TSH elevations as the first laboratory evidence for pseudohypoparathyroidism type Ib (PHP-Ib)
| Autor: | Giuseppina De Marco, Angelo Molinaro, Outi Mäkitie, Patrizia Agretti, Marta Christov, Marie-Laure Kottler, Dov Tiosano, William E. Russell, Nikolas Koscielniak, Rieko Takatani, Massimo Tonacchera, Petteri Ahtiainen, Dionisios Chrysis, Harald Jüppner |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
musculoskeletal diseases
Adult Male medicine.medical_specialty endocrine system endocrine system diseases Endocrinology Diabetes and Metabolism PSEUDOHYPOPARATHYROIDISM Chromosomes Human Pair 20 Parathyroid hormone Thyrotropin EPIGENETICS HYPOTHYROIDISM PTH GNAS Syntaxin 16 Article Epigenesis Genetic Exon Hyperphosphatemia Young Adult Internal medicine GNAS complex locus Medicine Humans Orthopedics and Sports Medicine Pseudohypoparathyroidism Subclinical infection biology business.industry Infant Newborn Infant Exons medicine.disease Endocrinology Child Preschool biology.protein STX16 Female business hormones hormone substitutes and hormone antagonists Hormone |
| Popis: | Hypocalcemia and hyperphosphatemia because of resistance toward parathyroid hormone (PTH) in the proximal renal tubules are the most prominent abnormalities in patients affected by pseudohypoparathyroidism type Ib (PHP-Ib). In this rare disorder, which is caused by GNAS methylation changes, resistance can occur toward other hormones, such as thyroid-stimulating hormone (TSH), that mediate their actions through G protein-coupled receptors. However, these additional laboratory abnormalities are usually not recognized until PTH-resistant hypocalcemia becomes clinically apparent. We now describe four pediatric patients, first diagnosed with subclinical or overt hypothyroidism between the ages of 0.2 and 15 years, who developed overt PTH-resistance 3 to 20 years later. Although anti-thyroperoxidase (anti-TPO) antibodies provided a plausible explanation for hypothyroidism in one of these patients, this and two other patients revealed broad epigenetic GNAS abnormalities, which included loss of methylation (LOM) at exons AS, XL, and A/B, and gain of methylation at exon NESP55; ie, findings consistent with PHP-Ib. LOM at GNAS exon A/B alone led in the fourth patient to the identification of a maternally inherited 3-kb STX16 deletion, a well-established cause of autosomal dominant PHP-Ib. Although GNAS methylation changes were not detected in additional pediatric and adult patients with subclinical hypothyroidism (23 pediatric and 39 adult cases), hypothyroidism can obviously be the initial finding in PHP-Ib patients. One should therefore consider measuring PTH, along with calcium and phosphate, in patients with unexplained hypothyroidism for extended periods of time to avoid hypocalcemia and associated clinical complications. |
| Databáze: | OpenAIRE |
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