Endocrinology department research profile

Many within the Endocrinology department at Great Ormond Street Hospital are regarded as international opinion leaders, generating research publications of international quality.

Members participate in key roles in national and international Endocrine societies including:

• British Society for Paediatric Endocrinology and Diabetes
• European Society for Paediatric Endocrinology

Research interests include:

• pituitary and midline disorders
• disorders of sex development
• congenital hyperinsulinism
• diabetes mellitus
• adrenal disorders

Areas of developmental endocrinology that we research, including:

• development of the hypothalamus and pituitary (Group leader: Professor Mehul Dattani)
• the regulation of sexual differentiation in the human (Group leader: Prof John Achermann)
• studies in pancreatic islet cell function in the condition of persistent hyperinsulinaemic hypoglycaemia of infancy (Group leader: Dr Antonia Dastamani)

Emphasis on the sexual dimorphism of the growth process and the role of early growth on 'programming' of the endocrine axis.

Current work centres on:

• placental growth hormone production and regulation of secretion
• genetic and environmental determinants of blood pressure in early childhood (Group leader: Professor PC Hindmarsh)
• animal models of inducible hypertension and regulated growth

Areas of neuroendocrinology of growth and pubertal development that we research, including:

• effects of hormonal deficiencies on higher functioning
• perturbations in the growth hormone axis as a result of congenital adrenal hyperplasia
• genetics of hypogonadotrophic hypogonadism
• blood pressure regulation in patients with congenital adrenal hyperplasic

Areas of diabetes that we research, includes:

• psychological consequences of diabetes
• motivational behaviour interventions in diabetes
• inflammatory effects of insulin therapy
• pancreatic beta cell function

Achermann JC, Eugster EA, Shulman DI (2011) Ambiguous genitalia. J Clin Endocrinol Metab 96 (3): 33A, 34A

Al-Mahdi M, Al Mutair A, Al Balwi M, Hussain K (2010) Successful transfer from insulin to oral sulfonylurea in a 3-year-old girl with a mutation in the KCNJ11 gene. Ann Saudi Med 30 (2): 162-4

Alatzoglou KS, Dattani MT (2010) Genetic causes and treatment of isolated growth hormone deficiency-an update. Nat Rev Endocrinol 6 (10): 562-76

Alatzoglou KS, Kelberman D, Cowell CT, Palmer R, Arnhold IJ, Melo ME, Schnabel D, Grueters A, Dattani MT (2011) Increased transactivation associated with SOX3 polyalanine tract deletion in a patient with hypopituitarism. J Clin Endocrinol Metab 96 (4): E685-90

Arnoux JB, de Lonlay P, Ribeiro MJ, Hussain K, Blankenstein O, Mohnike K, Valayannopoulos V, Robert JJ, Rahier J, Sempoux C, Bellanné C, Verkarre V, Aigrain Y, Jaubert F, Brunelle F, Nihoul-Fékété C (2010) Congenital hyperinsulinism. Early Hum Dev 86 (5): 287-94

Bashamboo A, Ferraz-de-Souza B, Lourenço D, Lin L, Sebire NJ, Montjean D, Bignon-Topalovic J, Mandelbaum J, Siffroi JP, Christin-Maitre S, Radhakrishna U, Rouba H, Ravel C, Seeler J, Achermann JC, McElreavey K (2010) Human male infertility associated with mutations in NR5A1 encoding steroidogenic factor 1. Am J Hum Genet 87 (4): 505-12

Bashamboo A, Ledig S, Wieacker P, Achermann JC, McElreavey K (2010) New technologies for the identification of novel genetic markers of disorders of sex development (DSD). Sex Dev 4 (4-5): 213-24

Bennett K, James C, Hussain K (2010) Pancreatic β-cell KATP channels: Hypoglycaemia and hyperglycaemia. Rev Endocr Metab Disord 11 (3): 157-63

Bennett K, James C, Mutair A, Al-Shaikh H, Sinani A, Hussain K (2011) Four novel cases of permanent neonatal diabetes mellitus caused by homozygous mutations in the glucokinase gene. Pediatr Diabetes 12 (3 Pt 1): 192-6

Brain CE, Creighton SM, Mushtaq I, Carmichael PA, Barnicoat A, Honour JW, Larcher V, Achermann JC (2010) Holistic management of DSD. Best Pract Res Clin Endocrinol Metab 24 (2): 335-54

Chan LF, Vaidya M, Westphal B, Allgrove J, Martin L, Afshar F, Hindmarsh PC, Savage MO, Grossman AB, Storr HL (2011) Use of intravenous etomidate to control acute psychosis induced by the hypercortisolaemia in severe paediatric Cushing's disease. Horm Res Paediatr 75 (6): 441-6

Chatterjee SS, Uddin MJ, Rahman AK, Hussain KS, Rahman MS, Hossain MA, Mitra KK, Saha J, Siddiqui KN, Agarwal D (2010) Percuteneous mitral balloon valvuloplasty in patients with post surgical mitral restenosis: result of 70 cases. Indian Heart J 62 (1): 17-20

Cherubini V, Bagalini LS, Ianilli A, Marigliano M, Biagioni M, Carnielli V, Iasonni V, Berbellini A, Hussain K, Gabrielli O (2010) Rapid genetic analysis, imaging with 18F-DOPA-PET/CT scan and laparoscopic surgery in congenital hyperinsulinism. J Pediatr Endocrinol Metab 23 (1-2): 171-7

Cooley SM, Donnelly JC, Geary MP, Rodeck CH, Hindmarsh PC (2010) Maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGF BP-3 and the hypertensive disorders of pregnancy. J Matern Fetal Neonatal Med 23 (7): 658-61

Cooley SM, Donnelly JC, Collins C, Geary MP, Rodeck CH, Hindmarsh PC (2010) The relationship between maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGFBP-3 to gestational age and preterm delivery. J Perinat Med 38 (3): 255-9

El-Khairi R, Martinez-Aguayo A, Ferraz-de-Souza B, Lin L, Achermann JC (2011) Role of DAX-1 (NR0B1) and steroidogenic factor-1 (NR5A1) in human adrenal function. Endocr Dev 20 (): 38-46

Faisal Ahmed S, Achermann JC, Arlt W, Balen A, Conway G, Edwards Z, Elford S, Hughes IA, Izatt L, Krone N, Miles H, O'Toole S, Perry L, Sanders C, Simmonds M, Michael Wallace A, Watt A, Willis D (2011) UK Guidance On The Initial Evaluation Of An Infant Or An Adolescent With A Suspected Disorder Of Sex Development. Clin Endocrinol (Oxf) Apr: 16

Ferraz-de-Souza B, Hudson-Davies RE, Lin L, Parnaik R, Hubank M, Dattani MT, Achermann JC (2011) Sterol O-acyltransferase 1 (SOAT1, ACAT) is a novel target of steroidogenic factor-1 (SF-1, NR5A1, Ad4BP) in the human adrenal. J Clin Endocrinol Metab 96 (4): E663-8

Ferraz-de-Souza B, Lin L, Shah S, Jina N, Hubank M, Dattani MT, Achermann JC (2011) ChIP-on-chip analysis reveals angiopoietin 2 (Ang2, ANGPT2) as a novel target of steroidogenic factor-1 (SF-1, NR5A1) in the human adrenal gland. FASEB J 25 (4): 1166-75

Ferraz-de-Souza B, Lin L, Achermann JC (2011) Steroidogenic factor-1 (SF-1, NR5A1) and human disease. Mol Cell Endocrinol 336 (1-2): 198-205

Flanagan SE, Kapoor RR, Mali G, Cody D, Murphy N, Schwahn B, Siahanidou T, Banerjee I, Akcay T, Rubio-Cabezas O, Shield JP, Hussain K, Ellard S (2010) Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations. Eur J Endocrinol 162 (5): 987-92

Flanagan SE, Patch AM, Locke JM, Akcay T, Simsek E, Alaei M, Yekta Z, Desai M, Kapoor RR, Hussain K, Ellard S (2011) Genome-wide homozygosity analysis reveals HADH mutations as a common cause of diazoxide-responsive hyperinsulinemic-hypoglycemia in consanguineous pedigrees. J Clin Endocrinol Metab 96 (3): E498-502

Flanagan SE, Kapoor RR, Hussain K (2011) Genetics of congenital hyperinsulinemic hypoglycemia. Semin Pediatr Surg 20 (1): 13-7

Flanagan SE, Kapoor RR, Banerjee I, Hall C, Smith VV, Hussain K, Ellard S (2011) Dominantly acting ABCC8 mutations in patients with medically unresponsive hyperinsulinaemic hypoglycaemia. Clin Genet 79 (6): 582-7

França MM, Jorge AA, Alatzoglou KS, Carvalho LR, Mendonca BB, Audi L, Carrascosa A, Dattani MT, Arnhold IJ (2011) Absence of GH-releasing hormone (GHRH) mutations in selected patients with isolated GH deficiency. J Clin Endocrinol Metab 96 (9): E1457-60

Frapsauce C, Ravel C, Legendre M, Sibony M, Mandelbaum J, Donadille B, Achermann JC, Siffroi JP, Christin-Maitre S (2011) Birth after TESE-ICSI in a man with hypogonadotropic hypogonadism and congenital adrenal hypoplasia linked to a DAX-1 (NR0B1) mutation. Hum Reprod 26 (3): 724-8

Garin I, Edghill EL, Akerman I, Rubio-Cabezas O, Rica I, Locke JM, Maestro MA, Alshaikh A, Bundak R, del Castillo G, Deeb A, Deiss D, Fernandez JM, Godbole K, Hussain K, O'Connell M, Klupa T, Kolouskova S, Mohsin F, Perlman K, Sumnik Z, Rial JM, Ugarte E, Vasanthi T, Neonatal Diabetes International Group, Johnstone K, Flanagan SE, Martínez R, Castaño C, Patch AM, Fernández-Rebollo E, Raile K, Morgan N, Harries LW, Castaño L, Ellard S, Ferrer J, Perez de Nanclares G, Hattersley AT (2010) Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis. Proc Natl Acad Sci U S A 107 (7): 3105-10

Gaston-Massuet C, Andoniadou CL, Signore M, Jayakody SA, Charolidi N, Kyeyune R, Vernay B, Jacques TS, Taketo MM, Le Tissier P, Dattani MT, Martinez-Barbera JP (2011) Increased Wingless (Wnt) signaling in pituitary progenitor/stem cells gives rise to pituitary tumors in mice and humans. Proc Natl Acad Sci U S A 108 (28): 11482-7

Gault EJ, Perry RJ, Cole TJ, Casey S, Paterson WF, Hindmarsh PC, Betts P, Dunger DB, Donaldson MD, British Society for Paediatric Endocrinology and Diabetes (2011) Effect of oxandrolone and timing of pubertal induction on final height in Turner's syndrome: randomised, double blind, placebo controlled trial. BMJ 342 (): d1980

Gozzi T, Flück C, L'allemand D, Dattani MT, Hindmarsh PC, Mullis PE (2010) Do centimetres matter? Self-reported versus estimated height measurements in parents. Acta Paediatr 99 (4): 569-74

Guclu M, Lin L, Erturk E, Achermann JC, Cangul H (2010) Puberty, stress, and sudden death. Lancet 376 (9751): 1512

Hindmarsh PC, Bryan S, Geary MP, Cole TJ (2010) Effects of current size, postnatal growth, and birth size on blood pressure in early childhood. Pediatrics 126 (6): e1507-13

Hindmarsh PC (2010) Current indications for growth hormone therapy. Preface. Endocr Dev 18 (): VII

Hussain K (2010) Mutations in pancreatic ß-cell Glucokinase as a cause of hyperinsulinaemic hypoglycaemia and neonatal diabetes mellitus. Rev Endocr Metab Disord 11 (3): 179-83

Hussain K (2010) Congenital hyperinsulinism and neonatal diabetes mellitus. Rev Endocr Metab Disord 11 (3): 155-6

Ismail D, Hussain K (2010) Role of 18F-DOPA PET/CT imaging in congenital hyperinsulinism. Rev Endocr Metab Disord 11 (3): 165-9

Ismail D, Smith VV, de Lonlay P, Ribeiro MJ, Rahier J, Blankenstein O, Flanagan SE, Bellanné-Chantelot C, Verkarre V, Aigrain Y, Pierro A, Ellard S, Hussain K (2011) Familial focal congenital hyperinsulinism. J Clin Endocrinol Metab 96 (1): 24-8

Kapoor RR, Heslegrave A, Hussain K (2010) Congenital hyperinsulinism due to mutations in HNF4A and HADH. Rev Endocr Metab Disord 11 (3): 185-91

Kapoor RR, Flanagan SE, James CT, McKiernan J, Thomas AM, Harmer SC, Shield JP, Tinker A, Ellard S, Hussain K (2011) Hyperinsulinaemic hypoglycaemia and diabetes mellitus due to dominant ABCC8/KCNJ11 mutations. Diabetologia 54 (10): 2575-83

Kayemba-Kay's S, Ribrault A, Burguet A, Gouyon JB, Riethmuller D, Menget A, Hindmarsh PC (2010) Maternal smoking during pregnancy and fetal growth. Effects in preterm infants of gestational age less than 33 weeks. Swiss Med Wkly 140 (): w13139

Khadilkar VV, Khadilkar AV, Kapoor RR, Hussain K, Hattersley AT, Ellard S (2010) KCNJ11 activating mutation in an Indian family with remitting and relapsing diabetes. Indian J Pediatr 77 (5): 551-4

Köhler B, Achermann JC (2010) Update--steroidogenic factor 1 (SF-1, NR5A1). Minerva Endocrinol 35 (2): 73-86

Kumaran A, Kar S, Kapoor RR, Hussain K (2010) The clinical problem of hyperinsulinemic hypoglycemia and resultant infantile spasms. Pediatrics 126 (5): e1231-6

Kumaran A, Kapoor RR, Flanagan SE, Ellard S, Hussain K (2010) Congenital hyperinsulinism due to a compound heterozygous ABCC8 mutation with spontaneous resolution at eight weeks. Horm Res Paediatr 73 (4): 287-92

Männikkö R, Flanagan SE, Sim X, Segal D, Hussain K, Ellard S, Hattersley AT, Ashcroft FM (2011) Mutations of the same conserved glutamate residue in NBD2 of the sulfonylurea receptor 1 subunit of the KATP channel can result in either hyperinsulinism or neonatal diabetes. Diabetes 60 (6): 1813-22

McCabe MJ, Alatzoglou KS, Dattani MT (2011) Septo-optic dysplasia and other midline defects: the role of transcription factors: HESX1 and beyond. Best Pract Res Clin Endocrinol Metab 25 (1): 115-24

O'Riordan SM, Dattani MT, Hindmarsh PC (2010) Cystic fibrosis-related diabetes in childhood. Horm Res Paediatr 73 (1): 15-24

Padidela R, Hindmarsh PC (2010) Mineralocorticoid deficiency and treatment in congenital adrenal hyperplasia. Int J Pediatr Endocrinol 2010 (): 656925

Padidela R, Kapoor RR, Moyo Y, Gilbert C, Flanagan SE, Ellard S, Hussain K (2010) Focal congenital hyperinsulinism in a patient with septo-optic dysplasia. Nat Rev Endocrinol 6 (11): 646-50

Park SE, Flanagan SE, Hussain K, Ellard S, Shin CH, Yang SW (2011) Characterization of ABCC8 and KCNJ11 gene mutations and phenotypes in Korean patients with congenital hyperinsulinism. Eur J Endocrinol 164 (6): 919-26

Peters C, Langham S, Mullis PE, Dattani MT (2010) Use of combined liothyronine and thyroxine therapy for consumptive hypothyroidism associated with hepatic haemangiomas in infancy. Horm Res Paediatr 74 (2): 149-52

Powell PD, Bellanné-Chantelot C, Flanagan SE, Ellard S, Rooman R, Hussain K, Skae M, Clayton P, de Lonlay P, Dunne MJ, Cosgrove KE (2011) In vitro recovery of ATP-sensitive potassium channels in β-cells from patients with congenital hyperinsulinism of infancy. Diabetes 60 (4): 1223-8

Sahakitrungruang T, Soccio RE, Lang-Muritano M, Walker JM, Achermann JC, Miller WL (2010) Clinical, genetic, and functional characterization of four patients carrying partial loss-of-function mutations in the steroidogenic acute regulatory protein (StAR). J Clin Endocrinol Metab 95 (7): 3352-9

Salmi H, Hussain K, Lapatto R (2011) Change in plasma and erythrocyte thiol levels in children undergoing fasting studies for investigation of hypoglycaemia. Pediatr Endocrinol Diabetes Metab 17 (1): 14-9

Shimomura K, Flanagan SE, Zadek B, Lethby M, Zubcevic L, Girard CA, Petz O, Mannikko R, Kapoor RR, Hussain K, Skae M, Clayton P, Hattersley A, Ellard S, Ashcroft FM (2009) Adjacent mutations in the gating loop of Kir6.2 produce neonatal diabetes and hyperinsulinism. EMBO Mol Med 1 (3): 166-77

Simpson MA, Irving MD, Asilmaz E, Gray MJ, Dafou D, Elmslie FV, Mansour S, Holder SE, Brain CE, Burton BK, Kim KH, Pauli RM, Aftimos S, Stewart H, Kim CA, Holder-Espinasse M, Robertson SP, Drake WM, Trembath RC (2011) Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. Nat Genet 43 (4): 303-5

Tomaselli S, Megiorni F, Lin L, Mazzilli MC, Gerrelli D, Majore S, Grammatico P, Achermann JC (2011) Human RSPO1/R-spondin1 is expressed during early ovary development and augments β-catenin signaling. PLoS One 6 (1): e16366

Walker MG, Hindmarsh PC, Geary M, Kingdom JC (2010) Sonographic maturation of the placenta at 30 to 34 weeks is not associated with second trimester markers of placental insufficiency in low-risk pregnancies. J Obstet Gynaecol Can 32 (12): 1134-9

Webb EA, O'Reilly MA, Orgill J, Dale N, Salt A, Gringras P, Dattani MT (2010) Rest-activity disturbances in children with septo-optic dysplasia characterized by actigraphy and 24-hour plasma melatonin profiles. J Clin Endocrinol Metab 95 (10): E198-203

Webb EA, Dattani MT (2010) Diagnosis of growth hormone deficiency. Endocr Dev 18 (): 55-66

Webb EA, Pringle PJ, Robinson IC, Hindmarsh PC (2010) Repetitive stimulation of the pituitary with growth-hormone-releasing hormone alters the proportion of 22 and 20 kilodalton human-growth hormone released. Int J Pediatr Endocrinol 2010 (): 781317

Zani A, Nah SA, Ron O, Totonelli G, Ismail D, Smith VV, Ashworth M, Blankenstein O, Mohnike W, De Coppi P, Eaton S, Hussain K, Pierro A (2011) The predictive value of preoperative fluorine-18-L-3,4-dihydroxyphenylalanine positron emission tomography-computed tomography scans in children with congenital hyperinsulinism of infancy. J Pediatr Surg 46 (1): 204-8

Kelberman D, Rizzoti K, Lpvell-Badge R, Robinson ICAF, Dattani MT (2009) Genetic Regulation of pituitary gland development in human and mouse. Endocrine Reviews 30 (7): 790-829

Petkovic V, Godi M, Pandey AV, Lochmatter D, Buchanan CR, Dattani MT, Eblé A, Flück CE, Mullis PE (2010) Growth hormone (GH) deficiency type II: a novel GH-1 gene mutation (GH-R178H) affecting secretion and action. J Clin Endocrinol Metab 95 (2): 731-9

Bockenhauer D, van't Hoff W, Dattani M, Lehnhardt A, Subtirelu M, Hildebrandt F, Bichet DG (2010) Secondary nephrogenic diabetes insipidus as a complication of inherited renal diseases. Nephron Physiol 116 (4): p23-9

Schoenmakers E, Agostini M, Mitchell C, Schoenmakers N, Papp L, Rajanayagam O, Padidela R, Ceron-Gutierrez L, Doffinger R, Prevosto C, Luan J, Montano S, Lu J, Castanet M, Clemons N, Groeneveld M, Castets P, Karbaschi M, Aitken S, Dixon A, Williams J, Campi I, Blount M, Burton H, Muntoni F, O'Donovan D, Dean A, Warren A, Brierley C, Baguley D, Guicheney P, Fitzgerald R, Coles A, Gaston H, Todd P, Holmgren A, Khanna KK, Cooke M, Semple R, Halsall D, Wareham N, Schwabe J, Grasso L, Beck-Peccoz P, Ogunko A, Dattani M, Gurnell M, Chatterjee K (2010) Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans. J Clin Invest 120 (12): 4220-35

Idkowiak J, O'Riordan S, Reisch N, Malunowicz EM, Collins F, Kerstens MN, Köhler B, Graul-Neumann LM, Szarras-Czapnik M, Dattani M, Silink M, Shackleton CH, Maiter D, Krone N, Arlt W (2011) Pubertal presentation in seven patients with congenital adrenal hyperplasia due to P450 oxidoreductase deficiency. J Clin Endocrinol Metab 96 (3): E453-62

França MM, Jorge AA, Alatzoglou KS, Carvalho LR, Mendonca BB, Audi L, Carrascosa A, Dattani MT, Arnhold IJ (2011) Absence of GH-releasing hormone (GHRH) mutations in selected patients with isolated GH deficiency. J Clin Endocrinol Metab 96 (9): E1457-60

McCabe MJ, Gaston-Massuet C, Tziaferi V, Gregory LC, Alatzoglou KS, Signore M, Puelles E, Gerrelli D, Farooqi IS, Raza J, Walker J, Kavanaugh SI, Tsai PS, Pitteloud N, Martinez-Barbera JP, Dattani MT (2011) Novel FGF8 Mutations Associated with Recessive Holoprosencephaly, Craniofacial Defects, and Hypothalamo-Pituitary Dysfunction. J Clin Endocrinol Metab 96 (10): E1709-18