Prolactinomas.

Hyperprolactinemia, defined by a level of serum prolactin above the standard upper limit of normal range, is a common finding in clinical practice and prolactinomas are the main pathological cause. Prolactinomas lead to signs and symptoms of hormone oversecretion, such as galactorrhea and hypogonadism, as well as symptoms of mass effect, including visual impairment, headaches and intracranial hypertension. Diagnosis involves prolactin measurement and sellar imaging, but several pitfalls are involved in this evaluation, which may difficult the proper management. Treatment is medical in the majority of cases, consisting of dopamine agonists, which present high response rates, with a very favorable safety profile. Major adverse effects that should be monitored consist of cardiac valvulopathy and impulse control disorders. Other treatment options include surgery and radiotherapy. Temozolomide may be used for aggressive or malignant carcinomas. Finally, pregnancy outcomes are similar to general population even when dopamine agonist treatment is maintained.

Diagnosis and Management of Breast Milk Oversupply.

Managing breastfeeding problems is an essential part of newborn care. While much is written on breast milk undersupply, little is written on oversupply, sometimes known as hyperlactation or hypergalactia. Infants of mothers with oversupply may have increased or decreased weight gain. Some may have large, frothy stools. They may develop a disordered latch. Mothers may report overly full, leaking breasts. Thyroid function should be assessed. Treatment is mostly anecdotal and includes methods to maintain breast fullness, such as block feedings. Pseudoephedrine and oral contraceptive pills may decrease the supply. Dopamine agonists such as carbergoline can be used as a last resort.

Challenges and pitfalls in the diagnosis of hyperprolactinemia.

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.

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.

Clinical and laboratory features greatly overlap in patients with macroprolactinemia or monomeric hyperprolactinemia.

AIM: The aim of this study was to evaluate the clinical and laboratory features of 64 patients with macroprolactinemia and to compare them to those of individuals with monomeric hyperprolactinemia. METHODS: The study included 64 patients (54 women and 10 men) with macroprolactinemia and 96 patients (70 women and 26 men) with monomeric hyperprolactinemia (32 with prolactinomas). RESULTS: Symptoms related to prolactin (PRL) excess were found in about 44% of individuals from the macroprolactinemia group and in 88.5% of patients with monomeric hyperprolactinemia (P<0.0001). However, the frequency of menstrual disturbances (oligomenorrhea or amenorrhea), galactorrhea and erectile dysfunction did not differ in both groups. In contrast, the association of galactorrhea and menstrual disturbances was significantly more prevalent in women with monomeric hyperprolactinemia. Although mean PRL levels were higher in patients with monomeric hyperprolactinemia (565.9+/-2726.4 vs 113.3+/-94.5 ng/mL, P<0.001), there was a great overlap between both groups. Among macroprolactinemic patients, pituitary magnetic resonance imaging revealed an image suggestive of a microadenoma in 7 (10.9%) and a macroadenoma in 1 (1.6%). Normalization of PRL levels during therapy with dopamine agonists was significantly more frequent in patients with monomeric hyperprolactinemia than in subjects with macroprolactinemia (78.6% vs 32%, P=0.0006). CONCLUSION: Our data show that symptoms related to PRL excess are frequently found in subjects with macroprolactinemia. Moreover, no clinical or laboratory features could reliably differentiate macroprolactinemic patients from those with monomeric hyperprolactinemia. Therefore, the screening for macroprolactin should not be restricted to asymptomatic patients.

Cushing's disease arising from a clinically nonfunctioning pituitary adenoma.

A 49-yr-old woman with a large pituitary tumor leading to visual loss and galactorrhea- amenorrhea was submitted to transcranial pituitary surgery, when a clinically nonfunctioning pituitary adenoma was partially removed. Histopathology and immunohistochemistry confirmed the diagnosis of "non-secreting atypical adenoma." At that time, serum and urinary free cortisol were normal, with low T4 levels and hyperprolactinemia. The patient was discharged on thyroxine and bromocriptine and treated with conventional radiotherapy. Two years later, she presented high free urinary cortisol levels and a positive ACTH response to desmopressin testing on dexametasone 2 mg overnight. A pituitary biopsy confirmed aggressive growth as well as positive immunoreactivity for ACTH, p53, Ki-67, and c-erb-B2. The patient was then treated with radiosurgery on ketoconazole therapy. The overall clinical, laboratory, and pathological data suggest a transition from a clinically nonfunctioning to a hypersecreting ACTH-producing tumor. Putative mechanisms of tumor transformation and the possibility of a silent corticotropinoma evolving into clinical Cushing s syndrome are discussed.

Hypopituitarism and amenorrhea-galactorrhea syndrome caused by thrombosis of both internal carotid artery and giant intrasellar aneurysm: case report.

Giant intra and parasellar aneurysm with a spontaneous thrombosis of internal carotid artery is rare. We report the case of a 34 years old woman presenting a unique giant sellar and parasellar aneurysm associated with hypopituitarism and amenorrhea-galactorrhea syndrome. Computed tomographic scans and magnetic resonance images were suggestive of a sellar tumor with a cystic component. Digital cerebral angiography showed spontaneous thrombosis of a intrasellar and parasellar carotid artery aneurysm and left internal carotid artery in the neck. A transseptal endoscopic biopsy was done and confirmed a thrombosed aneurysm. No other surgical treatment was required in this patient but permanent endocrinological treatment was necessary.

Hiperprolactinemias e prolactinomas: uma atualização / Hyperprolactinemias and prolactinoms: an updating

A hiperprolactinemia é uma entidade clínica freqüente que pode representar processos patológicos importantes, como os prolactinomas, ou refletir apenas anormalidades funcionais que envolvem a hipófise, como a utilização de algumas drogas que competem com ou que inibem a dopamina, causando a elevação sérica de prolactina e suas conseqüências, tais como: amenorréia, galactorréia, infertilidade, diminuição da libido e sintomas do chamado "efeito de massa", como cefaléia e distúrbios visuais, em caso específico de tumores. O tratamento é principalmente clínico, com agonistas da dopamina, durante um período prolongado. A neurocirurgia e a radioterapia têm suas indicações restritas, porém são muito utilizadas em casos de falha do tratamento clínico. O objetivo dos autores no presente trabalho é promover uma revisão atualizada sobre o assunto.

[Disappearance of the radiographic image of a macroprolactinoma after treatment with bromocriptine]. / Desaparición de la imagen radiográfica de un macroprolactinoma con bromocriptina.

A young woman with amenorrhea-galactorrhea induced by a prolactin (PRL) secreting pituitary macroadenoma, was treated with bromocriptine 5 mg/day per os. Serum PRL levels were normal at 6 weeks and menstruation appeared at 8 weeks of treatment. When twenty months of treatment were completed, a tomographic study of the pituitary was unable to show any enlargement. Controversies related to macroprolactinomas treatment are discussed and it is suggested that treatment with dopamine agonists must be the elective treatment for patients with macroprolactinoma.

Desaparición de la imagen radiográfica de un macroprolactinoma con bromocriptina / Radiographic image description, of a macroprolactinoma with bromocriptine

Se informa a una paciente con síndrome de amenorrea galactorrea ocasionado por un macroadenoma hipofisario secretor de prolactina (PRL), el cual fue tratado médicamente con 5 mg/día de bromocriptina, normalizándose las cifras de PRL a las seis semanas y reapareciendo la menstruación a las ocho semanas de tratamiento. Después de 20 meses de tratamiento, se realizó un segundo estudio tomográfico de la hipófisis el cual fue normal. Se revisan las controversias en el manejo de los macroprolactinomas y se propone el manejo médico con agonistas dopaminérgicos como el tratamiento electivo para estas pacientes

Consenso acerca de la recuperación del ciclo mentrual y fertilidad posterior al uso de anticonceptivos hormonales / A consensus upon menstrual cyclo and fertility restoration after hormonal contraception

Se revisa la frecuencia de amenorrea y esterilidad a la suspención de anticonceptivos hormonales, concluyéndose que ésta es baja. Destaca que la población más susceptible de presentar alteraciones en este sentido es aquella con anteceentes de disfunción hipotálamo-hipofisaria