In this study of 29 adults with PWS, mean hair cortisol levels were significantly higher than hair cortisol in 105 sex and age matched population-based controls. Hair cortisol increased with BMI and reported stress in patients with PWS.
The stress hormone cortisol, produced in the adrenals, is important in maintaining body homeostasis by modulating neuroendocrine functions, the sympathetic nervous system and the immune function. Cortisol levels are regulated by activity in the hypothalamus and pituitary and secreted in a pulsatile circadian rhythm with increased secretion in response to stress. Cortisol is commonly measured in blood, and saliva, but these methods only reflect the time point at which the sampling is done or the past 24 h cortisol production when 24 h urine is collected. Multiple samplings are often needed. However, during the past decade, the measurement of hair cortisol has emerged as a non-invasive method to estimate the cortisol concentrations over months (6, 14, 17). Hair grows at a relatively stable rate of approximately 1 cm/month, and cortisol accumulates in hair. Thus, cortisol in hair retrospectively represents the average cortisol level over the corresponding period. There is no discomfort associated with collection of the hair sample and no special storage precautions are required for the samples. This is an attractive procedure, especially in a population such as PWS where the psychological and behavioral features might complicate advanced sampling procedures. We found that collection of the hair samples worked out well in our PWS cohort, although some men could not participate because of too short hair for sufficient analyses. In addition, four patients declined participation because they felt that even the small hairless spot on the scalp after cutting the hair would stigmatize them further, although the sampling spot at the back of the scalp is usually too small to be visible afterwards.
In our cohort of patients with PWS, hair cortisol levels were clearly increased in patients who had reported significant stressful events. This is in accordance with several studies showing that the content of cortisol in hair is higher in individuals exposed to stress and stress-related disorders (12, 17–24). Some of the patients in the present study with normal to low normal hair cortisol reported nonspecific stressful situations, but the analysis of hair cortisol was probably not sensitive enough to detect minor or short-lived alterations of the HPA-axis (25).
Cortisol levels have been found to correlate positively with waist to hip ratio and waist circumference (26, 27, 19) and to be higher in obese individuals compared to normal-weight people (28, 29). To retain all patients with PWS in the statistical analyses, matching for BMI between patients with PWS and controls was not done since some severely obese patients with PWS could not be matched with controls. However, similar to previous studies of hair cortisol (30) we found an increase in hair cortisol with BMI in the patients with PWS.
It is well known that some patients with PWS suffer from diseases secondarily to obesity, such as diabetes, cardiovascular diseases, respiratory diseases and arthrosis (31). Chronic stress might exacerbate comorbidity and therefore, it can be of interest to be able to indirectly quantify chronic stress in patients with PWS, by measuring hair cortisol to guide monitoring and early treatment.
Furthermore, PWS is associated with a decreased life expectancy, with an annual death rate reported to be as high as 3% (32, 33). Nevertheless, a number of reported deaths were unexpected and unexplained, and it has been speculated if central adrenal insufficiency might have been the cause of some of the deaths (6). While the ACTH stimulation test provides information about the maximum response of the adrenal gland under stress hair cortisol concentrations provide information about average cortisol concentrations over a longer period. Our results warrant for larger and potentially randomized studies, but measurement of hair cortisol in PWS is attractive due to its non-invasive and simple performance. This is of great importance in individuals like patients with PWS, in whom a complicated procedure is a challenge. It is also an advantage that hair cortisol gives information on long-term cortisol exposure and might in the future be a baseline test for evaluation of the adrenal function and consideration for further evaluation.
PWS is a rare disease, and the number of participants in the present study was too small for more complex analyses and comparisons with the control group.
Another limitation in our study is the assessment of stress, which in both groups was interpreted from reported stress during different duration of time and different questionnaires, which potentially might have affected the results. Moreover, in the PWS group most of the questionnaires were answered by the patients’ caretakers and not directly by themselves and the questions on stress were not validated. Finally, patients with PWS who were able and willing to participate, might represent a selected group of quite healthy and well-functioning adults with PWS.