Falsely low serum prolactin in two cases of invasive macroprolactinoma.

Department of Clinical Endocrinology, Hannover Medical School, 30623 Hannover, Germany.
Pituitary (Impact Factor: 2.67). 02/2002; 5(4):261-5. DOI: 10.1023/A:1025334001748
Source: PubMed

ABSTRACT The differential diagnosis of tumors at the base of the skull comprises meningiomas, neurinomas, gliomas, metastatic carcinomas, chordomas, epidermoids, and pituitary adenomas. About half of the pituitary adenomas are prolactinomas which are unique in a sense that medical therapy causes rapid tumor shrinkage and symptomatic improvement. We report on two patients in which the diagnosis of an invasive macroprolactinoma was masked by apparently low prolactin levels caused by a high-dose hook effect in the chemiluminometric assay. The first case a 49 year old male with impairment of hearing on the left side was presented in the Department of Otorhinolaryngology. A massive invasively growing tumor was demonstrated on a cranial MRI. Endocrine tests revealed normal pituitary function and normoprolactinemia. The patient underwent debulking surgery, occipitocervical fusion because of destruction of the first cervical vertebra and subsequent irradiation. The histopathological diagnosis was invasive prolactinoma. A repeat prolactin (PRL) sample, which was assayed using serial dilutions, revealed a real PRL level of 89,700 ng/ml. Dopamine agonist therapy was initiated under which PRL levels declined in parallel with tumor size. The second case a 40 year old male was presented with acute visual loss. Cranial MRI showed a large tumor at the base of the skull. Based on a transnasal biopsy, the preliminary diagnosis was a poorly differentiated carcinoma for which emergency irradiation was performed. Endocrine tests demonstrated partial hypopituitarism and moderate hyperprolactinemia. Hydrocortisone was substituted and dopamine agonist therapy was started because of moderate hyperprolactinemia. The final histopathological diagnosis was invasive prolactinoma. A repeat PRL sample assayed in serial dilution demonstrated an apparent rise in PRL with a maximum value of 6,460 ng/ml. Under dopamine agonist therapy, PRL declined to normal values, tumor size decreased and cranial nerve palsies disappeared. The apparently falsely low prolactin levels in the initial work-up of both patients were caused by a high-dose hook effect in the PRL assay. Serial dilutions of serum PRL samples is, therefore, mandatory in the diagnostic work-up of patients with large invasive tumors at the base of the skull. This avoids unnecessary aggressive and dangerous treatment like surgery or radiotherapy in cases where pharmacological treatment may be the choice.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Giant prolactinoma are rare tumours, representing only 2-3 % of all prolactin-secreting tumours and raising special diagnostic and therapeutic challenges. Based on several considerations developed in this review, their definition should be restricted to pituitary adenomas with a diameter of 40 mm or more, significant extrasellar extension, very high prolactin concentrations (usually above 1000 µg/L), and no concomitant GH or ACTH secretion. Giant prolactinomas are much more frequent in young to middle-aged men than in women with a male to female ratio of about 9:1. Endocrine symptoms are often present but overlooked for a long period of time and diagnosis is eventually made when neurological complications arise from massive extension into the surrounding structures, leading to cranial nerve palsies, hydrocephalus, temporal epilepsy or exophthalmos. Prolactin concentrations are usually in the range of 1,000 to 100,000 µg/L, but may be underestimated by the so-called 'high dose hook effect'. As in every prolactinoma, dopamine agonists are the first-line treatment allowing rapid alleviation of neurologic symptoms in the majority of the cases, a significant reduction of tumour size in ¾ of the patients and PRL normalization in 60-70%. These extensive tumours are usually not completely resectable and neurosurgery has significant morbidity and mortality. It should therefore be restricted to acute complications such as apoplexy or leakage of cerebrospinal fluid (often induced by medical treatment), or to patients with insufficient tumoral response or progression. Irradiation and temozolomide are useful adjuvant therapies in a subset of patients with aggressive/invasive tumours which are not controlled despite combined medical and surgical treatments. Because of these various challenges, we advocate a multidisciplinary management of these giant tumours in expert centres.
    European Journal of Endocrinology 02/2014; · 3.14 Impact Factor
  • Source
    02/2012; , ISBN: 978-953-51-0166-6
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Giant prolactinomas are an unusual subset of macroprolactinomas and are more commonly found in men. The goal of this review is to propose a giant prolactinoma definition and discuss the available therapeutic options for biochemical and tumour volume control. METHODS: A comprehensive search of all published studies was performed between April and November 2012 in electronic databases (PubMed and Ovid). RESULTS: A giant prolactinoma should be defined as an adenoma with a maximum diameter of more than 4 cm that is associated with serum prolactin above 5300 mIU/L. Regarding treatment, cabergoline is the preferred dopamine agonist for medical management of giant prolactinomas because of its excellent efficacy and tolerability. Normalisation of prolactin level and significant tumour reduction may be achieved in the majority of patients. Combined therapy, particularly cabergoline and surgery, may be necessary due to the large tumour load. Radiotherapy and temozolomide may be used for patients with aggressive giant prolactinomas in whom tumour volume control is not achieved with cabergoline and surgery. CONCLUSION: There is a scarcity of large studies about the management of giant prolactinoma. Cabergoline is the first-line treatment. However, caution should be exercised when comparing efficacy rates among the different treatment modalities due to the variability in study design and data quality. In this scenario, a "standard" definition for giant prolactinomas and larger series may be helpful to assess the real efficacy and safety of each therapeutic modality. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 05/2013; · 3.40 Impact Factor