Acromegaly is associated with decreased skin transepidermal water loss and temperature, and increased skin pH and sebum secretion partially reversible after treatment

Abstract

Background

Acromegaly is characterized by an acquired progressive somatic disfigurement, mainly involving the face and extremities, besides many other organ involvement. Wet and oily skin was described in acromegaly patients and it was attributed to hyperhidrosis and increased sebum production but this suggestion has not been evaluated with reliable methods.

Objective

The aim of this study was to examine the skin parameters of patients with acromegaly using measurements of skin hydration, sebum content, transepidermal water loss, pH and temperature and particularly the effects of 12 months of treatment on these parameters.

Methods

52 patients with acromegaly and 24 healthy control subjects were included in this two blinded prospective study. Skin properties were measured on forehead and forearm by Corneometer CM825, Sebumeter SM810, Tewameter TM210 and Phmeter PH900 as non-invasive reliable measuring methods. Serum GH, IGF-1 and all measurements of skin properties on forehead and forearm were repeated at the end of the 3, and 6 months of therapy in 20 cases. Patients were treated with appropriate replacement therapy for deficient pituitary hormones.

Results

The sebum content and pH of the skin of acromegalic patients were significantly higher and transepidermal water loss and skin temperature were found to be significantly lower in acromegalic patients when compared to the control group both on forehead and forearm. GH and IGF-1 levels were positively correlated with sebum levels and negatively correlated with skin temperature on both forehead and forearm. The sebum levels of the patients were significantly decreased both on forehead and forearm at 3rd and 6th months of treatment.

Conclusion

The present study demonstrated increased sebum secretion, decreased transepidermal water loss, alkali and hypothermic skin surface in patients with acromegaly by reliable methods for the first time. These data suggest that GH and/or IGF-I may have a modulatory role on several skin characteristics which can be at least partially reversible with treatment.

Introduction

Endocrine and metabolic diseases, besides affecting other organs, can result in changes in cutaneous function and morphology. Acromegaly is a disease almost always caused by a growth hormone (GH) secreting pituitary adenoma. The elevated GH and insulin-like growth factor-1 (IGF-1) levels are associated with a wide range of respiratory, endocrine and metabolic comorbidities [1], [2].

Bony and soft tissue changes are responsible for the characteristic appearance of patients with acromegaly. The changes are most prominent on the face, hands and feet. Increased perspiration, skin puffiness and doughy consistency are seen. Eyelids are edematous and thickened, nasolabial and forehead folds are deepened. Skin tags, acantosis nigricans, Reynaud's syndrome and cutis vertisis gyrate are also described in acromegaly. ‘Wet and oily skin’, which is attributed to hyperhidrosis and increased sebum production, is one of the classical symptoms [1], [3], [4].

The evidence-based data regarding skin changes in acromegaly include skin thickening due to slightly increased fibroblasts and glycosaminoglycan deposition in dermis on histological examination [5], hyperhidrosis demonstrated by sweat test and skin biopsy [6], [7] and increased elasticity of the skin measured by computerized suction device [8].

Although described as common, functional changes of the skin such as ‘wet and oily skin’ in acromegaly has not previously been shown by reliable methods, at least according to our knowledge. The aim of the present study was to objectively demonstrate the functional skin changes and the effects of treatment on these changes in patients with acromegaly. For this reason we measured skin humidity, sebum content, transepidermal water loss, pH and temperature, and examined the effects of treatment (surgery or somatostatin analogs) on these parameters.

The study was carried out in Erciyes University Medical School Departments of Dermatology and Venereology, and Endocrinology between 2008 and 2010. The local ethics committee of the Erciyes University Medical School approved the study. 52 patients with acromegaly and 24 healthy control subjects were included in the study. Acromegaly was biochemically diagnosed as the presence of increased IGF-1 levels according to age and sex and lack of GH suppression to less than 1 μg/L following a 75 g oral glucose load [9]. 26 patients were newly diagnosed and treatment naive. The other 26 patients had active acromegaly (increased IGF-1 levels according to age and sex with or without increased GH levels) who were previously treated by surgery and/or somatostatin analogs. All the patients had underwent surgery for adenoma removal and none of them received radiotherapy previously. 2 patients were on octreotide-LAR alone, one received 20 mg/month and the other 30 mg/month and 2 patients were on cabergoline (1 mg/week) alone at the time of basal evaluation. Patients with pituitary insufficiency were given appropriate replacement therapy. Accompanying pituitary hormone deficiencies were as: isolated ACTH in 6, combined ACTH and TSH in 2 and isolated gonadotropin in 2. 40 out of 52 patients (77%) were free of medical treatment of acromegaly or pituitary insufficiency.

Eleven of 20 patients who were prospectively followed-up were commenced on octreotide-LAR and 9 of them underwent transsphenoidal surgery for adenoma removal. Treatment response was defined as ‘complete’ if the patient had normal IGF-1 levels according to age and sex and a safe basal GH level of ≤ 2.5 μg/L. All other cases were defined as ‘treatment failure’ [9]. Treatment response was determined in prospectively investigated patients. Patients with pituitary hormone deficiencies were treated appropriately before skin measurements.

None of the patients and control subjects were using topical moisturizing creams, and cosmetics were stopped at least 48 h before the evaluation. Skin properties were measured by Corneometer CM825, Sebumeter SM810, Tewameter TM210 and Phmeter PH900 as non-invasive reliable measuring methods [10], [11], [12], [13]. The Corneometer CM 825 (C + K Electronic GmbH, Cologne, Germany) determines the hydration level of the stratum corneum by measuring electrical capacitance. Alterations of epidermal skin hydration lead to a change in capacitance of the measuring condensator. The probe is applied to the skin for 1 second at a pressure of 7.1 N/cm². The degree of skin capacitance is indicated in system specific units [14], [15], [16], [17]. One unit represents a water content of stratum corneum of 0.02 mg/cm², at a measuring depth of 20 nm. The Sebumeter SM 810 (C + K Electronic GmbH, Cologne, Germany) was used for quantitative measurements of skin surface lipids composed of sebum and corneal lipids. It consists of a fat-stain photometer that measures the level of light transmission of a plastic sheet coated with sebum. The method is insensitive to humidity. A probe is pressed on the skin region under investigation for 30 seconds at a constant pressure of 9.4 N/cm². The Sebumeter device measures the variation of light transmission through the strip. The change in sheet transparency is computed, and the results displayed in units that are then converted into μg/cm [14], [15]. The variation of light transmission is proportional to the quantity of lipids absorbed. Any decreasing agent affecting the skin sebum was not used, and sebum casual level was presented as sebum content. Transepidermal water loss (TEWL) was measured with an evaporation meter (Tewameter TM 210; C + K Electronic, Cologne, Germany). Measurements (expressed in g/m²/h) were performed according to the European Group for Efficacy Measurements on Cosmetics and Other Topical Products Guidance for the assessment of TEWL [18]. Temperature was also measured by using TEWL, and skin pH measured by using pHmeter (PH900, C + K Electronic GmbH, Cologne, Germany). All procedures were performed by the same investigator (MB), who was not aware of the clinical diagnosis, treatment and time of evaluation. Treatments were conducted for all patients without any information about skin properties. Measurements were performed on two sites, forehead as a representative of seborrhoeic area, and volar side of the forearm as a non-seborrhoeic skin.

Serum GH levels were measured by two-site immunoradiometric assay (IRMA with Active Human Growth Hormone DSL-1900 (Texas, USA) (calibrated to WHO 88/624). The lower detection limit for GH was 0.01 μg/L with intraassay coefficients of variation (CVs) ranging from 3.1% to 5.4% and interassay CVs ranging from 5.9% to 11.5%. Serum IGF-1 levels were measured by Active Non-extraction IGF-1 IRMA DSL-2800 (Texas, USA). The lower detection limit for IGF-1 was 2.06 μg/L with intraassay CVs ranging from 3.9% to 7% and interassay CVs ranging from 3.8% to 7.4%.

GH, IGF-1 and all measurements of skin properties on forehead and forearm were repeated at the end of the 3, and 6 months of therapy for individual cases.

The room temperature was set to 20–22 °C and the humidity level to 40–45%. Before the measurements, patients were held in the test room for 30 minutes, leaving the measurement sites uncovered, for adaptation of skin to room temperature and humidity. Measurements were performed between 2 and 4 pm to exclude diurnal variations.

Results are given as the mean ± standard deviation. Kolmogorov–Smirnov test was used to show desperations. Mann–Whitney U or Unpaired t tests were used where appropriate to analyze differences between the results of skin capacitance, sebum, temperature, TEWL and pH in patients and controls. Correlations between measured hormonal and skin parameters were tested by Spearman correlation analysis. Friedman and two related Wilcoxon rank test as post hoc were used to determine the differences between the repeated measures. Bonferroni test was used for corrections. p < 0.05 was considered as statistically significant (Table 1).