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PRTH  -  pituitary resistance to thyroid hormone

Homo sapiens

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Disease relevance of PRTH


High impact information on PRTH

  • Resistance to thyroid hormone (RTH), with elevated serum free thyroid hormones and nonsuppressed thyrotropin levels, is either relatively asymptomatic, suggesting a generalized disorder (GRTH) or associated with thyrotoxic features, indicating possible selective pituitary resistance (PRTH) [6].
  • We have examined the c-erbA beta thyroid hormone receptor gene in a kindred, G.H., with a member, patient G.H., who had a severe form of selective pituitary resistance to thyroid hormones (PRTH) [7].
  • The mutant TR displays normal or enhanced function on stimulatory thyroid hormone response elements found in peripheral tissues, but has defective function on inhibitory thyroid hormone response elements found in the TRH and TSH subunit genes and explains the PRTH phenotype [8].
  • In a patient with PRTH, a novel mutation of a conserved arginine residue adjacent to the ninth heptad of TR-beta selectively disrupts TR homodimer formation [8].
  • Association of the PRTH phenotype with in vitro behavior of the mutant TR has proved elusive [9].

Chemical compound and disease context of PRTH


Biological context of PRTH

  • Previously, we identified a point mutation of the T3 receptor (TR) beta gene (R338W) in a patient with pituitary resistance to thyroid hormone (PRTH) [13].
  • Molecular genetic studies have shown that even within a single kindred the same receptor mutation was associated with both, GRTH or PRTH, and therefore suggest that these two forms represent part of a variable clinical spectrum of a single genetic disorder.(ABSTRACT TRUNCATED AT 250 WORDS)[14]
  • A 29-yr-old woman with pituitary resistance to thyroid hormones (PRTH) was found to harbor a novel point mutation (T337A) on exon 9 of the thyroid hormone receptor beta (TRbeta) gene [15].
  • In the current study a patient with PRTH diagnosed at age 15 yr underwent separate therapeutic trials with Brc and Triac, during which time physical parameters, thyroid function tests, systolic time intervals (STI), and oxygen consumption (VO2) were measured [16].

Anatomical context of PRTH

  • For unclear reasons, in PRTH, the pituitary gland is resistant to the feedback inhibitory effects of circulating thyroid hormones while peripheral tissues respond normally, causing patients to experience the toxic peripheral effects of thyroid hormone excess [1].
  • These results conform to the clinical features of R316H which is associated with apparent pituitary resistance of thyroid hormone (PRTH) [17].

Associations of PRTH with chemical compounds

  • PRTH is ideally treated by chronically suppressing TSH secretion with medications such as D-thyroxine, TRIAC, octreotide, or bromocriptine [1].
  • Although the metoclopramide test results confirmed the existence of an increased dopaminergic inhibitory tone in nonneoplastic inappropriate secretion of TSH, the outcome of bromocriptine treatment indicated that the dopaminergic control over TSH release was not enough in this case of PRTH [18].
  • DESIGN AND PATIENTS: Eight patients with TSH-oma and four with PRTH underwent the acute test with somatostatin analogue Octreotide (0.1 mg subcutaneously), as well as long-acting Octreotide-LAR (30 mg intramuscularly every 28 days) for two months [19].
  • Particular emphasis is given to the clinical and hormonal outcome after 2 years of triiodothyroacetic acid (TRIAC) treatment in an affected child with peripheral thyrotoxic features (pituitary RTH [PRTH]) [20].
  • The calculated MTT EC(50) values ranged from 2 microM (CF) to 651 microM (CBZ) in PLHC-1, and from 53 microM (FF) to 962 microM (GdCl(3)) in PRTH [21].

Other interactions of PRTH

  • Whether TR-beta mutations cause a selective form of RTH, which only leads to abnormal pituitary TSH secretion (PRTH), is unclear [8].
  • PRTH is a nonneoplastic disorder caused by inherited mutations in the gene for the thyroid hormone receptor beta; it is a poorly understood variant of GRTH [1].
  • (4) The differential dominant negative effect of mutant R316H (negative TRE > positive TRE) may explain, at least in part, the presentation of R316H as PRTH [17].
  • Two clinical variants, generalized resistance to thyroid hormone (GRTH) and selective pituitary resistance to thyroid hormone (PRTH), are, in most cases, caused by heterozygous mutations in the ligand-binding domain of the c-erbA beta thyroid hormone receptor gene [12].
  • In fact, growth velocity remained unchanged and no alteration of several parameters of thyroid hormone action at the tissue level was observed, whereas soluble interleukin-2 receptor levels improved significantly, confirming the safety and efficacy of long-term TRIAC therapy for PRTH also during childhood [20].

Analytical, diagnostic and therapeutic context of PRTH


  1. Central hyperthyroidism. McDermott, M.T., Ridgway, E.C. Endocrinol. Metab. Clin. North Am. (1998) [Pubmed]
  2. Dopaminergic modulation of TSH and its subunits: in vivo and in vitro studies. Cooper, D.S., Klibanski, A., Ridgway, E.C. Clin. Endocrinol. (Oxf) (1983) [Pubmed]
  3. G20210A PRTH gene mutation and other trombophilic polymorphisms in patients with cerebral vein thrombosis. Madonna, P., De Stefano, V., Coppola, A., Albisinni, R., Cerbone, A.M. Stroke (2000) [Pubmed]
  4. Thyrotoxicosis due to pituitary resistance to thyroid hormones. Successful control with D thyroxine: a study in three patients. Dorey, F., Strauch, G., Gayno, J.P. Clin. Endocrinol. (Oxf) (1990) [Pubmed]
  5. The variable clinical phenotype in thyroid hormone resistance syndrome. Beck-Peccoz, P., Chatterjee, V.K. Thyroid (1994) [Pubmed]
  6. Genetic analysis of 29 kindreds with generalized and pituitary resistance to thyroid hormone. Identification of thirteen novel mutations in the thyroid hormone receptor beta gene. Adams, M., Matthews, C., Collingwood, T.N., Tone, Y., Beck-Peccoz, P., Chatterjee, K.K. J. Clin. Invest. (1994) [Pubmed]
  7. An arginine to histidine mutation in codon 311 of the C-erbA beta gene results in a mutant thyroid hormone receptor that does not mediate a dominant negative phenotype. Geffner, M.E., Su, F., Ross, N.S., Hershman, J.M., Van Dop, C., Menke, J.B., Hao, E., Stanzak, R.K., Eaton, T., Samuels, H.H. J. Clin. Invest. (1993) [Pubmed]
  8. A novel C-terminal domain in the thyroid hormone receptor selectively mediates thyroid hormone inhibition. Flynn, T.R., Hollenberg, A.N., Cohen, O., Menke, J.B., Usala, S.J., Tollin, S., Hegarty, M.K., Wondisford, F.E. J. Biol. Chem. (1994) [Pubmed]
  9. Isoform variable action among thyroid hormone receptor mutants provides insight into pituitary resistance to thyroid hormone. Safer, J.D., Langlois, M.F., Cohen, R., Monden, T., John-Hope, D., Madura, J., Hollenberg, A.N., Wondisford, F.E. Mol. Endocrinol. (1997) [Pubmed]
  10. Anti-iodothyronine autoantibodies in a girl with hyperthyroidism due to pituitary resistance to thyroid hormones. Crinò, A., Borrelli, P., Salvatori, R., Cortelazzi, D., Roncoroni, R., Beck-Peccoz, P. J. Endocrinol. Invest. (1992) [Pubmed]
  11. Treatment of pituitary resistance to thyroid hormone (PRTH) in an 8-year-old boy. Pohlenz, J., Knöbl, D. Acta Paediatr. (1996) [Pubmed]
  12. Resistance to thyroid hormone in children. Usala, S.J. Curr. Opin. Pediatr. (1994) [Pubmed]
  13. Functional properties of a mutant T3 receptor beta (R338W) identified in a subject with pituitary resistance to thyroid hormone. Sasaki, S., Nakamura, H., Tagami, T., Miyoshi, Y., Nakao, K. Mol. Cell. Endocrinol. (1995) [Pubmed]
  14. Resistance to thyroid hormone--an uncommon cause of thyroxine excess and inappropriate TSH secretion. Chatterjee, V.K. Acta Med. Austriaca (1994) [Pubmed]
  15. Prenatal diagnosis of thyroid hormone resistance. Asteria, C., Rajanayagam, O., Collingwood, T.N., Persani, L., Romoli, R., Mannavola, D., Zamperini, P., Buzi, F., Ciralli, F., Chatterjee, V.K., Beck-Peccoz, P. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  16. Bromocriptine and Triac therapy for hyperthyroidism due to pituitary resistance to thyroid hormone. Dulgeroff, A.J., Geffner, M.E., Koyal, S.N., Wong, M., Hershman, J.M. J. Clin. Endocrinol. Metab. (1992) [Pubmed]
  17. The function of retinoid X receptors on negative thyroid hormone response elements. Takeda, T., Nagasawa, T., Miyamoto, T., Hashizume, K., DeGroot, L.J. Mol. Cell. Endocrinol. (1997) [Pubmed]
  18. Pituitary resistance to thyroid hormone action with preserved circadian rhythm of thyrotropin in a postmenopausal woman. Custro, N., Scafidi, V., Notarbartolo, A. J. Endocrinol. Invest. (1992) [Pubmed]
  19. Different responses to chronic somatostatin analogues in patients with central hyperthyroidism. Mannavola, D., Persani, L., Vannucchi, G., Zanardelli, M., Fugazzola, L., Verga, U., Facchetti, M., Beck-Peccoz, P. Clin. Endocrinol. (Oxf) (2005) [Pubmed]
  20. Clinical and hormonal outcome after two years of triiodothyroacetic acid treatment in a child with thyroid hormone resistance. Radetti, G., Persani, L., Molinaro, G., Mannavola, D., Cortelazzi, D., Chatterjee, V.K., Beck-Peccoz, P. Thyroid (1997) [Pubmed]
  21. Effects of human pharmaceuticals on cytotoxicity, EROD activity and ROS production in fish hepatocytes. Laville, N., Aït-Aïssa, S., Gomez, E., Casellas, C., Porcher, J.M. Toxicology (2004) [Pubmed]
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