title: A Patient With a Thyrotropin-Secreting Microadenoma and Resistance to Thyroid Hormone (P453T).
abstract: BACKGROUND
  Resistance to thyroid hormone (RTH) β is due to mutations in the β-isoform of the thyroid hormone receptor (TR). TSH-secreting adenomas (TSHomas) are presumed to represent clonal expansion and have been reported to contain TRβ gene mutations. Mice with a knock-in mutation in the TRβ gene spontaneously develop TSHomas, although as yet no patient has been reported to have both a TSHoma and RTHβ.
  
  
  OBJECTIVE
  We investigated a 12-year-old girl with elevated serum T4 concentration, inappropriately high TSH levels, and a pituitary adenoma.
  
  
  METHODS
  Clinical, biochemical, and radiological assessments were performed at baseline and after a transsphenoidal pituitary adenomectomy.
  
  
  RESULTS
  The patient's laboratory results included: TSH, 21.12 mIU/L (0.35-4.94 mIU/L); free T3, 14.25 pmol/L (2.63-5.7 pmol/L); free T4, 28.79 pmol/L (9.01-19.05 pmol/L); serum glycoprotein hormone alpha-subunit (α-GSU), 0.32 ng/ml (0.22-0.39 ng/ml); and α-GSU/TSH, 0.15. Thyroid radioiodine uptake was increased by 94.4% at 24 hours. A T3 suppression test showed incomplete suppression of the serum TSH concentration and blunted response of the peripheral thyroid hormone markers. The sequence of TRβ exons confirmed a P453T mutation in the TRβ gene. Pituitary magnetic resonance imaging revealed a microadenoma in the left side of the pituitary. The patient underwent transsphenoidal pituitary adenomectomy. Histologically, the tumor stained positively for TSH-β, human Chorionic Gonadotropin alpha (HCG-α), GH, prolactin, and ACTH. After removal of the tumor, the patient's thyroid function improved significantly, and she experienced the onset of menarche and an increase in linear growth as well.
  
  
  CONCLUSIONS
  This patient with RTHβ had a TSHoma consistent with previous findings linking somatic TRβ mutations to TSHomas.
authors: Department of Endocrinology and Metabolism (X.T., T.J., W.T., Z.S.), Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China; Molecular Endocrinology Laboratory (G.A.B.), Veterans Affairs Greater Los Angeles Healthcare System, Departments of Medicine and Physiology, UCLA David Geffen School of Medicine, Los Angeles, California 90073; and Department of Neurosurgery (A.W.), The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors: Xiaochun
authors: X
authors: Teng
authors: Department of Endocrinology and Metabolism (X.T., T.J., W.T., Z.S.), Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China; Molecular Endocrinology Laboratory (G.A.B.), Veterans Affairs Greater Los Angeles Healthcare System, Departments of Medicine and Physiology, UCLA David Geffen School of Medicine, Los Angeles, California 90073; and Department of Neurosurgery (A.W.), The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors: Ting
authors: T
authors: Jin
authors: Department of Endocrinology and Metabolism (X.T., T.J., W.T., Z.S.), Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China; Molecular Endocrinology Laboratory (G.A.B.), Veterans Affairs Greater Los Angeles Healthcare System, Departments of Medicine and Physiology, UCLA David Geffen School of Medicine, Los Angeles, California 90073; and Department of Neurosurgery (A.W.), The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors: Gregory A
authors: GA
authors: Brent
authors: Department of Endocrinology and Metabolism (X.T., T.J., W.T., Z.S.), Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China; Molecular Endocrinology Laboratory (G.A.B.), Veterans Affairs Greater Los Angeles Healthcare System, Departments of Medicine and Physiology, UCLA David Geffen School of Medicine, Los Angeles, California 90073; and Department of Neurosurgery (A.W.), The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors: Anhua
authors: A
authors: Wu
authors: Department of Endocrinology and Metabolism (X.T., T.J., W.T., Z.S.), Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China; Molecular Endocrinology Laboratory (G.A.B.), Veterans Affairs Greater Los Angeles Healthcare System, Departments of Medicine and Physiology, UCLA David Geffen School of Medicine, Los Angeles, California 90073; and Department of Neurosurgery (A.W.), The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors: Weiping
authors: W
authors: Teng
authors: Department of Endocrinology and Metabolism (X.T., T.J., W.T., Z.S.), Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China; Molecular Endocrinology Laboratory (G.A.B.), Veterans Affairs Greater Los Angeles Healthcare System, Departments of Medicine and Physiology, UCLA David Geffen School of Medicine, Los Angeles, California 90073; and Department of Neurosurgery (A.W.), The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors: Zhongyan
authors: Z
authors: Shan
mesh_terms: D000236:Adenoma / Q000378:metabolism*; D019943:Amino Acid Substitution; D002648:Child; D005260:Female; D006801:Humans; D006964:Hyperpituitarism / Q000209:etiology; D009384:Paraneoplastic Endocrine Syndromes / Q000150:complications*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011392:Proline / Q000235:genetics; D013912:Threonine / Q000235:genetics; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*; D018382:Thyroid Hormone Resistance Syndrome / Q000150:complications* / Q000235:genetics; D013972:Thyrotropin / Q000378:metabolism*
chemical_list: D037042:Thyroid Hormone Receptors beta; D013912:Threonine; D013972:Thyrotropin; D011392:Proline