When Cushing's disease [ kʊʃɪŋ ] or Cushing disease (rare disease Itsenko-Cushing to the umbrella term of Cushing's syndrome to distinguish), named after Harvey Williams Cushing (and after Nikolai Mikhailovich Itsenko ), a disease is known, in which a tumor too much ACTH is produced in the ACTH-producing (corticotropic) cells of the pituitary gland , which leads to increased stimulation of the adrenal cortex with adrenal hyperplasia and, as a result, excessive cortisol production . The symptoms are called Cushing's syndrome (hypercortisolism, "too much cortisol"). Cushing's syndrome can also have other causes, but these are not referred to as Cushing 's disease .
Synonyms are: pituitary Cushing's syndrome , corticotropic pituitary adenoma , pituitary corticotropic microadenoma , basophilism and basophilic adenoma .
Cushing's disease, as differentiated from Cushing's syndrome , is based on an overproduction of ACTH (adrenocorticotropic hormone) in the anterior pituitary gland or an overproduction of CRH in the hypothalamus , which stimulates the production of the glandotropic hormone ACTH. It does not describe the presence of too much cortisol per se (Cushing's syndrome - for example due to an adrenal tumor ), but the central overproduction of liberins or glandotropic hormones, which secondarily cause an overproduction of the hormone cortisol. Overproduction of ACTH is accompanied by increased pigmentation of the skin . This is due to the production of ACTH, which is obtained from its precursor POMC , from which α-MSH is also formed. In all cases, the prerequisite for Cushing's disease are autonomous cell aggregates that no longer respond to the natural, negative feedback mechanism.
In 1937 Harvey Cushing summarized the symptoms into one clinical picture. The clinical picture generally corresponds to Cushing's syndrome :
Symptoms of the disease can include a round moon face , trunk obesity (thin arms and legs, thick torso with a " bull neck "), weight gain, decreased muscle mass and increased bone fragility ( osteoporosis ), increased blood pressure ( arterial hypertension ), disorders of the carbohydrate metabolism (increased thirst and frequent urination ), Impotence and, in children, a combination of stunted growth and obesity. The increased gluconeogenesis ensures a diabetic metabolic situation and thus a possible steroid diabetes.
Diagnosis and therapy
In addition to the characteristic appearance of Cushing's syndrome, there are numerous endocrinological tests for the detection, exclusion or differentiation of Cushing's syndrome (see there).
If a tumor is suspected, MRI imaging is also possible, although the tumor is not always visible.
The following therapeutic options exist: transnasal / transsphenoidal surgical removal of adenoma, radiation (radiotherapy) of the adenoma, drug blocking of ACTH secretion with the somatostatin analogue pasireotide, if unsuccessful bilateral adrenalectomy with subsequent lifelong glucocorticoid and mineralocorticoid substitution.
- Mathias Riebold et al .: A C-terminal HSP90 inhibitor restores glucocorticoid sensitivity and relieves a mouse allograft model of Cushing disease. In: Nature Medicine , volume 21, pp. 276-280 (2015) doi: 10.1038 / nm.3776
- Siegfried Schwarz et al .: Pathophysiology - molecular cellular systemic basis of diseases W. Maudrich Verlag, Vienna 2007, ISBN 978-3-85175-860-3 .
- Ludwig Weissbecker: Cushing's disease (basophilism or basophilic adenoma, Cushing's disease). In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition ibid 1961, p. 1007 f.
- Gerd Herold and colleagues: Internal Medicine 2020. Self-published, Cologne 2020, ISBN 978-3-9814660-9-6 , p. 790.
- Max Planck Society : Silibinin - plant-based active ingredient against brain tumors. February 9, 2015.
- Max Planck Society: IBI licenses Silibinin for the treatment of Cushing's disease. July 10, 2018
- Silibinin: New Approach to Cushing's Disease? In: Pharmazeutische Zeitung , July 12, 2018.