X-linked hypopituitarism: clinical and biochemical features of a rare cause of short stature
TM Barber1, T Cheetham1 & SG Ball1,2
Familial hypopituitarism is a heterogeneous group of disorders with variable clinical, biochemical and genetic characteristics. X-linked forms have been described in rare kindreds, though clinical and molecular features are not well defined. We present a case of X-linked hypopituitarism in a young male.
The patient, currently 39 years, had an early course complicated by neonatal jaundice, seizures and subsequent failure to thrive. Hypothyroidism was diagnosed at 4 years and thyroxine therapy commenced. At 10 years height was 106 centimetres, weight 15 kilograms (both below the third centile), height velocity (HV) 2.1 centimetres per year with significant bone age delay (minus 2 SD). There was no evidence of puberty. Peak cortisol and growth hormone (GH) following hypoglycaemia were 535 nanomoles per litre and 7.4 milliUnits per litre respectively. Pituitary-derived GH was commenced at 15 milligrams per week. Over the next 4 years HV ranged from 2.5 to 6.9 centimetres per year. Testosterone therapy was introduced at 17 years because of persistent hypogonadotrophic hypogonadism (HH), with minimal impact on HV. GH therapy was stopped at age 19 with final height 140.5 centimetres and testosterone was discontinued age 21. The patient was lost to regional follow-up. He re-presented at 38 years with tiredness and clinical features of hypogonadism. Endocrine studies confirmed absolute HH. Peak cortisol following high dose synacthen was 305 nanomoles per litre and peak GH following arginine/GRF stimulation was 3.5 milliUnits per litre. Thyroid function (on thyroxine) was in the normal range. Bone density was reduced with T scores at lumbar spine and hip minus 5.4 SD and minus 4.3 SD respectively. Pituitary MRI noted hypoplasia with ectopic posterior pituitary. He commenced hydrocortisone and low dose testosterone with good clinical improvement. Repeat family history revealed a nephew with a recent diagnosis of panhypopituitarism consistent with X-linked inheritance.
This case demonstrates the potential for a progressive endocrinopathy in X-linked hypopituitarism and the differences in outcome between historical and current management.