Rheumatic and bone disorders associated with acromegaly
- Lesley D Hordon, MD
Lesley D Hordon, MD
- Consultant in Rheumatology
- University of Leeds, United Kingdom
- Section Editors
- Peter H Schur, MD
Peter H Schur, MD
- Editor-in-Chief — Rheumatology
- Section Editor — Basic Science
- Professor of Medicine
- Harvard Medical School
- Marc K Drezner, MD
Marc K Drezner, MD
- Section Editor — Bone Disease
- Professor of Medicine
- University of Wisconsin Medical School
- Peter J Snyder, MD
Peter J Snyder, MD
- Editor-in-Chief — Endocrinology
- Section Editor — Pituitary Disease; Male Reproductive Endocrinology
- Professor of Medicine
- University of Pennsylvania School of Medicine
Acromegaly is a rare disorder characterized by excess secretion of growth hormone (GH) and its principle mediator, insulin-like growth factor (IGF)-1. Rheumatic problems are frequently seen in acromegaly including an arthropathy, which can be severe and disabling; carpal tunnel syndrome, which is often reversible; and a peripheral neuropathy . These findings may, in some cases, be a prominent initial sign of acromegaly. Acromegaly should be remembered as a rare but important cause of osteoarthritis (OA), particularly if OA is premature or associated with carpal tunnel syndrome.
The rheumatologic and bone disorders associated with acromegaly are reviewed here. The causes, other clinical manifestations, diagnosis, and treatment of acromegaly are presented separately. (See "Causes and clinical manifestations of acromegaly" and "Diagnosis of acromegaly" and "Treatment of acromegaly".)
Joint and spine disorders, most likely due to acceleration of the normal growth process, are common in acromegaly and may dominate the clinical picture.
Pathophysiology — Growth hormone (GH) and insulin-like growth factor (IGF)-1 are essential for normal growth, differentiation, and repair of cartilage and bone. Excess GH leads to a form of osteoarthritis (OA). A mechanism has been proposed to explain this process based upon in vitro studies assessing the effects of GH and IGF-1 on cartilage and connective tissue .
●Excess GH and IGF-1 cause proliferation of articular chondrocytes and increased matrix production. This leads to thickened articular cartilage and widening of the joint spaces.
Subscribers log in hereLiterature review current through: Jul 2017. | This topic last updated: Apr 29, 2016.References
- Lieberman SA, Björkengren AG, Hoffman AR. Rheumatologic and skeletal changes in acromegaly. Endocrinol Metab Clin North Am 1992; 21:615.
- Biermasz NR, Wassenaar MJ, van der Klaauw AA, et al. Pretreatment insulin-like growth factor-I concentrations predict radiographic osteoarthritis in acromegalic patients with long-term cured disease. J Clin Endocrinol Metab 2009; 94:2374.
- KELLGREN JH, BALL J, TUTTON GK. The articular and other limb changes in acromegaly; a clinical and pathological study of 25 cases. Q J Med 1952; 21:405.
- Ezzat S, Forster MJ, Berchtold P, et al. Acromegaly. Clinical and biochemical features in 500 patients. Medicine (Baltimore) 1994; 73:233.
- Layton MW, Fudman EJ, Barkan A, et al. Acromegalic arthropathy. Characteristics and response to therapy. Arthritis Rheum 1988; 31:1022.
- Wassenaar MJ, Biermasz NR, van Duinen N, et al. High prevalence of arthropathy, according to the definitions of radiological and clinical osteoarthritis, in patients with long-term cure of acromegaly: a case-control study. Eur J Endocrinol 2009; 160:357.
- Dons RF, Rosselet P, Pastakia B, et al. Arthropathy in acromegalic patients before and after treatment: a long-term follow-up study. Clin Endocrinol (Oxf) 1988; 28:515.
- Podgorski M, Robinson B, Weissberger A, et al. Articular manifestations of acromegaly. Aust N Z J Med 1988; 18:28.
- Detenbeck LC, Tressler HA, O'Duffy JD, Randall RV. Peripheral joint manifestations of acromegaly. Clin Orthop Relat Res 1973; :119.
- Scarpa R, De Brasi D, Pivonello R, et al. Acromegalic axial arthropathy: a clinical case-control study. J Clin Endocrinol Metab 2004; 89:598.
- Ibbertson HK, Manning PJ, Holdaway IM, et al. The acromegalic rosary. Lancet 1991; 337:154.
- Rajasoorya C, Holdaway IM, Wrightson P, et al. Determinants of clinical outcome and survival in acromegaly. Clin Endocrinol (Oxf) 1994; 41:95.
- Biermasz NR, Pereira AM, Smit JW, et al. Morbidity after long-term remission for acromegaly: persisting joint-related complaints cause reduced quality of life. J Clin Endocrinol Metab 2005; 90:2731.
- Miller A, Doll H, David J, Wass J. Impact of musculoskeletal disease on quality of life in long-standing acromegaly. Eur J Endocrinol 2008; 158:587.
- Biermasz NR, van 't Klooster R, Wassenaar MJ, et al. Automated image analysis of hand radiographs reveals widened joint spaces in patients with long-term control of acromegaly: relation to disease activity and symptoms. Eur J Endocrinol 2012; 166:407.
- Wassenaar MJ, Biermasz NR, Bijsterbosch J, et al. Arthropathy in long-term cured acromegaly is characterised by osteophytes without joint space narrowing: a comparison with generalised osteoarthritis. Ann Rheum Dis 2011; 70:320.
- Jones AC, Chuck AJ, Arie EA, et al. Diseases associated with calcium pyrophosphate deposition disease. Semin Arthritis Rheum 1992; 22:188.
- Colao A, Marzullo P, Vallone G, et al. Reversibility of joint thickening in acromegalic patients: an ultrasonography study. J Clin Endocrinol Metab 1998; 83:2121.
- Colao A, Cannavò S, Marzullo P, et al. Twelve months of treatment with octreotide-LAR reduces joint thickness in acromegaly. Eur J Endocrinol 2003; 148:31.
- Colao A, Marzullo P, Vallone G, et al. Ultrasonographic evidence of joint thickening reversibility in acromegalic patients treated with lanreotide for 12 months. Clin Endocrinol (Oxf) 1999; 51:611.
- Claessen KM, Ramautar SR, Pereira AM, et al. Increased clinical symptoms of acromegalic arthropathy in patients with long-term disease control: a prospective follow-up study. Pituitary 2014; 17:44.
- Dinn JJ, Dinn EI. Natural history of acromegalic peripheral neuropathy. Q J Med 1985; 57:833.
- Tagliafico A, Resmini E, Nizzo R, et al. Ultrasound measurement of median and ulnar nerve cross-sectional area in acromegaly. J Clin Endocrinol Metab 2008; 93:905.
- Resmini E, Tagliafico A, Nizzo R, et al. Ultrasound of peripheral nerves in acromegaly: changes at 1-year follow-up. Clin Endocrinol (Oxf) 2009; 71:220.
- Inzucchi SE, Robbins RJ. Growth hormone and the maintenance of adult bone mineral density. Clin Endocrinol (Oxf) 1996; 45:665.
- Ohlsson C, Bengtsson BA, Isaksson OG, et al. Growth hormone and bone. Endocr Rev 1998; 19:55.
- Halse J, Melsen F, Mosekilde L. Iliac crest bone mass and remodelling in acromegaly. Acta Endocrinol (Copenh) 1981; 97:18.
- Ezzat S, Melmed S, Endres D, et al. Biochemical assessment of bone formation and resorption in acromegaly. J Clin Endocrinol Metab 1993; 76:1452.
- White HD, Ahmad AM, Durham BH, et al. Effect of active acromegaly and its treatment on parathyroid circadian rhythmicity and parathyroid target-organ sensitivity. J Clin Endocrinol Metab 2006; 91:913.
- Albright F, Reifenstein EC. The parathyroid glands and metabolic bone disease: Selected studies, Williams and Wilkins, Philadelphia 1948. p.188.
- Diamond T, Nery L, Posen S. Spinal and peripheral bone mineral densities in acromegaly: the effects of excess growth hormone and hypogonadism. Ann Intern Med 1989; 111:567.
- Ho PJ, Fig LM, Barkan AL, Shapiro B. Bone mineral density of the axial skeleton in acromegaly. J Nucl Med 1992; 33:1608.
- Kayath MJ, Vieira JG. Osteopenia occurs in a minority of patients with acromegaly and is predominant in the spine. Osteoporos Int 1997; 7:226.
- Kotzmann H, Bernecker P, Hübsch P, et al. Bone mineral density and parameters of bone metabolism in patients with acromegaly. J Bone Miner Res 1993; 8:459.
- Scillitani A, Chiodini I, Carnevale V, et al. Skeletal involvement in female acromegalic subjects: the effects of growth hormone excess in amenorrheal and menstruating patients. J Bone Miner Res 1997; 12:1729.
- Jockenhövel F, Rohrbach S, Deggerich S, et al. Differential presentation of cortical and trabecular peripheral bone mineral density in acromegaly. Eur J Med Res 1996; 1:377.
- Lesse GP, Fraser WD, Farquharson R, et al. Gonadal status is an important determinant of bone density in acromegaly. Clin Endocrinol (Oxf) 1998; 48:59.
- Biermasz NR, Hamdy NA, Pereira AM, et al. Long-term maintenance of the anabolic effects of GH on the skeleton in successfully treated patients with acromegaly. Eur J Endocrinol 2005; 152:53.
- Battista C, Chiodini I, Muscarella S, et al. Spinal volumetric trabecular bone mass in acromegalic patients: a longitudinal study. Clin Endocrinol (Oxf) 2009; 70:378.
- Vestergaard P, Mosekilde L. Fracture risk is decreased in acromegaly--a potential beneficial effect of growth hormone. Osteoporos Int 2004; 15:155.
- Bonadonna S, Mazziotti G, Nuzzo M, et al. Increased prevalence of radiological spinal deformities in active acromegaly: a cross-sectional study in postmenopausal women. J Bone Miner Res 2005; 20:1837.
- Mazziotti G, Bianchi A, Bonadonna S, et al. Prevalence of vertebral fractures in men with acromegaly. J Clin Endocrinol Metab 2008; 93:4649.
- Wassenaar MJ, Biermasz NR, Hamdy NA, et al. High prevalence of vertebral fractures despite normal bone mineral density in patients with long-term controlled acromegaly. Eur J Endocrinol 2011; 164:475.
- Mazziotti G, Biagioli E, Maffezzoni F, et al. Bone turnover, bone mineral density, and fracture risk in acromegaly: a meta-analysis. J Clin Endocrinol Metab 2015; 100:384.
- Mazziotti G, Bianchi A, Porcelli T, et al. Vertebral fractures in patients with acromegaly: a 3-year prospective study. J Clin Endocrinol Metab 2013; 98:3402.
- Claessen KM, Kroon HM, Pereira AM, et al. Progression of vertebral fractures despite long-term biochemical control of acromegaly: a prospective follow-up study. J Clin Endocrinol Metab 2013; 98:4808.
- Madeira M, Neto LV, de Paula Paranhos Neto F, et al. Acromegaly has a negative influence on trabecular bone, but not on cortical bone, as assessed by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab 2013; 98:1734.