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Thyroid hormone resistance, generalized, autosomal dominant(GRTHD)

MedGen UID:
424846
Concept ID:
C2937288
Disease or Syndrome
Synonyms: GRTHD; HYPERTHYROXINEMIA, FAMILIAL EUTHYROID, SECONDARY TO PITUITARY AND PERIPHERAL RESISTANCE TO THYROID HORMONES; Thyroid Hormone Resistance, Autosomal Dominant
 
Gene (location): THRB (3p24.2)
 
Monarch Initiative: MONDO:0008569
OMIM®: 188570

Definition

Generalized thyroid hormone resistance (GRTH) is characterized by elevated serum levels of free thyroid hormones with inappropriately elevated thyroid-stimulating hormone (TSH) as well as clinical and biochemical evidence of decreased thyroid hormone action. Affected individuals also show unresponsiveness to large doses of exogenous thyroid hormones (summary by Parrilla et al., 1991). [from OMIM]

Clinical features

From HPO
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Attention deficit hyperactivity disorder
MedGen UID:
220387
Concept ID:
C1263846
Mental or Behavioral Dysfunction
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.
Increased circulating thyroglobulin concentration
MedGen UID:
1375023
Concept ID:
C4476805
Finding
An abnormal elevation of the concentration of thyroglobulin, a protein produced in the thyroid gland that acts as a precursor to thyrroid hormones.
Goiter
MedGen UID:
42270
Concept ID:
C0018021
Disease or Syndrome
An enlargement of the thyroid gland.
Increased circulating free T3
MedGen UID:
867466
Concept ID:
C4021843
Finding
An elevated concentration of free 3,3',5-triiodo-L-thyronine in the blood circulation.
Generalized resistance to thyroid hormone
MedGen UID:
1654700
Concept ID:
C4722330
Disease or Syndrome
Reduced sensitivity of end organs to thyroid hormone characterized by elevated serum levels of free thyroid hormone with nonsuppressed thyroid stimulating hormone.
Increased circulating free T4 concentration
MedGen UID:
1771990
Concept ID:
C5421591
Finding
An elevated concentration of free thyroxine (fT4) in the blood circulation.

Professional guidelines

PubMed

Pappa T, Anselmo J, Mamanasiri S, Dumitrescu AM, Weiss RE, Refetoff S
J Clin Endocrinol Metab 2017 Oct 1;102(10):3775-3782. doi: 10.1210/jc.2017-01251. PMID: 28938413Free PMC Article

Recent clinical studies

Etiology

Pappa T, Anselmo J, Mamanasiri S, Dumitrescu AM, Weiss RE, Refetoff S
J Clin Endocrinol Metab 2017 Oct 1;102(10):3775-3782. doi: 10.1210/jc.2017-01251. PMID: 28938413Free PMC Article
Weinert LS, Ceolin L, Romitti M, Camargo EG, Maia AL
Arq Bras Endocrinol Metabol 2012 Feb;56(1):67-71. doi: 10.1590/s0004-27302012000100010. PMID: 22460197
Brucker-Davis F, Skarulis MC, Grace MB, Benichou J, Hauser P, Wiggs E, Weintraub BD
Ann Intern Med 1995 Oct 15;123(8):572-83. doi: 10.7326/0003-4819-123-8-199510150-00002. PMID: 7677297

Diagnosis

Sun H, Cao L, Zheng R, Xie S, Liu C
Ital J Pediatr 2020 Nov 11;46(1):168. doi: 10.1186/s13052-020-00929-x. PMID: 33176840Free PMC Article
Pappa T, Anselmo J, Mamanasiri S, Dumitrescu AM, Weiss RE, Refetoff S
J Clin Endocrinol Metab 2017 Oct 1;102(10):3775-3782. doi: 10.1210/jc.2017-01251. PMID: 28938413Free PMC Article
Olateju TO, Vanderpump MP
Ann Clin Biochem 2006 Nov;43(Pt 6):431-40. doi: 10.1258/000456306778904678. PMID: 17132274
Refetoff S
Acta Paediatr Jpn 1994 Feb;36(1):1-15. doi: 10.1111/j.1442-200x.1994.tb03121.x. PMID: 8165897
Refetoff S
Thyroid 1994 Fall;4(3):345-9. doi: 10.1089/thy.1994.4.345. PMID: 7833674

Therapy

Carbone A, Verrienti A, Cito DS, Sponziello M, Pecce V, Bruno R
Endocrine 2024 Aug;85(2):598-600. Epub 2024 Apr 1 doi: 10.1007/s12020-024-03795-3. PMID: 38558372
Akahori H, Usuda R
J Med Case Rep 2021 Sep 25;15(1):473. doi: 10.1186/s13256-021-03061-4. PMID: 34560890Free PMC Article
Brucker-Davis F, Skarulis MC, Grace MB, Benichou J, Hauser P, Wiggs E, Weintraub BD
Ann Intern Med 1995 Oct 15;123(8):572-83. doi: 10.7326/0003-4819-123-8-199510150-00002. PMID: 7677297
Refetoff S
Acta Paediatr Jpn 1994 Feb;36(1):1-15. doi: 10.1111/j.1442-200x.1994.tb03121.x. PMID: 8165897
Mixson AJ, Hauser P, Tennyson G, Renault JC, Bodenner DL, Weintraub BD
J Clin Invest 1993 May;91(5):2296-300. doi: 10.1172/JCI116458. PMID: 8486789Free PMC Article

Prognosis

Pappa T, Anselmo J, Mamanasiri S, Dumitrescu AM, Weiss RE, Refetoff S
J Clin Endocrinol Metab 2017 Oct 1;102(10):3775-3782. doi: 10.1210/jc.2017-01251. PMID: 28938413Free PMC Article
Slezak R, Lukienczuk T, Noczynska A, Karpinski P, Lebioda A, Misiak B, Sasiadek MM
Horm Metab Res 2012 Sep;44(9):704-7. Epub 2012 Jun 13 doi: 10.1055/s-0032-1312666. PMID: 22696245

Clinical prediction guides

Slezak R, Lukienczuk T, Noczynska A, Karpinski P, Lebioda A, Misiak B, Sasiadek MM
Horm Metab Res 2012 Sep;44(9):704-7. Epub 2012 Jun 13 doi: 10.1055/s-0032-1312666. PMID: 22696245
Grasberger H, Mimouni-Bloch A, Vantyghem MC, van Vliet G, Abramowicz M, Metzger DL, Abdullatif H, Rydlewski C, Macchia PE, Scherberg NH, van Sande J, Mimouni M, Weiss RE, Vassart G, Refetoff S
J Clin Endocrinol Metab 2005 Jul;90(7):4025-34. Epub 2005 May 3 doi: 10.1210/jc.2005-0572. PMID: 15870119
Leonard CM, Martinez P, Weintraub BD, Hauser P
Am J Med Genet 1995 Jun 19;60(3):238-43. doi: 10.1002/ajmg.1320600314. PMID: 7573179
Takeda K, Sakurai A, DeGroot LJ, Refetoff S
J Clin Endocrinol Metab 1992 Jan;74(1):49-55. doi: 10.1210/jcem.74.1.1727829. PMID: 1727829
Magner JA, Petrick P, Menezes-Ferreira MM, Stelling M, Weintraub BD
J Endocrinol Invest 1986 Dec;9(6):459-70. doi: 10.1007/BF03346968. PMID: 3571851

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