Cosmetic agents causing endocrinopathy in an African immigrant

It has become common practice for African men and women to chemically alter their natural skin tone for aesthetic purposes. This is realized by the use of cosmetic skin-bleaching agents, which are sold without regulation. These products have potential for adverse health effects, including nephrotoxicity, neurologic symptoms, and suppression of the hypothalamic-pituitary-adrenal (HPA) axis. We report a case of a woman using one such preparation, presenting with exogenous Cushing syndrome and uncontrolled diabetes.

Case

Alisha was a 46-year-old woman who had been living in Canada for 1 year. She was an immigrant from Africa. Alisha presented to the emergency department with a several-day history of weakness, polyuria, polydipsia, and new-onset hyperglycemia (blood glucose level of 41.1 mmol/L). Her past medical history included a 6-year positive HIV status, and she was receiving highly active antiretroviral treatment at the time of admission. Her CD4 cell count from 3 months earlier was 804 cells/mm³ of blood. Other past medical history included pulmonary tuberculosis, hepatitis C, pancreatitis secondary to isoniazid therapy, and ovarian abscess. Her medications included abacavir, atazanavir, moxifloxacin, folic acid, cycloserine, and pyridoxine. There was no family history of diabetes mellitus or other endocrinologic disorders.

On history, Alisha reported a 5-kg weight loss in recent weeks and complained of fatigue, generalized weakness, and blurred vision without diplopia. She did not have symptoms of concurrent infection. She had had difficulty climbing stairs and standing from a seated position for months to years. Further questioning elicited a history of easy bruising and oligomenorrhea. Alisha denied observing a darkening of her skin tone; rather, she told us that her skin had become lighter secondary to a bleaching cream she had been using for several years. Upon arriving in Canada she had changed brands of bleaching product. Alisha showed pictures taken at the time of her arrival in Canada in which her skin colour was considerably lighter than at presentation.

On examination, the patient was obese, with supraclavicular and dorsal-cervical fat fullness. Her blood pressure was 100/75 mm Hg, and her pulse rate was 86 beats/min. There were no skin striae, bruises, hirsutism, wasting, or lipodystrophy. The thyroid gland was not palpable. Mild proximal muscle weakness was present. Laboratory data revealed the following: a hemoglobin A_1c level of 13.2%; a morning serum cortisol level of 14 nmol/L (reference range 120 to 535 nmol/L); undetectable serum corticotropin levels; and a 24-hour urine cortisol level of 27 nmol/L (reference range 100 to 250 nmol/L). The patient was then sent for dynamic testing with 250 μg of cosyntropin. At time zero, the cortisol level was 17 nmol/L; 30 minutes later it was 149 nmol/L, and at 60 minutes it was 202 nmol/L. A normal response is a cortisol level of greater than 550 nmol/L. This response, although brisk, is subnormal, reflecting adrenal gland reduced cortisol reserve.

The diagnosis of exogenous Cushing syndrome was made. Alisha discontinued the bleaching cream. She was started on a tapering dose of hydrocortisone, as well as insulin for management of hyperglycemia. Imaging was undertaken to rule out an adrenal tumour, which had negative findings.

Follow-up blood tests completed 2 months after discontinuation of the bleaching cream demonstrated normalized corticotropin and cortisol levels. Accordingly, Alisha was able to use half the original dose of insulin to control the hyperglycemia. Later follow-up blood tests, however, showed cyclical low corticotropin and morning cortisol levels (Table 1).

Table 1.

Timeline of activity or laboratory investigations

DATE	ACTIVITY OR LABORATORY INVESTIGATION
May 2–4 (2007)	Patient presented to emergency department Cortisol level measured at 9 nmol/L (random level)
May 10	Patient advised to discontinue use of the bleaching cream
May 14	24-hour urine cortisol level measured at 30.7 nmol/L
June 4	Corticotropin level measured at < 2 pmol/L Cortisol level measured at 3 nmol/L (morning level)
July 19	Corticotropin level measured at 8 pmol/L Cortisol level measured at 217 nmol/L (random level) Patient admitted to resuming use of the bleaching cream
September 21	Corticotropin level measured at 3 pmol/L
November 23	Corticotropin level measured at < 2 pmol/L Cortisol level measured at 8 nmol/L (morning level) Patient was again encouraged to discontinue use of the bleaching cream
January 23 (2008)	Corticotropin level measured at 7 pmol/L Cortisol level measured at 262 nmol/L (morning level) 24-hour urine cortisol level measured at 202 nmol/L

Discussion

Several social pressures favouring lighter skin tone among Africans have been previously identified,¹ including media advertisements in Africa (which glorify lighter skin tone) and the rating of skin colour as a determinant of social class. A study from Togo illustrated how broadly skin-bleaching products are used in African countries, revealing that 58.9% of the 910 female participants used cosmetic skin-bleaching creams.²

These products have potential for adverse health effects; however, most medical practitioners outside of Africa are unaware of their widespread use. According to dermatologists practising in Nigeria, these products are sold solely in local shops patronized by Africans, rather than traditional pharmacies or cosmetic shops.³ Most are sold as cosmetic products in nonmedical stores without warning about adverse effects or contraindications.⁴

Many skin-bleaching creams contain hazardous compounds. Analysis of the products consumers reported using in the Togo questionnaire revealed that 18.5% contained topical corticosteroids. In 25.6% the composition of the product was not specified.² Sales of these sensitive products are unregulated and they can be obtained without prescription, leading to potential abuse by consumers.

Complications of skin-bleaching creams depend on the active ingredients and are considerably influenced by the extent and duration of use. The creams are often applied to the whole body (large surface areas) and under hot and humid conditions in which percutaneous absorption is enhanced. Furthermore, continued use of the product is necessary to maintain the light complexion. With long-term abuse, chronic adverse effects become increasingly prevalent.

With regard to cutaneous adverse effects, including hypopigmentation, hyperpigmentation, and atrophy, dermatologists studying patients who use such products found an adverse effect rate of 69.2%.² Unfortunately, when cutaneous complications occur, rather than discontinuing use of the bleaching products, most individuals actually intensify their use, hoping to bleach away the imperfections and even out the skin tone.

More serious complications abound. Potent corticosteroids are well known to cause infections, exogenous Cushing syndrome, and suppression of the HPA axis. Other adverse effects include nephrotoxicity⁵ and neurologic manifestations.⁶

Our patient’s clinical case was consistent with adrenal insufficiency in the setting of Cushing syndrome secondary to exogenous glucocorticoid steroid administration and withdrawal. Systemic absorption of a noncortisol steroid would suppress the HPA axis, resulting in low corticotropin and cortisol levels. The level of novel steroid in her blood would not be detected by testing, which is specific to the cortisol molecule.

In Nigeria, Cushing syndrome is more commonly encountered in chronic skin bleachers. Patients present with overt features of Cushing syndrome, such as moon facies, truncal obesity, and the characteristic wide erythematous striae and folliculitis of the lower axillae.³ Patients might present with systemic manifestations of Cushing syndrome, including glucose intolerance and hypertension.

In regard to the cyclically low cortisol and corticotropin levels, we postulate that Alisha had difficulty discontinuing use of the bleaching product for physiologic as well as psychosocial reasons. Steroid addiction syndrome is a clinical phenomenon that results from chronic daily use of a potent glucocorticoid applied to areas of highly vascularized skin (eg, face, neck, scrotum, and vulva) for greater than 1 month. When patients attempt to withdraw the topical steroids, they experience a burning pain that is soothed upon reapplication of the steroid.

Conclusion

Physicians need to be aware that patients of African origin might be using skin-bleaching treatments, and they should inquire specifically about such treatments when evaluating endocrine disorders, particularly Cushing syndrome. African patients with complications secondary to skin-bleaching agents can present anywhere in the world. Such products are commonly used in both men and women, with one study citing 58.9% of female participants using such products.² These products are unregulated and contain potentially hazardous substances. Skin bleaching is a cultural phenomenon that has a strong social component.

EDITOR’S KEY POINTS

• Cosmetic skin-bleaching agents are sold without regulation. These products have potential for adverse health effects, including nephrotoxicity and neurologic symptoms.

• Most medical practitioners outside of Africa are unaware of the widespread use of skin-bleaching products. Physicians need to be aware that patients of African descent might be using these treatments to lighten their skin tone.

• This report highlights the importance of taking a detailed social and drug history, as some of the cosmetic agents are responsible for causing exogenous Cushing syndrome.

POINTS DE REPÈRE DU RÉDACTEUR

• Les agents cosmétiques de blanchiment de la peau sont vendus sans être réglementés. Ces produits peuvent avoir des effets néfastes sur la santé, notamment la néphrotoxicité et des symptômes neurologiques.

• La plupart médecins praticiens en dehors de l’Afrique ne sont pas au courant de l’utilisation très répandue de produits de blanchiment de la peau. Les médecins doivent savoir que les patients d’origine africaine sont susceptibles d’utiliser ces traitements pour pâlir la couleur de leur peau.

• Ce rapport met en évidence l’importance de faire un bilan détaillé de la situation sociale et des médicaments des patients, car certains de ces agents cosmétiques sont à l’origine du syndrome de Cushing exogène.