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      Pituitary Macroprolactinoma with Mildly Elevated Serum Prolactin: Hook Effect

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          Abstract

          CASE PRESENTATION A 45-year-old man was admitted in our department with complaints of severe headache for over 6 months period. He also suffered from several problems such as visual field defect, decreased energy and libido, body hair loss, cold intolerance, decreased appetite and dry skin. On physical examination, he was afebrile: blood pressure (BP): 110/70 mm/Hg, pulse rate (PR) :65 beat/min, body mass index (BMI): 24. He had no terminal hair on face or chest and subcutaneous adipose tissue mass had been decreased substantially. Laboratory tests revealed; Hb: 12 g/dL (N: 14–17 g/dL), Total testosterone: 1.2 ng/mL (N: –-10 ng/mL), Luteinizing hormone (LH):3.3MIU/mL (N: 1–8 MIU/mL), Follicle Stimulating hormone (FSH): 1.3 MIU/mL (N: 1–7 MIU/mL), T4:3.4 micg/dL (N:4–12 micg/dL), TSH:0.6 MIU/mL (N: 0.5–5 MIU/mL), Prolactin:100 ng/mL (2–24 ng/mL), serum cortisol:6 MIU/mL (N: 4–21 MIU/mL), IGF1: 162 ng/mL (50–245). Pituitary MRI showed macroadenoma (29*16*14 mm) in left side of sella turcica which bulged to suprasellar cistern with pressure effect on left optic nerve (figure 1, 2). Visual field examination revealed mild temporal hemianopia. These findings are consistent with macroadenoma and mild prolactin elevation. We also observed a discrepancy between pituitary tumor size and prolactin level. The correct estimate of serum prolactin was obtained after serial dilutional measurement. Serum prolactin after dilution was 6470 ng/mL. With these findings pituitary macroprolactinoma was diagnosed and treatment with cabergoline (dopamine agonist) 0.5 mg/week was started. After one month follow-up he had no symptoms, visual field defect was improved and pituitary MRI showed significant shrinkage of tumor. LEARNING POINTS Pituitary adenomas are the most common of sellar masses; prolactinoma accounts for 45% of the pituitary adenomas. Microadenoma is most commonly seen in female and macroadenomas in males (1). Overall, there is a relationship between the level of prolactin and the size of adenomas. Patients with macroprolactinoma often have serum level of prolactin above 1000 ng/mL, but this association is not a rule (2). The hook effect is a cause for discrepancy between prolactin level and the size of the adenoma. Interpretation of serum prolactin concentration between 20 and 200 ng/mL in the presence of macroadenoma due to hook effects should be done with caution. This problem can be avoided by repeating the assay using a 1:100 dilution of serum. (3). Figure 1 Axial (without gadolinium) and sagittal (with gadolinium) views of brain MRI showing pituitary macroadenoma (29*16*14 mm) in left side of sella turcica which bulges to suprasellar cistern with pressure effect on left optic nerve Hook effect is seen in 20% of macroprolactinoma (1). Macroprolactinoma in men tends to occur at an advanced age, with a peak during the fourth decade of life. Symptoms at the time of diagnosis are decreased libido, hypogonadism, headache, and reduced visual field (4). The goals of the treatment of macroprolactinoma are to reduce the size of the mass and improve visual field defect. The first line of treatment is the use of dopamine agonist. Cabergoline has fewer side effects compared with bromocriptine and has a more positive effect on reduction of serum prolactin (5). Dopamine agonists can reduce the size of mass in a few days after initiating therapy (1).

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          Giant prolactinomas in women.

          To characterise distinctive clinical features of giant prolactinomas in women. A multicentre, retrospective case series and literature review. We collected data from 15 female patients with a pituitary tumour larger than 4 cm and prolactin levels above 1000 μg/l and identified 19 similar cases from the literature; a gender-based comparison of the frequency and age distribution was obtained from a literature review. The initial PubMed search using the term 'giant prolactinomas' identified 125 patients (13 women) responding to the inclusion criteria. The female:male ratio was 1:9. Another six female patients were found by extending the literature search, while our own series added 15 patients. The median age at diagnosis was 44 years in women compared with 35 years in men (P<0.05). All cases diagnosed before the age of 15 years were boys. In women (n=34), we observed a minor peak incidence during the third decade of life and a major peak during the fifth decade. Amenorrhoea was a constant feature with seven cases of primary amenorrhoea. In eight women with onset of secondary amenorrhoea before the age of 40 years, the diagnosis was made 2-31 years later (median 9 years) and in all but one because of tumour pressure symptoms. The prolactin levels were above 10,000 μg/l in 15/34 and misdiagnosis due to 'hook effect' occurred in two of them. Eighteen patients were treated with cabergoline; standard doses (<2.0 mg/week) were able to normalise prolactin in only 4/18 patients, and 7/18 patients were resistant to weekly doses ranging from 3.0 to 7.0 mg. Giant prolactinomas are rare in women, often resistant to dopamine agonists and seem to be distributed in two age groups, with a larger late-onset peak.
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            Unusual clinical presentations of giant prolactinomas.

            Giant prolactinomas are rare pituitary tumors which have scarcely been reported in the literature. We describe three men with unusual presenting features of prolactin-secreting giant pituitary adenomas: prolonged and increasingly disturbing intolerance to light and noise; strange behavior and mood disturbances; and rhinorrhea followed by a finding of cerebrospinal fluid leakage. Treatment with dopamine agonist alleviated all symptoms, with concomitant suppression of plasma prolactin levels and a significant reduction in tumor mass. These cases emphasize the importance of considering unusual symptoms in the differential diagnosis of giant prolactinomas and the effectiveness of medical treatment.
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              Giant prolactinoma: case report and review of literature

              “Invasive giant prolactinoma” is a large prolactinoma (>4 cm in dimension) presenting with serum prolactin levels of >1000 ng/dL and mass related clinical symptoms. Here we report a patient with a giant prolactinoma presented with central hypogonadism, suppressed adrenal and thyroid function, supra sellar extension, visual field impairment and high prolactin level. The patient was treated with cabergoline, levothyroxin and prednisolone. After 18 months, tumor size markedly reduced, associated with adrenal function and visual field improvement, but central hypogonadism and secondary hypothyroidism persisted. Previous studies showed normalization of thyrotropin secretion after treatment but it remained low in our patient even after 18 months follow up.
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                Author and article information

                Journal
                Adv J Emerg Med
                Adv J Emerg Med
                AJEM
                Advanced Journal of Emergency Medicine
                Tehran University of Medical Sciences (Tehran, Iran )
                2588-400X
                Autumn 2018
                28 April 2018
                : 2
                : 4
                Affiliations
                [1 ]Department of Internal Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
                [2 ]Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences institute, Tehran University of Medical Sciences, Tehran, Iran.
                Author notes
                [* ]Corresponding author: Mahbube Ebrahimpur, Email: m-ebrahimpur@tums.ac.ir
                Article
                10.22114/AJEM.v0i0.84
                6548154
                © 2018 Tehran University of Medical Sciences

                This open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 License (CC BY-NC 4.0). ( https://creativecommons.org/licenses/by-nc/4.0/)

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                Case Based Learning Points

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