Endocrine Abstracts

Introduction: Acromegaly is usually not a difficult condition to diagnose if the possibility of this diagnosis has been raised. However, there are a few conditions presenting with some aspects of acromegaly or gigantism but without growth hormone excess. Such cases are described as ‘pseudoacromegaly’ (acromegaloidism).

Methods: A female patient was first investigated for GH excess at 10 y for tall stature since infancy (over 97^th percentile). Height and weight was +3SD, bone-age 15y with full set of permanent teeth except wisdom teeth. Typical acromegalic features, large hands/feet (shoe size 43EU/UK9), large jaw, tongue, hoarse deep voice and headache. Her performance in school was below average with difficulties in concentration and learning. Pubertal development was corresponding to her chronological age. No clinical features of Sotos syndrome was found. Normal sella Xray and GGT and insulin-arginine-TRH-LHRH test. Ethinyloestradiol & medroxyprogesterone was given for 2 y which successfully stopped further height increase (171 cm and 78.4 kg). Although her growth rate plateaued, coarsening of the facial features and acral enlargement led to investigations for acromegaly on at least four occasions during her life-time with negative results. At 52 y weight gain, sweating, sleep apnoea, headaches, joint pain and enlarged tongue led to reassessment with normal GH axis. Genetic testing was performed with a macrocephaly/overgrowth syndrome panel including CUL4B, EZH2, GLI3, NSD1, PTEN and UPF3B.

Results: A heterozygous mutation was identified in the NSD1 (c.6605G>C; p.Cys2202Ser) gene known to cause Sotos syndrome. This variant has not been previously described but mutations affecting the same cysteine residue have been identified in other patients with Sotos syndrome. DNA samples from her parents found no mutation suggesting that the mutation had occurred de novo.

Conclusion: There are a number of conditions which can mimic the clinical manifestations of acromegaly or gigantism, like Sotos syndrome, which can be recognised with careful clinical assessment.