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Recommended reading: key published papers from 2018

Recommended reading: key published papers from 2018
  • Endocrinology and metabolism
  • Thyroid disorder

Resource type



Recommended references

There has been a plethora of papers published on the thyroid during 2018. Manage Thyroid Online asked each of our contributing Scientific Committee Members, Professor George J Kahaly (Mainz, Germany), Professor Nemencio A Nicodemus Jr (Manila, The Philippines) and Professor Gabriela Brenta (Buenos Aires, Argentina) for a short list of the papers that have particularly caught their eye during the year. These are presented below, in no particular order:


Kahaly GJ, Bartalena L, Hegedüs L, Leenhardt L, Poppe K, Pearce SH.

2018 European Thyroid Association Guideline for the Management of Graves' Hyperthyroidism.

Eur Thyroid J 2018;7:16-186.

These guidelines for the management of Graves’ disease are the first European guidelines to both structurally define the diagnostic and treatment approaches, as well as to accurately diagnose and timely treat autoimmune hyperthyroidism in childhood, during pregnancy as well as in adulthood. This document has been drafted by six European endocrine experts internationally acknowledged in their field. This guideline also reveals significant differences between European and American management of this complex disease

Available from:

Bartalena L, Bogazzi F, Chiovato L, Hubalewska-Dydejczyk A, Links TP, Vanderpump M.

2018 European Thyroid Association (ETA) Guidelines for the Management of Amiodarone-Associated Thyroid Dysfunction. 

Eur Thyroid J. 2018 Mar;7(2):55-66.

The amiodarone guidelines neatly and precisely amalgamate the available data offering informative algorithms to manage severe amiodarone-induced hypo-and hyperthyroidism. These are the first guidelines worldwide on amiodarone.

Available from:

Kahaly GJ, Riedl M, König J, Pitz S, Ponto K, Diana T, Kampmann E, Kolbe E, Eckstein A, Moeller LC, Führer D, Salvi M, Curro N, Campi I, Covelli D, Leo M, Marinò M, Menconi F, Marcocci C, Bartalena L, Perros P, Wiersinga WM; 

European Group on Graves' Orbitopathy (EUGOGO). Mycophenolate plus methylprednisolone versus methylprednisolone alone in active, moderate-to-severe Graves' orbitopathy (MINGO): a randomised, observer-masked, multicentre trial. 

Lancet Diabetes Endocrinol 2018 Apr;6(4): 287-298. 

This Lancet research paper reports on a large observer-blind, randomized, prospective trial demonstrating the beneficial additive effect of an anti-proliferative drug, mycophenolate, in patients with active and severe thyroid eye disease, thus significantly increasing response rate and ophthalmic signs and symptoms. This trial was conducted by the recognized multidisciplinary expert group ‘European Group on Graves’ Orbitopathy’ or EUGOGO.

Available from:

Nazarpour S, Ramezani Tehrani F, Simbar M, Tohidi M, Minooee S, Rahmati M, Azizi F.

Effects of levothyroxine on pregnant women with subclinical hypothyroidism, negative for thyroidperoxidase antibodies. 

J Clin Endocrinol Metab2018 Mar 1;103(3):926-935. 

This study evaluated the benefits of LT4 treatment on pregnancy outcomes in SCH-TPOAb negative women in a single-blind randomized clinical trial. The primary outcome was the rate of preterm delivery. The authors found that using the TSH cutoff of 2.5 mIU/L, no significant difference in preterm delivery was observed between treated and untreated groups. What makes this paper noteworthy is that the authors did a further log-binomial model analysis based on a cut-point of 4.0 mIU/L which suggested that LT4 could decrease preterm delivery using the cut-off ≥4.0 mIU/L. This will need to be validated in a larger study.

Available from:

Barczyński M, Konturek A, Hubalewska-Dydejczyk A, Gołkowski F, Nowak W.

Ten-year follow-up of a randomized clinical trial of total thyroidectomy versus dunhill operation versus bilateral subtotal thyroidectomy for multinodular non-toxic goiter. 

World J Surg2018 Feb;42(2):384-392. 

The aim of this study was to validate, in a 10-year follow-up, the initial outcomes of various thyroid resection methods for multinodular non-toxic goiter (MNG). The authors of the study concluded that total thyroidectomy can be considered the preferred surgical approach for patients with MNG, as it abolishes the risk of goiter recurrence and the need for future revision thyroidectomy when compared with more limited thyroid resections, whereas the prevalence of permanent morbidity is not increased in experienced hands. I find this article noteworthy because it documents the long term outcomes of three types of surgical techniques often used for the treatment of MNG. With this paper, the superiority of one technique, total thyroidectomy, is established.

Available from:

Rajendram R, Taylor PN, Wilson VJ, Harris N, Morris OC, Tomlinson M, Yarrow S, Garrott H, Herbert HM, Dick AD, Cook A, Gattamaneni R, Jain R, Olver J, Hurel SJ, Bremner F, Drummond SR, Kemp E, Ritchie DM, Rumsey N, Morris D, Lane C, Palaniappan N, Li C, Pell J, Hills R, Ezra DG, Potts MJ, Jackson S, Rose GE, Plowman N, Bunce C, Uddin JM, Lee RWJ, Dayan CM.

Combined immunosuppression and radiotherapy in thyroid eye disease (CIRTED): a multicentre, 2 × 2 factorial, double-blind, randomised controlled trial. 

Lancet Diabetes Endocrinol. 2018 Apr;6(4):299-309. 

This study aimed to establish whether orbital radiotherapy or antiproliferative immunosuppression would confer any additional benefit for the treatment for thyroid eye disease. This was a multicentre, double-blind, randomised controlled trial with a 2x2 factorial design. Adults with active moderate-to-severe thyroid eye disease associated with proptosis or ocular motility restriction were recruited. Patients all received a 24-week course of oral prednisolone and were randomly assigned to receive either radiotherapy or sham radiotherapy and azathioprine or placebo. The authors concluded that radiotherapy did not add benefit, and nor did the addition of azathioprine. However, their conclusions are limited by the high number of patients who withdrew from treatment.

Available from:

Pozdeyev N, Gay LM, Sokol ES, Hartmaier R, Deaver KE, Davis S, French JD, Borre PV, LaBarbera DV, Tan AC, Schweppe RE, Fishbein L, Ross JS, Haugen BR, Bowles DW.

Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers. 

Clin Cancer Res 2018 Jul 1;24(13):3059-3068. 

This article deals with a large-scale analysis of advanced thyroid cancer and introduces new genetic alterations revealed using targeted next-generation sequencing cancer-associated gene panels - MSK-IMPACT and FoundationOne. It opens the field for new therapeutic drugs.

Available from:

Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY, Schellens JHM, Soria JC, Wen PY, Zielinski C, Cabanillas ME, Urbanowitz G, Mookerjee B, Wang D, Rangwala F, Keam B.

Dabrafenib and trametinib treatment in patients with locally advanced or metastatic BRAF V600-mutant anaplastic thyroid cancer. 

J Clin Oncol2018 Jan 1;36(1):7-13. 

Anaplastic thyroid cancer (ATC) has a median survival of 5 to 12 months and a 1-year overall survival of 20–40%. Between 20% and 50% of ATCs harbor activating B-Raf kinase (BRAF) V600 mutations. In this phase II, open-label trial, patients with predefined BRAF V600E-mutated malignancies received dabrafenib 150 mg twice daily and trametinib 2 mg once daily. Dual inhibition of the MAPK signaling pathway had an overall response rate of 69% which is a meaningful therapeutic advance for this orphan disease.

Available from:

Cibas ES, Ali SZ.

The 2017 Bethesda System for Reporting Thyroid Cytopathology. 

Thyroid 2017 Nov;27(11):1341-1346.

In 2017, the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was revised. It was reaffirmed that every thyroid FNA report should begin with one of six diagnostic categories, the names of which remain unchanged since they were first introduced. However, their new suggestion is that each institution use only one name for some of the categories which have synonymous terms (e.g., AUS and FLUS). Also, the risks of malignancy (ROM) for each category was re-calculated based on data post 2010, however, it was clarified that ROM may vary according to the inclusion or exclusion of the NIFTP from the list of thyroid carcinomas.

Available from:

Tuttle RM, Fagin JA, Minkowitz G, Wong RJ, Roman B, Patel S, Untch B, Ganly I, Shaha AR, Shah JP, Pace M, Li D, Bach A, Lin O, Whiting A, Ghossein R, Landa I, Sabra M, Boucai L, Fish S, Morris LGT.

Natural history and tumor volume kinetics of papillary thyroid cancers during active surveillance. 

JAMA Otolaryngol Head Neck Surg 2017 Oct 1;143(10):1015-1020. 

Active surveillance of low-risk papillary thyroid cancer (PTC) was undertaken in a cohort study of 291 patients in the US and similarly to a pioneer study in Japan. The rates of tumor growth were low - a median doubling time of 2.2 years was shown in those few tumors that grew. It was concluded that serial measurement of tumor volumes may facilitate early identification of tumors that will continue to grow and thereby inform the timing of surveillance imaging and therapeutic interventions.

Available from:

Rosenfarb J, Sforza N, Rujelman R, Morosan Allo Y, Parisi C, Blanc E, Frigerio C, Fossati P, Caruso D, Faingold C, Meroño T, Brenta G.

Relevance of TSH evaluation in elderly in-patients with non-thyroidal illness. 

J Endocrinol Invest 2018 Oct 26. 

Non-thyroidal illness (NTI) is frequent in hospitalized patients and its recovery is characterized by a rise in TSH levels once the disease is resolved. However, the clinical significance of a higher TSH level at the beginning of hospitalization is not yet clear.

In this study of hospitalized elderly patients with NTI, higher TSH values at admission were associated with a reduced recovery of TSH levels later on.

Therefore, the assessment of TSH levels on day 1 of hospitalization may be of value to assess the clinical evolution of this specific population.

Available from:

Duntas LH, Brenta G.

A renewed focus on the association between thyroid hormones and lipid metabolism

Front Endocrinol (Lausanne). 2018 Sep 3;9:511. 

In this review, the regulation of thyroid hormones on lipopoprotein metabolism is revisited with a focus on the influence of age and gender. The differential effects by 3,5-diiodothyronine (T2), a thyroid analog on lipogenesis is described, as well as the benefits that adding levothyroxine might confer to conventional hypolipidemic drugs.

Available from:

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