Pseudohypoparathyroidism type 1a and insulin resistance in a child

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 microg 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 microg 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.

Diagnosis and management of pseudohypoparathyroidism and related disorders: first international consensus statement

“…Patients with PHP1A and PHP1B can develop early-onset obesity, usually in the first 2 years of life 28,44,49,[108][109][110][111] . Noticeably, obesity in adulthood is less severe and less common than in childhood 28 .…”

Pseudohypoparathyroidism in Children

“…A Q35X mutation in exon 1 has been associated with growth-hormone deficiency (Germain-Lee, 2003), whereas a de novo, missense mutation, W281R in exon 11, has been linked to progressive osseous heteroplasia, a rare, autosomal-dominant condition that presents in childhood as dermal ossification that progresses to involve deep skeletal muscles (Chan, 2004). Germain-Lee et al(Germain-Lee, 2003) identified a patient with a Q29X mutation, and Nwosu et al (Nwosu, 2009) reported the association of Q29X mutation with a phenotype that includes Albright hereditary osteodystrophy, morbid obesity, acanthosis nigricans, insulin resistance, growth-hormone deficiency, hypothyroidism, and subcutaneous calcification.…”

“…In those patients in whom defective growth-hormone secretion is suspected, the epiphyseal defects, commonly mischaracterized as bone-age advancement, should not disqualify these children from being considered for growth-hormone therapy. In addition to its effect on statural growth, growth-hormone therapy also seems to improve body composition in patients with PHP 1a (Nwosu, 2009). …”

“…Germain-Lee et al (Germain-Lee, 2003) reported a patient with acanthosis nigricans in a cohort of 13 patients with PHP 1a who had normal hemoglobin A1c and fasting insulin levels. Nwosu et al (Nwosu, 2009) described a child with PHP 1a with acanthosis nigricans and insulin resistance (Figure 2). A patient with Albright hereditary osteodystrophy-like syndrome with a normal GNAS gene that was complicated by type 2 diabetes mellitus with severe insulin resistance, growthhormone deficiency and diabetes insipidus has been described (Sakaguchi, 1998).…”

“…2. Acanthosis nigricans of the neck folds in a patient with Albright Hereditary Osteodystrophy (Nwosu, 2009) The insulin receptor belongs to a large class of tyrosine kinase receptors, and is structurally distinct from the heptahelical G s receptors. The development of insulin resistance in the patient shown in Figure 2 most probably resulted from the combined effects of obesity, growth-hormone treatment, a family history of type 2 diabetes mellitus, and abnormal melanocortin signaling, as noted above.…”