The symptoms and signs associated with HAIR-AN syndrome are caused by hyperandrogenism, insulin resistance and acanthosis nigricans [1].

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 [2]. 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 [3].

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 [4].

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.

• Weight Gain

  15-year-old adolescent girl presented with weight gain, irregular menstrual cycle, skin lesions suggestive of acanthosis nigricans and hirsutism. [semanticscholar.org]

  Overall, Cushing's syndrome is a very rare cause of weight gain. In other words, most weight gain that occurs in the United States is a result of diet and exercise behaviors, and not Cushing's syndrome. [endocrinediseases.org]

  HAIR-AN Syndrome: Inside Story Artigo | IMSEAR | ID: sea-184373 ABSTRACT ABSTRACT 15-year-old adolescent girl presented with weight gain, irregular menstrual cycle, skin lesions suggestive of acanthosis nigricans and hirsutism. [pesquisa.bvsalud.org]

  Along with irregular periods, the first signs of PCOS may be the growth of facial and male-patterned body hair, thinning scalp hair, acne, and weight gain. Weight gain, however, is not always present. Normal-weight women can also have PCOS. [hormone.org]

  Anamnesis: the patient reported polyuropolydipsic syndrome and the notion of weight gain without eating disorders, making a total of 28 kg in 6 months. [endocrine-abstracts.org]

• Pathologist

  It is an essential reference for all pathologists, and an important review aid for GYN residents preparing for their Boards. [books.google.com]

  “She didn’t think it was uncombable hair syndrome, because of how rare it is, but they took samples and a pathologist looked at it under a special microscope.” [scarymommy.com]

  From Fox5Atlanta: After studying Lock's hair under a special microscope, an [Emory University] pathologist confirmed he has one of about 100 known cases of uncombable hair syndrome. [boingboing.net]

  She said Locklan’s diagnosis of UHS was confirmed after a pathologist examined his hair samples under a microscope. [everydayhealth.com]

  After studying Lock's hair under a special microscope, a pathologist confirmed he has one of about 100 known cases of uncombable hair syndrome. "The hair strand is like a triangle shape and twisted," Katelyn Samples says. [fox5atlanta.com]

• Abdominal Obesity

  Physical examination also can detect high blood pressure and increased abdominal obesity as risk factors for diabetes and cardiovascular disease in individuals who are overweight. [obgyn.ucla.edu]

  Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. [medscape.com]

• Hypertension

  BPD was followed by disappearance of co-morbidities of the syndrome, such as IGT, hypertension and hyperlipemia. [ncbi.nlm.nih.gov]

  We report the case of a 25-year-old Caucasian woman with HAIR-AN syndrome, impaired glucose tolerance (IGT), mild hyperlipemia, and hypertension, associated with sclerodermatous skin changes on the extremities and trunk. [synergypublishers.com]

  11430453 ) Elmer K.B....George R.M. 2001 7 Clearance of acanthosis nigricans associated with the HAIR-AN syndrome after partial pancreatectomy: an 11-year follow-up. ( 10474728 ) Pfeifer S.L....Gawkrodger D.J. 1999 8 Development of diabetes mellitus and hypertension [malacards.org]

• Hirsutism

  The most common cause of hirsutism is polycystic ovarian syndrome. Patients with "idiopathic" hirsutism have normal ovulatory cycles and androgen levels. [ncbi.nlm.nih.gov]

  The latter is a determining element in the severity of hirsutism [7]. There can even exist a stronger correlation with the severity of hirsutism than the level of observed hyperandrogenism [8]. [hindawi.com]

  She had facial acne, sweaty palms, multiple abdominal striae, hirsutism on the arms and legs, a deep voice, and clitoromegaly. [pmj.bmj.com]

  Comparison of flutamide and spironolactone in the treatment of hirsutism: a randomized controlled trial. Fertil Steril. 1994 Feb. 61(2):281-7. [Medline]. Van der Spuy ZM, le Roux PA. Cyproterone acetate for hirsutism. [medscape.com]

• Alopecia

  Conclusions Although a number of treatments are effective in arresting androgenic alopecia, they are not FDA approved for use in women with alopecia, nor in hirsutism. [obgyn.net]

  […] similar nonscarring alopecias. [jamanetwork.com]

  Insights and Images| Volume 199, P282-282.e1, August 01, 2018 Allison Zarbo, MD Allison Zarbo Affiliations Henry Ford Hospital Department of Dermatology Detroit, Michigan Keywords light microscopy anagen hair alopecia pediatric alopecia trichoscopy children [jpeds.com]

  Consider the following conditions: Alopecia areata. This is one of the most notable causes of pattern baldness. The symptoms of alopecia areata are thought to be caused by underlying inflammation. [healthline.com]

  Progression of alopecia in our patient, its clinical features and histology of the scalp helped to rule out androgenic alopecia and alopecia areata. [ijdvl.com]

• Sweating

  The patients underwent a complete ophthalmological examination, color test (Ishihara and Farnsworth D-15), ecography, angiography, laboratory and dermatological tests, sweat test, light microscopy and scanning electron microscopy of the hair. [scielo.br]

  Glean all essential, up-to-date, need-to-know information with new chapters on Papulosquamous and Lichenoid Disorders, Acneiform and Sweat-gland disorders and two individual chapters on Vascular Malformations and Vascular Tumors. [books.google.de]

  This period is also marked by the onset of amenorrhea, increased body and facial hair, increased pigmentation of skin, increased sweating and alopecia. [endocrine-abstracts.org]

  According to the National Centre for Advancing Translational Sciences, UHS is mostly isolated, but in some cases it has been linked to ectodermal dysplasias (a group of genetic disorders of the teeth, hair, nails and sweat glands), Bork syndrome and Angel-shaped [globalnews.ca]

  Synonyms Tooth/Nail Syndrome Nail Dysplasias With Hypodontia Witkop Syndrome is a Rare Genetic Condition Characterized by the Following Teeth Normal to small primary teeth Partial to total absence of permanent teeth Sweat Glands Normal Nails Thin, small [nfed.org]

• Skin Disease

  On DermNet NZ Defects of the hair shaft Psychological effects of hair loss Books about skin diseases See the DermNet NZ bookstore. [dermnetnz.org]

  Napolitano M, Megna M, Monfrecola G (2015) Insulin Resistance and Skin Diseases. Sci World J 1-11. [longdom.org]

  Chronic skin ailments: Since a major function of the hair is to protect the skin, skin ailments can lead to hirsutism. Clinical evaluation for skin diseases is necessary. [hirsutism.com]

  The most common symptoms are skin disease and susceptibility to certain bacterial infections that can be severe and affect virtually any part of the body. [primaryimmune.org]

  Nutrition and skin. Rev Endocr Metab Disord. 2016 Sep;17(3):443–8. 7 Katta R, Desai SP. Diet and Dermatology: the role of dietary intervention in skin disease. J Clin Aesthet Dermatol. 2014 Jul;7(7):46–51. 8 Paoli A, Rubini A, Volek JS, Grimaldi KA. [jeanhailes.org.au]

• Amenorrhea

  At a Glance Amenorrhea is the absence of menstrual blood flow. [clinicaladvisor.com]

  The patient presented here is a 21 year-old woman who has secondary amenorrhea, hirsutism, and hyperpigmented skin changes. The patient was given oral contraceptive and spironolactone. [agris.fao.org]

  [Amenorrhea, insulin resistance and acanthosis nigricans. A hyperandrogenic and a normoandrogenic clinical forms]. Devoto E, Aravena L, Pacheco D, Fluxá F. Devoto E, et al. Rev Med Chil. 1993 Feb;121(2):170-5. Rev Med Chil. 1993. [pubmed.ncbi.nlm.nih.gov]

  Key clinical features: (1) hyperandrogenism (2) insulin resistance, with increased serum insulin levels (3) acanthosis nigricans Features of hyperandrogenism may include: (1) acne (2) alopecia (3) hirsutism (4) variable clitorimegaly (5) amenorrhea (6 [meducator3.net]

  In addition, women may present with menstrual abnormalities, such as amenorrhea and infertility, or may note masculinization of the body with increased muscle mass, loss of breast tissue or androgenic alopecia. 3 View/Print Figure FIGURE 1. [aafp.org]

• Secondary Amenorrhea

  The patient presented here is a 21 year-old woman who has secondary amenorrhea, hirsutism, and hyperpigmented skin changes. The patient was given oral contraceptive and spironolactone. [agris.fao.org]

  A 20-year-old girl, having had a five-year-old secondary amenorrhea. [hindawi.com]

  "A case of HAIR-AN syndrome presenting as secondary amenorrhea". Saudi Med J. 1996; 17: 520–2. 2. Barbieri RL, Ryan KJ. [annsaudimed.net]

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 [5] [6]. 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 [7]. 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 [8].

• Hypercholesterolemia

  The blood sample showed hyperglycemia at 1.3 g/dl, hyperprogesteronemia at 0.63 ng/mL, hypertestosteronemia at 0.87 ng/mL and hypercholesterolemia at 2.63 g/L. Ultrasound of the uterus showed polycystic ovaries. [omicsonline.org]

• Insulin Increased

  […] the epidermis. 3 This is clinically manifest as acanthosis nigricans, a cutaneous marker for tissue resistance to insulin with insulinaemia. 1-3 IGF receptors are also present in the ovarian stroma and, when bound by insulin, increased androgen production [pmj.bmj.com]

  When cells can’t use insulin properly, the body’s demand for insulin increases. The pancreas makes more insulin to compensate. Extra insulin triggers the ovaries to produce more male hormones. Obesity is a major cause of insulin resistance. [healthline.com]

Of the patients, 80% were compliant with the follow-up and treatment regimen, 60% maintained or reduced their weight, 95% had regular menstrual cycles, and in most patients, the acne and/or hirsutism were the same or better than at the start of treatment [ncbi.nlm.nih.gov]

This treatment program is frequently helpful and widely used by endocrinologists in the treatment of alopecia, as well as hirsutism and stubbornly resistant cystic acne. [obgyn.net]

Effect of Treatment with Metformin on Omentin-1, Ghrelin and other Biochemical, Clinical Features in PCOS Patients. [connection.ebscohost.com]

This means it cannot be managed by attempting traditional hair care treatments like relaxers, perms, or keratin treatments that would offer better manageability for textured hair. UHS is considered a very rare disease. [healthline.com]

Can treatments help and does race play a role? Garza said theoretically chemical hair treatments or straightening could help the condition, but they would all be temporary. [eu.usatoday.com]

LAHS has a good prognosis with spontaneous improvement during adolescence or adulthood, and topical minoxidil can be used as first-line therapy [ 2 ]. [dpcj.org]

Prognosis - Sabinas brittle hair syndrome Not supplied. Treatment - Sabinas brittle hair syndrome Encourage gentle hair care to avoid further hair loss. Also, suggest wearing a wig, cap, or scarf, if appropriate. [checkorphan.org]

What is the outlook (prognosis) of hair tourniquet syndrome? With early diagnosis and treatment, hair tourniquet syndrome has a very good prognosis. Your baby’s wound should heal quickly and they shouldn’t need any additional treatment. [my.clevelandclinic.org]

Read: Boy, 10, Spends 2 Years Growing Hair He Donated to Make Wig for Friend, 12, With Alopecia “[There is] no cure for this, but the prognosis of this is really good,” Dr. Bree said. [insideedition.com]

Treatment and prognosis The condition is lethal and affected males typically die by age 2-3 years. Pneumonia or respiratory infection is the usual cause of death. Treatment is mainly supportive. [radiopaedia.org]

Identification of the underlying etiology does not alter management, but detects patients at risk for infertility, diabetes, cardiovascular disease and endometrial carcinoma. [ncbi.nlm.nih.gov]

Several etiologies are incriminated but the hyperandrogenism-insulin resistance-acanthosis nigricans syndrome is rare. Observation. A 20-year-old girl, having had a five-year-old secondary amenorrhea. [hindawi.com]

The etiology is controversial [ 30 ]. [intechopen.com]

Understanding this etiologic mechanism can be helpful by early diagnosing and preventing the progression of severe complications such as penile amputation (4). [numonthly.com]

Polycystic Ovary Syndrome (PCOS)ETIOLOGY & PATHOPHYSIOLOGY PCOS 7 8. PCOS: Etiology• Neuroendocrine derangement: ↑LH relative to FSH• Hyperinsulinemia: defect in insulin action or secretion• Androgen excess: ovarian and adrenal PCOS 8 9. [slideshare.net]

Includes all-new chapters on cytology, immunohistochemistry, flow cytometry, molecular biology, and epidemiology and biostatistics. [books.google.com]

The discussion covers the phenotype spectrum, epidemiology, mode of inheritance, pathogenesis, and clinical profile of each condition, all of which is accompanied by a wealth of illustrations. [books.google.it]

Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clinical Epidemiology. 2014;6:1-13. doi:10.2147/CLEP.S37559. George, Kathleen. “HAIR-AN Syndrome: A Multisystem Challenge – American Family Physician”. [thehealthsite.com]

Main Outcome Measures Epidemiologic data for all forms of alopecia were ascertained, such as sex, age at onset, age at the time of evaluation, and clinical diagnosis. [jamanetwork.com]

Pathophysiology Primary abnormality Insulin Resistance causes increased Insulin Secondary abnormality Excess androgen secretion from ovaries IV. Associated Conditions V. Differential Diagnosis VI. Labs VII. [fpnotebook.com]

The proposed pathophysiology of this syndrome is also discussed. [ncbi.nlm.nih.gov]

HAIR-AN syndrome is characterized by high insulin resistance, obesity, and hyperinsulinemia as compared to PCOS and could represent adipose tissue dysfunction as the primary pathophysiologic trigger. [karger.com]

This requires immediate medical assistance to prevent any long-term damage. [verywellfamily.com]

Prevention - Sabinas brittle hair syndrome Not supplied. Diagnosis - Sabinas brittle hair syndrome Symptoms include brittle hair, mild mental retardation and nail dysplasia. [checkorphan.org]

We conclude that HAIR-AN syndrome is a common disease in young women and multifaceted, aggressive treatment appears to be effective in reducing the severity of symptoms and preventing further consequences. [ncbi.nlm.nih.gov]

Early diagnosis and appropriate treatment would help in preventing complications of obesity, insulin resistance leading to coronary artery disease, Type 2 diabetes mellitus, hyperlipidemia. [pesquisa.bvsalud.org]

A healthy lifestyle of nutritious food and physical activity can help to treat PCOS and prevent it. [jeanhailes.org.au]

1. Somani N, Harrison S, Bergfeld WF. The clinical evaluation of hirsutism. Dermatol Ther. 2008 Sep-Oct;21(5):376-91.
2. Friedman CI, Richards S, Kim MH. Familial acanthosis nigricans. A longitudinal study. J Reprod Med. 1987 Jul;32(7):531-6.
3. Magsino CH, Spencer J. Insulin receptor antibodies and insulin resistance. South Med J. 1999;92:717–9.
4. Pinhas-Hamiel O, Zeitler P. Clinical problem-solving. The importance of a name. N Engl J Med. 1999;340:1418–21.
5. ACOG technical bulletin. Evaluation and treatment of hirsute. Int J Gynaecol Obstet. June. 49:341-6.
6. Hoffman DI, Klove K, Lobo RA. The prevalence and significance of elevated dehydroepiandrosterone sulfate levels in anovulatory women. Fertil Steril. 1984 Jul.; 42(1):76-81.
7. Habif TP. Clinical dermatology. Fifth edition. 2009. Edinburgh; Mosby.
8. Gordon CM. Menstrual disorders in adolescents. Excess androgens and the polycystic ovary syndrome. Pediatr Clin North Am. 1999;46:519–43.