Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Case Study
  • Published:

Pseudohypoparathyroidism type 1a and insulin resistance in a child

Nature Reviews Endocrinology volume 5, pages 345–350 (2009)Cite this article

Abstract

Background. A 5-year-old white girl with a history of hypothyroidism in infancy presented to the endocrinology clinic of a tertiary hospital. Her physical examination noted a stocky physique, broad chest, short neck and short digits. Two years later, skin examination revealed subcutaneous nodules and acanthosis nigricans.

Investigations. Measurement of levels of serum phosphate, parathyroid hormone, ionized calcium and insulin; measurement of peak growth hormone by the arginine–levodopa stimulation test; calculation of homeostasis model assessment of insulin resistance; assessment of bone age; DNA analysis of the GNAS gene.

Diagnosis. Pseudohypoparathyroidism type 1a in a patient with Albright hereditary osteodystrophy, characterized by hypocalcemia, hypothyroidism, growth-hormone deficiency and insulin resistance.

Management. The child continued to take levothyroxine 25 µg once daily, and at 5 years of age she was started on 40 mg/kg elemental calcium as calcium carbonate daily, and calcitriol (active vitamin D) 0.25 µg twice daily. Lifestyle modifications were also recommended for weight control. At 6 years and 4 months of age, treatment with growth hormone was initiated at a dose of 0.3 mg/kg weekly.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Features suggestive of Albright hereditary osteodystrophy in the patient.
Figure 2

References

  1. Levy, J. C. et al. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care 21, 2191–2192 (1998).

    Article  CAS  Google Scholar 

  2. Murphy, M. J. et al. Distribution of adiponectin, leptin, and metabolic correlates of insulin resistance: a longitudinal study in British children; 1: prepuberty (EarlyBird 15). Clin. Chem. 54, 1298–1306 (2008).

    Article  CAS  Google Scholar 

  3. Balagopal, P. et al. Lifestyle-only intervention attenuates the inflammatory state associated with obesity: a randomized controlled study in adolescents. J. Pediatr. 146, 342–348 (2005).

    Article  Google Scholar 

  4. Keskin, M. et al. Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 115, e500–e503 (2005).

    Article  Google Scholar 

  5. Greulich, W. W. & Pyle, S. I. (eds) Radiographic Atlas of Skeletal Development of the Hands and Wrists, 2nd edn (Stanford University Press, Stanford, 1959).

    Book  Google Scholar 

  6. Sambrook, J. (ed.) Molecular Cloning: a Laboratory Manual. (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1989).

    Google Scholar 

  7. Germain-Lee, E. L. et al. Growth hormone deficiency in pseudohypoparathyroidism type 1a: another manifestation of multihormone resistance. J. Clin. Endocrinol. Metab. 88, 4059–4069 (2003).

    Article  CAS  Google Scholar 

  8. Weinstein, L. S. & Shenker, A. G. Protein mutations in human disease. Clin. Biochem. 26, 333–338 (1993).

    Article  CAS  Google Scholar 

  9. Lietman, S. A. et al. Preimplantation genetic diagnosis for severe Albright hereditary osteodystrophy. J. Clin. Endocrinol. Metab. 93, 901–904 (2008).

    Article  CAS  Google Scholar 

  10. Brickman, A. S. et al. Responses to glucagon infusion in pseudohypoparathyroidism. J. Clin. Endocrinol. Metab. 63, 1354–1360 (1986).

    Article  CAS  Google Scholar 

  11. Weinstein, L. S. et al. Minireview: GNAS: normal and abnormal functions. Endocrinology 145, 5459–5464 (2004).

    Article  CAS  Google Scholar 

  12. Long, D. N. et al. Body mass index differences in pseudohypoparathyroidism type 1a versus pseudopseudohypoparathyroidism may implicate paternal imprinting of Gαs in the development of human obesity. J. Clin. Endocrinol. Metab. 92, 1073–1079 (2007).

    Article  CAS  Google Scholar 

  13. Pohlenz, J. et al. A new heterozygous mutation (L338N) in the human Gsα (GNAS1) gene as a cause for congenital hypothyroidism in Albright's hereditary osteodystrophy. Eur. J. Endocrinol. 148, 463–468 (2003).

    Article  CAS  Google Scholar 

  14. Chan, I. et al. Progressive osseous heteroplasia resulting from a new mutation in the GNAS1 gene. Clin. Exp. Dermatol. 29, 77–80 (2004).

    Article  CAS  Google Scholar 

  15. Scott, D. C. & Hung, W. Pseudohypoparathyroidism type Ia and growth hormone deficiency in two siblings. J. Pediatr. Endocrinol. Metab. 8, 205–207 (1995).

    Article  CAS  Google Scholar 

  16. Chen, Y. J. et al. Pseudohypoparathyroidism: report of seven cases. Acta Paediatr. Taiwan 46, 374–380 (2005).

    PubMed  Google Scholar 

  17. de Wijn, E. M. & Steendijk, R. Growth and maturation in pseudo-hypoparathyroidism: a longitudinal study in 5 patients. Acta Endocrinol. (Copenh.) 101, 223–226 (1982).

    Article  CAS  Google Scholar 

  18. Steinbach, H. L. & Young, D. A. The roentgen appearance of pseudohypoparathyroidism (PH) and pseudo-pseudohypoparathyroidism (PPH). Differentiation from other syndromes associated with short metacarpals, metatarsals, and phalanges. Am. J. Roentgenol. Radium Ther. Nucl. Med. 97, 49–66 (1966).

    Article  CAS  Google Scholar 

  19. Kobayashi, T. et al. PTHrP and Indian hedgehog control differentiation of growth plate chondrocytes at multiple steps. Development 129, 2977–2986 (2002).

    CAS  PubMed  Google Scholar 

  20. Tavella, S. et al. Targeted expression of SHH affects chondrocyte differentiation, growth plate organization, and Sox9 expression. J. Bone Miner. Res. 19, 1678–1688 (2004).

    Article  CAS  Google Scholar 

  21. van der Eerden, B. C. et al. Expression of Indian hedgehog, parathyroid hormone-related protein, and their receptors in the postnatal growth plate of the rat: evidence for a locally acting growth restraining feedback loop after birth. J. Bone Miner. Res. 15, 1045–1055 (2000).

    Article  CAS  Google Scholar 

  22. Schuster, V. & Sandhage, K. Intracardiac calcifications in a case of pseudohypoparathyroidism type Ia (PHP-Ia). Pediatr. Cardiol. 13, 237–239 (1992).

    Article  CAS  Google Scholar 

  23. Sakaguchi, H. et al. A case of Albright's hereditary osteodystrophy-like syndrome complicated by several endocrinopathies: normal Gsα gene and chromosome 2q37. J. Clin. Endocrinol. Metab. 83, 1563–1565 (1998).

    CAS  PubMed  Google Scholar 

  24. Caprio, S. Insulin resistance in childhood obesity. J. Pediatr. Endocrinol. Metab. 15 (Suppl. 1), 487–492 (2002).

    Google Scholar 

  25. Bastard, J. P. et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur. Cytokine Netw. 17, 4–12 (2006).

    CAS  PubMed  Google Scholar 

  26. Sasaka-Suzuki, N. et al. GH inhibition of glucose uptake in adipocytes occurs without affecting GLUT-4 translocation through an IRS-2PI 3-kinase-dependent pathway. J. Biol. Chem. 284, 6061–6070 (2009).

    Article  Google Scholar 

  27. Meigs, J. B. et al. Genotype score in addition to common risk factors for prediction of type 2 diabetes. N. Engl. J. Med. 359, 2208–2219 (2008).

    Article  CAS  Google Scholar 

  28. Spiegel, A. M. et al. Deficiency of hormone receptor-adenylate cyclase coupling protein: basis for hormone resistance in pseudohypoparathyroidism. Am. J. Physiol. 243, E37–E42 (1982).

    CAS  PubMed  Google Scholar 

  29. Balavoine, A. S. et al. Hypothyroidism in patients with pseudohypoparathyroidism type Ia: clinical evidence of resistance to TSH and TRH. Eur. J. Endocrinol. 159, 431–437 (2008).

    Article  CAS  Google Scholar 

  30. Abraham, M. R. & Khadori, R. K. Pseudohypoparathyroidism. eMedicine [online], (2007).

    Google Scholar 

Download references

Acknowledgements

Written consent for publication was obtained from the patient's mother. Charles P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

Author information

Authors and Affiliations

  1. Division of Pediatric Endocrinology, Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, USA

    Benjamin U. Nwosu & Mary M. Lee

Authors
  1. Benjamin U. Nwosu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mary M. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Benjamin U. Nwosu.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nwosu, B., Lee, M. Pseudohypoparathyroidism type 1a and insulin resistance in a child. Nat Rev Endocrinol 5, 345–350 (2009). https://doi.org/10.1038/nrendo.2009.81

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrendo.2009.81

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing