Serum PRL Research Articles

Diagnosis of hyperprolactinemia by single serum prolactin determination: Challenges and recommendations

Secretion of prolactin follows a circadian rhythm of secretion, and several factors play an important role in the regulation of its secretion. An accurate diagnostic evaluation is essential for the proper management of the patient, which can be accomplished through a narrow observation and critical analysis of all the prolactin results which are above the standard upper limit of normal. If the circulating prolactin level exceeds five times the upper normal limit, a single test is sufficient to diagnose hyperprolactinemia. However, mildly elevated (20–40 ng/ml) results should be confirmed with at least two tests to counteract the circadian fluctuation or other factors causing transitory elevation. Repeat analysis of circulating prolactin on a later date preferably with 2–3 samples collected at few min interval is also recommended to minimize the effect of pulsatility when the elevation of serum PRL is doubtful (may be due to venipuncture induced stress) or when results are inconsistent with the clinical features. This review article presents an overview of the biological and analytical aspects of prolactin along with the impact of stress on prolactin secretion, as well as the current approach employed to tackle the chances of misdiagnosis and overtreatment. However, to understand the exact mechanism of stress induced hyperprolactinemia and its implications, further research is required.

Differences between GH and PRL co-secreting and GH-secreting pituitary adenomas. A series of 604 cases.

To evaluate differences in clinical presentation and in surgical outcomes between growth hormone-secreting pituitary adenomas (GH-PAs) and GH and prolactin co-secreting pituitary adenomas (GH&PRL-PAs). Multicenter retrospective study of 604 patients with acromegaly submitted to pituitary surgery. Patients were classified into two groups according to serum PRL levels at diagnosis and immunohistochemistry (IHC) for PRL: a) GH&PRL-PAs when PRL levels were above the upper limit of normal and IHC for GH and PRL was positive or PRL levels were >100ng/and PRL IHC was not available (n=130) and b) GH-PAs who did not meet the previously mentioned criteria (n=474). GH&PRL-PAs represented 21.5% (n=130) of patients with acromegaly. The mean age at diagnosis was lower in GH&PRL-PAs than in GH-PAs (P<0.001). GH&PRL-PAs were more frequently macroadenomas (90.6% vs. 77.4%, P=0.001) and tended to be more invasive (33.6% vs. 24.7%, P=0.057) than GH-PAs. Furthermore, they had presurgical hypopituitarism more frequently (OR 2.8, 95% CI 1.83-4.38). IGF-1 upper limit of normality (ULN) levels at diagnosis were lower in patients with GH&PRL-PAs (median 2.4 [IQR 1.73-3.29] vs. 2.7 [IQR 1.91-3.67], P=0.023). There were no differences in the immediate (41.1% vs 43.3%, P=0.659) or long-term post-surgical acromegaly biochemical cure rate (53.5% vs. 53.1%, P=0.936) between groups. However, there was a higher incidence of permanent arginine-vasopressin deficiency (AVP-D) (7.3% vs. 2.4%, P=0.011) in GH&PRL-PAs patients. GH&PRL-PAs are responsible for 20% of acromegaly cases. These tumors are more invasive, larger and cause hypopituitarism more frequently than GH-PAs and are diagnosed at an earlier age. The biochemical cure rate is similar between both groups, but patients with GH&PRL-PAs tend to develop permanent postsurgical AVP-D more frequently.

PITUITARY TUMORS-01 HYPERPROLACTINEMIA AS A CLINICAL MARKER OF INVASIVE PROLACTINOMAS

Abstract BACKGROUND Prolactinomas can acquire an invasion feature and challenge the management. Many features of invasive pituitary adenomas have been investigated in the literature, from radiological, histopathological to molecular perspectives. Here, we have decided to focus on serum prolactin level and evaluate its behavior in invasive prolactinoma patients. METHODS It is a retrospective and consecutive view of 75 prolactinomas patients registered at the Hassan II University Hospital of Fez in Morocco. Patients were categorized into two groups: invasive and noninvasive prolactinoma. A non-parametric predicted ROC curve was performed to investigate the sensitivity and specificity of serum PRL level according to the invasiveness. RESULTS A total of 31 patients (41.3%) represented the invasive group and the mean age was 35.6 years old compared to the group of noninvasive (34,1 years old). Males are more likely to be affected by invasive tumor than women (&amp;lt;0,00001). Serum PRL level was higher (2048.6 ± 1882.4) in invasive prolactinoma (p=0.001) and almost all invasive tumors had a PRL level greater than 1000 ng/ml. The predicted ROC curve of the distribution of the serum PRL levels showed an area under curve (AUC) of 89.8% and the calculated value of the threshold to fit a good sensitivity of 80% and false positive rate of 11.6% was estimated to 900 ng/ml. CONCLUSION Based on clinical manifestations, hyperprolactinemia and MRI scan, the prolactinoma patients – especially men – presenting a larger tumor size and serum PRL level higher than 900ng/ml, should be considered as an invasive prolactinoma patient. As a matter of fact, with those patients an appropriate treatment should begin as soon as possible.

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 (&amp;lt;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&amp;lt;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

FRI303 PRL-R Variants Are Not Only Associated With Prolactinomas But Also With Dopamine Agonist Resistance

Abstract Disclosure: A.R. Moreira: None. E.B. Trarbach: None. A. Glezer: None. G.A. Maciel: None. C.B. Bueno: None. A.S. Monteiro: None. M. Padula: None. I.P. Grande: None. M.D. Bronstein: None. Introduction: Knockout prolactin receptor gene (PRL-R) mice are animal models for prolactinomas and PRL acts via autocrine/paracrine inhibiting lactotroph proliferation. Recent studies identified variants in PRL-R gene in patients with prolactinoma and two of them Glu400(376)Gln/p.Asn516(492)Ile, were more common in patients compared to controls. Functional analysis of the p.Asn516(492)Ile variant showed an increase in Akt expression and cell proliferation induced by PRL. However, the association between PRL-R variants and response to cabergoline (CAB) treatment has not been investigated. Objective: This study aims to analyze the PRL-R gene in an extensive cohort of patients with sporadic prolactinomas and evaluate its association with clinical, laboratorial and tumor imaging characteristics, as well as CAB treatment resistance. Methods: DNA was extracted from peripheral blood samples of 178 patients with prolactinoma and 146 were classified according to cabergoline response. The PRL-R gene was analyzed by PCR techniques and automated Sanger-type sequencing. Four in silico tools were used for analysis. Results: We found six PRL-R variants: p.Ile100(76)Val (n=18), p.Ile170(146)Leu (n=6), p.Glu400(376)Gln/p.Asn516(492)Ile (n=3), p.Glu470Asp (n =1) and p.Ala591Pro (n=1), the last two described for the first time in prolactinomas´ patients. The variants p.Glu400(376)Gln/p.Asn516(492)Ile and p.Ala591Pro were more frequent amongst patients compared to genomic databases and the p.Asn516(492)Ile showed pathogenic potential using in silico analysis. PRL-R variants were associated with male sex (P=0.015), higher serum PRL levels (P=0.007), larger tumors (P=0.001), higher frequency of macroadenomas (P=0.031) and cabergoline resistance (P&amp;lt;0.001). Considering together only the PRL-R variants classified as pathogenic/probably pathogenic (p.Ile170(146)Leu, p.Glu400(376)Gln/Asn516(492) and p.Ala591Pro) versus the benign variants (p.Ile100(76)Val, p.Glu470Asp and wild type) we also observed a higher levels of serum PRL (P=0.008), largest tumor diameter (P=0.028) and higher frequency of CAB resistance (P=0.048).Conclusion: Our study showed a higher frequency of the PRL-R variants p.Glu400(376)Gln/p.Asn516(492)Ile, and p.Ala591Pro in patients with prolactinomas when compared to Brazilian and international databases, suggesting that these variants could play a role in the prolactinoma tumorigenesis. Patients with PRL-R variants presented male predominance, higher serum PRL levels, larger tumor size at diagnosis and higher frequency of CAB resistance. More studies evaluating germinative and somatic PRL-R variants are needed to clarify the PRL/PRL-R system role in the tumorigenesis and progression of prolactinomas and their interesting association with CAB resistance. Presentation: Friday, June 16, 2023

Assessment Of Serum Progesterone And Serum Prolactin In Patients With Carcinoma Thyroid Before And After Thyroidectomy: A Pilot Study

Introduction: To assess the effect of total thyroidectomy on Serum progesterone and Serum prolactin present in patients with thyroid carcinoma. Method: This is a hospital-based prospective study carried out between November 2020 to November 2022 on patients diagnosed with a case of carcinoma thyroid who were admitted to J.N. Medical college and hospital. This study was done in the Department of Surgery, Jawaharlal Nehru Medical College and Rajiv Gandhi Centre of Diabetes and Endocrinology, Aligarh Muslim University, Aligarh. The patient's blood samples were collected and assessed for serum progesterone and serum prolactin (S. PRL) prior to and after 3 months postoperatively after total thyroidectomy. Result: There was an increase in the value of S. PRL. There was no change in the value of S. Progesterone. Conclusion: There was a significant change in the hormonal status after thyroidectomy. Serum PRL increased and Serum Progesterone showed no change. To our best knowledge, this was the first of a kind study to evaluate hormones following thyroidectomy in cancer patients.

Metabolic Abnormalities, Inflammatory Markers and Endothelial Dysfunction in Hyperprolactinemia due to Prolactinoma before and after Normalization of Serum Prolactin: A Prospective Case Control Study.

Hyperprolactinemia is associated with obesity, dyslipidemia, insulin resistance, and low-grade inflammation which may promote endothelial dysfunction (EnD). Limited work has been done on EnD in prolactinomas and we, therefore, studied serum markers of inflammation and EnD in patients with prolactinomas before and after treatment with dopamine agonists. Fifty-six treatment naïve patients with prolactinomas and fifty-three (apparently healthy age and sex-matched) controls were enrolled in the study and subjected to clinical assessment and laboratory investigations including blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, urea, creatinine, uric acid, erythrocyte sedimentation rate (ESR), highly sensitive C-reactive protein (hsCRP) and markers of EnD i.e., intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Patients were treated with a dopamine agonist (cabergoline) and parameters (like ESR, hsCRP, ICAM-1, and VCAM-1) were measured at 12 weeks. The majority of the patients (84%) were female, more than half (52%) had metabolic syndrome and over a third (36%) were obese. Blood glucose fasting, HbA1c, lipid fractions, ESR, hsCRP, ICAM-1, and VCAM-1 were significantly higher in patients than in controls. Median ICAM-1 was 1331.95 ng/ml (IQR 803.43-1825.99) in patients vs 753.04 ng/ml (IQR 402.04-871.55) in controls, P < 0.001 and median VCAM-1in patients was 971.35 ng/ml (IQR 695.03-1285.23) as against 634.56 ng/ml (IQR 177.49-946.50) in controls, p0.001. Serum ICAM-1 and VCAM-1 correlated positively with hsCRP. On multivariate regression analysis, serum hsCRP was the only significant predictor of change in ICAM-1 and VCAM-1. Normalization of serum PRL with CAB resulted in a significant decrease in metabolic parameters, ESR, hsCRP, ICAM-1, and VCAM-1. Hyperprolactinemia because of prolactinoma is associated with EnD secondary to systemic inflammation and metabolic abnormalities which improve after treatment with DA.

Reproductive Performance of Zi-Goose Promoted by Red Color Illumination.

The color of light affects the reproductive performance of poultry, but it is not clear what efficient illumination strategy could be adopted to improve the reproductive performance of Zi-goose. Red light can increase the average weekly egg production rate, egg production, and qualified production. It can increase the serum GnRH level and decrease the serum PRL, MT, and T4 levels. In our study, red light for 12 h increased the average weekly laying rate, average qualified egg production, and hatching rate of Zi-goose eggs, and increased the serum levels of FSH, LH, P4, E2, MT, T3, and T4. Blue light at 14 h improved the average weekly egg production rate, average egg production, and average qualified egg production, and reduce serum PRL and MT levels to ensure the improvement of reproductive performance of goose. A total of 705,714 overlapping group sequences, 471,145 transcript sequences, and 268,609 single gene sequences were obtained from 18 sequencing samples, with a total length of 323.04, 668.53, and 247.88 M, respectively. About 176,416 unigenes were annotated successfully in six databases, accounting for 65.68% of the total unigenes obtained. 2,106, 2,142, and 8,892 unigenes were identified in the hypothalamus, pituitary gland, and ovary of the birds respectively, with different expressions of light regulation. The hypothalamus, ovary, and pituitary were involved in 279, 327, and 275 KEGG (Kyoto Encyclopedia of Genes and Genomes) metabolic pathways in response to light, respectively. Through further significance analysis and differential discovery rate control, a total of five metabolic pathways were obtained which were closely related to the reproductive hormones of goose. Ten candidate genes related to the reproductive performance of goslings were selected according to the identification results of differentially expressed genes of goslings under red light and white light conditions and the genes involved in metabolic pathways significantly related to the reproductive hormones of goslings. The expression levels of GnRh-1 in the hypothalamus, GnRH-R, FSH β and LH β in the pituitary gland, and FSH-R and LH-R candidate genes in the ovary were higher under the 12 h red light treatment than white light. However, the expression levels of VIP, PRL, and PRL-R candidate genes in the hypothalamus, pituitary and ovary were lower under 12 h red light than under 12 h white light.

Lactogenic effect of Polyscias scutellaria extract to maintain postpartum prolactin and oxytocin in lactating rats

BackgroundHypogalactia remains a challenge for mother to complete exclusive breastfeeding. Shield aralia (Polysicias scutellaria) has been used by Indonesian society to increase breast milk production. ObjectiveThis study aimed to elucidate the novel galactopoietic effect of P. scutellaria extract (PSE) in lactating rats for three weeks. Materials and methodsPSE were assayed for total phenolic content (TPC), total flavonoid content (TFC), and antioxidant capacity. The secondary metabolites of PSE were determined by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). After parturition, dams were randomly divided into four groups: lactating rats (LR) + distilled water (LRO), LR + Asifit, and LR + PSE at doses of 250 and 500 mg/kg body weight (BW). Virgin rats served as the control group. The treatments were given for 14 days. ResultsThere were no significant differences (p > 0.05) in TPC, TFC, and antioxidant capacity among the three solvents. LC-HRMS revealed 22 compounds greater than 70 of the best-match, which were categorised as flavonoids, terpenoids, phenolic acids, and lignan. PSE increased the weight gain and survival rate of pups from our 3-week observation. Serum Prl was significantly higher (p < 0.05) in lactating rats treated with PSE 250 mg/kg BW at the first and third weeks than in the LRO group. Oxt serum was significantly higher (p < 0.05) in lactating rats treated with PSE (500 mg/kg BW) in the first and second weeks than in the LRO group. ConclusionPSE-rich polyphenols are promising galactopoietics by orchestrating Prl and Oxt and reducing the mortality of pups.

Mathematical model for prolactin secretion in healthy adults using lognormal distribution

The concentration of prolactin in healthy persons is the focus of this investigation. The concentration of serum PRL in blood is determined by gender based. Traditional employment, sleeping patterns, psychological stress, and medicine are maintained for both genders. As a result of the research, the concentrations of PRL in men and women are linked. Log-Normal distributions were employed in the Mathematical Model. The medical results were analysed using the mathematical model that corresponded to them.

Gonadotropin profile in experimentally induced hypothyroid and hyperthyroid cyclic female rats

The current study examined the association of thyroid disorders with reproductive dysfunction by determining its effect on gonadotropin secretion in cyclic female rats. Sixty cyclic females were assigned to three groups (20 each) and supplemented, for 30 days plus two consequent estrous cycles, with drinking water (control), methimazole in drinking water (0.02% w/v) (hypothyroid group), and thyroxine in drinking water (0.002% w/v) and gastric gavage of 200 μg/kg body weight (hyperthyroid group). At late proestrus, ten females from each group (for each cycle) were anesthetized and dissected. Blood samples were obtained to assess thyroid-stimulating hormone, free and total triiodothyronine, free and total thyroxin, follicle-stimulating hormone, luteinizing hormone, and prolactin concentrations. Ovarian and pituitary tissue samples were obtained for molecular analysis of ovarian thyroid receptor genes and pituitary TSH, FSHβ, and LHβ genes. In comparison with control, the Hypo group revealed increased serum concentrations of TSH and PRL and the expression levels of pituitary TSH and ovarian TRsTRs genes and significant decrease of FT3, TT3, FT4, TT4, FSH, and LHLH concentrations and the expression levels of pituitary FSHβ and LHβ genes. In contrast, the Hyper group showed increased serum FT3, TT3, FT4, TT4, and LHLH concentrations and the expression levels of pituitary LHβ and ovarian TRsTRs genes and decreased serum TSH FSH and PRL concentrations and pituitary FSHβ and TSH gene expression levels. It is concluded that thyroid dysfunction is associated with altered serum gonadotropin secretion and reproductive failure.

The hypothalamic-pituitary-gonad axis in male Cushing's disease before and after curative surgery.

Gonadal and sexual disturbances are commonly encountered in patients with Cushing's disease. Nevertheless, the prevalence of hypogonadism in male Cushing's disease, the risk factors as well as the recovery time have been scarcely reported. Therefore, we aimed to explore the prevalence of hypogonadism at baseline and its determinants. In addition, the recovery time of hypogonadism and risk factors for unrecovered gonadal axis in male Cushing's disease with biochemical remission were investigated. We reviewed medical records of males with Cushing's disease managed between 2010 and 2020. Fifty-two male patients were enrolled according to the criteria. Each case attained biochemical remission after transsphenoidal surgery. Demographic details, clinical features, 24-hour UFC, hormonal profile [serum PRL, FSH, LH, TT, ACTH, cortisol, TT4/FT4, TT3/ FT3, TSH and IGF-1] were measured at baseline and during follow-up. The maximal tumor diameter on MRI was recorded at diagnosis. Hypogonadotropic hypogonadism was observed in thirty-nine patients (75%) at diagnosis. Total testosterone was negatively correlated with ACTH and 24-hour UFC. Midnight serum ACTH level at diagnosis was significantly associated with hypogonadism after adjusting for confounding factors. Thirty-two (80%) patients achieved eugonadism within 12 months after the surgery, of which twenty-eight (87.5%) achieved eugonadism within 3 months. Seven patients were persistently hypogonadal during the follow-up (≥1 year), mainly due to the hypopituitarism as a complication of the therapies such as surgery. Hypogonadotropic hypogonadism is frequent in male Cushing's disease, but it is reversible in most cases within one-year follow-up after remission.

A prolactin-dependent sexually dimorphic mechanism of migraine chronification.

Determination of possible sex differences in mechanisms promoting migraine progression and the contribution of prolactin and the prolactin long (PRLR-L) and short (PRLR-S) receptor isoforms. The majority of patients with chronic migraine and medication overuse headache are female. Prolactin is present at higher levels in women and increases migraine. Prolactin signaling at the PRLR-S selectively sensitizes nociceptors in female rodents, while expression of the PRLR-L is protective. Medication overuse headache was modeled by repeated sumatriptan administration in male and female mice. Periorbital and hindpaw cutaneous allodynia served as a surrogate of migraine-like pain. PRLR-L and PRLR-S isoforms were measured in the trigeminal ganglion with western blotting. Possible co-localization of PRLR with serotonin 5HT1B and 5HT1D receptors was determined with RNAscope. Cabergoline, a dopamine receptor agonist that inhibits circulating prolactin, was co-administered with sumatriptan. Nasal administration of CRISPR/Cas9 plasmid was used to edit expression of both PRLR isoforms. PRLR was co-localized with 5HT1B or 5HT1D receptors in the ophthalmic region of female trigeminal ganglion. A single injection of sumatriptan increased serum PRL levels in female mice. Repeated sumatriptan promoted cutaneous allodynia in both sexes but down-regulated trigeminal ganglion PRLR-L, without altering PRLR-S, only in females. Co-administration of sumatriptan with cabergoline prevented allodynia and down-regulation of PRLR-L only in females. CRISPR/Cas9 editing of both PRLR isoforms in the trigeminal ganglion prevented sumatriptan-induced periorbital allodynia in females. We identified a sexually dimorphic mechanism of migraine chronification that involves down-regulation of PRLR-L and increased signaling of circulating prolactin at PRLR-S. These studies reveal a previously unrecognized neuroendocrine mechanism linking the hypothalamus to nociceptor sensitization that increases the risk of migraine pain in females and suggest opportunities for novel sex-specific therapies including gene editing through nasal delivery of CRISPR/Cas9 constructs.

Ovarian Hyperthecosis: Hyperandrogenism in a Post-Menopausal Woman

Introduction: Ovarian Hyperthecosis (OH) is a disorder characterized by severe hyperandrogenism and insulin resistance. It is a rare cause of hyperandrogenism primarily among postmenopausal women. We present a case report about a patient with adrenal incidentalomas and later found to have ovarian hyperthecosis during her evaluation. Case Description: 62-year-old post-menopausal female was referred to the Endocrinology clinic for evaluation of adrenal incidentalomas which were discovered on imaging work-up for hematuria. MRI Abdomen and Pelvis revealed a 17mm right and 14mm left sided adrenal nodules, with signal dropout suggesting benign adenomas. Patient stated she had menopause at age 39 years old, one child, and multiple miscarriages during her reproductive years. Examination revealed BMI of 31.1 kg/m2, moderate hirsutism, and skin tags near the neck. There was no evidence of hyperpigmentation or abdominal striae. Patient had phenotype suggestive of insulin resistance-without diagnosis of diabetes. Results: Laboratory workup revealed normal levels of 24-hour metanephrines, cortisol, renin, aldosterone, and DHEA-S suggesting that the adrenal adenomas were not hyperfunctioning. Further workup revealed: Total Testosterone: 220 [2 - 45 ng/dL]; Free Testosterone 23.8 [0.1 - 6.4 pg/mL]; DHEA-S 43 [12 - 133 mcg/dL]. Prolactin 6.3 [Postmenopausal 2.0-20.0 ng/mL]. A1c 5.4 [<5.7%]. Serum FSH, LH, PRL, and IGF-1 were within normal reference ranges. The patient, with adrenal adenomas, elevated testosterone, and a normal DHEA-S suggested a non-adrenal source. Patient was evaluated by OB/GYN with finding of normal postmenopausal ovaries on transvaginal ultrasonography. Based on a high suspicion for OH, patient underwent hysterectomy with bilateral salpingo-oophorectomy which confirmed pathological diagnosis of Bilateral OH. On follow-up 2 months post-op, Total/Free Testosterone had normalized 36 [2 - 45 ng/dL] and 3 [0.1 - 6.4 pg/mL] respectively). Conclusion: In women presenting with elevated testosterone (>150 ng/dL) and clinical features of hyperandrogenism, proper laboratory and imaging evaluation is imperative to determine the source of excess androgen production. Untreated, OH is associated with increased mortality from type 2 diabetes, cardiovascular disease, and endometrial carcinoma. The diagnosis of OH can be confirmed only by histologic examination of the ovaries. Often, ovarian imaging is negative, therefore, surgical intervention is recommended. Hence, clinicians should rely on the clinical assessment in making management decisions in patients with OH.

A Case of Giant Prolactinoma Characterized by a Nasopharyngeal Extension and Diagnosed by Nasal Cavity Biopsy

Abstract Introduction: Giant prolactinomas represent 2-3% of all prolactinomas and less than 0.5% of all pituitary lesions. Uncommon extensions of giant pituitary adenomas to areas such as nasopharynx or paranasal sinuses are even rarer. There are about 50 cases described in the literature. Here, we report a giant prolactinoma case diagnosed by biopsy from the nasal cavity. Case: A 40-year-old male patient applied to the emergency room after falling on ice. Cranial CT revealed a giant sellar mass destroying the clivus and the sphenoid bone corpus. The patient has had frontotemporal headache for 5 years, and also loss of libido and erectile dysfunction. He had right superolateral visual field defect and right-sided ptosis. Pituitary MRI showed a T2-hyperintense sellar mass measuring 58x58x70 mm, with extension to the nasopharyngeal wall, right cavernous sinus, right petrous apex and ethmoid spaces at the base of the skull. A punch biopsy was taken from the vascular mass located in the right nasal cavity, in between the middle concha and the septum. Pathological examination revealed a neoplasm that showed strong diffuse immunostaining with PRL and CK8, and focal staining with GH. Ki-68 proliferation index was 2%. Serum PRL level was 11881 ng/mL, FSH: 1.5 mIU/mL, LH: 1.3 mIU/mL, testosterone: 35.7 ng/dL, GH: 0.5 ng/mL, IGF-1: 520 ng/mL, ACTH: 73 pg/mL, cortisol: 12 mcg/dL, TSH: 0.04 uIU/mL, fT4: 14.2 pmol/L, fT3: 4.9 pmol/L and electrolytes were normal. Five days later, a right pterygonal craniotomy was performed. The mass showed the same immunostaining characteristics as the earlier biopsy specimen, and also included fibrin, monotonous cells with ischemic necrosis and distorted architecture of the reticulin pattern. According to the post-operative MRI, the right cavernous and clival part of the mass was reduced in size. Cabergoline (0.5 mg/w), levothyroxine (100 mcg/d) and testosterone propionate (250 mg/m) were started. The patient received conventional radiotherapy in a total dose of 1250 Gy, because of the residual mass. Sixth months after radiotherapy, the nasopharyngeal part of the tumor was not visualized. Cabergoline was up-titrated to a maximum dose of 3 mg/w. Prolactin levels decreased to 136 and 22 ng/mL at the third and sixth months of the treatment, respectively. Superolateral right-sided visual field defect persisted. Five years after surgery, secondary hypocortisolism has emerged, and 5 mg/day prednisolone was added to the therapy. Eight years after diagnosis, MRI revealed significant reduction in the size of the heterogeneous residual mass lesion. Discussion: Giant macroadenomas extending to nasopharynx are mostly prolactinomas, but other functional or non-functional pituitary adenomas may also have the same presentation. These lesions tend to be surgically hard to excise due to uncommon localizations, as in our case, and radiotherapy may be needed to control the residual mass.

Elevated ovarian pentraxin 3 in polycystic ovary syndrome

PurposePentraxin 3 (PTX3) plays a crucial role in cumulus expansion and fertilization. The ovarian PTX3 level in polycystic ovary syndrome (PCOS) remains uncertain. In the present study, we investigated the follicular PTX3 levels and found the influence of reproductive hormones on ovarian PTX3 concentration.MethodsThis study was based on 204 healthy-weight women (102 PCOS and 102 normal ovulating subjects) undergoing in vitro fertilization (IVF). Follicular fluid (FF) was collected during oocyte retrieval. The PTX3 levels and other hormone levels in FF samples were analyzed by enzyme-linked immunosorbent assay (ELISA).ResultsThe PTX3 level in the follicle was significantly higher in the healthy-weight PCOS women than controls. Positive correlations were found between ovarian PTX3 level and the existence of PCOS, cycle length, basal LH to FSH ratio and TT in serum, antral follicle count, and ovarian insulin and androgen level, and inverse correlations with the basal serum PRL and ovarian SHBG. In multivariant linear regression analysis, the presence of PCOS diagnosis, participants’ basal LH to FSH ratio, and ovarian androstenedione level were the main predictors of ovarian PTX3 level among the enrolled subjects.ConclusionElevated ovarian PTX3 level supports the low-grade chronic inflammatory state in the follicles of PCOS. The existence of PCOS, disturbed pituitary gland, and ovarian hyperandrogenism might also be related to this state of low-grade chronic inflammation and could be a subject of further study.

Retinal layers in prolactinoma patients: a spectral-domain optical coherence tomography study.

Prolactinomais a type ofpituitary tumourthat produces an excessive amount of the hormone prolactin. It is the mostcommontype of hormonally-activepituitary tumour. These tumours can cause ocular complications such as vision loss and visual fields (VF) defect. In this study, we aimed to evaluate the thickness of chorioretinal layers in patients with prolactinoma. We enrolled 63 eyes of 32 prolactinoma patients and 36 eyes of 18 age and gender-matched healthy controls. All participants underwent complete hormonal and ophthalmological examination, including spectral-domain optical coherence tomography (SD-OCT) and VF test.The complete biochemical response was defined as serum PRL concentration ≤ 20ng/mL at the time of evaluation.The seven layers were retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), and retinal pigment epithelium (RPE). The results of prolactinoma patients were compared with the control group. The mean RNFL, GCL, IPL, INL, ONL, and RPE were thinner in prolactinoma patients than the control group (p < 0.05) while OPL was similar between groups (p > 0.05).None of the patients had VF defect.The thickness of retinal layers was similar in patients with and without complete biochemical response (p > 0.05). To our knowledge, this is the first study that evaluates the thickness of chorioretinal layers in patients with prolactinoma.Most of the layers were thinner than the control group.Therefore, detailed eye assessment should be a routine component of the follow-up visits of prolactinoma patients and further studies related to this condition are required.

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) &lt;40%). The mean pre-PEG and post-PEG values were 52.5 ng/mL and 19.2 ng/mL (RR: 36.5%; p-value &lt;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.

Increased Prolactin is an Adaptive Response to Protect Against Metabolic Disorders in Obesity

ObjectiveProlactin (PRL) is a polypeptide hormone named for its crucial role in lactation. Recently, PRL has been recognized as a metabolic hormone that regulates energy metabolism. The current study aimed to investigate the relationship between circulating PRL and metabolic alterations in overweight/obese patients and the effect of weight loss through bariatric surgery on circulating PRL. MethodsA total of 448 overweight/obese patients aged between 18 and 40 years and 120 age- and sex-matched healthy controls with normal weight were enrolled. Among all participants, 156 obese patients underwent bariatric surgery. ResultsCirculating PRL levels were significantly increased in the overweight (15.27 ± 9.58 μg/L) and obese (17.75 ± 9.15 μg/L) groups compared with the normal weight (13.57 ± 9.03 μg/L) group. Multiple regression analyses demonstrated that the adipose tissue insulin resistance (adipo-IR) level was an independent predictor for PRL (β = −0.451, P < .01). Despite comparable anthropometric parameters, the overweight/obese patients with a higher PRL tertile had decreased levels of triglycerides, nonesterified fatty acids, homeostasis model assessment of insulin resistance, and adipo-IR compared with the patients in the moderate and lower PRL tertiles. Serum PRL levels were significantly decreased following the alleviation of metabolic parameters after bariatric surgery (from 17.12 ± 8.27 to 13.00 ± 5.78 μg/L, P < .05), and the decrease in PRL levels was significantly greater in the lower adipo-IR group than in the higher adipo-IR group (P < .01). ConclusionAn increased serum PRL level might be an adaptive response for protecting against metabolic disorders in obesity.

Effect of Hordei Fructus Germinatus on differential gene expression in the prolactin signaling pathway in the mammary gland of lactating rats

Ethnopharmacological relevanceIn China, Hordei Fructus Germinatus (HFG) is the germinated and dried fruit of Hordeum vulgare L, which is commonly used in clinical Chinese medicine. Traditional Chinese Medicine (TCM) theory holds that HFG can be both medicinal and edible, which means that it is derived from food medicine. Raw HFG and roasted HFG are used to treat hypogalactia, hyperprolactinemia and indigestion. In recent years, the lactogenic and galactophygous effects of HFG have attracted increasing attention. Nevertheless, there is much confusion over the use of raw and processed HFG, and the mechanism of its lactogenic effect seems remains poorly understood. Aim of the studyThis study aimed to explore the lactogenic effect of raw HFG and roasted HFG on rats with overloaded lactation and to reveal the underlying molecular mechanism. Materials and methodsRaw and processed HFG water decoctions were given to overloaded lactation model rats at a dose of 1.7800 g kg−1·d−1, and the control group was given the same volume of water. The lactogenic effect of raw and processed HFG was evaluated by measuring daily lactation, body weight and pup body weight, serum PRL, E2, and GH contents after parturition, and the pathological characteristics of mammary tissue sections. cDNA microarrays can be used to screen diverse gene expression patterns and signaling pathways related to prolactin. The expression of relevant differentially expressed genes was verified by real-time PCR and western blotting. ResultsIn vivo experiments demonstrated that the raw HFG water decoction stimulated mammogenesis, accelerated the transformation of the lobular acinar system, resulted in denser mammary epithelial cells and thicker glandular ducts that were full of milk and facilitated the secretion of milk. Moreover, HFG increased PRL, E2, and GH levels, pup body weight, daily lactation and the body weight of lactating rats. Following gene chip identification, KEGG pathway enrichment analysis revealed genes that were highly related to prolactin in the prolactin signaling pathway and JAK-STAT signaling pathway, and the main differentially expressed genes were Jak2 (down), Stat5α (up), cyclin D1 (up), SOCS1 (up), CISH (down) and PRLR (up). Compared with the control group, RT-PCR results indicated that Jak2 and CISH were downregulated and that Stat5α, cyclin D1, SOCS1 and PRLR were upregulated. Western blot assays showed that PRLR, STAT5α and cyclin D1 levels in the mammary glands of the raw HFG water decoction group were significantly increased, which was consistent with the results of cDNA microarray screening. ConclusionThe present study reveals that raw HFG effectively enhances lactation in rats, possibly by influencing the prolactin/JAK-STAT signaling pathway.