New Insights Into the Relationship Between the Skin and Endocrine Disorders.

As dermatologists, we pride ourselves on being Sherlock Holmes in the House of Medicine, employing our keen clinical diagnostic skills as we expertly read the signs of internal disease that manifest on the skin.Whilemuchattention is paid to the dermatologic aspects of paraneoplastic, inflammatory, and autoimmune disorders, abnormalities of the endocrine system also deserve no less of our attention. In this issue of JAMADermatology, 2 articles highlight the important role that thedermatologist plays in identifying and characterizingpatientswith commonskindisorderswhomay be at risk for metabolic and androgen-mediated disease. Schmidt et al1 describe cutaneous findings and their associations with insulin resistance and hyperandrogenemia among a group of women referred to their multidisciplinary center deemed at high risk for polycystic ovary syndrome (PCOS). In a standardized fashion, they evaluated clinical and laboratory findings that distinguished women who met diagnostic criteria for PCOS as compared with those who did not within this referral population. Next, Nagpal et al2 report, to our knowledge, the largest cohort to date examining the prevalence of insulin resistance and metabolic syndrome in postadolescent males with acne of varying severity. Polycystic ovary syndrome is a multifaceted syndrome of unclear etiology that reflects a complex interplay between excess androgenproductionandhyperinsulinemia thatmanifests clinically as chronic oligo-ovulation, hyperandrogenism, polycystic ovaries, andmetabolic abnormalities. It is one of the most common endocrinopathies among women of reproductive age. Prevalence estimates range from up to 8% using the National Institutes of Health criteria to up to 18% when the broader Rotterdam diagnostic criteria are applied.3 Whereas clinicalmanifestations can vary amongwomen, eachaspect is associatedwithsignificant long-termhealthconsequences.Menstrual irregularities inwomenwithPCOS represent themost common cause of anovulatory infertility and also put women at risk for the development of endometrial hyperplasia and endometrial carcinoma. When women with PCOS do become pregnant, they are more likely to experience complications such as gestational diabetes, pregnancyinducedhypertension,preeclampsia, andprematuredelivery.4 Metabolic abnormalities are also commonly seen in women with PCOS. Up to 47% meet criteria for the metabolic syndrome, which manifests as obesity, hypertension, impaired glucose tolerance, and dyslipidemia.While it is controversial as to whether PCOS represents an independent risk factor for the development of cardiovascular disease, these patients do require closemonitoring and strategies for risk factormodification. Of further consequence are higher rates of obstructive sleep apnea, nonalcoholic steatohepatitis, and psychiatricdisorders, suchasanxiety,depression, andeatingdisorders, associated with this syndrome. Women with PCOS also report decreased quality of life, with hirsutism and obesity playing the most prominent roles.5,6 Positioned at the interface between the skin and the endocrine system, dermatologists play a central role in the identification and diagnosis of women with PCOS. All of the clinical manifestations of hyperandrogenism are cutaneous: acne, hirsutism, and, less commonly, androgenic alopecia.Acanthosisnigricans, aknownmarkerofhyperinsulinemia, is alsocommonlypresent,but its relationshiptohyperandrogenemia is less wellknown.7Upto37%ofwomenwithmoderate tosevereacne meet thediagnostic criteria forPCOS, andup to60%ofwomen with PCOS will manifest hirsutism. Traditionally, acne that is localized to the jawandneck, has its onset orworsens in adulthood, or is associated with hirsutism and premenstrual flares hasbeenconsidered“hormonal” acne. It is a challenge fordermatologists to determinewho among these patientsmayhave PCOS because this form of acne commonly results from the local effects of increased androgen receptor sensitivity and increased activity of 5α-reductasewithin the pilosebaceous unit rather than fromhyperandrogenemia related to anunderlying endocrinopathy. Similarly, whereas hirsutism can be amarker of elevated serum androgen levels, it can also result from increased local follicular 5α-reductase activity and can vary significantly by ethnicity, with higher prevalence among South Asian women and lower rates among Japanese women.3 Atypical indicationforaPCOSworkupamongwomenwithhormonal acne and/or hirsutism is accompanying menstrual irregularity. However, 16% of women with PCOS have normal menses and therefore relying on menstrual history alone to trigger a workupmay be insufficient.8 The findings of the retrospective cross-sectional study by Schmidt et al1 offer guidance for the dermatologist faced with determining whether their patient warrants a workup for PCOS. This is one of the largest studies published to date that offers characterization of a PCOS population from the dermatologic perspective, and the most important of its kind published in a major dermatology journal. Strengths of the work include the authors’ efforts to collect laboratory data prospectively and their use of standardized disease severity scales to measure acne, hirsutism, and insulin resistance in Related articles pages 391 and 399 Opinion