Acromegaly affects both males and females equally and the average age at diagnosis ranges from 40 to 50 years (up to 5% of cases < the age 20). Due to insidious onset and slow progression, acromegaly is often diagnosed five to more than ten years after its onset. The typical coarsening of facial features include furrowing of fronthead, pronounced brow protrusion, enlargement of the nose and the ears, thickening of the lips, skin wrinkles and nasolabial folds, as well as mandibular prognathism that leads to dental malocclusion and increased interdental spacing. Excessive growth of hands and feet (predominantly due to soft tissue swelling) is present in the vast majority of acromegalic patients. Gigantism accounts for up to 5% of cases and occurs when the excess of GH becomes manifest in the young, before the epiphyseal fusion. The disease also has rheumatologic, cardiovascular, respiratory, neoplastic, neurological, and metabolic manifestations which negatively impact its prognosis and patients quality of life. Less than 15% of acromegalic patients actively seek medical attention for change in appearance or enlargement of the extremities. The presentation of acromegaly is more often related to its systemic comorbidities or to local tumor effects.

The expression of dopamine receptor subtypes has been reported in corticotroph adenomas, and this finding support the possibility for medical treatment of Cushing's disease (CD) with dopamine agonists when conventional treatment has failed. The aim of this study was to evaluate the effectiveness of cabergoline (at doses of up 3 mg/week), alone or combined with relatively low doses of ketoconazole (up to 400 mg/day), in 12 patients with CD unsuccessfully treated by transsphenoidal surgery. After 6 months of cabergoline therapy, normalization of 24 h urinary free cortisol (UFC) levels occurred in three patients (25%) at doses ranging from 2-3 mg/week, whereas reductions ranging from 15.0 to 48.4% were found in the remaining. The addition of ketonocazole to the nine patients without an adequate response to cabergoline was able to normalize UFC excretion in six patients (66.7%) at doses of 200 mg/day (three patients), 300 mg/day (two patients) and 400 mg/day (one patient). In the remaining patients UFC levels did not normalize but a significant reduction ranging from to 44.4 to 51.7% was achieved. In two of the six responsive patients to combination therapy, the weekly dose of cabergoline could be later reduced from 3 to 2 mg. Our findings demonstrated that cabergoline monotherapy was able to reverse hypercortisolism in 25% of patients with CD unsuccessfully treated by surgery. Moreover, the addition of relatively low doses of ketoconazole led to normalization of UFC in about two-thirds of patients not achieving a full response to cabergoline.

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 Keywords Hyperprolactinemia; diagnostic pitfalls; hook effect; macroprolactinemia; pituitary incidentalomas RESUMO 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 outr...