Hyperandrogenism tends to present with acne, hirsutism, seborrhea and menstrual abnormalities, such as amenorrhea or infertility. Increased levels of androgens can also induce symptoms including clitoromegaly, androgenic alopecia, an increased muscle mass and a deep voice.
Insulin resistance is a pathological condition, in which the organism's tissues fail to respond to insulin, which is secreted when glucose in released into the bloodstream, due to the catabolization of fats and carbohydrates . Insulin resistance may co-exist with normal or increased levels of serum glucose and is further sub-divided into two categories: type A and B. Type A insulin resistance is a rare inherited condition, caused by genetic mutations in the insulin receptors or varied target cell disorders in insulin response. Type B insulin resistance typically co-exists with less profound manifestations of acanthosis nigricans and is associated with autoantibodies against insulin receptors and antinuclear antibodies .
The third manifestation of HAIR-AN syndrome is acanthosis nigricans, a skin pigmentation disorder that encompasses regionalized areas of hyperpigmented skin with a velvety texture. They usually appear mostly on the axilla, neck, and groin and are a result of prolonged exposure of keratinocytes to insulin in patients with HAIR-AN. Acanthosis nigricans is observed in 60-80% of teenagers with diabetes mellitus type 2 .
Lastly, HAIR-AN syndrome may also be accompanied by depression, which can often be attributed to hypothalamic irregularities and usually subsides with the administration of contraceptives per os.
The first step towards diagnosing HAIR-AN syndrome includes laboratory tests, such as a complete blood cell count, serum prolactin, glucose and insulin evaluation, thyroid function tests and serum electrolytes. Given the fact that hyperlipidemia and subsequent coronary artery disease are often diagnosed when hyperandrogenism is detected, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, as well as a triglyceride count should be performed. Additionally, the patient requires testing for antinuclear antibodies and erythrocyte sedimentation rate (ESR), due to the syndrome's frequent association with other autoimmune abnormalities.
Laboratory confirmation of hyperandrogenism is also mandatory, should there be suspicions towards it. Morning cortisol after the administration of a mild dexamethasone dose, dehydroepiandrosterone sulfate (DHEAS) and 17a-hydroxyprogesterone need to be measured, along with testosterone levels. In fact, testosterone measurement is required in order to detect a virilizing tumor, as increased DHEAS is indicative, but not diagnostic of, an androgen-producing tumor of the adrenal glands  . Testosterone is usually measured two to three times, for the results to be considered definitive. Lutenizing and follicle-stimulating hormone (LH, FSH) should also be evaluated.
Finally, in cases where acanthosis nigricans is extensive and other cancer-associated signs are observed, meticulous investigation to rule out a potential malignancy should be carried out . An abdominal or pelvic magnetic resonance imaging scan (MRI) or computed tomography scan (CT), along with upper and/or lower endoscopy are some of the modalities that can be employed for detecting a lesion .