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.

Thickened pituitary stalk associated with a mass in the sphenoidal sinus: an alarm to suspect hypophysitis by immunoglobulin g4?

Introduction Hypophysitis is a chronic inflammation of the pituitary gland of complex and still incompletely defined pathogenesis. It belongs to the group of non-hormonesecreting sellar masses, sharing with them comparable clinical presentation and radiographic appearance. Objectives Describe the case of immunoglobulin G4 (IgG4)-related hypophysitis presenting as a mass in the sphenoid sinus. Resumed Report A 40-year-old Brazilian man had a diagnosis of central diabetes insipidus since 2001 associated with pituitary insufficiency. Pituitary magnetic resonance imaging revealed a centered pituitary stalk with focal nodular thickening and the presence of heterogeneous materials inside the sphenoid sinus. The patient was treated with testosterone replacement therapy. Laboratory results revealed increased IgG4 serum. Conclusion IgG4-related hypophysitis should be considered in patients with pituitary insufficiency associated with sellar mass and/or thickened pituitary stalk. IgG4 serum measurement for early diagnosis of IgG4-related hypophysitis should be performed.

Alterações neuroendócrinas em pacientes com traumatismo cranioencefálico / Neuroendocrine disorders in traumatic brain injury patients

O traumatismo cranioencefálico (TCE) corresponde a uma das principais causas de morte em adultos jovens. Alguns pacientes com TCE podem ser vítimas de várias alterações hormonais decorrentes do trauma. Algumas são facilmente reconhecíveis, como diabetes insipidus, enquanto outras podem passar despercebidas inicialmente, como a deficiência do hormônio do crescimento (GH). As alterações neuroendócrinas após a ocorrência de trauma podem cursar com deficiências da hipófise anterior, da posterior ou de ambas, acometer apenas um eixo hormonal ou vários e, ainda, ser transitórias ou permanentes. A grande maioria dos pacientes que apresentam disfunção neuroendócrina foi vítima de traumas considerados moderados ou graves pela escala de Glasgow. No entanto, a maioria dos estudos não evidenciou relação entre a gravidade da lesão e a ocorrência de alteração hipofisária pósTCE. As deficiências hipofisárias devem ser tratadas precocemente, uma vez que déficits hormonais hipofisários dificultam a recuperação dos pacientes traumatizados, constituindo-se em fator de pior prognóstico. Apesar da frequência com que ocorrem os TCE, existem poucos estudos a respeito das complicações neuroendócrinas decorrentes...

Traumatic brain injury (TBI) is one of the main causes of death in young adults. Some cases of TBI could lead to the development of easily recognizable diabetes insipidus. In other cases it can lead to alterations in the endocrine axis that are more difficult to notice at the beginning and that can occur together with other hormone deficiencies. The majority of patients with neuroendrocrine dysfunction were TBI victims with a Glasgow Coma Scale scores of 3-13 (moderate and severe trauma). However, previous studies did not show correlationships between the severity of injury and pan-hypopituitarism after TBI. The pituitary disorders have to be treated as soon as possible because it makes the recovery of TBI patients more difficult and lead to a worse prognosis. Despite the number of studies about TBI, actually there are only a few studies concerning the secondary neuroendocrine complications...

Transitory increase in creatinine levels after parathyroidectomy: evidence of another action of the parathyroid glands? / Alteração transitória da creatinina após paratireoidectomia: evidência de outra ação das glândulas paratireoides?

OBJECTIVE: Little information is available on glomerular function changes after surgical treatment of primary hyperparathyroidism. The acute effects of some head and neck operations on renal function were studied. MATERIAL AND MATHODS: Retrospective analysis of changes in creatinine levels and estimated glomerular filtration rate (eGFR) after surgery. Preoperative values were compared with values available until 72 hours after the operation. RESULTS: In tertiary hyperparathyroidism, mean preoperative and postoperative eGFR values were 57.7 mL/min and 40.8 mL/min (p < 0.0001), respectively. A similar decrease was observed after parathyroidectomy for primary hyperparathyroidism, from 85.4 mL/min to 64.3 mL/min (p < 0.0001). After major head and neck procedures, there was a slight increase in eGFR (from 94.3 mL/min to 105.4 mL/min, p = 0.002). CONCLUSION: Parathyroidectomy may be followed by a transient decrease in eGFR that is not often observed in other head and neck operations.

OBJETIVO: Há pouca informação sobre alterações da função glomerular após o tratamento cirúrgico do hiperparatireoidismo primário. O efeito agudo sobre a função renal foi estudado após algumas operações em cirurgia de cabeça e pescoço. MATERIAIS E MÉTODOS: Análise retrospectiva dos níveis de creatinina e da taxa de filtração glomerular estimada (eGFR). Os valores pré-operatórios foram comparados aos valores disponíveis até 72 horas após a operação. RESULTADOS: No hiperparatireoidismo terciário, os valores médios pré e pós-operatórios da eGFR foram 57,7 mL/min e 40,8 mL/min (p < 0,0001), respectivamente. O decréscimo após paratireoidectomia por hiperparatireoidismo primário foi de 85,4 mL/min para 64,3 mL/min (p < 0,0001). Após operações maiores de cabeça e pescoço, houve leve elevação da eGFR (de 94,3 mL/min para 105,4 mL/min, p = 0,002). CONCLUSÕES: A paratireoidectomia pode ser seguida de uma redução transitória na eGFR que não é frequentemente observada após outras operações em cabeça e pescoço.

Síndrome de Cushing como complicação do tratamento de líquen plano oral erosivo / Cushing´s Syndrome as a complication of treatment of oral lichen planus

O líquen plano oral (LPO) é uma doença mucocutânea inflamatória crônica relacionada com alterações na imunidade mediada por células T. Diversos medicamentos têm sido utilizados no tratamento desta doença, especialmente nas formas erosivas e ulcerativas, com resultados variados. O objetivo deste trabalho é descrever e discutir um caso clínico de líquen plano oral erosivo tratado com corticóide sistêmico que resultou em Síndrome de Cushing, que se manteve com o uso de corticóide tópico.

Oral lichen planus (OLP) is a chronic mucocutaneous inflammatory disease involving T cells-mediated immunity. Several drugs have been used to treat OLP, specially the erosive and ulcerative forms, with varying results. The aim of this paper was to describe and discuss one clinical case of erosive oral lichen planus treated with systemic corticosteroids that resulted in Cushing´s syndrome that maintained with topical corticosteroid.

Pituitary tumor apoplexy / Apoplexia em tumor hipofisário

Pituitary tumor apoplexy is a medical emergency due to acute infarction or hemorrhage in the pituitary gland. In this review, the authors discuss the sellar anatomy, the pituitary gland and adenomas' vascularization and the general aspects of the syndrome such as its ethiopatogenesis, predisposing factors, clinical features, treatment and prognosis.

A apoplexia em tumor hipofisário é uma emergência médica decorrente do infarto agudo ou hemorrágico na glândula hipófise. Nesta revisão os autores discutem a anatomia da região selar, a vascularização da hipófise e adenomas hipofisários, e demais aspectos da síndrome como etiopatogenia, fatores predisponentes, quadro clínico, tratamento e prognóstico.

Mixed germ cell tumor of the pituitary-hypothalamic region presenting as craniopharyngioma: case report and review of the literature / Tumor misto de células germinativas da região hipotálamo-hipofisária apresentando-se como craniofaringioma: relato de caso e revisão da literatura

Craniopharyngiomas and germ cell tumors (GCT) may affect the pituitary-hypothalamic region during childhood. Although different in origin, their clinical and radiological features may be similar. In this article we present a 5-year-old girl with clinical and radiological findings (computer tomography calcification) that were initially considered as craniopharyngioma. However clinical outcome, blood and cerebral spinal fluid tumoral markers, and results from anatomopathology and immunohistochemistry disclosed a mixed GCT. This case report highlights that some clinical features and radiological findings of pituitary-hypothalamic tumors may be misdiagnosed as craniopharyngioma mainly when there is a mature teratoma with cartilaginous tissue differentiation.

Craniofaringiomas e tumores mistos de células germinativas (TCG) podem acometer a região hipotálamo-hipofisária durante a infância. Embora tenham diferentes origens, as manifestações clínicas e achados radiológicos podem ser semelhantes. Nosso objetivo é relatar o caso de uma paciente de 5 anos de idade, cujas manifestações clínicas e achados radiológicos (presença de calcificações à tomografia computadorizada [TC]) foram inicialmente considerados como provável craniofaringioma. No entanto, a piora clínica progressiva, marcadores tumorais séricos e liquóricos elevados, assim como os resultados do estudo anatomopatológico e imunoistoquímico revelaram tratar-se de TCG. Este caso enfatiza que alguns achados clínicos e radiológicos de tumores da região hipotálamo-hipofisária podem ser erroneamente diagnosticados como craniofaringiomas, principalmente se houver presença de teratoma maduro com diferenciação em tecido cartilaginoso.

Cabergolina como alternativa no tratamento clínico de prolactinonas: experiência na intolerância/resistência à bromocriptina / Cabergoline as an alternative in prolactinomas clinical treatment: experience in the bromocriptine intolerance/resistance

Cabergolina (CAB, Pharmacia) é um agonista dopaminérgico derivado do ergot com longa ação após administração oral, que já tem demonstrado ser de utilidade para o tratamento da hiperprolactinemia. Quarenta e cinco pacientes (36 mulheres, 9 homens) com prolactinomas (27 micro, 18 macro), intolerantes e/ou resistentes à bromocriptina (BRC) foram tratados com dose semanal de CAB de 0,25 a 7mg (mediana: 1mg) dividida de 1 a 7 administrações. O tratamento, em compassionate basis, variou de 1 a 38 meses (mediana: 12 meses). Entre os 38 pacientes com intolerância persistente à BRC (sintomas digestivos, n=27; hipotensão postural, n=13; congestão nasal, n=5; manifestações psiquiátricas, n=4; retenção urinária, n=1), somente 5 permaneceram intolerantes à CAB (sintomas digestivos, n=2; hipotensão postural, n=2; congestão nasal, n=1). Todos aqueles que toleraram bem a BRC também o fizeram com CAB. Onze casos alcançaram normalização da prolactina durante o uso de BRC. Estes pacientes e outros 19 também resolveram a hiperprolactinemia com CAB. Entretanto, somente 3 dos 7 pacientes resistentes (dose diária de BRC de 10 a 25mg) tiveram a prolactina sérica normalizada durante o uso de CAB. Redução tumoral foi documentada por ressonância mag-nética ou tomografia computadorizada em 7 macroprolactinomas durante o tratamento com CAB. Assim, devido à sua excelente eficácia, tolerabilidade e comodidade posológica, a CAB apresenta-se como importante alternativa no tratamento clínico dos prolactinomas.

Alteraçöes sexuais na epilepsia: resultados de uma avaliaçäo multidisciplinar / Sexual disorders in epilepsy: results of a multidisciplinary evaluation

Onze pacientes do sexo masculino com epilepsia e queixa de alteração foram submetidos a avaliação multidisciplinar. A média de idade foi 27 anos (20-34), a duração média da epilepsia foi 19 anos (0,5-32) e a frequência média das crises foi duas por semana (0-7). Dez pacientes apresentavam crises parciais e um, mioclônicas. Dez pacientes recebiam drogas antiepilépticas (difenil-hidantoína - 1, carbamazepina - 8, clonazepam -3, clobazam -2, valproato -3, vigabatrina -1). Segundo os critérios do DSM III - R, as queixas foram disfunção erétil (9), redução da libido (4), froteurismo (4), inibição do orgasmo (3), ejaculação precoce (3), fetichismo (2), voyeurismo (2), exibicionismo (2), pedofilia (1) e aversão sexual (1). A avaliação endocrinológica mostrou hipogonadismo hipogonadotrófico em dois pacientes. A avaliação urológica revelou disfunção erétil orgânica em outros dois. Em um paciente a alteração sexual foi considerada psicogênica. Em seis pacientes não foi possível estabelecer diagnóstico etiológico definitivo. Este estudo mostra que a alteração da sexualidade na epilepsia é multifatorial e necessita de abordagem multidisciplinar.

Impact of recombinant human growth hormone (RH-RG) treatment on psychiatric, neuropsychological and clinical profiles of GH deficient adults

Background: Untreated GH-deficient adults have a diversity of dysfunctions (e.g. reduced muscle strength, emotional instability during strress, depressive symptons) that may cause deletrious effects on quality of life, and may be positively influenced by recombinant human growth hormone (rh-GH) therapy. Aim: To evaluate the impact of a clinical intervention with rh-GH therapy on GH-deficient adults. Method: The physical, psychiatric and neuropsychological status of 9 GH-deficient adults was determined before and after the administration of rh-GH (0.250 IU/Kg/week) in a double blind placebo-controlled trial for six months. Patients then received rh-GH for a further period of 6 months and their status was re-evaluated. Results: Rh-GH was significant better than placebo at 6th month (p<0.05), producing increased serum Insulin like growth factor-I (IGF-1) levels, reduced body mas index (BMI) and body fat, increased lean body mass and water, reduced wains/hip ratio and increased energy expenditure. The rh-GH therapy was also significantly better than placebo on depressive features as measured by the Hamilton Depression Scale (17-itens) (p=0.0431) and the Beck Depression Inventory (p=0.0431). Neuropsychological evaluations showed significant improvements in measures of Attention: Digit Backward (p=0.035), Verbal Flency (FAS) (p=0.02) and Cognitive Efficiency (WAIS-R tests): Vocabulary (p=0.027), Picture Arrangements (p=0.017), and Comprehension (p=0.01) following rh-GH therapy. Conclusion: The clinical, psychiatric, and neuropsychological impairements of untreated GH-deficient adults can be decresed by rh-GH therapy.

Macroprolactinomas masquerading as pseudoprolactinomas: the high dose hook effect

Serum prolactin level is very important to discriminate prolactiomas from other causes of hyperprolactinemia, specially pseudoprolactinomas. We describe two hyperprolactinemic men: case 1 is 28y old with headache, left eye visual loss and ptosis associated with a huge mass of the sellar region who was operated on elsewhere by transcranial route. These was no visual amelioration. Two months after surgery the patient was admitted to our Unit with impairment of right eye vision. Galactorrhea was found and imaging evaluation showed persistence of a large tumor. After blood sampling for hormonal assessment, oral bromocriptine (10 mg/day) was started and a dramatic right visual improvement was noticed. However, basal prolactin by immunoradiometric assay (IRMA) was 97mug/L. Due to the clinical signs and response suggesting prolactinoma, prolactin level was reassessed. A two-incubation and serial dilution of the same sample up to 1:1,200 disclosed a prolactin value of 25,572 mug/L. Case 2 is 20y old with headache, bitemporal hemianopsia, seizures and hypogonadism secondary to a giant tumor arising from the sellas region. Initial serum prolactin level measured by IRMA was 104 mug/L, which after two-incubations and dilutions up to 1:200 disclosed a value of 17,736 mug/L; clinical treatment was instituted with good results. In order to avoid unnecessary surgeries, we recommend a two-incubation procedure in routine prolactin determinations when IRMA is used.