China
Africa
Explore chapters and articles related to this topic
Cushing's syndrome
Published in Nadia Barghouthi, Jessica Perini, Endocrine Diseases in Pregnancy and the Postpartum Period, 2021
Contraindicated, ineffective, or under-studied medical treatmentsCyproheptadine reduced ACTH secretion and was safely used in three cases; however, it was not effective.5Aminoglutethimide inhibits several steps along the steroid biosynthesis pathway.6 It should be avoided due to fetal masculinization and teratogenic effects.3,5Mitotane is an adrenolytic agent that directly suppresses the adrenal cortex and alters peripheral metabolism of steroids. Its use is contraindicated in pregnancy due to teratogenic effects.1,4,5Radiotherapy is contraindicated during pregnancy due to delayed results and teratogenic effects.1,4Pasireotide, a somatostatin analog, has a lack of published data and studies in pregnancy.14
Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
In the UK, mitotane is recommended by NICE for the symptomatic treatment of advanced or inoperable adrenocortical carcinoma. Its main use is in those patients with persistent disease despite surgical resection, and in those who have metastatic disease or who are not suitable candidates for surgery. It is also used in veterinary medicine to treat pituitary-dependent Cushing’s syndrome in dogs.
Endocrine and Neuroendocrine Tumors
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Natasha Shrikrishnapalasuriyar, P.N. Plowman, Márta Korbonits, Ashley B. Grossman
The mainstay of treatment is surgery with a complete margin-negative resection. When a high level of suspicion of ACC exists, open surgical oncological resection is recommended as lymph removal may improve diagnostic accuracy and therapeutic outcome. Laparoscopic adrenalectomy can be considered for tumors with a size up to 6 cm without any evidence of local invasion, but biopsy is contraindicated when there is suspicion of malignancy as there is a risk of seeding. For residual or inoperable tumors, the mainstay of therapy is the adrenolytic drug mitotane; its mode of action is unclear but it directly suppresses the adrenal cortex and modifies the peripheral metabolism of steroids. Mitotane is administered orally in increasing doses to a maintenance daily dose establishing a “therapeutic level” of 14–20g/L. Levels above this cause nausea, fatigue, and severe neurological disturbance, as mitotane is stored in lipid-rich tissues including the myelin sheath. Lower levels appear to be less effective therapeutically. It should also be noted that patients will often require hydrocortisone replacement once any evidence of Cushing’s syndrome is treated, and that serum cortisol estimations are highly unreliable in this situation. Chemotherapy with etoposide, platinum, and doxorubicin is standard first-line therapy; the usefulness of second-line chemotherapy is questionable. Immunotherapy has not been markedly successful in therapy so far.72
Mitotane liposomes for potential treatment of adrenal cortical carcinoma: ex vivo intestinal permeation and in vivo bioavailability
Published in Pharmaceutical Development and Technology, 2020
Patricia Zancanella, Daniele M. L. Oliveira, Bonald H. de Oliveira, Thiago D. Woiski, Cesar C. Pinto, Maria H. A. Santana, Eliana B. Souto, Patrícia Severino
The oral administration of mitotane associated with foodstuff (e.g., chocolate, oils, milk, or other emulsions) increase its plasma levels compared to the oral intake of conventional tablets (Zancanella et al. 2006). These findings substantiate the need to develop new mitotane formulations in order to improve its solubility, intestinal permeation, and thus its oral bioavailability. Attempts to formulate mitotane in lipid nanocarriers, e.g., oil-in-water (o/w) microemulsions (Attivi et al. 2010; Lin et al. 2011), and in lipid nanoparticles have already been published (Grando et al. 2013; Severino et al. 2013). Self-microemulsifying drug delivery systems (SMEDDS) containing mitotane were developed and their intestinal permeation evaluated in vivo (Attivi et al. 2010). The bioavailability tested in rabbits was 3.4 times greater for mitotane-loaded SMEDDS than the commercial product (Lysodren®).
New and emerging drug therapies for Cushing’s disease
Published in Expert Opinion on Pharmacotherapy, 2018
Sylvère Störmann, Jochen Schopohl
Another drug derived from amphenone B is mitotane, a drug approved for and primarily used in advanced or inoperable adrenocortical carcinoma. Fundamentally, it is cytotoxic to the adrenal gland, but is also an inhibitor of the cholesterol side-chain cleavage enzyme. To a lesser extent, it also inhibits 11β- and 18-hydroxylase and 3β-hydroxysteroid dehydrogenase [35]. In the long term, it leads to permanent adrenal atrophy equivalent to a chemical adrenalectomy. Its main cytotoxic effect is mediated by an apoptotic process activated by the disruption of mitochondria, and is restricted to the zona reticularis and the zona fasciculata [155,156]. Clinically, the use of mitotane causes a significant reduction in adrenal cortisol and androgen synthesis. Onset of action is slow and due the lipophilic nature of the drug it has a very long half-life so that it may have effects lasting months after discontinuation. Mitotane has a wide range of side effects including nausea, vomiting, and neurotoxicity. Its use in CD is limited to select cases, but only after careful consideration. In the largest series to date, 67 patients with CD were treated with mitotane, of which 72% achieved UFC normalization after 5–8 months [157]. However, after discontinuation of mitotane among patients considered in remission, recurrence occurred in as much as 71%.
Adrenal disorders in pregnancy, labour and postpartum – an overview
Published in Journal of Obstetrics and Gynaecology, 2020
Madhavi Manoharan, Prabha Sinha, Shabnum Sibtain
Recommendations for the management of ACC in pregnancy are difficult in view of the rarity of the condition. From the limited number of case series, adrenal surgery after MRI evaluation is possible. As complete resection of the tumour is the most efficient treatment with the best prognosis, it should be recommended in any trimester of pregnancy. As preterm delivery is high collaboration with the obstetric and neonatal team is important. In view of the very poor prognosis of pregnancy-associated tumours, Mitotane treatment could be offered, even in tumours limited to the adrenal gland. Mitotane is not advisable during pregnancy, however, can be prescribed post-delivery. Breastfeeding is not advisable while on Mitotane.