PMC4503293_01
Patient family tree. Our patient's family tree a at initial consultation and b at last follow-up after discovery of several other symptomatic and asymptomatic relatives who were subsequently confirmed to carry the same c.784-9G > A MEN1 mutation as our proband
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Fig1
Initial family history revealed an inter-generational multiply consanguineous family (Fig. 1a), with one maternal first half-cousin once removed treated with cabergoline at age 18 years and one paternal first half-cousin once removed undergoing transsphenoidal surgery at age 45 years, both for macroprolactinomas. Subsequent questioning revealed a history of renal stones and primary hyperparathyroidism in our patient's mother and two maternal aunts, as well as a history consistent with MEN-1 (macroprolactinoma, primary hyperparathyroidism and gastrinoma) in his deceased maternal grandmother (Fig. 1b) who had been managed by our adult colleagues in the United Kingdom two decades earlier.
Patient MRI images and biochemistry results. Serial T1-weighted MRI images with gadolinium contrast demonstrating appearances of our patient's giant prolactinoma a-b at diagnosis, c-d at first progression, e-f after first debulking, g-h at second progression, i-j after second debulking and radiotherapy, k-l at last follow-up. Arrows indicate tumor mass whilst arrowheads indicate sites of progression. m Serial prolactin concentrations (black line) and corresponding cabergoline dose (gray shaded area) in our patient since diagnosis illustrating multiple biochemical relapses despite multimodality treatment
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Fig2
Magnetic resonance imaging revealed a large, avidly-enhancing heterogeneous sellar and suprasellar mass merging with the pituitary gland, compressing the optic chiasm and encasing both internal carotid arteries with a maximal transverse diameter of 5.5 cm (Fig. 2a-b). Despite an initial excellent PRL reduction in response to therapy, his tumor became extremely drug-resistant despite cabergoline dose escalation to 3.5 mg/week (Fig. 2m). Multiple relapses threatening vision required two transcranial interhemispheric debulking procedures and adjuvant proton beam irradiation, with the second debulking and radiotherapy undertaken at the Children's Hospital of Philadelphia (CHOP, Fig. 2c-l).