Endocrine Abstracts

Introduction: Pseudohypoparathyroidism type la (PHP-1a) is an uncommon disorder that results from an inactivating mutation in the GNAS gene. It can present with resistance to several hormones, in addition to parathyroid hormone (PTH). A characteristic skeletal phenotype also results, referred to as Albright’s hereditary osteodystrophy, that occurs because of the crucial role of Gs-α signaling in the growth, differentiation, and structure of these tissues.

Objective: To report a rare case of pseudohypoparathyroidism type Ia, presenting with hypothyroidism and insulin resistance, and review the related literature.

Case report: A male patient with PHP type 1a caused by a heterozygous mutation of the GNAS gene (c.568_571del) is presented.

In addition to PHP, the patient presents hypothyroidism and insulin resistance. GH levels are within normal range. The phenotype includes obesity, mild mental retardation, psychosis, calcifications of basal ganglia and Albright’s hereditary osteodystrophy.

The genetic study of the mather is still pending.

Discussion/conclusion: Patients diagnosed with PHP1a should be further evaluated for associated endocrinopathies. Hypothyroidism is the most common endocrinophathy in this context, that is frequently subclinical in infancy.

Severe obesity is characteristic of PHP1a. It has been postulated that paternal imprinting of Gsα occurs in the hypothalamus such that maternal Gsα mutations lead to loss of the melanocortin signaling cascade, which is important for energy balance.

Insulin resistance has not commonly been described. It most probably results from the combined effects of obesity, family history, and abnormal melanocortin signaling.

Soft-tissue calcification has been reported in various body parts, especially in the subcutaneous tissues, and rarely in the brain and cardiac septum.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.