An acromegaly case treated with clomiphene citrate: add-on treatment in primary medical therapy
Tóm tắt
Acromegaly is a disease with various comorbidities and hypogonadism is a common comorbidity in patients with acromegaly. Herein, we aim to present our experience with clomiphene citrate in a patient with acromegaly accompanied by hypogonadism, who declined surgery. A 40-year-old male patient with impaired fasting glucose, hyperlipidemia, and psychosis and who complained of increasing tongue growth, snoring, enlargement of the hands, spacing between the teeth, and loss of libido for the last 6 years was followed up. Acromegaly was diagnosed, with high levels of insulin-like growth factor-1 (IGF-1) and a pituitary neuroendocrine tumor measuring 11 mm; the patient had concomitant hypogonadism. Lanreotide was started as the initial primary medical treatment. Clomiphene citrate was added to the patient’s treatment. The patient, whose IGF-1 level was high during follow-up, did not want to use the intramuscular testosterone esters for hypogonadism. In the third month of clomiphene citrate treatment, IGF-1 normalization was achieved and the patient’s total testosterone level increased. Biochemical control is not always achieved with somatostatin receptor ligands and dopamine agonists in the treatment of acromegaly. Therefore, we support the use of clomiphene citrate (CC) as a cost-effective oral add-on treatment option in selected hypogonadal acromegaly cases.
Tài liệu tham khảo
Katznelson L, Kleinberg D, Vance ML, Stavrou S, Pulaski KJ, Schoenfeld DA, Hayden DL, Wright ME, Woodburn CJ, Klibanski A (2001) Hypogonadism in patients with acromegaly: data from the multi-centre acromegaly registry pilot study. Clin Endocrinol 54(2):183–188. https://doi.org/10.1046/j.1365-2265.2001.01214.x
Giustina A, Barkhoudarian G, Beckers A, Ben-Shlomo A, Biermasz N, Biller B, Boguszewski C, Bolanowski M, Bollerslev J, Bonert V, Bronstein MD, Buchfelder M, Casanueva F, Chanson P, Clemmons D, Fleseriu M, Formenti AM, Freda P, Gadelha M, Geer E, Gurnell M, Heaney AP, Ho KKY, Ioachimescu AG, Lamberts S, Laws E, Losa M, Maffei P, Mamelak A, Mercado M, Molitch M, Mortini P, Pereira AM, Petersenn S, Post K, Puig-Domingo M, Salvatori R, Samson SL, Shimon I, Strasburger C, Swearingen B, Trainer P, Vance ML, Wass J, Wierman ME, Yuen KCJ, Zatelli MC, Melmed S (2020) Multidisciplinary management of acromegaly: a consensus. Rev Endocr Metab Disord 21(4):667–678. https://doi.org/10.1007/s11154-020-09588-z
Jørgensen JO, Christensen JJ, Vestergaard E, Fisker S, Ovesen P, Christiansen JS (2005) Sex steroids and the growth hormone/insulin-like growth factor-I axis in adults. Horm Res 64(Suppl 2):37–40. https://doi.org/10.1159/000087752
Duarte FH, Jallad RS, Bronstein MD (2015) Clomiphene citrate for treatment of acromegaly not controlled by conventional therapies. J Clin Endocrinol Metab 100(5):1863–1869. https://doi.org/10.1210/jc.2014-3913
Clemmons DR, Underwood LE, Ridgway EC, Kliman B, Kjellberg RN, Van Wyk JJ (1980) Estradiol treatment of acromegaly. Reduction of immunoreactive somatomedin-C and improvement in metabolic status. Am J Med 69(4):571–575. https://doi.org/10.1016/0002-9343(80)90470-2
Domené HM, Marín G, Sztein J, Yu YM, Baron J, Cassorla FG (1994) Estradiol inhibits growth hormone receptor gene expression in rabbit liver. Mol Cell Endocrinol 103(1–2):81–87. https://doi.org/10.1016/0303-7207(94)90072-8
Leung KC, Johannsson G, Leong GM, Ho KK (2004) Estrogen regulation of growth hormone action. Endocr Rev 25(5):693–721. https://doi.org/10.1210/er.2003-0035
Leung KC, Doyle N, Ballesteros M, Sjogren K, Watts CK, Low TH, Leong GM, Ross RJ, Ho KK (2003) Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2. Proc Natl Acad Sci USA 100(3):1016–1021. https://doi.org/10.1073/pnas.0337600100
Fernández L, Flores-Morales A, Lahuna O, Sliva D, Norstedt G, Haldosén LA, Mode A, Gustafsson JA (1998) Desensitization of the growth hormone-induced Janus kinase 2 (Jak 2)/signal transducer and activator of transcription 5 (Stat5)-signaling pathway requires protein synthesis and phospholipase C. Endocrinology 139(4):1815–1824. https://doi.org/10.1210/endo.139.4.5931
Cozzi R, Attanasio R, Oppizzi G, Orlandi P, Giustina A, Lodrini S, Da Re N, Dallabonzana D (1997) Effects of tamoxifen on GH and IGF-I levels in acromegaly. J Endocrinol Invest 20(8):445–451. https://doi.org/10.1007/BF03348000
Dimaraki EV, Symons KV, Barkan AL (2004) Raloxifene decreases serum IGF-I in male patients with active acromegaly. Eur J Endocrinol 150(4):481–487. https://doi.org/10.1530/eje.0.1500481
Attanasio R, Barausse M, Cozzi R (2003) Raloxifene lowers IGF-I levels in acromegalic women. Eur J Endocrinol 148(4):443–448. https://doi.org/10.1530/eje.0.1480443
Bützow TL, Kettel LM, Yen SS (1995) Clomiphene citrate reduces serum insulin-like growth factor I and increases sex hormone-binding globulin levels in women with polycystic ovary syndrome. Fertil Steril 63(6):1200–1203. https://doi.org/10.1016/s0015-0282(16)57597-9
de Leo V, la Marca A, Morgante G, Ciotta L, Mencaglia L, Cianci A, Petraglia F (2000) Clomiphene citrate increases insulin-like growth factor binding protein-1 and reduces insulin-like growth factor-I without correcting insulin resistance associated with polycystic ovarian syndrome. Hum Reprod 15(11):2302–2305. https://doi.org/10.1093/humrep/15.11.2302
Palacios JD, Komotar RJ, Kargi AY (2018) Successful treatment of acromegaly and associated hypogonadism with first-line clomiphene therapy. Case Rep Endocrinol 2018:7925019. https://doi.org/10.1155/2018/7925019