HAIR-AN syndrome: An extreme subphenotype of polycystic ovary syndrome. Be aware of the adolescent with extremely high androgen levels and severe hyperinsulinaemia. Queensland Paediatric and Adolescent Gynaecology Service

Abstract

Introduction HAIR-AN - a syndrome of hyperandrogenism (HA), insulin resistance (IR), and acanthosis nigricans (AN) - is a specific subtype of polycystic ovary syndrome characterised by severe insulin resistance and very high levels of testosterone. Severe, and potentially irreversible manifestations of obesity, acne, irregular menses, hirsutism, and acanthosis nigricans usually appear around puberty, causing significant impact on the affected adolescent's quality of life (QoL). Case An 11 year old female was referred to PAG with premature adrenarche, hyperandrogenism, and obesity. Adrenarche started at age 8 years with gradual onset of worsening hirsutism, acne, deepening of the voice and menarche at age 11. Her BMI was 35.3, and she had severe acanthosis nigricans, acne and hirsutism. Breast development was Tanner stage 4 and pubic hair at stage 5. Investigations showed normal FBC, LH, FSH and oestradiol. Androgens were markedly elevated, with testosterone 122 pmol/L (range 10-45) androstenedione 10 nmol (range 0.8-6.1). Adrenal hormones were normal. Insulin levels were grossly elevated at 266 mU/L (normal 2.0-23) with a HbA1c 6.1%. Imaging to exclude hypothalamic/pituitary/adrenal tumour were negative. US/ MRI Pelvis showed massively enlarged ovaries. Ovarian tumour markers were negative. Emergency laparoscopic ovarian wedge biopsy to exclude bilateral androgen secreting tumours showed polycystic ovaries. A multidisciplinary approach was taken involving an endocrinologist, adolescent gynaecologist, dietician, and psychologist. She was commenced on metformin and a COCP containing 35mcg ethinylestradiol and 2 mg cyproterone, with close review. Discussion HAIR-AN syndrome represents an extreme subtype of PCOS. High insulin levels, associated with mutations in insulin receptor gene, directly stimulate steroidogenesis in the ovaries, raising androgens. This unique subphenotype is seen in 5% of all females with hyperandrogenism. Weight loss and lifestyle modification is the primary objective in overweight adolescents with HAIR-AN syndrome. This reduces the manifestations by lowering peripheral estrogen production, insulin resistance, and ovarian androgen production, and lowers the risk of associated CVD. COCP and metformin, an insulin sensitising agent, are first-line therapy to reduce insulin resistance and regulate the menstrual cycle. Spironolactone is clinically indicated for patients with moderate/severe hirsutism. Importantly, the psychological sequalae including depression, self esteem issues and QoL in affected adolescents should be considered and addressed. Conclusion HAIR-AN syndrome is an extreme presentation of PCOS in adolescents, associated with significant morbidity and suffering. Early detection, diagnosis, and treatment are imperative to reduce morbidity, improve self-esteem, and have a positive impact on the QoL of these young women.L6215698322018-04-11 <br />