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Observation |

Potential Role of Human Growth Hormone in Melanoma Growth Promotion

Marc Z. Handler, MD; Andrew L. Ross, BA; Michael I. Shiman, MD; George W. Elgart, MD; James M. Grichnik, MD, PhD
Arch Dermatol. 2012;148(10):1179-1182. doi:10.1001/archdermatol.2012.2149.
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Background  Human growth hormone (HGH) and insulin-like growth factor-1 (IGF-1) have been shown to play a role in the malignant transformation and progression of a variety of cancers. HGH is also known to upregulate molecular signaling pathways implicated in the pathogenesis of melanoma. Although HGH has previously been implicated in promoting the clinical growth of both benign and malignant melanocytic neoplasms, to our knowledge there are no conclusive studies demonstrating an increased risk of melanoma following HGH therapy. Nevertheless, there are reports of melanoma developing subsequent to HGH coadministered with either other hormones or following irradiation.

Observation  A 49-year-old white man presented with a new pigmented papule that was diagnosed as melanoma. The patient reported using HGH for 3 months prior to the diagnosis. His 51-year-old wife, who also was white, had also been using exogenous HGH for 3 months and had been diagnosed as having a melanoma 2 weeks prior.

Conclusions  Given the unlikelihood of 2 unrelated people developing melanoma within a short time span, it is reasonable to assume that a common environmental component (HGH or other shared exposure) contributed to the development of both melanomas. Because of the increased use of exogenous HGH as an antiaging agent, it is important to be aware of the growth-promoting effects of this hormone. Until better data are available that determines the true risk of exogenous HGH, its use as an antiaging agent merits increased surveillance.

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Figures

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Figure 1. Clinical image revealing an 8-mm melanocytic lesion on the male patient's left lower back at the waistline. It did not match the pattern of his other moles, and he and his wife indicated that it was new.

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Figure 2. Dermoscopic features of a lesion on the male patient. These include irregular pigment network, nonuniform borders with streaks at approximately the 9- to 10-o’clock position and peripheral dots at approximately the 11- to 2-o’clock position, and a bluish-white veil.

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Figure 3. Histopathologic review of a specimen from the male patient. A and B, Findings revealed disorganized and noncohesive melanocytic cells at the dermal epidermal junction with nests and single melanocytic cells noted in the dermis with lymphocytic infiltration and pigmented macrophages with superficial dermal fibrosis and scattered melanocytic cells in the upper levels of the epidermis. (Hematoxylin-eosin, original magnification ×40.)

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Grahic Jump Location

Figure 4. Exogenous human growth hormone (HGH) stimulates the liver to produce insulinlike growth factor 1 (IGF-1). IGF-1 in turn binds to IGF-1 receptors (IGF-1R) on melanocytes. This both promotes growth through the mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) pathway and inhibits apoptosis via the phosphoinositide 3-kinase (PI3K) pathway. Exogenous HGH also directly activates mitogenic signaling pathways by binding to HGH receptors (GH-R) located on melanocytes. GH-R agonism by HGH also causes the endogenous melanocytic production of IGF-1 via the janus kinase signal transducer and activator of transcription (JAK-STAT), which can then feed into the aforementioned signaling loop. Melanocytes also possess growth hormone releasing hormone receptors (GHRH-R). While GHRH-R are known to promote tumorigenesis in other cancer models via cyclic adenosine monophosphate (cAMP), this pathway has not been studied in melanoma. Although other GHRH-R positive cancers did not produce HGH, it is uncertain if GHRH-Rs in melanoma are capable of initiating the synthesis and secretion of GH.

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