Acanthosis nigricans and insulin sensitivity in patients with achondroplasia and hypochodroplasia due to FGFR3 mutations

J Clin Endocrinol Metab. 2009 Oct;94(10):3959-63. doi: 10.1210/jc.2009-0322. Epub 2009 Jul 21.


Background and aims: Acanthosis nigricans (AN) has been reported in association with severe skeletal dysplasias due to activating mutations in FGFR3, including thanatophoric dysplasia, severe achondroplasia (ACH) with developmental delay and AN (SADDAN syndrome), and Crouzon syndrome with AN. There are isolated reports of patients with ACH and AN. In this series, we report clinical and biochemical data on five male patients, four with ACH and one with hypochondroplasia (HCH), who developed AN without SADDAN.

Methods and results: We compared the results of a 1.75 g/kg oral glucose tolerance test performed in patients with ACH/HCH and AN with age-, sex-, and puberty-matched short children. Three of the patients were treated with recombinant human GH (dose range, 45-50 microg/kg/d), one patient had discontinued treatment 6 months before presentation, and one had never been treated. All patients had a fasting plasma glucose of less than 6 mmol/liter, and no patient had a plasma glucose greater than 7.8 mmol/liter at 2 h after ingestion of a glucose load. Although body mass index was higher in patients with skeletal dysplasia (28.9 +/- 7.3 vs. 20 +/- 0.6 kg/m(2); P = 0.01), mean fasting plasma insulin concentration was greater in controls (14.4 +/- 4.8 vs. 6.0 +/- 4.5 mU/liter; P = 0.03), as was homeostasis assessment index for insulin resistance (2.5 +/- 0.9 vs. 1.17 +/- 0.8; P = 0.05).

Conclusion: Our findings suggest that the development of AN in patients with ACH/HCH is not due to insulin insensitivity either on its own or secondary to treatment with recombinant human GH. Whether the AN is due to altered melanocyte function in these individuals remains to be established.

Publication types

  • Comparative Study

MeSH terms

  • Acanthosis Nigricans / blood
  • Acanthosis Nigricans / genetics*
  • Achondroplasia / blood
  • Achondroplasia / genetics*
  • Adolescent
  • Blood Glucose / metabolism*
  • Body Height
  • Case-Control Studies
  • Child
  • Glucose Tolerance Test
  • Human Growth Hormone / therapeutic use
  • Humans
  • Insulin / blood*
  • Insulin Resistance / genetics*
  • Male
  • Mutation*
  • Puberty
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics*
  • Recombinant Proteins / therapeutic use


  • Blood Glucose
  • Insulin
  • Recombinant Proteins
  • Human Growth Hormone
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3