Irene Campi1,2, Gabriella Cammarata3, Stefania Bianchi Marzoli3, Paolo Beck-Peccoz4, Diletta Santarsiero3, Davide Dazzi5, Alessandra Bottari de Castello6, Elena Giuliana Taroni6, Francesco Viola4,6, Caterina Mian7, Sara Watutantrige-Fernando7, Carla Pelusi8, Marina Muzza9, Maria Antonia Maffini9, Luca Persani1,4. 1. Division of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Research, Istituto Di Ricovero e Cura a Carattere Scientifico, Istituto Auxologico Italiano, 20149 Milan, Italy. 2. Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy. 3. Neuro-Ophthalmology Service, Electrophysiology Laboratory, Department of Ophthalmology, Istituto Di Ricovero e Cura a Carattere Scientifico, Istituto Auxologico Italiano, 20149 Milan, Italy. 4. Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy. 5. Division of Internal Medicine, Ospedale Vaio, 43036 Fidenza, Parma, Italy. 6. Ophthalmology Unit, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico Ca' Granda, 20122 Milan, Italy. 7. Department of Medicine, Endocrinology Unit-University of Padua, 35128 Padova, Italy. 8. Department of Medical and Surgical Sciences, Division of Endocrinology, University of Bologna, Sant'Orsola-Malpighi Hospital, 40138 Bologna, Italy. 9. Endocrine Unit, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico Ca' Granda, 20122 Milan, Italy.
Abstract
Context: 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. Objective: To investigate RP functions in RTHβ. Design, Setting, and Participants: Case-control study involving 27 RTHβ patients and 31 age/sex-matched controls, conducted in two tertiary referral centers in Italy. Main Outcome Measures: 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. Results: 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. Conclusions: 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.
Context: 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. Objective: To investigate RP functions in RTHβ. Design, Setting, and Participants: Case-control study involving 27 RTHβ patients and 31 age/sex-matched controls, conducted in two tertiary referral centers in Italy. Main Outcome Measures: 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. Results: 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. Conclusions: 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.
Authors: Carla Moran; Abdelhadi M Habeb; George J Kahaly; Christoph Kampmann; Marina Hughes; Jan Marek; Odelia Rajanayagam; Adam Kuczynski; Faraneh Vargha-Khadem; Mofeed Morsy; Amaka C Offiah; Ken Poole; Kate Ward; Greta Lyons; David Halsall; Lol Berman; Laura Watson; David Baguley; John Mollon; Anthony T Moore; Graham E Holder; Mehul Dattani; Krishna Chatterjee Journal: J Endocr Soc Date: 2017-08-08