Adenoma hipofisário (prolactinoma) proveniente da disfunção hormonal da prolactina: revisão de literatura / Pituitary adenoma (prolactinoma) from prolactin hormonal dysfunction: literature review

Os adenomas hipofisários são, geralmente, tumores benignos com características de hipersecreção ou hipersecreção hormonal, diagnosticados conforme o crescimento tumoral, síndromes de hiperprodução, deficiência da secreção dos hormônios, alterações visuais e cefaleias. A hiperprolactinemia é a produção excessiva de prolactina (PRL), apresentando níveis elevados de prolactina sérica, o que resulta no aparecimento de adenomas lactotróficos (prolactinomas), predominante em mulheres com idade fértil. O prolactinoma é um adenoma hipofisário secretor de prolactina, classificado como adenoma hipofisário microadenoma, em mulheres, e macroadenoma, em homens. Nas mulheres, o prolactinoma apresenta indícios como galactorreia, amenorreia, disfunção sexual e infertilidade. Em homens, a sintomatologia pauta-se em ganho de peso, disfunção erétil e infertilidade. Os exames laboratoriais, como dosagem de prolactina sérica, e os exames de imagem, principalmente a ressonância magnética (RM), são importantes para confirmar o diagnóstico e a escolha da terapêutica ideal. O tratamento medicamentoso inicial dá-se por drogas agonistas dopaminérgicos (AD), sendo padrão-ouro a cabergolina (CAB), em razão da eficácia e dos efeitos colaterais reduzidos. Quando agonistas dopaminérgicos não surtem efeitos, indica-se submissão a tratamento cirúrgico. Em casos de tumores agressivos ou prolactinomas malignos, indica-se radioterapia. Sendo assim, este artigo corresponde a uma revisão bibliográfica que visa relacionar o adenoma hipofisário (prolactinoma) com a produção excessiva de prolactina (PRL).

Pituitary adenomas are generally benign tumors with characteristics of hypersecretion or hormonal hypersecretion, diagnosed according to tumor growth, hyperproduction syndromes, deficiency in hormone secretion, visual changes and headaches. Hyperprolactinemia is the excessive production of prolactin (PRL), with high levels of serum prolactin, resulting in the appearance of lactotrophic adenomas (prolactinomas), predominant in women of childbearing age. Prolactinoma is a prolactin-secreting pituitary adenoma, classified as pituitary adenoma microadenoma in women and macroadenoma in men. In women, prolactinoma shows signs such as galactorrhea, amenorrhea, sexual dysfunction and infertility. In men, the symptoms are based on weight gain, erectile dysfunction and infertility. Laboratory tests, such as serum prolactin levels, and imaging tests, especially magnetic resonance imaging (MRI), are important to confirm the diagnosis and choose the ideal therapy. The initial drug treatment is done by dopaminergic agonist drugs (AD), with cabergoline (CAB) being the gold standard, due to the reduced efficacy and side effects. When dopaminergic agonists have no effect, submission to surgical treatment is indicated. In cases of aggressive tumors or malignant prolactinomas, radiotherapy is indicated. Thus, this article corresponds to a bibliographic review that aims to relate pituitary adenoma (prolactinoma) with excessive prolactin production (PRL).

Profil épidémiologique et aspect à l'IRM des pathologies hypophysaires au CHU de Brazzaville / Epidemiological profile and MRI appearance of pituitary pathologies at Brazzaville University Hospital

Objectif :Décrire le profil épidémiologique et remnologique des pathologies retrouvées chez les patients adressés pour IRM hypophysaire dans le service d'imagerie médicale du CHU-B. Patients et Méthode :il s'agissait d'une étude transversale descriptive, réalisée au service d'imagerie médicale du CHU de Brazzaville de janvier 2014 à décembre 2018. Tous les patients adressés pour IRM hypophysaire étaient inclus. Les examens ont été réalisés sur une IRM de haut champ de 1,5 Tesla sans et avec injection de produit de contraste. Les données épidémiologiques, l'indication et les résultats retrouvés ont été traitées avec le logiciel Microsoft Excel 2013. Résultats :Cinquante-huit IRM étaient retenues durant la période d'étude. L'âge moyen des patients était de 38,24 ± 11,52 ans avec des extrêmes allant de 12 à 74 ans et un âge médian de 36 ans. Le sexe ratio (F/H) était de 4,8 avec 48 femmes (82,76%). La galactorrhée était le motif de consultation le plus fréquemment retrouvé (21,88% des cas), suivie des aménorrhées (18,75%). L'adénome hypophysaire était la pathologie la plus fréquente devant les selles turciques vides et les kystes de la poche de Rathke. Conclusion :La pathologie hypophysaire est l'apanage du sujet jeune de sexe féminin. Son mode de révélation le plus fréquent est celui de troubles gynécologiques et/ou endocriniens. Les adénomes constituent la quasi-totalité de la pathologie hypophysaire avec une nette prédominance de macroadénome. L'IRM apporte des informations essentielles au diagnostic de cespathologies malgré son accessibilité et sa disponibilité qui restent encore limité.

Non-functioning pituitary adenomas and pregnancy: one-center experience and review of the literature

SUMMARY The usual clinical presentation of non-functioning pituitary adenoma (NFPA) consists of symptoms of mass effect and hypopituitarism. NFPA is a rare condition in young women and an uncommon complication during pregnancy. We present the outcome of three patients with NFPA during pregnancy. Case 1: a 38-year-old woman was referred at 32nd week of spontaneous pregnancy because of diagnosis of a pituitary macroadenoma discovered in the context of progressive visual loss. Hormonal deficiency and hypersecretion were ruled out. Prolactin levels were high as expected. She developed diplopia and severe headache despite the use of dopamine agonists and corticosteroids, so pregnancy was interrupted at 34th week. After an uncomplicated delivery of a healthy newborn, transsphenoidal surgery was performed. The pathology was consistent with a gonadotroph adenoma. She recovered visual field, and remained with normal pituitary function. Postsurgical tumor remnant increased in size during the follow-up. Case 2: a 34-year-old woman was referred due to secondary amenorrhea and galactorrhea. A macroadenoma with suprasellar extension was discovered. Transsphenoidal surgery confirmed a gonadotroph adenoma. Two years after surgery she had a normal pregnancy. Six years after surgery a small tumor recurrence occurred. Case 3: a 23-year-old woman was referred due to a microincidental pituitary adenoma. Laboratory testing was normal. No findings on physical examination. A wait and see approach was decided. Two years after diagnosis, the patient got pregnant without complications. Image remained stable. This article may contribute new cases and provides an extensive review of NFPA during pregnancy.

Spontaneously Regressed Rathke's Cleft Cyst

We report two rare cases of spontaneously regressed Rathke's cleft cyst (RCC). A 52-year-old woman presented with headache. A pituitary hormone study was normal. Brain magnetic resonance imaging (MRI) showed a 0.45-cm³ cystic sellar lesion. The cyst was hyperintense on T1-weighed imaging and hypointense on T2-weighted imaging without rim enhancement, comparable to a RCC. Six months later, brain MRI showed no change in the cyst size. Without any medical treatments, brain MRI 1 year later revealed a spontaneous decrease in cyst volume to 0.05 cm³. A 34-year-old woman presented with headache and galactorrhea lasting 1 week. At the time of the visit, the patient's headache had disappeared. Her initial serum prolactin level was 81.1 ng/mL, and after 1 week without the cold medicine, the serum prolactin level normalized to 11.28 ng/mL. Brain MRI showed a RCC measuring 0.71 cm³. Without further treatments, brain computed tomography 6 months later showed a spontaneous decrease in cyst volume to 0.07 cm³. Another 6 months later, brain MRI revealed that the cyst had remained the same size. Neither patient experienced neurological symptoms, such as headache or visual disturbance, during the period of cyst reduction. The RCCs in both patients underwent spontaneous regression without any medical treatment during a period of 6 months to 1 year. Although spontaneous regression of a RCC is rare, it is still possible and a sufficient follow-up period should be considered.

Spontaneously Regressed Rathke's Cleft Cyst

We report two rare cases of spontaneously regressed Rathke's cleft cyst (RCC). A 52-year-old woman presented with headache. A pituitary hormone study was normal. Brain magnetic resonance imaging (MRI) showed a 0.45-cm³ cystic sellar lesion. The cyst was hyperintense on T1-weighed imaging and hypointense on T2-weighted imaging without rim enhancement, comparable to a RCC. Six months later, brain MRI showed no change in the cyst size. Without any medical treatments, brain MRI 1 year later revealed a spontaneous decrease in cyst volume to 0.05 cm³. A 34-year-old woman presented with headache and galactorrhea lasting 1 week. At the time of the visit, the patient's headache had disappeared. Her initial serum prolactin level was 81.1 ng/mL, and after 1 week without the cold medicine, the serum prolactin level normalized to 11.28 ng/mL. Brain MRI showed a RCC measuring 0.71 cm³. Without further treatments, brain computed tomography 6 months later showed a spontaneous decrease in cyst volume to 0.07 cm³. Another 6 months later, brain MRI revealed that the cyst had remained the same size. Neither patient experienced neurological symptoms, such as headache or visual disturbance, during the period of cyst reduction. The RCCs in both patients underwent spontaneous regression without any medical treatment during a period of 6 months to 1 year. Although spontaneous regression of a RCC is rare, it is still possible and a sufficient follow-up period should be considered.

Hypothyroïdie auto-immune revelée par une galactorrhée à Cotonou

La galactorrhée est l'un des signes révélateurs de l'hyperprolactinémie dont les étiologies sont multiples et variées. Si certaines de ces étiologies sont fréquemment retrouvées, d'autres par contre, telle que l'hypothyroïdie frustre semblent être rares. Nous rapportons ici un cas d'hypothyroïdie frustre auto-immune révélée par une hyperprolactinémie symptomatique qui a été traitée exclusivement avec succès par une hormonothérapie substitutive

Dose Dependent Course of Hyperprolactinemic and Normoprolactinemic Galactorrhea Induced by Venlafaxine

Venlafaxine is a serotonergic and noradrenergic reuptake inhibitor which is used for the treatment of depression. We report a case of galactorrhea in a patient with major depressive disorder after starting treatment with venlafaxine. In particular, we discuss the course of hyper and normoprolactinemic galactorrhea. We managed this side effect initially by dose reduction and further by switching to essitalopram. Physicians should be aware of endocrinologic side effects such as galactorrhea during the serotonin and noradrenaline reuptake inhibitor treatment.

Galactorrhea Probably Related with Switching from Osmotic-release Oral System Methylphenidate (MPH) to Modified-release MPH: An Adolescent Case

Galactorrhea, as an adverse effect of psychotropic medications, usually develops due to high dose of antipsychotics. Selective serotonin reuptake inhibitors (SSRIs) have also been reported to be related to galactorrhea. To the best of our knowledge, no previous study reported galactorrhea with methylphenidate (MPH) use. Hereby, we report a case of an adolescent girl who developed galactorrhea after increasing his modifed-release oral MPH to 50 mg/day while under treatment of sertraline and very low dose haloperidol.

Pituicitoma hipofisario, un hallazgo diagnóstico inusual: reporte de caso / Pituitary pituicytoma, finding of an unusual diagnosis: a case report

Los pituicitomas son tumores infrecuentes de la región selar y supraselar, originados de la neurohipófisis, que suelen ser confundidos con otros tumores al compartir características imaginológicas. Se reporta el caso de una mujer de 36 años de edad, con un pituicitoma en la región selar, que fue diagnosticado como un adenoma hipofisario debido a los hallazgos clínicos e imaginológicos preoperatorios y se realiza una revisión de la literatura.

The Pituicytomas are rare tumors of the sellar and suprasellar region originated of the neurohypophysis and are usually confused with other tumors when sharing imagining features. It is reported a case of a 36 years old woman with pituicytoma in the sellar region that was diagnosed as a pituitary adenoma due to the presurgical clinical and imaging findings and, it is revised the literature.

Galactorreia: como abordar essa complicação incomum após mamoplastia de aumento / Galactorrhea: how to address this unusual complication after augmentation mammoplasty

INTRODUÇÃO: Galactorreia e formação de galactocele após mamoplastia de aumento é uma complicação descrita na literatura, porém a causa permanece desconhecida. MÉTODOS: Apresentamos um caso de uma paciente de 28 anos que foi submetida à cirurgia de mamoplastia de aumento via sulco inframamário, com implante colocado no plano subfascial, que evoluiu, no 7º dia pós-operatório, com galactorreia exteriorizada pela incisão, e propomos um algoritmo para diagnóstico e tratamento de galactorreia após mamoplastias. RESULTADOS: A complicação foi tratada com o uso de agente supressor da lactação, a cabergolina, apresentando boa evolução. CONCLUSÃO: Galactorreia é uma complicação incomum após mamoplastias de aumento, que deve ser sempre lembrada em casos de drenagem de secreção pela incisão por tratar-se de um diagnóstico diferencial com infecção.

INTRODUCTION: Galactorrhea and galactocele formation after breast augmentation are complications reported in the literature, but the cause remains unknown. METHODS: We present a case of a 28-year-old patient who underwent breast augmentation surgery via the inframammary fold with an implant placed in the subfascial plane, which developed galactorrhea from the incision on the seventh postoperative day, and we propose an algorithm for the diagnosis and treatment of galactorrhea after mammoplasties. RESULTS: The complication was treated with the use of a lactation suppressor, cabergoline, presenting good outcomes. CONCLUSION: Galactorrhea is an uncommon complication after augmentation mammoplasties, which should always be considered in cases of secretions from an incision because it is a differential diagnosis for infections.

Reliability of Breast Ultrasound BI-RADS Final Assessment in Mammographically Negative Patients with Nipple Discharge and Radiologic Predictors of Malignancy / 한국유방암학회지

PURPOSE: The purpose of this study was to retrospectively investigate the reliability of breast ultrasound (US) Breast Imaging Reporting and Data System (BI-RADS) final assessment in mammographically negative patients with pathologic nipple discharge, and to determine the clinical and ultrasonographic variables associated with malignancy in this group of patients. METHODS: A total of 65 patients with 67 mammographically negative breast lesions that were pathologically confirmed through US-guided biopsy were included. RESULTS: Of the 53 BI-RADS category 4 and 5 lesions, eight (15.1%) were malignant (six ductal carcinomas in situ, one invasive ductal carcinoma, and one solid papillary carcinoma). There was no malignancy among the remaining 14 category 3 lesions. Malignant lesions more frequently displayed a round or irregular shape (75.0%, 6/8; p=0.030) and nonparallel orientation (33.3%, 4/12; p=0.029) compared to the benign lesions. The increase in the BI-RADS category corresponded with a rise in the malignancy rate (p=0.004). CONCLUSION: The BI-RADS lexicon and final assessment of breast US reliably detect and characterize malignancy in mammographically negative patients with pathologic nipple discharge.

Emerging Hyperprolactinemic Galactorrhea in Obsessive Compulsive Disorder with a Stable Dose of Fluoxetine

While fluoxetine (FXT) is a frequently prescribed selective serotonin reuptake inhibitor (SSRI), with few major side-effects; altered serotonergic transmissions in hypothalamic pathways might lead to a distressing, and often embarrassing, manifestation of galactorrhea by altering prolactin release in those on FXT. We report here a case of FXT-induced hyperprolactinemic galactorrhea developing late into treatment on a stable regimen, who responded well to subsequent replacement with sertraline. Based on present finding, we suggest that while SSRIs may share similar mechanisms of action, there exist individual differences in their effects on prolactin secretion pathways.

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.

Treatment of antipsychotic drug-induced phlegm dampness type amenorrhea by Wuji Powder and a small dose aripiprazole: a clinical study / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To assess the efficacy and safety of Wuji Powder (WP) and a small dose aripiprazole in treatment of antipsychotic drug-induced phlegm dampness type amenorrhea.</p><p><b>METHODS</b>Seventy female schizophrenic patients with antipsychotic drug-induced galactorrhea-amenorrhea syndrome (GAS) were recruited and randomly assigned to the treatment group and the control group, 35 in each group. All patients received antipsychotic drug therapy. Patients in the treatment group additionally took WP, while those in the control group took aripiprazole (at the daily dose of 5 mg, once daily). The therapeutic course for all was 4 weeks. Prolactin levels and obesity indices[body weight, waist aircumstance, body mass index (BMI) and waist-hit ratio (WHR)] were determined before and after treatment. The efficacy was evaluated.</p><p><b>RESULTS</b>The treatment course was completed in 95.71% of patients. The total effective rate of the 33 patients of the treatment group was 93.94% (31/33), while it was 91.18% (31/34) in the 34 patients of the control group. There was no difference in the total effective rate between the two groups (P > 0.05). Prolactin levels in both group after treatment were significantly lower than those of the baseline (P < 0.01). There was no significant difference in prolactin levels between the two groups after treatment (P > 0.05). Compared with before treatment, body weight, BMI, waist circumstance, and waist-hip ratio obviously decreased after treatment, showing significant difference when compared with the control group (P < 0.05). There was no significant difference in body weight, BMI, waist circumstance, and waist-hip ratio in the control group between before and after treatment (P > 0.05).</p><p><b>CONCLUSIONS</b>Both WP and aripiprazole could lower high prolactin levels of schizophrenics with phlegm dampness type amenorrhea. They showed equivalent efficacy. But WP showed more obvious effect in reducing obesity indices.</p>

Hiperprolactinemia / Hyperprolactinemia

A hiperprolactinamia é a alteração hormonal mais comum do eixo hipotalâmico-hipofisário encontrada na prática clinica Apresenta predomínio na população feminina e está associada com a galactorréia, distúrbios mentruais, infertilidade, hipogonadismo e diminuição da libido. As causas são numerosas, sendo o uso de fármacos a causa geral mais comum, e os prolactinomas a causa patológica mais frequente. Atualmente o tratamento farmacológico com agonistas dopaminérgicos tem se apresentado como primeira opção no tratamento, ficando a cirurgia e a radioterapia indicadas a casos reservados. O presente artigo versará sobre os aspectos etilógicos, as manifestações clinicas, investigação diagnóstica e opções de tratamento de hiperprolactinemia.

Radiotherapy for pituitary adenomas: long-term outcome and complications

PURPOSE: To evaluate long-term local control rate and toxicity in patients treated with external beam radiotherapy (EBRT) for pituitary adenomas. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 60 patients treated with EBRT for pituitary adenoma at Korea University Medical Center from 1996 and 2006. Thirty-five patients had hormone secreting tumors, 25 patients had non-secreting tumors. Fifty-seven patients had received postoperative radiotherapy (RT), and 3 had received RT alone. Median total dose was 54 Gy (range, 36 to 61.2 Gy). The definition of tumor progression were as follows: evidence of tumor progression on computed tomography or magnetic resonance imaging, worsening of clinical sign requiring additional operation or others, rising serum hormone level against a previously stable or falling value, and failure of controlling serum hormone level so that the hormone level had been far from optimal range until last follow-up. Age, sex, hormone secretion, tumor extension, tumor size, and radiation dose were analyzed for prognostic significance in tumor control. RESULTS: Median follow-up was 5.7 years (range, 2 to 14.4 years). The 10-year actuarial local control rates for non-secreting and secreting adenomas were 96% and 66%, respectively. In univariate analysis, hormone secretion was significant prognostic factor (p = 0.042) and cavernous sinus extension was marginally significant factor (p = 0.054) for adverse local control. All other factors were not significant. In multivariate analysis, hormone secretion and gender were significant. Fifty-three patients had mass-effect symptoms (headache, dizziness, visual disturbance, hypopituitarism, loss of consciousness, and cranial nerve palsy). A total of 17 of 23 patients with headache and 27 of 34 patients with visual impairment were improved. Twenty-seven patients experienced symptoms of endocrine hypersecretion (galactorrhea, amenorrhea, irregular menstruation, decreased libido, gynecomastia, acromegaly, and Cushing's disease). Amenorrhea was abated in 7 of 10 patients, galactorrhea in 8 of 8 patients, acromegaly in 7 of 11 patients, Cushing's disease in 4 of 4 patients. Long-term complication was observed in 4 patients; 3 patients with cerebrovascular accident, 1 patient developed dementia. Of these patients, 3 of 4 received more than 60 Gy of irradiation. CONCLUSION: EBRT is highly effective in preventing recurrence and reducing mass effect of non-secreting adenoma. Effort to improve tumor control of secreting adenoma is required. Careful long-term follow-up is required when relatively high dose is applied. Modern radiosurgery or proton RT may be options to decrease late complications.