Hyperprolactinemia associated with psychiatric disorders / Hiperprolactinemia asociada con trastornos psiquiátricos

Abstract Hyperprolactinemia may be associated with psychiatric disorders in the context of two scenarios: antipsychotic-induced hyperprolactinemia and psychiatric disorders arising from the medical treatment of hyperprolactinemia. Both situations are particularly common in psychiatric and endocrine clinical practice, albeit generally underestimated or unrecognized. The aim of this article is to provide tools for the diagnosis and treatment of hyperprolactinemia associated with psychiatric disorders to raise awareness, especially among psychiatrists and endocrinologists, so that these professionals can jointly focus on the appropriate management of this clinical entity.

Resumen La hiperprolactinemia puede asociarse con trastornos psiquiátricos en el contexto de dos escenarios: la hiperprolactinemia inducida por antipsicóticos y trastornos psiquiátricos surgidos por el tratamiento médico de la hiperprolactinemia. Ambas situaciones son particularmente comunes en la práctica clínica psiquiátrica y endocrinológica, aunque generalmente subestimadas o inadvertidas. El objetivo de este artículo es proporcionar herramientas de diagnóstico y tratamiento de la hiperprolactinemia asociada a trastornos psiquiátricos, para concientizar particularmente a psiquiatras y endocrinólogos a enfocar en conjunto el manejo apropiado de esta entidad.

Quiste de bolsa de Rathke e hiperprolactinemia, una causa infrecuente de amenorrea primaria / Rathke cleft cysts and hyperprolactinemia, an uncommon cause of primary amenorrhea

El quiste de la bolsa de Rathke es una lesión epitelial benigna de la región selar, formada a partir de remanentes embrionarios. La mayoría de los casos son asintomáticos, aunque pudiera presentarse con cefalea, disfunción hipofisaria y trastornos visuales, muy infrecuentemente como apoplejía hipofisaria. Se presenta el caso de una paciente que, habiendo presentado amenorrea primaria, se le realiza el diagnóstico de quiste de la bolsa de Rathke con hiperprolactinemia, logrando menarquia luego del tratamiento con cabergolina.

Rathke's cyst is a benign epithelial lesion of the sellar region, formed from embryonic remnants. Most cases are asymptomatic although it could present with headache, pituitary dysfunction and visual disorders, very infrequently as pituitary stroke. We present the case of a patient who, having presented primary amenorrhea, is diagnosed with Rathke's cyst with hyperprolactinemia, achieving menarche after treatment with cabergoline.

Importancia de la anamnesis exhaustiva ante una ginecomastia unilateral inexplicada en un niño / Importance of the exhaustive anamnesis to an unexplained unilateral gynecomastia in a child

La ginecomastia es el crecimiento de la mama por un desequilibrio hormonal entre estrógenos y andrógenos. Un crecimiento importante y unilateral requiere descartar patologías subyacentes. Una causa poco frecuente es la traumática, que provoca aumento de tamaño por estimulación repetida. Se presenta el caso de un niño de 6 años con ginecomastia unilateral. Se destaca como único hallazgo en las pruebas complementarias hiperprolactinemia. Rehistoriando, se detecta una continua autoestimulación mamaria manual y oral a través de mordiscos de meses de evolución. Tras el cese del estímulo, se observa la involución de la mama y la normalización de los niveles de prolactina séricos.

Gynecomastia consists of breast enlargement due to a hormonal imbalance between estrogens and androgens. Unilateral and important breast growth requires ruling underlying pathologic disorders out. Mechanical cause is uncommon, causing enlargement by repeated stimulation. We report a 6-year-old boy with unilateral gynecomastia. Hyperprolactinemia is the only abnormal finding at laboratory tests. After repeated inquiries, a continuous breast selfstimulation is detected. Its relation with gynecomastia is verified because prolactin normalizes and breast regressed in further revisions, after stopping stimulus.

Controversial issues in the management of hyperprolactinemia and prolactinomas - An overview by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Prolactinomas are the most common pituitary adenomas (approximately 40% of cases), and they represent an important cause of hypogonadism and infertility in both sexes. The magnitude of prolactin (PRL) elevation can be useful in determining the etiology of hyperprolactinemia. Indeed, PRL levels > 250 ng/mL are highly suggestive of the presence of a prolactinoma. In contrast, most patients with stalk dysfunction, drug-induced hyperprolactinemia or systemic diseases present with PRL levels < 100 ng/mL. However, exceptions to these rules are not rare. On the other hand, among patients with macroprolactinomas (MACs), artificially low PRL levels may result from the so-called "hook effect". Patients harboring cystic MACs may also present with a mild PRL elevation. The screening for macroprolactin is mostly indicated for asymptomatic patients and those with apparent idiopathic hyperprolactinemia. Dopamine agonists (DAs) are the treatment of choice for prolactinomas, particularly cabergoline, which is more effective and better tolerated than bromocriptine. After 2 years of successful treatment, DA withdrawal should be considered in all cases of microprolactinomas and in selected cases of MACs. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) is to provide a review of the diagnosis and treatment of hyperprolactinemia and prolactinomas, emphasizing controversial issues regarding these topics. This review is based on data published in the literature and the authors' experience.

Investigación electrónica del tratamiento de la hiperprolactinemia en Brasil: endocrinólogos contra ginecólogos / Electronic survey of management of hyperprolactinemia in Brazil: Endocrinologists versus gynecologists

Hyperprolactinemia is a frequent condition in clinical practice, responsible for 20-25% of secondary amenorrhea cases. We performed an electronic survey among members of the Brazilian Society of Metabolism and Endocrinology (SBEM) and the Brazilian Federation of Association of Gynecology and Obstetrics (FEBRASGO) to assess diagnostic and therapeutic preferences for management of hyperprolactinemia. Electronic addresses of SBEM and FEBRASGO members were obtained from the directories of these societies, and these members were invited, through electronic messages (e-mail), to answer an online questionnaire that included 10 questions about the treatment of micro and macropro-lactinomas, maximum dose of dopamine agonist, how to exclude primary hypothyroidism and macroprolactinemia, hyperprolactinemia and pregnancy. We received responses to the questionnaire by e-mail from 521 SBEM members and 233 FEBRASGO members. The results of this survey demonstrate that there are many area of agreement between SBEM and FEBRASGO members and most of their responses follow the latest Endocrine Society Guideline. Relative to a survey performed several years ago, our findings show that SBEM members have incorporated some of latest recommendations in this field. The principal issues of concern for both groups are duration of dopamine agonist treatment for patients with microprolactinoma and dopamine agonist withdrawal during pregnancy.

La hiperprolactinemia es una alteración frecuente, siendo responsable del 20 al 25% de los casos de amenorrea secundaria. Se realizó una investigación electrónica entre los miembros de la Sociedad Brasileña de Endocrinología y Metabología (SBEM) y de la Federación Brasileña de Ginecología y Obstetricia (FEBRASGO) para evaluar sus preferencias en el diagnóstico y el tratamiento de la hiperprolactinemia. Las direcciones electrónicas de miembros SBEM y de FEBRASGO se obtuvieron a partir de los directorios de esas sociedades. Se invitó a estos miembros a responder un cuestionario que incluía 10 cuestiones sobre el tratamiento de los micro y macroprolactinomas, dosis máxima del agonista dopaminérgico, hiperprolactinemia e hipotiroidismo primario, macroprolactinemia, prolactinoma y embarazo. Hemos recibido respuestas de 521 miembros de la SBEM y de 233 miembros FEBRASGO. Los resultados demuestran que hay bastantes áreas de concordancia entre los miembros de la SBEM y de la FEBRASGO y que la mayoría de las respuestas están de acuerdo con el último consenso de la Endocrine Society. En cuanto a una encuesta similar realizada hace años, nuestros resultados muestran que los socios de SBEM incorporaron algunas de las últimas recomendaciones propuestas en esa área. Los principales aspectos de interés en ambos grupos son la duración del tratamiento con el agonista dopaminérgico y la retirada del mismo durante el embarazo.

Hiperprolactinemia y disfunción sexual en el varón / Hyperprolactinemia and sexual dysfunction among males

Hyperprolactinemic males usually have a hypoactive libido and less commonly, erectile dysfunction and disturbances of orgasm and ejaculation. Hyperprolactinemia alters the balance between neurotransmitters, neuropeptides and hormones involved in libido and erection, affecting dopaminergic tone. An imbalance between dopamine, that stimulates sexual function and serotonin that inhibits it, is generated. In the central nervous system, hyperprolactinemia inhibits centers controlling sexual desire and erection. At the neuroendocrine level, it decreases GnRH, LH and testosterone pulses, resulting in a hypogonadotrophic hypogonadism. Erection is also inhibited peripheral actions of low testosterone and high prolactin levels. There is a disturbance of penile smooth muscle relaxation and of the parasympathetic sacrum-penis reflex arch. In experimental animals, acute hyperprolactinemia hampers the central erection mechanism whereas in chronic conditions, peripheral disturbances also occur. Even correcting low testosterone levels, the adverse effects of hyperprolactinemia on sexual function persist. The use of dopaminergic agonists may achieve normal prolactin and testosterone levels resulting in normal sexual function. Chronic hyperprolactinemia results in progressive deterioration of sexual function and a higher hypothalamic damage that does not respond to clomiphene. In this situation and in the presence of sellar tumors that destroy gonadotrophic cells, there is indication of androgenic replacement maintaining the use of dopaminergic agonists...

Challenges and pitfalls in the diagnosis of hyperprolactinemia / Desafios e armadilhas no diagnóstico da hiperprolactinemia

The definition of the etiology of hyperprolactinemia often represents a great challenge and an accurate diagnosis is paramount before treatment. Although prolactin levels > 200-250 ng/mL are highly suggestive of prolactinomas, they can occasionally be found in other conditions. Moreover, as much as 25% of patients with microprolactinomas may present prolactin levels < 100 ng/mL, which are found in most patients with pseudoprolactinomas, drug-induced hyperprolactinemia, or systemic diseases. On the other hand, some conditions may lead to falsely low PRL levels, particularly the so-called hook effect, that is an assay artifact caused by an extremely high level of PRL, and can be confirmed by repeating assay after a 1:100 serum sample dilution. The hook effect must be considered in all patients with large pituitary adenomas and PRL levels within the normal range or only modestly elevated (e.g., < 200 ng/mL). An overlooked hook effect may lead to incorrect diagnosis and unnecessary surgical intervention in patients with prolactinomas. Another important challenge is macroprolactinemia, a common finding that needs to be identified, as it usually requires no treatment. Although most macroprolactinemic patients are asymptomatic, many of them may present galactorrhea or menstrual disorders, as well as neuroradiological abnormalities, due to the concomitance of other diseases. Finally, physicians should be aware that pituitary incidentalomas are found in at least 10% of adult population. Arq Bras Endocrinol Metab. 2014;58(1):9-22.

A definição da etiologia da hiperprolactinemia muitas vezes representa um grande desafio e um diagnóstico preciso é fundamental antes do tratamento. Embora níveis de prolactina > 200-250 ng/mL sejam altamente sugestivos de prolactinomas, ocasionalmente podem ser encontrados em outras condições. Além disso, até 25% dos pacientes com microprolactinomas podem apresentar-se com níveis de prolactina < 100 ng/mL, os quais são evidenciados na maioria dos pacientes com pseudoprolactinomas, hiperprolactinemia induzida por drogas ou doenças sistêmicas. Por outro lado, deve-se atentar às condições que podem levar a valores de prolactina falsamente baixos, particularmente o chamado efeito gancho. Este último é um artefato causado por um nível extremamente elevado de PRL e que pode ser confirmado pela repetição do exame após diluição do soro a 1:100. O efeito gancho deve ser considerado em todo paciente com grandes adenomas hipofisários e níveis de prolactina dentro da faixa normal ou apenas moderadamente elevados (p. ex., < 200 ng/mL). Um efeito gancho não detectado pode levar a diagnóstico incorreto e intervenção cirúrgica desnecessária em pacientes com prolactinomas. Outro desafio importante é a macroprolactinemia, um achado comum que precisa ser identificado visto que geralmente não requer tratamento. Ainda que a maioria dos pacientes seja assintomática devido à concomitância de outras doenças, muitos podem apresentar galactorreia ou distúrbios menstruais, bem como anormalidades neurorradiológicas. Finalmente, os médicos devem estar cientes de que incidentalomas hipofisários são encontrados em pelo menos 10% da população adulta. Arq Bras Endocrinol Metab. 2014;58(1):9-22.

Macroprolactinemia e hiperprolactinemia intermediária: manifestações clínicas e achados radiológicos / Macroprolactinemia and intermediate hyperprolactinemia: clinical manifestations and image

OBJETIVOS: Caracterizar as pacientes com valores indeterminados de hiperprolactinemia (teste de PEG para identificação de macroprolactinemias com recuperação entre 30 e 65 por cento) (PRLi) ou macroprolactinemia (PRLm), quanto às características clínicas, como intensidade e variação dos sintomas e presença ou não de tumores no sistema nervoso central. MÉTODOS: Estudo transversal, retrospectivo, de levantamento de prontuários, no qual foram incluídas 24 pacientes com diagnóstico de hiperprolactinemia (PRL>25 ng/dL), em idade reprodutiva, em seguimento em ambulatório de ginecologia endócrina. Foram incluídas 11 pacientes com PRLm e 13 com PRLi. Dos dois grupos (PRLm e PRLi), foram considerados para a análise registros dos dados relativos à idade, à paridade, ao índice de massa corporal, à presença de galactorreia, à infertilidade e ao tumor do sistema nervoso central. Os dados antropométricos foram expressos em média e desvio padrão e, para a comparação entre os grupos quanto à presença de tumor no sistema nervoso central, galactorreia e infertilidade, utilizou-se o teste t de Student. RESULTADOS: A galactorreia foi mais prevalente nas pacientes com PRLi (p=0,01). Setenta por cento das mulheres com PRLi apresentaram microprolactinoma de hipófise, enquanto que este achado foi evidente em 17 por cento das mulheres com PRLm (p=0,04). Dentre as pacientes com PRLm e PRLi, nove não foram investigadas com imagem do sistema nervoso central por apresentarem níveis pouco elevados de prolactina (cinco portadoras de PRLm e quatro de PRLi). Não houve diferença significativa quanto à ocorrência de infertilidade ou de ciclos menstruais irregulares. CONCLUSÕES: Mulheres com hiperprolactinemia intermediária apresentam mais sintomas de galactorreia e maior incidência de tumores do sistema nervoso central do que aquelas com macroprolactinemia.

PURPOSE: To characterize patients with indeterminate values of hyperprolactinemia (PEG test for the identification of macroprolactinemias with recovery between 30 and 65 percent) (PRLi) or macroprolactinemia (PRLm), in relation to clinical characteristics, such as the presence or absence of symptoms, as well as their intensity and variation, and the presence or absence of central nervous system tumors. METHODS: This is a cross-sectional retrospective survey of records of 24 patients with hyperprolactinemia, in reproductive ages, with prolactin >25 ng/dL. Eleven women with PRLm and 13 with PRLi were included. Records from the two groups were extracted for analysis: age, parity, body mass index, presence of galactorrhea, infertility, and central nervous system tumor. Anthropometrics data were expressed as mean and standard deviation. To compare groups regarding the presence of central nervous system tumor, galactorrhea, as well as infertility we used the Student's t-test. RESULTS: Galactorrhea was more prevalent in patients with PRLi (p=0.01). Seventy percent of women with PRLi presented pituitary tumor (microprolactinoma), whereas this finding was evident in 17 percent of the PRLm Group (p=0.04). Among the patients with and PRLm PRLi, nine were not investigated with the image of the central nervous system because they have low levels of prolactin (five carriers and four PRLm PRLi). There were no significant differences regarding the occurrence of infertility or irregular menstrual cycles between groups. DISCUSSION: Women with intermediate hyperprolactinemia present more galactorrhea symptoms as well as central nervous system tumors than women with macroprolactinemia.

Diagnóstico diferencial de los prolactinomas / Differential diagnosis of prolactinomas

La hiperprolactinemia puede deberse tanto a adenomas hipofisarios que secretan prolactina (prolactinomas) como a tumores selares no funcionantes (denominados seudoprolactinomas). La relación entre el tamaño del tumor y el grado de prolactinemia habitualmente permite distinguir los prolactinomas de los seudoprolactinomas; este diagnóstico diferencial es esencial, dado que la terapia es completamente diferente (médica en el primer caso, quirúrgica en el último). La posible coexistencia de otras causas fisiológicas, patológicas o yatrogénicas de hiperprolactinemia, así como artefactos de laboratorio (efecto gancho) y la presencia de variantes de prolactina desprovistas de actividad biológica (macroprolactinas) puede dar origen a errores. Los médicos deben conocer estos trastornos, dado que cuando no se reconocen se pueden realizar tratamientos inapropiados.

Macroprolactin; a frequent cause of misdiagnosed hyperprolactinemia in clinical practice

Macroprolactin is a significant cause of misdiagnosis, unnecessary investigation, and inappropriate treatment in patients with hyperprolactinemia. Its frequency has not been clearly established due to technical difficulties in identifying it. Most laboratories and clinicians are unaware of macroprolactin interferences in prolactin assays. A comprehensive literature search was conducted on the websites of the National Library of Medicine [http:/www.ncbl.nlm.nih.gov] and PubMed Central, the US National Library of Medicine's digital archive of life sciences literature [http:/www.pubmedcentral.nih.gov/]. The data were also looked for in relevant books and journal. Macroprolactin is a non-bioactive prolactin isoform usually composed of a prolactin monomer and an IgG molecule having a prolonged clearance rate similar to that of immunoglobulins. This isoform is clinically non-reactive but it interferes with immunological assays used for the detection of prolactin. There is a need to understand and explore the recent progress in the diagnosis and pathophysiology of macroprolactinemia for improving patient care

Presencia de macroprolactina en sueros con normo e hiperprolactinemia: comparación de dos métodos de detección / Comparison of two techniques to detect the presence of macroprolactin in serum

Background: Macroprolactin is biologically inactive but may be detected by immnoassays. This leads to errors in diagnosis and inadequate treatment of patients with hyperprolactinemia. Aim:To assess two techniques to detect the presence of macroprolactin. Material and Methods: Prolactin was measured by immunoassay in 57 serum samples (from 4 males and 53 females aged33 +/- 13 years), before and after precipitation with polyethyleneglycol (PEG) and separation by ultrafiltration. A significant level of macroprolactin was considered to be present when prolactin detected in the supernatant after PEG precipitation or in the ultrafiltrate was less than 40 percent of the initial concentration of prolactin. Results: Prolactin levels fluctuated from 5 to 411 ng/ml. The percentages of recuperation were independent of the initial prolactin concentration. In 12 and 14 percent of samples, using polyethyleneglycol and ultrafiltration respectively, there was a prolactin recuperation of less than 40 percent. Eight and 11 percent of samples with a prolactin concentration of more than 30 ng/ml, had a recuperation of less than 40 percent using polyethyleneglycol and ultrafiltration respectively. Conclusions: Approximately 10 percent of samples with a prolactin concentration over 30ng/ml have recuperation values suggestive of the presence of macroprolactin. There is a good concordance between precipitation using polyethyleneglycol or ultrafiltration.

Hiperprolactinemia en la población infantojuvenil: un tema vigente / Hyperprolactinaemia in child an adolescent population: a current issue

La hiperprolactinemia constituye la altelaración endocrina más común del eje hipotálamo-hipofisario, aunque su prevalencia en la población infantojuvenil no está aún claramente definida. Además de la Prolactina (PRL) nativa (23Kda), se han descripto numerosas variantes moleculares, algunas de ellas con menor o ausente actividad biológica. Todo proceso que interrumpa la secreción de dopamina, interfiera con su liberación hacia los vasos portales hipofisarios o bloquee los receptores dopaminérgicos de las células lactotróficas, puede causar hiperprolactinemia. Si bien la patología tumoral constituye el diagnóstico de mayor relevancia, los prolactinomas son poco frecuentes en nios y adolescentes, aunque tienen en general una particular presentación clínica: de acuerdo con nuestra experiencia, el retraso puberal puede observarse en aproximadamente el 50% de las pacientes de sexo femenino. En pacientes con hiperprolactinemia asintomática debe evaluarse la presencia de proporciones alteradas de isoformas de PRL. La cromatografía en columna con sephadex G100, la precipitación con suspención de proteína A o con PEG y la ultracentrifugación constituyen los métodos más frecuentemente empleados para la detección de las distintas isoformas de PRL. En nuestra experiencia la B PRL constituyó el 6,6 - 32,6% de la PRL total y la BB PRL contituyó el 40 y el 72% de çesta en este gruo de pacientes. En cuanto al tratamiento por su efectividad y tolerancia, los agonistas dopaminérgicos constituyen la terapia inicial de elección en pacientes en edad pediátrica. La bromocriptina y la cabergolina han sido empleadas y con resultados similares a los de los pacientes adultos.

Mayer-rokitansky-kuster-hauser syndrome with hyperprolactinemia

Mayer-Rokitansky-Kuster-Hauser Syndrome in association with hyperprolactinemia is very rare. An 18-year-old, Saudi, single, virgin female was accompanied by her mother seeking medical advice regarding absent menses. She had normal breasts, normal axillary and pubic hair, normal vulva, urethra, and labial folds, however, the vagina was blind, approximately 2 cm length. Pelvic magnetic resonance imaging showed normal appearing ovaries, a small uterus and small cervix and vagina. Investigations showed initial high serum prolactin of 1,517 mIU/L. Cranial MRI was normal. The patient was diagnosed as mullerian hypoplasia class I American Fertility Society. After an extensive literature search, we present a unique case of concomitant occurrence of MRKH, in the form of mullerian hypoplasia, and hyperprolactinemia

Clinical and etiological profile of hyperprolactinemia--data from a tertiary care centre.

OBJECTIVE: To study the clinical presentation and etiology of hyperprolactinemia, a common disorder encountered in endocrine practice. METHODS: We analyzed the clinical data, hormone profile and imaging reports of 187 females with documented hyperprolactinemia, over a period of 6 years (5 years retrospective analysis and one year prospective study). RESULTS: Majority of the 187 subjects studied presented in 3rd or 4th decade. Galactorrhoea was the commonest presenting symptom occurring in 159 subjects (85%), followed by amenorrhea in 68.9%; both amenorrhea and galactorrhea were seen in 45.4%. A microprolactinoma was demonstrated in 67 patients (35.8%), a nonfunctioning pituitary macroadenoma with stalk hyperprolactinemia occurred in 30 patients (16%) and polycystic ovarian disease was documented in 24 (12.8%). In 52 patients (27.8%) no apparent cause could be ascertained. CONCLUSIONS: Syndrome of amenorrhea and/or galactorrhea is the commonest presentation in hyperprolactinemia. Microprolactinoma was the most frequent identifiable etiology followed by idiopathic and stalk hyperprolactinemia in our series.

La macroprolactina, diagnóstico diferencial de la hiperprolactinemia / The macroprolactina, differential diagnosis of the hyperprolactinaemia

La macroprolactina es una isoforma de la prolactina (PRL) humana que se encuentra en escasa proporción en el plasma y que en algunos pacientes se puede encontrar anormalmente elevada, causando hiperprolactinemia, que puede presentarse como asintomática, pero también presentar sintomatología dada por el exceso de prolactina, también ha sido relacionada a adenomas hipofisiarios. Por esta causa es necesario contar con métodos confiables para su detección y medición. El origen de esta macromolécula, patogenia, regulación hormonal e historia natural aun no está esclarecido, se postula que corresponde a un complejo antigénico IgG-PRL, con bioactibidad reducida.El Gold Standard para la determinación de la macroprolactina es la Cromatografía de filtración en gel, pero su uso se restringe a la investigación por su alto costo y tiempo de desarrollo. Existen otros métodos para su detección, siendo hasta ahora el de precipitación por Polietilenglicol el más aceptado.

Macroprolactin is an isoform of human prolactin (PRL) existing in low doses in plasma. In some patients, prolactine can be found in higher proportion, causing hyperprolactinaemia, in asyntomaticor symptomatic form. This abnormality has been also related to hypophysis adenome, doing necessary to count on reliable methods for its detection and measurement. The origin of this macromolecule, patogenia, hormonal regulation and natural history are not even clear, an antigenic complex IgG-PRL with reduced bioactivity is proposed. The Gold Standard for determination of macroprolactin is gel filtration chromatography, but its high costs and slowness restricts its use toresearch. Other methods for its detection already exist, the Polyethylene glycol precipitation is beingmostly accepted.

effect of age, type and duration of infertility on prolactin concentration in the serum of hyperprolactinemic infertile women

Physiological prolactin level is necessary for normal GnRH secretion and necessary for the maintenance of Inteal function. High prolactin secretion may interfere with the ovulation through inhibition of gonadotropin secretion and with the function of corpus luteum as demonstrated by short luteal phase and decrease progesterone. The objectives of this study were to 1] determine the upper normal value of prolactin hormone in Iraqi women and its range; 2] study the effect of age, type and duration of infertility on prolactin concentration. One hundred forty seven hyperprolactinemic infertile women were enrolled in this study. Those were compared with 125 control women. Serum prolactin hormone were estimated in cycle day 2, 12 and 21. The present study showed that the prolactin level in the serum of hyperprolactinemic infertile patients were significantly higher compared to control group in regard to the age of patients, duration, and type of infertility. There were no significant differences in the level of prolactin hormone between primary and secondary infertile patients. The upper limit for normal prolactin value in small sample Iraqi women was 20ng/ml with a range between 5-9 and 20 ng/ml. Age has a significant effect on prolactin concentration in infertile hyperprolactinemic women. Prolactin increased with increasing the duration of infertility

hook effect in prolactin immunoassays

We describe a young female patient with giant invasive sellar and suprasellar tumor and modest elevation of prolactin to 165 ng/ml normal range 3-29. A diagnosis was made of non functional pituitary adenoma with stalk effect, causing moderate prolactin elevation. A surgery for the removal of the tumor was advised but the patient declined. Treatment with a dopamine agonist was not offered. The patient presented 2 years later with deterioration of her vision and serum prolactin of >16000 ng/ml. Debulking transsphenoidal surgery was performed. The staining of tissue confirmed prolactinoma. Medical treatment with bromocriptine was initiated. We believe that the discrepancy between the 2 values of serum prolactin, is most probably caused by a hook effect in the initial prolactin assay. The mechanism of the hook effect and its occurrence with prolactin immunoassays and methods to eliminate this effect is discussed. Hook effect needs to be suspected in every patient with a giant pituitary or parasellar mass and serum prolactin <200 ng/ml. Assaying a diluted serum will usually unmask this phenomenon and allow accurate diagnosis and management

Del Castello syndrome--an unusual presentation.

Del Castello syndrome in a 28-year-old female, characterised by bilateral galactorrhoea, amenorrhoea and hyperinvoluted uterus, has been described. She had hyperprolactinaemia without any demonstrable pituitary tumour. She was successfully treated with two short courses of bromocriptine and was spontaneously cured after her second conception. The case is discussed with a brief review of the literature.