Untreated Hyperprolactinemia Research Articles

Abstract #1163858: Hyperprolactinemia in a postmenopausal woman. To treat or not to treat?

We describe a case of a postmenopausal woman who presented with untreated hyperprolactinemia with longstanding galactorrhea and low bone density. Challenges including differentiation of prolactin-induced menopause vs age-related menopause and whether to treat with a dopamine agonist are discussed

Different effects of fenofibrate on cardiometabolic risk factors in young women with and without hyperprolactinemia.

Elevated prolactin levels are associated with increased cardiometabolic risk. No previous study has compared the effect of hypolipidemic therapy on plasma levels of lipids and other cardiometabolic risk factors in patients with and without hyperprolactinemia. The study included three age-, weight-, blood pressure- and lipid-matched groups of premenopausal women: 18 women with untreated hyperprolactinemia, 19 women with bromocriptine-treated hyperprolactinemia and 20 drug-naïve women with normal prolactin levels. Because of concomitant atherogenic dyslipidemia, all patients were treated with fenofibrate (200 mg daily) for 12 weeks. Plasma lipids, glucose homeostasis markers, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were assessed at baseline and at the end of hypolipidemic treatment. Unlike similar baseline lipid levels, plasma concentrations of the remaining investigated cardiometabolic risk factors were higher in women with elevated prolactin levels than in patients with normal prolactin levels. The impact of fenofibrate on total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels, as well as on uric acid, hsCRP, homocysteine, and fibrinogen was less pronounced in women with untreated hyperprolactinemia than in women with bromocriptine-treated hyperprolactinemia and drug-naïve women with normal prolactin levels. The results of our study indicate that cardiometabolic effects of fenofibrate depend on plasma prolactin levels.

Increased carotid intima media thickness is associated with prolactin levels in subjects with untreated prolactinoma: a pilot study

Hyperprolactinemia is associated with endothelial dysfunction and atherogenic risk factors, but carotid intima media thickness (IMT) has not been studied in hyperprolactinemic patients. To determine whether untreated hyperprolactinemia contributes to increased carotid IMT. Thirty-one prolactinoma patients and 60 healthy controls were respectively studied. Participants underwent hormone evaluation. Anthropometric parameters (body mass index and blood pressure), inflammatory markers (high-sensitivity C-reactive protein and fibrinogen), serum glucose, insulin, lipid and apolipoprotein profiles were also determined. Endothelial function measured as the flow-mediated dilation (FMD) of a brachial artery and carotid IMT were evaluated using high-resolution ultrasonography. Multivariate linear regression analysis was applied to identify independent determinants of FMD and carotid IMT. Triglycerides, homeostasis model assessment of insulin resistance, apolipoprotein (apo)B/apoA-I ratio, high-sensitivity C-reactive protein (hsCRP) and fibrinogen were significantly higher, while apoA-I was significantly lower in patients with prolactinomas than in the controls. Meanwhile, decreased FMD and increased carotid IMT were observed in hyperprolactinemic group. Serum prolactin was positively correlated with triglycerides, apoB/apoA-I ratio, hypogonadal, hsCRP and fibrinogen (P < 0.05), but inversely associated with apoA-I and HDL-C (P ≤ 0.001). Moreover, prolactin was found negatively correlated with FMD (r = -0.576, P < 0.0001), and positively correlated with mean carotid IMT (r = 0.652, P < 0.0001). Multivariate regression analysis revealed that prolactin determined, independent of traditional risk factors, FMD (B = -0.589, 95% confidence interval (CI) -2.525 to -0.804, P = 0.001) and mean carotid IMT (B = 0.527, 95% CI 0.027-0.069, P < 0.0001). Hyperprolactinemia may be involved in the preclinical increase in carotid IMT, directly or by promoting atherogenic factors, including insulin resistance, low-grade inflammation and endothelial dysfunction. Additional studies are warranted to confirm our findings and explore the mechanisms underlying prolactin-associated early atherosclerosis.

Hypogonadism Due to Hyperprolactinemia and Subsequent First Episode of Psychosis

Hyperprolactinemia causes hypogonadotrophic hypogonadism. Hyperprolactinemia can be pre-existing in some patients with schizophrenia. Dopamine is the most important prolactin-inhibiting factor, and dopaminergic hyperactivity has been implicated in the pathophysiology of psychosis. Since dopamine is a prolactin-inhibiting factor and dopamine imbalanced has been implicated in the pathophysiology of psychotic disorders, we investigated the probable relationship between hyperprolactinemia and the development of psychotic symptoms, in a patient with hypogonadism due to hyperprolactnemia and subsequent first episode of psychosis. Since dopamine is a prolactin-inhibiting factor and dopamine imbalance has been implicated in the pathophysiology of psychotic disorders, we investigated the probable relationship between hyperprolactinemia and the development of psychotic symptoms. We present the case of a patient with hypogonadism secondary to chronic, untreated hyperprolactinemia who developed acute psychotic symptoms. Psychotic symptoms resolved soon after treatment with aripiprazole in conjunction with cabergoline, with a concomitant decrease in serum prolactin level. This is an interesting case illustrating a complicated relationship among hypogonadism secondary to a prolactinoma and dopamine and psychosis.

Vertebral fractures in males with prolactinoma

Data on osteoporotic fractures in hyperprolactinemia are limited. An increased prevalence of radiological vertebral fractures was recently observed in women with prolactin (PRL)-secreting adenoma, whereas it is unknown whether this observation may reflect a more general increased risk of fractures in this disease and whether the prevalence of fractures in males is affected by gonadal status. Thirty-two males (median age 47 years, range: 22-79) with PRL-secreting pituitary adenoma (10 with microadenoma and 22 with macroadenoma) and 64 control males, with normal PRL values and with comparable age to patients with hyperprolactinemia, were evaluated for vertebral fractures by a morphometric approach and for bone mineral density (BMD) by a dual-energy X-ray absorptiometry at lumbar spine. Vertebral fractures were shown in 12 patients with PRL-secreting adenoma (37.5%) and in 5 controls (7.8%, P < 0.001). Fractured patients had lower BMD T-score (P = 0.007) and longer duration of disease (P < 0.001) as compared to patients who did not fracture. Fractures occurred more frequently (P = 0.03) in patients with untreated hyperprolactinemia versus patients treated with cabergoline whose frequency of vertebral fractures was still higher than control subjects. The prevalence of vertebral fractures was not significantly different between eugonadal and hypogonadal patients (33.3% vs. 38.5%; P = 0.8). Moreover, no significant (P = 0.4) difference in serum testosterone values was found between fractured and not fractured males. Hyperprolactinemia is associated with high prevalence of radiological vertebral fractures in men with PRL-secreting adenoma. These findings would also suggest that PRL excess may produce negative skeletal effects independently of hypogonadism.

High prevalence of radiological vertebral fractures in women with prolactin-secreting pituitary adenomas

Hyperprolactinemia may cause bone loss but data on fractures are scanty. The aim of this study was to evaluate the prevalence of vertebral fractures in women with prolactin (PRL)-secreting adenoma. In this cross-sectional study, 78 women (median age 45.5 years, range: 20-81) with PRL-secreting pituitary adenoma (66 with microadenoma and 12 with macroadenoma) and 156 control subjects, with normal PRL values and with comparable age to patients with hyperprolactinemia, were evaluated for vertebral fractures by a morphometric approach and for bone mineral density (BMD) by a dual-energy X-ray absorptiometry at lumbar spine. Vertebral fractures were shown in 25 patients with PRL-secreting adenoma (32.6%) and in 20 controls (12.8%, P < 0.001). Fractured patients were significantly older (P < 0.001) and had lower BMD T-score (P < 0.001), longer duration of disease (P < 0.001), higher serum PRL (P = 0.004) and lower serum IGF-I (P < 0.001) values as compared to patients who did not fracture. The prevalence of vertebral fractures was significantly (P < 0.001) higher in post-menopausal women with PRL-secreting adenoma as compared to pre-menopausal patients. Fractures occurred more frequently (P = 0.01) in patients with untreated hyperprolactinemia versus patients treated with cabergoline. Logistic regression analysis demonstrated that duration of disease maintained a significant correlation with vertebral fractures (odds ratio 1.16, C.I. 95% 1.02-1.33) even after correction for age, menopausal status, treatment with cabergoline, BMD, serum IGF-I and serum PRL values. Hyperprolactinemia is associated with high prevalence of radiological vertebral fractures in women with PRL-secreting adenoma.

Frequency of anticardiolipin Ac in patients with hyperprolactinemia

Sir, Association between hyperprolactinemia and autoimmune diseases has been demonstrated.[12] We assessed the frequency of anticardiolipin (ACL IgG and IgM by ELISA) and thyroperoxidase (ATPO by chemiluminescence) antibodies, in 23 patients with hyperprolactinemia, subdivided into two groups: Group 1, untreated hyperprolactinemic patients (n = 14; 42.5 ± 14.7 years) and Group 2, treated hyperprolactinemic patients (n = 9, 39.4 ± 12.1 years). Group 3, control, consisted of 20 individuals without thyroid and autoimmune diseases (n = 20; 47.1 ± 13.6 years). Positivity of ACL was observed in none of the control, in two patients with treated hyperprolactinemia (one IgM and one IgG) and in one with treatment-free hyperprolactinemia (IgM) [Table 1]. ACL IgG levels were significantly higher in the group with hyperprolactinemia (2.1 ± 2.5 GPL) compared to the control group (0.7 ± 0.2 GPL), P = 0.018. ATPO was detected in 11/23 (47%) patients with hyperprolactinemia and in 1/20 (5%) of controls and the mean was significantly higher in the hyperprolactinemic group compared to control (P = 0.004).Table 1: Positivity and variation of the levels of anticardiolipin and thyroperoxidase in hyperprolactinemic and control groupsThe anticardiolipin antibody is organ-nonspecific, occurring in many autoimmune diseases such as rheumatoid arthritis and SLE, and in general population low levels of ACL (IgG < 4.3 μ/ml, IgM < 3.55 μ/ml and polivalent ACA < 4.55 μ/m) are described as well as positivity for IgM and IgG ACL around 4.6%.[3] In agreement we found no positivity of ACL in control group. Moreover, we detected positivity and mean level of ACL significantly higher in patients with hyperprolactinemia, treated or not, corroborating a previous study that reported positive results of ACL in 27% of women with hyperprolactinemia, with no symptoms of autoimmune diseases.[4] The result of the ACL presented here, as well as the knowledge that hyperprolactinemic individuals have significantly higher percentage of total lymphocytes and CD2-positive cells[2] and that levels of PRL in SLE patients are higher than in the general population[12] reinforce the immunomodulating role of prolactin, interacting with environmental and genetic factors for the development of autoimmune diseases. Increased levels of ATPO were detected in approximately half of patients with treated or untreated hyperprolactinemia. The presence of ATPO has already been linked to both hyperprolactinemia[4] and to the low reserve of PRL[5] and hyperprolactinemic women show higher prevalence of thyroid autoimmune disease than the general population.[4] Although some studies suggest that the presence of the ACL in thyroid autoimmune disease may be a non-specific marker for the activation of the immune system, this association is controversial and the influence of these antibodies in the course of thyroidopathy has not been totally explained yet. Data are conflicting regarding this issue, with reports of increased prevalence and no correlation between ACL and autoimmune thyroid disease.[6] The present findings of highest prevalence of ACL and ATPO in patients with hyperprolactinemia reinforce the concern over possible development of autoimmune diseases in prolonged hyperprolactinemia. However, the correlation between these factors remains unclear, suggesting the need for further studies.

Association between Systemic Lupus Erythematosus, Rheumatoid Arthritis, Hyperprolactinemia and Thyroid Autoantibodies

Hyperprolactinemia (hyperPRL) has been associated with autoimmune rheumatic disorders and the presence of thyroid autoantibodies (tAb). The interrelation between these variables was the focus of this prospective study. The study assessed six groups of individuals: 26 with systemic lupus erythematosus (SLE), 20 with rheumatoid arthritis (RA), 28 with tAb (tAb+), 14 with untreated hyperprolactinemia (hyperPRL), 10 with treated hyperPRL, and a control group (n = 28). Prolactin (PRL), free thyroxin, TSH, antibodies against thyroglobulin (TgAb), thyroid microsomal antigen (MsAb) and/or thyroid peroxidase (TPOAb) were determined in all patients. Those with hyperPRL had macroprolactin investigated by the polyethylene glycol (PEG) precipitation method. PRL (ng/mL) levels in the SLE, RA, and tAb+ groups were, respectively, 21.3 +/- 12.6, 11.5 +/- 7.4, and 12.5 +/- 8.6, and were significantly greater in the SLE group (p = 0.006) than in the controls (12.5 +/- 6.5) and in the other groups. Five patients had hyperPRL: three with SLE, one with RA, and one with tAb+. Macroprolactinemia was detected in three of the untreated hyperprolactinemic patients and in the hyperprolactinemic patient of the tAb+ group. Positivity for any of the tAb was 15% in the SLE, 15% in the RA, 57.1% in the untreated hyperPRL, 10% in the hyperPRL on treatment, and 3.6% in the control group. The presence of antibodies was significantly more frequent in the untreated hyperPRL group than in the control group (p = 0.001). The results indicate that the PRL level is higher in SLE patients and that in the presence of hyperPRL there is increased prevalence of antithyroid antibodies, evidencing the association of PRL and autoimmunity and pointing to the appropriateness of assessing and monitoring the progress of these markers in patients affected by these disorders.

Outcome of pregnancies in women with treated or untreated hyperprolactinemia

The outcome of 103 pregnancies in 64 women with constant hyperprolactinemia was evaluated. Seventy-eight pregnancies had been induced with bromocriptine and 25 occurred without any treatment. In all, 66% of the pregnancies ended in delivery, 17% in miscarriage, 10% in tubal pregnancy and 7% in induced abortion. The pregnancy of women with untreated hyperprolactinemia was more frequently ectopic when compared to those in women treated by bromocriptine. Obstetric complications as well as signs of tumoral enlargement during pregnancy were rare in hyperprolactinemic women treated or untreated with bromocriptine. Untreated hyperprolactinemia as a risk factor in tubal pregnancy is proposed.

The Natural History of Untreated Hyperprolactinemia

Clinical Research Center and Depamnents of Internal Medicine, Obstetrics and Gynecology, and Radiology, Universny of Iowa, Iowa City, Iowa

To treat or not to treat: hyperprolactinemia

ABSTRACT Physicians are overtreating hyperprolactinemia, says Michele C. S. Koppelman, MD, of the National Institute of Child Health and Development (NICHD), Bethesda, Md.At the recent meeting of the Endocrine Society in San Francisco, Koppelman reported on a follow-up study of 25 female patients with long-standing, untreated hyperprolactinemia. Most of the patients' conditions remained stable or improved clinically over the years, and some showed apparent regression of pituitary adenomas.On average, the onset of the patients' symptoms predated the follow-up study by 11.3 years and the diagnoses of hyperprolactinemia by 5.3 years. Half of the women had had initial serum prolactin levels higher than 200 ng/mL, and two thirds had had levels exceeding 100 ng/mL. In 15 patients, skull x-ray films and polytomography of the pituitary fossa had shown abnormalities in the sella turcica. None of the patients with these abnormalities had visual field defects, but several had headaches.At the