Endocrine Abstracts

JOINT394

Introduction: Familial partial lipodystrophy, Dunnigan type (FPLD2), is a rare genetic disorder characterized by the loss of subcutaneous adipose tissue from the trunk, buttocks, and limbs. Its prevalence is estimated to be less than 1/100,000 in Europe. FPLD2 is commonly associated with metabolic complications, elevated androgen levels and consequently disruptions in the hypothalamic-pituitary-ovarian axis.

Case Presentation: A 14-year-old patient presented with primary amenorrhea and significant hirsutism that developed over the past two years. Clinically, she had a BMI of +1.6SD, full moon facies, acanthosis nigricans, hirsutism, and muscular hypertrophy. Laboratory findings revealed dyslipidemia, marked insulin resistance, and hormonal hyperandrogenism. Pelvic ultrasound showed ovaries with a predominantly stromal appearance. Progestin therapy was recommended to induce menstruation, with follow-up planned for further investigation. At 19 years, the patient returned with a diagnosis of high blood pressure. Menarche occurred at 15 under progestin therapy, but bradymenorrhea persisted. Her BMI was 28 kg/m², with absence of adipose tissue in the limbs, chest, abdomen, but accumulation in the facial, cervical, axillary, and inguinal regions, giving a Cushingoid appearance with muscular hypertrophy and phlebomegaly. Hirsutism and acanthosis nigricans worsened. Clinical examination revealed normal external genitalia, and the breasts had a tubular appearance with sparse adipose tissue. Biochemical analysis showed severe mixed dyslipidemia, significant insulin resistance (HOMA-IR = 13), and evolving ovarian hyperandrogenism (FAI=10.8%). Pelvic ultrasound revealed micro-polycystic ovaries. Cardiac examination indicated grade III hypertension without structural heart changes. Further investigations with FIBROMAX revealed a NashTest-Score of 0.5 (N1). Next-generation sequencing (NGS) identified a heterozygous mutation in the LMNA gene (chr1-156106775 C>T, NM_170707.4 c.1444C>T), confirming the diagnosis of FPLD2. We resumed the anamnesis and found that the patient’s paternal grandmother had a similar phenotype and died from complications of type 2 diabetes. The father also exhibits suggestive traits and will undergo evaluation.

Conclusion: This case highlights the importance of a multidisciplinary approach integrating endocrinologic, genetic and metabolic assessments in evaluating adolescent girls with primary amenorrhea. Understanding the connection between metabolic disturbances, hormonal imbalances, and reproductive dysfunction is crucial. Early diagnosis and management of FPLD2 are essential for preventing long-term reproductive issues and mitigating the risks of severe insulin resistance, dyslipidemia, and cardiovascular disease.