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A woman with isolated prolactin deficiency

2001; Informa; Volume: 80; Issue: 4 Linguagem: Inglês

10.1034/j.1600-0412.2001.080004368.x

1600-0412

Tsutomu Douchi, Mitsuhiro Nakae, Shinako Yamamoto, Ichiro Iwamoto, Toshimichi Oki, Yukihiro Nagata,

Hypothalamic control of reproductive hormones

Acta Obstetricia et Gynecologica ScandinavicaVolume 80, Issue 4 p. 368-370 Free Access A woman with isolated prolactin deficiency Tsutomu Douchi, From the Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, JapanSearch for more papers by this authorMitsuhiro Nakae, From the Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, JapanSearch for more papers by this authorShinako Yamamoto, From the Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, JapanSearch for more papers by this authorIchiro Iwamoto, From the Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, JapanSearch for more papers by this authorToshimichi Oki, From the Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, JapanSearch for more papers by this authorYukihiro Nagata, From the Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, JapanSearch for more papers by this author Tsutomu Douchi, From the Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, JapanSearch for more papers by this authorMitsuhiro Nakae, From the Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, JapanSearch for more papers by this authorShinako Yamamoto, From the Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, JapanSearch for more papers by this authorIchiro Iwamoto, From the Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, JapanSearch for more papers by this authorToshimichi Oki, From the Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, JapanSearch for more papers by this authorYukihiro Nagata, From the Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, JapanSearch for more papers by this author First published: 15 January 2002 https://doi.org/10.1034/j.1600-0412.2001.080004368.xCitations: 1 Address for correspondence: Tsutomu DouchiDepartment of Obstetrics and GynecologyFaculty of MedicineKagoshima University8–35–1 SakuragaokaKagoshima 890–8520Japan AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Abbreviations: PRL prolactin LH lutenizing hormone FSH follicle-stimulating hormone BMI body mass index E2 estradiol GnRH gonadotropin-releasing hormone TRH thyrotropin releasing hormone TSH thyroid-stimulating hormone ACTH adrenocorticotropic hormone GH growth hormone RIA radioimmunoassay CC clomiphene citrate MPHD multiple anterior pituitary hormone deficiency It is well established that hyperprolactinemia due to either pituitary prolactinoma or hypothalamic derangement interferes with normal cyclic feed back mechanism. However, there are reports that prolactin (PRL) oversuppression to below normal levels causes the impairment of progesterone synthesis in normal cycling women (1, 2). It appears that a certain plasma level of PRL is required for progesterone synthesis to proceed normally. However, this concept is based on circumstances where PRL deficiency was surgically or medically induced. Thus, the clinical significance of hypoprolactinemia remains to be elucidated. We report a very rare case of isolated PRL deficiency, and discuss the relationship between hypoprolactinemia and reproductive function such as lactogenesis and ovarian function. Case report In 1998, a 26-year-old Japanese woman returned to our clinic complaining of post-partum amenorrhea. However, her menstrual cycle had been irregular prior to pregnancy. She remembered nothing unusual about her body composition during pubertal development. She experienced menarche at 14 years. In 1995, at 23 years, she had presented with oligomenorrhea. At the initial visit, her height, weight, and body mass index (BMI, weight/height2) were 162 cm, 61 kg, and 23.2 kg/m2, respectively. The development of pubic hair was consistent with Tanner classification IV. However, breast was atrophic. Serum LH, FSH, estradiol (E2), and PRL levels were 9.2 IU/L (normal limits [NL]=2 to 17), 9.7 IU/L (NL=2 to 9), 43 pg/mL (158 pmol/L, NL=>40 pg/mL), and <0.1 ng/mL (NL=1 to 14), respectively. However, there was no medical intervention undertaken for oligomenorrhea for various reasons. She married at 23 years of age in 1996, and conceived spontaneously a year later despite persistent oligomenorrhea. Thereafter, she delivered a healthy female baby. The course of vaginal delivery was uneventful. However, she could not breast-feed at all after parturition because of alactogenesis. There was no evidence of familial occurrence of alactogenesis. At 26 years old in 1998, she returned to our hospital, complaining of secondary amenorrhea for two years after parturition. Her height, weight, and BMI were 162 cm, 62 kg, and 23.6 kg/m2, respectively. On gynecological evaluation, the uterine corpus was of normal size and consistency, and both adnexa were normal. Bilateral ovaries and uterus were of normal size on transvaginal ultrasonography. Serum LH, FSH, E2, and PRL levels were 9.5 IU/L, 8.0 IU/L, 39 pg/mL (143 pmol/L), and <0.1 ng/mL, respectively. Repeated serum PRL levels were all <0.1 ng/mL. Table I presents the outcome of pituitary stimulation test using GnRH (LH-RH, Tanabe Co. Ltd, Osaka, 100 μg, intravenously) and TRH (TRH, Tanabe Co. Ltd, Osaka, Japan, 500 μg, intravenously). Serum levels of LH, FSH, and thyroid stimulating hormone (TSH) normally rose by 30 minutes after GnRH and TRH administration. However, PRL remained undetectable on TRH stimulation test. Repeated basal levels of growth hormone (GH), TSH, and adrenocorticotropic hormone (ACTH) were as follows: GH, 2.3 and 2.8 ng/mL (NL=<0.1 to 3); TSH, 1.4 and 1.7 μU/mL (NL=0.4 to 5), and ACTH, 58 and 65 pg/mL (NL=10 to 100). She was treated by clomiphene citrate (CC, Clomid, Shionogi Co. Ltd, Osaka, Japan). At a dose of 50 mg/day for 5 days, basal body temperature remained monophasic, but she was successfully treated by 100 mg/day for 5 days. Serum progesterone levels at the mid-luteal phase was 12.3 ng/mL (38.7 nmol/L, NL=> 10 ng/mL,), indicating normal luteal function. Serum levels of ACTH, GH, TSH, LH, FSH, PRL, E2, and progesterone were measured using commercially available radioimmunoassay (RIA) kits. ACTH II IRMA kit was obtained from Mitsubishi Petrochemicals, Tokyo, Japan. GH kit was obtained from Eiken Chemical, Tokyo, Japan. TSH RIA BEAD II kit was purchased from Dynabot, Tokyo, Japan. LH, FSH, PRL, E2, and progesterone kits were obtained from Daiichi Radioisotope Laboratories, Tokyo, Japan. The intra- and inter-assay coefficients of variation were less than 5.1% and 7.4%, respectively for each hormone. Discussion This patient demonstrated isolated deficiency of PRL, by clinical and laboratory data. Serum concentrations of all other pituitary hormones were within normal limits, as were GnRH and TRH stimulation, test of pituitary function and reserve. To our best knowledge, this is the fourth report about isolated PRL deficiency in world literature (based on MEDLINE search, May 1966–January 2000 using the search term ‘isolated PRL deficiency’). This patient showed absolute lactation failure because of puerperal alactogenesis. Our observation agrees with all of the previous three reports (3, 4–5). Table II presents the summary of the findings in the literature including ours for isolated PRL deficiency. PRL is important for the development and growth of the breasts, lactogenesis during pregnancy, and the initiation and maintenance of lactation after delivery. Thus, it appears that lactation failure is a consequence of the lack of PRL. However, subnormal mammary development was observed in this patient alone. Thus, it is likely that not PRL deficiency but estrogen deficiency contributes to the poorly developed breast, because only our case showed postpartum amenorrhea for two years. Zarger et al. (3) reported familial occurrence of alactogenesis in a woman and her mother, then postulated the possibility of a genetically transmitted isolated PRL deficiency. However, in our case and the other two reports (4, 5), familial occurrence of alactogensis was not observed. Isolated PRL deficiency seems to be ‘sporadic’ rather than ‘simplex’, because of its very low incidence. Familial occurrence of multiple anterior pituitary hormone deficiency (MPHD) is unusual and has been described as being transmitted in an autosomal recessive, autosomal dominant, or X-linked recessive manner (6). Some instances of familial occurrence of MPHD have been attributable to dominant and recessive mutations of gene for pituitary transcription factor, POU1F1, which is critical for the differentiation of somatotrophs, thyrotrophs, and lactotrophs (6). In several families as well as in sporadic cases, however, it has been recently demonstrated that mutation of PROP1 gene can cause gonadotropin deficiency in addition to somatotropin, TSH, and PRL deficiency (7). Thus, minor or partial mutation of the POU1F1 and/or PROP1 genes may be associated with the occurrence of isolated PRL deficiency. Significant disagreement persists with regard to the relation of isolated PRL deficiency to ovarian function. This patient showed oligomenorrhea, and post-partum amenorrhea in her menstrual history. Although there is evidence of delayed puberty in rats hypoprolactinemia (8, 9), delayed puberty was observed in only one report (5). The role of PRL in the onset of puberty may differ between humans and rats. Despite continuing oligomenorrhea, our patient conceived spontaneously, then delivered a healthy baby. Falk (4) reported an oligomenorrheic patient with isolated PRL deficiency, who conceived after treatment with clomiphene citrate. However, it is difficult to say whether ovarian dysfunction in these patients (including ours and that of Falk (4)) was related to hypoprolactinemic states. Zargar et al. (3) reported a familial occurrence of isolated PRL deficiency in mother and daughter, and then together two women conceived spontaneously eight times and carried through all pregnancies to full term without any luteal support. Kauppila et al. (5) also reported a normally menstruating patient with isolated PRL deficiency. With these findings taken into consideration, it is likely that isolated PRL deficiency does not have a major impact on fertility, even though causing mild ovulatory disturbances which can be treated with clomiphene citrate. In conclusion hypoprolactinemia has a stronger impact on lactogenesis than on ovarian function. Thus, we can say that, in humans, the dominant role of PRL is lactogenesis during pregnancy and lactation after delivery. References 1 Bohnet HG, Mühlenstedt D, Hanker JPF & Schneider HPG. Prolactin oversuppression.Gynäkologie1977; 223: 173– 178. CrossrefCASPubMedWeb of Science®Google Scholar 2 Schulz KD, Geiger W, Del Pozo E & Küning HJ. Pattern of sexual steroids, prolactin, and gonadotropic hormones during prolactin inhibition in normally cycling women.Am J Obstet Gynecol1978; 132: 561– 566.CASPubMedWeb of Science®Google Scholar 3 Zargar AH, Masoodi SR, Laway BA, Shah NA & Salahudin M. Familial puerperal alactogenesis: possibility of a genetically transmitted isolated prolactin deficiency.Br J Obstet Gynaecol1997; 104: 629– 631.Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 4 Falk RJ. Isolated prolactin deficiency: a case report.Fertil Steril1992; 58: 1060– 1062.CrossrefCASPubMedWeb of Science®Google Scholar 5 Kauppila A, Chatelain P, Kirkinen P, Kivinen S & Ruokonen A. Isolated prolactin deficiency in a woman with puerperal lactogenesis.J Clin Endocrinol Metab1987; 64: 309– 312.CrossrefCASPubMedWeb of Science®Google Scholar 6 Rosenbloom AL, Almonte AS, Brown MR, Fisher DA, Baumbach L & Parks JS. Clinical and biochemical phenotype of familial anterior hypopituitarism from mutation of the PROP1 gene.J Clin Endocrinol Metab1999; 84: 50– 57.CrossrefCASPubMedWeb of Science®Google Scholar 7 Cogan JD, Wu W, PhillipsIIIJA, Arnhold IJP, Agapito A & Fofanova OVet al. The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency.J Clin Endocrinol Metab1998; 83: 3346– 3349.CrossrefCASPubMedWeb of Science®Google Scholar 8 Gonzales MD, Lopez F & Aguilar E. Involvement of prolactin in the onset of puberty in female rats.J Clin Endocrinol Metab1984; 101: 63– 68. Google Scholar 9 Advis JP, Smith WS & Ojeda SR. Delayed puberty induced by chronic suppression of prolactin release in the female rat.Endocrinology1981; 109: 1321– 1330.CrossrefCASPubMedWeb of Science®Google Scholar Citing Literature Volume80, Issue4April 2001Pages 368-370 ReferencesRelatedInformation