Possible Pseudohypoparathyroidism


Question

I wonder if you could help us with a lady who is now 27 years old initially presented to hospital in 2005 with seizures. CT brain at that time showed bilateral symmetrical calcification of basal ganglia. Corrected serum calcium at that time was 1.79 mmol/l(2.20-2.54), phosphate 1.82 mmol/l(0.75-1.40) with normal albumin and alkaline phosphatase. She was lost to follow up.

Presented again in 2009 with seizures and low calcium and was seen by endocrinology team. She had short statute ( height 150.8 cm), BMI of 25.5, no ectopic calcification normal metacarpals and metatarsals. She was clinically euthyroid and had normal TSH and T4 levels. Periods normal, delivered normal baby 6 months ago.Her adjusted calcium was 1.75 mmol/l, parathyroid hormone level 27.2 pmol/l(1.1-4.2), vitamin D level 13.7 mcg/l(10-60). Dexa scan showed osteopenia of spine only. Urine calcium was 0.01 mmol/l, urine creatinine 32.5 mmol/l. Genetic testing for GNAS1 did not detect any mutations.

The corrected serum calcium has improved to 1.84 on 1alphahydroxy cholecalciferol and calcium supplements. We are increasing the doses depending on the levels. However there is no confirmed diagnosis for genetic counselling and prognostic assesment.

I would be grateful for your opinion regarding further investigations. Dr Subash Sivaraman,

University hospital, Coventry, UK.

Response

Your patient has some classical features of pseudohypoparathyroidism type 1. She lacks heterotopic ossification of the skin, abnormal fingers and toes and, of course, no definable genetic mutation. I think that she can be successfully treated without full knowledge of her underlying problem. Some hypocalcemic patients need higher doses of calcitriol or 1 alpha hydoxycholecalciferol than others. I would not hesitate to raise the dose quickly so that a normocalcemic state can be achieved. A calcium intake of 1000-1500mg daily should be appropriate and if the vitamin D level is 25OHD I believe the patient should also be treated with cholecalciferol or ergocalciferol to raise the level to at least 30 ug/L. If serum 25OHD has not been measured, it should be as vitamin D deficiency is common and would influence the clinical course of the patient. The response to treatment with vitamin D metabolites is rapid so that within about a week you should achieve normocalcemia. If you produce hypercalcemia inadvertently this should be reversible within a few days after lowering the dose. As to the etiology of this case I would suggest you communicate with Michael Whyte in Saint Louis, Mo. for his opinion. He has a very large experience of genetic disorders affecting mineral metabolism. His email address is mwhyte@Shrinenet.org. Let me know if I can answer any other questions. Frederick R. Singer, M.D.