Measurement Of Prolactin Research Articles

The Stress-Induced Hyperprolactinemia Might Not Be that Stress-Induced as Argued: Observational Case-Control Study

ObjectiveThe mechanism behind prolactin (PRL) elevation in stress-induced hyperprolactinemia (si-HP) in humans is unclear. This study aimed to investigate the effect of psychological stress and venous puncture (VP) pain on si-HP. MethodsThe study included 91 individuals (9 males, 82 females) referred for HP. Anxiety levels were assessed using the Anxiety Sensitivity Index-3 (ASI-3) and the State-Trait Anxiety Inventory (STAI-1 and STAI-2), and visual scales were used to evaluate trypanophobia, nosocomephobia, and scanxiety. Serial PRL measurements were performed with venous cannula (VC) at 0 minute (min), 30 min, and 60 min for the first 32 patients and with the VP method at the same intervals for the following 59 patients. si-HP was defined as PRL levels at 60 min (PRL 60min) decreasing to normal limits according to gender. ResultsThere were 23 HP (−), 25 HP (+), and 19 si-HP individuals, as well as 24 with macroprolactinaemia. The frequency of si-HP in the VC group (n = 7/32) was similar to that in the VP group (12/59, P = .9). The prolactin levels at 0 minute (PRL0min) and prolactin levels at 60 minutes (PRL60min) levels of the VC group were similar to those of the VP group. Trypanophobia, nosocomephobia, scanxiety, ASI-3, STAI-1, and STAI-2 scale scores were similar between the si-HP group and other groups. Trypanophobia, nosocomephobia, scanxiety, ASI-3, STAI-1, and STAI-2 scales scores were not correlated with PRL0min or PRL60min levels. ConclusionSi-HP is independent of states momentary or trait anxiety, and phobias trypanophobia, nosocomephobia and scanxiety. In this context, the relevance of the nomenclature of si-HP is controversial.

Diagnostic Utility of the Prolactin Decrease Rate in the Diagnosis of Mild Hyperprolactinemia.

Background Previous studies have yielded conflicting findings on the routine use of serial prolactin (PRL) measurement in patients with inconsistent signs or symptoms of mild hyperprolactinemia (HP). Therefore, we aimed to evaluate the effectiveness of serial PRL measurement and a previously undefined parameter which is the PRL decrease rate (PDR) method in the diagnosis of mild HP and prolactinoma. Materials and methods The data obtained from medical charts of patients in the sample population included serial PRL values at 0 minute (min), 30 min, and 60 min as well as macroprolactinemia (mPRL) levels. PDR was defined as the ratio of the difference between the PRL levels at 0 min and 60 min to the PRL level at 0 min. Results We obtained referral PRL (rPRL) levels from the files of 221 of 268 patients referred for HP. Of those referred, 153 (69.2%) had mild HP. Of the 165 patients in the serial PRL measurement group, HP was detected in 76 (46.1%), and stress-induced PRL elevation was found in 24 (14.5%). Of the 101 patients in the single PRL measurement group, HP was detected in 72 (69.9%; p<0.001). Moreover, a PDR score of 38.1% had 99% specificity and 26% sensitivity in HP exclusion, and a PDR score of 20.6% had 100% specificity and 30% sensitivity in prolactinoma exclusion. Conclusion In cases where clinical findings are insufficient, the serial PRL measurement method combined with the PDR for the diagnosis of prolactinoma and HP appears to be more reliable than the single measurement method.

6917 Multiple Red Herrings Complicating the Diagnosis of Cyclic Cushing’s Syndrome

Abstract Disclosure: A. Grover: None. R. McGlotten: None. L.K. Nieman: None. Introduction: Cyclic Cushing’s syndrome (CCS) is a rare disorder characterized by intermittent hypercortisolemia. It may be caused by pituitary tumor (Cushing disease), ectopic ACTH tumor secretion (EAS), or primary adrenal disease. We present a case of CCS with multiple red herrings complicating the diagnosis. Case: A 57-year-old Cushingoid appearing woman presented elsewhere with weight gain, brain fog, weakness, hypertension, worsening diabetes, and OSA. Screening tests showed more than three episodes of hypercortisolism with interval eucortisolism: salivary and 24-urine cortisol (UFC) ranged from 0.06-0.34 µg/dL (reference range, RR, ≤0.09 µg/dL) and 59.7-137.1 µg/24 h (RR 4-50 µg/24 h) respectively. The patient was symptomatic throughout. Differential diagnosis was CCS vs a physiologic non-neoplastic condition. As she had no clear etiology for the latter, further testing was performed. ACTH was indeterminate (23-27 pg/mL, RR &amp;lt;46). Pituitary MRI showed a left 7 mm lesion. Inferior petrosal sinus sampling (IPSS) with Corticotropin Releasing Hormone (CRH) administration showed peripheral baseline ACTH levels of 9.0 and 10.0 pg/mL, suggesting that she had cycled out of a hypercortisolemic phase. The left petrosal baseline values were low (9 pg/mL,16 pg/mL), suggesting poor catheterization, which was confirmed by a low prolactin-normalized ACTH ratio. The petrosal levels were lower than expected (maximum 767 pg/ml), due to suppression of normal corticotropes vs poor tumor response. However, a central:peripheral step-up was consistent with Cushing's disease (CD) or pseudo-CS. She was referred to us for re-evaluation. A low FSH, LH, low normal TSH, and UFC of 160 µg/24h supported a diagnosis of CS. ACTH was 14.6 pg/mL. Pituitary MRI showed a 1.3 cm x 0.8 cm mass extending into the left cavernous sinus. She did not suppress cortisol during a dexamethasone suppression test (DST). After CRH administration ACTH levels doubled. Based on the macroadenoma and CRH response, CD was established; IPSS was not repeated. After transsphenoidal hypophysectomy, pathology revealed ACTH positive adenoma. Post-operative adrenal insufficiency required hydrocortisone replacement. Conclusion: CCS can pose a diagnostic challenge due to unpredictable duration and frequency of hypercortisolism. Intermittently elevated cortisol levels with CS symptoms should raise suspicion for CCS. In our case, low peripheral ACTH levels further suggested this possibility. DST may give spurious results in CCS owing to spontaneous falls or rises in cortisol at the time of testing. Prolonged hypercortisolism is required in all patients to ensure suppression of normal corticotropes, which if not complete, may confound results in patients with EAS. Finally, inadequate catheterization may affect accuracy of lateralization in any patient with CS and is ideally evaluated both by venography and prolactin measurement. Presentation: 6/1/2024

Confusion in the interpretation of prolactin levels caused by inappropriately low reference intervals.

Serum prolactin measurements are important in the differential diagnosis of pituitary masses and subfertility. We observed discrepancies in serum prolactin levels in several patients measured with different immunoassays. Despite differences in assay results, the reference intervals derived by the manufacturers were similar. In this study we aimed to investigate prolactin assay differences and to re-establish RIs for different prolactin immunoassays. For the assay comparison, serum samples were collected from men and women visiting our the Amsterdam UMC hospital. Prolactin levels were measured using the AtellicaTM IM analyzer (Siemens Healthineers) and the Cobas (Roche Diagnostics) immunoassay. Reference intervals for prolactin were re-established for men, premenopausal women and postmenopausal women for both the Atellica and Cobas immunoassay. Prolactin levels measured using the Cobas immunoassay were 1.75 times higher than those measured using the Atellica immunoassay. The re-established reference intervals for Atellica and Cobas confirmed these findings and were <0.32 U/L; <0.55 U/L for men; <0.64 U/L; <0.86 U/L for premenopausal women and <0.31 U/L; <0.59 U/L for postmenopausal women, respectively for Atellica and Cobas assays. The re-established RIs of the Atellica assay matched the current and manufacturer RIs whereas those for Cobas differed substantially. Prolactin levels are assay dependent and the re-established reference intervals are different for the Atellica and Cobas assays. We recommend that laboratory specialists and manufacturers periodically review prolactin assay RIs as incorrect reference intervals can lead to misinterpretation of prolactin levels and unnecessary referrals and further laboratory testing, as we have experienced.

Traumatic brain injury and prolactin.

Traumatic brain injury (TBI) is a well-known etiologic factor for pituitary dysfunctions, with a prevalence of 15% during long-term follow-up. The most common hormonal disruption is growth hormone deficiency, followed by central adrenal insufficiency, central hypogonadism, and central hypothyroidism in varying order across studies. The prevalence of serum prolactin disturbances ranged widely from 0 to 85%. Prolactin release is mainly regulated by hypothalamic dopamine inhibition, and mediators such as TRH, serotonin, cytokines, and neurotransmitters have modulatory effects. Many factors, such as hypothalamic and/or pituitary gland injuries, as well as fluctuations in dopaminergic activity and other mediators and stress response, may cause derangements in serum prolactin levels after TBI. Although it is challenging to investigate the direct effects of TBI on serum prolactin levels due to many confounders, basal prolactin measurements and stimulation tests provide insight into the functionality of the hypothalamus and pituitary gland after TBI. Moreover, during the acute phase of TBI, prolactin levels appear to correlate with TBI severity. In contrast, in the chronic phase, hypoprolactinemia may function as an indirect indicator of pituitary dysfunction and reduced pituitary volume. Further investigations are needed to elucidate the pathophysiologic mechanisms underlying the prolactin trend following TBI, its significance, and its associations with other pituitary hormone dysfunctions. In this article, we re-evaluated our patients' TBI data regarding prolactin levels during prospective long-term follow-up, and reviewed the literature regarding the prevalence, pathophysiology, and clinical implications of serum prolactin disturbances during acute and chronic phases following TBI.

Overview of prevalence, etiology, clinical features, diagnosis, and management of primary ovarian insufficiency

Primary ovarian insufficiency (POI) is the development of primary hypogonadism before the age of 40 years in women with normal karyotypes. Patients present with symptoms that are similar to those of menopause, including irregular periods, reduced fertility, and climacteric symptoms due to hypoestrogenism, such as hot flashes, vaginal dryness, dyspareunia, irritability, and night sweats. The incidence of spontaneous POI is approximately 1 in 250 by 35 years of age and 1 in 100 by 40 years of age. Genetic, inflammatory, metabolic, autoimmune, and idiopathic factors contribute to POI. POI pathophysiology is explained by the presence of fewer primordial follicles and their rapid degeneration. Detailed history and examination are important for diagnosis. Diagnosis requires biochemical evidence and laboratory testing, including measurements of follicle-stimulating hormone, thyroid-stimulating hormone, prolactin, and estradiol (E2) levels. In addition, transvaginal ultrasound is preferred to evaluate ovarian reserve. POI should be managed through a multidisciplinary approach involving gynecologists, endocrinologists, and psychologists. Hormonal replacement therapy is the mainstay treatment for all women with POI. Lifestyle modifications such as weight-bearing exercises, smoking cessation, and Vitamin D and calcium supplementation are highly recommended to improve bone density and reduce fractures. Psychological care has been suggested to improve self-esteem and social support, along with family planning guidance. Despite recent discoveries, additional screening techniques are needed.

Is there a relationship between the psychological state of infertile patient and ovarian reserve indicators?

This study explored the relationship between reduced ovarian reserve and the psychological state of infertile women. This cross-sectional, single-center study was conducted with 106 infertile women. The Beck Depression Inventory (BDI) was used to assess patients' propensity for depression. The data relating to infertility, such as causes of infertility, type of infertility (primary or secondary), duration of infertility, and treatment status [previous assisted reproductive technologies (ART) treatment and ART treatment failure] were recorded for each patient. The ovarian reserve was determined using laboratory tests [anti-Mullerian hormone (AMH); follicle-stimulating hormone (FSH)] and transvaginal ultrasonography to measure the antral follicle count (AFC) in each ovary. There was no significant relationship between the total score obtained from the Beck depression scale and AFC, AMH, thyroid-stimulating hormone, FSH, estradiol, and prolactin measurements (p>0.05). There was no significant difference between the groups regarding depression levels based on the cause of infertility (p=0.412). Additionally, the type of infertility (primary, secondary) did not differ between the groups (p=0.586). There were no differences on the BDI scale regarding the level of depression between patients who underwent in vitro fertilization (IVF) treatment (history of previous IVF treatment failure) and those who did not. There was no significant association between AFC and AMH levels and the depression state of infertile patients.

Evaluating the TRH Test: Prolactin Cutoff Level on the Prevalence of Reactive Hyperprolactinemia Among PCOS Women [ID 2683598

INTRODUCTION: The prolactin cutoff value is currently under discussion, although accepted values range between 15 and 25 ng/mL. The thyrotropin-releasing hormone (TRH) test is a validated methodology for the study of reactive hyperprolactinemia, but there is no consensus for which group of patients it should be used, especially in those women diagnosed with polycystic ovary syndrome (PCOS). The objective of this study was to classify the prolactin values obtained from the TRH test in women of reproductive age but previously diagnosed with PCOS, according to ranges: group A: PRL, less than 15 ng/mL; group B: PRL, 15–20 ng/mL; and group C: PRL, 20–25 ng/mL. METHODS: Three hundred seventy-eight women between 12 and 40 years old, previously diagnosed with PCOS according to Rotterdam criteria, and without a diagnosis of hyperprolactinemia or use of antipsychotics were considered. An initial prolactin measurement was performed, the TRH test was performed after 15 and 30 minutes, and the resulting values were classified in groups A, B, and C, respectively. RESULTS: The number of patients obtained was 266. Group A (n=199) had 34.17% (68) of patients with an altered TRH test, whereas in group B (n=42) 47.62% (20) had an abnormality in the test. Finally, in group C (n=25), 28.00% (7) showed an altered TRH test. CONCLUSION: Group B is the one with the highest prevalence of reactive hyperprolactinemia compared to groups A and C. It is concluded that the application of the TRH test is suggested in those patients with PCOS with prolactin ranges between 15 and 20 ng/mL.

Prolactin Hormone

Prolactin (PRL) is mainly produced by pituitary lactotrophs and is tonically inhibited by the hypothalamus by the neurotransmitter dopamine. The discovery of multiple extra pituitary sites of PRL secretion also increases the range of known functions of this hormone. Prolactin is a 23 kDa single chain protein of 199 amino acids synthesized and released principally by autotrophs in the anterior pituitary gland. The secretion is mainly under inhibitory control by hypothalamic dopamine and regulated in a negative feedback manner, with prolactin itself providing the afferent signal: short-loop feedback. The main function of prolactin is during pregnancy and lactation in the development of mammary glands, milk synthesis and maintenance of milk secretion. Serum prolactin levels rise rapidly during pregnancy with increase in the size and number of lactotrophs. During lactation suckling induces rapid secretion of prolactin via a neuroendocrine reflex pathway. In the absence of pregnancy, hyperprolactinemia may present with symptoms of hypogonadotropic hypogonadism including menstrual disturbance and infertility or visual symptoms from a pituitary mass effect by a prolactinoma, the most common pituitary tumour. Hyperprolactinaemia is diagnosed by laboratory measurement of serum prolactin. There is considerable variability in routinely available prolactin immunoassays as a result of differing reactivity towards monomeric prolactin and macro prolactin and lack of commutability of the WHO 3rd International Standard between routine methods. Macroprolactinaemia is a relatively common cause of interference in the prolactin assay that may lead to incorrect diagnosis and unnecessary investigations. Measurement of prolactin post polyethylene glycol precipitation (PEG) when prolactin levels are above the reference interval is routinely used to identify macro prolactin, however harmonization of PEG precipitation process and reporting may improve clinical care.

Clinical Impact of New Reference Intervals for the Roche Prolactin II Immunoassay.

The Roche prolactin immunoassay is used throughout the world. It reports higher values than the Siemens immunoassay but the manufacturer-defined reference intervals are similar. Patient results are often above the Roche upper limit but within the Siemens interval, causing diagnostic confusion. Establish new reference intervals for the Roche and Siemens prolactin immunoassays. We established new reference intervals for the Roche and Siemens immunoassays using 374 specimens from healthy outpatients. We performed chart review for unnecessary testing and treatment for 298 patients in a 6-month period with at least 1 Roche prolactin value above the manufacturer-defined upper limit and below our new upper limit. The new upper limit for the Roche assay was 37.8 ng/mL (females) and 22.8 ng/mL (males). The manufacturer-defined limits were 23.3 ng/mL and 15.2 ng/mL, respectively. New intervals for the Siemens assay matched the manufacturer. No cases of clinically significant pathophysiologic prolactin excess were identified in patients with values between the manufacturer-defined upper reference limit and our new Roche upper limit. Unnecessary further evaluation in these patients included 459 repeat prolactin measurements, 57 macroprolactin measurements, 39 magnetic resonance imaging studies, and 28 endocrine referrals. Eleven patients received dopamine agonists. The minimum cost of excess care using Medicare reimbursement rates was $34 134, with substantially higher amounts billed to patients and their insurance providers. Adoption of new upper reference limits for the Roche prolactin assay of 37.8 ng/mL (females) and 22.8 ng/mL (males) would not delay diagnosis or necessary intervention in patients with clinically significant pituitary tumors but would reduce unnecessary evaluation in patients without pathophysiologic prolactin excess.

Use of low-dose Aripiprazole to lower the antipsychotic medication - induced hyperprolactinemia.

IntroductionHyperprolactinemia (HPL) is a condition associated with disturbing consequences. Antipsychotic medications are one of the main causes of nontumoral hyperprolactinemia. Prolactin release in the hypothalamic tuberoinfundibular tract is increased through dopaminergic inhibition, which occurs more frequently with high- potency typical antipsychotics (40%–90%). Less commonly than typical antipsychotics, atypical antipsychotics can also result in hyperprolactinemia. In the presence of symptoms, clinicians frequently struggle with the decision of whether to stop using the suspected offending agent, lower the dosage, switch to another medication, or even add a full or partial dopamine agonist to the patient&amp;#39;s current treatment. The issue is exacerbated by the fact that finding a suitable agent for each patient is sometimes a challenging task.ObjectivesDue to the partial D2 receptor agonistic activity of aripiprazole, there is enough dopaminergic tone to continue the inhibition of prolactin release. Aripiprazole has been recommended in literature either as an adjunctive treatment in low doses or as a switch in therapy.MethodsIn the Psychiatric clinic of the General Hospital of Corfu, a low-dose (5mg/day) of aripiprazole is being used as adjunctive therapy in patients with antipsychotic-induced hyperprolactinemia. More specifically in total 42 subjects, 19 male and 22 female, with a mean prolactin level of 862ng/ml, were introduced to the prior therapy. We whereupon conducted prolactin measurements to evaluate the response at the first, the third, and the sixth month of treatment.ResultsOf the 42 subjects, 38 responded with an average reduction of prolactin to the level of 530ng/ml (mean reduction 38,5%).ConclusionsHaving noticed the beneficial effect of low-dose Aripiprazole in patients with antipsychotic-induced hyperprolactinemia, we consider it appropriate that the literature recommendations concerning this additional use of aripiprazole should not be overlooked in clinical practice.Disclosure of InterestNone Declared

Effect of Metformin and Vitamin D Supplementation on Metabolic and Hormonal Profiles in Polycystic Ovary Syndrome Women: A Follow-Up Study

Background: Insulin resistance in association with obesity is implicated in the pathogenesis of polycystic ovarian syndrome and its primary characteristic of hyperandrogenism. Metformin at a dose of (1700-2000) mg/day, with and without lifestyle, is associated with a beneficial enhancement in BMI and menstrual cycles. We aimed to determine the role of free testosterone: dihydrotestosterone ratio, and sex hormone binding globulin in the evaluation of the efficacy of metformin and vitamin D in the treatment of polycystic ovary syndrome. Methods: This cross-sectional study included 50 infertile women who were diagnosed with PCOS with an age range of (18-40 years). They were classified into Group I: Twenty-five women treated with metformin 850 mg/twice daily and followed for 8 weeks; Group II: Twenty-five women treated with vitamin D3 50.000 IU/wk for the same period. Serum investigations included measurements of prolactin, 25 hydroxyvitamin D, LH, FSH, free testosterone, DHT and SHBG by ELISA technique. Results: This study revealed that the mean values of BMI, HOMA-IR, prolactin and free testosterone: dihydrotestosterone ratio were significantly improved (by lowering) after treatment with metformin and vitamin D. Moreover, Polycystic Ovary Syndrome women treated with metformin revealed significant negative association between HOMA-IR with SHBG (r= -0.593, p=0.009), also significant positive association between HOMA-IR with BMI (r= 0.631, p=0.003). Conclusion: Serum measurements of free testosterone: dihydrotestosterone ratio, along with SHBG, are good biochemical markers that reflect the enhancement of insulin resistance and BMI in Polycystic Ovary Syndrome women post metformin treatment or vitamin D supplementation.

Serum Zinc Levels in Women with Polycystic Ovarian Syndrome are Lower as Compared to Those without Polycystic Ovarian Syndrome: A Cohort Study.

Zinc is an essential micronutrient, a vital stabiliser and a cofactor in many enzymes such as superoxide dismutase and phospholipase C and also acts as an antioxidant by protecting the sulfhydryl groups of different proteins and enzymes against free radicals. It is unclear if serum zinc levels are correlated with polycystic ovary syndrome (PCOS) and its pathophysiology, although relation between diabetes and insulin resistance has been established. This study aimed to investigate circulating serum zinc levels in PCOS subjects compared with non-PCOS subjects. In this cohort study, PCOS subjects were compared with normal subjects aged between 18 and 35. All the included subjects underwent measurement of anthropometric parameters, fasting insulin, luteinising hormone, follicle-stimulating hormone, thyroid-stimulating hormone, prolactin, progesterone, oestrogen and serum zinc levels. These values were taken on days 2-5 of the menstrual cycle. Univariate analysis and linear regression were performed for serum zinc levels and fasting insulin levels in PCOS subjects and non-PCOS subjects using SPSS (version 21) and Microsoft Excel (2019). Serum zinc levels in the PCOS group were lower than in the control group (P = 0.012). Fasting insulin levels in the PCOS group were higher than in non-PCOS subjects (P = 0.001). We found a negative correlation between zinc and fasting insulin (r = -0.580, P < 0.0001) in the normal group and (r = -0.332, P = 0.019) in the PCOS group. A positive correlation was found between body mass index (BMI) and fasting insulin levels in both the PCOS group (r = 0.227, P = 0.112) and normals (r = 0.612, P < 0.0001). A negative statistically significant correlation between BMI and zinc in both the PCOS group (r = -0.378, P = 0.007) and the non-PCOS group (r = -0.7452, P < 0.0001) was seen. The data suggest that serum zinc levels were found to be lower in PCOS subjects as compared to normal controls and evaluation of these levels may indicate that zinc has a vital role in PCOS pathophysiology.

Reporting of Hyperprolactinaemia Post-polyethylene Glycol (PEG) Precipitation at Hospital Tengku Ampuan Rahimah Klang, Malaysia

Introduction: Macroprolactinaemia is defined as hyperprolactinaemia due to excess macroprolactin in the presence of normal monomeric prolactin. Failure to identify macroprolactinaemia may result in patients being subjected to unnecessary investigations and inappropriate treatment for hyperprolactinaemia. In our centre, screening for macroprolactinaemia is currently performed at the request of the treating physician. The study thus aimed to determine the frequency of macroprolactinaemia in samples with serum prolactin ≥700 mIU/L in Hospital Tengku Ampuan Rahimah (HTAR) and to determine the presence of true hyperprolactinaemia in these cases. Methods: A cross-sectional study among hyperprolactinaemic subjects in HTAR, using serum specimens received by the laboratory for measurement of prolactin between October 2018 and September 2019. Samples with prolactin ≥700 mIU/L were screened for macroprolactinaemia using the polyethylene glycol (PEG) precipitation technique. Macroprolactinaemia was present when the percentage recovery of prolactin post-PEG was &lt;40%. Assay-specific post-PEG monomeric prolactin levels were also reported, with levels above the upper limit of reference intervals indicated the presence of true hyperprolactinaemia. Results: A total of 101 samples were subjected to PEG precipitation. Macroprolactinaemia was found in four (4%) samples, whilst eight (7.9%) were categorised as indeterminate (percentage recovery of 40-60%). The remaining 89 (88.1%) samples had a percentage recovery &gt;60%, hence considered negative for macroprolactinaemia. All four samples with macroprolactinaemia also had raised monomeric prolactin levels indicating the co-existence of macroprolactinaemia in subjects with true hyperprolactinaemia. Similarly, in the indeterminate group, all eight had raised monomeric prolactin levels. Conclusion: In one-year period in HTAR, macroprolactinaemia was detected in 4% of subjects with prolactin ≥700 mIU/L, all of whom also had raised monomeric prolactin levels. The common occurrence of both macroprolactinaemia and true hyperprolactinaemia warrants the reporting of both percentage recovery and monomeric prolactin levels post-PEG.

Prolactin Monomeric Polyethylene Glycol Measurement Method and Study of Reference Value Verification

Purpose: Prolactin in the blood is separated into three types, and over 90% of prolactin presents as a double monomer (23 KDa). Rarely, it can exist in the size of big prolactin (150 KDa), which is called macroprolactin and is known as an autoantibody complex. When macroprolactin accounts for more than 60% of prolactin in the blood, it is called macroprolactinemia. The presence of such macroprolactin was first reported in a patient with hyperprolactinemia but without typical symptoms. Macroprolactinemia is emerging as an important cause of idiopathic hyperprolactinemia. The polyethylene glycol (PEG) precipitation method using the property of precipitating large-molecular-weight proteins is simple and recently has been widely used as a screening test. The results are in good agreement with the results of gel chromatography. The purpose of this study was to confirm the measurement method and reference value verification of monomeric prolactin in blood prolactin using the PEG precipitation method. Materials and Methods: For 40 examinees who visited the Gangnam Center of Seoul National University Hospital in 2021, the prolactin level was verified using radioimmunoassay (RIA). For macroprolactinemia PEG precipitation method, 25% PEG (molecular weight 6000kDa) solution and serum were mixed in equal amounts in a test tube, then left at room temperature for 20 minutes and centrifuged at 4℃ for 30 minutes (1500g). The prolactin level was measured in the supernatant. Results : After confirming that more than 90% of the 40 tested samples within the reference range &lt;25 ng/mL, the same value as the reference value for prolactin was applied. Since the concentration of monomeric prolactin in serum from which macroprolactin has been removed from blood is diluted 1:1 with PEG, our laboratory is currently reporting the result by multiplying the result by a dilution factor of 2. Conclusion: Radioimmunoassay using PEG precipitation method using the property of precipitating large molecular weight proteins is simple and effective for quantitative measurement of monomeric prolactin in blood prolactin.

Bilateral inferior petrosal sinus sampling with human CRH stimulation in ACTH-dependent Cushing's syndrome: results from a retrospective multicenter study.

Bilateral inferior petrosal sinus sampling (BIPSS) is regarded as gold standard to differentiate between Cushing´s disease (CD) and ectopic Cushing's syndrome (ECS). However, published data e.g. on the diagnostic value of additional prolactin analysis is controversial. Thus, we evaluated the diagnostic performance of BIPSS with and without prolactin in a multicenter study. Retrospective study in 5 European reference centers. Patients with overt adrenocorticotropin (ACTH)-dependent Cushing's syndrome at the time of BIPSS with human corticotropin-releasing hormone stimulation were eligible. Cut-offs for the inferior petrosal sinus (IPS) to peripheral (P) ACTH ratio and the normalized ACTH:prolactin IPS:P ratio were calculated via receiver operator characteristics analyses (reference: CD). 156 patients with BIPSS were identified. Of these, 120 patients (92 (77%) females; 106 (88%) CD, 14 (12%) ECS) had either histopathologically confirmed tumors or biochemical remission and/or adrenal insufficiency after surgery; only this subgroup was analyzed by ROC analysis. The optimal cut-offs for the ACTH IPS:P ratio were ≥1.9 at baseline (sensitivity 82.1% (95%CI 73.2-88.6), specificity 85.7% (95%CI 56.2-97.5), AUC 0.86) and ≥2.1 at 5 minutes post-CRH (sensitivity 91.3% (95%CI 83.6-95.7), specificity 92.9%(95%CI 64.1-99.6), AUC 0.96). A subgroup underwent additional prolactin analysis. An optimal cut-off of ≥1.4 was calculated for the normalized ACTH:prolactin IPS:P ratio (sensitivity 96.0% (95%CI 77.7-99.9), specificity 100% (95%CI 56.1-100), AUC 0.99). Our study confirms the high accuracy of BIPSS in the differential diagnosis of ACTH-dependent Cushing's syndrome and suggests that the simultaneous measurement of prolactin might further improve the diagnostic performance of this test.

Effect of Ramadan Fasting on Sex Hormones in Infertile Male

Ramadan fasting is one of the 5 pillars of Islam and one of the most significant Ibadat (worships) of Islam. Throughout the world, millions of Muslims fast during Ramadan to fulfill this religious obligation. Aims: The aim of the study is to determine changes in the serum concentrations of gonadotropins, testosterone and prolactin hormones in infertile males after fasting of Ramadan and whether fasting improves fertility in the male. Participants and Methods: This is a case series study was conducted on 54 infertile male subjects aged (25-50 years) who fasted during Ramadan. Two blood samples were taken from each patient, one before and the other after fasting of Ramadan. Serum FSH, LH, prolactin and testosterone measurement was done by using Enzyme Linked Immune Sorbent Assay (ELISA). Results: There was no significant difference in serum FSH, LH, prolactin hormones when we compared them before and after Ramadan fasting. Concerning serum testosterone hormone, there was a decrease in its level after fasting but not reach significance when compared with its level before fasting. Conclusion: Serum levels of FSH, LH, prolactin and testosterone were unchanged after fasting of Ramadan.

Association of prolactin with all-cause and cardiovascular mortality among patients with type 2 diabetes: a real-world study.

The association between prolactin and mortality has been less studied, and findings were inconsistent among different populations. We aimed to investigate the association between serum prolactin (PRL) and mortality among patients with type 2 diabetes. We performed a retrospective cohort study of 10 907 patients with at least 2 prolactin measurements within 2 years since their first inpatient diagnosis of type 2 diabetes. Baseline and mean values of serum PRL were used as exposures. A multivariable-adjusted Cox proportional hazards model was used to estimate the association between PRL and mortality. During a mean follow-up of 5.34 years, 863 patients died, of whom 274 were due to cardiovascular events. Multivariable-adjusted hazard ratios (aHRs) based on different levels of baseline PRL (<100, 100-199, 200-299, and ≥300 mIU/L) were 1.00, 1.10 [95% confidence interval (CI), 0.90-1.36], 1.35 (95% CI 1.11-1.67), and 1.49 (95% CI 1.18-1.84) for all-cause mortality and 1.00, 1.24 (95% CI 0.86-1.81), 1.71 (95% CI 1.14-2.62), and 2.42 (95% CI 1.55-3.78) for cardiovascular mortality, respectively. Positive associations were also found when we used the mean values of PRL as the exposure. These associations were consistent among patients of different baseline characteristics. Further sensitivity analyses excluding patients with subclinical or clinical hypothyroidism at baseline and who died within the first 6 months since baseline demonstrated similar results. A positive association between baseline PRL and mortality was observed among patients with type 2 diabetes. Prolactin may be considered a potential biomarker of mortality among patients with type 2 diabetes.

Serum Prolactin as an Early Biomarker for Detection of Gestational Diabetes Mellitus-An Experience at CMH Quetta

Objective: To determine the association between elevated serum prolactin and the development of gestational diabetes mellitus in the first trimester.&#x0D; Study Design: Prospective longitudinal study.&#x0D; Place and Duration of Study: Pathology Department, Combined Military Hospital, Quetta Pakistan, from Apr 2021 to Mar 2022.&#x0D; Methodology: One hundred and twenty-one patients had a measurement of serum prolactin in the first trimester, along with an oral glucose tolerance test in the second and third trimester, at the Pathology Department Combined Military Hospital Quetta Pakistan.&#x0D; Results: In the study group, serum prolactin levels were raised in 51(42.1%) patients in the first trimester. A total of 44(36.3%) patients with raised serum prolactin had impaired oral glucose tolerance tests. A significant association was found between raised serum prolactin and subsequent development of gestational diabetes mellitus in pregnant females.&#x0D; Conclusion: Serum prolactin can be an important biomarker for early diagnosis and monitoring of gestational diabetes mellitus.

Effect of CoQ10 Supplement on Spermogram Parameters and Sexual Function of Infertile Men Referred to The Infertility Center of Fatemieh Hospital, Hamadan, Iran, 2019: A Randomized Controlled Trial Study.

The aim of this study was to investigate the effects of the antioxidant supplement of CoQ10 and placebo in the male infertility treatment. The randomized controlled trial study was designed as a clinical trial. Samples in each group consisted of 30 members. The first group received 1 daily dose of 100 mg coenzyme Q10 capsules and the second group received a placebo treatment. Treatment in both groups lasted 12 weeks. Before and after the intervention of semen analysis, hormonal measurement of testosterone, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyroid stimulating hormone (TSH) were done. Sexual function was assessed before and after the intervention by using the International Index of Erectile Dysfunction questionnare. The mean age of participants was 34.07 (5.26) years in the CoQ10 group and 34.83 (6.22) in the placebo one. Normal volume of semen (P=0.10), viscosity (P=0.55), sperm count (P=0.28), and sperm motility (P=0.33) in the CoQ10 group increased without statistically significant differences. But the normal sperm morphology increased with statistically significant differences in the CoQ10 group (P=0.01). There was an increase in normal FSH levels and testosterone levels in the CoQ10 group compared with the placebo patients, but these differences were not statistically significant (respectively P=0.58, P=0.61). The results also revealed that the scores of erectile function (P=0.95), orgasm (P=0.86), satisfaction with sexual intercourse (P=0.61), overall satisfaction (P=0.69) and the score of the International Index of Erectile Function (IIEF, P=0.82) were greater after the intervention in the CoQ10 group than in the placebo group although the difference was not statistically significant. The use of CoQ10 supplement can improve sperm morphology; however, in other sperm parameters and also in some hormones increased after the intervention, this was not statistically significant and therefore the result is not conclusive (registration number: IRCT20120215009014N322).