Cause Of Hyperprolactinemia Research Articles

Relationship between TSH, T4, T3 and Prolactin in overweight and lean Sudanese PCOS Patients

Objectives: to examine the role of PCOS in alteration of TSH, T4, T3 and prolactin as well as correlating the outcome to obesity. Methods: One Hundred female patients with PCOS based on Rotterdam 2003 criteria. Together with fifty healthy volunteer females included as controls. Serum levels of Thyroid Stimulating Hormone (TSH), Thyroxine (T4), Triiodothyronine (T3) and prolactin were tested in the two groups. Body mass index (BMI) evaluated to be a part of the correlation. Results: A significant increase was found in TSH and prolactin (P 0.05). Conclusions: PCOS linked to hypothyroidism, and the latter may cause hyperprolactinemia in the same individual. Association of hyperprolactinemia and PCOS entails assessment of alternative causes of hyperprolactinemia, and this assessment should include thyroid function.

Hyperprolactinemia due to spontaneous intracranial hypotension.

OBJECT Spontaneous intracranial hypotension is an increasingly recognized cause of headaches. Pituitary enlargement and brain sagging are common findings on MRI in patients with this disorder. The authors therefore investigated pituitary function in patients with spontaneous intracranial hypotension. METHODS Pituitary hormones were measured in a group of 42 consecutive patients with spontaneous intracranial hypotension. For patients with hyperprolactinemia, prolactin levels also were measured following treatment. Magnetic resonance imaging was performed prior to and following treatment. RESULTS The study group consisted of 27 women and 15 men with a mean age at onset of symptoms of 52.2 ± 10.7 years (mean ± SD; range 17-72 years). Hyperprolactinemia was detected in 10 patients (24%), ranging from 16 ng/ml to 96.6 ng/ml in men (normal range 3-14.7 ng/ml) and from 31.3 ng/ml to 102.5 ng/ml in women (normal range 3.8-23.2 ng/ml). In a multivariate analysis, only brain sagging on MRI was associated with hyperprolactinemia. Brain sagging was present in 60% of patients with hyperprolactinemia and in 19% of patients with normal prolactin levels (p = 0.02). Following successful treatment of the spontaneous intracranial hypotension, hyperprolactinemia resolved, along with normalization of brain MRI findings in all 10 patients. CONCLUSIONS Spontaneous intracranial hypotension is a previously undescribed cause of hyperprolactinemia. Brain sagging causing distortion of the pituitary stalk (stalk effect) may be responsible for the hyperprolactinemia.

Reference ranges for serum total and monomeric prolactin for the current generation Abbott Architect assay.

Exclusion of macroprolactinaemia, a well-recognised interference, as the cause of hyperprolactinaemia is essential to avoid potential misdiagnosis and mismanagement of patients. We have derived gender-specific serum total and post-polyethylene glycol (PEG) precipitation monomeric reference ranges for the recently re-standardised Abbott Architect prolactin assay. Prolactin was measured in serum samples obtained from males (n=49) and females (n=52) using the current Abbott Architect immunoassay pre- and post-PEG precipitation. Gender-specific reference ranges were derived for total and monomeric (post-PEG) prolactin. Routine patients' samples (n=175) with a serum total prolactin >700 mIU/L were screened for macroprolactinaemia to assess classification compared with our previous post-PEG precipitation percentage recovery-based approach. Reference ranges for serum total prolactin were 58-419 mIU/L (male) and 63-561 mIU/L (female). Male and female monomeric prolactin reference ranges were 32-309 mIU/L and 39-422 mIU/L, respectively. Mean (SD) post-PEG percentage recovery of the IS 84/500 prolactin standard was 80 (2.3)%. Of 175 patients' samples screened for macroprolactinaemia, 149 had monomeric prolactin concentrations (median monomeric prolactin=1035 mIU/L; median recovery=83%) above the gender-specific reference range. Monomeric prolactin concentrations (median monomeric prolactin=162 mIU/L; median recovery=20%) in the remaining 26 were within the reference ranges. One patient classified as macroprolactin positive and another classified as macroprolactin negative would not have been identified as such using the previous recovery-based approach. The use of post-PEG monomeric reference ranges not only identifies hyperprolactinaemia due solely to macroprolactinaemia but has the added advantage of identifying patients who have simultaneous true monomeric hyperprolactinaemia and elevated concentrations of macroprolactin.

Serum prolactin in advanced chronic liver disease.

Hyperprolactinemia is a frequent endocrine disorder with well known harmful effects on the reproductive system and bone metabolism. Besides prolactinomas several drugs and disorders such as renal failure and hypothyroidism have been shown to cause hyperprolactinemia. Based on former studies, liver cirrhosis has also been suggested to cause hyperprolactinemia, while mechanisms have not been identified yet. In this study, we set out to investigate the prevalence and predictors of hyperprolactinemia in 178 patients with liver cirrhosis of different etio-logies. Eighteen out of 178 patients - 7 females and 11 males - displayed elevated serum pro-lactin levels. When patients were excluded who suffered from co-morbidities or took medication that are discussed to potentially interfere with prolactin metabolism, only 3 males displayed increased serum prolactin levels. Prolactin levels were similar in patients with liver cirrhosis of different etiologies. Our data suggest that hyperprolactinemia is not commonly found in patients with liver cirrhosis, but is mostly associated with intake of drugs or presence of comorbidites which are known to potentially cause hyperprolactinemia. We thus hypothesize that in contrast to former studies liver cirrhosis is not a common cause of hyperprolactinemia and that in the absence of co-morbidities or drugs that are known to potentially increase prolactin levels, marked hyperprolactinemia needs further investigation in patients with liver cirrhosis.

Serum prolactin in advanced chronic liver disease

Hyperprolactinemia is a frequent endocrine disorder with well known harmful effects on the reproductive system and bone metabolism. Besides prolactinomas several drugs and disorders such as renal failure and hypothyroidism have been shown to cause hyperprolactinemia. Based on former studies, liver cirrhosis has also been suggested to cause hyperprolactinemia, while mechanisms have not been identified yet. In this study, we set out to investigate the prevalence and predictors of hyperprolactinemia in 178 patients with liver cirrhosis of different etio­logies. Eighteen out of 178 patients – 7 females and 11 males – displayed elevated serum pro­lactin levels. When patients were excluded who suffered from co-morbidities or took medication that are discussed to potentially interfere with prolactin metabolism, only 3 males displayed increased serum prolactin levels. Prolactin levels were similar in patients with liver cirrhosis of different etiologies. Our data suggest that hyperprolactinemia is not commonly found in patients with liver cirrhosis, but is mostly associated with intake of drugs or presence of comorbidites which are known to potentially cause hyperprolactinemia. We thus hypothesize that in contrast to former studies liver cirrhosis is not a common cause of hyperprolactinemia and that in the absence of co-morbidities or drugs that are known to potentially increase prolactin levels, marked hyperprolactinemia needs further investigation in patients with liver cirrhosis.

Alternative method of macroprolactin evaluation as a cause of hyperprolactinaemia

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Chapter 13 - Hyperprolactinemia and prolactinoma

Prolactinomas are the most frequent pituitary adenomas. In patients with prolactinomas the primary cause of hyperprolactinemia is excessive and autonomic production of prolactin by lactotroph cells. In other conditions, except in case of macroprolactinemia, hyperprolactinemia is secondary to circumstances that stimulate secretion of prolactin by intrinsically normal lactotroph cells, or, rarely, that are the result of decreased clearance of prolactin. In general, cabergoline is the preferred treatment for micro- and macroprolactinomas, because it is more effective with respect to normalization of prolactin levels and reduction of prolactinoma size and because it has fewer side-effects compared to bromocriptine. Recently, it has been suggested that a standardized, individualized, stepwise, dose-escalating regimen of cabergoline may normalize prolactin levels and reduce prolactinoma size in patients who were otherwise considered to be dopamine agonist resistant. In general, the cardiac adverse effects of dopamine agonists reported in Parkinson's disease are not of clinical concern in the treatment of prolactinomas, which are treated with much lower doses. Nonetheless, there is uncertainty with respect to the dose and duration of cabergoline treatment, which requires echocardiographic follow-up. Although withdrawal of dopamine agonists may be considered in patients with prolactinomas well controlled by dopamine agonists, especially in postmenopausal women, recurrence of signs and symptoms may occur in a considerable portion of patients.

Hyperprolactinémies induites par les antipsychotiques : physiopathologie, clinique et surveillance

Hyperprolactinemia is a frequent but neglected adverse effect observed in patients treated with antipsychotic-drugs. In this review, we summarize its physiopathogenetic mechanism, its clinical manifestations in men and women, and the way to manage it. Prolactin is a hormone secreted by lactotroph cells in the anterior pituitary. Its synthesis and release are under the control of peptides, steroids and neurotransmitters. The main inhibitory regulation is made by dopamine, which binds dopamine receptors D2 on the membrane of lactotroph cells. Antipsychotic-drugs block these receptors and thus remove the inhibitory effect of dopamine on prolactin secretion. All antipsychotic-drugs block D2 receptors and all can induce hyperprolactinemia. Nonetheless, it seems that the faster the antipsychotic-drug dissociates from D2 receptors, the lesser the increase of prolactin in the plasma. Another way to explain hyperprolactinemia is the ability of antipsychotic-drugs to cross the blood-brain barrier. The role of their metabolites should also be considered. For these reasons, one can distinguish prolactin-raising (conventional neuroleptics, amisulpride, risperidone) and prolactin-sparing (clozapine, aripiprazole, olanzapine) antipsychotics. An English study showed that 18% of men and 47% of women treated with antipsychotics for severe mental illness had a prolactin level above the normal range. Hyperprolactinemia is in fact more frequent in women than in men. Sometimes it is asymptomatic, but the higher the prolactin level is, the more patients have clinical manifestations. Some symptoms are due to the hypogonadism caused by prolactin, which disturbs hypothalamic-pituitary axis function, and others are due to direct effects on target tissues. Consequently, patients can suffer from sexual dysfunction, infertility, amenorrhea, gynecomastia or galactorrhoea. Data suggest that these symptoms are common, but patients don't mention them spontaneously and clinicians underestimate their prevalence. In the long-term, hypogonadism involves a premature bone loss in men and women. Klibanski and colleagues showed that this loss is significant only in women with hyperprolactinemia associated with amenorrhea. That suggests that prolactin is not directly responsible for this clinical feature. Nevertheless, prolactin seems to be involved in the development of breast cancer, but its role is unclear for prostate cancer. Our review promotes a check-up before beginning a treatment with antipsychotic agents. First, a baseline prolactin level should be measured. It should also include the research on previous treatment with antipsychotic-drugs and the assessment of adverse effects suggestive of hyperprolactinemia. Questioning should finally look for any contra-indication to antipsychotics. Monitoring during antipsychotic treatment has been studied by a group of international experts in psychiatry, medicine, toxicology and pharmacy who made a critical review of clinical guidance on hyperprolactinemia. Experts notify that it is important to check whether patients have any sexual dysfunction, such as loss of libido or menstrual irregularity, and galactorrhoea. Prolactin level should also be controlled after three months of stable dose treatment, or if any clinical feature of hyperprolactinemia appears. If a patient prescribed antipsychotic-drugs has a confirmed prolactin level above the normal range, it is necessary to exclude other causes of hyperprolactinemia. If antipsychotics are really involved, the management should be adapted with the prolactin level and the patient him/herself. To summarize, clinicians can decrease the dose of the antipsychotic or switch to a prolactin-sparing drug. Oral contraceptives can be added whether to prevent pregnancy or to prevent bone loss and osteoporosis. Finally, experts recommend reserving dopamine agonists to treat antipsychotic-induced hyperprolactinemia in very exceptional circumstances as it can worsen the mental illness.

Prevalence of hyperprolactinaemia in female premenopausal blood donors

The prevalence of asymptomatic hyperprolactinaemia has been widely studied in certain populations such as antipsychotic drugs users, infertile women or patients with primary hypothyroidism, but data on the prevalence of hyperprolactinaemia and macroprolactinaemia in the healthy population are very scarce in the literature. We aimed to obtain an unbiased estimation of the prevalence in premenopausal women of: (i) hyperprolactinaemia and (ii) its aetiology, including macroprolactinaemia and stress-related hyperprolactinaemia, while considering simultaneously the use of hormonal contraceptives. Prevalence survey. Three-hundred and ninety-three consecutive premenopausal women reporting spontaneously for blood donation. We performed an exhaustive clinical history and physical examination, establishing the presence of hirsutism, acne, alopecia, menstrual dysfunction and reproductive history. We also measured serum prolactin (PRL) (ruling out macroprolactinaemia when indicated), thyrotrophin, total testosterone, androstendione, sex hormone binding globulin and dehydroepiandrosterone sulphate concentrations. Serum PRL concentrations were increased in 16 of 393 women (4·1% prevalence, 95% CI: 2·1-6·0). The prevalence of macroprolactinaemia was 0·6% (95% CI: 0-1) in the total female blood donor population and was 12·5% (95% CI: 6-31) among hyperprolactinaemic patients. The remaining hyperprolactinaemic women had stress-related hyperprolactinaemia as the more likely aetiology. Finally, the frequency of hyperprolactinaemia was similar in users and nonusers of hormonal contraceptives (4·5% and 3·9% respectively, P=0·209). The prevalence of hyperprolactinaemia in healthy female blood donors is low and is not influenced by the use of hormonal contraceptives. Pathological causes are very rare with stress-related hyperprolactinaemia and macroprolactinaemia being the most frequent causes of hyperprolactinaemia in these women.

Tuberous sclerosis: an uncommon cause of hyperprolactinemia

Tuberous sclerosis: an uncommon cause of hyperprolactinemia

Tuberous sclerosis: an uncommon cause of hyperprolactinemia

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

1376 – Anti-psychotic drugs: a major cause of hyperprolactinemia in a general medicine practice

Introduction Elevated prolactin levels in a general medicine practice invariably raise the suspicion of prolactinoma. Prolactinoma is, a benign adenoma or tumor of the pituitary gland often producing clinically significant levels of prolactin. The finding of elevated prolactin levels is therefore associated with distinct clinical and therapeutic implications. However antipsychotic medications are a major cause of hyperprolactinemia and recognition of this fact may obviate complicated and expensive testing in these patients. Objectives To evaluate the cause of hyperprolactinemia in patients seen in a general medicine practice. Aims To document the role played by anti-psychotic medications in hyperprolactinemia. Methods We identified 364 consecutive office patients who had their prolactin levels routinely measured during an 8 month period. None of these patients were pregnant or lactating. Testing was done by a commercial laboratory and normal levels were defined as 4.0 ng/ml to 15.2 ng/ml. Results Of 364 patients (203(56%) males, 161 (44%)females [ages 26 to 82]), 84 (23%) had elevated prolactin levels. Of these 55(65%) were in patients who were on antipsychotic medications. 29(35%) patients had non-psychiatric cause of hyperprolactinemia. Conclusions Prolactin levels are normally elevated during pregnancy and lactation. Elevated prolactin levels are also seen in many medical conditions including prolactinoma and primary hypothyroidism. Levels may also be elevated with the use of SSRI and SNRI medications and during times of extreme emotional stress. This study shows that the vast majority of patients seen in an general medicine practice with elevated prolactin levels have mental illnesses and are on anti-psychotic medications.

1403 – Hyperprolactinemia and antipsychotic use in psychiatric patients

Hyperprolactinemia is a common, but neglected, adverse effect of conventional and some atypical antipshycotics, such as risperidone, paliperidone, amisulpride and zotepine, usually known as “prolactin-raising” antipshycotics. It occurs in almost 42% of men and in 75% of women with schizophrenia taking risperidone and involves prolactin levels greater than 210-420 mUI/L and 210-520 mUI/L, respectively. Atypical antipsychotics such as clozapine, quetiapine, olanzapine, aripiprazole and ziprazidone have a minimal or no significant effect in prolactin levels, being known as “prolactin-sparing” antipsychotics. This work aims to review the recent literature data concerning the management of the antipsychotic taking patients with hyperprolactinemia, regarding the clinical evaluation, differential diagnosis, therapeutic strategies and international recommendations. With the exception of the “Maudsley Prescribing Guidelines” and the “National Collaborating Centre for Mental Health”, none of the current international psychiatric guidelines recommend a routine baseline prolactin determination, neither periodic prolactin levels without the presence of any hyperprolactinemia symptoms. These symptoms include gynaecomastia, galactorrhoea, menstrual irregularities, infertility, sexual dysfunction, acne and hirsutism. Antipsychotic treatment is the most common cause of hyperprolactinemia in psychiatric patients, although it may also occur during the use of tricyclic and tetracyclic antidepressants, selective serotonin reuptake inhibitors and monoaminoxidase inhibitors, and in the presence of hyphotalamic and pituitary neoplasic disease. Antipsychotic-induced hyperprolactinemia therapeutic strategies may include antipsychotic dosage reduction, switching to a “prolactin-sparing” antipsychotic or using a dopamine receptor agonist (bromocriptine, cabergoline or amantadine). Given the osteopenic/ osteoporosis risk, combined oral contraceptives must be considered in women in fertile age with amenorrhoea for a year.

Hyperprolactinemia

Prolactin (PRL) is an anterior pituitary hormone which has its principle physiological action in initiation and maintenance of lactation. In human reproduction, pathological hyperprolactinemia most commonly presents as an ovulatory disorder and is often associated with secondary amenorrhea or oligomenorrhea. Galactorrhea, a typical symptom of hyperprolactinemia, occurs in less than half the cases. Out of the causes of hyperprolactinemia, pituitary tumors may be responsible for almost 50% of cases and need to be investigated especially in the absence of history of drug induced hyperprolactinemia. In women with hyperprolactinemic amenorrhea one important consequence of estrogen deficiency is osteoporosis, which deserves specific therapeutic consideration. Problem in diagnosing and treating hyperprolactinemia is the occurrence of the ‘big big molecule of prolactin’ that is biologically inactive (called macroprolactinemia), but detected by the same radioimmunoassay as the biologically active prolactin. This may explain many cases of very high prolactin levels sometimes found in normally ovulating women and do not require any treatment. Dopamine agonist is the mainstay of treatment. However, presence of a pituitary macroadenoma may require surgical or radiological management.

Clinical and diagnostic characteristics of hyperprolactinemia in childhood and adolescence

Pituitary adenoma is the most common cause of hyperprolactinemia, which is a rare endocrine disorder encountered in pediatric patient care. Epidemiological and clinical information about hyperprolactinemia in childhood and adolescence is limited. Clinical signs of hyperprolactinemia are very heterogeneous. In girls, disturbances in menstrual function and galactorrhea may be seen, whereas in boys, headache, visual disturbances, delayed pubertal development and hypogonadism are often present. Owing to the ease of ordering a serum prolactin measurement, an evidence-based, cost-effective approach to the management of this endocrine disorder is required. Before a diagnosis of hyperprolactinemia is made, drug use, renal insufficiency, hypothyroidism, and parasellar tumors should be excluded. The main objectives of treatment are normalization of prolactin level, adenoma shrinkage, and recovery from clinical signs related to hyperprolactinemia. In patients with microadenoma, invasive or non-invasive macroadenoma, and even in patients with visual field defects, dopamine agonists are the first-line treatment. Surgical treatment is indicated in patients who are unresponsive or intolerant to medical treatment or who have persistent neurological signs. Radiotherapy should be considered as a supportive treatment for patients in whom surgery fails or medical response is not achieved.

A case of hyperprolactinemia, probably induced by eletriptan

A 25-year-old woman with a severe migraine begins to use a migraine specific agent, eletriptan (40 mg/d). One month later, she had oligomenorrhea and galactorrhea. We ruled out all causes of hyperprolactinemia. To our knowledge, this is the first published postmarketing case report of eletriptan- induced hyperprolactinemia, presented as oligomenorrhea and galactorrhea in a patient. The Naranjo probability scale indicates a probable relationship between hyperprolactinemia and eletriptan therapy.

Hiperprolactinémia em doentes psiquiátricos.

Hyperprolactinemia is a common, but neglected, adverse effect of conventional antipschycotics and of some of the atypical antipshycotics. It occurs in almost 42% of men and in 75% of women with schizophrenia who are treated with prolactin-raising antipshycotics, even though it has aroused minimal interest within the scientific community when compared with extra-pyramidal effects. Conventional antipsychotics and some of the atypical antipsychotics, such as risperidone, paliperidone, amisulpride and zotepine, are frequently associated with the raise in prolactin plasma levels. Because of this increment in prolactin secretion, they are usually known as prolactin-raising antipshycotics. On the contrary, some of the atypical antipsychotics, such as clozapine, quetiapine, olanzapine, aripiprazole and ziprazidone, have a minimal or no significant effect in prolactin levels, being known as prolactin-sparing antipsychotics. Hyperprolactinemia clinical symptoms include gynaecomastia, galactorrhoea, menstrual irregularities, infertility, sexual dysfunction, acne and hirsutism. Some of these symptoms are due to the prolactin direct action in body tissues, while a couple of them can be due to a hypothalamic-pituitary-gonadal axis dysregulation mediated by the elevation of prolactin. Some studies seem to point the evidence of an association between hyperprolactinemia and long-term consequences, such as bone mineral density decrement and breast cancer. However, these results must be confirmed through further studies. Antipsychotic treatment is the most common cause of hyperprolactinemia in psychiatric patients. However, the evidence of a prolactin increased plasma level demands the differential diagnosis with other pathologies, such as hyphotalamic and pituitary neoplasic disease. The management of a patient with antipsychotic-induced hyperprolactinemia must be adapted to each patient and it may include a reduction in the dosage of the offending antipsychotic, switching to a prolactin-sparing antipsychotic or the use of a dopamine receptor agonist, such as bromocriptine, cabergoline and amantadine. Given the osteopenic and osteoporosis risk, combined oral contraceptives must be considered in female patients in fertile age which have amenorrhoea for at least a one year period. With the exception of the Maudsley Prescribing Guidelines and the National Collaborating Centre for Mental Health, none of the current international psychiatric guidelines recommend a routine baseline prolactin determination, neither periodic prolactin levels without the presence of any hyperprolactinemia symptoms.

The importance of measuring macroprolactin in the differential diagnosis of hyperprolactinemic patients

This study investigated the differences in clinical and laboratory features as well as treatment response in 70 outpatients with macroprolactinemia and monomeric hyperprolactinemia treated with dopamine agonists. After precipitation of the patients’ serum samples with poly-ethylene-glycol (PEG), serum prolactin (PRL) levels were measured. We also measured serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol for women and testosterone for men. Clinical symptoms and signs were recorded. All patients received brain magnetic resonance imaging (MRI). After excluding patients with macroadenoma, 66 patients were treated with the dopamine agonist cabergoline. After 1 year, the clinical responses to cabergoline were recorded and PRL levels measured. Of the initial 70 patients with hyperprolactinemia, 15 patients (21.4%) were found to have macroprolactinemia, while the rest had monomeric hyperprolactinemia. The two groups did not differ with regard to galactorrhea, menstrual disturbances or impotence. There were no significant group differences in serum LH, FSH, estradiol or testosterone levels. Patients with macroprolactinemia, however, had a significantly lower infertility rate than those with true hyperprolactinemia (6.7% vs. 32.7%, p=0.005). A greater percentage of macroprolactinemic patients had normal MRI pituitary images than those with hyperprolactinemia (73.3% vs. 34.5%, p=0.029). Compared to those with true hyperprolactinemia, patients with macroprolactinemia were found to have no significant changes in clinical features and PRL levels after 1 year of cabergoline therapy (after PEG precipitation, pre- and post-PRL levels: 59.3±100.2 to 13.8±9.5ng/mL vs. 6.1±5.3 to 5.1±4.3ng/mL, p=0.002). In conclusion, while macroprolactinemia is a common cause of hyperprolactinemia, many clinical and laboratory features cannot be used reliably to differentiate macroprolactinemia from true hyperprolactinemia. Routine screening for all hyperprolactinemic sera with PEG might prevent the unnecessary use of image studies and medical treatments for people with hyperprolactinemia.

Detection of Macroprolactinemia and Molecular Characterization of Prolactin Isoforms in Blood Samples of Hyperprolactinemic Women

Detection of Macroprolactinemia and Molecular Characterization of Prolactin Isoforms in Blood Samples of Hyperprolactinemic WomenProlactin (PRL) circulates in the blood in the form of monomeric prolactin, dimeric prolactin and macroprolactin. Macroprolactin is a common cause of hyperprolactinemia. The objective of this study was to assess the prevalence of macroprolactinemia in hyperprolactinemic women and to undertake the biochemical characterization of macroprolactin. A retrospective cross-sectional study was conducted on one hundred hyperprolactinemic patients. All the sera were subjected to polyethylene glycol (PEG) precipitation and were divided into true hyperprolactinemics (PRL recovery >60%), probable macroprolactinemics (PRL recovery between 40 and 60%) and macroprolactinemics (PRL recovery < 40%). The prevalence of macroprolactinemia was found to be 34%. Sera from each group were further analyzed for isoforms of prolactin by gel filtration chromatography (GFC). The clinical spectrum of presenting complaints in the hyperprolactinemic cohort included oligomenorrhea, galactorrhea and infertility, but the presentation did not differ between macroprolactinemic and truly hyperprolactinemic patients. GFC showed three major PRL isoforms, viz., 23.5 kDa (monomeric), 47 kDa (dimeric) and 150-174.6 kDa (PRL-IgG complexes) along with the medium and heavy weight aggregates of prolactin. The results of the study showed that macroprolactinemia is one of the causes of hyperprolactinemia with high prevalence. It is recommended that all hyperprolactinemic patients be screened for macroprolactinemia.

Macroprolactinemia: new insights in hyperprolactinemia

Hypersecretion of prolactin by lactotroph cells of the anterior pituitary may lead to hyperprolactinemia in physiological, pathological and idiopathic conditions. Most patients with idiopathic hyperprolactinemia may have radiologically undetected microprolactinomas, but some may present other causes of hyperprolactinemia described as macroprolactinemia. This condition corresponds to the predominance of higher molecular mass prolactin forms (big-big prolactin, MW > 150 kDa), that have been postulated to represent prolactin monomer complexed with anti-prolactin immunoglobulins or autoantibodies. The prevalence of macroprolactinemia in hyperprolactinemic populations between 15-46% has been reported. In the pathophysiology of macroprolactinemia it seems that pituitary prolactin has antigenicity, leading to the production of anti-prolactin autoantibodies, and these antibodies reduce prolactin bioactivity and delay prolactin clearance. Antibody-bound prolactin is big enough to be confined to vascular spaces, and therefore macroprolactinemia develops due to the delayed clearance of prolactin rather than increased production. Although the clinical symptoms are less frequent in macroprolactinemic patients, they could not be differentiated from true hyperprolactinemic patients, on the basis of clinical features alone. Although gel filtration chromatography (GFC) is known to be the gold standard for detecting macroprolactin, the polyethylene glycol precipitation (PEG) method has offered a simple, cheap, and highly suitable alternative. In conclusion, macroprolactinemia can be considered a benign condition with low incidence of clinical symptoms and therefore hormonal and imaging investigations as well as medical or surgical treatment and prolonged follow-up are not necessary.