Endocrine Abstracts

JOINT2035

Background: Pseudohypoparathyroidism type 1A is a rare endocrine disorder in children due to mutations in GNAS gene. Typical presentations include hypocalcemia, hypothyroidism. Phenotypic characteristics (obesity, skeletal findings, short stature, developmental delay). Short stature with poor final adult height is a common presentation. Resistance to GHRH is described, there are cases of GH deficiency. GH has been used in the treatment of patients with PHP type 1A. There are no reports of combined use of GH and letrozole in patients with pseudohypoparathyroidism type 1A.

Objectives: To describe a rare case when a child was diagnosed with pseudohypoparathyroidism type 1 A later due to milder presentation, who was also later diagnosed with GH deficiency and had a great response to treatment with GH in conjunction with letrozole use.

Methods: A 4 years old male presented with obesity. Work up revealed mild hypothyroidism TSH=11.8 UIU/ml (reference 0.3-4.5), fT4=0.94 ng/ml (reference 0.89-1.7), negative thyroid antibodies. Newborn screen borderline for congenital hypothyroidism, patient was presumed to have mild form of congenital hypothyroidism, started on levothyroxine. At age 5 developed low calcium 8.3 mg/dl (reference 8.7- 10.4) with low 25 vitamin D, started vitamin D with improvement in calcium. At age 12 years calcium 6.7mg/dl, PTH =447 pg/ml (reference 18-88). Physical exam short 4^th metacarpals. Genetic testing confirmed GNAS gene mutation, patient was diagnosed with pseudohypoparathyroidism type 1A. Started calcitriol, calcium carbonate. Physical exam at age 12: Tanner III, advanced bone age. GH stim test peak of GH=15 ng/ml. patient was not a candidate for GH therapy, started on letrozole. Growth velocity decreased, patient had another GH stim test with peak of GH=4.1 ng/ml. Started GH therapy with increase in growth velocity from 3.6 cm/year to 8.8 cm/year.

Results: This is a case report of a child with PHP type 1A, whose diagnosis was delayed due to late presentation of hypocalcemia. Patient developed GH deficiency, treated with GH and aromatase inhibitor with great height outcome.

Conclusion: PHP type 1A is a rare disorder with multiple endocrine disorders related to hormonal resistance. Diagnosis can be delayed as hormonal problems may develop later in life. Earlier and fast progressing puberty happens in male patients with PHP type 1A, can worsen short stature. Testing for GH deficiency is important to reveal patients that can benefit from GH use. Combination of GH and aromatase inhibitor helps to improve final adult height in patients with PHP type 1A.