2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism
Persani L.a,b • Brabant G.c • Dattani M.d • Bonomi M.a,b • Feldt-Rasmussen U.e • Fliers E.f • Gruters A.g,h • Maiter D.i • Schoenmakers N.j • van Trotsenburg A.S.P.k
a Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
b Division of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy
c Experimental and Clinical Endocrinology Medical Clinic I – University of Lübeck, Lübeck, Germany
d Genetics and Genomic Medicine Programme, UCL GOS Institute of Child Health, London, United Kingdom
e Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
f Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
g Department for Pediatric Endocrinology and Diabetes, Charité University Medicine, Berlin, Germany
h University Hospital Heidelberg, Heidelberg, Germany
i Department of Endocrinology and Nutrition, UCL Cliniques Saint-Luc, Brussels, Belgium
j University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke’s Hospital and National Institute for Health Research Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, United Kingdom
k Department of Pediatric Endocrinology, Emma Children’s Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Central hypothyroidism (CeH) is a rare form of hypothyroidism characterized by insufficient thyroid stimulation due to disturbed pituitary and/or hypothalamic functioning.
Due to its origin and the whole clinical context, CeH represents a challenging condition in clinical practice as it is characterized by suboptimal accuracy of clinical and biochemical parameters for diagnosis and management.
Since no expert consensus or guidance for this condition is currently available, a task force of experts received the commitment from the European Thyroid Association (ETA) to prepare this document based on the principles of clinical evidence.
The task force started to work in February 2017 and after a careful selection of appropriate references (cohort studies, case reports, expert opinions), a preliminary presentation and live discussion during the 2017 ETA meeting, and several revision rounds, has prepared a list of recommendations to support the diagnosis and management of patients with CeH.
Due to the particular challenges of this rare condition in the different ages, the target users of this guidance are pediatric and adult endocrinologists.
Experts agreed on the need to recognize and treat overt CeH at all ages, whereas treatment of milder forms may be dispensable in the elderly (> 75 years).
Despite the lack of randomized controlled clinical trials, the experts provide 34 recommendations supported by variable levels of strength that should improve the quality of life of the affected patients and reduce the metabolic and hormonal consequences of inadequate management.
Which Patients Are at Risk of CeH?
The existence of CeH should be suspected in all subjects with a subnormal circulating concentration of FT4 together with an inappropriately low serum TSH.
Importantly, thyroid hormone levels change markedly during childhood and adult reference intervals are not universally applicable to children. 
Therefore, the establishment of the reference interval of TSH and FT4 is critical in the diagnosis of CeH as these values can be affected by age, gender, iodine nutrition, and ethnicity [23