From the Research
To diagnose pseudohypoparathyroidism (PHP) in an adolescent male with autism, chronic hypocalcemia, elevated PTH, and normal phosphate levels, I recommend a comprehensive approach including laboratory testing, physical examination, and genetic analysis, as outlined in the most recent study 1. The diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly, and early-onset obesity, as well as molecular genetic analysis 2. Key steps in the diagnosis include:
- Confirming the biochemical profile by measuring serum calcium, phosphate, PTH, vitamin D, and urinary calcium excretion
- Performing an Ellsworth-Howard test to assess PTH resistance by measuring urinary cAMP and phosphate excretion after PTH administration
- Looking for physical features of Albright hereditary osteodystrophy (AHO) such as short stature, round face, brachydactyly, and subcutaneous ossifications
- Ordering genetic testing for GNAS mutations or methylation defects, which are the molecular basis of PHP
- Assessing thyroid and gonadal function, as these systems may also be affected by hormone resistance Given the normal phosphate levels, PHP type 1b should be considered, as this variant typically presents with PTH resistance without the physical features of AHO 3. The combination of hypocalcemia with elevated PTH indicates end-organ resistance to PTH action, which is the hallmark of pseudohypoparathyroidism, distinguishing it from primary hypoparathyroidism where PTH levels would be low 4. A life-long coordinated and multidisciplinary approach is recommended, starting as far as possible in early infancy and continuing throughout adulthood with an appropriate and timely transition from pediatric to adult care 3.