Case Report: A 20-year-old boy presented with lower limb
pain. He had
walking difficulty in childhood, which was diagnosed as CED and managed with
prednisolone. He later discontinued treatment and was lost to follow-up. Current re-evaluation showed short stature (-3.6 standard deviation), low weight (-4.3 standard deviation), and
delayed puberty with delayed bone age (13 years). He was found to have secondary
hypogonadism (
luteinizing hormone level, 0.1 mIU/mL [1.7-8.6 mIU/mL];
follicle-stimulating hormone level, 1.0 mIU/mL [1.5-12.4 mIU/mL]; and
testosterone level, 0.087 nmol/L [9-27 nmol/L]),
growth hormone deficiency (low
insulin-like growth factor I level, 120 ng/mL [226-903 ng/mL] and peak
growth hormone level of 7 ng/mL on
insulin-induced
hypoglycemia), and secondary hypocortisolism (
cortisol level, 105 nmol/L [170-550 nmol/L] and
adrenocorticotropic hormone level, 6 pg/mL [5-65 pg/mL]). Serum
prolactin level was normal (8.3 ng/mL [5-20 ng/mL]), and he was euthyroid on
levothyroxine replacement. Magnetic resonance imaging revealed a partially empty sella. Sanger sequencing revealed a missense mutation (p.R218C/c.652C>T) in exon 4 of the TGFβ1 gene. The patient was treated with
zoledronate,
losartan, and oral
prednisolone and continued on
levothyroxine and
testosterone replacement, which resulted in symptomatic improvement.
Discussion: The index case manifested severe CED requiring multimodality
therapy. Later, he developed combined pituitary
hormone deficiencies, which were managed with thyroid and
gonadal hormone replacement with the continuation of
glucocorticoids. The partial efficacy of
bisphosphonates in CED has been reported in the literature.
Conclusion: