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Familial Hyperthyroidism due to Mutations in TSH Receptor

Resistance to Thyroid Stimulating Hormone


Presentation

  • Craniosynostosis was present in half the patients [ 30, 49 ]. Symptoms of developmental impairment (such as mental retardation and speech disturbances) and hydrocephalus were also present in almost half of the affected patients [ 30, 49 ].[karger.com]
  • Given the variability in clinical presentation in all patients with RTH, it is difficult to classify patients as having purely PRTH or RTH, as some patients with the identical Tr beta mutation may present with either PRTH or RTH.[endocrinologyadvisor.com]
  • Recurrent pregnancy-induced thyrotoxicosis presenting as hyperemesis gravidarum: case report. Br J Obstet Gynaecol 1985 ;92: 413 - 415 9. Krentz AJ, Redman H, Taylor KG. Hyperthyroidism associated with hyperemesis gravidarum.[nejm.org]
  • Thyroid autoantibodies are frequently present . TSH-R Ab are specific but anti-TPO and anti-TG may also be present. In clinical practice, anti-TPO is often measured, as measurement of TSH-R Ab is not readily available.[ocw.tufts.edu]
  • Newborns with congenital hyperthyroidism due to maternal Graves' disease seem to present significant transitory ocular manifestations more frequently, but again no infiltrative ophtalmopathy requiring specific therapy is present.[thieme-connect.com]
Delayed Speech Development
  • speech development Impaired speech and language development Impaired speech development Language delay Language delayed Language development deficit Late-onset speech development Poor language development Speech and language delay Speech and language[rarediseases.info.nih.gov]
Morning Sickness
  • Morning sickness and thyroid function. Br J Obstet Gynaecol 1986 ;93: 520 - 522 19. Rosenthal FD, Jones C, Lewis SI. Thyrotoxic vomiting. BMJ 1976 ;2: 209 - 211 20. Depue RH, Bernstein L, Ross RK, Judd HL, Henderson BE.[nejm.org]
Advanced Bone Age
  • bone age Early bone maturation [ more ] 0005616 Agitation 0000713 Global developmental delay 0001263 Hyperactivity More active than typical 0000752 Motor delay 0001270 Sleep disturbance Difficulty sleeping Trouble sleeping [ more ] 0002360 1%-4% of people[rarediseases.info.nih.gov]
  • All these features (prematurity, low birth weight and advanced bone age) are typical for congenital hyperthyroidism but are not specific for PSNAH. Craniosynostosis was present in half the patients [ 30, 49 ].[karger.com]
Skin Lesion
  • lesions and fibrous dysplasia of bone, as in typical McCune-Albright syndrome). (5) Negative family history of non-autoimmune hyperthyroidism. (6) Various consequences of prolonged neonatal hyperthyroidism, such as craniosynostosis or low birth weight[karger.com]
Delayed Speech and Language Development
  • speech and language development Deficiency of speech development Delayed language development Delayed speech Delayed speech acquisition Delayed speech development Impaired speech and language development Impaired speech development Language delay Language[rarediseases.info.nih.gov]
Language Delays
  • delay Language delayed Language development deficit Late-onset speech development Poor language development Speech and language delay Speech and language difficulties Speech delay [ more ] 0000750 Hyperthyroidism Overactive thyroid 0000836 Intellectual[rarediseases.info.nih.gov]
Encephalopathy
  • Atelosteogenesis type I Atelosteogenesis type III Autosomal dominant Larsen syndrome Boomerang dysplasia Spondylocarpotarsal synostosis Auriculocondylar syndrome Autosomal agammaglobulinemia Autosomal dominant hypocalcemia Early infantile epileptic encephalopathy[csbg.cnb.csic.es]

Workup

  • […] athyreosis should be differentiated from severe hypoplasia and ectopic thyroid either clinically (by scintiscan) or postmortem Thyroid dysgenesis is often being a part of complex syndrome with extrathyroid comorbidities, which needs further diagnostic workup[pathologyoutlines.com]
Thrombocytosis
  • […] gestational hyperthyroidism Hypothyroidism due to TSH receptor mutations Thyroid hypoplasia Essential thrombocythemia Myelofibrosis with myeloid metaplasia Autosomal dominant hyper-IgE syndrome Fibronectin glomerulopathy Budd-Chiari syndrome Familial thrombocytosis[csbg.cnb.csic.es]

Treatment

  • Make the best clinical decisions with an enhanced emphasis on evidence-based practice and expert opinions on treatment strategies. Zero in on the most relevant and useful references with the aid of a more focused, concise bibliography.[books.google.com]
  • You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.[rarediseases.info.nih.gov]
  • Patients receiving amiodarone (pre-treatment, then every six months until off treatment for a year) or lithium (pre-treatment, every six to twelve months whilst on treatment). Following neck irradiation (annual TFTs).[patient.info]

Prognosis

  • Thyroid cancer represents 6% of new cancer cases in women, and 60% of affected individuals are under age 55.1 Although most thyroid cancers are the well-differentiated, papillary, or follicular subtypes that carry a good prognosis, papillary thyroid cancers[targetedonc.com]
  • Differentiated Thyroid Cancer (DTC) has a relatively favourable prognosis if treated and monitored properly. The clinical use of thyroid testing in a general practice has increased by 50% over the last decade [5].[austinpublishinggroup.com]
  • […] avoid the negative consequences of persistent or relapsing hyperthyroidism. (2) Immediate treatment of overt neonatal hyperthyroidism with methimazole (not propylthiouracil because of its association with severe liver injury) is recommended for a good prognosis[karger.com]
  • One recurrent tentation when dealing with pathogenic mutation in human disease, is to try to correlate genotype and phenotype, with the hope there could be a kind of genetic prognosis following the genetic diagnosis.[em-consulte.com]

Etiology

  • The etiology of persistent neonatal hyperthyroidism was clarified by the discovery of an activating germ-line mutation in the thyroid-stimulating hormone (TSH) receptor in 1995.[neoreviews.aappublications.org]
  • Multiple etiologies can lead to a common clinical state of “thyrotoxicosis,” which is a consequence of the high thyroid hormone levels and their action on different tissues of the body.[comprehensivephysiology.com]
  • Note Defects in TSHR are found in patients affected by hyperthyroidism with different etiologies.[genecards.org]
  • For reasons that remain somewhat unclear, but are presumably related to the etiology of hyperemesis in this setting, beta-blocking agents rapidly improve the symptoms and signs.[endotext.org]
  • Hashimoto K, 1998 The etiology of isolated thyroid stimulating hormone deficiency. Intern Med 37: 231-232. 2. Shuman CR, 1953 Hypothyroidism due to thyrotropin deficiency without other manifestations of hypopituitarism.[hormones.gr]

Epidemiology

  • […] hyperthyroidism - Resistance to thyroid stimulating hormone Classification (Orphanet): - Rare circulatory system disease - Rare endocrine disease - Rare genetic disease - Rare renal disease Classification (ICD10): - Endocrine, nutritional and metabolic diseases - Epidemiological[csbg.cnb.csic.es]
  • Genatlas disease for TSHR Gene hypothyroidism,congenital,with high TSH,TSH unresponsiveness (TSHR defect in few cases),including thyroid hypoplasia Relevant External Links for TSHR Genetic Association Database (GAD) TSHR Human Genome Epidemiology (HuGE[genecards.org]
  • Epidemiology/Pathophysiology Graves' disease is the most common form of hyperthyroidism accounting for 60-70% of all cases. It occurs in up to 3% of the population.[ocw.tufts.edu]
  • […] dysgenesis (dysthyroidosis, thyroid dysgenetic disorder) is a collective term for various anomalies in the anatomic development of the thyroid, including thyroid gland proper abnormalities (agenesis, hemiagenesis and hypoplasia) and ectopic thyroid tissue Epidemiology[pathologyoutlines.com]
  • Iodine‐induced hyperthyroidism: Occurrence and epidemiology. Thyroid 8: 83‐100, 1998. 86. Sundaraiya S, Dizdarevic S, Miles K, Quin J, Williams A, Wheatley T, Zammitt C.[comprehensivephysiology.com]
Sex distribution
Age distribution

Pathophysiology

  • Epidemiology/Pathophysiology Graves' disease is the most common form of hyperthyroidism accounting for 60-70% of all cases. It occurs in up to 3% of the population.[ocw.tufts.edu]
  • Thyroid stimulating hormone receptor (TSHR) and its endogenous ligand thyroid stimulating hormone (TSH) are pivotal factors in physiologic function and pathophysiology of benign and malignant thyroid diseases.[targetedonc.com]
  • The pathophysiologic mechanism is believed to be promiscuous stimulation of the thyrotropin receptor by the excess chorionic gonadotropin. 4,5 The explanation for this stimulation is the close structural relations between chorionic gonadotropin and thyrotropin[nejm.org]
  • […] show absence of the left lobe with a left:right ratio of 4:1 ( J Clin Endocrinol Metab 1981;52:247 ) Thyroid hemiagenesis has several variations: absent lobe, absent lobe and isthmus, absent isthmus, absent both lateral lobes with remaining isthmus Pathophysiology[pathologyoutlines.com]
  • Genetic Etiology and Pathophysiology FNAH and PSNAH are caused by constitutively activating TSHR germline mutations [ 31, 50, 51 ]. This gene is encoded by 10 exons which extend over 60 kb on chromosome 14q31 (OMIM 603372).[karger.com]

Prevention

  • […] in a term newborn suggests hypothyroidism of prenatal onset ( Braverman, Cooper: Werner & Ingbar's The Thyroid, 10th Edition, 2012 ) Prognostic factors Early diagnosis and treatment (not later than 3 months of age) of hypothyroidism are critical to prevent[pathologyoutlines.com]
  • The outlook for this preventable cause of growth restriction and intellectual disability has been transformed by newborn screening. [ 21 ][patient.info]
  • […] consequences of persistent or relapsing hyperthyroidism. (2) Immediate treatment of overt neonatal hyperthyroidism with methimazole (not propylthiouracil because of its association with severe liver injury) is recommended for a good prognosis and for the prevention[karger.com]
  • This is not a purely academic problem, in that presymptomatic diagnosis in children of affected families may prevent the developmental or psychological complications associated with infantile or juvenile hyperthyroidism.[clinicalgate.com]
  • Thionamides Thionamides (propylthiouracil [PTU] and methimazole) inhibit thyroid hormone synthesis through inhibition of thyroidal peroxidase , prevention of oxidation of trapped iodine, inhibition of coupling of iodotyrosines, inhibition of conversion[ocw.tufts.edu]

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