Macroprolactinemia in a Patient with Invasive Macroprolactinoma: A Case Report and Minireview

Hindawi Publishing Corporation Case Reports in Endocrinology Volume 2013, Article ID 634349, 5 pages http://dx.doi.org/10.1155/2013/634349 Case Report Macroprolactinemia in a Patient with Invasive Macroprolactinoma: A Case Report and Minireview Atanaska Elenkova, Zdravka Abadzhieva, Nikolai Genov, Vladimir Vasilev, Georgi Kirilov, and Sabina Zacharieva ������ ��cad� ��an Pentc�e��� Clinical Centre o� �ndocrinolog� and �erontolog�� �edical �ni�ersit���o�a� � �dra�e �treet� ���� �o�a� Bulgaria Correspondence should be addressed to Atanaska Elenkova; Received 3 December 2012; Accepted 24 December 2012 Academic Editors: J. P. Frindik and H. Hattori Copyright © 2013 Atanaska Elenkova et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Macroprolactin, the high-molecular prolactin isoform, is considered to be an inactive in vivo product with extrapituitary origin. Patients with macroprolactinemia are usually asymptomatic, with negative pituitary imaging. Based on these data, most authors do not recommend treatment and long-term followup in subjects with macroprolactinemia. However, there is evidence for overlapping clinical features among subjects with hyperprolactinemia due to monomeric or “big big” PRL isoform. Case Presentation. We present a 35-year-old female patient with secondary amenorrhea, mild obesity, hirsutism, headache and blurred vision. Hormonal evaluation revealed an extreme hyperprolactinemia (PRL = 10 610 mIU/L) almost exclusively due to macroprolactin isoform (MPRL = 10 107 mIU/L; recovery aer PEG precipitation 4.7%) and hypogonadotropic hypogonadism. An invasive pituitary macroadenoma was visualized on MRI, and cabergoline therapy was initiated. Disappearance of clinical signs and symptoms, normalization of gonadotropin levels, and restoration of regular ovulatory menstrual cycles aer 1 year of treatment are arguments in favor of preserved-macroprolactin bioactivity in this case. e signi�cant decrease in MPRL levels and tumor volume in response to dopamine agonist therapy is suggestive for the tumoral origin of this isoform. Conclusions. Although macroprolactinemia is considered to be a benign condition, pituitary imaging, dopamine agonist treatment, and prolonged followup should be recommended in some particular cases. 1. Background ree different isoforms of circulating human prolactin (PRL) have been identi�ed: a monomeric (“little” PRL with a molecular weight of 23 kDa), a 50 kDa “big” PRL, and a highmolecular form (>l00 kDa), termed “big big” or macroprolactin [1, 2]. In physiological conditions the monomeric PRL accounts for 80–90%, the “big” PRL represents less than 10%, and macroprolactin (MPRL) represents a negligibly small percentage of the total PRL amount. Macroprolactinemia is a state of hyperprolactinemia characterized by predominant presence of the high-molecular PRL isoform in the circulation which has been considered biologically nonactive [3, 4]. On the other hand, there are published data about overlapping of the main hyperprolactinemia-related clinical symptoms in subjects with true hyperprolactinemia and those with macroprolactinemia [5–11]. is paper describes a case of invasive pituitary macroadenoma and secondary amenorrhoea with extremely elevated PRL levels almost exclusively due to macroprolactinemia successfully treated with dopamine agonist. A minireview of the literature on this topic is also included in the paper as a separate section. 2. Case Presentation We present a 35-year-old female patient complaining of secondary amenorrhea, mild obesity, hirsutism, severe headache, and blurred vision. She had menarche at 15 followed by regular periods till the age of 20 when an oligomenorrhea occurred. Aer gynaecological consultation, treatment with Dydrogesterone (duphaston) was started using a standard dosage regimen: 10 mg daily from the 16th 2 Case Reports in Endocrinology T 1: Main clinical, laboratory, and instrumental �ndings. Parameters Prolactin, PRL (mIU/mL) Macroprolactin, MPRL (mIU/mL) Recovery, % Tumor size (mm) (on MRI) Body mass index, BMI (kg/m2 ) Main patient’s complaints Hirsutism, Ferriman-Gallwey score Menstrual cycle Pelvic ultrasound 1 35-year-old female patient Baseline 1-Year Follow-up1 10 610 295 10 107 106 4.7% 36% 21 × 13 mm 9 × 8 mm 31.2% 28.6% Severe headache; blurred vision No headache; normal vision 13 13 Secondary amenorrhea Regular Anovulation Normal Treatment with Cabergoline 2.0 mg/week; cumulative dose = 96 mg. to the 25th day of the menstrual cycle. A good therapeutic response was initially achieved, and the patient could maintain regular menstrual cycle for about one year. Aer that, recurrence of oligomenorrhea occurred in spite of the twofold increase of Didrogesterone dose. e treatment was discontinued which resulted in a permanent amenorrhea. e patient was referred to the University Hospital of Endocrinology where full clinical and hormonal evaluations were carried out. Physical examination revealed mild hirsutism (Ferriman-Gallwey score = 13), visceral obesity (BMI = 31.2%), and no galactorrhea. Hormonal analysis: Venous blood samples were taken in the morning, aer 30 minutes of rest (sampling referred to the second and third admissions made during the early follicular phase of the menstrual cycle) (Table 1). Serum PRL, E2, LH, FSH, and Testosterone (T) levels were measured by the use of commercially available kits “Immunotech” (Beckman-Coulter, France) with analytical sensitivity: for PRL < 14.5 mIU/L; for LH and FSH < 0.2 IU/L; for E2 < 22.02 pmol/L; and for T < 0.087 nmol/L, respectively; reference ranges (female subjects): PRL < 550 mIU/L; LH (follicular phase): 2,0–10,0 U/L; FSH (follicular phase): 1,0–10,0 U/L; E2 (follicular phase): 90–550 pmol/L; T: 0.3–3.5 nmol/L. A sensitive immunoradiometric assay (intra- and interassay CV: 2.8% and 8%, resp.,) was used for PRL detection in which concentrations were determined twice, in the serum immediately aer thawing and in the supernatant aer precipitation with polyethylene glycol (PEG 8000). Percentage of macroprolactin (MPRL) was calculated using the following formula: MPRL% = (PRL serum − PRL supernatant) × 100/PRL serum. Results of the PEG precipitation test were presented as a recovery % (free PRL) = 100% − MPRL%. Macroprolactinemia was considered present when a recovery % was <40%, and monomeric PRL levels aer PEG treatment were within the normal range [12– 15]. Hormonal analysis showed normal thyroid function (TSH = 0.85 mIU/L; FT4 = 10.3 pmol/L), testosterone levels (T = 2.4 nmol/L), extremely high serum PRL levels (PRL = 10 610 mIU/L), and suppressed gonadotropins levels (LH = 1,1 U/L; FSH = 1,2 U/L; E2 = 235 pmol/L). PEG precipitation test revealed that hyperprolactinemia was almost exclusive due to the presence of the high-molecul (...truncated)