Endocrine Abstracts

Introduction: Arthrogryposis multiplex congenita is a rare congenital disorder characterised by multiple joint contractures. The association with hypopituitarism has only been reported once before. We report two further children with multiple pituitary hormone deficiencies (MPHD) and arthrogryposis.

Case reports: Case 1: this 12-year-old girl was born to consanguineous parents; a previously affected sibling had died. She was dysmorphic with multiple joint ankylosis, dislocated hips and right knee, multicystic dysplastic kidney, sensorineural deafness, optic nerve hypoplasia and hydrocephalus requiring ventriculostomy. Septum pellucidum was absent on MRI. Thyroxine was commenced at 2.1 years (free T₄ of 8.8 pmol/l (10.2–24.5) and TSH 15.4 mU/l (0.4–5)). IGF1 (2.4 nmol/l (4–20)) and IGFBP-3 (0.6 mg/l (0.5–2.9)) were both low. Glucagon stimulation test at 5 years showed low peak GH (3.4 mU/l) and cortisol (232 nmol/l). She was started on GH and hydrocortisone supplementation, the former was stopped after 1 year due to worsening of kyphoscoliosis requiring spinal surgery and instrumentation.

Case 2: this 3-year old boy with arthrogryposis had dysmorphism, contractures of hips, knees, shoulder, elbows, club feet, windswept deformity of hands, joint dimpling and finger webbing. He also had micropenis, undescended testis and hypoplastic scrotum. LHRH testing was normal but the synacthen response suboptimal (403 nmol/l). Hydrocortisone, thyroxine and testosterone (25 mg monthly for 3 months) were commenced with good response. He required herniotomy, bilateral orchidopexy, triceps release and Achilles tenotomy. Microarrays and MRI scan performed at 16 months were normal. Glucagon stimulation test at 2.8 years for poor growth and low IGF1 (<3.3 nmol/l) demonstrated a peak GH response of 2.8 μg/l and GH therapy was commenced.

Conclusion: These cases illustrate an association between MPHD and arthrogryposis. The mechanism is yet to be elucidated. We plan to undertake further genetic studies to evaluate the causality of this association.