Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1974 Jun;53(6):1588–1598. doi: 10.1172/JCI107709

Hypothalamic-Pituitary Function in Diverse Hyperprolactinemic States

R M Boyar 1,2, S Kapen 1,2, J W Finkelstein 1,2, M Perlow 1,2, J F Sassin 1,2, D K Fukushima 1,2, E D Weitzman 1,2, Leon Hellman 1,2
PMCID: PMC302654  PMID: 4208470

Abstract

Prolactin secretion in normal adults is characterized by periods of episodic secretion which increase in magnitude during sleep. In this study, we report the 24-h mean prolactin concentrations, prolactin secretory patterns, and associated pituitary hormone function in nine patients (seven women and two men) with hyperprolactinemia of diverse etiologies. Four of the women and one of the men had clinically demonstrable pituitary tumors, one boy had a hypothalamic tumor, and the three other women had “functional” hyperprolactinemia. The 24-h mean prolactin concentrations derived from averaging the 20-min interval samples for 24 h ranged from 28.6 to 1,220 ng/ml. The plasma prolactin patterns in these patients showed persistence of episodic secretion in all and loss of the normal sleep-wake difference in plasma prolactin in seven of nine. Three of the patients with galactorrhea and comparable 24-h mean prolactin concentrations (58.3, 59.7, and 64.3 ng/ml) showed similar prolactin secretory patterns despite different etiologic mechanisms. Evaluation of the secretory patterns of luteinizing hormone (LH) in these patients showed loss of normal pulsatile LH release and a low 24-h mean LH concentration in the patient with the pituitary tumor, while the two patients without clinically demonstrable pituitary tumors (“post-pill” galactorrhea and “idiopathic” galactorrhea) showed normal LH secretory patterns and 24-h mean LH concentrations. The 24-h mean cortisol concentrations and secretory patterns were normal in five of the seven patients who had these parameters measured. The patient with the hypothalamic tumor had a low 24-h mean cortisol concentration and production rate and absent response to metyrapone. The patient with “idiopathic” galactorrhea had an elevated 24-h mean cortisol concentration but normal cortisol production rate and urinary 17-hydroxycorticoid excretion. Growth hormone secretion was abnormal in four of the patients (one with the hypothalamic tumor and three with pituitary tumors). Thyrotropin-releasing hormone (TRH) administration in four patients resulted in normal TSH release in two patients (one of whom developed galactorrhea after the test), an absent response in the patient with the hypothalamic tumor, and a blunted response in one of the women with a pituitary tumor. The two men had low 24-h mean plasma testosterone concentrations (69 and 30 ng/100 ml) and symptoms of impotence and loss of libido. Five of the women (four with pituitary tumors and one with Chiari-Frommel syndrome) had either low 24-h mean LH concentrations, abnormal LH secretory patterns, or both. These data indicate that patients with hyperprolactinemia encompassing a varied etiological range frequently show loss of the normal sleep-associated increase in prolactin secretion as well as abnormalities in the regulation of the other hypothalamic pituitary-regulated hormones. The finding that the abnormalities in LH, growth hormone, thyrotropin, and cortisol (adrenocorticotrophic) secretion were almost uniformly confined to the patients with the clinically demonstrable hypothalamic or pituitary tumors suggests that the size of the lesion is the critical factor.

Full text

PDF
1588

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boyar R. M., Finkelstein J. W., David R., Roffwarg H., Kapen S., Weitzman E. D., Hellman L. Twenty-four hour patterns of plasma luteinizing hormone and follicle-stimulating hormone in sexual precocity. N Engl J Med. 1973 Aug 9;289(6):282–286. doi: 10.1056/NEJM197308092890602. [DOI] [PubMed] [Google Scholar]
  2. Boyar R., Finkelstein J., Roffwarg H., Kapen S., Weitzman E., Hellman L. Synchronization of augmented luteinizing hormone secretion with sleep during puberty. N Engl J Med. 1972 Sep 21;287(12):582–586. doi: 10.1056/NEJM197209212871203. [DOI] [PubMed] [Google Scholar]
  3. Boyar R., Perlow M., Hellman L., Kapen S., Weitzman E. Twenty-four hour pattern of luteinizing hormone secretion in normal men with sleep stage recording. J Clin Endocrinol Metab. 1972 Jul;35(1):73–81. doi: 10.1210/jcem-35-1-73. [DOI] [PubMed] [Google Scholar]
  4. Brown R. D., Van Loon G. R., Orth D. N., Liddle G. W. Cushing's disease with periodic hormonogenesis: one explanation for paradoxical response to dexamethasone. J Clin Endocrinol Metab. 1973 Mar;36(3):445–451. doi: 10.1210/jcem-36-3-445. [DOI] [PubMed] [Google Scholar]
  5. DREKTER I. J., HEISLER A., SCISM G. R., STERN S., PEARSON S., McGAVACK T. H. The determination of urinary steroids. I. The preparation of pigment-free extracts and a simplified procedure for the estimation of total 17-ketosteroids. J Clin Endocrinol Metab. 1952 Jan;12(1):55–65. doi: 10.1210/jcem-12-1-55. [DOI] [PubMed] [Google Scholar]
  6. Foley T. P., Jr, Jacobs L. S., Hoffman W., Daughaday W. H., Blizzard R. M. Human prolactin and thyrotropin concentrations in the serums of normal and hypopituitary children before and after the administration of synthetic thyrotropin-releasing hormone. J Clin Invest. 1972 Aug;51(8):2143–2150. doi: 10.1172/JCI107021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Forsyth I. A., Besser G. M., Edwards C. R., Francis L., Myres R. P. Plasma prolactin activity in inappropriate lactation. Br Med J. 1971 Jul 24;3(5768):225–227. doi: 10.1136/bmj.3.5768.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Frantz A. G., Kleinberg D. L., Noel G. L. Studies on prolactin in man. Recent Prog Horm Res. 1972;28:527–590. [PubMed] [Google Scholar]
  9. Frantz A. G., Kleinberg D. L. Prolactin: evidence that it is separate from growth hormone in human blood. Science. 1970 Nov 13;170(3959):745–747. doi: 10.1126/science.170.3959.745. [DOI] [PubMed] [Google Scholar]
  10. Friesen H., Guyda H., Hwang P., Tyson J. E., Barbeau A. Functional evaluation of prolactin secretion: a guide to therapy. J Clin Invest. 1972 Mar;51(3):706–709. doi: 10.1172/JCI106859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Friesen H., Webster B. R., Hwang P., Guyda H., Munro R. E., Read L. Prolactin synthesis and secretion in a patient with the Forbes Albright syndrome. J Clin Endocrinol Metab. 1972 Jan;34(1):192–199. doi: 10.1210/jcem-34-1-192. [DOI] [PubMed] [Google Scholar]
  12. Fukushima D. K., Bradlow H. L., Hellman L., Gallagher T. F. Further studies of cortisol production rate. J Clin Endocrinol Metab. 1969 Aug;29(8):1042–1045. doi: 10.1210/jcem-29-8-1042. [DOI] [PubMed] [Google Scholar]
  13. GLICK S. M., ROTH J., YALOW R. S., BERSON S. A. IMMUNOASSAY OF HUMAN GROWTH HORMONE IN PLASMA. Nature. 1963 Aug 24;199:784–787. doi: 10.1038/199784a0. [DOI] [PubMed] [Google Scholar]
  14. Gallagher T. F., Yoshida K., Roffwarg H. D., Fukushima D. K., Weitzman E. D., Hellman L. ACTH and cortisol secretory patterns in man. J Clin Endocrinol Metab. 1973 Jun;36(6):1058–1068. doi: 10.1210/jcem-36-6-1058. [DOI] [PubMed] [Google Scholar]
  15. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  16. Hellman L., Nakada F., Curti J., Weitzman E. D., Kream J., Roffwarg H., Ellman S., Fukushima D. K., Gallagher T. F. Cortisol is secreted episodically by normal man. J Clin Endocrinol Metab. 1970 Apr;30(4):411–422. doi: 10.1210/jcem-30-4-411. [DOI] [PubMed] [Google Scholar]
  17. Hellman L., Weitzman E. D., Roffwarg H., Fukushima D. K., Yoshida K. Cortisol is secreted episodically in Cushing's syndrome. J Clin Endocrinol Metab. 1970 May;30(5):686–689. doi: 10.1210/jcem-30-5-686. [DOI] [PubMed] [Google Scholar]
  18. Honda Y., Takahashi K., Takahashi S., Azumi K., Irie M., Sakuma M., Tsushima T., Shizume K. Growth hormone secretion during nocturnal sleep in normal subjects. J Clin Endocrinol Metab. 1969 Jan;29(1):20–29. doi: 10.1210/jcem-29-1-20. [DOI] [PubMed] [Google Scholar]
  19. Hwang P., Guyda H., Friesen H. A radioimmunoassay for human prolactin. Proc Natl Acad Sci U S A. 1971 Aug;68(8):1902–1906. doi: 10.1073/pnas.68.8.1902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jacobs L. S., Mariz I. K., Daughaday W. H. A mixed heterologous radioimmunoassay for human prolactin. J Clin Endocrinol Metab. 1972 Mar;34(3):484–490. doi: 10.1210/jcem-34-3-484. [DOI] [PubMed] [Google Scholar]
  21. Kamberi I. A., Mical R. S., Porter J. C. Prolactin-inhibiting activity in hypophysial stalk blood and elevation by dopamine. Experientia. 1970 Oct 15;26(10):1150–1151. doi: 10.1007/BF02112730. [DOI] [PubMed] [Google Scholar]
  22. Kleinberg D. L., Frantz A. G. Human prolactin: measurement in plasma by in vitro bioassay. J Clin Invest. 1971 Aug;50(8):1557–1568. doi: 10.1172/JCI106643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Krieger D. T., Glick S. M. Growth hormone and cortisol responsiveness in Cushing's syndrome. Relation to a possible central nervous system etiology. Am J Med. 1972 Jan;52(1):25–40. doi: 10.1016/0002-9343(72)90005-8. [DOI] [PubMed] [Google Scholar]
  24. Loewenstein J. E., Mariz I. K., Peake G. T., Daughaday W. H. Prolactin bioassay by induction of N-acetyllactosamine synthetase in mouse mammary gland explants. J Clin Endocrinol Metab. 1971 Aug;33(2):217–224. doi: 10.1210/jcem-33-2-217. [DOI] [PubMed] [Google Scholar]
  25. Malarkey W. B., Jacobs L. S., Daughaday W. H. Levodopa suppression of prolactin in nonpuerperal galactorrhea. N Engl J Med. 1971 Nov 18;285(21):1160–1163. doi: 10.1056/NEJM197111182852102. [DOI] [PubMed] [Google Scholar]
  26. Murphy B. E. Some studies of the protein-binding of steroids and their application to the routine micro and ultramicro measurement of various steroids in body fluids by competitive protein-binding radioassay. J Clin Endocrinol Metab. 1967 Jul;27(7):973–990. doi: 10.1210/jcem-27-7-973. [DOI] [PubMed] [Google Scholar]
  27. Nasr H., Mozaffarian G., Pensky J., Pearson O. H. Prolactin secreting pituitary tumors in women. J Clin Endocrinol Metab. 1972 Oct;35(4):505–512. doi: 10.1210/jcem-35-4-505. [DOI] [PubMed] [Google Scholar]
  28. Nieschlag E., Loriaux D. L. Radioimmunoassay for plasma testosterone. Z Klin Chem Klin Biochem. 1972 Apr;10(4):164–168. doi: 10.1515/cclm.1972.10.4.164. [DOI] [PubMed] [Google Scholar]
  29. Nokin J., Vekemans M., L'Hermite M., Robyn C. Circadian periodicity of serum prolactin concentration in man. Br Med J. 1972 Sep 2;3(5826):561–562. doi: 10.1136/bmj.3.5826.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Odell W. D., Wilber J. F., Utiger R. D. Studies of thyrotropin physiology by means of radioimmunoassay. Recent Prog Horm Res. 1967;23:47–85. doi: 10.1016/b978-1-4831-9826-2.50005-2. [DOI] [PubMed] [Google Scholar]
  31. Parker D. C., Rossman L. G., Vander Laan E. F. Sleep-related, nychthermeral and briefly episodic variation in human plasma prolactin concentrations. J Clin Endocrinol Metab. 1973 Jun;36(6):1119–1124. doi: 10.1210/jcem-36-6-1119. [DOI] [PubMed] [Google Scholar]
  32. SILBER R. H., PORTER C. C. The determination of 17,21-dihydroxy-20-ketosteroids in urine and plasma. J Biol Chem. 1954 Oct;210(2):923–932. [PubMed] [Google Scholar]
  33. Sachs B. A., Siegel E., Horwitt B. N., Siegel E. Bread iodine content and thyroid radioiodine uptake: a tale of two cities. Br Med J. 1972 Jan 8;1(5792):79–81. doi: 10.1136/bmj.1.5792.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sassin J. F., Frantz A. G., Kapen S., Weitzman E. D. The nocturnal rise of human prolactin is dependent on sleep. J Clin Endocrinol Metab. 1973 Sep;37(3):436–440. doi: 10.1210/jcem-37-3-436. [DOI] [PubMed] [Google Scholar]
  35. Sassin J. F., Frantz A. G., Weitzman E. D., Kapen S. Human prolactin: 24-hour pattern with increased release during sleep. Science. 1972 Sep 29;177(4055):1205–1207. doi: 10.1126/science.177.4055.1205. [DOI] [PubMed] [Google Scholar]
  36. Sassin J. F., Parker D. C., Mace J. W., Gotlin R. W., Johnson L. C., Rossman L. G. Human growth hormone release: relation to slow-wave sleep and sleep-walking cycles. Science. 1969 Aug 1;165(3892):513–515. doi: 10.1126/science.165.3892.513. [DOI] [PubMed] [Google Scholar]
  37. Sinha Y. N., Selby F. W., Lewis U. J., VanderLaan W. P. A homologous radioimmunoassay for human prolactin. J Clin Endocrinol Metab. 1973 Mar;36(3):509–516. doi: 10.1210/jcem-36-3-509. [DOI] [PubMed] [Google Scholar]
  38. Takahashi Y., Kipnis D. M., Daughaday W. H. Growth hormone secretion during sleep. J Clin Invest. 1968 Sep;47(9):2079–2090. doi: 10.1172/JCI105893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Turkington R. W. Ectopic production of prolactin. N Engl J Med. 1971 Dec 23;285(26):1455–1458. doi: 10.1056/NEJM197112232852604. [DOI] [PubMed] [Google Scholar]
  40. Turkington R. W. Inhibition of prolactin secretion and successful therapy of the Forbes-Albright syndrome with L-dopa. J Clin Endocrinol Metab. 1972 Feb;34(2):306–311. doi: 10.1210/jcem-34-2-306. [DOI] [PubMed] [Google Scholar]
  41. Turkington R. W., MacIndoe J. H. Hyperprolactinemia in sarcoidosis. Ann Intern Med. 1972 Apr;76(4):545–549. doi: 10.7326/0003-4819-76-4-545. [DOI] [PubMed] [Google Scholar]
  42. Turkington R. W. Measurement of prolactin activity in human serum by the induction of specific milk proteins in mammary gland in vitro. J Clin Endocrinol Metab. 1971 Aug;33(2):210–216. doi: 10.1210/jcem-33-2-210. [DOI] [PubMed] [Google Scholar]
  43. Turkington R. W. Secretion of prolactin by patients with pituitary and hypothalamic tumors. J Clin Endocrinol Metab. 1972 Jan;34(1):159–164. doi: 10.1210/jcem-34-1-159. [DOI] [PubMed] [Google Scholar]
  44. Turkington R. W. Serum prolactin levels in patients with gynecomastia. J Clin Endocrinol Metab. 1972 Jan;34(1):62–66. doi: 10.1210/jcem-34-1-62. [DOI] [PubMed] [Google Scholar]
  45. Turkington R. W., Underwood L. E., Van Wyk J. J. Elevated serum prolactin levels after pituitary-stalk section in man. N Engl J Med. 1971 Sep 23;285(13):707–710. doi: 10.1056/NEJM197109232851302. [DOI] [PubMed] [Google Scholar]
  46. Tyson J. E., Friesen H. G., Anderson M. S. Human lactational and ovarian response to endogenous prolactin release. Science. 1972 Sep 8;177(4052):897–900. doi: 10.1126/science.177.4052.897. [DOI] [PubMed] [Google Scholar]
  47. Weitzman E. D., Fukushima D., Nogeire C., Roffwarg H., Gallagher T. F., Hellman L. Twenty-four hour pattern of the episodic secretion of cortisol in normal subjects. J Clin Endocrinol Metab. 1971 Jul;33(1):14–22. doi: 10.1210/jcem-33-1-14. [DOI] [PubMed] [Google Scholar]
  48. Weitzman E. D., Schaumburg H., Fishbein W. Plasma 17-hydroxycorticosteroid levels during sleep in man. J Clin Endocrinol Metab. 1966 Feb;26(2):121–127. doi: 10.1210/jcem-26-2-121. [DOI] [PubMed] [Google Scholar]
  49. de Lacerda L., Kowarski A., Migeon C. J. Integrated concentration of plasma cortisol in normal subjects. J Clin Endocrinol Metab. 1973 Feb;36(2):227–238. doi: 10.1210/jcem-36-2-227. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES