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

Disclosures

Clin Endocrinol. 2006;65(5):579-585. 

In This Article

Discussion

The present study demonstrated for the first time that the sebum content and skin hydration were significantly decreased in GH deficient patients with Sheehan's syndrome, and 6 months of GHRT significantly increased the sebum content on forehead in particular.

The skin is a target organ for various hormones. The role of GH in the skin growth and development is strongly supported by clinical states of GH excess. Increased GH levels in acromegalic patients are associated with thickened, coarse, oily skin, skin tags and acanthosis nigricans.[12,24] Normalization of GH levels in acromegalic patients leads to a reduction in the skin thickness indicating that the effects of GH in the skin are reversible.[25] In contrast, patients lacking growth hormone receptor activity (Laron syndrome) and those with GH deficiency display thin skin and/or reduced elasticity due to a reduction in dermal thickness.[26,27] Treatment of GH deficient men revealed that GH could augment the androgenic effects on pubic hair development in the skin.[28,29,30] Furthermore, male GH-transgenic mice exhibit a greater increase in skin thickness and the skin surface area when compared with their female counterparts. Castration of these mice prevents the increase in skin thickness and thus confirms a role for synergy between GH and androgens in skin growth.[31] The observed effects of GH on the skin thickness, and in some cases mechanical strength, are primarily due to an increase in collagen content of the dermis and are not due to epidermal expansion.[32] GH can bind to cultured human fibroblasts, via GH receptors, and elicit a proliferative response. Studies of GH action on avian fibroblasts revealed that GH alone could stimulate the production of collagen. In addition, IGF-I can synergize with GH and increases collagen production to the levels greater than that achieved by either growth factor alone and provides further explanation for the increase in dermal thickness seen in conditions of GH excess.[27]

Role of GH in thermoregulation and sweat secretion has been previously demonstrated.[33,34,35,36,37] In a study by Hasan et al.[33] skin biopsies have been obtained from GH deficient patients and changes in morphology and innervation parameters for the eccrine sweat glands have been examined. They have demonstrated a sweating defect in adult GHD which is accompanied by a reduction in acetylcholinesterase (AChE) and vasoactive intestinal polypeptide (VIP) levels in the nerve supply to sweat glands. Following 6-12 months of GHRT therapy, an increase in AChE and VIP staining were reported in the sudomotor nerves accompanied by restoration of sweat rates. In an early cornerstone study, Juul et al.[35] concluded that decreased sweating and impaired thermoregulation are components of the adult GHD syndrome, and GH deficient patients are at risk of developing hyperthermia during exercise in hot environments.

The above-mentioned studies clearly demonstrated decreased skin thickness with decreased collagen content and decreased sweating in patients with GHD. However there are not enough data regarding the impact of GH and/or IGF-I in skin characteristics including pilosebaceous unit function.[28] In an elegant study evaluating the histomorphology of skin, Lange et al.[12] did not find any structural changes on the sebaceous glands in patients with GHD and acromegaly when compared with the controls. However they have not investigated functional aspects of the sebaceous glands including the sebum content. The present study clearly demonstrated that the sebum content was significantly reduced on forehead but not on forearm in the patients with GHD when compared to the controls. The difference of sebumeter measurements between the patients and controls is more evident on forehead, which may be postulated to be one of the seborrhoaeic areas. Moreover in the GH treated group but not in the placebo group, there was a significant increase in the sebum content on forehead. Consistent with our findings, Deplewski & Rosenfield[38] have reported that in a cell culture model GH acts directly on sebocyte differentiation. Hydration of the skin (skin capacitance) on both forehead and forearm was clearly lower in the patients when compared with the control subjects. But we did not find any significant increase in the skin capacitance after GHRT suggesting that 6 months of GHRT may not be sufficient to normalize the skin hydration and long-term follow-up is necessary.

Sheehan's syndrome is characterized by severe and long duration of GH deficiency.[8,11] In patients with Sheehan's syndrome, GH is one of the earliest hormones lost, and well characterized skin changes are described as early ageing of the skin and typical facial appearance with fine wrinkling.[11] Although skin changes in GH deficiency are described clinically, we measured skin properties with a noninvasive objective measurement technique for the first time, and showed distinct changes especially including decreased sebum content and capacitance on the face of the patients with Sheehan's syndrome. These findings are consistent with the term of 'dry skin' described in patients with GHD implying that dry skin, at least in part, is associated with both decreased sebum content and skin hydration. Moreover 6 months of GHRT partially reverses some of these changes.

The water content of the stratum corneum (capacitance) and the skin surface lipids form a balance that is important for the appearance and function of the skin. These binding substances of the skin act together as a barrier to the environment. If this balance is disrupted, a dermatological condition known as 'dry skin' (which may make the skin more sensitive to the various infections, allergies and eczemas) ensues. Sebum has a beneficial effect to keep the skin surface supple and moist. If the glands produce too much sebum, the skin surface becomes oily; if the glands produce too little sebum, the skin surface becomes dry. Indeed, patients with skin disorder such as atopic dermatitis were reported to be associated with decreased levels of skin sebum and hydration.[20] On the other hand, TEWL value may reflect the skin condition; it decreases in case of strained or injured skin.[17] Therefore the noninvasive measurement technique which was used in the present study may be useful in clinical practice in several conditions including atopic dermatitis, eczemas and skin injuries.

Apart from GH, several hormones including glucocorticoids, oestrogen, and thyroid hormones play important roles in pilosebaceous unit development and function.[28] To rule out the effects of the deficient hormones, at baseline appropriate replacement therapies except GH had been given according to generally accepted principles. Moreover a significant increase in the sebum content on forehead in GH treated group but not in placebo group clearly implies that GH and/or IGF-I per se has several effects on skin characteristics. The presence of GH receptor in human skin and its appendages suggests a direct effect of GH on skin characteristics,[9,10] but the exact mechanism by which GH exerts its effect is unclear. However in a previous study using PCR the abundance of IGF-I receptor mRNA in human skin biopsies could suggest an IGF-I mediated action on skin.[39]

In conclusion, this study clearly shows that the sebum content on forehead and skin hydration on forehead and forearm are significantly decreased in GH deficient patients with Sheehan's syndrome. However 6 months of GHRT significantly increased only the sebum content on the forehead. These data suggest that GH and/or IGF-I may have a modulatory role on several skin characteristics. Further functional and histomorphological studies are warranted to clarify the effects of GH on skin physiology and the potential role of GH replacement therapy.


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