Elias Cecília Pacheco, Antunes Daniela Espíndola, Coelho Michella Soares, de Lima Caroline Lourenço, Rassi Nelson, de Melo Ana Paula Meireles, Amato Angélica Amorim
Unit of Endocrinology, Hospital Alberto Rassi-General Hospital of Goiânia (HGG), Avenida Anhanguera, 6479 - St. Oeste, Goiânia, GO CEP 74120-080 Brazil.
2Unit of Endocrinology, Hospital das Clínicas, Federal University of Goiás (HC-UFG), Goiânia, Brazil.
Diabetol Metab Syndr. 2019 Jan 3;11:1. doi: 10.1186/s13098-018-0396-4. eCollection 2019.
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.
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).
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.
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.
家族性部分脂肪营养不良（FPL）是一种罕见的遗传性疾病，其特征是身体脂肪异常，进而导致胰岛素抵抗（IR）。与较轻胰岛素抵抗相关的临床病症，如2型糖尿病（T2D）和代谢综合征，与下丘脑 - 垂体 - 肾上腺（HPA）轴异常有关，但关于其在FPL中的活性知之甚少。
符合FPL临床标准的患者接受人体测量、生化和激素分析。进行了一项基因研究，以确定编码过氧化物酶体增殖物激活受体γ（PPARγ）的基因突变。研究了多囊卵巢综合征和肝脂肪变性，并通过双能X线吸收法（DXA）分析患者的身体成分。通过基础指标[皮质醇、促肾上腺皮质激素（ACTH）、皮质醇结合球蛋白、夜间唾液皮质醇和尿游离皮质醇（UFC）]以及动态抑制试验（0.5mg和1mg地塞米松后的皮质醇）评估HPA轴。
纳入了6名年龄在17至42岁之间的患者（5名女性和1名男性）。在DXA分析中，所有表型的躯干与下肢脂肪量比（FMR）均>1.2。1名患者在PPARγ基因中检测到确诊突变：外显子5处p.Arg 212 Trp（c.634C>T）的新型杂合子替代。所有6名患者的HPA对糖皮质激素反馈的敏感性均得以保留，并且观察到基础血清皮质醇、血清ACTH和UFC值有降低的趋势。
我们的研究结果表明，尽管基础皮质醇和ACTH值有低至正常的趋势以及UFC水平较低，但FPL与HPA轴的明显异常无关。这些结果表明，与T2D和常见代谢综合征中HPA轴功能异常相反，FPL中出现的极端胰岛素抵抗可能导致HPA轴活性降低，而不改变其对糖皮质激素反馈的敏感性。
