Myasthenia gravis : clinical aspects and possible involvement of prolactin

Myasthenia gravis (MG) is an autoimmune disease characterized by the production of antibodies against the skeletal muscle acetylcholine receptor (AChR). MG is usually associated with thymic disorders including thymoma (about 10%) and lymphofollicular hyperplasia (HPL) (up to 80%). Patients with thymoma have been considered to have a poor prognosis compared to those with other thymic disorders. Neuroendocrine interactions are important for the immune regulation. Prolactin (PRL) as well other hormones have been suggested to play a role in autoimmune diseases. Acting through its receptor, PRL modulates the immune system by stimulating cell proliferation and survival. PRL has multiple effects on the immune system. It stimulates and activates many immune cells, such as T cells, B cells, natural killer cells, macrophages, neutrophils, CD34+ hematopoietic cells and antigen-presenting dendritic cells. It also stimulates production of autoantibodies.

Study I describes an association of MG with raised levels of plasma PRL in female patients. Since PRL has stimulating effects on the immune system, the increased levels might be implied in the pathophysiology of MG. A case control study of PRL levels was performed in 192 MG patients and 192 healthy controls. The levels of plasma PRL were raised in 101 women with MG, but not in 91 men. There was an association between high prolactin levels and high levels of autoantibodies against the AChR. There was no association between PRL levels and thymic histology.

Study II is based on comparison of 537 MG patients with different thymic histology. Two hundred eleven patients constitute a separate non-thymectomized group. Most patients with HPL were women (79%); the sex distribution in other groups was equal. Initially, pure ocular MG was most often found in non-thymectomized patients (20%), a mild to moderate MG in patients with HPL (75%) and the most severe MG in patients with thymoma (43%). In five thymoma patients MG appeared after the thymectomy. Transsternal surgical approach with removing all thymic tissue was used for 255 (78%) patients. Suprasternal approach was used for 71 patients of whom 39 were reoperated by a transsternal method because of insufficient effect.

The occurrence of thyroid disorders in the whole MG population, as well as rheumatoid arthritis and SLE were somewhat increased. Out of 530 investigated patients 466 (88 %) had circulating antibodies against AChR. In total, 300 patients (56%) got immunosuppressive treatment. Patients with thymorna needed immunosuppressive drugs more often (85%) than patients with HPL (37%), those with normal thymic histology (74%) or not thymectomized patients (57%). Totally, 438 patients (82%) improved or went into remission.

To conclude, we found an association with raised PRL level in women affected by MG. There was an association between high prolactin levels and high levels of autoantibodies against the acetylcholine receptor. Thus, PRL might be of importance for MG pathogenesis. The prognosis of MG is good in our material irrespective of the thymic gland histology. We assume that this may be due to early thymectomy and the use of immunomodulating agents.

List of scientific papers

I. Tsinzerling N, Pirskanen R, Matell G, Zhulev NM, Chukhlovina ML, Lefvert AK (2006). Raised prolactin levels in myasthenia gravis: two case reports and a study of two patient populations. Acta Neurol Scand. 114(5): 346-9.
https://pubmed.ncbi.nlm.nih.gov/17022784

II. Tsinzerling N, Lefvert AK, Matell G, Pirskanen R (2006). Myasthenia gravis: A long term follow-up study of Swedish patients. [Manuscript]