Endocrine Abstracts

Introduction

Primary ovarian insufficiency (POI) occurs in 1% of women between puberty and 40 years old. Despite being idiopathic in 74–90% of the cases, there are other etiologies, such as genetic causes (in up to 16% of cases). Triple-X syndrome (TXS) is a common (estimated incidence of 1/1000 women) but frequently undiagnosed chromosomal abnormality. Most women are phenotypically normal, despite this fact, POI can still develop. We present a case of a woman with POI caused by a mosaicism 46XX/47XXX.

Case report

Female, 40 years old, with past medical history of idiopathic pulmonary thromboembolism, treated with apixaban. Gynecological history: 1G/1P, dystocic delivery, menarche at 11 years-old and menstrual cycles with duration of 28 days. Family history: maternal grandmother with early menopause and a paternal aunt with cognitive deficit. She presented with secondary amenorrhea, along with vasomotor symptoms, asthenia, insomnia, and headache. She had no history of previous menstrual irregularities, hirsutism, acne, alopecia, vaginal dryness, reduction of libido, visual impairment, or nipple secretion. In the physical examination, she had a body mass index of 31.6 kg/m², no signs of vitiligo, acanthosis nigricans, ecchymoses, moon face, buffalo hump, striae, or galactorrhoea. She also had no hypotonia, clinodactyly, scoliosis or known genitourinary anomalies. Her blood work showed: estradiol 172 pg/ml, FSH 47.9 mUI/ml, LH 53.7 mUI/ml, total testosterone 0.6 ng/ml, sDHEA 241 µg/dl, androstenedione 2.67 ng/ml, 17-OH-Progesterone 1.8 ng/ml, prolactin 12.0 ng/ml, free urinary cortisol 171.6 µg/day, TSH 2.05 µUI/ml and negative 21-hydroxylase antibodies. Bone densitometry had no evidence of osteoporosis. Karyotyping revealed a mosaicism 47, XXX[8]/46, XX[46]. She was diagnosed with POI secondary to TXS and was supplemented with calcium and vitamin D. She was not treated with oestrogen given the history of pulmonary thromboembolism, absence of osteoporosis and tolerance to the vasomotor symptoms.

Discussion

Although most POI cases are idiopathic, it is important to consider and investigate other etiologies, even in the absence of phenotypic traits. This patient did not show any phenotypic trait suggesting chromosomal aneuploidies and the reason for this might be due to the fact that only some cells presented this abnormality. Nevertheless, women with 47, XXX karyotype can be phenotypically normal. To the best of our knowledge, these women are not at risk of having children who carry a chromosomal abnormality.