Cushing’s disease represents a condition in which the body experiences hypercortisolism, which is an overproduction of cortisol. This imbalance is caused by a pituitary adenoma (tumor of the pituitary gland), which in turn results in increased production and secretion of ACTH.
What is Cushing’s disease?
Named after the American neurologist Harvey Williams Cushing, Cushing’s disease refers to a disorder of the anterior pituitary gland in which an ACTH-producing tumor causes the adrenal cortex to be overstimulated and, subsequently, to secrete too much cortisol. Thus, Cushing’s disease represents a type of hypercortisolism. The resulting symptoms are called Cushing’s syndrome. Cushing’s disease in itself refers to a tumor of the pituitary gland, so that too much ACTH is produced and released into the blood: Adrenocorticotropic hormone, or ACTH, represents a vital hormone produced in the anterior pituitary gland. Overproduction of ACTH also increases the production of mineral corticoids, glucocorticoids and sex hormones. The resulting typical clinical picture of this excess of ACTH is manifested, among other things, in severe weight gain, especially [[moon face]] and truncal obesity (thick torso and rather thin legs and arms), as well as a reduction in muscle mass and other metabolic disorders and systemic diseases.
Causes
The exact, reproducible cause of ACTH-producing pituitary tumor or Cushing’s disease is not scientifically known. The disease occurs about once in 100,000 people, with women affected up to four times more often than the male sex. Cushing’s disease itself is a special and at the same time the most frequent cause of the so-called Cushing’s syndrome: In about 70 percent of those affected by Cushing’s syndrome, a tumor of the pituitary gland, usually a benign pituitary adenoma, is the reason for the strongly increased cortisol level in the body. In this case and when the tumor cells of the pituitary gland produce excessive ACTH, which leads to increased secretion of cortisol by the adrenal glands in the body, physicians speak of Cushing’s disease. However, the exact mechanism of origin of the pituitary alteration with the hormonal and far-reaching changes mentioned has not been completely clarified. The rare disease occurs preferentially between the second and fifth decade of life.
Symptoms, complaints, and signs
The diagnosis is usually made because the patient comes to the doctor with the typical – for him possibly not as such assignable – symptoms of Cushing’s disease: a facial swelling, the “full moon face” and a significant weight gain, especially in the neck (the so-called “buffalo neck”), are part of the characteristic appearance of Cushing’s disease, although legs and arms are relatively rather slim. The skin also becomes thinner and develops bruises more quickly than usual, and there may also be general muscle weakness or muscle breakdown, bone loss (osteoporosis), high blood pressure, metabolic disorders (such as diabetic metabolism), irregular menstruation, as well as concentration disorders and mood swings, even depression and other illnesses. If the physician wants to diagnostically clarify a suspicion of Cushing’s disease based on the physical symptoms, a special blood count is first used. Laboratory blood tests can detect an excess of ACTH caused by Cushing’s disease in a deviating amount of glucocorticoids, mineral corticoids, sex hormones as well as CRH and ACTH. In the case of an alteration or tumor of the anterior pituitary, ACTH levels, sex hormones, glucocorticoids, and mineral corticoids are increased, whereas CRH is decreased. However, a single measurement of glucocorticoids is not sufficient for a reliable diagnosis, since glucocorticoid levels fluctuate throughout the day and are higher in the morning than in the evening, for example. Contraceptives, various medications, obesity and stress also have an influence on glucocorticoid production, so that several measurements must always be taken in order to make a reliable diagnosis, especially of the ACTH level. A 24-hour urine measurement can also provide information about glucocorticoid levels and be used to confirm the blood test.In addition to laboratory tests, imaging procedures are also used in cases of suspected Cushing’s disease in order to clearly confirm possible changes or tumors of the pituitary gland. Computer tomography (CT) or magnetic resonance imaging are available as modern diagnostic methods to confirm or refute the suspicion of a pituitary adenoma. Tumors are not always clearly visible. In addition, there is the so-called dexamethasone suppression test, which can also be consulted in cases of suspected Cushing’s disease and can determine hormonal gland hyperfunction.
Complications
Cushing’s disease primarily causes severe swelling in the patient’s face. Those affected thus suffer from the typical full-moon face and thus, in many cases, from inferiority complexes or lowered self-esteem. However, the other regions of the body tend to remain slim, resulting in unusual proportions. Likewise, the disease leads to high blood pressure and not infrequently to muscle weakness, so that the resilience of the affected person decreases significantly. Disturbances in concentration or mood swings are common, which significantly reduce the quality of life of the affected person. Depression and other psychological upsets are also not uncommon. Especially in children, Cushing’s disease can lead to severe limitations in development and thus slow it down. Treatment of Cushing’s disease is primarily by removing the tumor that is responsible for the symptoms. Affected patients are dependent on taking medication. No particular complications occur. However, some affected individuals rely on taking medications and supplements for the rest of their lives.
When should you see a doctor?
Uniform swelling of the face that is not due to weight gain or the side effect of taking pills should be evaluated by a physician. If a popularly known moon face, rounded facial shape, or other visual abnormalities of the affected person occur, the observations should be discussed with a physician. In case of a weakening of the usual muscular strength, disturbances of concentration as well as a decrease of the usual physical as well as mental performance, a doctor is needed. Rapid fatigability, lassitude or internal weakness are signs of an existing disorder that needs to be investigated and treated. If everyday requirements can no longer be met, behavioral problems occur or hormonal disorders develop, a visit to the doctor is necessary. If sexually mature women suffer from irregularity of the menstrual cycle, they should consult a doctor. Changes in libido are also signs of a present disease. Mood swings, high blood pressure and irritability are considered unusual. If existing complaints persist unabated for several weeks, or if they continually increase in severity, a visit to the doctor is advisable. A doctor should be consulted in case of strong changes in weight, a permanently increased inner stress experience and conspicuousness of the skin appearance. Characteristic of the disease is an altered perception of health during the course of the day. In the morning, the affected person often feels worse than in the evening.
Treatment and therapy
Therapy for Cushing’s disease primarily involves surgical removal of the pituitary tumor. The tumor is surgically removed via the so-called transsphenoidal approach, in which the procedure is performed through the nose and sphenoid bone. In some cases, for example when surgery cannot be performed, radiotherapy of the pituitary adenoma is also possible, depending on the extent of the tumor and the individual prognosis. This radiotherapy damages the tumor cells in such a way that they die after some time; however, in this case, the treatment successes can be expected only after several months. If neither radiation nor surgical removal is successful (or feasible), there is the possibility of therapeutically targeting the adrenal glands: So-called adrenostatics can be used to permanently prevent the adrenal glands from producing glucocorticoids, mineral corticoids and sex hormones.If drug inhibition is not sufficiently possible to effectively control the consequences and symptoms due to ACTH overproduction, adrenectomy may also be considered. In this case, both adrenal glands are surgically removed to permanently control the momentous ACTH excess. If the physicians decide to take this measure, a lifelong substitution of glucocorticoids and mineral corticoids is subsequently necessary. Synthetic glucocorticoids such as dexamethasone and prednisolone are also increasingly used in the treatment of Cushing’s disease. Due to their special chemical preparation, they have a higher stability as well as other positive properties in hormone metabolism, so that these can also be used in the treatment of Cushing’s disease.
Outlook and prognosis
The prognosis in Cushing’s disease is positive, provided that the causative tumor is detected and treated in time. The use of synthetic drugs such as prednisolone or dexamethasone improves the stability of glucocorticoid receptors in the brain. When taken regularly, combined with surgical intervention, Cushing’s disease can be well treated. However, prescribed cortisol can cause various side effects and interactions. These include strokes, cardiovascular problems and fractures. Surgery promises about an 80 percent chance of curing Cushing’s disease. ACTH levels normalize immediately after surgery and physical symptoms should resolve rapidly. If left untreated, the prognosis is much worse, as the tumor grows, causing ACTH levels to become increasingly unbalanced, which can result in a variety of physical symptoms. If the syndrome occurs during long-term treatment with certain drugs, the complaints also disappear after the preparations are discontinued. Bronchial carcinomas offer a somewhat poorer prognosis than adrenal carcinomas, which, provided they have not yet spread, can be treated well. The chances of recovery from Cushing’s syndrome are 50 to 80 percent. If treatment is successful, the patient’s life expectancy is not reduced.
Prevention
Prevention or individual prevention of Cushing’s disease per se is probably not possible according to current knowledge. The extent to which risk factors or a possible genetic predisposition play a role in this disease also cannot yet be said with certainty. However, due to the diverse and sometimes severe symptomatology, it can be recommended to seek medical advice in case of suspicious changes and in case of doubt in order to improve the prognosis and chances of therapy in case of emergency.
Follow-up
Even after successful removal of the causative tumor, regular follow-up of the patient is necessary. For example, there is a risk of residual cells remaining within the body. With the help of control examinations, possible neoplasms of the tumor can be detected and treated in time. Following the operation, a pathologist examines the removed tissue under a microscope. If a sufficient amount of healthy tissue is present, this is considered an indication that the tumor has been completely removed. However, complete certainty can only be achieved by inspecting the remaining tissue, which is not yet possible. Individual altered cells are also not yet detectable. However, if a certain amount is formed again, this leads to an increase in the level of cortisone in the blood. Imaging examination methods such as magnetic resonance imaging (MRI) provide information about the renewed growth of a tumor. With the help of various follow-up procedures, the recurrence can be detected before it causes new symptoms. The earlier a recurrence of Cushing’s disease is diagnosed, the greater the chances of success. The right time for follow-up examinations plays an important role in follow-up care. However, various factors such as the speed of tumor growth and its extent and position are decisive for this. The physician must take all factors into account during follow-up care, using empirical values for sensible intervals for the check-ups.
You can do it yourself
The success of therapy for Cushing’s disease depends crucially on the cooperation of the patient: The most important prerequisite is to reliably take the medication in the dosage prescribed by the doctor and to keep the treatment and follow-up appointments. Comprehensive information about the disease and its possible effects is of great importance, especially at the beginning: A checklist is a good way to ensure that no important question is forgotten when visiting the doctor. Psychological support can be helpful, especially in the early stages, in order to better accept the disease and to be able to cope with the changed situation. Psychotherapeutic help should also be sought in the case of hormone-related depressive moods or anxiety states; in addition, learning stress management and relaxation techniques contributes to mental stability. In a self-help group, patients have the opportunity to exchange experiences. For close relatives, it may also be useful to seek professional counseling. Recovery after a successful operation or after the start of drug therapy can take some time. Until there is a noticeable improvement in symptoms, it is important not to exceed one’s own performance limits: Patients should not be afraid to accept help with everyday activities during this phase. Light physical exercise and a healthy diet can contribute significantly to increasing mental and physical well-being.
