Aim: To investigate the metabolic effects of recombinant human growth hormone (rhGH) in an Alström syndrome patient with growth hormone deficiency. Methods: A 15-year-old Alström syndrome boy with growth hormone deficiency received rhGH therapy for 1 year. Biochemical parameters, including hepatic enzyme levels, lipid profiles, and insulin sensitivity, were measured. Body composition analysis and computed tomography scans of the liver were performed. Results: After 1 year of rhGH treatment, body fat mass, fat infiltration in the liver, and serum lipid profiles had all decreased. Insulin sensitivity and acanthosis nigricans improved. Conclusion: rhGH therapy might have beneficial effects on body composition, liver fat content, lipid profiles, and insulin resistance in Alström syndrome patients, with improvement of the glucose homeostasis.

1.
Macari F, Lautier C, Girardet A, Dadoun F, Darmon P, Dutour A, Renard E, Bouvagnet P, Claustres M, Oliver C, Grigorescu F: Refinement of genetic localization of the Alström syndrome on chromosome 2p12–13 by linkage analysis in a North African family. Hum Genet 1998;103:658–661.
2.
Collin GB, Marshall JD, Ikeda A, So WV, Russell-Eggitt I, Maffei P, Beck S, Boerkoel CF, Sicolo N, Martin M, Nishina PM, Naggert JK: Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alström syndrome. Nat Genet 2002;31:74–78.
3.
Marshall JD, Ludman MD, Shea SE, Salisbury SR, Willi SM, LaRoche RG, Nishina PM: Genealogy, natural history, and phenotype of Alström syndrome in a large Acadian kindred and three additional families. Am J Med Genet 1997;73:150–161.
4.
Rasmussen MH, Hvidberg A, Juul A, Main KM, Gotfredsen A, Skakkebaek NE, Hilsted J: Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects. J Clin Endocrinol Metab 1995;80:1407–1415.
5.
Argente J, Caballo N, Barrios V, Pozo J, Muñoz MT, Chowen JA, Hernandez M: Multiple endocrine abnormalities of the growth hormone and insulin-like growth factor axis in prepubertal children with exogenous obesity: Effect of short- and long-term weight reduction. J Clin Endocrinol Metab 1997;82:2076–2083.
6.
Johannsson G, Mårin P, Lönn L, Ottsson M, Stenlöf K, Björntorp P, Sjöström L, Bengtsson BÅ: Growth hormone treatment of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism, and reduces diastolic blood pressure. J Clin Endocrinol Metab 1997;82:727–734.
7.
Kamel A, Norgren S, Elimam A, Danielsson P, Marcus C: Effects of growth hormone treatment in obese prepubertal boys. J Clin Endocrinol Metab 2000;85:1412–1419.
8.
Salomon F, Cuneo RC, Umpleby AM, Sönksen PH: Interactions of body fat and muscle mass with substrate concentrations and fasting insulin levels in adults with growth hormone deficiency. Clin Sci (Colch) 1994;87:201–206.
9.
Al-Shoumer KA, Page B, Thomas E, Murphy M, Beshyah SA, Johnston DG: Effects of four years’ treatment with biosynthetic human growth hormone (GH) on body composition in GH-deficient hypopituitary adults. Eur J Endocrinol 1996;135:559–567.
10.
Hwu CM, Kwok CF, Lai TY, Shih KC, Lee TS, Hsiao LC, Lee SH, Fang VS, Ho LT: Growth hormone (GH) replacement reduces total body fat and normalizes insulin sensitivity in GH-deficient adults: A report of one-year clinical experience. J Clin Endocrinol Metab 1997;82:3285–3292.
11.
Hussain MA, Schmitz O, Mengel A, Glatz Y, Christiansen JS: Comparison of the effects of growth hormone and insulin-like growth factor I on substrate oxidation and on insulin sensitivity in growth hormone-deficient humans. J Clin Invest 1994;94:1126–1133.
12.
Yang S, Björntorp P, Liu X, Eden S: Growth hormone treatment of hypophysectomized rats increases catecholamine-induced lipolysis and the number of β-adrenergic receptors in adipocytes: No differences in the effects of growth hormone on different fat depots. Obes Res 1996;4:471–478.
13.
Alter CA, Moshang T Jr: Growth hormone deficiency in two siblings with Alström syndrome. Am J Dis Child 1993;147:97–99.
14.
Sheldon WR Jr, DeBold CR, Evans WS, DeCherney GS, Jackson RV, Island DP, Thorner MO, Orth DN: Rapid sequential intravenous administration of four hypothalamic releasing hormones as a combined anterior pituitary function test in normal subjects. J Clin Endocrinol Metab 1985;60:623–630.
15.
Wass JA: Hypopituitarism; in Besser GM, Cudworth AG (eds): Clinical Endocrinology: An Illustrated Text. Philadelphia, Lippincott, 1987, pp 1–14.
16.
Lanes R, Hurtado E: Oral clonidine – an effective growth hormone-releasing agent in prepubertal subjects. J Pediatr 1982;100:710–714.
17.
Lukaski HC, Johnson PE, Bolonchuk WW, Lykken GI: Assessment of fat free mass using bioelectrical impedance measurements of human body. Am J Clin Nutr 1985;41:810–817.
18.
Satman I, Yilmaz MT, Gürsoy N, Karşidağ K, Dinççağ N, Ovali T, Karadeniz Ş, Uysal V, Buğra Z, Ökten A, Devrim S: Evaluation of insulin resistant diabetes mellitus in Alström syndrome: A long-term prospective follow-up of three siblings. Diabetes Res Clin Pract 2002;56:189–196.
19.
Ricci C, Longo R, Gioulis E, Bosco M, Pollesello P, Masutti F, Croce LS, Paoletti S, de Bernard B, Tiribelli C, Dalla Palma L: Noninvasive in vivo quantitative assessment of fat content in human liver. J Hepatol 1997;27:108–113.
20.
Sheu WH, Lee WJ, Chen YT: Plasma homocysteine concentrations and insulin sensitivity in hypertensive subjects. Am J Hypertens 2000;13:14–20.
21.
Seminara S, Merello G, Masi S, Filpo A, La Cauza F, D’Onghia G, Martelli E, Loche S: Effect of long-term growth hormone treatment on carbohydrate metabolism in children with growth hormone deficiency. Clin Endocrinol (Oxf) 1998;49:125–130.
22.
Al-Shoumer KA, Gray R, Anyaoku V, Hughes C, Beshyah S, Richmond W, Johnston DG: Effects of four years’ treatment with biosynthetic human growth hormone (GH) on glucose homeostasis, insulin secretion and lipid metabolism in GH-deficient adults. Clin Endocrinol (Oxf) 1998;48:795–802.
23.
Lund S, Flyvbjerg A, Holman GD, Larsen FS, Pedersen O, Schmitz O: Comparative effects of IGF-I and insulin on the glucose transporter system in rat muscle. Am J Physiol 1994;267:E461–E466.
24.
Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E, McCullough AJ, Forlani G, Melchionda N: Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 1999;107:450–455.
25.
Osono Y, Nakajima K, Hata Y: Hypertriglyceridemia and fatty liver: Clinical diagnosis of fatty liver and lipoprotein profiles in hypertriglyceridemic patients with fatty liver. J Atheroscler Thromb 1995;2(suppl 1):47S–52S.
26.
Goto T, Onuma T, Takebe K, Kral JG: The influence of fatty liver on insulin clearance and insulin resistance in non-diabetic Japanese subjects. Int J Obes Relat Metab Disord 1995;19:841–845.
27.
Holder M, Hecker W, Gilli G: Impaired glucose tolerance leads to delayed diagnosis of Alström syndrome. Diabetes Care 1995;18:698–700.
28.
Connolly MB, Jan JE, Couch RM, Wong LT, Dimmick JE, Rigg JM: Hepatic dysfunction in Alström syndrome. Am J Med Genet 1991;40:421–424.
29.
Awazu M, Tanaka T, Sato S, Anzo M, Higuchi M, Yamazaki K, Matsuo N: Hepatic dysfunction in two sibs with Alström syndrome: case report and review of the literature. Am J Med Genet 1997;69:13–16.
30.
Garry P, Collins P, Devlin JG: An open 36-month study of lipid changes with growth hormone in adults: Lipid changes following replacement of growth hormone in adult acquired hormone deficiency. Eur J Endocrinol 1996;134:61–66.
31.
Cruz PD Jr, Hud JA Jr: Excess insulin binding to insulin-like growth factor receptors: Proposed mechanism for acanthosis nigricans. J Invest Dermatol 1992;98(6 suppl):82S–85S.
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