0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Observation |

Potential Role of Human Growth Hormone in Melanoma Growth Promotion FREE

Marc Z. Handler, MD; Andrew L. Ross, BA; Michael I. Shiman, MD; George W. Elgart, MD; James M. Grichnik, MD, PhD
[+] Author Affiliations

Author Affiliations: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida.


Arch Dermatol. 2012;148(10):1179-1182. doi:10.1001/archdermatol.2012.2149.
Text Size: A A A
Published online

ABSTRACT

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.

Figures in this Article

We report 2 cases of new-onset cutaneous melanoma subsequent to the initiation of exogenous human growth hormone (HGH), an anabolic peptide hormone synthesized by the anterior pituitary gland. Endogenous HGH secretion is regulated by growth hormone–releasing hormone (GHRH) produced in the hypothalamus. Most of HGH's effects on growth and metabolism are mediated by insulin-like growth factor 1 (IGF-1). IGF-1 is produced primarily in the liver following stimulation by HGH. The use of exogenous HGH as an antiaging agent is gaining acceptance and increasing in prevalence despite its negative adverse effects,1,2 including oncogenic transformation and neoplastic progression.3

Human growth hormone's direct effects are predominantly mediated through the mitogen-activated protein kinase/extracellular-signal–regulated kinase (MAPK/ERK)4 and janus kinase signal transducer and activator of transcription (JAK-STAT)5 pathways. IGF-1 directly upregulates the MAPK/ERK6 and phosphoinositide 3-kinase (PI3K)7 pathways. Given that overstimulation of these pathways has been implicated in the pathogenesis of melanoma,8 there may be indication to closely monitor patients using exogenous HGH for development of malignant disease.

REPORT OF A CASE

A 49-year-old white man presented with a new pigmented papule on his left lower back (Figure 1 and Figure 2). A biopsy was performed, and findings were consistent with a diagnosis of melanoma (Breslow depth, 0.32 mm) (Figure 3). Although there was no family history of melanoma among his genetic relatives, his 51-year-old wife, who also was white, had been diagnosed as having a melanoma on the right arm 2 weeks prior (Breslow depth, 0.75 mm). Both patients noted that 3 months previously they had begun an antiaging regimen that included exogenous HGH. The man's regimen included daily subcutaneous injection of HGH (0.58 mg) and testosterone. His wife's regimen included daily subcutaneous administration of HGH (0.29 mg) plus topical testosterone, progesterone, and estrogen to her inguinal region and axillae. On discovery of the melanomas, both discontinued their exogenous hormone regimens.

Place holder to copy figure label and caption
Graphic Jump Location

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.

Place holder to copy figure label and caption
Graphic Jump Location

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.

Place holder to copy figure label and caption
Graphic Jump Location

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.)

COMMENT

There is one similar report in the literature of a 26-year-old woman who developed melanoma following hormone therapy with HGH, thyroid hormone, and estrogen.9 Although this report suggested that estrogen replacement was the causal agent, it could not rule out the role of HGH via the Naranjo adverse drug reaction causality algorithm. Although estrogen has been implicated as a risk factor in the development of melanoma,10 subcutaneously administered exogenous HGH was the only agent common to all 3 regimens.

It is well established that pigmentation is regulated by a variety of signaling pathways, including peptide hormones.11 Consequently, it is possible that there exists a direct correlation between exogenous HGH administration and the development of melanoma. This correlation may also extend to benign melanocytic neoplasms. Supporting evidence includes a previous study that demonstrated that administration of exogenous HGH accelerates the rate of nevus growth.12 There is also evidence that nevi in individuals treated with HGH exhibit abnormal melanosome architecture, increased Ki-67 staining, and increased anisokaryosis compared with matched controls.13 However, it should be noted that other studies of patients failed to confirm this correlation.1416

Although the aforementioned series did not demonstrate the development of melanoma in any of the patients younger than 18 years, there is a report of malignant melanoma developing in both a 9-year-old girl and 15-year-old boy following 3.0 and 1.5 years of exogenous HGH replacement, respectively.16 One aspect unique to both of these cases was that the patients had previously received craniospinal irradiation. Consequently, an underlying mutation generated by irradiation could have primed the melanocytes to grow in response to the HGH in an abnormal manner. Meanwhile, it is likely that minors studied in the other reports did not contain predisposing mutations when treated with HGH and thus were less susceptible to tumor growth. Finally, it is possible that predisposing UV-induced mutations that accumulated over time in sun-damaged skin primed the 2 cases of melanoma presented herein to grow in response to HGH. The couple shared outdoor activities in the Florida sun, and the wife had a history of basal cell and squamous cell carcinoma.

Despite the data against a correlation between HGH and benign melanocytic neoplasms, there is molecular evidence that HGH has the potential to play a role in the pathogenesis of melanoma (Figure 4). First, growth hormone receptors (GH-R) are known to be upregulated in malignant melanocytic lesions compared with their benign counterparts.17 Direct stimulation of these receptors results in the upregulation of the MAPK/ERK pathway,4 and thus HGH is likely to contribute directly to the promotion of mitogenic signaling in evolving melanomas. Second, both benign and malignant melanocytes are known to possess receptors for IGF-1,1820 the major downstream mediator of HGH. As mentioned herein, IGF-1 upregulates the MAPK/ERK and PI3K pathways. It is thus not surprising that IGF-1 inhibits apoptosis7 and accelerates the in vitro growth of malignant melanocytes.21 In addition, interruption of IGF-1 receptor binding has been shown to result in growth inhibition and decreased MAPK signaling.6 The mechanistic data support the notion that IGF-1 may play a role in the progression of early malignant lesions22 in addition to promoting progression and dissemination.23

Place holder to copy figure label and caption
Graphic 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.

Curiously, melanoma may have an endogenous growth promoting loop for the HGH/IGF-1 pathway. Supporting evidence includes the presence of GH-Rs on melanoma cells24 and the fact that melanoma cells synthesize IGF-1.25 It is also interesting to note that melanomas express growth hormone–releasing hormone receptors (GHRH-Rs).26 Although, to our knowledge, direct production of HGH by melanoma cells has not been noted in the literature, activation of the GHRH-Rs has been shown to have growth-promoting functions in other tumors. Given the proliferative effects of each member of this pathway, specific antagonists to each receptor may also have a therapeutic benefit in melanomas.

Given the unlikelihood of 2 unrelated people developing melanoma within a 3-month period, it is plausible that a common environmental component (HGH or other shared exposure) contributed to the pathogenesis. In this situation, it is possible that HGH provided the growth stimulatory signaling necessary to unmask previously quiescent melanoma clones, thus allowing the tumors to proliferate. Because both HGH and IGF-1 are known to promote malignant transformation and progression,3 it may be necessary to closely monitor patients prescribed HGH antiaging regimens for melanoma.

ARTICLE INFORMATION

Correspondence: James M. Grichnik, MD, PhD, Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Room 912, BRB, 1501 NW 10th Ave, Miami, FL 33136 (grichnik@miami.edu).

Accepted for Publication: April 30, 2012.

Author Contributions: Drs Handler, Ross, Shiman, and Grichnik had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Shiman and Grichnik. Acquisition of data: Elgart and Grichnik. Analysis and interpretation of data: Handler, Ross, and Grichnik. Drafting of the manuscript: Handler, Ross, Shiman, Elgart, and Grichnik. Critical revision of the manuscript for important intellectual content: Ross and Grichnik. Administrative, technical, and material support: Handler, Ross, and Grichnik. Study supervision: Shiman and Grichnik.

Financial Disclosure: Dr Grichnik is a major shareholder for DigitalDerm Inc, has received grants from and done consulting for Spectral Image Inc, and has been a consultant for Genentech.

Funding/Support: This study was supported in part by the Department of Dermatology and the Anna Fund Melanoma Program at Sylvester Comprehensive Cancer Center, University of Miami.

Additional Contributions: The Department of Dermatology, Anna Fund Melanoma Program, and Sylvester Comprehensive Cancer Center at the University of Miami provided ongoing support.

REFERENCES

Savine R, Sönksen P. Growth hormone: hormone replacement for the somatopause?  Horm Res. 2000;53:(suppl 3)  37-41
PubMed   |  Link to Article
Blackman MR, Sorkin JD, Münzer T,  et al.  Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial.  JAMA. 2002;288(18):2282-2292
PubMed   |  Link to Article
Perry JK, Emerald BS, Mertani HC, Lobie PE. The oncogenic potential of growth hormone.  Growth Horm IGF Res. 2006;16(5-6):277-289
PubMed   |  Link to Article
Anderson NG. Growth hormone activates mitogen-activated protein kinase and S6 kinase and promotes intracellular tyrosine phosphorylation in 3T3-F442A preadipocytes.  Biochem J. 1992;284(pt 3):649-652
PubMed
Argetsinger LS, Campbell GS, Yang X,  et al.  Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase.  Cell. 1993;74(2):237-244
PubMed   |  Link to Article
Molhoek KR, Shada AL, Smolkin M,  et al.  Comprehensive analysis of receptor tyrosine kinase activation in human melanomas reveals autocrine signaling through IGF-1R.  Melanoma Res. 2011;21(4):274-284
PubMed   |  Link to Article
Capoluongo E. Insulin-like growth factor system and sporadic malignant melanoma.  Am J Pathol. 2011;178(1):26-31
PubMed   |  Link to Article
Yajima I, Kumasaka MY, Thang ND,  et al.  RAS/RAF/MEK/ERK and PI3K/PTEN/AKT signaling in malignant melanoma progression and therapy.  Dermatol Res Pract. 2012;2012:354191
PubMed
Caldarola G, Battista C, Pellicano R. Melanoma onset after estrogen, thyroid, and growth hormone replacement therapy.  Clin Ther. 2010;32(1):57-59
PubMed   |  Link to Article
Koomen ER, Joosse A, Herings RM, Casparie MK, Guchelaar HJ, Nijsten T. Estrogens, oral contraceptives and hormonal replacement therapy increase the incidence of cutaneous melanoma: a population-based case-control study.  Ann Oncol. 2009;20(2):358-364
PubMed   |  Link to Article
Slominski A, Tobin DJ, Shibahara S, Wortsman J. Melanin pigmentation in mammalian skin and its hormonal regulation.  Physiol Rev. 2004;84(4):1155-1228
PubMed   |  Link to Article
Bourguignon JP, Piérard GE, Ernould C,  et al.  Effects of human growth hormone therapy on melanocytic naevi.  Lancet. 1993;341(8859):1505-1506
PubMed   |  Link to Article
Piérard GE, Piérard-Franchimont C, Nikkels A, Nikkels-Tassoudji N, Arrese JE, Bourguignon JP. Naevocyte triggering by recombinant human growth hormone.  J Pathol. 1996;180(1):74-79
PubMed   |  Link to Article
Bozzola E, Giacchero R, Barberi S, Borroni G. Sutton's nevus and growth hormone therapy.  Minerva Pediatr. 2004;56(3):349-351
PubMed
Zvulunov A, Wyatt DT, Laud PW, Esterly NB. Lack of effect of growth hormone therapy on the count and density of melanocytic naevi in children.  Br J Dermatol. 1997;137(4):545-548
PubMed   |  Link to Article
Wyatt D. Melanocytic nevi in children treated with growth hormone.  Pediatrics. 1999;104(4, pt 2):1045-1050
PubMed
Lincoln DT, Sinowatz F, Kölle S, Takahashi H, Parsons P, Waters M. Up-regulation of growth hormone receptor immunoreactivity in human melanoma.  Anticancer Res. 1999;19(3A):1919-1931
PubMed
Fleming MG, Howe SF, Graf LH Jr. Expression of insulin-like growth factor I (IGF-I) in nevi and melanomas.  Am J Dermatopathol. 1994;16(4):383-391
PubMed   |  Link to Article
Tavakkol A, Elder JT, Griffiths CE,  et al.  Expression of growth hormone receptor, insulin-like growth factor 1 (IGF-1) and IGF-1 receptor mRNA and proteins in human skin.  J Invest Dermatol. 1992;99(3):343-349
PubMed   |  Link to Article
Chatelain P, Naville D, Avallet O,  et al.  Paracrine and autocrine regulation of insulin-like growth factor I.  Acta Paediatr Scand Suppl. 1991;372:92-96
PubMed   |  Link to Article
Rodeck U, Herlyn M, Menssen HD, Furlanetto RW, Koprowsk H. Metastatic but not primary melanoma cell lines grow in vitro independently of exogenous growth factors.  Int J Cancer. 1987;40(5):687-690
PubMed   |  Link to Article
Satyamoorthy K, Li G, Vaidya B, Kalabis J, Herlyn M. Insulin-like growth factor-I-induced migration of melanoma cells is mediated by interleukin-8 induction.  Cell Growth Differ. 2002;13(2):87-93
PubMed
Kanter-Lewensohn L, Dricu A, Girnita L, Wejde J, Larsson O. Expression of insulin-like growth factor-1 receptor (IGF-1R) and p27Kip1 in melanocytic tumors: a potential regulatory role of IGF-1 pathway in distribution of p27Kip1 between different cyclins.  Growth Factors. 2000;17(3):193-202
PubMed   |  Link to Article
Ginarte M, García-Caballero T, Fernández-Redondo V, Beiras A, Toribio J. Expression of growth hormone receptor in benign and malignant cutaneous proliferative entities.  J Cutan Pathol. 2000;27(6):276-282
PubMed   |  Link to Article
Slominski A, Malarkey WB, Wortsman J, Asa SL, Carlson A. Human skin expresses growth hormone but not the prolactin gene.  J Lab Clin Med. 2000;136(6):476-481
PubMed   |  Link to Article
Chatzistamou I, Volakaki AA, Schally AV, Kiaris H, Kittas C. Expression of growth hormone-releasing hormone receptor splice variant 1 in primary human melanomas.  Regul Pept. 2008;147(1-3):33-36
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Graphic Jump Location

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.

Place holder to copy figure label and caption
Graphic Jump Location

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.

Place holder to copy figure label and caption
Graphic Jump Location

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.)

Place holder to copy figure label and caption
Graphic 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.

Tables

References

Savine R, Sönksen P. Growth hormone: hormone replacement for the somatopause?  Horm Res. 2000;53:(suppl 3)  37-41
PubMed   |  Link to Article
Blackman MR, Sorkin JD, Münzer T,  et al.  Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial.  JAMA. 2002;288(18):2282-2292
PubMed   |  Link to Article
Perry JK, Emerald BS, Mertani HC, Lobie PE. The oncogenic potential of growth hormone.  Growth Horm IGF Res. 2006;16(5-6):277-289
PubMed   |  Link to Article
Anderson NG. Growth hormone activates mitogen-activated protein kinase and S6 kinase and promotes intracellular tyrosine phosphorylation in 3T3-F442A preadipocytes.  Biochem J. 1992;284(pt 3):649-652
PubMed
Argetsinger LS, Campbell GS, Yang X,  et al.  Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase.  Cell. 1993;74(2):237-244
PubMed   |  Link to Article
Molhoek KR, Shada AL, Smolkin M,  et al.  Comprehensive analysis of receptor tyrosine kinase activation in human melanomas reveals autocrine signaling through IGF-1R.  Melanoma Res. 2011;21(4):274-284
PubMed   |  Link to Article
Capoluongo E. Insulin-like growth factor system and sporadic malignant melanoma.  Am J Pathol. 2011;178(1):26-31
PubMed   |  Link to Article
Yajima I, Kumasaka MY, Thang ND,  et al.  RAS/RAF/MEK/ERK and PI3K/PTEN/AKT signaling in malignant melanoma progression and therapy.  Dermatol Res Pract. 2012;2012:354191
PubMed
Caldarola G, Battista C, Pellicano R. Melanoma onset after estrogen, thyroid, and growth hormone replacement therapy.  Clin Ther. 2010;32(1):57-59
PubMed   |  Link to Article
Koomen ER, Joosse A, Herings RM, Casparie MK, Guchelaar HJ, Nijsten T. Estrogens, oral contraceptives and hormonal replacement therapy increase the incidence of cutaneous melanoma: a population-based case-control study.  Ann Oncol. 2009;20(2):358-364
PubMed   |  Link to Article
Slominski A, Tobin DJ, Shibahara S, Wortsman J. Melanin pigmentation in mammalian skin and its hormonal regulation.  Physiol Rev. 2004;84(4):1155-1228
PubMed   |  Link to Article
Bourguignon JP, Piérard GE, Ernould C,  et al.  Effects of human growth hormone therapy on melanocytic naevi.  Lancet. 1993;341(8859):1505-1506
PubMed   |  Link to Article
Piérard GE, Piérard-Franchimont C, Nikkels A, Nikkels-Tassoudji N, Arrese JE, Bourguignon JP. Naevocyte triggering by recombinant human growth hormone.  J Pathol. 1996;180(1):74-79
PubMed   |  Link to Article
Bozzola E, Giacchero R, Barberi S, Borroni G. Sutton's nevus and growth hormone therapy.  Minerva Pediatr. 2004;56(3):349-351
PubMed
Zvulunov A, Wyatt DT, Laud PW, Esterly NB. Lack of effect of growth hormone therapy on the count and density of melanocytic naevi in children.  Br J Dermatol. 1997;137(4):545-548
PubMed   |  Link to Article
Wyatt D. Melanocytic nevi in children treated with growth hormone.  Pediatrics. 1999;104(4, pt 2):1045-1050
PubMed
Lincoln DT, Sinowatz F, Kölle S, Takahashi H, Parsons P, Waters M. Up-regulation of growth hormone receptor immunoreactivity in human melanoma.  Anticancer Res. 1999;19(3A):1919-1931
PubMed
Fleming MG, Howe SF, Graf LH Jr. Expression of insulin-like growth factor I (IGF-I) in nevi and melanomas.  Am J Dermatopathol. 1994;16(4):383-391
PubMed   |  Link to Article
Tavakkol A, Elder JT, Griffiths CE,  et al.  Expression of growth hormone receptor, insulin-like growth factor 1 (IGF-1) and IGF-1 receptor mRNA and proteins in human skin.  J Invest Dermatol. 1992;99(3):343-349
PubMed   |  Link to Article
Chatelain P, Naville D, Avallet O,  et al.  Paracrine and autocrine regulation of insulin-like growth factor I.  Acta Paediatr Scand Suppl. 1991;372:92-96
PubMed   |  Link to Article
Rodeck U, Herlyn M, Menssen HD, Furlanetto RW, Koprowsk H. Metastatic but not primary melanoma cell lines grow in vitro independently of exogenous growth factors.  Int J Cancer. 1987;40(5):687-690
PubMed   |  Link to Article
Satyamoorthy K, Li G, Vaidya B, Kalabis J, Herlyn M. Insulin-like growth factor-I-induced migration of melanoma cells is mediated by interleukin-8 induction.  Cell Growth Differ. 2002;13(2):87-93
PubMed
Kanter-Lewensohn L, Dricu A, Girnita L, Wejde J, Larsson O. Expression of insulin-like growth factor-1 receptor (IGF-1R) and p27Kip1 in melanocytic tumors: a potential regulatory role of IGF-1 pathway in distribution of p27Kip1 between different cyclins.  Growth Factors. 2000;17(3):193-202
PubMed   |  Link to Article
Ginarte M, García-Caballero T, Fernández-Redondo V, Beiras A, Toribio J. Expression of growth hormone receptor in benign and malignant cutaneous proliferative entities.  J Cutan Pathol. 2000;27(6):276-282
PubMed   |  Link to Article
Slominski A, Malarkey WB, Wortsman J, Asa SL, Carlson A. Human skin expresses growth hormone but not the prolactin gene.  J Lab Clin Med. 2000;136(6):476-481
PubMed   |  Link to Article
Chatzistamou I, Volakaki AA, Schally AV, Kiaris H, Kittas C. Expression of growth hormone-releasing hormone receptor splice variant 1 in primary human melanomas.  Regul Pept. 2008;147(1-3):33-36
PubMed   |  Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Cancer and body height. Pathophysiology Published online May 13, 2014.;
JAMAevidence.com

Users' Guides to the Medical Literature
Melanoma

The Rational Clinical Examination
Make the Diagnosis: Melanoma