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Classification of Pseudohypoparathyroidism and Differential Diagnosis

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Hypoparathyroidism

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Abstract

Pseudohypoparathyroidism (PHP) exemplifies a quite unusual form of hormone resistance as the underlying molecular defect is a partial deficiency of the α subunit of the stimulatory G protein (Gsα), a key regulator of cAMP signaling pathway, rather than the hormone receptor itself. PHP, together with Albright hereditary osteodystrophy (AHO), is a rare disorder encompassing heterogeneous features, such as brachydactyly, ectopic ossifications, short stature, mental retardation, and endocrine deficiencies due to resistance to the action of different hormones, primarily PTH. The two main subtypes of PHP are caused by mutations and/or methylation defects within the imprinted GNAS cluster, whose main transcript is Gsα. Moreover, mutations in the PRKAR1A and PDE4D genes, both crucial as GNAS for cAMP-mediated signaling, have been demonstrated in patients with acrodysostosis, a disease of bone formation with characteristics similar to AHO, while small deletions of chromosome 2 may also lead to the AHO phenotype. The clinical and molecular overlap among these different but related disorders represents a challenge for endocrinologists as to differential diagnosis and genetic counseling.

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  1. Endocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via F. Sforza, 35, Milan, 20122, Italy

    Giovanna Mantovani MD, PhD & Francesca M. Elli

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  1. Unit of Metabolic and Bone Diseases, University of Florence, Florence, Italy

    Maria Luisa Brandi

  2. Division of Endocrinology, Diabetes and Hypertension, Harvard Medical School and Brigham & Women's Hospital, Boston, Massachusetts, USA

    Edward Meigs Brown

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Mantovani, G., Elli, F.M. (2015). Classification of Pseudohypoparathyroidism and Differential Diagnosis. In: Brandi, M., Brown, E. (eds) Hypoparathyroidism. Springer, Milano. https://doi.org/10.1007/978-88-470-5376-2_32

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