Investigation of the Skin Characteristics in Patients with Severe GH Deficiency and the Effects of 6 Months of GH Replacement Therapy: A Randomized Placebo Controlled Study

Fatih Tanriverdi; Murat Borlu; Hulusi Atmaca; Cagdas Atasavun Koc; Kursad Unluhizarci; Serap Utas; Fahrettin Kelestimur


Clin Endocrinol. 2006;65(5):579-585. 

In This Article

Patients and Methods


The study was performed in Erciyes University Medical School Departments of Endocrinology and Dermatology. The Local Ethics Committee of the Erciyes University Medical School approved the study. All the patients and the control subjects gave their informed consent of participation in the study.

Sixteen women with Sheehan's syndrome, with a mean age of 48·1 ± 10·9 years, and 20 age-matched women (mean age 44·7 ± 6·4 years) as control subjects were included in the study. Menopausal status of the study groups was also similar (4 controls were premenopausal, the others were postmenopausal). Background characteristics of the patients are summarized in Table 1 . The criteria for the diagnosis of Sheehan's syndrome included:

  • history of postpartum haemorrhage and/or history of postpartum failure of lactation and/or secondary amenorrhoea;

  • varying degrees of loss of pituitary hormone reserve;

  • good clinical response to hormonal replacement therapy;

  • exclusion of pituitary mass lesion and empty sella on MRI.[6]

In all cases, hormone deficiencies other than GH ( Table 1 ) had been adequately replaced with levothyroxine, and adrenal steroids (prednisolone). Only 3 patients were currently taking replacement sex steroids (ethinyl oestradiol 20 µg and degestrol 150 µg, orally). Thirteen patients who were > 45 years old had taken replacement sex steroids after diagnosis until menopausal age (45 years). The diagnosis of GHD was established by insulin tolerance test (ITT) and defined as a peak GH response < 9 mIU/l (3 µg/l) to the ITT ( Table 1 ). After an overnight fast, the ITT was performed using intravenous regular insulin (0·1 U/kg) and serum glucose, cortisol and GH levels were measured before and after 30, 45, 60 and 90 minutes. All patients had serum glucose levels < 2·2 mmol/l during ITT. Patients with diabetes mellitus, other systemic illnesses, skin disorders and malignancies were excluded from the study. None of the patients or the controls was using any topical moisturizing cream or cosmetic.

Administration of GH and Placebo

Ten patients received recombinant GH (Genotropin; Pfizer Stockholm, Sweden) for 6 months (treatment group) and 6 patients received placebo (placebo group) during this period. GH treatment was given according to the recommendations of the Growth Hormone Research Society Workshop.[16]

GH was self-administered at night s.c and drug compliance was assessed by vial count. Treatment with GH was started at a dose of 0·45 IU (0·15 mg)/per day in month 1, increased to 0·9 IU (0·30 mg)/per day in month 2. Maintenance dose (ranging from 1·5 IU to 1·8 IU/per day until the end of month 6) was adjusted according to IGF-I levels relevant to the age of each patient (individualized dosing regimen).

Analytical Methods

Skin characteristics were measured by Corneometer CM825, Sebumeter SM810, Tewameter TM210 and Phmeter PH900 (Courage-Khazaka Electronic GmbH, Cologne, Germany) as noninvasive reliable measuring methods.[17,18,19,20] The baseline measurements in 16 patients with GHD and 20 healthy controls were performed initially. In the patient group, skin characteristics were re-evaluated 6 months after the administration of GH (treatment group) and placebo (placebo group).

All procedures were performed by the same investigator (MB), who was unaware of the clinical diagnosis and the group of the subjects, in a room with constant temperature and humidity. The room temperature was 21 °C with a humidity level of 40-45%. Before the measurements, the patient was given time to adapt to room conditions without covering the measurement sites with clothes. Measurements were performed between 1400 h and 1600 h in all the patients to exclude diurnal variations.

The Corneometer CM 825 (Courage-Khazaka Electronic GmbH, Cologne, Germany) determines the humidity level of the stratum corneum by measuring electrical capacitance. Alterations in epidermal skin hydration lead to a change in capacitance of the measuring condensator. The probe is applied to the skin for one second at a pressure of 7·1 N/cm2. The degree of skin capacitance is indicated in system-specific units.[21,22] One unit represents a water content of stratum corneum of 0·02 mg/cm2, at a measuring depth of 20 nm. The interpretation of the corneometer CM 825 results is as follows: very dry < 30; dry 30-45; sufficiently moisturized > 45.

The Sebumeter SM 810 (Courage-Khazaka 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 s 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 result displayed in units that are then converted to µg/cm2.[19,20] The variation of light transmission is proportional to the quantity of lipids absorbed. Degreasing agents affecting the skin sebum were not used and sebum casual level was presented as sebum content.

TEWL was measured with an evaporation meter (Tewameter TM 210; Courage and Khazaka, 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.[23] The temperature and the moisture sensors, as well as the measuring electronic and the calibration data are located inside the probe. The physical basis for measuring TEWL is the diffusion law discovered by Adolf Fick in 1855. The probe of the Tewameter is equipped with temperature and moisture sensors that enable the measurement of the diffusion flow of water, maintaining the homogenous zone by the narrow cylinder of the probe. The interpretation of the TEWL results are as follows: 0-10, very healthy condition; 10-15, healthy condition; 15-25, normal condition; 25-30, strained skin; > 30, critical condition.

Temperature was also measured using TEWL and Skin pH was measured using a pHmeter (Courage-Khazaka Electronic GmbH, Cologne, Germany). The measuring range of pHmeter is pH 0-12 and the measurement resolution is 0·01 pH. Measurements were performed on two sites; forehead and the volar side of the forearm, which were kept free from garments before the measurements.

Serum GH levels were measured by using immunoradiometric assay with a commercial kit (DSL, Webster, TX, USA) intra- and inter-assay coefficients of variation (CV) were 3·1% and 5·9%, respectively, and GH standards were calibrated according to the WHO reference standard 88/624. IGF-I was measured by immunoradiometric assay after formic acid-ethanol extraction (BC1010, Biocode SA, Liege, Belgium); intra- and inter-assay coefficients of variation were 3·4% and 8·4%, respectively. The minimum detectable concentration of IGF-I was 5 ng/ml, and the reference ranges (mean ± 2 SD) for the relevant ages were 83-570 ng/ml (30-45 years) and 61-430 ng/ml (46-60 years).

Statistical Analysis

Statistical analysis was performed by using SPSS 10·00 program. Results were given as median (range; minimum-maximum), because the data were not normally distributed. The results of the study were analysed by a two-sided paired sample Wilcoxon test (measurements before and after GHRT) and Mann-Whitney-U-test (measurements in healthy controls and patients with GHD). P < 0·05 was considered as significant.


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