Increased levels of sex hormone-binding globulin
Estrogens can increase blood levels of the protein sex hormone-binding globulin (SHBG), which binds free testosterone (the active form) more strongly than estrogen, leading to decreased action of testosterone in male breast tissue. Conditions such as hyperthyroidism and chronic liver disease affect levels of SHBG, leading to symptomatic gynecomastia. Androgen resistance
Dysfunction in the androgen receptor prevents the effects of testosterone from acting on its target tissues. Androgen insensitivity syndromes result from the different degrees of resistance to the effects of androgens, and can cause external genitalia that may not be aligned with the genotype of the individuals sex chromosomes. Complete androgen insensitivity syndrome results in the failure to develop external genitalia such as the penis and scrotum along with development of breasts in an individual with testes. Partial androgen insensitivity syndrome may result in a variety of presentations. Minimal androgen insensitivity syndrome may present as gynecomastia in adolescence and may additionally be associated with infertility. Medications
Medications are known to cause gynecomastia through several different mechanisms. These mechanisms include increasing estrogen levels, mimicking estrogen, decreasing levels of testosterone or other androgens, blocking androgen receptors, increasing prolactin levels, or through unidentified means. Potential sources of estrogen include oral contraceptive pills, spironolactone, and anabolic steroids.High levels of prolactin in the blood (which may occur as a result of certain tumors or as a side effect of certain medications) has been associated with gynecomastia. A high level of prolactin in the blood can inhibit the release of gonadotropin-releasing hormone and therefore cause secondary hypogonadism.
This occurs secondary to the chemicals mentioned above, as well as damage from the infection, and involves signals to immune cells (T cells and macrophages) to come to the site of the infection.Rickettsia bacteria species like R. africae replicate around the area of the initial tick bite, causing necrosis (cell death) and lymph node inflammation. This is the cause of the characteristic eschar. Diagnosis
Many patients with ATBF who live in areas with a high number of infections (Africa and the West Indies) do not visit a doctor, as most patients only have mild symptoms. This disease can, however, cause more serious symptoms in travelers who have never been exposed to the Rickettsia africae bacterium before and are not immune. Travelers who present to a doctor after a trip to affected areas can be hard to diagnose, as many tropical diseases cause a fever similar to that of ATBF. Other diseases that may look similar are malaria, dengue fever, tuberculosis, acute HIV and respiratory infections. In addition to questions about symptoms, doctors will ask patients for an accurate travel history and whether he/she was near animals or ticks. Microbiological tests are available for doctors, but are expensive and often must be done by special laboratories.The antibiotic treatment available for rickettsiae infections has very few side effects, so if a doctor has a high suspicion of the disease, he or she may simply treat without doing more laboratory tests. Blood tests
Diagnosis of ATBF is mostly based on symptoms, as many laboratory tests are not specific for ATBF.