| Summary: | Abstract Background Familial partial lipodystrophy (FPL) is a rare genetic disease characterized by body fat abnormalities that lead to insulin resistance (IR). Clinical conditions linked to milder IR, such as type 2 diabetes (T2D) and metabolic syndrome, are associated with abnormalities of the hypothalamic–pituitary–adrenal (HPA) axis, but little is known about its activity in FPL. Methods Patients meeting the clinical criteria for FPL were subjected to anthropometric, biochemical and hormone analyses. A genetic study to identify mutations in the genes encoding peroxisome proliferator-activated receptor gamma (PPARγ) was performed. Polycystic ovary syndrome and hepatic steatosis were investigated, and the patient body compositions were analyzed via dual X-ray energy absorptiometry (DXA). The HPA axis was assessed via basal [cortisol, adrenocorticotrophic hormone (ACTH), cortisol binding globulin, nocturnal salivary cortisol and urinary free cortisol (UFC)] as well as dynamic suppression tests (cortisol post 0.5 mg and post 1 mg dexamethasone). Results Six patients (five female and one male) aged 17 to 42 years were included. In DXA analyses, the fat mass ratio between the trunk and lower limbs (FMR) was > 1.2 in all phenotypes. One patient had a confirmed mutation in the PPARγ gene: a novel heterozygous substitution of p. Arg 212 Trp (c.634C>T) at exon 5. HPA sensitivity to glucocorticoid feedback was preserved in all six patients, and a trend towards lower basal serum cortisol, serum ACTH and UFC values was observed. Conclusions Our findings suggest that FPL is not associated with overt abnormalities in the HPA axis, despite a trend towards low-normal basal cortisol and ACTH values and lower UFC levels. These findings suggest that the extreme insulin resistance occurring in FPL may lead to a decrease in HPA axis activity without changing its sensitivity to glucocorticoid feedback, in contrast to the abnormalities in HPA axis function in T2D and common metabolic syndrome.
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