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Hormonally Active Drugs and the Fetus

  • Robin Mortimer
Part of the Endocrine Updates book series (ENDO, volume 15)

Abstract

The concept that the placenta acts as a barrier blocking transfer of drugs from mother to fetus can no longer be supported and it now must be accepted that most drugs taken by the pregnant woman reach her unborn child (1). The extent to which the fetus is exposed to a maternally derived drug and the results of this exposure depend on many factors. These include maternal issues such as dosing regimen, bioavailability and clearance, the physicochemical properties of the drug, the structure and blood supply of the placenta and clearance of the drug from the feto-placental unit. The effect of maternally derived drugs on the fetus depends, in turn, on the stage of gestation, the ontogeny of drug receptors and metabolic systems and fetal physiology. Many of the drugs used to manage pituitary disease have widespread effects on neurotransmission and possibly on brain development and may also adversely affect development and function of the adrenal, gonads and external genitalia. For many of the drugs there is little information about possible detrimental fetal effects and what information is available is often limited to rather crude estimates of fetal well being such as the absence of malformations and survival.

Keywords

Growth Hormone Thyroid Hormone Amniotic Fluid Fetal Liver Neural Tube Defect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Reference

  1. 1.
    Morgan, D.J. 1997. Drug disposition in mother and foetus.Clin Exp Pharmacol Physiol.24:869–73.PubMedGoogle Scholar
  2. 2.
    Davison, J.M., and M.D. Lindheimer. 1989. Volume homeostasis and osmoregulation in human pregnancy.Baillieres Clin Endocrinol Metab.3:451–72.PubMedGoogle Scholar
  3. 3.
    Rudolph, A.M. 1995. Pharmacodynamics in the maternal-fetal-placental unit.NIDA Res Monogr.154:163–74.Google Scholar
  4. 4.
    Brace, R.A. 1994. Fetal fluid balance.InTextbook of fetal physiology. G.D. Thorburn, Harding, R., editor. Oxford University Press, Oxford. 205–18.Google Scholar
  5. 5.
    Lankas, G.R., L.D. Wise, M.E. Cartwright, T. Pippert, and D.R. Umbenhauer. 1998. Placental P-glycoprotein deficiency enhances susceptibility to chemically induced birth defects in mice.Reprod Toxicol.12:457–63.PubMedGoogle Scholar
  6. 6.
    Smit, J.W., M.T. Huisman, O. van Tellingen, H.R. Wiltshire, and A.H. Schinkel. 1999. Absence or pharmacological blocking of placental P-glycoprotein profoundly increases fetal drug exposure.JClin Invest.104:1441–7.Google Scholar
  7. 7.
    Hill, M.D., and F.P. Abramson. 1988. The significance of plasma protein binding on the fetal/maternal distribution of drugs at steady-state.Clin Pharmacokinet.14:156–70.PubMedGoogle Scholar
  8. 8.
    Hakkola, J., O. Pelkonen, M. Pasanen, and H. Raunio. 1998. Xenobiotic-metabolizing cytochrome P450 enzymes in the human feto-placental unit: role in intrauterine toxicity.Crit Rev Toxicol.28:35–72.PubMedGoogle Scholar
  9. 9.
    Juchau, M., R., Symms, K.G., Zachariah, P.K. 1974. Drug-metabolising enzymes in the placenta.InPerinatal Pharmacology. Dancis, J, Hwang, J.C., editor. Raven Press, Amsterdam. 89–95.Google Scholar
  10. 10.
    Ring, J.A., H. Ghabrial, M.S. Ching, R.A. Smallwood, and D.J. Morgan. 1999. Fetal hepatic drug elimination.Pharmacol Ther.84:429–45.PubMedGoogle Scholar
  11. 11.
    Pacifici, G.M., M. Franchi, L. Giuliani, and A. Rane. 1989. Development of the glucuronyltransferase and sulphotransferase towards 2-naphthol in human fetus.Dev Pharmacol Ther.14:108–14.PubMedGoogle Scholar
  12. 12.
    .Mollgard, K., and N.R. Saunders. 1986. The development of the human blood-brain and blood-CSF barriers. Neuropathol Appl Neurobiol. 12:337-58. PubMedGoogle Scholar
  13. 13.
    Fromm, M.F. 2000. P-glycoprotein: a defense mechanism limiting oral bioavailability and CNS accumulation of drugs.Int J Clin Pharmacol Ther.38:6974.Google Scholar
  14. 14.
    .Suzuki, H. 1999. [Analysis of xenobiotic detoxification system mediated by efflux transporters]. Yakugaku Zasshi. 119:822-34. PubMedGoogle Scholar
  15. 15.
    van Kalken, C., G. Giaccone, P. van der Valk, C.M. Kuiper, M.M. Hadisaputro, S.A. Bosma, R.J. Scheper, C.J. Meijer, and H.M. Pinedo. 1992. Multidrug resistance gene (P-glycoprotein) expression in the human fetus.Am J Pathol.141:1063–72.PubMedGoogle Scholar
  16. 16.
    Szeto, H.H., J.G. Umans, and S.I. Rubinow. 1982. The contribution of transplacental clearances and fetal clearance to drug disposition in the ovine maternal-fetal unit.Drug Metab Dispos.10:382–6.PubMedGoogle Scholar
  17. 17.
    .Bernus, I., M.S. Roberts, R.L. Rasiah, and R.H. Mortimer. 1999. Statistical moments for placental transfer of solutes in man. J Pharm Pharmacol. 51:1381-9. PubMedGoogle Scholar
  18. 18.
    Atkinson, H.C., E.J. Begg, and B.A. Darlow. 1988. Drugs in human milk. Clinical pharmacokinetic considerations.Clin Pharmacokinet.14:217–40.PubMedGoogle Scholar
  19. 19.
    Fadalti, M., I. Pezzani, L. Cobellis, F. Springolo, M.M. Petrovec, G. Ambrosini, F.M. Reis, and F. Petraglia. 2000. Placental corticotropin-releasing factor. An update.Ann N Y Acad Sci.900:89–94.PubMedGoogle Scholar
  20. 20.
    Chrousos, G.P., D.J. Torpy, and P.W. Gold. 1998. Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: clinical implications.Ann Intern Med.129:229–40.PubMedGoogle Scholar
  21. 21.
    .Parker, C.R., Jr., A.M. Stankovic, and R.S. Goland. 1999. Corticotropin-releasing hormone stimulates steroidogenesis in cultured human adrenal cells. Mol Cell Endocrino!. 155:19-25. Google Scholar
  22. 22.
    Osamura, R.Y. 1977. Functional prenatal development of anencephalic and normal anterior pituitary glands. In human and experimental animals studied by peroxidaselabeled antibody method.Acta Pathol Jpn.27:495–509.Google Scholar
  23. 23.
    Economides, D.L., K.H. Nicolaides, and S. Campbell. 1991. Metabolic and endocrine findings in appropriate and small for gestational age fetuses.J Perinat Med.19:97–105.PubMedGoogle Scholar
  24. 24.
    Thorpe-Beeston, J.G., K.H. Nicolaides, C.V. Felton, J. Butler, and A.M. McGregor. 1991. Maturation of the secretion of thyroid hormone and thyroid-stimulating hormone in the fetus.NEngl JMed.324:532–6.Google Scholar
  25. 25.
    Fisher, D.A., Polk, D.H. 1994. Development of the fetal thyroid system.InTextbook of fetal physiology. G.D. Thorburn, Harding, R., editor. Oxford University Press, Oxford. 359–68.Google Scholar
  26. 26.
    Thorpe-Beeston, J.G., K.H. Nicolaides, and A.M. McGregor. 1992. Fetal thyroid function.Thyroid.2:207–17.PubMedGoogle Scholar
  27. 27.
    .Roti, E., G. Robuschi, A. Alboni, R. Emanuele, L. d’Amato, E. Gardini, M. Salvi, E. Dall’Aglio, A. Gnudi, and L.E. Braverman. 1984. Inhibition of foetal growth hormone (GH) and thyrotrophin (TSH) secretion after maternal administration of somatostatin. Acta Endocrino! (Copenh). 106:393-9. Google Scholar
  28. 28.
    Shimon, I., J.E. Taylor, J.Z. Dong, R.A. Bitonte, S. Kim, B. Morgan, D.H. Coy, M.D. Culler, and S. Melmed. 1997. Somatostatin receptor subtype specificity in human fetal pituitary cultures. Differential role of SSTR2 and SSTR5 for growth hormone, thyroid-stimulating hormone, and prolactin regulation.J Clin Invest.99:789–98.PubMedGoogle Scholar
  29. 29.
    Dubois, P.M. 1990. [Ontogenesis of gonadotropic cells].Ann Endocrino! (Paris).51:47–53.Google Scholar
  30. 30.
    Biswas, S., and C.H. Rodeck. 1976. Plasma prolactin levels during pregnancy.Br J Obstet Gynaecol.83:683–7.PubMedGoogle Scholar
  31. 31.
    Bigazzi, M., R. Ronga, I. Lancranjan, S. Ferraro, F. Branconi, P. Buzzoni, G. Martorana, G.F. Scarselli, and E. Del Pozo. 1979. A pregnancy in an acromegalic woman during bromocriptine treatment: effects on growth hormone and prolactin in the maternal, fetal, and amniotic compartments.J Clin Endocrino! Metab.48:9–12.Google Scholar
  32. 32.
    Biswas, S. 1976. Prolactin in amniotic fluid: its correlation with maternal plasma prolactin.Clin Chim Acta.73:363–7.PubMedGoogle Scholar
  33. 33.
    de Wit, W., H.J. Coelingh Bennink, and L.J. Gerards. 1984. Prophylactic bromocriptine treatment during pregnancy in women with macroprolactinomas: report of 13 pregnancies.Br J Obstet Gynaecol.91:1059–69.PubMedGoogle Scholar
  34. 34.
    Handwerger, S., E. Markoff, and R. Richards. 1991. Regulation of the synthesis and release of decidual prolactin by placental and autocrine/paracrine factors.Placenta.12:121–30.PubMedGoogle Scholar
  35. 35.
    Golander, A., J. Barrett, T. Hurley, S. Barry, and S. Handwerger. 1979. Failure of bromocriptine, dopamine, and thyrotropin-releasing hormone to affect prolactin secretion by human decidual tissue in vitro.J Clin Endocrinol Metab.49:787–9.Google Scholar
  36. 36.
    Gluckman, P.D., M.M. Grumbach, and S.L. Kaplan. 1981. The neuroendocrine regulation and function of growth hormone and prolactin in the mammalian fetus.Endocr Rev.2:363–95.PubMedGoogle Scholar
  37. 37.
    .Frankenne, F., M.L. Scippo, J. Van Beeumen, A. Igout, and G. Hennen. 1990. Identification of placental human growth hormone as the growth hormone-V gene expression product. J Clin Endocrinol Metab. 71:15-8. Google Scholar
  38. 38.
    Frankenne, F., J. Closset, F. Gomez, M.L. Scippo, J. Smal, and G. Hennen. 1988. The physiology of growth hormones (GHs) in pregnant women and partial characterization of the placental GH variant.J Clin Endocrinol Metab.66:1171–80.PubMedGoogle Scholar
  39. 39.
    Goodyer, C.G., C.L. Branchaud, and Y. Lefebvre. 1993. Effects of growth hormone (GH)-releasing factor and somatostatin on GH secretion from early to midgestation human fetal pituitaries.J Clin Endocrinol Metab.76:1259–64.PubMedGoogle Scholar
  40. 40.
    Mizutani, S., K. Goto, M. Tsujimoto, H. Nakazato, K. Matsuzawa, Y. Furuhashi, K. Arii, and Y. Tomoda. 1996. Possible effects of placental leucine aminopeptidase on the regulation of brain-gut hormones in the fetoplacental unit.Biol Neonate.69:307–17.PubMedGoogle Scholar
  41. 41.
    Potter, J.M., U.W. Mueller, P.E. Hickman, and C.A. Michael. 1987. Corticosteroid binding globulin in normotensive and hypertensive human pregnancy.Clin Sci.72:725–35.PubMedGoogle Scholar
  42. 42.
    Heazelwood, V.J., J.P. Galligan, G.R. Cannell, F. Bochner, and R.H. Mortimer. 1984. Plasma cortisol delivery from oral cortisol and cortisone acetate: relative bioavailability.Br JClin Pharmacol.17:55–9.Google Scholar
  43. 43.
    Dodds, H.M., P.J. Taylor, L.P. Johnson, R.H. Mortimer, S.M. Pond, and G.R. Cannell. 1997. Cortisol metabolism and its inhibition by glycyrrhetinic acid in the isolated perfused human placental lobule.J Steroid Biochem Mol Biol.62:337–43.PubMedGoogle Scholar
  44. 44.
    Addison, R.S., D.J. Maguire, R.H. Mortimer, M.S. Roberts, and G.R. Cannell. 1993. Pathway and kinetics of prednisolone metabolism in the human placenta.J Steroid Biochem Mol Biol.44:315–20.PubMedGoogle Scholar
  45. 45.
    Edwards, C.R., R. Benediktsson, R.S. Lindsay, and J.R. Seckl. 1996. II betaHydroxysteroid dehydrogenases: key enzymes in determining tissue-specific glucocorticoid effects.Steroids.61:263–9.PubMedGoogle Scholar
  46. 46.
    Sun, K., S.L. Adamson, K. Yang, and J.R. Challis. 1999. Interconversion of cortisol and cortisone by Il beta-hydroxysteroid dehydrogenases type 1 and 2 in the perfused human placenta.Placenta.20:13–9.PubMedGoogle Scholar
  47. 47.
    Law, C. 1995. Fetal influences on adult hypertension.J Hum Hypertens.9:649–51.PubMedGoogle Scholar
  48. 48.
    Barker, D.J. 1995. Fetal origins of coronary heart disease.Bmj.311:171–4.PubMedGoogle Scholar
  49. 49.
    Dodic, M., A. Peers, J.P. Coghlan, and M. Wintour. 1999. Can Excess Glucocorticoid, Predispose to Cardiovascular and Metabolic Disease in Middle Age?Trends Endocrino! Metab.10:86–91.Google Scholar
  50. 50.
    Seckl, J.R., M. Cleasby, and M.J. Nyirenda. 2000. Glucocorticoids, I 1 betahydroxysteroid dehydrogenase, and fetal programming.Kidney Int.57:1412–7.PubMedGoogle Scholar
  51. 51.
    Kliewer, S.A., J.T. Moore, L. Wade, J.L. Staudinger, M.A. Watson, S.A. Jones, D.D. McKee, B.B. Oliver, T.M. Willson, R.H. Zetterstrom, T. PerImann, and J.M. Lehmann. 1998. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway.Cell.92:73–82.PubMedGoogle Scholar
  52. 52.
    EI-Sankary, W., N.J. Plant, G.G. Gibson, and D.J. Moore. 2000. Regulation of the CYP3A4 gene by hydrocortisone and xenobiotics: role of the glucocorticoid and pregnane X receptors.Drug Metab Dispos.28:493–6.Google Scholar
  53. 53.
    Cote, C.J., H.J. Meuwissen, and R.J. Pickering. 1974. Effects on the neonate of prednisone and azathioprine administered to the mother during pregnancy.J Pediatr.85:324–8.PubMedGoogle Scholar
  54. 54.
    Fraser, F.C., and A. Sajoo. 1995. Teratogenic potential of corticosteroids in humans.Teratology.51:45–6.PubMedGoogle Scholar
  55. 55.
    Rayburn, W.F. 1998. Connective tissue disorders and pregnancy. Recommendations for prescribing.JReprod Med.43:341–9.Google Scholar
  56. 56.
    Glinoer, D. 1997. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology.Endocr Rev.18:404–33.PubMedGoogle Scholar
  57. 57.
    Mandel, S.J., P.R. Larsen, E.W. Seely, and G.A. Brent. 1990. Increased need for thyroxine during pregnancy in women with primary hypothyroidism [see comments].N Engl J Med.323:91–6.Google Scholar
  58. 58.
    Haddow, J.E., G.E. Palomaki, W.C. Allan, J.R. Williams, G.J. Knight, J. Gagnon, C.E. O’Heir, M.L. Mitchell, R.J. Hermos, S.E. Waisbren, J.D. Faix, and R.Z. Klein. 1999. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child [see comments].N Eng! J Med.341:549–55.Google Scholar
  59. 59.
    Pop, V.J., J.L. Kuijpens, A.L. van Baar, G. Verkerk, M.M. van Son, J.J. de Vijlder, T. Vulsma, W.M. Wiersinga, H.A. Drexhage, and H.L. Vader. 1999. Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy [see comments].Clin Endocrino! (Oxj).50:149–55.Google Scholar
  60. 60.
    Mitchell, A.M., S.W. Manley, and R.H. Mortimer. 1992. Uptake of L-triiodothyronine by human cultured trophoblast cells.J Endocrinol.133:483–6.PubMedGoogle Scholar
  61. 61.
    Mortimer, R.H., J.P. Galligan, G.R. Cannell, R.S. Addison, and M.S. Roberts. 1996. Maternal to fetal thyroxine transmission in the human term placenta is limited by inner ring deiodination.J Clin Endocrino! Metab.81:2247–9.Google Scholar
  62. 62.
    Vulsma, T., M.H. Gons, and J.J. de Vijlder. 1989. Maternal-fetal transfer of thyroxine in congenital hypothyroidism due to a total organification defect or thyroid agenesis [see comments].N Eng! J Med.321:13–6.Google Scholar
  63. 63.
    Varma, S.K., M. Collins, A. Row, W.S. Haller, and K. Varma. 1978. Thyroxine, triiodothyronine, and reverse tri-iodothyronine concentrations in human milk.J Pediatr.93:803–6.PubMedGoogle Scholar
  64. 64.
    Davison, J.M., E.A. Sheills, P.R. Philips, W.M. Barron, and M.D. Lindheimer. 1993. Metabolic clearance of vasopressin and an analogue resistant to vasopressinase in human pregnancy.Am J Physiol.264:F348–53.PubMedGoogle Scholar
  65. 65.
    Tahara, A., J. Tsukada, Y. Tomura, K. Wada, T. Kusayama, N. Ishii, T. Yatsu, W. Uchida, and A. Tanaka. 2000. Pharmacologic characterization of the oxytocin receptor in human uterine smooth muscle cells.BrJPharmacol.129:131–9.Google Scholar
  66. 66.
    Matsui, K., T. Kimura, K. Ota, K. Iitake, M. Shoji, M. Inoue, and K. Yoshinaga. 1985. Resistance of 1-deamino-[8-D-arginine]-vasopressin to in vitro degradation as compared with arginine vasopressin.Endocrinol Jpn.32:547–57.PubMedGoogle Scholar
  67. 67.
    Ray, J.G. 1998. DDAVP use during pregnancy: an analysis of its safety for mother and child.Obstet Gynecol Surv.53:450–5.PubMedGoogle Scholar
  68. 68.
    Nijland, M.J., M.G. Ross, L.K. Kullama, K. Bradley, and M.G. Ervin. 1995. DDAVP-induced maternal hyposmolality increases ovine fetal urine flow.Am J Phys i ol.268: R3 5 8–65.Google Scholar
  69. 69.
    Roti, E., G. Robuschi, A. Alboni, L. d’Amato, M. Montermini, E. Gardini, M. Salvi, E. Borciani, E. Dall’Aglio, S. Bisi, and et al. 1986. Human foetal prolactin but not thyrotropin secretion is decreased by bromocriptine.Acta Endocrinol (Copenh).112:35–42.Google Scholar
  70. 70.
    Fang, Y., and O.K. Ronnekleiv. 1999. Cocaine upregulates the dopamine transporter in fetal rhesus monkey brain.JNeurosci.19:8966–78.Google Scholar
  71. 71.
    Turkalj, I., P. Braun, and P. Krupp. 1982. Surveillance of bromocriptine in pregnancy.Jama.247:1589–91.PubMedGoogle Scholar
  72. 72.
    Krupp, P., and C. Monka. 1987. Bromocriptine in pregnancy: safety aspects.Klin Wochenschr.65: 823–7.PubMedGoogle Scholar
  73. 73.
    Raymond, J.P., E. Goldstein, P. Konopka, M.F. Leleu, R.E. Merceron, and Y. Loria. 1985. Follow-up of children born of bromocriptine-treated mothers.Norm Res.22:239–46.Google Scholar
  74. 74.
    Weil, C. 1986. The safety of bromocriptine in long-term use: a review of the literature.Curr Med Res Opin.10:25–51.PubMedGoogle Scholar
  75. 75.
    Katz, M., D. Kroll, I. Pak, A. Osimoni, and M. Hirsch. 1985. Puerperal hypertension, stroke, and seizures after suppression of lactation with bromocriptine.Obstet Gynecol.66:822–4.PubMedGoogle Scholar
  76. 76.
    Iffy, L., J.J. McArdle, and V. Ganesh. 1996. Intracerebral hemorrhage in normotensive mothers using bromocriptine postpartum.Zentralbi Gynakol.118:392–5.Google Scholar
  77. 77.
    Rains, C.P., H.M. Bryson, and A. Fitton. 1995. Cabergoline. A review of its pharmacological properties and therapeutic potential in the treatment of hyperprolactinaemia and inhibition of lactation.Drugs.49:255–79.PubMedGoogle Scholar
  78. 78.
    Robert, E., L. Musatti, G. Piscitelli, and C.I. Ferrari. 1996. Pregnancy outcome after treatment with the ergot derivative, cabergoline.Reprod Toxicol.10:333–7.PubMedGoogle Scholar
  79. 79.
    Caron, P., C. Gerbeau, L. Pradayrol, C. Simonetta, and F. Bayard. 1996. Successful pregnancy in an infertile woman with a thyrotropin-secreting macroadenoma treated with somatostatin analog (octreotide).J Clin Endocrinol Metab.81:1164–8.PubMedGoogle Scholar
  80. 80.
    Slama, A., M.T. Bluet-Pajot, F. Mounier, C. Videau, C. Kordon, and J. Epelbaum. 1996. Effects of neonatal administration of octreotide, a long-lasting somatostatin analogue, on growth hormone regulation in the adult rat.Neuroendocrinology.63:173–80.PubMedGoogle Scholar
  81. 81.
    Sanchez, R., E. Boix, M. del Pino Navarro, and A. Pico. 1999. [Pregnancy in an acromegalic patient treated with lanreotide and bromocryptin (letter)].Med Clin (Bart).113:198.Google Scholar
  82. 82.
    de Menis, E., D. Billeci, E. Marton, and G. Gussoni. 1999. Uneventful pregnancy in an acromegalic patient treated with slow-release lanreotide: a case report [letter; comment].J Clin Endocrino! Metab.84:1489.Google Scholar
  83. 83.
    Kageyama, K., F. Tozawa, N. Horiba, H. Watanobe, and T. Suda. 1998. Serotonin stimulates corticotropin-releasing factor gene expression in the hypothalamic paraventricular nucleus of conscious rats.Neurosci Lett.243:17–20.PubMedGoogle Scholar
  84. 84.
    Ishibashi, M., and T. Yamaji. 1981. Direct effects of thyrotropin-releasing hormone, cyproheptadine, and dopamine on adrenocorticotropin secretion from human corticotroph adenoma cells in vitro.JClin Invest.68:1018–27.Google Scholar
  85. 85.
    Delarue, C., V. Contesse, H. Lefebvre, S. Lenglet, L. Grumolato, J.M. Kuhn, and H. Vaudry. 1998. Pharmacological profile of serotonergic receptors in the adrenal gland.Endocr Res.24:687–94.PubMedGoogle Scholar
  86. 86.
    Krieger, D.T., L. Amorosa, and F. Linick. 1975. Cyproheptadine-induced remission of Cushing’s disease.N Engl J Med.293:893–6.PubMedGoogle Scholar
  87. 87.
    .Chow, S.A., and L.J. Fischer. 1987. Metabolism and disposition of cyproheptadine and desmethylcyproheptadine in pregnant and fetal rats. Drug Metab Dispos. 15:740-8. Google Scholar
  88. 88.
    Chow, S.A., and L.J. Fischer. 1986. Susceptibility of fetal rat endocrine pancreas to the diabetogenic action of cyproheptadine.Toxicol Appl Pharmacol.84:264–77.PubMedGoogle Scholar
  89. 89.
    Kasperlik-Zaluska, A., B. Migdalska, W. Hartwig, J. Wilczynska, L. Marianowski, U. Stopinska-Gluszak, and D. Lozinska. 1980. Two pregnancies in a woman with Cushing’s syndrome treated with cyproheptadine. Case report.Br J Obstet Gynaecol.87:1171–3.PubMedGoogle Scholar
  90. 90.
    Griffith, D.N., and E.J. Rose. 1981. Pregnancy after cyproheptadine treatment for Cushing’s disease [letter].N Engl J Med.305:893–4.PubMedGoogle Scholar
  91. 91.
    Khir, A.S., J. How, and P.D. Bewsher. 1982. Successful pregnancy after cyproheptadine treatment for Cushing’s disease.Eur J Obstet Gynecol Reprod Biol.13:343–7.PubMedGoogle Scholar
  92. 92.
    Colao, A., R. Pivonello, F.S. Tripodi, F. Orio, Jr., D. Ferone, G. Cerbone, C. Di Somma, B. Merola, and G. Lombardi. 1997. Failure of long-term therapy with sodium valproate in Cushing’s disease.JEndocrinol Invest.20:387–92.Google Scholar
  93. 93.
    Fowler, D.W., M.J. Eadie, and R.G. Dickinson. 1989. Transplacental transfer and biotransformation studies of valproic acid and its glucuronide(s) in the perfused human placenta.J Pharmacol Exp Ther.249:318–23.PubMedGoogle Scholar
  94. 94.
    Johannessen, S.I. 1992. Pharmacokinetics of valproate in pregnancy: mother-foetusnewborn.Pharm Weekbl Sci.14:114–7.PubMedGoogle Scholar
  95. 95.
    Piontek, C.M., S. Baab, K.S. Peindl, and K.L. Wisner. 2000. Serum valproate levels in 6 breastfeeding mother-infant pairs.J Clin Psychiatry.61:170–2.PubMedGoogle Scholar
  96. 96.
    Lindhout, D., and J.G. Omtzigt. 1992. Pregnancy and the risk of teratogenicity.Epilepsia.33 Suppl 4:S41–8.Google Scholar
  97. 97.
    Dean, J.C., S.J. Moore, A. Osborne, J. Howe, and P.D. Turnpenny. 1999. Fetal anticonvulsant syndrome and mutation in the maternal MTHFR gene.Clin Genet.56:216–20.PubMedGoogle Scholar
  98. 98.
    Craig, J., P. MorrisonJ.Morrow, and V. Patterson. 1999. Failure of periconceptual folic acid to prevent a neural tube defect in the offspring of a mother taking sodium valproate. Seizure.8:253–4.PubMedGoogle Scholar
  99. 99.
    Sonino, N., M. Boscaro, G. Merola, and F. Mantero. 1985. Prolonged treatment of Cushing’s disease by ketoconazole.JClin Endocrinol Metab.61:718–22.Google Scholar
  100. 100.
    Mortimer, R.H., G.R. Cannell, C.M. Thew, and J.P. Galligan. 1991. Ketoconazole and plasma and urine steroid levels in Cushing’s disease.Clin Exp Pharmacol Physiol.18:563–9.PubMedGoogle Scholar
  101. 101.
    Pasanen, M., T. Taskinen, M. Iscan, E.A. Sotaniemi, M. Kairaluoma, and O. Pelkonen. 1988. Inhibition of human hepatic and placental xenobiotic monooxygenases by imidazole antimycotics.Biochem Pharmacol.37:3861–6.PubMedGoogle Scholar
  102. 102.
    Boass, A., and S.U. Toverud. 1995. Suppression of circulating calcitriol and duodenal active Ca transport by ketoconazole in pregnant rats.Am J Physiol.269:E934–9.PubMedGoogle Scholar
  103. 103.
    Amado, J.A., C. Pesquera, E.M. Gonzalez, M. Otero, J. Freijanes, and A. Alvarez. 1990. Successful treatment with ketoconazole of Cushing’s syndrome in pregnancy.Postgrad Med J.66:221–3.PubMedGoogle Scholar
  104. 104.
    Berwaerts, J., J. Verhelst, C. Mahler, and R. Abs. 1999. Cushing’s syndrome in pregnancy treated by ketoconazole: case report and review of the literature.Gynecol Endocrinol.13:175–82.PubMedGoogle Scholar
  105. 105.
    Wanscher, M., E. Tonnesen, M. Huttel, and K. Larsen. 1985. Etomidate infusion and adrenocortical function. A study in elective surgery.Acta Anaesthesio! Scand.29:483–5.Google Scholar
  106. 106.
    Allolio, B., H.M. Schulte, D. Kaulen, M. Reincke, C. Jaursch-Hancke, and W. Winkelmann. 1988. Nonhypnotic low-dose etomidate for rapid correction of hypercortisolaemia in Cushing’s syndrome.Klin Wochenschr.66:361–4.PubMedGoogle Scholar
  107. 107.
    Schulte, H.M., G. Benker, D. Reinwein, W.G. Sippell, and B. Allolio. 1990. Infusion of low dose etomidate: correction of hypercortisolemia in patients with Cushing’s syndrome and dose-response relationship in normal subjects.J Clin Endocrino! Metab.70:1426–30.Google Scholar
  108. 108.
    Drake, W.M., L.A. Perry, C.J. Hinds, D.G. Lowe, R.H. Reznek, and G.M. Besser. 1998. Emergency and prolonged use of intravenous etomidate to control hypercortisolemia in a patient with Cushing’s syndrome and peritonitis.J Clin Endocrino! Metab.83:3542–4.Google Scholar
  109. 109.
    Gregory, M.A., and D.G. Davidson. 1991. Plasma etomidate levels in mother and fetus.Anaesthesia.46:716–8.PubMedGoogle Scholar
  110. 110.
    Crozier, T.A., C. Flamm, C.P. Speer, W. Rath, W. Wuttke, W. Kuhn, and D. Kettler. 1993. Effects of etomidate on the adrenocortical and metabolic adaptation of the neonate.Br JAnaesth.70:47–53.Google Scholar
  111. 111.
    Rabe, T., R. Mosch, C. Franke, N. Nobakht, and B. Runnebaum. 1983. Inhibition of human placental progesterone and estrogen synthesis in early human gestation by aminoglutethimide in vivo.JSteroid Biochem.18:291–6.Google Scholar
  112. 112.
    Coulter, C.L., and R.B. Jaffe. 1998. Functional maturation of the primate fetal adrenal in vivo: 3. Specific zonal localization and developmental regulation of CYP2IA2 (P450c21) and CYP11BI/CYPI1B2 (P450c11/aldosterone synthase) lead to integrated concept of zonal and temporal steroid biosynthesis.Endocrinology. 139:5144–50. Google Scholar
  113. 113.
    Gormley, M.J., D.R. Hadden, T.L. Kennedy, D.A. Montgomery, G.A. Murnaghan, and B. Sheridan. 1982. Cushing’s syndrome in pregnancy--treatment with metyrapone.Clin Endocrino! (OxJ). 16:283–93. Google Scholar
  114. 114.
    Close, C.F., M.C. Mann, J.F. Watts, and K.G. Taylor. 1993. ACTH-independent Cushing’s syndrome in pregnancy with spontaneous resolution after delivery: control of the hypercortisolism with metyrapone.Clin Endocrino! (Ox..39:375–9.Google Scholar
  115. 115.
    Connell, J.M., J. Cordiner, D.L. Davies, R. Fraser, B.M. Frier, and S.G. McPherson. 1985. Pregnancy complicated by Cushing’s syndrome: potential hazard of metyrapone therapy. Case report.Br J Obstet Gynaecol.92:1192–5.PubMedGoogle Scholar
  116. 116.
    Leiba, S., H. Kaufman, G. Winkelsberg, and C.M. Bahary. 1978. Pregnancy in a case of Nelson’s syndrome.Acta Obstet Gynecol Scand.57:373–5.PubMedGoogle Scholar
  117. 117.
    Knappe, G., H. Gerl, M. Ventz, and W. Rohde. 1997. [The long-term therapy of hypothalamic-hypophyseal Cushing’s syndrome with mitotane (o,p’-DDD)].Dtsch Med Wochenschr.122:882–6.PubMedGoogle Scholar
  118. 118.
    Leiba, S., R. Weinstein, B. Shindel, M. Lapidot, E. Stern, H. Levavi, Y. Rusecki, and A. Abramovici. 1989. The protracted effect of o,p’-DDD in Cushing’s disease and its impact on adrenal morphogenesis of young human embryo.Ann Endocrino! (Paris).50:49–53.Google Scholar
  119. 119.
    Sartor, O., and G.B. Cutler, Jr. 1996. Mifepristone: treatment of Cushing’s syndrome.Clin Obstet Gynecol.39:506–10.PubMedGoogle Scholar
  120. 120.
    Hill, N.C., M. Selinger, J. Ferguson, and I.Z. MacKenzie. 1991. Transplacental passage of mifepristone and its influence on maternal and fetal steroid concentrations in the second trimester of pregnancy.Hum Reprod.6:458–62.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Robin Mortimer
    • 1
  1. 1.Royal Brisbane Hospital and the University of QueenslandBrisbaneAustralia

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