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Hypothyroidism, congenital, nongoitrous, 7(CHNG7)

MedGen UID:
349957
Concept ID:
C1861106
Disease or Syndrome
Synonyms: CHNG7; Resistance to thyrotropin-releasing hormone syndrome; Thyrotropin-releasing hormone resistance, generalized
SNOMED CT: Resistance to thyrotropin-releasing hormone syndrome (725462002); TRH (thyrotropin-releasing hormone) resistance syndrome (725462002); Congenital central hypothyroidism due to thyrotropin-releasing hormone receptor deficiency (725462002)
 
Gene (location): TRHR (8q23.1)
 
Monarch Initiative: MONDO:0032819
OMIM®: 618573

Definition

A type of central congenital hypothyroidism with characteristics of low levels of thyroid hormones due to insufficient release of thyroid-stimulating hormone (TSH) caused by pituitary resistance to thyrotropin-releasing hormone (TRH). It may or may not be observed from birth. The clinical manifestations are often subtle, probably as a result of trans-placental passage of some maternal thyroid hormone or due to the fact that many infants have some thyroid production of their own. More specific symptoms and signs often do not develop until several months of age. Common clinical features and signs include decreased activity and increased sleep, feeding difficulty and constipation, prolonged jaundice. Slow linear growth and developmental delay are usually apparent by 4-6 months of age. Caused by mutations in the TRH receptor gene (TRHR; 8q23). [from SNOMEDCT_US]

Clinical features

From HPO
Fatigue
MedGen UID:
41971
Concept ID:
C0015672
Sign or Symptom
A subjective feeling of tiredness characterized by a lack of energy and motivation.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Lethargy
MedGen UID:
7310
Concept ID:
C0023380
Sign or Symptom
A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks.
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Decreased circulating T4 concentration
MedGen UID:
1611997
Concept ID:
C4531078
Finding
A reduction below the normal concentration of thyroxine in the blood. Thyroxine (also known as T4) is the main hormone secreted by the thyroid gland into the blood. It can be converted into the active form triiodothyronine (also known as T3).
Reduced TSH response to thyrotrophin-releasing hormone stimulation test
MedGen UID:
1759429
Concept ID:
C5421596
Finding
A lower than normal TSH response to thyrotrophin-releasing hormone stimulation test.

Recent clinical studies

Etiology

Bagattini B, Cosmo CD, Montanelli L, Piaggi P, Ciampi M, Agretti P, Marco GD, Vitti P, Tonacchera M
Eur J Endocrinol 2014 Nov;171(5):615-21. doi: 10.1530/EJE-14-0621. PMID: 25305309
Gaitan E, Cooksey RC, Meydrech EF, Legan J, Gaitan GS, Astudillo J, Guzman R, Guzman N, Medina P
J Clin Endocrinol Metab 1989 Aug;69(2):359-63. doi: 10.1210/jcem-69-2-359. PMID: 2753978

Diagnosis

Li Y, Sun J, Jiao Y, Li N, Zhao W
J Clin Endocrinol Metab 2024 Feb 20;109(3):691-700. doi: 10.1210/clinem/dgad607. PMID: 37831130
Martín M, Bernal Barquero CE, Geysels RC, Papendieck P, Peyret V, Masini-Repiso AM, Chiesa AE, Nicola JP
Thyroid 2019 Jul;29(7):1023-1026. Epub 2019 Jul 2 doi: 10.1089/thy.2019.0046. PMID: 31115276
Hahn HB
Postgrad Med 1975 Jun;57(7):71-4. doi: 10.1080/00325481.1975.11714074. PMID: 48245

Therapy

Martín M, Bernal Barquero CE, Geysels RC, Papendieck P, Peyret V, Masini-Repiso AM, Chiesa AE, Nicola JP
Thyroid 2019 Jul;29(7):1023-1026. Epub 2019 Jul 2 doi: 10.1089/thy.2019.0046. PMID: 31115276
Bagattini B, Cosmo CD, Montanelli L, Piaggi P, Ciampi M, Agretti P, Marco GD, Vitti P, Tonacchera M
Eur J Endocrinol 2014 Nov;171(5):615-21. doi: 10.1530/EJE-14-0621. PMID: 25305309
Gaitan E, Cooksey RC, Meydrech EF, Legan J, Gaitan GS, Astudillo J, Guzman R, Guzman N, Medina P
J Clin Endocrinol Metab 1989 Aug;69(2):359-63. doi: 10.1210/jcem-69-2-359. PMID: 2753978
Hahn HB
Postgrad Med 1975 Jun;57(7):71-4. doi: 10.1080/00325481.1975.11714074. PMID: 48245

Prognosis

Martín M, Bernal Barquero CE, Geysels RC, Papendieck P, Peyret V, Masini-Repiso AM, Chiesa AE, Nicola JP
Thyroid 2019 Jul;29(7):1023-1026. Epub 2019 Jul 2 doi: 10.1089/thy.2019.0046. PMID: 31115276

Clinical prediction guides

Martín M, Bernal Barquero CE, Geysels RC, Papendieck P, Peyret V, Masini-Repiso AM, Chiesa AE, Nicola JP
Thyroid 2019 Jul;29(7):1023-1026. Epub 2019 Jul 2 doi: 10.1089/thy.2019.0046. PMID: 31115276
Bagattini B, Cosmo CD, Montanelli L, Piaggi P, Ciampi M, Agretti P, Marco GD, Vitti P, Tonacchera M
Eur J Endocrinol 2014 Nov;171(5):615-21. doi: 10.1530/EJE-14-0621. PMID: 25305309

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