Skip to main content
SpringerLink
Log in

Familial inappropriate TSH secretion: evidence suggesting a dissociated pituitary resistance to T3 and T4

  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

The study of pituitary thyroid relationships of a 40 - year-old woman, suffering from recurrent goiter, is presented. The characteristics of this case were the following: i) constant hyperthyrotropinemia (range 8.2 to 29 μU/ml) despite high thyroid hormone levels (mean total T4: 13.4 μg/dl; mean total T3: 255 ng/dl) and clinical euthyroidism; ii) thisTSH hypersecretion is not regulated by an excess of T4, while a suppressive effect is easily observed with T3. Together with the clinical effects observed with administration of T3 and T4, this suggests that thyroid hormone resistance predominates at the pituitary level, for T4 while not for T3; iii) evidence is presented for the familial distribution of the trait and its mode of transmission. The clinical aspect and the pattern of resistance exhibited by the propositus and her progeny appear distinct from those of previous observations of thyroid hormone resistance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jailer J.W., Holub DA Remission of Graves’ disease following radioteherapy of a pituitary neoplasm. Am. J. Med. 28: 497, 1960.

    Article  PubMed  CAS  Google Scholar 

  2. Lamberg B.A., Ripatti A.G., Juustila H., Sivula A., Björkesten G. Chromophobe pituitary adenoma with acromegaly and TSH-induced hyperthyroidism associated with parathyroid adenoma. Acta Endocrinol. (Kbh.) 60: 157, 1969.

    CAS  Google Scholar 

  3. Hamilton CR., Adams L.C., Maloof F. Hyperthyroidism due to thyrotropin-producing pituitary chromophobe adenoma. N. Engl. J. Med. 283: 1077, 1970.

    Article  PubMed  Google Scholar 

  4. Faglia G., Ferrari C., Neri V., Beck-Peccoz P., Ambrosi B., Valentini F. High plasma thyrotropin levels in two patients with pituitary tumor. Acta Endocrinol. (Kbh.) 69: 649, 1972.

    CAS  Google Scholar 

  5. Mornex R., Tommasi M., Cure M., Farcot J., Orgiazzi J., Rousset B. Hyperthyroide associée à un hypopituitarisme au cours de l’évolution d’une tumeur hypophysarie sécrétant TSH. Ann. Endocrinol. (Paris) 33: 390, 1972.

    CAS  Google Scholar 

  6. Emerson C.H., Utiger R.D. Hyperthyroidism and excessive thyrotropin secretion. N. EngL J. Med. 287: 328, 1972.

    Article  PubMed  CAS  Google Scholar 

  7. O’Donnell J., Hadden R.D., Weaver J.A. Thyrotoxicosis recurring after surgical removal of a thy rotropin pituitary adenoma Proc. R. Soc. Med. 66: 441, 1973.

    Google Scholar 

  8. Horn K., Erhardt F., Fahlbusch R., Pickardt C.R., Werder K.V., Scriba P.C. Recurrent goiter, hyperthyroidism, galactorrhea and amenorrhea due to thyrotropin and prolactin-producing pituitary tumor. J. Clin. Endocrinol. Metab. 43: 137, 1976.

    Article  PubMed  CAS  Google Scholar 

  9. Smallridge R.C., Wartofsky L, Dimond R.C. Inappropriate secretion of thyrotropin: discordance between the suppressive effects of corticosteroids and thyroid hormones. J. Clin. Endocrinol. Metab. 48: 700, 1979.

    Article  PubMed  CAS  Google Scholar 

  10. Waldhäusl W., Bratusch-Marrain P., Nowotny P., Büchler M., Forssmann W.G., Lujf A., Schuster H. Secondary hyperthyroidism due to thyrotrpin hypersecretion: study of pituitary tumor morphology and thyrotropin chemistry and release. J. Clin. Endocrinol. Metab. 49: 879, 1979.

    Article  PubMed  Google Scholar 

  11. Refetoff S., DeGroot L.J., Benard B., De Wind L.T. Studies of a sibship with apparent hereditary resistance to the intracellular action of thyroid hormone. Metabolism 21: 723, 1972.

    Article  PubMed  CAS  Google Scholar 

  12. Agerbaek H. Congenital goiter presumably resulting from tissue resistance to thyroid hormone. Isr. J. Med. Sci. 8: 1859, 1972.

    Google Scholar 

  13. Lamberg B.A. Congenital euthyroid goiter and partial peripheral resistance to thyroid hormones. Lancet 1: 854, 1973.

    Article  PubMed  CAS  Google Scholar 

  14. Bode H.H., Danon M., Weintraub B.D., Maloof F., Crawford J.D. Partial target-organ resistance to thyroid hormone. J. Clin. Invest. 52: 776, 1973.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  15. Schneider G., Keiser H.R., Bardin C.W. Peripheral resistance to thyroxine: a cause of short stature in a boy without goitre. Clin. Endocrinol. (Oxf.) 4: 111, 1975.

    Article  CAS  Google Scholar 

  16. Gershengorn M.C., Weintraub B.D. Thyrotropin-induced hyperthyroidism caused by selective pituitary resistance to thyroid hormone. A new syndrome of “inappropriate secretion of TSH”. J. Clin. Invest. 56: 633, 1975.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. Elewaut A., Mussche M., Vermeulen A. Familial partial target organ resistance to thyroid hormones. J. Clin. Endocrinol. Metab. 43: 375, 1976.

    Article  Google Scholar 

  18. Hood S., Vaughan-Jackson J.D., Farid N.D. Inappropriate TSH secretion. Paradoxical use in serum TSH in response to thyroxine therapy. J. Clin. Endocrinol. Metab. 43: 1360, 1976.

    Article  PubMed  CAS  Google Scholar 

  19. Novogroder M., Utiger R., Boyar R., Levine L.S. Juvenile hyperthyroidism with elevated thyrotropin (TSH) and normal 24 hours FSH, LH, GH and prolactin secretory patterns. J. Clin. Endocrinol. Metab. 45: 1053, 1977.

    Article  Google Scholar 

  20. Lamberg B.A., Rosengard S., Liewendhahl K., Saarinen P., Evered D.C. Familial partial peripheral resistance to thyroid hormones. Acta Endocrinol. 87: 303, 1978.

    PubMed  CAS  Google Scholar 

  21. Seif F.J., Scherbaum W., Klingler W. Syndrome of elevated thyroid hormone and TSH blood levels. A case report. Acta Endocrinol. (Kbh.) 87: (Suppl. 215): 81, 1978.

    Google Scholar 

  22. Tamagna E., Carlson H., Hershman J.M., Reed A. Pituitary and peripheral resistance to thyroid hormones. Clin. Endocrinol. (Oxf.) 10: 431, 1979.

    Article  CAS  Google Scholar 

  23. Daubresse J.C., Dozin-van Roye B., De Nayer Ph., De Visscher M. Partial resistance to thyroid hormones: reduced affinity of lymphocyte nuclear receptors for T3 in two siblings. In: Stockigt J.R., Nagataki S. (Eds.), Thyroid reseach VIII. Australian Academy of Science, Sidney, 1980, p. 295.

    Google Scholar 

  24. Barker S.B., Humphrey M.J., Soley M.H. The clinical determination of protein-bound-iodine. J.Clin. Invest. 30: 55, 1951.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  25. Vandalem J.L., Ketelslegers J.M., Pirens G., Closset J., Hennen G. Dosage radioimmunologique de l’hormone thyréostimulante. Etude immunologique du système et application clinique. Acta Clin. Belg. 30: 521, 1975.

    PubMed  CAS  Google Scholar 

  26. Vandalem J.L., Pirens G., Closset J., Hennen G. Selective radioimmunoassays for human luteinizing hormone (hLH) and human chorionic gonadotropin (hCG). Arch. Int. Physiol. Biochim. 83: 753, 1975.

    Article  PubMed  CAS  Google Scholar 

  27. Vandalem J.L., Pirens G., Hennen G., Gaspard U. Thyroliberin and gonadoliberin tests during pregnancy and the Puerperium. Acta Endocrinol. (Kbh.) 86: 695, 1977.

    CAS  Google Scholar 

  28. Closset J., Vandalem J.L., Hennen G., Lequin R.M. Human luteinizing hormone. Isolation and characterization of the native hormone and its alpha and beta subunits. Eur. J. Biochem. 57: 325, 1975.

    Article  PubMed  CAS  Google Scholar 

  29. Hennen G., Vandalem J.L., Pirens G., Closset J., Maghuin-Rogister G. Glycoprotein hormone: molecular characteristics and specific measurements during pregnancy. In: Peeters H. (Ed.), Protides of biological fluids. Pergamon Press, Brugge, 1976, p. 53.

    Google Scholar 

  30. McKenzie J.M., Zakarija M. A reconsideration of a thyroid-stimulating immunoglobulin as the cause of hyperthyroidism in Graves’ disease. J. Clin. Endocrinol. Metab. 42: 778, 1976.

    Article  PubMed  CAS  Google Scholar 

  31. Maghuin-Rogister G., Closset J., Combarnous Y., Hennen G., Dechenne C., Ketelslegers J.M. Studies of FSH receptors in testing using a homologous system. Binding of porcine follitropin to plasma membrane from immature porcine testis and correlation with adenylate cyclase stimulation. Eur. J. Biochem. 86: 121, 1978.

    Article  PubMed  CAS  Google Scholar 

  32. Golstein-Golaire J., Vanhaelst L. Gel filtration profile of circulating immunoreactive thyrotropin and subunits of myxoedematous sera. J. Clin. Endocrinol. Metab. 41: 575, 1975.

    Article  PubMed  CAS  Google Scholar 

  33. Kourides I.A., Weintraub B.D., Maloof F. Large molecular weight TSH-beta: the sole immunoac-tive form of TSH beta in certain human sera. J. Clin. Endocrinol. Metab. 47: 24, 1978.

    Article  PubMed  CAS  Google Scholar 

  34. Erhardt F.W., Scriba P.C. High molecular weight thyrotropin (“Big” TSH) from human pituitaries: preparation and partial characterization. Acta Endocrinol. (Kbh.) 85: 698, 1977.

    CAS  Google Scholar 

  35. Vanhaelst L., Golstein-Golaire J. Gel filtration profile of immunoreactive thyrotropin and subunits on human pituitaries. J. Clin. Endocrinol. Metab. 43: 836, 1976.

    Article  PubMed  CAS  Google Scholar 

  36. Tager H., Given B., Baldwin D., Mako M., Markese J., Rubenstein A., Olefsky J., Kobayashi M., Kolterman O., Poucher R. A structurally abnormal insulin causing human diabetes. Nature 281: 122, 1979.

    Article  PubMed  CAS  Google Scholar 

  37. Axelrod L., Neer R.M., Kliman B. Hypogonadism in a male with immunologically active, biologically inactive luteinizing hormone: an exception to a venerable rule. J. Clin. Endocrinol. Metab. 48: 279, 1979.

    Article  PubMed  CAS  Google Scholar 

  38. Faglia G., Bitensky L., Pinchera A., Ferrari C., Paracchi A., Beck-Peccoz P., Ambrosi B., Spada A. Thyrotropin secretion in patients with central hypothy roidism: evidence for reduced biological activity of immunoactive thyrotropin. J. Clin. Endocrinol. Metab. 48: 989, 1979.

    Article  PubMed  CAS  Google Scholar 

  39. Kourides I.A., Weintraub B.D., Rosen S.W., Ridgway E.C., Kliman G., Maloof F. Secretion of alpha subunit of glycoprotein hormones by pituitary adenomas. J. Clin. Endocrinol. Metab. 43: 97, 1976.

    Article  PubMed  CAS  Google Scholar 

  40. Kourides I.A., Ridgway E.C., Weintraub B.D., Bigos S.T., Gershengorn M.C., Maloof F. Thyrotropin induced hyperthyroidism: use of alpha and beta subunits levels to identify patients with pituitary tumors. J. Clin. Endocrinol. Metab. 45: 534, 1977.

    Article  PubMed  CAS  Google Scholar 

  41. Refetoff S., De Wind L.T., DeGroot L.J. Familial syndrome combining deaf-mutism, stippled epiphyses, goiter and abnormally high PBI: Possible target organ refractoriness to thyroid hormone. J. Clin. Endocrinol. Metab. 27: 279, 1967.

    Article  PubMed  CAS  Google Scholar 

  42. Bernal J., Refetoff S., DeGroot L.J. Abnormalities of triiodothyronine binding to lymphocyte and fibroblast nuclei from a patient with peripheral tissue resistance to thyroid hormone action. J. Clin. Endocrinol. Metab. 47: 1266, 1978.

    Article  PubMed  CAS  Google Scholar 

  43. Wenzel K.W., Meinhold H., Schleusener H. Different effects of oral doses of triiodothyronine or thyroxine on the inhibition of thyrotropin releasing hormone (TRH) mediated thyrotropin (TSH) response in man. Acta Endocrinol. (Kbh.) 80: 42, 1975.

    CAS  Google Scholar 

  44. Sawin C.T., Hershman J.M., Chopra I.J. The comparative effect of T4 and T3 on TSH response to TRH in young adult men. J. Clin. Endocrinol. Metab. 44: 273, 1977.

    Article  PubMed  CAS  Google Scholar 

  45. Kourides I.A., Ridgway E.C., Maloof F. Discordant response of thyrotropin and its free alpha and beta subunits after thyrotropin-releasing hormone with incremental thyroid hormone replacement in primary hypothyroidism. J. Clin. Endocrinol. Metab. 49: 700, 1979.

    Article  PubMed  CAS  Google Scholar 

  46. Krugman L.G., Hershman J.M., Chropra I.J., Levine G.A., Pekary A.E., Geffner D.L., Chua Teco G.N. Patterns od recovery of the hypothalamic-pituitary-thy-roid axis in patients taken off chronic thyroid therapy. J. Clin. Endocrinol. Metab. 41: 70, 1975.

    Article  PubMed  CAS  Google Scholar 

  47. Vagenakis A.G., Braverman L.E., Azizi F., Portnay G.J., Ingbar S.H. Recovery of pituitary thyrotropic function after withdrawal of prolonged thyroid-suppression therapy. N. Engl. J. Med. 293: 681, 1975.

    Article  PubMed  CAS  Google Scholar 

  48. Nilson G., Petterson V., Levin K., Hughes R. Studies on replacement and suppressive dosages of L-thyroxine. Acta Med. Scand. 202: 257, 1977.

    Article  Google Scholar 

  49. Cotton G.E., Gorman C.A., Mayberry W.E. Suppression of thyrotropin (hTSH) in serums of patients with myxoedema of varying etiology treated with thyroid hormones. N. Engl. J. Med. 285: 529, 1971.

    Article  PubMed  CAS  Google Scholar 

  50. Evered D., Young E.T., Ormston B.J., Menzies R., Smith P.A., Hall R. Treatment of hypothyroidism: A reappraisal of thyroxine therapy. Med. J. 3: 131, 1973.

    Article  CAS  Google Scholar 

  51. Stock J.M., Surks M.I., Oppenheimer J.H. Replacement dosage of L-thyroxine in hypothyroidism. A re-evaluation. N. Engl. J. Med. 290: 529, 1974.

    Article  PubMed  CAS  Google Scholar 

  52. Riesco G., Taurog A., Larsen P.R. Variations in the response of the thyroid gland of the rat to different low-iodine diets: correlation with iodine content of diet. Endocrinology 99: 270, 1976.

    Article  PubMed  CAS  Google Scholar 

  53. Silva J.E., Larsen P.R. Pituitary nuclear 3,5,3′-triiodothyronine and thyrotropin secretion: an explanation for the effect of thyroxine. Science 198: 617, 1977.

    Article  PubMed  CAS  Google Scholar 

  54. Silva J.E., Larsen P.R. Contributions of plasma triiodothyronine and local thyroxine monodeiodination to triiodothyronine to nuclear triiodothyronine receptor saturation in pituitary, lever and kidney of hypothyroid rats. Further evidence relating saturation of pituitary nuclear triiodothyronine receptor and the acute inhibition of thyroid-stimulating hormone release. J. Clin. Invest. 61: 1247, 1978.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section d’Endocrinologie, Départment de Clinique et de Séméiologie Médicales, Institut de Pathologie, Centre Hospitalier Universitaire, B23, B4000, Sart Tilman par Liège I, Belgium

    J. L. Vandalem M.D., G. Pirens & G. Hennen

Authors
  1. J. L. Vandalem M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Pirens
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Hennen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vandalem, J.L., Pirens, G. & Hennen, G. Familial inappropriate TSH secretion: evidence suggesting a dissociated pituitary resistance to T3 and T4 . J Endocrinol Invest 4, 413–422 (1981). https://doi.org/10.1007/BF03348305

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03348305

Key-words

Search

Navigation