Endocrine Abstracts

Pseudohypoparathyroidism type 1b is a disorder of calcium metabolism resulting from renal resistance to PTH, the genetic basis caused by abnormal imprinting and thus expression of the gene encoding the Gs alpha-subunit (G_Sα) of the stimulatory G protein.

For patients with PHP 1b, pregnancy raises issues regarding management of calcium and vitamin D homeostasis as well as more difficult aspects such as genetic counselling.

Here, we report a 30-year-old woman referred for investigation of hypocalcaemia. Investigations confirmed a metabolic profile of hypocalcaemia, hyperphosphataemia, normal alkaline phosphatase, normal renal and liver profile, while parathyroid hormone measurement revealed markedly elevated levels (925 pg/ml). She was morphologically normal, with no cognitive abnormality, and a diagnosis of PHP type 1b was made.

Abnormal imprinting of GNAS, the gene encoding the G_Sα subunit have been identified in patients with PHP 1b. The STX16, 3 kb microdeletion was not identified in this patient, thus making a diagnosis of the familial form unlikely. However, broad methylation changes were identified in the GNAS gene, thus rendering the sporadic form more likely.

She was treated with calcium and vitamin D replacement with improvement in her biochemical parameters. She subsequently became pregnant and her PTH normalized with titration of her active vitamin D analogue and calcium supplement. Calcium metabolism is subtly altered in pregnancy, in relation to altered albumin levels and increased levels of parathyroid hormone. The effects on calcium homeostasis in pseudohypoparathyroidism during pregnancy are less clear, largely due to its rarity.

She is also concerned regarding genetic implications for her children.

Since this patient demonstrates the imprinting abnormality of the GNAS gene complex seen in the sporadic form of PHP 1b and most cases of the sporadic form are unknown, the risk to subsequent generations is difficult to quantify.