Endocrine Abstracts

Primary amenorrhea is a rare disease that affects <1% of adolescent girls. The most common causes of primary amenorrhea include chromosomal abnormalities, hypothalamic and pituitary disorders, lack or structural abnormality of reproductive organs.

18 years old woman was referred to us by her pediatric physician for evaluation of primary amenorrhea and hirsutism. She had low birth weight, 1.9 kg, and hypostaturism. At the age of 6 years underwent to clonidine provocation test that showed normal values of growth hormone secretion. At the age of 17 the patient noticed some signs of masculinization (fine hairs on her cheeks) in the absence of menarche or evidence of sex development.

She is currently eighteen years old, her height is 132 cm (20 cm <3rd percentile), her weight 33 kg (BMI=18.9). Clinical evaluation of hirsutism according to Ferriman and Gallway has given a score of 23 (severe), no signs of acanthosis nigricans on the neck.

Endocrinological evaluation showed high levels of testosterone (3.4 ng/ml), with normal gonadotropins, estradiol, TSH and thyroid hormones, PRL, GH, IGF1, PTH, ACTH, 17-OH-P, DHEA-S. Pelvis ultrasonography showed microplolycystic ovaries and a small uterus. Metabolic assessment revealed fasting hyperinsulinemia (88 μU/ml) with normal fasting plasma glucose (89 mg/dl), but diabetes at 2 h of oral glucose tolerance test (289 mg/dl) with very high insulin levels (2123 μU/ml). Given the basal and glucose tolerance test insulin levels, considering the possibility of insulin receptor gene alterations, DNA direct sequencing of the exons 17–21 of the insulin receptor gene, encoding the tyrosine kinase domain, was maden.

An heterozygous mutation in exon 19 with arginine substituting glycine in position 1146 was found. The rest of the family is currently under investigation. Patient started therapy with flutamide 125 mg once a day per os, and metformin 850 mg three time/daily. After 6 month from the beginning of therapy menarche occurs.

Conclusions: To the best of our knowledge, this is the third Italian patient with severe insulin resistance due to a mutation of IR gene and the first patient presenting with primary amenorrhea.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.