Retinal Photoreceptor Functions Are Compromised in Patients With Resistance to Thyroid Hormone Syndrome (RTHβ)

• Published in: The journal of clinical endocrinology and metabolism 2017-07, Vol.102 (7), p.2620-2627
• Main Authors: Campi, Irene, Cammarata, Gabriella, Bianchi Marzoli, Stefania, Beck-Peccoz, Paolo, Santarsiero, Diletta, Dazzi, Davide, Bottari de Castello, Alessandra, Taroni, Elena Giuliana, Viola, Francesco, Mian, Caterina, Watutantrige-Fernando, Sara, Pelusi, Carla, Muzza, Marina, Maffini, Maria Antonia, Persani, Luca
• Format: Article
• Language: English
• Subjects: Adult; Animal models; Case-Control Studies; Color; Color matching; Color sensitivity; Color vision; Color Vision - physiology; Color Vision Defects - diagnosis; Cones; Electrophysiology; Electroretinograms; Electroretinography - methods; Female; Humans; Italy; Male; Middle Aged; Optical Coherence Tomography; Photoreceptor Cells, Vertebrate - pathology; Photoreceptors; Prenatal experience; Prenatal exposure; Reference Values; Retina; Rods; Sensitivity; Statistics, Nonparametric; Tertiary Care Centers; Thyroid Function Tests; Thyroid gland; Thyroid hormone resistance syndrome; Thyroid Hormone Resistance Syndrome - physiopathology; Tomography, Optical Coherence - methods; Wavelength; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2016-3671

In animal models, disruption of thyroid hormone (TH) receptor-β (TRβ) reduces the long/medium wavelength (L/M) and increases the short-wavelength (S) cones. Retinal photoreceptor (RP) functions are unknown in patients with resistance to TH syndrome (RTHβ) with dominant-negative TRβ mutations. To investigate RP functions in RTHβ. Case-control study involving 27 RTHβ patients and 31 age/sex-matched controls, conducted in two tertiary referral centers in Italy. Color vision sensitivity assessed by Farnsworth; central macular thickness (CMT) of the outer retinal layer measured by spectral-domain optical coherence tomography; and retinal function tested by full-field electroretinogram (ERG) and S-cone ERG. Color sensitivity was worse in RTHβ patients than controls (P = 0.002). CMT was overlapping between the study groups but directly correlated with sex hormone-binding globuline levels in RTHβ. We found a significant reduction in amplitude of the cone (P = 0.024) and of the rod response (P = 0.006) in the ERG of RTHβ patients compared with controls. The response of the L/M cones measured by a specialized ERG test was lower in RTHβ than controls (P = 0.027), whereas no differences were found in the S-cone response. No correlations were found between TH levels, total error score, or electrophysiological results. Furthermore, no differences were found between patients with maternal or de novo/paternal inheritance. We report, to our knowledge, the first in vivo evidence of functional defects of RP in RTHβ. These changes occur independently of endogenous TH levels or the prenatal exposure to high or normal maternal TH.