bilateral in 5 of these patients (36%). None of the controls had HI. No specific etiology was found in patients with HI, and no differences were identified in age at diagnosis, age at initiation of levothyroxine (LT<sub>4</sub>) therapy, gender, or ethnicity between patients with and without HI. A nonsignificant trend toward lower mean screening TT<sub>4</sub> levels was found in patients with HI (compared to those without HI) (3.42 vs. 5.34 μg/dL, p = 0.095). No pathogenic variants in genes attributed to HI were identified by NGS in the 5 patients with sensorineural deafness, indicating that HI in these patients was likely attributable to CH rather than other genetic etiologies. Conclusions: Our findings indicate a high prevalence of HI among patients with CH, predominantly of the conductive type. HI was not associated with the etiology of CH or with delayed initiation of LT<sub>4</sub> therapy. Audiometry is recommended for children diagnosed with CH and repeat monitoring may be warranted to identify acquired HI and to prevent long-term sequelae of undiagnosed deafness.

Free access
Solène Castellnou Hospices Civils de Lyon, Groupement Hospitalier Est, Fédération d’Endocrinologie, Bron, France

Search for other papers by Solène Castellnou in
Google Scholar
PubMed
Close
,
Patricia Bretones Service d’Endocrinologie Pédiatrique, Hospices Civils de Lyon, Groupement Hospitalier Est, Bron, France

Search for other papers by Patricia Bretones in
Google Scholar
PubMed
Close
,
Juliette Abeillon Hospices Civils de Lyon, Groupement Hospitalier Est, Fédération d’Endocrinologie, Bron, France

Search for other papers by Juliette Abeillon in
Google Scholar
PubMed
Close
,
Myriam Moret Hospices Civils de Lyon, Groupement Hospitalier Est, Fédération d’Endocrinologie, Bron, France

Search for other papers by Myriam Moret in
Google Scholar
PubMed
Close
,
Pauline Perrin Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Groupement Hospitalier Est, LBMMS, Bron, France

Search for other papers by Pauline Perrin in
Google Scholar
PubMed
Close
,
Karim Chikh Centre de Biologie et de Pathologie Sud, Hospices Civils de Lyon, Groupement Hospitalier Sud, LBMMS, Saint Genis Laval, France

Search for other papers by Karim Chikh in
Google Scholar
PubMed
Close
, and
Véronique Raverot Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Groupement Hospitalier Est, LBMMS, Bron, France

Search for other papers by Véronique Raverot in
Google Scholar
PubMed
Close

Introduction: Maternal TSH receptor antibodies (TRAbs) can cross the placenta and affect fetal and neonatal thyroid function. Maternal TSH receptor-blocking antibodies (TBAbs) are a rare cause of congenital hypothyroidism. Case Report: Following the discovery of a highly elevated TSH on her neonatal screening test, a 10-day-old girl with no familial history of thyroid disorder was referred to the pediatric endocrinology unit. Hypothyroidism was confirmed with a highly elevated TSH (817 mIU/L, reference range 0.4–3.1) and very low levels of FT4 (1.8 pmol/L, reference range 12–22). Anti-TPO antibodies were at 81 IU/mL (reference range <34), TRAbs at 1.7 IU/L (reference range <1.75), and thyroglobulin at 9.4 µg/L (reference range 3.5–77). The thyroid appeared normal on ultrasonography, and no radioiodine uptake was seen on the scintigraphy after the perchlorate discharge test. Concomitantly, a severe maternal hypothyroidism was discovered (TSH 224 mIU/L). The maternal ultrasound appeared normal, anti-TPO antibodies were moderately elevated, and TRAbs were at 3.2 IU/L. TBAbs activity was measured in the mother and her daughter, and a very high and similar blocking activity was observed in both patients (TBAbs 89%, reference range <10%). L-thyroxine treatment was introduced in the newborn and was successfully discontinued at 6.5 months of age, as the TBAbs activity decreased. Conclusion: We report herein a case of transient congenital hypothyroidism with a normal neonatal TRAbs level. In case of maternal TBAbs, similar activity of maternal TBAbs must be expected in the neonate, independently of the neonatal level of TRAbs.

Free access
Jacqueline Jonklaas Division of Endocrinology, Georgetown University, Washington, District of Columbia, USA

Search for other papers by Jacqueline Jonklaas in
Google Scholar
PubMed
Close
,
Antonio C. Bianco Section of Adult and Pediatric Endocrinology and Metabolism, University of Chicago, Chicago, Illinois, USA

Search for other papers by Antonio C. Bianco in
Google Scholar
PubMed
Close
,
Anne R. Cappola Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Search for other papers by Anne R. Cappola in
Google Scholar
PubMed
Close
,
Francesco S. Celi Division of Endocrinology, Diabetes and Metabolism, Virginia Commonwealth University, Richmond, Virginia, USA

Search for other papers by Francesco S. Celi in
Google Scholar
PubMed
Close
,
Eric Fliers Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center, Amsterdam, The Netherlands

Search for other papers by Eric Fliers in
Google Scholar
PubMed
Close
,
Heike Heuer Department of Endocrinology, Diabetes and Metabolism, University Duisburg-Essen, Essen, Germany

Search for other papers by Heike Heuer in
Google Scholar
PubMed
Close
,
Elizabeth A. McAninch Division of Endocrinology, Rush University, Chicago, Illinois, USA

Search for other papers by Elizabeth A. McAninch in
Google Scholar
PubMed
Close
,
Lars C. Moeller Department of Endocrinology, Diabetes and Metabolism, University Duisburg-Essen, Essen, Germany

Search for other papers by Lars C. Moeller in
Google Scholar
PubMed
Close
,
Birte Nygaard Center for Endocrinology and Metabolism, Department of Internal Medicine, Herlev and Gentofte Hospitals, Herlev, Denmark

Search for other papers by Birte Nygaard in
Google Scholar
PubMed
Close
,
Anna M. Sawka Division of Endocrinology, University Health Network and University of Toronto, Toronto, Ontario, Canada

Search for other papers by Anna M. Sawka in
Google Scholar
PubMed
Close
,
Torquil Watt Department of Endocrinology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

Search for other papers by Torquil Watt in
Google Scholar
PubMed
Close
, and
Colin M. Dayan Thyroid Research Group, School of Medicine, Cardiff University, Cardiff, United Kingdom

Search for other papers by Colin M. Dayan in
Google Scholar
PubMed
Close

Background: Fourteen clinical trials have not shown a consistent benefit of combination therapy with levothyroxine (LT4) and liothyronine (LT3). Despite the publication of these trials, combination therapy is widely used and patients reporting benefit continue to generate patient and physician interest in this area. Recent scientific developments may provide insight into this inconsistency and guide future studies. Methods: The American Thyroid Association (ATA), British Thyroid Association (BTA), and European Thyroid Association (ETA) held a joint conference on November 3, 2019 (live-streamed between Chicago and London) to review new basic science and clinical evidence regarding combination therapy with presentations and input from 12 content experts. After the presentations, the material was synthesized and used to develop Summary Statements of the current state of knowledge. After review and revision of the material and Summary Statements, there was agreement that there was equipoise for a new clinical trial of combination therapy. Consensus Statements encapsulating the implications of the material discussed with respect to the design of future clinical trials of LT4/LT3 combination therapy were generated. Authors voted upon the Consensus Statements. Iterative changes were made in several rounds of voting and after comments from ATA/BTA/ETA members. Results: Of 34 Consensus Statements available for voting, 28 received at least 75% agreement, with 13 receiving 100% agreement. Those with 100% agreement included studies being powered to study the effect of deiodinase and thyroid hormone transporter polymorphisms on study outcomes, inclusion of patients dissatisfied with their current therapy and requiring at least 1.2 µg/kg of LT4 daily, use of twice daily LT3 or preferably a slow-release preparation if available, use of patient-reported outcomes as a primary outcome (measured by a tool with both relevant content validity and responsiveness) and patient preference as a secondary outcome, and utilization of a randomized placebo-controlled adequately powered double-blinded parallel design. The remaining statements are presented as potential additional considerations. Discussion: This article summarizes the areas discussed and presents Consensus Statements to guide development of future clinical trials of LT4/LT3 combination therapy. The results of such redesigned trials are expected to be of benefit to patients and of value to inform future thyroid hormone replacement clinical practice guidelines treatment recommendations.

Free access
Camilla Bøgelund Larsen Department of Endocrinology, Odense University Hospital, Odense, Denmark
Department of Clinical Research, University of Southern Denmark, Odense, Denmark

Search for other papers by Camilla Bøgelund Larsen in
Google Scholar
PubMed
Close
,
Eva Rabing Brix Petersen Department of Clinical Biochemistry and Immunology, Hospital of Southern Jutland, Aabenraa, Denmark

Search for other papers by Eva Rabing Brix Petersen in
Google Scholar
PubMed
Close
,
Martin Overgaard Department of Clinical Research, University of Southern Denmark, Odense, Denmark
Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark

Search for other papers by Martin Overgaard in
Google Scholar
PubMed
Close
, and
Steen Joop Bonnema Department of Endocrinology, Odense University Hospital, Odense, Denmark
Department of Clinical Research, University of Southern Denmark, Odense, Denmark

Search for other papers by Steen Joop Bonnema in
Google Scholar
PubMed
Close

Introduction: Analytical problems should be considered in case of a discrepancy between the results of biochemical tests and the clinical findings. Macro-hormones often artefactually elevate biochemical tests. Case Presentation: A young male was referred with persistently elevated TSH (148 mIU/L) measured by a sandwich electrochemiluminescence immunoassay, ECLIA (Cobas; Roche, Basel, Switzerland). The patient’s complaints were unspecific, and he appeared clinically euthyroid. The plasma levels of free T4 and free T3 were within the normal range, thyroid autoantibodies were negative, and thyroid ultrasonography was normal. During a short trial of thyroid hormone substitution, the level of TSH decreased to near-normal levels, but hyperthyroid symptoms emerged. TSH analysed by a different immunoassay (Architect; Abbott, Chicago, IL, USA) yielded similar results. In addition, serial dilutions were performed showing linearity, without detection of heterophilic antibody interference. Gel filtration chromatography confirmed the presence of macro-TSH. Conclusion: The patient harboured macro-TSH, which is a rare condition. The complex binding of TSH to other plasma proteins, most often immunoglobulins, results in elevated plasma TSH. However, the biologically active fraction of TSH is normal, reflected by clinical and biochemical euthyroidism.

Free access