Case of Familial Partial Lipodystrophy in a Female Presenting with Acromegaloid and Masculine Features

Familial partial lipodystrophy (FPL) is a rare metabolic disorder defined by a loss of subcutaneous fat in the extremities but there is great heterogeneity in its presentation. We present a case of FPL in a female with acromegaloid facial appearance and complaint of “masculine appearance”.

Case Description:

A 36 year old female was seen in our endocrinology clinic for change in facial and body features. She reported increased sweating, increased shoe, and hand size, lower jaw prominence, widening of her temples, increased neck size, and broadening of her shoulders. She was distressed by comments from family and strangers that she had a masculine appearance, with well-defined musculature of the extremities despite lack of weight training. She denied a history of galactorrhea, easy bruising, striae, clitoromegaly, deepening of voice, or change in vision. She also denied the use of testosterone supplements or exogenous steroids. She had type 2 diabetes (HbA1c 7.2% on metformin alone), hyperlipidemia, polycystic ovarian syndrome, and depression. She had liposuction and abdominoplasty in the p</span>ast. There was no known family history of inherited disorders. Her physical exam was notable for BMI 29, blood pressure 140/110, increased spacing of her upper incisors, mild prognathism, coarse hair follicles over the upper lip and chin, and acanthosis nigricans. She had prominent biceps, triceps, calf, and thigh muscles. Her workup revealed normal testosterone indices, DHEA-S, and estradiol-17B. Her pituitary panel revealed normal gonadotrophic hormones, insulin-like growth factor I, growth hormone, and mildly elevated TSH (4.820, ref 0.270-4.20) with normal fT4. Dexamethasone suppression testing was normal. Despite her initial presentation suggestive of acromegaly or androgen-producing tumor, her biochemical workup rules these out. Given her constellation of symptoms associated with insulin resistance and hyperandrogenism, we obtained genetic testing for FPL which revealed a heterozygous PPARG gene variant (c.1273C >T). This rare variant is associated with FPL type 3 and has been reported in two individuals with autosomal dominant FPL. She was started on dulaglutide and pioglitazone with improvement in her weight and in her appearance with less central adiposity

Discussion:

FPL syndromes are a rare, heterogeneous group of disorders characterized by variable loss of adipose tissue from extremities with associated metabolic derangements. Our patient presented with a primary complaint of “masculine appearance” related to muscular extremities which improved with an insulin-sensitizing agent and a GLP-1RA. This is a reminder to clinicians that lipodystrophy can present in non-traditional ways.