Skin Often a 'Window' Into Underlying Endocrine Disorders

Pam Harrison

January 04, 2016

Two separate studies have provided new insights into cutaneous manifestations of common endocrine disorders that, if they are present, should prompt clinicians to explore patients for underlying metabolic abnormalities that could be a harbinger for future serious complications.

In the first study, US investigators under lead author Timothy Schmidt, MD, PhD, from the University of California, San Francisco, discovered that hirsutism and the skin pigmentation disorder acanthosis nigricans, especially if located in the axillae, are the most reliable cutaneous markers of the polycystic ovary syndrome (PCOS) in women; when present, such findings should trigger further diagnostic evaluation for metabolic comorbidities that can lead to long-term complications in PCOS.

In the second study, Mohit Nagpal, MD, from the Postgraduate Institute of Medical Education and Research, Chandigarh, India, and colleagues found that postadolescent males with acne are more likely to have insulin resistance and that they, too, should be followed up for a period of time in order to detect any conditions that might develop because of the current state of insulin resistance.

Both studies were published online December 23 in JAMA Dermatology.

In an accompanying editorial, Rachel Reynolds, MD, from Beth Israel Deaconess Medical Center, Boston, Massachusetts, says the two studies "highlight the important role that the dermatologist plays in identifying and characterizing patients with common skin disorders who may be at risk for metabolic and androgen-mediated disease."

Skin Disorders in Racially Diverse Women With PCOS

In the US study, Dr Schmidt and colleagues found that out of 401 racially diverse women with suspected PCOS seen at the University of California's Polycystic Ovary Syndrome Multidisciplinary Clinic, 68.8% of patients met the Rotterdam diagnostic criteria for PCOS while 12% did not.

The remaining 19.2% of women were excluded from the analysis because of insufficient data or for other reasons.

Approximately 92% of the women who met the Rotterdam criteria had at least one skin finding. On average, women meeting PCOS criteria had a mean of 1.97 cutaneous findings compared with a mean of 1.25 among those who did not meet the PCOS criteria (P < .001).

Hirsutism was significantly associated with acanthosis nigricans in women meeting PCOS criteria (P < .001), and one-quarter of women who had either of these cutaneous manifestations of PCOS had both.

Multiple cutaneous findings were also more likely to be present in women who met the criteria for PCOS compared with those who did not, but the differences between the groups were not all statistically significant.

Prevalence of Cutaneous Findings Among Women Suspected of Having PCOS
Cutaneous finding Did not meet PCOS criteria (%)
Met the PCOS criteria (%)
Acne 40.4 61.2 .004
Hirsutism 31.2 53.3 .005
Acanthosis nigricans 20 36.9 .03
Androgenic alopecia 11.4 22.4 .10
Seborrheic dermatitis 17.8 30.4 .08
Individual Cutaneous Findings: Messages for Clinicians

Looking at individual cutaneous findings, Dr Schmidt and colleagues identified several distinctions between women who met PCOS criteria and those who did not. For example, women who met the Rotterdam criteria had more severe truncal hirsutism and higher rates of axillary acanthosis nigricans than women who did not.

Hirsutism when present in PCOS was also associated with higher levels of insulin resistance, at 4.18, compared with 3.38 in non-PCOS women (P = .002); with greater body mass index (BMI), at 32.3 vs 29 kg/m2 (P < .001); and with higher triglyceride levels, at 114 mg/dL vs 104 mg/dL, respectively (P = .04).

PCOS women also had lower levels of HDL, at 52 mg/dL vs 59 mg/dL for non-PCOS women (P < .001).

And when present in women with PCOS, acanthosis nigricans was associated with a significantly increased prevalence of free testosterone elevations, at 53.3% vs 27% for women without acanthosis nigricans (P < .001).

Acanthosis nigricans in PCOS women was similarly associated with significantly increased measures of insulin resistance, at 7.13 vs 2.05 for PCOS women without acanthosis nigricans (P < .001), as well as higher BMIs, higher levels of total cholesterol, and higher levels of LDL cholesterol and triglycerides, as well as lower mean HDL-cholesterol levels.

It was not associated with abnormal 2-hour glucose tolerance results, however.

In contrast, the presence of acne and androgenic alopecia, though prevalent in women with PCOS, were both deemed to be unreliable markers for the syndrome.

"Our research team believes that this study is important because it identified two skin findings — hirsutism and acanthosis nigricans — as signs of underlying systemic abnormalities in women with PCOS," senior author Kanade Shinkai, MD, PhD, University of California, San Francisco, told Medscape Medical News in an email.

"Both were associated with increased prevalence of insulin resistance, obesity, and abnormal cholesterol/lipid levels," he added, "and when present in a patient with PCOS, clinicians should consider doing additional diagnostic evaluations to screen patients for these potential [disorders]."

The other important message for clinicians, Dr Shinkai said, is that even in high-risk patients, acne and hair loss — although common in women with PCOS — are not specific enough findings for the diagnosis.

"Referral to a dermatologist to aid in diagnosis and management of cutaneous signs of PCOS may be very helpful in the evaluation of a woman suspected of having the condition," Dr Shinkai suggested.

India Study: Acne Associated With Metabolic Abnormalities

The Indian study was cross-sectional and involved 100 male patients with acne and 100 age-matched male controls without acne. Participants were recruited from a dermatology outpatient department of a tertiary-care institute. Insulin resistance was measured using the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) measure, while the metabolic syndrome was diagnosed using criteria from the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III).

It is noteworthy that among men in India, a BMI of 23 through to 24.9 kg/m2 is considered overweight while a BMI of 25 through 29.9 kg/m 2 is considered to be moderately obese.

As Dr Nagpal and colleagues report, the mean HOMA-IR value in men with acne was significantly higher, at 2.0, than in controls, at 1.7 (P = .049), while insulin resistance — arbitrarily predefined as a HOMA-IR value greater than 2.5 — was detected in 22% of men with acne compared with 11% of controls, which was significantly different (P = .036).

Both the mean systolic and mean diastolic blood pressure of men with acne were also significantly higher than that of the controls (P = .01 and .002, respectively), as were mean fasting plasma glucose levels, at 88.2 mg/dL in men with acne, compared with 84.5 mg/dL among controls (P = .008).

In contrast, the prevalence of the metabolic syndrome — in 17% of men with acne compared with 9% of controls — was not statistically different between the two groups, and mean fasting insulin levels were comparable, too.

When men were categorized into four categories of acne severity, investigators found that the mean BMI in those with very severe acne was significantly higher than the mean BMI in those with mild acne, but there were no differences among the different acne severity groups in blood pressure, height, or waist circumference.

On the other hand, mean fasting plasma glucose levels in all acne severity categories were higher than in controls (P = .55).

The Dermatologist as Detective: Complete Cutaneous Exam

In her editorial, Dr Reynolds commented that the results from the Schmidt study emphasize the importance of doing a complete cutaneous examination of patients suspected of having PCOS, because hirsutism on the trunk and acanthosis nigricans of the axillae proved to be the most specific and strongest clinical predictors of elevated serum androgen levels and a PCOS diagnosis.

"These findings are novel and have the potential to improve the diagnostic abilities of the dermatologist caring for these patients," she added.

As for the Indian study, Dr Reynolds noted that the findings should encourage clinicians to consider evaluating their adult male patients with acne for all components of the metabolic syndrome: "Once again, the role of the sebaceous gland reminds us of the intimate relationship between the skin and the endocrine system."

"The findings of these two studies remind us that as dermatologists, our detective work goes beyond identifying patterns on the surface to clinch a diagnosis," she concluded.

The Schmidt et al study was funded in part by the National Center for Advancing Translational Sciences, National Institutes of Health. Dr Schmidt had no relevant financial relationships; disclosures for the coauthors are listed in the article. Dr Nagpal and coauthors report no relevant financial relationships, nor did Dr Reynolds.

JAMA Dermatol. Published online December 23, 2015. Schmidt abstract, Nagpal abstract, Editorial


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