ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2015) 38 P306 | DOI: 10.1530/endoabs.38.P306

Unique clinical picture in patients with X-linked acrogigantism

Donato Iacovazzo1, Sian Jose2, Benjamin Bunce3, Richard Caswell3, Laura Cristina Hernández-Ramírez1, Francisca Caimari1, Francesco Ferraù1, Sonal Kapur1, Plamena Gabrovska1, Mary N Dang1, Celia Rodd4, Mary Lee Vance5, Claudia Ramírez6, Moises Mercado6, Anthony P Goldstone7, Michael Buchfelder8, Christine Burren9, Pinaki Dutta10, Catherine Choong11, Timothy Cheetham12, Federico Roncaroli13, Sian Ellard3, Julian Sampson2 & M Korbonits1

1Endocrinology, Barts and The London School of Medicine, London, UK; 2Institute of Medical Genetics, Cardiff University, Cardiff, UK; 3Molecular Genetics, University of Exeter, Exeter, UK; 4Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada; 5Endocrinology, University of Virginia, Charlottesville, USA; 6Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades Centro Médico Nacional Siglo XXI, IMSS, UNAM, Mexico City, Mexico; 7Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust, London, UK; 8Neurosurgery, University of Erlangen-Nürnberg, Erlangen, Germany; 9Paediatric Endocrinology, University Hospitals Bristol NHS Foundation Trust, Bristol, UK; 10Endocrinology, PGIMER, Chandigarh, India; 11Pediatric Endocrinology & Diabetes, Princess Margaret Hospital for Children, Subiaco, Australia; 12Paediatric Endocrinology, Royal Victoria Infirmary, Newcastle, UK; 13Brain Sciences, Imperial College, London, UK.

Introduction: Non-syndromic pituitary gigantism can result from AIP mutations and the recently identified Xq26.3 microduplications causing X-LAG.

Patients and methods: DNA samples and clinical data were collected from 151 patients with pituitary gigantism. All samples were tested for AIP mutations; AIP mutation negative cases (AIPneg) were screened for Xq26.3 microduplications.

Results: Xq26.3 microduplications were found in ten female simplex patients (6.6%). Two X-LAG cases we previously clinically described (Igreja Hum. Mut. 2010) were included in Trivellin NEJM 2014 and Daly ERC 2015. Median age at onset (1.6 years (0.9–2.6)) and diagnosis (3.8 years (2.4–6)) was earlier compared to AIPpos (onset: 15 years (12.5–15); diagnosis: 16 years (13–20)) and AIPneg cases (onset: 15 years (11.2–16); diagnosis: 18 years (14–23)), P<0.0001. Mean IGF-1 was 3×ULN±1.17, not different from AIPpos (2.2±1.33) and AIPneg cases (2.6±1.37). 90% of patients had hyperprolactinaemia, as opposed to 23% of AIPpos and 31% of AIPneg cases (P<0.005). Eight patients had macroadenomas, two had pituitary hyperplasia. Five patients were first managed with medical treatment (SSAs and/or dopamine agonists) with poor results. Seven macroadenoma patients had surgery, resulting in remission in three, the other four also received radiotherapy. Among these, remission was achieved in one; two patients are controlled on SSAs, and one on pegvisomant. One patient was treated with intrasellar Yttrium implants and is now controlled with SSAs. One hyperplasia case was treated with total hypophysectomy; the other did not respond to SSAs and her disease is now controlled on pegvisomant. No other tumours or manifestations other than gigantism were found, including the two oldest patients (now aged 29 and 50 years).

Conclusions: The clinical picture in X-LAG is distinct, being characterised by a very young age at onset, high prevalence of affected females and associated hyperprolactinaemia. Treatment of these patients is challenging, although multi-modal treatment can eventually lead to the successful control of GH excess.

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