Pseudohypoparathyroidism

Pseudohypoparathyroidism results from resistance to the actions of parathyroid hormone (PTH) produced by a loss of G-protein-mediated signaling.

Different types are distinguished by the presence or absence of a characteristic skeletal phenotype, the responsiveness to PTH, the underlying mutations, and the inheritance pattern.

Manifests clinically with hypocalcemia, hyperphosphatemia, and elevated PTH levels.

Some patients have associated endocrinopathies. Hypothyroidism is the most common, but hypogonadism is also seen.

The mainstay of treatment is the normalization of calcium and phosphate levels using calcium supplementation, vitamin D, and thiazide diuretics. Associated endocrinopathies, if present, are treated with hormone replacement.

The underlying signaling defects are incurable.

Pseudohypoparathyroidism (PHP) results from an insensitivity of target tissues to the biologic actions of parathyroid hormone (PTH). It is caused by genetic mutations in the PTH signaling pathway.[1]Mantovani G, Bastepe M, Monk D, et al. Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement. Nat Rev Endocrinol. 2018 Aug;14(8):476-500. https://www.nature.com/articles/s41574-018-0042-0 http://www.ncbi.nlm.nih.gov/pubmed/29959430?tool=bestpractice.com [2]Mantovani G, Bastepe M, Monk D, et al. Recommendations for diagnosis and treatment of pseudohypoparathyroidism and related disorders: an updated practical tool for physicians and patients. Horm Res Paediatr. 2020;93(3):182-96. https://www.doi.org/10.1159/000508985 http://www.ncbi.nlm.nih.gov/pubmed/32756064?tool=bestpractice.com The disease manifests clinically with hypocalcemia, high PTH levels, and hyperphosphatemia. The disease may be symptomatic or asymptomatic. The diverse presentations relate to tissue specificity of expression, splice variations, and carrier status. Some forms of the disease are associated with a characteristic skeletal phenotype of short stature, stocky habitus, obesity, round face, dental hypoplasia, brachymetacarpals, brachymetatarsals, and soft-tissue calcification/ossification referred to as Albright hereditary osteodystrophy.