C. W. H. Havard

Humoral immunity before and after thymectomy in myasthenia gravis

Humoral immunity was studied in 10 patients with myasthenia gravis before thymectomy, in 15 different patients over 10 years after thymectomy, and in normal controls. Antibody titers to acetylcholine receptor were significantly (p < 0.01) lower in the post-thymectomy group. However, other antibody titers to common viruses, and to Escherichia coli, and isohemagglutinins showed no significant change. Levels of IgM and IgE (with atopic subjects excluded) decreased following thymectomy (p < 0.05). Autoantibodies persisted, apart from those directed against the acetylcholine receptor. The absence of any significant changes in humoral immunity after thymectomy for myasthenia gravis suggests that there is no generalized loss of helper T-cell function.

Polycystic ovary syndrome.

The most frequent presenting feature of polycystic ovarian disorder is menstrual disturbance usually oligomenorrhea or secondary amenorrhea. Hirsutism is next most common but true virilization is rare. Infertility is common. Many women with polycystic ovaries have abdominal pain. Obesity is infrequent. Laparoscopy or laparotomy with ovarian biopsy give the best diagnosis. Histological examination shows subcapsular fibrosis follicular cysts in the cortex and many atretic follicles. There is no single biochemical test to diagnose the condition. Plasma testosterone assay is the most helpful single test with levels often above the normal female range. Hyperestrogenism has been postulated in the polycystic ovary syndrome. The increased incidence of endometrial carcinoma reported in women under age 40 with polycystic ovarian disease may be thus explained. Basophil pituitary adenomata Cushings syndrome adrenal or ovarian tumors or congenital adreanl hyperplasia may produce or be associated with polycystic ovaries. Ovarian wedge resection may restore regular menses and fertility in women with enlarged cystic ovaries suggesting a primary ovarian cause. The mechanism of this result is not clear. Normally ove r half of the circulating testosterone in women is derived from peripheral conversion of androstenedione. Direct secretion from the ovary or adrenals contributes only a small proportion. However in hirsute women increased circulating testosterone results essentially from the ovaries or adrenals. Usually the primary lesion is thought to be hypothalamic with increased ovarian androgen production the result of gonadotropin stimulation. An inherited genetic factor may be involved. Treatment with clomiphene citrate may produce ovulation in 80% of cases with pregnancy 40%. When ovulation occurs but pregnancy does not follow ovarian wedge resection or added human chorionic gonadotropin may achieve success. Corticosteroids have also been reported as being beneficial. Combined oral contraceptives have been used to reduce hirsutism but some progestogens may aggravate the condition. A more estrogenic regimen is advised. Bromocriptine is a dopamine receptor agonist. It inhibits the secretion of prolactin. Inital results of its use for polycystic ovarian disease are encouraging. Choice of treatment is determined by the clinical presentation and the main complaint.

Use of clomiphene and luteinizing hormone/follicle stimulating hormone-releasing hormone in investigation of ovulatory failure.

A luteinizing hormone/follicle-stimulating hormone-releasing hormone (LH/FSH-RH) test was performed in 70 women with amenorrhoea or anovulatory infertility, or both, and a clomiphene stimulation test was also performed in 24 of these patients. Most patients responded to LH/FSH-RH with significant increases in LH and FSH. In women with gonadal dysgenesis or premature ovarian failure exaggerated responses were observed after LH/FSH-RH and there was no change in high basal LH levels after clomiphene. Patients with absent or impaired responses to LH/FSH-RH failed to respond to clomiphene. All patients with anovulatory menstrual cycles responded to both LH/FSH-RH and clomiphene, while seven out of 13 amenorrhoeic patients with a normal LH/FSH-RH response showed an early LH rise during clomiphene treatment and six were unresponsive. These results suggest a difference between the two groups at hypothalamic level with consequent therapeutic implications.

Myasthenia Gravis Pathogenesis and Current Concepts in Management

SummaryMyasthenia gravis is a disorder of autoimmunity in which neuromuscular transmission is impaired by autoantibodies to the acetylcholine receptor (AChR). There is evidence for more than one form of the disorder with differing genetic susceptibilities. The aetiology is unknown, but thymic involvement is suggested by abnormal histology and by the beneficial response of the disorder to thymectomy in more than two-thirds of patients. Thymectomy is indicated in most patients unless the symptoms are minimal or are confined to the extraocular muscles alone, or the patient is elderly. Thymectomy alone results in remission in about one-third of patients, but, in addition, most patients require symptomatic anticholinesterase drugs to prolong the action of acetylcholine at the muscle end-plate. Overdosage of these drugs can also cause weakness.Immunosuppression with corticosteroids or azathioprine may also improve myasthenia; at present, these drugs are used mainly in patients who do not respond to thymectomy or in those patients considered unsuitable for operation. Plasma exchange can cause a rapid, though temporary, involvement in myasthenia, but it probably has no long term place in its treatment. Future therapy will probably involve specific immunotherapy, such as anti-idiotype antibodies.