Skin anomalies in acromegalic patients (Review of the practical aspects)

Sandru,Florica; Popa,Adelina; Paduraru,Dan Nicolae; Filipescu,Alexandru; Carsote,Mara; Ghemigian,Adina

doi:10.3892/etm.2021.10765

Skin anomalies in acromegalic patients (Review of the practical aspects)

Authors:
- Florica Sandru
- Adelina Popa
- Dan Nicolae Paduraru
- Alexandru Filipescu
- Mara Carsote
- Adina Ghemigian
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Affiliations: Department of Dermatology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania, Department of Dermatology, ‘Elias’ Emergency Hospital, 011461 Bucharest, Romania, Department of General Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania, Department of Obstetrics and Gynecology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania, Department of Endocrinology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania
Published online on: September 20, 2021 https://doi.org/10.3892/etm.2021.10765
Article Number: 1330

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Abstract

Acromegaly is a hormonal disorder which occurs as the result of growth hormone (GH) and insulin growth factor 1 (IGF‑1) over‑secretion; both hormones are related to skin anomalies. The skin acts as a large endocrine organ, hosting GH receptors in every cell while IGF‑1 receptors are expressed only in keratinocytes. This review is a literature review of skin anomalies found in acromegaly, either related to the disease itself or associated with related complications such as secondary diabetes mellitus, or involving associated conditions such as genetic syndromes. The following clinical points are mentioned as follows. Excessive skin and enlargement of soft tissue are due to glycosaminoglycan deposits, edema, and hyperhidrosis (mostly facial and acral). Acanthosis nigricans, a body fold dermatosis associated with insulin resistance, involves local or diffuse hyperkeratotic plaques with or without hyperpigmentation, caused by growth factors including GH/IGF‑1. Other findings include cherry angiomas (due to the effects of lipid anomalies on small vessels); oily skin features with keratosis, epidermoid cysts, crochordons, pseudo‑acanthosis nigricans; a potentially higher prevalence of varicose veins and psoriasis; low level of evidence for basal cell carcinoma, respective hidroadenitis suppurativa has been noted. In addition, complicated uncontrolled secondary diabetes mellitus (DM) may result in necrobiosis lipoidica diabeticorum, diabetic dermopathy, skin bacterial infections, dermatological complications of diabetic neuropathy, and nephropathy. Finally, associated hereditary syndromes may cause collagenomas, fibromas/angiofibromas, lipomas in multiple endocrine neoplasia type 1 (MEN1) syndrome; café‑au‑lait macules, early onset neurofibromas, juvenile xanthogranuloma (involving non‑Langerhans cell histiocytes), and intertriginous freckling in neurofibromatosis type 1. Clinical findings are differentiated from pseudo‑acromegaly such as pachydermoperiostosis. Iatrogenic rash, lipodystrophy (lipoatrophy with/without lipohypertrophy) are rarely reported after pegvisomant/somatostatin analogues or after insulin use for DM. Experiments using human cell lines have shown that GH/IGF‑1 over‑secretion are prone to epithelial‑to‑mesenchymal transition (EMT) in melanoma. In non‑acromegalic subjects, the exact role of GH/IGF‑1 in skin tumorigenesis is yet to be determined. Skin in acromegaly speaks for itself, either as the first step of disease identification or as a complication or part of a complex syndromic context.

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1	Vilar L, Vilar CF, Lyra R, Lyra R and Naves LA: Acromegaly: Clinical features at diagnosis. Pituitary. 20:22–32. 2017.PubMed/NCBI View Article : Google Scholar
2	Broersen LHA, Zamanipoor Najafabadi AH, Pereira AM, Dekkers OM, van Furth WR and Biermasz NR: Improvement in symptoms and health-related quality of life in acromegaly patients: A systematic review and meta-analysis. J Clin Endocrinol Metab. 106:577–587. 2021.PubMed/NCBI View Article : Google Scholar
3	Giustina A, Barkhoudarian G, Beckers A, Ben-Shlomo A, Biermasz N, Biller B, Boguszewski C, Bolanowski M, Bollerslev J, Bonert V, et al: Multidisciplinary management of acromegaly: A consensus. Rev Endocr Metab Disord. 21:667–678. 2020.PubMed/NCBI View Article : Google Scholar
4	Kanaka-Gantenbein C, Kogia C, Abdel-Naser MB and Chrousos GP: Skin manifestations of growth hormone-induced diseases. Rev Endocr Metab Disord. 17:259–267. 2016.PubMed/NCBI View Article : Google Scholar
5	Degirmentepe EN, Gungor S, Kocaturk E, Kiziltac U, Adas M, Ozekinci S and Khachemoune A: Dermatologic manifestations of acromegaly: A case in point and a focused review. Dermatol Online J. 23(13030/qt50s903qh)2017.PubMed/NCBI
6	Lause M, Kamboj A and Fernandez Faith E: Dermatologic manifestations of endocrine disorders. Transl Pediatr. 6:300–312. 2017.PubMed/NCBI View Article : Google Scholar
7	Alotaibi A, Habib A, Osman M, Alzahrani K and Alzahrani F: Pseudoacromegaly associated with non-functioning pituitary adenoma. Eur J Case Rep Intern Med. 7(001950)2020.PubMed/NCBI View Article : Google Scholar
8	Joshi A, Nepal G, Shing YK, Panthi HP and Baral S: Pachydermoperiostosis (touraine-solente-gole syndrome): A case report. J Med Case Rep. 13(39)2019.PubMed/NCBI View Article : Google Scholar
9	Prerna Ghosh R, Barua JK and Das AK: Pachydermoperiostosis mimicking acromegaly: A case report. Indian Dermatol Online J. 9:182–184. 2018.PubMed/NCBI View Article : Google Scholar
10	Tritos NA, Chanson P, Jimenez C, King D, Jönsson PJ, Klibanski A and Biller BM: Effectiveness of first-line pegvisomant monotherapy in acromegaly: An ACROSTUDY analysis. Eur J Endocrinol. 176:213–220. 2017.PubMed/NCBI View Article : Google Scholar
11	Gentile S, Strollo F and Ceriello A: AMD-OSDI Injection Technique Study Group. Lipodystrophy in insulin-treated subjects and other injection-site skin reactions: Are we sure everything is clear? Diabetes Ther. 7:401–409. 2016.PubMed/NCBI View Article : Google Scholar
12	Osher E and Macaulay VM: Therapeutic targeting of the IGF axis. Cells. 8(895)2019.PubMed/NCBI View Article : Google Scholar
13	Qian Y, Basu R, Mathes SC, Arnett NA, Duran-Ortiz S, Funk KR, Brittain AL, Kulkarni P, Terry JC, Davis E, et al: Growth hormone upregulates mediators of melanoma drug efflux and epithelial-to-mesenchymal transition in vitro and in vivo. Cancers (Basel). 12(3640)2020.PubMed/NCBI View Article : Google Scholar
14	Valea A, Ghervan C, Carsote M, Morar A, Iacob I, Tomesc F, Pop DD and Georgescu C: Effects of combination therapy: Somatostatin analogues and dopamine agonists on GH and IGF1 levels in acromegaly. Clujul Med. 88:310–313. 2015.PubMed/NCBI View Article : Google Scholar
15	Qian F and Huo D: Circulating insulin-like growth factor-1 and risk of total and 19 site-specific cancers: Cohort study analyses from the UK Biobank. Cancer Epidemiol Biomarkers Prev. 29:2332–2342. 2020.PubMed/NCBI View Article : Google Scholar
16	Knuppel A, Fensom GK, Watts EL, Gunter MJ, Murphy N, Papier K, Perez-Cornago A, Schmidt JA, Smith Byrne K, Travis RC and Key TJ: Circulating insulin-like growth factor-i concentrations and risk of 30 cancers: Prospective analyses in UK Biobank. Cancer Res. 80:4014–4021. 2020.PubMed/NCBI View Article : Google Scholar
17	An LF, Huang JW, Han X and Wang J: Downregulation of lncRNA H19 sensitizes melanoma cells to cisplatin by regulating the miR-18b/IGF1 axis. Anticancer Drugs. 31:473–482. 2020.PubMed/NCBI View Article : Google Scholar
18	Yuan TA, Yourk V, Farhat A, Guo KL, Garcia A, Meyskens FL and Liu-Smith F: A possible link of genetic variations in ER/IGF1R pathway and risk of melanoma. Int J Mol Sci. 21(1776)2020.PubMed/NCBI View Article : Google Scholar
19	Xie X, Xie S, Xie C, Fang Y, Li Z, Wang R and Jiang W: Pristimerin attenuates cell proliferation of uveal melanoma cells by inhibiting insulin-like growth factor-1 receptor and its downstream pathways. J Cell Mol Med. 23:7545–7553. 2019.PubMed/NCBI View Article : Google Scholar
20	Suleymanova N, Crudden C, Worrall C, Dricu A, Girnita A and Girnita L: Enhanced response of melanoma cells to MEK inhibitors following unbiased IGF-1R down-regulation. Oncotarget. 8:82256–82267. 2017.PubMed/NCBI View Article : Google Scholar
21	Terzolo M, Puglisi S, Reimondo G, Dimopoulou C and Stalla GK: Thyroid and colorectal cancer screening in acromegaly patients: Should it be different from that in the general population? Eur J Endocrinol. 183:D1–D13. 2020.PubMed/NCBI View Article : Google Scholar
22	Kasuki L, Rocha PDS, Lamback EB and Gadelha MR: Determinants of morbidities and mortality in acromegaly. Arch Endocrinol Metab. 63:630–637. 2019.PubMed/NCBI View Article : Google Scholar
23	Ku CR, Melnikov V, Zhang Z and Lee EJ: Precision therapy in acromegaly caused by pituitary tumors: How close is it to reality? Endocrinol Metab (Seoul). 35:206–216. 2020.PubMed/NCBI View Article : Google Scholar
24	Sandru F, Draghici CC, Predescu T, Constantin M, Petca RC, Constantin T, Petca A and Cristian Dumitraşcu M: Regressive melanoma in a female patient: A case report. Exp Ther Med. 20:87–90. 2020.PubMed/NCBI View Article : Google Scholar
25	Shirinpour Z, Farhangiyan Z, Akiash N and Rashidi H: Recurrent cardiac and skin myxomas along with acromegaly: A case report of carney complex. ARYA Atheroscler. 16:146–150. 2020.PubMed/NCBI View Article : Google Scholar
26	Kamilaris CDC, Faucz FR, Voutetakis A and Stratakis CA: Carney complex. Exp Clin Endocrinol Diabetes. 127:156–164. 2019.PubMed/NCBI View Article : Google Scholar
27	Subbiah S, Palikhe G, Bhadada SK, Mukherjee KK and Bhansali A: Acrogigantism and facial asymmetry: McCune-Albright syndrome. J Pediatr Endocrinol Metab. 24:835–837. 2011.PubMed/NCBI View Article : Google Scholar
28	Hozumi K, Fukuoka H, Odake Y, Takeuchi T, Uehara T, Sato T, Inoshita N, Yoshida K, Matsumoto R, Bando H, et al: Acromegaly caused by a somatotroph adenoma in patient with neurofibromatosis type 1. Endocr J. 66:853–857. 2019.PubMed/NCBI View Article : Google Scholar
29	Hannah-Shmouni F and Stratakis CA: Growth hormone excess in neurofibromatosis 1. Genet Med. 21:1254–1255. 2019.PubMed/NCBI View Article : Google Scholar
30	Cambiaso P, Galassi S, Palmiero M, Mastronuzzi A, Del Bufalo F, Capolino R, Cacchione A, Buonuomo PS, Gonfiantini MV, Bartuli A, et al: Growth hormone excess in children with neurofibromatosis type-1 and optic glioma. Am J Med Genet A. 173:2353–2358. 2017.PubMed/NCBI View Article : Google Scholar
31	Sandru F, Carsote M, Valea A, Albu SE, Petca RC and Dumitrascu MC: Somatostatinoma: Beyond neurofibromatosis type 1 (review). Exp Ther Med. 20:3383–3388. 2020.PubMed/NCBI View Article : Google Scholar
32	Valea A, Carsote M, Ghervan C and Georgescu C: Glycemic profile in patients with acromegaly treated with somatostatin analogue. J Med Life. 8 (Spec Issue):82–86. 2015.PubMed/NCBI
33	Ozarslan B, Russo T, Argenziano G, Santoro C and Piccolo V: Cutaneous findings in neurofibromatosis type 1. Cancers (Basel). 13(463)2021.PubMed/NCBI View Article : Google Scholar
34	Buchholzer S, Verdeja R and Lombardi T: Type I neurofibromatosis: Case report and review of the literature focused on oral and cutaneous lesions. Dermatopathology (Basel). 8:17–24. 2021.PubMed/NCBI View Article : Google Scholar
35	Kundak S and Çakır Y: Juvenile xanthogranuloma: Retrospective analysis of 44 pediatric cases (single tertiary care center experience). Int J Dermatol. 60:564–569. 2021.PubMed/NCBI View Article : Google Scholar
36	Anderson S: Café au lait macules and associated genetic syndromes. J Pediatr Health Care. 34:71–81. 2020.PubMed/NCBI View Article : Google Scholar
37	Ntala C and Biswas A: Spectrum of melanocytic proliferation/differentiation in a large series of cutaneous neurofibromas: An under-recognized histopathologic phenomenon and potential clue for neurofibromatosis type 1. Am J Dermatopathol. 42:165–172. 2020.PubMed/NCBI View Article : Google Scholar
38	Radman M and Milicevic T: A novel mutation of the MEN1 gene in a patient with multiple endocrine neoplasia type 1 and recurrent fibromyxoid sarcoma-a case report. BMC Med Genet. 21(190)2020.PubMed/NCBI View Article : Google Scholar
39	Pérez AD, Yu S and North JP: Multiple cutaneous collagenomas in the setting of multiple endocrine neoplasia type 1. J Cutan Pathol. 42:791–795. 2015.PubMed/NCBI View Article : Google Scholar
40	Sandru F, Carsote M, Albu SE, Valea A, Petca A and Dumitrascu MC: Glucagonoma: From skin lesions to the neuroendocrine component (review). Exp Ther Med. 20:3389–3393. 2020.PubMed/NCBI View Article : Google Scholar
41	Brown GT, Cowen EW and Lee CC: Malignant melanoma masquerading as an angiofibroma in a patient with MEN-1. JAMA Dermatol. 151:105–106. 2015.PubMed/NCBI View Article : Google Scholar
42	Keen MA, Shah IH and Sheikh G: Cutaneous manifestations of polycystic ovary syndrome: A cross-sectional clinical study. Indian Dermatol Online J. 8:104–110. 2017.PubMed/NCBI View Article : Google Scholar
43	Pardeshi SS, Khemani UN, Kamath RR, Kura MM and Jafferany M: Therapeutic implications of dermoscopic findings in acanthosis nigricans: A clinical and histopathological study. Dermatol Ther. 33(e14521)2020.PubMed/NCBI View Article : Google Scholar
44	Yilmaz B and Yildiz BO: Endocrinology of hirsutism: From androgens to androgen excess disorders. Front Horm Res. 53:108–119. 2019.PubMed/NCBI View Article : Google Scholar
45	Ng HY: Acanthosis nigricans in obese adolescents: Prevalence, impact, and management challenges. Adolesc Health Med Ther. 8:1–10. 2016.PubMed/NCBI View Article : Google Scholar
46	De Sanctis V, Soliman A, Marsciani A, Timoncini G, Reggiani L, Zucchini A and Altieri E: Acanthosis nigricans in adolescents: A practical approach. Georgian Med News. 73–78. 2013.PubMed/NCBI
47	Bhagyanathan M, Dhayanithy D, Parambath VA and Bijayraj R: Acanthosis nigricans: A screening test for insulin resistance-an important risk factor for diabetes mellitus type-2. J Family Med Prim Care. 6:43–46. 2017.PubMed/NCBI View Article : Google Scholar
48	Kutlubay Z, Engin B, Bairamov O and Tüzün Y: Acanthosis nigricans: A fold (intertriginous) dermatosis. Clin Dermatol. 33:466–470. 2015.PubMed/NCBI View Article : Google Scholar
49	Akoglu G, Metin A, Emre S, Ersoy R and Cakir B: Cutaneous findings in patients with acromegaly. Acta Dermatovenerol Croat. 21:224–229. 2013.PubMed/NCBI
50	Buslach N, Foulad DP, Saedi N and Mesinkovska NA: Treatment modalities for cherry angiomas: A systematic review. Dermatol Surg. 46:1691–1697. 2020.PubMed/NCBI View Article : Google Scholar
51	Darjani A, Rafiei R, Shafaei S, Rafiei E, Eftekhari H, Alizade N, Gharaei Nejad K, Rafiee B and Najirad S: Evaluation of lipid profile in patients with cherry angioma: A case-control study in Guilan, Iran. Dermatol Res Pract. 2018(4639248)2018.PubMed/NCBI View Article : Google Scholar
52	Resende M, Bolfi F, Nunes Vdos S and Miot HA: Prevalence of dermatologic disorders in 15 patients with acromegaly. An Bras Dermatol. 87:166–168. 2012.PubMed/NCBI View Article : Google Scholar
53	Füchtbauer L, Olsson DS, Coopmans EC, Bengtsson BÅ, Norrman LL, Neggers SJCMM, Hellström A and Johannsson G: Increased number of retinal vessels in acromegaly. Eur J Endocrinol. 182:293–302. 2020.PubMed/NCBI View Article : Google Scholar
54	Haddad A, Ashkenazi RI, Bitterman H, Feldhamer I, Greenberg-Dotan S, Lavi I, Batat E, Bergman I, Cohen AD and Zisman D: Endocrine comorbidities in patients with psoriatic arthritis: A population-based case-controlled study. J Rheumatol. 44:786–790. 2017.PubMed/NCBI View Article : Google Scholar
55	Bolfi F, Miot HA, Resende M, Mazeto GM, Romeiro FG, Yamashiro Fda S and Nunes Vdos S: Frequency of various types of neoplasia in a group of acromegalic patients. Arq Bras Endocrinol Metabol. 57:612–616. 2013.PubMed/NCBI View Article : Google Scholar
56	Scheinfeld N: Diseases associated with hidranitis suppurativa: Part 2 of a series on hidradenitis. Dermatol Online J. 19(18558)2013.PubMed/NCBI
57	Manavela M, Vigovich C, Danilowicz K, Juri A, Miechi L, Fernandez Valoni V and Bruno OD: Thyroid autoimmune disorders in patients with acromegaly. Pituitary. 18:912–915. 2015.PubMed/NCBI View Article : Google Scholar
58	Falcone M, Meier JJ, Marini MG, Caccialanza R, Aguado JM, Del Prato S and Menichetti F: Diabetes and acute bacterial skin and skin structure infections. Diabetes Res Clin Pract. 174(108732)2021.PubMed/NCBI View Article : Google Scholar
59	Papachristou S, Pafili K and Papanas N: Skin AGEs and diabetic neuropathy. BMC Endocr Disord. 21(28)2021.PubMed/NCBI View Article : Google Scholar
60	Naik PP and Farrukh SN: Clinical significance of diabetic dermatopathy. Diabetes Metab Syndr Obes. 13:4823–4827. 2020.PubMed/NCBI View Article : Google Scholar