PRL Values Research Articles

Clinical and Radiological Characteristics of a Patient with a Pituitary Tumor of the Prolactinoma Type — Case Report

Introduction. Prolactinoma is a benign tumor of the anterior lobe of the pituitary gland. It is the most common type of pituitary adenoma. In terms of size, micro- and macroprolactinomas are distinguished. Prolactinoma is mostly a benign tumor (>98%). Symptoms in hyperprolactinemia are the result of excess hormone and mass effect. Symptoms of the mass effect include headaches, visual disturbances and dizziness. Excess prolactin leads to infertility and “amenorrhea — galactorrhea” syndrome. Aim. To increase general understanding and awareness of the symptoms, causes, and treatments of patients diagnosed with prolactinomas. Case Report. A 54-year-old female patient was admitted to the department for diagnosis due to left-sided headaches occurring for 6 years. Magnetic resonance imaging (MRI) of the pituitary gland was performed, which showed a 20×10×17.5 mm lesion. Blood tests showed high PRL values of 272.0 ng/ml (N<23.3 ng/ml). The patient was treated conservatively with cabergoline, achieving normalization of PRL levels and a reduction in tumor dimensions on follow-up MRI examination. Discussion. Drug treatment of the patient with cabergoline led to normalization of prolactin levels and reduction in the size of the pituitary adenoma. Conservative treatment of hyperprolactinemia in the course of a prolactinoma adenoma is many years. Conclusions. Pituitary adenomas of the prolactinoma type respond well to conservative treatment with dopamine agonists. Pituitary tumors should be considered in the differential diagnosis in cases of headaches, and if menstrual disorders or irregular menses are additionally present, it is necessary to complete the diagnosis for hyperprolactinemia. (JNNN 2024;13(2):78–84)

FRI306 Natural History Of Untreated Prolactinoma

Abstract Disclosure: M. Sadek: None. N. Sandila: None. D.B. Clarke: None. S.A. Imran: None. BACKGROUND Prolactinomas (PRLomas) are the most common functioning pituitary tumors, and the majority are microPRLomas (<10 mm in size). Current guidelines do not support treating asymptomatic or minimally symptomatic microPRLomas based on older studies utilizing insensitive imaging and assay techniques, whereas only limited information is available about the natural history of microPRLomas based on new generation assay and advanced imaging modalities. OBJECTIVES This study aims to assess the natural history of medically untreated microPRLomas with regards to long-term trends of serum PRL, tumor growth, clinical symptoms, and their effect on other pituitary function. METHODS We conducted a retrospective review of all patients diagnosed with microPRLoma since 2005 from our comprehensive provincial pituitary registry in Nova Scotia, Canada. Secondary causes of hyperprolactinemia were excluded. Outcomes were extracted at diagnosis and each follow-up visit. PRL, % above upper limit of normal (AULN) and tumor size (mm) were modelled using linear mixed effects models and clinical symptoms were analyzed with McNemar’s Test. Increase in PRL was modeled with exact logistic regression with change in tumor size and symptoms as predictors. RESULTS A total of 28 patients were identified; median age at diagnosis was 37 yrs (IQR 27.5 - 47.5) and median follow-up was 70 months (IQR 41.5 - 123.5). No patient had additional pituitary hormonal abnormality except gonadal dysfunction. Median tumour size at diagnosis was 3 mm (IQR 2 - 4), and median PRL (AULN) was 50% (IQR 15.2 - 113.3). Twenty four (85.7%) had symptoms at diagnosis including: galactorrhea, oligomenorrhea and amenorrhea. At last follow-up, those without symptoms at diagnosis remained asymptomatic and the majority (80%) with symptoms at presentation had complete resolution of symptoms (p<0.01). Only 20% had persistent symptoms, commonest being galactorrhea, but none had worsening of symptoms. There was no evidence of any association between elevated serum prolactin and persistent symptoms. Overall, mean change in tumor size (mm) was -0.9286 (p-value = 0.0138), of which, 2 patients (7%) had an increase since diagnosis (mean increase = 2.5 mm) while the rest (93%) had either no change or a decrease in tumor size. Serum PRL (AULN) when adjusted for change over time (month) over during the entire follow-up period decreased in 20 (71.4%) patients by a median of -0.00793 (IQR -0.01556 - -0.00597) and increased in 8 (28.6%) by a median of 0.00321 (IQR 0.00181 - 0.01549).CONCLUSIONS Although limited by sample size, these findings suggest that when left untreated, the majority of microPRLomas remain stable both in terms of size and PRL values and clinical symptoms resolve in most patients over time. Presentation: Friday, June 16, 2023

Effect of High-Dose Cabergoline Therapy for Hyperprolactinemic Infertility among Bangladeshi Women

Background: Cabergoline is effective in the treatment of hyperprolactinemic hypogonadism. It is a highly effective and long-acting inhibitor of prolactin secretion. The rate of cabergoline-induced pregnancy in women with prolactinoma, is unknown. Objective: The aim of present study is to evaluate the efficacy and safety of high-dose cabergoline therapy for hyperprolactinemic infertility among Bangladeshi women. Method: This descriptive cross- sectional study was conducted among 50 patients from January, 2020 to January, 2022 in at The Medinova Diagnostic Centre, Sylhet, Bangladesh. Results: In our study, maximum (14) patients belong to the age group of 19 to 23 years, and minimum number of patients (4) was between 39 to 43 years. Maximum (52%) patients had the primary infertility and 48% had secondary infertility. The mean values of thyroid stimulating hormone (TSH), Follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin PRL is 3.93±6.58, 10.96±13.58, 9.83±6.8, and 12.46±14.39 respectively and these were significant. 12% patients had PCO and 88% patients were normal in our study. 78% semens were normal, 4% semen showed Azzospermia, 14% semens showed Oligo Astheno Spine and 4% semens showed Astheno spine. Conclusion: In infertile women with prolactinoma, cabergoline can achieve a high pregnancy rate with uneventful outcomes. The findings demonstrated that cabergoline can be used safely to improve menstrual cycles in hyperprolactinemia.

Metabolic effects of prolactin.

Over the last years, the metabolic role of PRL has emerged. PRL excess is known to promote weight gain, obesity, metabolic syndrome, and impairment in gluco-insulinemic and lipid profiles, likely due to the suppression of physiologic dopaminergic tone. Prolactin receptors and dopamine receptors type 2 have been demonstrated to be expressed on both human pancreatic β- cell and adipocytes, supporting a key role of prolactin and dopamine in peripheral metabolic regulation. Medical treatment with the dopamine agonists bromocriptine and cabergoline has been demonstrated to decrease the prevalence of metabolic syndrome and obesity, and significantly improve gluco-insulinemic and lipid profiles. In hyperprolactinemic men with concomitant hypogonadism, correction of hyperprolactinaemia and testosterone replacement has been proven to restore metabolic impairment. In turn, low prolactin levels have also been demonstrated to exert a detrimental effect on weight gain, glucose and lipid metabolism, thus leading to an increased prevalence of metabolic syndrome. Therefore, PRL values ranging from 25 to 100 mg/L, in absence of other recognizable pathological causes, have been proposed to represent a physiological response to the request for an increase in metabolic activity, and nowadays classify the so-called HomeoFIT- PRL as a promoter of metabolic homeostasis. The current review focuses mainly on the effects of hyperprolactinemia and its control by medical treatment with DAs on the modulation of food intake, body weight, gluco-insulinemic and lipid profile. Furthermore, it provides the latest knowledge about the metabolic impact of hypoprolactinemia.

Persistent Transsphenoidal/Craniopharyngeal Canal: A Rare Defect

A young child of 5.5 years of age presented with complaints of growth retardation .On examination, weight recorded was 11kg ;height was 91 cm .Micropenis was noted with poorly formed scrotum and testicular volume of ~1cc each.on Clonidine stimulation test ,GH values were found to be significantly low.LH,FSH and PRL values were also lower .gross motor skills ,language and social development was noted to be appropriate for age.working diagnosis of GH deficiency was made and imaging was done.

Comparison of Ki-67 index values between patients with operated giant prolactinomas and macroprolactinomas

Objective: Data on whether there is a histopathological difference in cellular features as determined with Ki-67 between giant prolactinomas and smaller macroprolactinomas are not fully clear. In this study, we aimed to compare Ki-67 value between patients followed-up with diagnosis of macroprolactinoma and giant prolactinoma and operated for different reasons.
 Methods: Files of 15 patients with giant prolactinomas and 16 patients with macroprolactinomas who had been operated with various indications were retrospectively evaluated. Similar number of patients were included to carry out a reasonable analysis. Patients’ demographics (age and gender), age at the time of diagnosis, tumor diameter during the diagnosis and at the last follow-up visit, initial and last PRL and Ki-67 values were compared between the groups. Ki-67 value was studied with MIB-1 monoclonal antibody method.
 Results: The mean age and gender were similar between the patients with macroprolactinomas and giant prolactinomas. The mean longest tumor diameter at diagnosis was measured as 18.13±9.42 mm in the macroprolactinoma and 47.07±9.70 mm in the giant prolactinoma group (p

Prevalence of Macroprolactinaemia by Polyethylene Glycol Precipitation Method: A Cross-sectional Study

Introduction: Macroprolactin, an immunoreactive molecule resulting from association of monomeric Prolactin (mPRL) and immunoglobulin G is a significant cause of misdiagnosis, unnecessary radiological investigation and treatment for hyperprolactinaemia. Data on its prevalence and clinical manifestation varies regionally. Case presentation can vary with assymptomatic cases to those with galactorrhea and irregular menses. Aim: To find the prevalence and clinical features associated with macroprolactin in cases of hyperprolactinaemia in hospital patients. Materials and Methods: A cross-sectional study was conducted in the Department of Biochemistry, Institute of Postgraduate Medical Education and Research and SSKM hospital, Kolkata, India, from November 2018 to April 2019. Serum samples were assayed for serum PRL levels in 1400 subjects by Chemiluminescence immunoassay (Immulite 1000 siemens) based on presenting symptoms of galactorrhoea, amenorrhoea and infertility. Serum PRL samples (n=240) above the manufacturer’s reference cut-off level (PRL ≥30 ng/mL) were obtained from patients with or without symptoms of hyperprolactinaemia. Retesting for PRL levels were done following precipitation of macroprolactin using Polyethylene Glycol (PEG, MW: 6000). Fourty cases with physiological causes of PRL excess, hypothyroidism, polycystic ovary syndrome, antidopaminergic drug intake, hepatorenal diseases and chest wall disorders were excluded. The results were expressed in terms of Mean±Standard Deviation (SD) and compared using student t-test. Results: Prevalence of macroprolactin was 16 (13.3%) out of 120 among true hyperprolactaemic cases (male=2; female, n=14) based on percentage recovery of PRL in post-PEG cases (Recovery Rate (RR) <40%). The mean pre-PEG and post-PEG values were 52.5 ng/mL and 19.2 ng/mL (RR: 36.5%; p-value <0.05), respectively. The mean pre PEG, PRL values were significantly lower in macroprolactaemic cases than those with true hyperprolactinaemia (52.5 ng/mL versus 74.57 ng/mL; p-value 0.038). Some of the Macro-PRL cases reported with complaints of galactorrhoea, menstrual irregularities and infertility. Conclusion: The results revealed a prevalence rate similar to those reported in other studies worldwide. Clinical features alone are an unreliable tool to distinguish between cases with true high PRL levels and macroprolactinaemia. Macro-PRL cases once diagnosed requires no extended endocrine review and long term management. Hence, in cases with high PRL levels discordant with clinical symptoms/radiological data routine PEG precipitation test is an inexpensive assay for initial screening for presence of macroprolactin and also monitoring of patients already started on dopamine agonists for hyperprolactinaemia of unknown aetiology.

The effect of manganese exposure on erythropoietic and reproductive system parameters

The aim of this study is determining the effect of manganese (Mn) exposure on erythropoietic and reproductive system. A study group consisting of 51 non-smoking welders older than 18 years old with Mn exposure, who visited Ankara Occupational and Environmental Diseases Hospital, and a control group consisting of 79 healthy office employees without Mn exposure, were chosen as study group. Blood Mn level, total testosterone (TT), freetestosterone (FT), alanine aminotransferase (ALT), aspartate aminotransferase(AST), thyroid stimulant hormone (TSH), triiodothyronine (T3), thyroxine (T4), uric acid, creatinine, complete blood count (CBC), prolactin, follicle stimulating hormone (FSH), luteinizing hormone (LH) levels were analysed along with the demographic data of the patient. The study and control groups consisting of a total of 130 persons were all male, 39.2% (n=51) of which represented the study group with manganese exposure and 60.8% (n=79) of which represented the healthy control group. A significant difference was identified statistically between Mn (t= 4,501, p= 0,000), FT (t= -6.959, p=0.000), TT (t= -2.835, p=0.005) values of those with and without manganese exposure. AST and ALT levels were not found significant although they were higher in the exposed group. When the values are examined according to uric acid, creatinine, TSH, T3, T4and complete blood count, it was observed that the values of exposure group and control group were almost identical. Although FHS, LH and PRL values were high in the study group, the differences were not found significant. Consequently, although Mn is a trace element, it was concluded that, in high levels,it might reduce the testosterone synthesis with direct toxic effect on the testicle in the long-term exposures leading.

HPA axis dysfunction: Is it a trait marker for bipolar disorder?

Results:Both inHCsand inMDDs,800hand2300hbasal PRL (BL PRL) andTRH-PRL responses (i.e. PRL)werehigher inwomen than inmen (all p<0.05). 2300hPRL and PRL (difference between 2300h and 800hPRL) were lower in drug-free female MDDs compared to female HCs (all p<0.02). In women only, 2300h-BL PRL and PRL (at 800h and 2300h) levels were higher after two weeks of ADT than at baseline (all p<0.005). These changes did not differ across the antidepressant drugs andwere not associatedwith clinical response. Conclusion: Our results confirm marked sex difference in PRL secretion among controls and patients. Blunted 2300hPRL and PRL values at baseline support an alteration of TRH receptor circadian chronesthesy in depressedwomen. After 2 weeks of ADT, changes in PRL levels in women suggest that different types of ADT could enhance TRH—and/or serotonin—transmission regardless of clinical outcome.

Chronobiological cortisol secretion and dopamine function in major depression

Results:Both inHCsand inMDDs,800hand2300hbasal PRL (BL PRL) andTRH-PRL responses (i.e. PRL)werehigher inwomen than inmen (all p<0.05). 2300hPRL and PRL (difference between 2300h and 800hPRL) were lower in drug-free female MDDs compared to female HCs (all p<0.02). In women only, 2300h-BL PRL and PRL (at 800h and 2300h) levels were higher after two weeks of ADT than at baseline (all p<0.005). These changes did not differ across the antidepressant drugs andwere not associatedwith clinical response. Conclusion: Our results confirm marked sex difference in PRL secretion among controls and patients. Blunted 2300hPRL and PRL values at baseline support an alteration of TRH receptor circadian chronesthesy in depressedwomen. After 2 weeks of ADT, changes in PRL levels in women suggest that different types of ADT could enhance TRH—and/or serotonin—transmission regardless of clinical outcome.

Prolactin variations during risperidone therapy in a sample of drug-naive children and adolescents.

The aim of this prospective observational study was to investigate the variations of serum prolactin hormone (PRL) in a sample of 34 drug-naive patients (mean age 13 years) who started risperidone therapy assuming that several factors may favor the increase in serum PRL. Serum PRL and hyperprolactinemia clinical signs were examined at baseline (T0) and after almost 3 months of treatment (T1). We considered sex, pubertal status, risperidone dosage, psychiatric diagnosis, and any personal/family history of autoimmune diseases. The mean serum PRL value increased between T0 and T1 (P=0.004). The mean serum PRL was higher in females in the pubertal/postpubertal stage and for risperidone dosage up 1 mg/day. Hyperprolactinemia was found in 20% of patients at T0 and in 38% of patients at T1 (P=0.03). The mean serum PRL increase was greater in early-onset schizophrenia spectrum psychosis patients compared with no-early-onset schizophrenia spectrum psychosis patients (P=0.04). The increase in PRL was higher in patients with a personal and a family history of autoimmune diseases. This study suggests that the increase in serum PRL in patients treated with risperidone may be linked not only to the drug and its dosage but also to several risk factors such as sex, pubertal stage, psychiatric disease, and autoimmune disorders.

Low Growth Hormone Levels in Short-Stature Children with Pituitary Hyperplasia Secondary to Primary Hypothyroidism.

Objective. The follow-up of GH levels in short-stature children with pituitary hyperplasia secondary to primary hypothyroidism (PPH) is reported in a few cases. We aimed to observe changes in GH secretion in short-stature children with PPH. Methods. A total of 11 short-stature children with PPH accompanied by low GH levels were included. They received levothyroxine therapy after diagnosis. Their thyroid hormones, IGF-1, PRL, and pituitary height were measured at baseline and 3 months after therapy. GH stimulation tests were performed at baseline and after regression of thyroid hormones and pituitary. Results. At baseline, they had decreased GH peak and FT3 and FT4 levels and elevated TSH levels. Decreased IGF-1 levels were found in seven children. Elevated PRL levels and positive thyroid antibodies were found in 10 children. The mean pituitary height was 14.3 ± 3.8 mm. After 3 months, FT3, FT4, and IGF-1 levels were significantly increased (all p < 0.01), and values of TSH, PRL, and pituitary height were significantly decreased (all p < 0.001). After 6 months, pituitary hyperplasia completely regressed. GH levels returned to normal in nine children and were still low in two children. Conclusion. GH secretion can be resolved in most short-stature children with PPH.

Pattern of Prolactin Secretion after Normal Vaginal Delivery and in Cesarean Delivery

ABSTRACTProlactin (PRL) is hormone of multiple biological actions and is best known for its role in milk production. This hospital-based study was undertaken to review the impact of PRL hormone in vaginal delivery and cesarean delivery. Our study is meant to create awareness in the society to promote breast feeding and the importance of promoting normal vaginal delivery whenever possible. In this study, we investigated the serum PRL values using enzyme-linked immunoflow assay method in 101 women who underwent normal (56) and cesarean delivery (45) in obstetrics and gynecology department of Kannur Medical College, Anjarakandy. Serum PRL at 24 and 48 hours blood sample was estimated among the two groups, mean PRL in vaginal delivery 24 hours 359.46 ± 119.70 ng/ml, 48 hours 386.67 ± 135.66 ng/ ml and in cesarean delivery 24 hours 245.49 ± 115.49 ng/ml, 48 hours 282.92 ± 69.59 ng/ml. The values of serum PRL are found to be significantly higher in the vaginal delivery group (p &lt; 0.001) as compared with the cesarean section group. Through this study, we concluded that the mothers who delivered by cesarean section had decreased PRL levels than the women who delivered vaginally which may have a significant role in establishment of breastfeeding.How to cite this articleManapatt AK, Anoop L, Tharammal D, Sathyapal A, Muneer Y. Pattern of Prolactin Secretion after Normal Vaginal Delivery and in Cesarean Delivery. Int J Infertility Fetal Med 2014;5(1):15-17.

Prolactinomas in Infertile Women: Clinical and Endocrine Characteristics Before and After 24 Months of Treatment with Bromocriptine

Prolactinomas are the most common tumors of the pituitary gland and cause of gonadal dysfunction and infertility. To determine the effects of bromcriptin to normalize prolactin, gonadal function more tumor mass and infertility. A prospective clinical study included 30 infertile women with micro-macro prolactinoma. We analyzed clinical parameters, the function of sex hormones, the maximum tumor diameter before and after 24-month therapy with bromocriptine. Micro prolactinomas were significantly (66.3% vs. 33.7%, p < 0.001) over-represented in infertile women compared to macro prolactinomas. Galactorrhea / amenorrhea, and infertility are common symptoms of macro-micro prolactinomas. Infertile women with present macro prolactinomas had significantly higher mean values of PRL (1900.3 vs. 7.8, p < 0.001), significantly lower mean FSH (3.4 vs. 4.6, p < 0.001), LH (2.9 vs. 5.2, p < 0.001), luteal progesterone (2.5 vs. 14.8, p < 0.001) and estradiol (E2) (98.2 vs. 180.1, p < 0.001) compared to the control group. Infertile women with micro prolactinomas had significantly higher values of PRL (170.4 vs. 7.8, p < 0.001), significantly lower mean FSH (4.1 vs. 4.6, p < 0.01), LH (3.8 vs. 5.2, p < 0.01) luteal progesterone (2.7 vs. 14.8, p < 0.001) and E2 (120.3 vs. 180.1, p < 0.001) compared to the control group. After 24-month therapy bromocriptine in infertile women with micro-macro prolactinomas followed by a significant decrease in PRL (p < 0.05), a significant reduction of the maximal tumor diameter (p <0.05), a significant increase in FSH, LH, E2 (p < 0.05) compared to baseline values before treatment and a significant reduction in fertility (p < 0.05). The syndrome amenorrhea/galactorrhea and infertility are the most common symptoms of prolactinomas. Micro prolactinomas are more frequent in women. Bromocriptine is an effective drug in the treatment of hyperprolactinemia with prolactinomas. It effectively normalize prolactin, establishing gonadal function and reduces tumor mass.

Hormone profiles at high altitude in man.

Altitude induced alterations in circulatory levels of PRL, LH, FSH and testosterone were studied in seven eugonadal men at sea level (SL), during their stay at high altitude (HA, 3500 m) and a week after return to SL. The mean plasma PRL level at SL was 5.83 +/- 1.7 SE ng/ml. On day one and seven of arrival at HA, the PRL values of 7.81 +/- 1.81 and 9.21 +/- 1.64 ng/ml respectively were not significantly different (p greater than 0.05) than the initial SL values. However, on day 18 of stay at HA, PRL levels were significantly increased (p less than 0.01) to 17.68 +/- 1.82 ng/ml and returned to initial SL values within seven days of return to SL. A significant decrease (p less than 0.01) in LH and testosterone was observed on seventh day of stay at HA and the decreased levels were maintained till day 18 of observations. Plasma testosterone returned to the initial SL values within a week of return to SL, whereas LH levels remained significantly lower (p less than 0.01). The FSH levels did not show any significant change during their stay at HA or after return to SL. These observations suggest that exposure to altitude is associated with hyperprolactenemia and an impaired pituitary gonadal function. The decreased levels of LH and testosterone at HA could either be due to hypoxic stress per se or secondary to altitude induced hyperprolactenemia.

Characterization of macroprolactin and assessment of markers of autoimmunity in macroprolactinaemic patients

It has been reported that macroprolactin is a complex of PRL and an immunoglobulin G (IgG). This study further characterizes macroprolactin and evaluates for other markers of autoimmunity using a cohort of macroprolactinaemic sera. PATIENTS AND NORMAL SUBJECTS: Following treatment of hyperprolactinaemic sera (n = 58) with polyethylene glycol (PEG), PRL values fell from 524-13 546 mU/l (Range) to 452-8455 mU/l, while in macroprolactinaemic sera (n = 41), PRL concentration fell from 525-5747 to 98-378 mU/l (PEG treated normoprolactinaemic reference range, 68-230 mU/l in males, 70-390 mU/l in females). PRL was measured in sera prior to and following gel filtration chromatography, ultrafiltration, treatment with protein A-sepharose, protein G-sepharose, antihuman IgG-agarose and sodium thiocyanate (NaSCN). The binding of radio-labelled PRL in macroprolactinaemic sera was also measured. Sera were assayed for antithyroid and antinuclear antibodies. C-reactive protein (CRP) and CD5 positive B cells were also measured. Comparisons were made between values obtained in normal, hyperprolactinaemic and macroprolactinaemic sera. Results Macroprolactinaemic sera indicated the presence of an IgG molecule and/or IgG fragments with one or more molecules of PRL. In 97% of the sera macroprolactin had a molecular weight of 204 kDa. Treatment of macroprolactinaemic sera with NaSCN caused dissociation of macroprolactin, releasing monomeric PRL. Macroprolactinaemic sera did not yield evidence of an increase in markers of autoimmunity when compared with hyperprolactinaemic or normal sera. Comprehensive analysis of macroprolactin confirmed its composition as an IgG molecule or fragment with a PRL molecule. The occurrence of macroprolactin does not appear to be associated with autoimmunity.

Diagnosis and management of hyperprolactinemia: Results of a Brazilian multicenter study with 1234 patients

The aim of the study was to evaluate clinical and laboratorial features of 1234 patients with different etiologies of hyperprolactinemia, as well as the response of 388 patients with prolactinomas to dopamine agonists. A total of 1234 hyperprolactinemic patients from 10 Brazilian endocrine centers were enrolled in this retrospective study. PRL measurement, thyroid function tests, and screening for macroprolactin were conducted. Patients were subdivided as follows: 56.2% had prolactinomas, 14.5% drug-induced hyperprolactinemia, 9.3% macroprolactinemia, 6.6% non-functioning pituitary adenomas, 6.3% primary hypothyroidism, 3.6% idiopathic hyperprolactinemia, and 3.2% acromegaly. Clinical manifestations were similar irrespective of the etiology of the hyperprolactinemia. The highest PRL levels were observed in patients with prolactinomas but there was a great overlap in PRL values between all groups. However, PRL>500 ng/ml allowed a clear distinction between prolactinomas and the other etiologies. Cabergoline (CAB) was more effective than bromocriptine (BCR) in normalizing PRL levels (81.9% vs 67.1%, p<0.0001) and in inducing significant tumor shrinkage and complete disappearance of tumor mass. Drug resistance was observed in 10% of patients treated with CAB and in 18.4% of those that used BCR (p=0.0006). Side-effects and intolerance were also more common in BCR treated patients. Prolactinomas, drug induced hyperprolactinemia, and macroprolactinemia were the 3 most common causes of hyperprolactinemia. Although PRL levels could not reliably define the etiology of hyperprolactinemia, PRL values >500 ng/ml were exclusively seen in patients with prolactinomas. CAB was significantly more effective than BCR in terms of prolactin normalization, tumor shrinkage, and tolerability.

Endothelin-3 and PRL levels in the maternal and fetal circulation at delivery

The aim of the present cross-sectional study was to test the hypothesis that endothelin-3 (ET-3) is involved in PRL secretion via systemic hormonal interaction during labor. Fifty healthy pregnant women with singleton pregnancies were included in the present study. At delivery, blood samples were drawn from umbilical vein and artery. At the same time, a blood sample was obtained from a peripheral vein of the mother. In all blood samples, plasma ET-3 and serum PRL concentrations were determined. The main outcome measures were the differences between maternal peripheral blood, umbilical artery and vein in terms of ET-3 and PRL levels, and the associations between ET-3 and PRL levels. ET-3 values (mean+/-SEM) in umbilical artery did not differ significantly from those in umbilical vein (4.94+/-0.27 vs 5.05+/-0.32 pg/ml) but were in both vessels significantly higher than in maternal vein (1.14+/-0.56 pg/ml, p<0.001). Serum PRL values showed similar patterns. There was a significant positive correlation of the ET-3 levels between umbilical artery and vein (r=0.906, p<0.001), but not between maternal peripheral venous blood and the umbilical vessels. Similar correlations were found for PRL values. However, no significant correlations were found between ET-3 and PRL levels in all vessels studied. The present study demonstrates for the first time that ET-3 levels are higher in fetal than in maternal circulation at term. The lack of correlation between ET-3 and PRL levels suggests that ET-3 does not play an important endocrine role in the control of maternal and fetal PRL secretion during labor.

Do the limits of serum prolactin in disconnection hyperprolactinaemia need re‐definition? A study of 226 patients with histologically verified non‐functioning pituitary macroadenoma

The differentiation of a pituitary non-functioning macroadenoma from a macroprolactinoma is important for planning appropriate therapy. Serum PRL levels have been suggested as a useful diagnostic indicator. However, values between 2500 and 8000 mU/l are a grey area and are currently associated with diagnostic uncertainty. We wished therefore, to investigate the serum PRL values in a large series of patients presenting with apparently non-functioning pituitary macroadenomas. All patients presenting to the Department of Endocrinology in Oxford with clinically non-functioning pituitary macroadenomas (later histologically verified) between 1990 and 2005 were studied. Information documented in the notes on the medications and on the presence of conditions capable of affecting the serum PRL levels at the time of blood sampling was also collected. Two hundred and twenty-six patients were identified (median age at diagnosis 55 years, range 18-88 years; 146 males/80 females; 143 gonadotroph, 46 null cell, 25 plurihormonal and 12 silent ACTH adenomas). All tumours had suprasellar extension. At the time of blood sampling 41 subjects were taking medications capable of increasing serum PRL. Hyperprolactinaemia was found in 38.5% (87/226) of the patients. The median serum PRL values in the total group were 386 mU/l (range 16-3257) (males: median 299 mU/l, range 16-1560; females: median 572 mU/l, range 20-3257) and in those not taking drugs capable of increasing serum PRL 363 mU/l (range 16-2565) (males: median 299 mU/l, range 16-1560; females: median 572 mU/l, range 20-2565). Serum PRL < 2000 mU/l was found in 98.7% (223/226) of the total group and in 99.5% (184/185) of those not taking drugs. Among the three subjects with serum PRL > 2000 mU/l, two were taking oestrogen preparations. Based on a large series of histologically confirmed cases, serum PRL > 2000 mU/l is almost never encountered in nonfunctioning pituitary macroadenomas. Values above this limit in the presence of a macroadenoma should not be surrounded by diagnostic uncertainty (after acromegaly or Cushing's disease have been excluded); a prolactinoma is the most likely diagnosis and a dopamine agonist should be considered as the treatment of choice.

Comparison and Problems of Measured Values of LH, FSH, and PRL among Measurement Systems

Several measurement systems are used for LH, FSH, and PRL in Japan, but the comparison of the measured values is difficult in some cases. In this study, we compared the measured values of 3 types of measurement systems widely used in Japan, SPAC-S, ARCHITECT, and Centaur, in females with a normal menstrual cycle and with various ovulatory disorders. Variant LH was discriminated by the criterion, SPAC-S LH/ARCHITECT LH ratio <0.5. Excluding the variant LH, the correlation of the measured LH values among the measurement systems was high, 0.94-0.99, and the value measured by ARCHITECT LH and Centaur LH was slightly higher than that measured by SPAC-S LH. As for FSH, the correlation was also high, 0.94-1.00, and the value measured by ARCHITECT FSH and Centaur FSH was slightly lower than that measured by SPAC-S FSH. The important judgment criterion of polycystic ovary syndrome (PCOS), a high level of LH relative to FSH, has been set to 1.0 or higher LH/FSH using SPAC-S. When the regression line of the LH/FSH ratio among the measurement systems was investigated, it can be said that 1.25 or higher by ARCHITECT and 1.40 or higher by Centaur are appropriate for the judgment criteria of a high level of LH relative to FSH. As for PRL, the correlation was high, 0.96-0.99, but the value showed large differences among the systems. For the diagnosis of hyperprolactinemia, the higher limit of the normal range may be 15 ng/mL for SPAC-S, 30 ng/mL for ARCHITECT, and 24 ng/mL for Centaur.