Normal Serum Prolactin Levels Research Articles

Significance of hyperprolactinemia for cytomorphologic features of breast secretions

Nipple discharge syndrome is a clinical entity capable of presenting various disorders such is mammary infection (nonpuerperal and puerperal mastitis), intraductal papillomas, fibrodenoma, breast cancer and hyperprolactinemia syndrome. The aim of the study was to determine differences in cytological features of mammary secretion in patients with hyperprolactinemia and those with normal serum prolactin levels and to define the role of growth hormone, follicle-stimulating hormone, luteinizing hormone and thyroid-stimulating hormone in creating cellular profile of breast secretion. The study included 50 patients with nipple discharge syndrome. The patients were devided into the clinical group (27 patients with hyperprolactinemia and nipple discharge) and the control group I (23 patients with normal serum prolactin and nipple discharge). The control group II included the patients of the clinical group achieving normalised serum prolactin levels after the treatment of hyperprolactinemia. Serum prolactin, follicle-stimulating hormone and luteinizing hormone levels were assessed by RIA using commercial kits IRMA hPRL, hLH and hFSH, (INEP, Zemun, Serbia) while serum growth hormone and thyroid-stimulating hormone levels were assessed by RIA using commercial kits LKB-wallac. Cytologic evaluation of samples, taken from all the patients with mammary secretion, was done using standard techniques of staining Haemathoxilin-eozine and May-Grünwald/Giemsa. Our results showed a significantly higher presence of lipid and protein material in clinical group, in comparison with the control group I (p < 0.01). Also, our data demonstrated significantly higher number of ductal epithelial cells (p < 0.05) and ductal histiocities (p < 0.001) in the clinical group, compared with the control group I. Macrophagies frequency was proportionally higher in clinical group (44.44%) compared the control group I (17.39%). Erythrocites were significantly lower in the clinical group (p < 0.001) than in the control group I. Significantly decreased mammary secretion (p < 0.01), lower lipid (p < 0.01) and protein synthesis (p < 0.01), and less presence of all cellular categories (p < 0.01) were obtained after normalization of serum prolactin levels. Growth hormone, follicle-stimulating hormone, luteinizing hormone and thyroid-stimulating hormone did not show significant influence on creating cytological features of mammary secretion. The most expressive role, hyperprolactinemia demonstrated in the domain of mammary ductal secretory activity, making mammary secretion reach in lipid and protein material and simultaneously increasing number of ductal epithelial cells, ductal histiocytes and "foam cells"--macrophages. These cytological findings indicate that hyperprolactinemia promote periductal and intraductal steril inflammation which withdraws after serum prolactin normalization.

A case of paroxetine-induced galactorrhoea with normal serum prolactin level

The following case report highlights an interesting observation of paroxetine-induced galactorrhoea at therapeutic dosage and serum prolactin values of this patient comes out to be normal. This observation merits a systematic study to find the causal relationship of this unusual phenomenon and further explanation.

Pregnancy and hyperprolactinemia

After endocrinological and radiological evaluation of a hyperprolactinemia 13 patients became pregnant under bromocriptine therapy. In two of these patients a selective adenomectomy was performed by the transphenoidal route because of a prolactin (PRL) secreting adenoma. In 12 patients the pregnancy was not complicated. The serum PRL levels were different but mostly in a normal range. The control of x-ray and visual field in patients with a rapid increase of the PRL levels did not result in a tumor recurrence. After a normal course of the serum PRL concentrations one patient with a microadenoma developed suddenly a chiasma syndrome in the 31th week of gestation. The further evaluation resulted in a pituitary tumor with suprasellar extension. The discrepancy between the radiological result and the normal serum PRL levels was explained by a hemorrhage into the adenoma. After the operation the chiasma syndrome was reversible within a short period. Altogether, the course of the pregnancies was not complicated. We did not see fetal malformations. Post partum the sella x-ray of all patients did not reveal any significant changes so far.

Hyperprolactinaemia among infertile patients and its effect on sperm functions.

The effects of hyperprolactinaemia on sperm function were investigated in 264 men with oligozoo-, asthenozoo-, or teratozoospermia and who were attending a male infertility clinic. None of the patients exhibited galactorrhea or complained of impotence. There was no correlation between abnormal values in spermiogram and hyperprolactinaemia. After multiple measurements of serum prolactin concentration, 15 cases (5.7%) were diagnosed as hyperprolactinaemic (> or = 10 ng ml-1). Six of these patients were taking cimetidine and six were taking anti-anxiety drugs. Serum prolactin returned to the normal level after discontinuation of these drugs; thus these 12 cases were considered as drug-induced hyperprolactinaemia. The other three patients were diagnosed as having pituitary microadenomas and received bromocriptine treatment; the serum prolactin levels normalized within 1 month. No changes in sperm concentration, motility or morphology were found after normalization of serum prolactin levels. Sperm fertilizing ability was monitored by the hamster test for 10 months in the three patients with pituitary microadenoma, and no improvement was observed. Results suggest that hyperprolactinaemia, which does not cause symptoms, has little effect on the impairment of sperm functions. Measurement of serum prolactin in infertile men could be justified, however, for early detection of pituitary adenomas.

Efficacy and Safety of Cabergoline as First Line Treatment for Invasive Giant Prolactinoma

Although cabergoline is effective in the treatment of micro- and macro-prolactinoma, little is known about its efficacy in the treatment of invasive giant prolactinoma. We investigated the efficacy and safety of cabergoline in 10 male patients with invasive giant prolactinoma. Before treatment, mean serum prolactin level was 11,426 ng/mL (range, 1,450-33,200 ng/mL) and mean maximum tumor diameter was 51 mm (range, 40-77 mm). Three months after initiation of cabergoline treatment, serum prolactin concentrations decreased more than 97% in 9 patients; at last follow-up (mean treatment duration, 19 months), the mean decrease in serum prolactin concentrations was 98%, with 5 patients having normal serum prolactin levels. At first MRI follow-up (3-12 months after initiation of cabergoline), the mean reduction in tumor size was 85±4% (range, 57-98%). Cabergoline treatment for more than 12 months caused a greater reduction in tumor size compared to the treatment for less than 12 months (97±1% vs. 78±7%, P<0.05). These findings indicate that cabergoline treatment led to a significant and rapid reduction in serum prolactin concentrations and tumor size in patients with giant prolactinoma. Therefore, cabergoline represents an effective and well-tolerated treatment for invasive giant prolactinoma.

Radiological features of breast benign lesions in patients with hyperprolactinemia

Background: The study was conducted to determine whether prolactin (PRL) influences radiological features of benign breast lesions. Methods: During the 4-year period, we observed 50 patients with nipple discharge: 23 with normal serum prolactin levels (group 1) and 27 with hyperprolactinemia (group 2a before hyperprolactinemia treatment and group 2b after hyperprolactinemia treatment). Patients observed during this study underwent breast ultrasonography (US) and mammography. Radiological findings in group 1, group 2a and group 2b were compared. Results: The most frequent radiological findings in group 2a were dilated lactiferous ducts and cystic lesions with statistical significances p&lt;0.001 and p&lt;0.01 in comparison to other radiological findings. In group 1 significantly less presence of dilated lactiferous ducts was observed (p&lt;0.05) and proportional lower frequency of solid lumps compared to group 2a. Our results showed significantly lower incidence (p&lt;0.001) of dilated lactiferous ducts, after hyperprolactinemia treatment (group 2b). In group 2b less presence of solid lumps and enlarged axillary lymph nodes is also observed in comparison to group 2a. Frequency of cystic lesions significantly decreased (p&lt;0.05) and pseudocysts completely withdrew in patients with normalized serum prolactin levels. Conclusion: Prolactin significantly influences radiological presentation of benign breast diseases. Treatment of hyperprolactinemia results in withdrawal of mammary duct ectasia, pseudocystic formations, cystic lesions and solid lumps. Breast ultra-sonography and mammography should be considered as routine diagnostic procedures in patients with hyperprolactinemia.

Effect of the copper-intrauterine device (TCu 380A) on subendometrial microvascularization and uterine artery blood flow

During this cohort study, the copper-intrauterine device (IUD) did not modify subendometrial microvascularization. However, subendometrial blood flow increased in patients who experienced IUD-induced side effects.

Female genital mutilation of a karyotypic male presenting as a female with delayed puberty

BackgroundFemale genital mutilation (FGM) is commonly practiced mainly in a belt reaching from East to West Africa north of the equator. The practice is known across socio-economic classes and among different ethnic, religious, and cultural groups. Few studies have been appropriately designed to measure the health effects of FGM. However, the outcome of FGM on intersex individuals has never been discussed before.Case presentationThe patient first presented as a female with delayed puberty. Hormonal analysis revealed a normal serum prolactin level of 215 Mu/L, a low FSH of 0.5 Mu/L, and a low LH of 1.1 Mu/L. Type IV FGM (Pharaonic circumcision) had been performed during childhood. Chromosomal analysis showed a 46, XY karyotype and ultrasonography verified a soft tissue structure in the position of the prostate.ConclusionFGM pose a threat to the diagnosis and management of children with abnormal genital development in the Sudan and similar societies.

Long-Term Remission Following Withdrawal of Dopamine Agonist Therapy in Subjects With Microprolactinomas

Although two thirds or more of patients with microprolactinoma achieve normal serum prolactin levels over the long term after withdrawal of dopamine agonist therapy, there is no agreement on the appropriate duration of treatment, and treatment is not always interrupted. In this retrospective analysis of 89 patients, 84 women and 5 men with a mean age of 33 years, remissions were analyzed in 67 patients treated with 0.5 to 3 mg cabergoline weekly and 22 others given 2.5 to 10 mg bromocriptine daily. The mean duration of therapy was 3.1 years, and patients were followed for at least 1 year after treatment ended. None of the patients received medication other than a dopamine agonist. Seven women discontinued treatment when they became pregnant. All patients were symptomatic and hyperprolactinemic when first seen. Among 57 patients (64%) who had a recurrence after treatment stopped were 46 (81%) who had recurrent symptomatic hyperprolactinemia within 12 months after stopping treatment. The average interval was 9.6 months. Thirty-two patients, 36% of the total, achieved remission after at least 1 year of follow up; the mean duration of remission was 3.6 years. Nearly 85% of these patients remained in remission for longer than 2 years. Four of them were asymptomatic despite being hyperprolactinemic. The 2 dopamine agonists were equally effective. The overall median duration before relapse after discontinuance of treatment was 12 months. Logistic regression analysis failed to demonstrate an association between the risk of recurrence and age at presentation, imaging of an adenoma, or the duration of treatment. When dopamine agonist therapy is abruptly withdrawn after 2 years or longer in patients with microprolactinoma, 30% to 40% achieve long-term remission without side effects. Because symptomatic hyperprolactinemia may develop more than 1 year after treatment stops, long-term follow up is essential.

PRL Secreting Adenomas in Male Patients

Prolactinomas are the most frequent pituitary tumors and their frequency varies with age and sex, occurring most frequently in females between 20-50 yr-old. In men, hyperprolactinaemia is often present for many years without symptoms, as generally the most important symptoms are the decrease in libido and/or sexual potency both underestimated by the majority of the patients. Prolactin (PRL) plays a role in the process of spermatogenesis, and normal serum PRL levels are required for normal testicular function. On the other hand, hyperprolactinaemia has multiple negative effects on the gonadal axis. As a consequences hyperprolactinemic males show alteration of sexual potency and seminal fluid quality. Cabergoline treatments is able to induce normalization of PRL levels and a reduction of tumor mass in the majority of patients and consequently restoring the normal semen quality and ameliorating the quality of life of men with pituitary PRL-secreting adenoma.

Extreme Elevation of Intrasellar Pressure in Patients with Pituitary Tumor Apoplexy: Relation to Pituitary Function

The dominant mechanism for hypopituitarism and hyperprolactinemia commonly observed in patients with pituitary macroadenomas was postulated to be increased intrasellar pressure (ISP) caused by the slow and gradual expansion of adenomas within the sella turcica. Hemorrhagic infarction of adenomas (pituitary tumor apoplexy) is associated with a rapid, rather than gradual, increase in intrasellar contents. The impacts of the sudden increase in intrasellar contents on ISP and pituitary function are unknown. ISP and pituitary function were determined in 13 patients with pituitary tumor apoplexy who had surgical decompression within 1 wk of symptoms' onset. ISP measurements were remarkably high (median, 47 mm Hg), whereas serum prolactin (PRL) concentrations were generally low (median, 3.5 microg/liter). There was an inverse correlation (r = -0.76; P < 0.01) between ISP measurements and serum PRL concentrations. Postoperatively, partial recovery or maintenance of pituitary function was noted in seven of 13 patients. These seven patients had higher (P = 0.013) serum PRL levels (9.3 +/- 7.4 microg/liter) and lower (P < 0.001) ISP measurements (35.9 +/- 7.3 mm Hg) than the respective values in the remaining six with persistent postoperative hypopituitarism (1.6 +/- 0.6 microg/liter and 55.9 +/- 2.4 mm Hg, respectively). The low serum PRL levels in patients with tumor apoplexy suggested that ischemic necrosis of the anterior pituitary resulting from sudden and extreme elevation of ISP was commonly observed in this setting. A normal or elevated serum PRL level in patients with non-PRL-secreting macroadenomas indicates the presence of viable pituitary cells and the high likelihood of postoperative recovery of pituitary function.

Digital hysteroscopy: A new diagnostic method for the mid-secretory endometrium

BACKGROUND: The study of luteal phase is extremely important in order to determine the physiological and pathological mechanisms associated with embryo implantation or pregnancy loss. Several methods were studied and compared, however, usually they are impractical and costs. Hysteroscopy is usually employed by the majority of infertility centers and, the endometrial appearance, although in a subjective way could be related with the female reproductive status. We propose the objective (digitalized) evaluation of glandular opening during the luteal phase hysteroscopy as a new method for the study of luteal phase. METHODS: We performed a cohort study with 6 female volunteers in order to videotape and digitalize the hysteroscopy which was performed during the midsecretory phase. The frame-images were evaluated by specific software in a semiautomatic faction. The primary endpoint was to determine the number of glandular openings. We analyzed the coefficient of reliability comparing our results with a rank provided by six blinded collaborators to validate this method. RESULTS: All patients had regular menstrual cycle and normal serum prolactin, TSH and FSH levels. The mean age was 30.7 years (±3.3), the concordance coefficient (reliability) was 97% among the ranking provided by specialists and the number of glandular openings measured by our software. CONCLUSIONS: The proposed method is a reliable new technology which can be, in the near future, used during the luteal phase investigation.

Effect of Risperidone on Prolactinoma

Risperidone induced galactorrhea and hyperprolactinemia have been reported but its role in the growth of prolactinoma is not yet conclusive, due to extreme rarity of such cases. We describe a woman, suffering from Bipolar Disorder-manic episode, who exhibited prolactinoma while on risperidone therapy. The withdrawal of risperidone resulted in disappearance of prolactinoma though her prolactin level remained elevated along with persistent galactorrhea. The change to olanzapine therapy did not show much change in serum prolactin level and galactorrhea. Ultimately, only adding of bromocriptine resulted in disappearance of symptoms of prolactinemia and normal serum prolactin level was achieved and galactorrhea stopped. Further study is recommended to find out relationship between the growth of prolactinoma and risperidone.

Long-Term Follow-Up of Prolactinomas: Normoprolactinemia After Bromocriptine Withdrawal

Long-term bromocriptine (BRC) therapy has been considered necessary in patients with prolactinoma, with discontinuance often followed by recurrent hyperprolactinemia and, at least after short-term treatment, regrowth of tumor. There are, however, some reports that these adverse effects are not inevitable. The present study examined the effects of BRC withdrawal in a series of 350 patients, 280 females and 70 males aged 10 to 70 years, with prolactinomas. Prolactin levels were followed after withdrawal of BRC in this retrospective study. Primary treatment was with BRC in 301 patients, the median dose being 5 mg. Seventy-two patients who continued having high serum prolactin despite surgery received BRC in a median dose of 7.9 mg. Of 131 patients with prolactinoma who achieved normal prolactin levels during BRC therapy, 27(20.6%) continued to have normal levels after withdrawal of the drug when followed for a median time of 44 months. No macroprolactinoma was seen to reexpand when monitored by CT and/or MR imaging. Persistently normal prolactin levels after drug withdrawal could not be predicted by patient age or gender, tumor size, the pretreatment prolactin level, the initial dose of BRC, or the time of treatment. Pregnancy, past surgery, and radiotherapy also failed to influence the course after withdrawal of BRC. About one in five prolactinoma patients in this study who received BRC maintained normal serum prolactin levels after withdrawal of the drug. The investigators believe that gradual dose reduction is worthwhile in patients with prolactinoma whose serum prolactin becomes normal during treatment with BRC or another dopamine agonist.

Resistance to Cabergoline as Compared With Bromocriptine in Hyperprolactinemia: Prevalence, Clinical Definition, and Therapeutic Strategy

di Sarno, Antonella; Landi, Maria Luisa; Cappabianca, Paolo; Di Salle, Francesco; Rossi, Francesca W.; Pivonello, Rosario; di Somma, Carolina; Faggiano, Antongiulio; Lombardi, Gaetano; Colao, Annamaria

Prolactinomas in adolescents: persistent bone loss after 2 years of prolactin normalization.

To evaluate the effect of hyperprolactinaemia and its treatment with dopamine-agonists on bone mass and turnover in adolescent patients compared to adults. Forty patients with hyperprolactinaemia (20 with disease onset during adolescence and 20 during adulthood) and 40 healthy control subjects. Open transverse (in patients and controls) and open longitudinal (in the patients). Bone mineral density (BMD) at lumbar spine and femoral neck, serum osteocalcin (OC) and urinary cross-linked N-telopeptides of type-1 collagen (Ntx) levels were evaluated in patients and controls. In the 40 patients, bone mass and turnover were re-evaluated after 12 and 24 months of treatment with bromocriptine (BRC, dose 2.5-10 mg daily), quinagolide (CV, dose 0.075-0.3 mg daily) or cabergoline (CAB, dose 0.5-1.5 mg weekly). Transverse study: BMD values were significantly lower in hyperprolactinaemic patients than in controls, both at lumbar spine (0.81 +/- 0.01 vs. 1.010 +/- 0.01 g/cm2; P < 0.001) and femoral neck (0.71 +/- 0.01 vs. 0.873 +/- 0.03 g/cm2; P < 0.001). Thirty-two patients (80%) had osteoporosis and/or osteopenia at one or both skeletal sites. A significant inverse correlation was found between T score values measured at lumbar spine and femoral neck and the estimated disease duration. BMD was significantly lower in young than adult patients both at lumbar spine (T score, -2.4 +/- 0.1 vs. -1.4 +/- 0.3, P < 0.01) and at femoral neck (T score, -2.1 +/- 0.05 vs. -1.5 +/- 0.2, P < 0.05). Similarly, serum OC levels were significantly lower (2.0 +/- 0.11 vs. 9.1 +/- 2.4 micrograms/l, P < 0. 01) while Ntx levels were significantly higher in patients than in controls (129.2 +/- 1.7 vs. 80.7 +/- 2.9 nmol Bone collagen equivalent (BCE)/mmol creatinine; P < 0.001). A significant inverse correlation was found between prolactin (PRL) levels and OC levels, lumbar and femoral T score values, as well as between disease duration and OC levels, lumbar and femoral T score values. A significant direct correlation was also found between Ntx levels and PRL levels and disease duration. Longitudinal study: Normalization of serum PRL levels was obtained in all patients after 6-12 months of treatment. A significant increase of serum OC levels together with a significant decrease of Ntx levels was observed after 12 and 24 months of treatment (P < 0.01). Urinary and serum calcium, phosphorus, creatinine, and serum alkaline phosphatase and parathyroid hormone levels did not change during the study period in all patients. After 12 months of therapy OC and Ntx concentrations were restored to normal. A slight but not significant increase of BMD values was recorded after 12 and 24 months of treatment. After 12 months of treatment the percent increment of BMD values in the whole group of patients was 1.13 +/- 0.6% at lumbar spine and 1.2 +/- 0.4% at femoral neck level, whereas after 24 months, it was 2.8 +/- 0.7% at lumbar spine and 3.5 +/- 0.7% at femoral neck level. After 12 months of treatment, the percent increment of BMD values was 0.7 +/- 0.2% and 1.6 +/- 1.1% at lumbar spine and 0.9 +/- 0.5% and 1.6 +/- 0.5% at femoral neck level in the young and adult patients, respectively, whereas after 24 months, it was 2.1 +/- 0.8% and 3.4 +/- 1.3% at lumbar spine and 2.6 +/- 0.8% and 4.4 +/- 1.0% at femoral neck level in the young and adult patients, respectively. Adolescents with prolactinoma have osteopenia or osteoporosis, a finding that strengthens the need for a prompt diagnosis. Since normalization of PRL concentrations by dopamine agonist therapy is unable to restore the bone mass, other therapeutic approaches should be considered in order to prevent further long-term problems.

Cabergoline in the Treatment of Hyperprolactinemia: A Study in 455 Patients

Many hyperprolactinemic patients do not tolerate bromocriptine or other dopamine agonists and, even if they do, often must take them two or three times each day. Cabergoline is a long-lasting dopamine agonist whose action lasts up to 2 weeks after a single dose so that it may be taken once or twice a week. This study evaluated cabergoline in 353 women and 102 men with pathologic hyperprolactinemia. Roughly 40 percent of the group had a microadenoma, and the same proportion had a macroadenoma. No cause was evident in 16 percent of cases. Of 292 patients who previously had received bromocriptine, 140 were intolerant and 58 were resistant to the drug. The median baseline serum prolactin was 124 μg/liter. Cabergoline therapy usually began at a dose of 0.25 or 0.5 mg twice weekly, and the dose was adjusted at 2- to 3-month intervals as needed to consistently reduce the prolactin level. Patients then were followed up every 4 to 6 months. Menstrual function became normal during cabergoline therapy in 89 percent of the women evaluated, several of whom became pregnant and delivered healthy children. The visual fields became normal in 70 percent of 47 patients. Migraine symptoms lessened significantly in 72 percent of 71 patients. Prolactin levels became normal in 86 percent of all patients and decreased by 75 percent or more in more than half of the others. The median lowest serum prolactin level, achieved in 8 months on average, was 5.6 μg/liter. The tumor shrank to some degree in two thirds of patients. At the end of follow-up, the median dose of cabergoline was 0.5 mg/week. Minor side effects were reported by 8.5 percent of patients, and major or persistent symptoms were reported by 4 percent. Headache and postural hypotension were the most common adverse effects. Of the 14 patients who withdrew because of intolerance, 12 had also failed to tolerate bromocriptine. Only 9 percent of bromocriptine-intolerant patients were also intolerant of cabergoline. Patients harboring a microprolactinoma required lower doses and were more likely than those with macroadenomas to achieve a normal serum prolactin level. The baseline and lowest serum prolactin levels correlated weakly but significantly. In more than two thirds of patients who had been resistant to bromocriptine, control was achieved with cabergoline. This large-scale study affirms the effectiveness and tolerance of cabergoline when used to treat pathologic hyperprolactinemia. J Clin Endocrinol Metab 1999;84:2518–2522

Neuroendocrine immune features of pediatric inflammatory rheumatic diseases.

Juvenile rheumatoid arthritis (JRA) and juvenile systemic lupus erythematosus (JSLE) are the most common autoimmune rheumatic diseases in children associated with high levels of autoantibodies and immune reactivity. JRA and JSLE are more common in girls. Disease activity is worse in the morning, improves during the daytime and worsens at night suggesting that neuroendocrine immune mechanisms are involved in disease pathophysiology. Adult patients with RA and SLE have excessive levels of prolactin (PL) while cortisol (CS) production is down-regulated for the degree of ongoing inflammation. PL has potent proinflammatory properties. Normal to low levels of cortisol have been observed in children with active JRA despite the high serum levels of IL-6, IL-1 beta, and TNF-alpha, which activate the hypothalamic-pituitary-adrenal axis (HPA). The CS levels are in fact subnormal because inflammatory stress activates the HPA. Normal serum PL levels were seen in children with JRA, most of whom were not active with higher levels in those with active ANA +ve JRA complicated by uveitis. A trend toward high PL levels was seen in 33 children with JSLE. High serum PL levels are seen in patients with active juvenile ankylosing spondylitis (JAS) only. Growth retardation is a feature of JRA. Patients with JRA have low to normal levels of growth hormone (GH) and low levels of insulin-like growth factor 1 (IGF-1). IGF-1 mediates the effects of GH. The observation of low IGF-1 in JRA raises the therapeutic possibility with IGF-1. Overall, high levels of follicle stimulating hormone and luteinizing hormone are found in children with JSLE while the levels in JRA tend to be normal. Testosterone levels are low in patients with JRA. No significant differences in estrogen levels have been found between patients with JRA and those with JSLE and matched controls. There is evidence that the autonomic nervous function is defective in patients with JRA.

Growth Hormone and Prolactin Gene Expression in Human Densely and Sparsely Granulated Somatotroph Adenomas by In Situ Hybridization with Digoxigenin-Labeled Probes

We studied growth hormone (GH) and prolactin (PRL) messenger ribonucleic acids (mRNAs) in 14 cases with densely granulated somatotroph (DG) adenomas and 10 cases with sparsely granulated somatotroph (SG) adenomas using in situ hybridization with digoxigenin-labeled probes and correlated these data with their immunohistochemical results. A good correlation between in situ hybridization results and immunohistochemical data was found in most cases examined. The DG adenomas generally had a diffuse and intense GH immunoreactivity and GH hybridization signal, whereas in SG adenomas the number of cells exhibiting a GH mRNA signal and the strength of the GH mRNA signal in these cells were relatively lower than those of DG adenomas, indicating that lower expression of the GH mRNA signal is responsible for lower GH production in SG adenomas. In addition, PRL mRNA expression differed in the two types of adenoma; in DG adenomas, seven cases (50%) expressed PRL mRNA signal with a focal or scattered distribution despite normal serum PRL levels, but two showed no PRL immunoreactivity. In contrast, in SG adenomas, only one case contained a few cells possessing a PRL mRNA signal despite having no PRL immunoreactivity. It can be concluded that DG and SG adenomas, which have been considered variants of the same tumor, display definite differences as to GH or PRL gene expression in each type of adenoma.

Morphologically unclassified GH-producing adenoma showing galactorrhea without acromegaly.

A 24-year-old woman with a large pituitary adenoma had amenorrhea and galactorrhea, but no physical stigmata of acromegaly despite slightly elevated serum growth hormone (GH) and normal serum prolactin (PRL) levels. Subtotal removal of the tumor cured galactorrhea and resulted in normalization of serum GH concentration. The question is raised whether amenorrhea and galactorrhea were related to excessive GH production in this patient. Absence of acromegaly might have been due to the short duration of the disease. The tumor was a chromophobic, periodic acid-Schiff-negative adenoma. Immunocytochemistry and in situ hybridization revealed focal GH immunoreactivity and diffuse, weak signal for GH messenger RNA. By electron microscopy, the tumor showed no features of GH or PRL-producing adenomas. Two different cell types could be distinguished: the majority were similar to null cells, whereas a small number of cells resembled somatotrophs and lactotrophs, possessing many secretory granules and exhibiting exocytosis. On the basis of its ultrastructure, this tumor can be classified as an atypical acidophil cell line adenoma in which adenomatous null cells transformed to the differentiated cells capable of producing GH.