The International Journal of Romanian Society of Endocrinology / Registered in 1938

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January - March 2005, Volume 1, Issue 1
Case Report

Fica SV, Popescu L, Ciprut T, Ardeleanu C, Terzea D, Trifanescu R, Coculescu M

Beneficial effects of gonadotropin releasing hormone analogs in pulmonary lymphangioleiomyomatosis

Acta Endo (Buc) 2005, 1 (1): 109-119
doi: 10.4183/aeb.2005.109

OBJECTIVE: To report an unusual cause of respiratory failure in a 33-year old Caucasian woman, diagnosed at 26 years with pulmonary lymphangioleiomyomatosis (LAM) and treated with gonadoliberin analogs (aGnRH) four years.\r\nMETHODS: The respiratory failure was diagnosed on functional tests (spirometry, oxymetry, diffusing capacity of carbon monoxide). High resolution chest computed tomographic (HRCT) scan and open lung biopsy with specific immunohistochemistry certified the diagnosis.\r\nRESULTS: The diagnosis of pulmonary LAM was established after one year on chest HRCT and lung biopsy which revealed the proliferation of smooth muscle of pulmonary vessels, positive for actin, desmin, vimentin, estrogen- and progesterone- receptors. Spirometry revealed mixed obstructive and restrictive dysfunction. A correlation between worsening of dyspnea and estradiol peaks occurred during three gestation periods. Despite a short treatment with medroxyprogesterone 10 mg/day and tamoxifen (20 mg/day), the patient?s symptoms and pulmonary function tests worsened. aGnRH treatment improved both symptoms and pulmonary function tests during the first year and was associated with a slow decline in pulmonary function tests and stabilization of the cystic lesions during the following 3 years. The patient did not develop LAM-complications such as: pneumothorax, chylothorax, or hemoptysis.\r\nCONCLUSION: Treatment with aGnRH is effective in slowing the evolution of pulmonary LAM.

Keywords: estrogen receptors, gonadoliberin analogs, lymphangioleiomyomatosis

Correspondence: Mihai Coculescu, Endocrinology Department, ?Carol Davila? University of Medicine and Pharmacy, 34-36 Bd. Aviatorilor, 011863, Bucharest, Romania, Tel/Fax: + 4021 3198718, e-mail:


1. Johnson S. Rare diseases. 1. Lymphangioleiomyomatosis: clinical features, management and basic mechanisms. Thorax 1999;54:254-264. [CrossRef]
2. Ferrans VJ, Yu ZX, Nelson WK et al. Lymphangioleiomyomatosis (LAM): a review of clinical and morphological features. J Nippon Med Sch. 2000;67:311-329. [CrossRef]
3. Rosai J ed. Rosai and Ackerman?s Surgical Pathology. 9th ed. Mosby. 2004.
4. Urban T, Lazor R, Lacronique J et al. Pulmonary lymphangioleiomyomatosis. A study of 69 patients. Groupe d?Etudes et de Recherche sur les Maladies ?Orphelines? Pulmonaires (GERM?O?P). Medicine (Baltimore) 1999;78:321-337. [CrossRef]
5. Denoo X, Hermans G, Degives R et al. Successful treatment of pulmonary lymphangioleiomyomatosis with progestins: a case report. Chest 1999;115:276-279. [CrossRef]
6. Klein M, Krieger O, Ruckser R et al. Treatment of lymphangioleiomyomatosis by ovariectomy, interferon alpha 2b and tamoxifen?a case report. Arch Gynecol Obstet. 1992;252:99-102. [CrossRef]
7. Laverdiere C, David M, Dubois J et al. Improvement of disseminated lymphangiomatosis with recombinant interferon therapy. Pediatr Pulmonol. 2000;29:321-324. [CrossRef]
8. Boehler A, Speich R, Russi EW et al. Lung transplantation for lymphangioleiomyomatosis. N Engl J Med. 1996;335:1275-1280. [CrossRef]
9. Desurmont S, Bauters C, Copin MC et al. [Treatment of pulmonary lymphangioleiomyomatosis using a GnRH agonist]. Rev Mal Respir. 1996;13:300-304.
10. Rossi GA, Balbi B, Oddera S et al. Response to treatment with an analog of the luteinizinghormone- releasing hormone in a patient with pulmonary lymphangioleiomyomatosis. Am Rev Respir Dis. 1991;143:174-176.
11. Clementsen PS, Folke K, and Faurschou P. [Lymphangioleiomyomatosis]. Ugeskr Laeger. 1995;157:298-299.
12. Chu SC, Horiba K, Usuki J et al. Comprehensive evaluation of 35 patients with lymphangioleiomyomatosis. Chest 1999;115:1041-1052. [CrossRef]
13. Bonetti F, Chiodera PL, Pea M et al. Transbronchial biopsy in lymphangiomyomatosis of the lung. HMB45 for diagnosis. Am J Surg Pathol. 1993;17:1092-1102. [CrossRef]
14. Logginidou H, Ao X, Russo I et al. Frequent estrogen and progesterone receptor immunoreactivity in renal angiomyolipomas from women with pulmonary lymphangioleiomyomatosis. Chest 2000;117:25-30. [CrossRef]
15. Matsui K, Takeda K, Yu ZX et al. Downregulation of estrogen and progesterone receptors in the abnormal smooth muscle cells in pulmonary lymphangioleiomyomatosis following therapy. An immunohistochemical study. Am J Respir Crit Care Med. 2000;161:1002-10
16. Baldi S, Papotti M, Valente ML et al. Pulmonary lymphangioleiomyomatosis in postmenopausal women: report of two cases and review of the literature. Eur Respir J. 1994;7:1013-1016.
17. Hu H, Wang W, and Wang X. [Clinical analysis of pulmonary lymphangioleiomyomatosis]. Zhonghua Yi Xue Za Zhi. 2001;81:1256-1260.
18. Kaptanoglu M, Hatipoglu A, Kutluay L et al. Bilateral chylothorax caused by pleuropulmonary lymphangiomyomatosis: a challenging problem in thoracic surgery. Scand Cardiovasc J. 2001;35:151- 154. [CrossRef]
19. Usuki J, Horiba K, Chu SC et al. Immunohistochemical analysis of proteins of the Bcl-2 family in pulmonary lymphangioleiomyomatosis: association of Bcl-2 expression with hormone receptor status. Arch Pathol Lab Med. 1998;122:895-902.
20. Moss J, DeCastro R, Patronas NJ et al. Meningiomas in lymphangioleiomyomatosis. JAMA 2001;286:1879-1881.
21. Carsillo T, Astrinidis A, and Henske EP. Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci U S A. 2000;97:6085-6090. [CrossRef]
22. Sato T, Seyama K, Fujii H et al. Mutation analysis of the TSC1 and TSC2 genes in Japanese patients with pulmonary lymphangioleiomyomatosis. J Hum Genet. 2002;47:20-28. [CrossRef]
23. Yu J, Astrinidis A, and Henske EP. Chromosome 16 loss of heterozygosity in tuberous sclerosis and sporadic lymphangiomyomatosis. Am J Respir Crit Care Med. 2001;164:1537-1540.
24. Inoue Y, King TE, Jr., Barker E et al. Basic fibroblast growth factor and its receptors in idiopathic pulmonary fibrosis and lymphangioleiomyomatosis. Am J Respir Crit Care Med. 2002;166:765-773. [CrossRef]
25. Valencia JC, Matsui K, Bondy C et al. Distribution and mRNA expression of insulin-like growth factor system in pulmonary lymphangioleiomyomatosis. J Investig Med. 2001;49:421-433. [CrossRef]
26. Evans SE, Colby TV, Ryu JH et al. Transforming growth factor-beta 1 and extracellular matrixassociated fibronectin expression in pulmonary lymphangioleiomyomatosis. Chest 2004;125:1063- 1070. [CrossRef]
27. Matsui K, Takeda K, Yu ZX et al. Role for activation of matrix metalloproteinases in the pathogenesis of pulmonary lymphangioleiomyomatosis. Arch Pathol Lab Med. 2000;124:267-275.
28. Hayashi T, Fleming MV, Stetler-Stevenson WG et al. Immunohistochemical study of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in pulmonary lymphangioleiomyomatosis (LAM). Hum Pathol. 1997;28:1071-1078. [CrossRef]
29. Dweik RA, Laskowski D, Ozkan M et al. High levels of exhaled nitric oxide (NO) and NO synthase III expression in lesional smooth muscle in lymphangioleiomyomatosis. Am J Respir Cell Mol Biol. 2001;24:414-418.
30. Johnson SR and Tattersfield AE. Decline in lung function in lymphangioleiomyomatosis: relation to menopause and progesterone treatment. Am J Respir Crit Care Med. 1999;160:628-633.
31. Zanella A, Toppan P, Nitti D et al. Pulmonary lymphangioleiomyomatosis: a case report in postmenopausal woman treated with pleurodesis and progesterone (medroxyprogesterone acetate). Tumori 1996;82:96-98.
32. Kitaichi M and Izumi T. Lymphangioleiomyomatosis. Curr Opin Pulm Med. 1995;1:417-424.
33. Svendsen TL, Viskum K, Hansborg N et al. Pulmonary lymphangioleiomyomatosis: a case of progesterone receptor positive lymphangioleiomyomatosis treated with medroxyprogesterone, oophorectomy and tamoxifen. Br J Dis Chest 1984;78:264-271. [CrossRef]
34. Zahner J, Borchard F, Fischer H et al. [Successful therapy of a postpartum lymphangioleiomyomatosis. Case report and literature review]. Schweiz Med Wochenschr. 1994;124:1626-1632.
35. Pechet TT, Meyers BF, Guthrie TJ et al. Lung transplantation for lymphangioleiomyomatosis. J Heart Lung Transplant 2004;23:301-308. [CrossRef]