Basal Prolactin Research Articles

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.

Diagnosis of hypoprolactinemia.

Prolactin is a polypeptide hormone composed of 199 amino acids, synthesized by lactotroph cells. Its primary effects are on the mammary gland and gonadal axes, but it also influences different organs and systems, particularly metabolic functions. Current literature has mainly focused on the diagnosis, monitoring, and treatment of hyperprolactinemia. Due to the lack of a well-established effective treatment for hypoprolactinemia, it is not clinically emphasized. Therefore, data on its diagnosis is limited. Hypoprolactinemia has been associated with metabolic dysfunctions such as type 2 diabetes mellitus, fatty liver, dyslipidemia, fertility problems, sexual dysfunction, and increased cardiovascular disease. While often seen as a part of combined hormone deficiencies due to pituitary damage, isolated prolactin deficiency is rare. Hypoprolactinemia can serve as a marker for extensive pituitary gland damage and dysfunction.Low or undetectable serum prolactin levels and the absence of a sufficient prolactin peak in the thyrotropin-releasing hormone (TRH) stimulation test are considered diagnostic for hypoprolactinemia. Gender appears to influence both basal prolactin levels and TRH stimulation test responses. Basal prolactin levels of, at least, 5 ng/mL for males and 7 ng/mL for females can be used as cut-off levels for normal prolactin reserve. Minimum peak prolactin responses of 18 ng/mL for males and 41 ng/mL for females to TRH stimulation can exclude hypoprolactinemia. However, larger population studies across different age groups and sexes are needed to better define normal basal prolactin levels and prolactin responses to the TRH stimulation test.

Effect of baseline prolactin levels on the pregnancy outcomes after fresh embryo transfer.

There is clinical disagreement on whether to treat hyperprolactinemia with medication before embryo transfer. The aim of this study is to identify the impact of basal prolactin (PRL) levels on pregnancy outcomes in fresh embryo transfer cycles. This retrospective study involved 2,648 women who underwent basal PRL level testing and fresh embryo transfer between January 2015 and December 2020 at our Hospital's Department of Assisted Reproduction. Basal PRL levels can be classified into three categories:<30 (n=2339), 30‑60 (n=255), and ≥60 (n=54) µg/l. Pregnancy outcome was defined as the primary outcome measure, and the live birth rate was defined as the second outcome measure. Subsequently, univariate and multivariable logistic regression analysis was used to reveal the association between basal PRL levels and pregnancy outcomes after considering several potential confounding factors. Elevated basal PRL levels were found not a risk factor for pregnancy outcomes in patients receiving good-quality embryo transfer (p>.05). For pregnancy or not, female age (OR: 1.03; 95% CI: 1.01-1.05), embryos transferred (OR: 0.52; 95% CI: 0.41-0.65), and normal fertilization rate (OR: 0.68; 95% CI: 0.48-0.97) were found to be an independent risk factor. For ongoing pregnancy or not, female age (OR: 1.07; 95% CI: 1.03-1.11), embryos transferred (OR: 0.57; 95% CI: 0.37-0.88), and menstrual cycle (OR: 1.76; 95% CI: 1.22-2.54) were also independent risk factors. There is no adverse impact on pregnancy outcomes during embryo transfer cycles with good-quality embryos when PRL levels are elevated.

Relationship between CCL25/CCR9 Levels in Follicular Fluid and High Ovarian Response in Patients with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is one of the prevalent gynecological endocrine disorders encountered in clinical practice. Women diagnosed with PCOS demonstrate increased ovarian responsiveness, rendering them more prone to ovarian hyperstimulation syndrome (OHSS) during controlled ovarian stimulation (COS) procedures. The current study aimed at investigating whether CCL25/CCR9 plays a role in the pathological process of high ovarian response (HOR) during COS procedures. Single-center retrospective cohort study. Patients. A total of 200 PCOS patients who received a fixed regimen of gonadotropin-releasing hormone (GnRH) antagonist were enrolled in this study. The cohort comprised 118 patients exhibiting HOR and 82 patients demonstrating a normal ovarian response (NOR). The age and body mass index (BMI) variances across the two groups did not differ significantly. Similarly, the two groups observed no statistically significant differences in the baseline levels of luteinizing hormone (LH), progesterone (P), estradiol (E2), basal prolactin (PRL), and testosterone (T). Compared to the NOR group, HOR patients exhibit markedly elevated levels of anti-Müllerian hormone (AMH), antral follicle count (AFC), basal follicle-stimulating hormone (FSH), and HOMA-IR (all p < 0.05). Conversely, no statistically significant differences were observed between the two groups with respect to COS parameters, encompassing initial gonadotropin (Gn) dose, stimulation duration, and total Gn dose. During COS, the number of oocytes with diameter ≥14 mm, the levels of E2 on the HCG day, and the number of retrieved oocytes were significantly higher in the HOR group than in the NOR group (all p < 0.001). Additionally, the levels of CCL25/CCR9, matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), TNF-α, and IL-6 were significantly higher in the FF of the HOR group than in the NOR group (all p < 0. 001), while the variance in IL-1β levels between the two cohorts did not reach statistical significance. The relevance analysis results indicated that the levels of CCL25/CCR9 in the FF of the HOR group are positively correlated with the number of retrieved oocytes and oocytes with diameters ≥14 mm during COS, AMH levels, and AFC. Concurrently, the CCL25 levels in the FF of the HOR group were positively correlated with HOMA-IR. Multivariable linear regression analysis revealed that the elevated AFC and HOMA-IR independently increase the CCL25 levels. The CCL25/CCR9 levels in FF are positively correlated with the clinical indicators of HOR, suggesting that CCL25/CCR9 may play a role in the pathogenesis of HOR in patients with PCOS.

Factors associated with oocyte recovery rates during in-vitro fertilization among Nigerian women.

the availability of oocytes is fundamental to in vitro fertilization (IVF). The factors associated with optimal or suboptimal oocyte recovery rates (ORR) in low-resource settings are not well known. This study aimed to determine the factors associated with ORR by comparing demographic and IVF cycle data of women undergoing IVF in our Centre. this was a prospective study of 110 infertile women undergoing IVF at Nisa Premier Hospital, Abuja Nigeria, from October 2020 to September 2021. All women had reached the stage of oocyte retrieval or further, after receiving ovarian stimulation with our routine protocols. Treatment was monitored by serial transvaginal ultrasonography. The oocyte retrieval procedures were performed under conscious sedation, 36 hours after the ovulatory trigger. Optimal ORR was when eggs were obtained from at least 80% of follicles punctured. Sub-optimal ORR was when it was less than 80%. Data analyses utilized SPSS statistical software and a p-value of < 0.05 was considered significant. the mean age of all women was 34.1±4.9 years. Sixty-nine women (62.7%) had sub-optimal ORR while 41 (37.3%) had optimal ORR. Six women (5.5%) had no oocytes retrieved. Significantly more women with sub-optimal ORR were obese (70.6 vs 29.4%) and had higher follicle-stimulating hormone (FSH) levels (8.11 vs 6.34 miu/ml), p-value- 0.039. Women with sub-optimal ORR had higher mean prolactin levels (17.10 ± 13.93 miu/ml) than women with optimal ORR 11.43 ± 6.65 miu/ml), p-value- 0.019). Significantly more oocytes (5.99 vs 10.37, p-value 0.001), and MII oocytes (5.78 vs 7.56, p-value 0.035) were retrieved in women with optimal than sub-optimal ORR. The duration of stimulation, total amounts of gonadotropins administered, and fertilized oocytes were not significantly different among both groups (p-value >0.05). this study has shown the factors associated with ORR in our setting to be basal FSH, prolactin, and obesity.

The association between serum prolactin levels and live birth rates in non-PCOS patients: A retrospective cohort study.

This paper aimed to analyze the relationship between baseline prolactin (PRL) levels and live birth rates (LBRs) in patients undergoing embryo transfer who did not have polycystic ovarian syndrome (PCOS) using a retrospective design. Patient(s): A total of 20,877 patients who had undergone IVF/intracytoplasmic sperm injection (ICSI) between December 2014 and December 2019. We examined the association between PRL concentrations and LBRs using multivariate regression analysis. In addition, a model for nonlinear relationships based on a two-part linear regression was developed. Following adjustment for confounding factors, multivariate regression analysis confirmed a statistically significant correlation between serum PRL and LBR. Particularly, when blood PRL content was less than 14.8 ng/mL, there exists a positive relation between serum PRL and LBRs. In contrast, once PRL concentrations surpassed the inflection point at 14.8 ng/mL, a meaningful relationship could no longer be inferred between serum PRL and LBR. Basal serum PRL levels were segmentally connected with LBRs.

The Value of ER∝ in the Prognosis of GH- and PRL-Secreting PitNETs: Clinicopathological Correlations.

Pituitary neuroendocrine tumors (PitNETs) are divided into multiple histological subtypes, which determine their clinical and biological variable behavior. Despite their benign evolution, in some cases, prolactin (PRL) and growth hormone (GH)-secreting PitNETs may have aggressive behavior. In this study, we investigated the potential predictive role of ER∝, alongside the clinicopathological classification of PitNETs (tumor diameter, tumor type, and tumor grade). A retrospective study was conducted with 32 consecutive cases of PRL- and mixed GH- and PRL-secreting PitNETs (5 patients with prolactinomas and 27 with acromegaly, among them, 7 patients with GH- and PRL- co-secretion) who underwent transsphenoidal intervention. Tumor specimens were histologically and immunohistochemical examined: anterior pituitary hormones, ki-67 labeling index, CAM 5.2, and ER∝; ER∝ expression was correlated with basal PRL levels at diagnosis (rho = 0.60, p < 0.01) and postoperative PRL levels (rho = 0.58, p < 0.001). In our study, the ER∝ intensity score was lower in female patients. Postoperative maximal tumor diameter correlated with Knosp grade (p = 0.02); CAM 5.2 pattern (densely/sparsely granulated/mixed densely and sparsely granulated) was correlated with postoperative PRL level (p = 0.002), and with ki-67 (p < 0.001). The IGF1 level at diagnosis was correlated with the postoperative GH nadir value in the oral glucose tolerance test (OGTT) (rho = 0.52, p < 0.05). Also, basal PRL level at diagnosis was correlated with postoperative tumor diameter (p = 0.63, p < 0.001). At univariate logistic regression, GH nadir in OGTT test at diagnostic, IGF1, gender, and invasion were independent predictors of remission for mixed GH- and PRL-secreting Pit-NETs; ER∝ can be used as a prognostic marker and loss of ER∝ expression should be considered a sign of lower differentiation and a likely indicator of poor prognosis. A sex-related difference can be considered in the evolution and prognosis of these tumors, but further studies are needed to confirm this hypothesis.

Population Pharmacokinetic Analysis of Follicle-Stimulating Hormone During Ovarian Stimulation: Relation with Weight, Prolactin and Gene Polymorphism in THADA and ADIPOQ.

Personalisation strategies of ovarian stimulation for in vitro fertilisation (IVF)/ intracytoplasmic sperm injection (ICSI) treatments using exogenous follicle-stimulating hormone (FSH) have been extensively studied over the past 20 years. This research aimed to develop a FSH population pharmacokinetic (PPK) model taking into account the contribution of gene polymorphisms in Chinese reproductive-age women. Data from 173 patients undergoing GnRH agonist down-regulation long protocols of IVF/ICSI treatment were collected. PPK analysis was subsequently conducted using the nonlinear mixed-effect model (NONMEM) software. Several covariates, including 18 single nucleotide polymorphisms, demographic factors and biological characteristics, were evaluated. The final PPK model was extensively validated using bootstrapping and normalised prediction error distribution, as well as external validation on an independent group of 35 patients. FSH PPK was accurately described by a one-compartment model with first-order absorption. The typical population value of apparent clearance was estimated to be 0.81 L/h [relative standard errors (RSE) 5.3%] with an inter-individual variability (IIV) of 16.0%. The typical apparent distribution volume was 8.36 L (RSE 9.7%, 59.7% IIV), and the absorption rate constant was estimated to be 0.0444 h-1 (RSE 9.1%). Body weight, basal prolactin concentration and the gene ADIPOQ (rs1501299) showed a significant covariate effect on the FSH clearance rate and exposure concentration. Genotypes of THADA (rs12478601) significantly influenced the distribution volume. Simulation results indicated that patients with the TT genotype of THADA (rs12478601) required a longer time to reach steady state and had less fluctuation in FSH levels. Model evaluations showed that the final model accurately and precisely described the observed data and demonstrated effective prediction performance. PPK models of FSH have been developed, which could potentially be used for FSH dosage individualisation in the clinical setting. This study has been registered with the Chinese Clinical Trials Registry (ChiCTR2100049142).

Determination of prolactin reference intervals in different age groups

BACKGROUND: Clinical diagnostic laboratories (CDL) have at their disposal various automated systems for the measurement of biochemical parameters and markers such as prolactin. Each of the test systems manufactures offers its own alternate design of the method, which makes standardization difficult. In endocrinological practice, the problem of result discrepancies often arises. In hormonal assays, the clinical picture of patients sometimes does not correspond to the reference values provided by the manufacturers, which determines the need to develop the method-specific reference values for a specific population. The difficulty in interpreting basal prolactin levels is not only due to a transient increase in the hormone levels caused by stress or excessive physical exertion, but also due to a significant variability of indicators in the same patient, even if all recommendations for blood sampling are followed.AIM: The aim of the study to determine the reference values in serum samples of women, men and children of different age groups for the VITROS Immunodiagnostic Systems and compare the results with the “expected prolactin levels” recommended by the method manufacturerMATERIALS AND METHODS: The monocentric study included 879 serum samples of apparently healthy subjects who were admitted to the Endocrinology Research Center. Measurements were performed using the VITROS ECi 3600 automatic chemiluminescence analyzer (Ortho-Clinical Diagnostics, Great Britain).RESULTS: For adult men and women reference values were 66–436 and 94–500 mIU/l respectively. When comparing the results of prolactin determination in women and men of the studied cohort with the “expected values” of the VITROS ECi 3600 manufacturer a systematic shift towards an increase in lower and upper limits of the reference values was found in both ­cohorts.CONCLUSION: The obtained reference values of prolactin can be use in the determination of prolactin in the Russian population for VITROS ECi 3600 Immunodiagnostic Systems.

Lower serum PRL is associated with the development of non-alcoholic fatty liver disease: a retrospective cohort study

BackgroundNon-alcoholic fatty liver disease (NAFLD) has become an epidemic worldwide and has been linked to a series of metabolic co-morbidities. Prolactin (PRL) has recently been found to have a negative effect on NAFLD, but a causal relationship is not well-understood. Here we investigated the causative relationship between PRL and NAFLD occurrence.MethodsIn this retrospective cohort study, we enrolled patients without NAFLD who were diagnosed by abdominal ultrasonography undergone serum PRL testing at 8.00 a.m. at baseline, and followed up for a median of 32 (19, 46) months.ResultsThis study enrolled 355 persons [215 men and 140 women; media age 56 (49, 64) years], in which 72 (20.28%) patients who eventually developed NAFLD. Compared with those in the non-NAFLD group, basal serum PRL levels of patients were lower in the NAFLD group [male: 7.35 (5.48, 10.60) vs. 9.13 (6.92, 12.50) ug/L, P = 0.002; female: 5.66 (4.67, 9.03) vs. 9.01 (6.31, 11.60) ug/L, P = 0.009]. The prevalence of NAFLD was significantly decreased along with the increased quartile of basal serum PRL levels in both genders (P < 0.05). Serum PRL concentration was independently associated with NAFLD development [male: OR, 0.881 (0.777, 0.998), P = 0.047; female: OR, 0.725 (0.554, 0.949), P = 0.019].ConclusionOur study is the first to find that basal serum PRL level can predict the occurrence of NAFLD and it may be a potential biomarker to prevent and treat NAFLD.

DRUG INDUCED HYPER PROLACTINEMIA: INTERESTING OBSERVATIONS.

Introduction: Drugs are a common cause of hyperprolactinemia. It is essential to differentiate this cause from other pathological causes which avoids unnecessary investigations.Thorough history will help us in finding the responsible drug and holding the same will be rewarding. Here we are reporting such cases of drug induced hyperprolactinemia. Methods: It was a cross-sectional observational study. Subjects were recruited from our outpatient department. Hyperprolactinemia was defined as blood prolactin levels &gt;30 ng/mL in females and &gt;24 ng/mL in males, regardless of the presence of symptoms.Serum prolactin was repeated one week after holding the suspected drug(s).Drug induced hyperprolactinemia defined,if holding of responsible drug made normalization of prolactin levels.Results: Total of 32 subjects were studied in this study with age of 35.5±10.8years.Predominantly female subjects were present with female to male ratio 5.4. Basal prolactin was 132±68.7ng/mL and after holding the drug prolactin value was 16.9±8.2. Proton pump inhibitors in combination with prokinetics were the leading cause (71.8%) and followed by multiple drug combinations (15.6%), anti-psychiatric drugs (9.3%) and oral contraceptives (3.1%). The mean prolactin in the combination of levosulpride was 176 ng/dl, whereas with domperidone it was 126 ng/dl &amp; with oral contraceptives, respiridone it was 134,151ng/dl respectively.Conclusion: Majority cases were clinically symptomatic. Among female subjects commonest presentation was galactorrhea followed by irregular menses and breast heaviness and men presented with erectile dysfunction.Contrary to common belief in our study PPI with prokinetic combination is the most common offending agent than anti-psychotic agents. Levosulpride being the most potent drug in inducing hyper prolactinemia than other agents, though the popular belief was with the Risperidone. As the utility of PPI prokinetic combination is increasing, this might replace anti-psychotic agents as most potent &amp; most common etiology for drug induced hyper prolactinemia.

Giant prolactinoma in children and adolescents: a single-center experience and systematic review.

Giant prolactinoma (GP) in childhood and adolescence is a rare entity with scarce literature. We aimed to describe clinical features, biochemistry, radiology, genetics, management, and outcome in pediatric (≤ 20years) GP. Retrospective record review of 18 pediatric GP patients from our center and systematic review including these and 77 from the literature (total cohort: 95). GP constituted 20% of our pediatric prolactinoma cohort. In the total cohort (age: 15.4 ± 3.5years), the majority (77, 82.8%) were males. Mass effect symptoms (88.6%), and pubertal delay/arrest in males (82.1%) were frequent. Median basal prolactin was 8649 (3246-17,532)ng/ml and the maximum tumor dimension was 5.5 ± 1.5cm. MEN1 and AIP mutations were noted in 7 (21.9%) and 6 (18.8%) patients, respectively. Males with central hypogonadism had baseline bi-testicular volume of 20.2 ± 8.4cc, lower LH than FSH (-2.04 ± 0.9 vs. -0.7 ± 1.6 SDS, p = 0.0075), and mostly, normal inhibin B. Majority (49/76, 64.5%) received dopamine agonist (DA) as first-line treatment with additional therapy in 35% (17/49). DA monotherapy arm had less frequent central hypothyroidism (42.9% vs 87.1%, p = 0.002) and central adrenal insufficiency (7.1% vs 66.7%, p = 0.0003) than multimodal therapy. A smaller tumor dimension (4.7 vs. 5.7cm, p = 0.04) was associated with normoprolactinemia on DA monotherapy and AIP mutations (33.3% vs. nil, p = 0.02) with multimodal therapy. GP is characterized by male predominance with frequent delay/arrest of puberty (82%), but relative sparing of the FSH-inhibin B axis in boys. DA monotherapy may be preferred as the first-line therapy in pediatric GP.

Hormones regulating energy homeostasis in breastfeeding versus formula feeding mothers.

To meet energy demands for lactogenesis and to sustain homeostatic conditions post-partum, the organism of breastfeeding mother undergoes combined endocrine and metabolic regulation. The main objective of this study was to determine basal serum concentrations of hormones involved in the maintenance and defense of energy balance in breastfeeding (BF) and formula feeding (FF) mothers. Twenty healthy exclusively breastfeeding mothers at 3rd month of lactation (EBF3), 17 healthy partially breastfeeding at 6th month of lactation (PB6) and 17 healthy FF mothers participated in this study. Fasting serum prolactin (PRL), acylated ghrelin (aGhr), total ghrelin (tGhr), leptin, adiponectin, insulin, and cortisol were determined for all study participants and correlations between studied parameters were calculated for BF women. We found significantly lower basal insulin (p = 0.0048) and cortisol (p = 0.0002) and significantly elevated basal prolactin (p = 0.0020) and leptin (p = 0.0416) in BF when compared with FF women. The differences were not associated with the duration of lactation (3 vs. 6 months), except for PRL, which was highest in EBF3. Levels of Ghr and adiponectin did not differ between study groups. In the BF group, the negative correlations were found between: aGhr and insulin, aGhr and adiponectin, leptin and cortisol, leptin and adiponectin, insulin and adiponectin, cortisol and adiponectin. Positive associations were noted between: insulin and leptin, leptin and aGhr, PRL and leptin, PRL and aGhr. Leptin and insulin correlated positively, whereas adiponectin negatively with BMI. These data may suggest that EBF3 and PB6 as compared with FF mothers, exhibit hormonal regulation which tends to be more advantageous for their metabolic profile and is not related to the duration of breastfeeding within the first 6 months of lactation.

The effects of delta-9-tetrahydrocannabinol exposure on female menstrual cyclicity and reproductive health in rhesus macaques

To determine the dose-dependent effect of contemporary marijuana exposure on female menstrual cyclicity and reproductive endocrine physiology in a nonhuman primate model. Research animal study. Research institute environment. Adult female rhesus macaques (6-12 years of age; n = 8). Daily delta-9-tetrahydrocannabinol (THC) edible at medically and recreationally relevant contemporary doses. Menstrual cycle length (MCL), anti-Müllerian hormone, prolactin, basal follicle-stimulating hormone (FSH), estradiol (E2) and progesterone, luteinizing hormone (LH), and thyroid-stimulating hormone. The average before THC weight was 6.9 kg (standard deviation, 0.8), and at the highest THC dosing, the average weight was 7.2 kg (standard deviation, 0.8). With increasing THC dosing, MCL and FSH concentrations increased, while basal E2 concentration was stable. The average MCL concentration increased 4.0 days for each mg/7 kg/day of THC (95% CI, 1.4-6.6 days). Follicle-stimulating hormone concentration increased significantly with increasing THC dose, 0.34 ng/mL for each mg/7 kg/day of THC (95% CI, 0.14-0.57 ng/mL). No significant trends were observed between THC dosing and average basal progesterone, anti-Müllerian hormone, prolactin, LH, or thyroid-stimulating hormone concentrations. In rhesus macaques, a dose response toward increased MCL and basal FSH concentrations but plateau of basal E2 and LH concentrations was observed with increasing THC dosing, suggesting ovulatory dysfunction. Further studies are needed to determine the effects of a longer duration of exposure and whether the significant increase in MCL and FSH concentrations results in reduced fecundity.

Drug Induced Hyperprolactinemia

Introduction: Drugs are a common cause of hyperprolactinemia. It is essential to differentiate this cause from other pathological causes which avoids unnecessary investigations. Detailed history will help us in identifying the responsible drug and withdrawing the same will be rewarding. Here we are reporting a case series of drug induced hyperprolactinemia. Methods: It was a cross-sectional observational study. Subjects were recruited from our outpatient department. Hyperprolactinemia was defined as blood prolactin levels >30 ng/mL in females and >24 ng/mL in males, regardless of the presence of symptoms. Serum prolactin was repeated one week after holding the suspected drug(s). Drug induced hyperprolactinemia is defined as normalisation of serum prolactin on discontinuation of the offending drug. Demographics, clinical presentation and offending drug name were entered in pre designed proforma.Results: Total of 32 subjects were studied in this study with age of 35.5±10.8years. Predominantly female subjects were present with female to male ratio 5.4. Basal prolactin was 132±68.7ng/mL and after holding the drug prolactin value was 16.9±8.2. Proton pump inhibitors in combination with prokinetics were the leading cause (71.8%) and followed by multiple drug combinations (15.6%), anti-psychiatric drugs(9.3%) and oral contraceptives(3.1%). Overall 86.75% of subjects were having symptomatic presentation. Commonest clinical presentation among the women was galactorrhea (88.9% of female subjects) followed by irregular menstrual cycles (59% of female subjects) and breast heaviness in 29.6%. Among the men erectile dysfunction was common presentation, noted among 80% of them. Asymptomatic presentation was there in 6.25% of subjects. All subjects were improved clinically after withdrawal of the the offending drug(s).Conclusions: Most of the subjects were clinically symptomatic. Most common symptom in female was galactorrhea followed by irregular menses and breast heaviness, and erectile dysfunction in males. All subjects were improved clinically after withdrawal of the offending drug(s). A detailed drug history is rewarding and avoids unnecessary investigations for hyperprolactinemia

Thyrotropin-Secreting Pituitary Adenoma Successfully Treated With Cabergoline

Background: Thyrotropin secreting pituitary adenomas (TSH-oma) account for less than 1% of pituitary adenomas and are a rare cause of hyperthyroidism. In this case, we describe the safe use of cabergoline with the subsequent achievement of euthyroid levels and the resolution of symptoms. Clinical Case: A 67-year-old female with a presumed history of hypothyroidism for the last 3 years managed with Armour thyroid was referred for fatigue associated with palpitations, intermittent diarrhea, insomnia, and anxiety. Her TSH was noted to be suppressed at that time, and her Amour thyroid was changed to Levothyroxine 25 mcg daily, which was eventually stopped as her symptoms persisted. Follow-up thyroid function tests (TFTs) showed elevated TSH (8.60 µU/mL, reference range 0.340 - 5.600 µU/mL), and elevated free T3 (10.8 pg/mL, reference range 2.7-4.7 pg/mL) and free T4 (2.0 ng/dL, reference range 0.8-1.5 ng/dL) levels. Further laboratory workup including basal prolactin, LH, FSH, hCG α-subunit, IGF-1, and ACTH levels were within the normal range. Physical examination showed diffuse thyroid enlargement. An I-123 thyroid uptake and scan showed uniform uptake throughout the gland with no focal hyperintense areas. A dedicated pituitary MRI was performed and revealed an 8 mm microadenoma in the posterior left adenohypophysis. The patient wanted to avoid any invasive treatment and refused trans-sphenoidal surgery and medical therapy was chosen. Unfortunately, using a somatostatin analog as part of the standard medical treatment was not an option due to the high cost and lack of insurance coverage. For these reasons, a trial of cabergoline was started to suppress TSH secretion. Atenolol 25 mg daily was added temporarily for the management of her sympathetic symptoms. On periodic follow-up, her symptoms gradually subsided, and TFTs remained within normal limits. Treatment was continued for one year. Conclusion: Clinical manifestations of hyperthyroidism with biochemical evidence of elevated thyroid hormone levels and TSH levels should raise a strong suspicion for central or secondary hyperthyroidism due to TSH secreting pituitary adenoma. Cabergoline might represent an effective alternative form of medical treatment for TSH-oma in certain situations where the first line therapeutic options are refractory, contraindicated, or declined.

Impact of chronic variable stress on neuroendocrine hypothalamus and pituitary in male and female C57BL/6J mice.

Chronic stress exerts multiple negative effects on the physiology and health of an individual. In the present study, we examined hypothalamic, pituitary and endocrine responses to 14days of chronic variable stress (CVS) in male and female C57BL/6J mice. In both sexes, CVS induced a significant decrease in body weight and enhanced the acute corticosterone stress response, which was accompanied by a reduction in thymus weight only in females. However, single-point blood measurements of basal prolactin, thyroid-stimulating hormone, luteinising hormone, growth hormone and corticosterone levels taken at the end of the CVS were not different from those of controls. Similarly, pituitary mRNA expression of Fshb, Lhb, Prl and Gh was unchanged by CVS, although Pomc and Tsh were significantly elevated. Within the adrenal medulla, mRNA for Th, Vip and Gal were elevated following CVS. Avp transcript levels within the paraventricular nucleus of the hypothalamus were increased by CVS; however, levels of Gnrh1, Crh, Oxt, Sst, Trh, Ghrh, Th and Kiss1 remained unchanged. Oestrous cycles were lengthened slightly by CVS and ovarian histology revealed a reduction in the number of preovulatory follicles and corpora lutea. Taken together, these observations indicate that 14days of CVS induces an up-regulation of the neuroendocrine stress axis and creates a mild disruption of female reproductive function. However, the lack of changes in other neuroendocrine axes controlling anterior and posterior pituitary secretion suggest that most neuroendocrine axes are relatively resilient to CVS.

Comparative Assessment of Thermotolerance in Dorper and Second-Cross (Poll Dorset/Merino × Border Leicester) Lambs.

Simple SummarySelection of animal breeds that are adapted to extreme climatic conditions may help to sustain livestock production in the face of climate change. We measured the thermotolerance of 4–5-month-old Dorper and second-cross lambs (Poll Dorset × (Border Leicester × Merino)) by assessing feed intake, physiological, blood biochemical and prolactin responses. Heat stress reduced feed intake only in second-cross lambs but not in Dorpers. As expected, heat stress also increased water intake, respiration rate, rectal temperature, and skin temperature in both genotypes, but to a lesser extent in Dorpers. The comparatively lower influence of heat stress on thermotolerance indices in Dorper indicates adaptability of this breed to heat challenge.The objective of this study was to compare the thermotolerance of second-cross (SC; Poll Dorset × Merino × Border Leicester) and Dorper lambs. Dorper and SC lambs (4–5 months of age) were subjected to cyclic heat stress (HS) (28–40 °C). The temperature was increased to 38–40 °C between 800 and 1700 h daily and maintained at 28 °C for the remainder of the day (30–60% relative humidity (RH)) in climatic chambers for 2 weeks (n = 12/group), with controls maintained in a thermoneutral (TN) (18–21 °C, 40–50% RH) environment (n = 12/group). Basal respiration rate (RR), rectal temperature (RT) and skin temperature (ST) were higher (p < 0.01) in SC lambs than in Dorpers. HS increased RR, RT and ST (p < 0.01) in both genotypes, but the levels reached during HS were lower (p < 0.01) in Dorpers. HS increased (p < 0.01) water intake to a greater extent in SC lambs, while feed intake was reduced (p < 0.05) by HS in SC lambs but not in Dorpers. HS increased (p < 0.01) blood urea nitrogen and creatinine in SC lambs only. Plasma non-esterified fatty acid concentrations were reduced (p < 0.05) by HS in SC lambs but increased (p < 0.05) in Dorpers. There was no effect of HS on pO2, cHCO3− and cSO2, but higher (p < 0.01) blood pH and lower (p < 0.01) pCO2 were recorded under HS in both genotypes. Blood electrolytes and base excess were reduced (p < 0.01) under HS, while a genotype difference (p < 0.05) was only observed in blood K+ and hemoglobin concentrations. Basal plasma prolactin concentrations were lower (p < 0.01) in Dorpers but were elevated at a similar level during HS (p < 0.01) in both genotypes. Dorper lambs are more resilient to HS than SC lambs. Future research should focus on confirming whether the better heat tolerance of Dorpers is translated to better returns in terms of growth performance and carcass traits over the summer months.

Letrozole Therapy versus Extended Clomiphene Citrate Therapy for Induction of Ovulation in Resistant Patients with Polycystic Ovarian Syndrome in Low Resource Communities

Background: many drugs can be used in ovulation induction in patients with clomiphene-resistant polycystic ovarian syndrome (PCOs). Objective: to evaluate the effect of letrozole therapy versus extended clomiphene citrate therapy for ovulation induction in clomiphene-resistant polycystic ovarian syndrome patients Patients and Methods: The study included 100 infertile patients who had failed induction by clomiphene for three cycles. They were randomly allocated to receive either letrozole or extended clomiphene therapy. The effects of these drugs on follicular volume, ovulation, endometrium thickness and occurrence of pregnancy were evaluated. Results: No significant difference was found between both groups regarding age, body mass index, basal FSH level, LH level, prolactin level, thyroid function and semen analysis of the husband. Use of letrozole or extended clomiphene led to improvement of number of growing follicles, ovulation rate and pregnancy rate after 3 cycles of ovulation induction. Conclusion: The results of this study revealed that use of letrozole or extended treatment with clomiphene did not show better outcomes over each other in number of growing follicles, ovulation rates, occurrence of pregnancy and pregnancy outcomes. Letrozole group showed a significant increase in the endometrium thickness than extended clomiphene group but this did not affect pregnancy rate.

Letrozole Therapy versus Extended Clomiphene Citrate Therapy for Induction of Ovulation in Resistant Patients with Polycystic Ovarian Syndrome in Low Resource Communities

Background: many drugs can be used in ovulation induction in patients with clomiphene-resistant polycystic ovarian syndrome (PCOs). Objective: to evaluate the effect of letrozole therapy versus extended clomiphene citrate therapy for ovulation induction in clomiphene-resistant polycystic ovarian syndrome patients Patients and Methods: The study included 100 infertile patients who had failed induction by clomiphene for three cycles. They were randomly allocated to receive either letrozole or extended clomiphene therapy. The effects of these drugs on follicular volume, ovulation, endometrium thickness and occurrence of pregnancy were evaluated. Results: No significant difference was found between both groups regarding age, body mass index, basal FSH level, LH level, prolactin level, thyroid function and semen analysis of the husband. Use of letrozole or extended clomiphene led to improvement of number of growing follicles, ovulation rate and pregnancy rate after 3 cycles of ovulation induction. Conclusion: The results of this study revealed that use of letrozole or extended treatment with clomiphene did not show better outcomes over each other in number of growing follicles, ovulation rates, occurrence of pregnancy and pregnancy outcomes. Letrozole group showed a significant increase in the endometrium thickness than extended clomiphene group but this did not affect pregnancy rate.