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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
Aminoglutethimide (Figure 8.13), the first aromatase inhibitor to be identified, was initially discovered, developed, and marketed as an anticonvulsant agent but was withdrawn from the clinic in 1966 after reports of adrenal insufficiency. It was subsequently found to inhibit several cytochrome P-450 enzymes involved in adrenal steroidogenesis by blocking the production of steroids from cholesterol. Aminoglutethimide was then re-developed as a “medical adrenalectomy” agent for use in advanced breast cancer, although it produced a number of side effects, including drowsiness and a skin rash which limited its use. The ability to cause drowsiness was related to its close structural similarity to the hypnotic agent glutethimide (DoridenTM) which had been developed in the 1950s as a potential replacement for the barbiturates (Figure 8.13). However, the discovery that its efficacy was mainly due to aromatase inhibition stimulated interest in the discovery and development of numerous new inhibitors during the 1980s and early 1990s, eventually leading to useful modern agents such as anastrozole (ArimidexTM).
Endocrine tumours
Published in Peter Hoskin, Peter Ostler, Clinical Oncology, 2020
Malignant tumours are rare, with a slight female predominance, arising at a younger age than most other carcinomas (median 35–55 years). Half are functioning and as with benign tumours are more frequent in females. Presentation is with vague abdominal symptoms, and up to one-third have signs of endocrine dysfunction, usually a combination of Cushing syndrome and virilism. Half have metastatic disease at presentation, haematogenous spread occurring to lung and liver. Investigation and treatment is as for benign tumours. In advanced disease metyrapone (250 mg–1 g qds) with physiological glucocorticoid replacement is useful for palliation of Cushing syndrome by inhibiting 2β-hydroxylase, but it might exacerbate virilism. Aminoglutethimide can be added if control is insufficient. An alternative is mitotane (o,p′-DDD), which causes necrosis and atrophy of normal adrenal tissue and differentiated carcinoma cells, reducing steroid output in 70% and giving objective tumour regression in one-third, although response is slow and glucocorticoid cover necessary.
Adrenal disorders in pregnancy, labour and postpartum – an overview
Published in Journal of Obstetrics and Gynaecology, 2020
Madhavi Manoharan, Prabha Sinha, Shabnum Sibtain
Medical treatment with anticortisolic drugs remains a second line of treatment (Lim et al. 2013; Touiti and Mghari 2015; Zieleniewski and Michalak 2017). The drugs commonly used are Metyrapone, Ketoconazole, Cyproheptidine, Amino-glutethemide, Mitotane and Cabergoline. They act by inhibiting steroid synthesis. Metyrapone is the most commonly used treatment with no side effects on maternal liver function or foetal development. This has been used in 69% of cases with good control of hyper cortisolism, in most of the cases (Lindsay et al. 2005; Blanco et al. 2006). However, Metyrapone can exacerbate high blood pressure and preeclampsia. Ketoconazole is not advisable in pregnancy because of risk of transplacental passage and its teratogenic and antiandrogenic effects on the fetus. (Berwaerts et al. 1999; Lindsay et al. 2005; Boronat et al. 2011). Mitotane and aminoglutethimide are also contraindicated during pregnancy because of risk of foetal masculinisation and teratogenicity (McClamrock and Adashi 1992). Cabergoline is not commonly used in pregnancy, unless the condition is persistent and recurrent (Woo and Ehsanipoor 2013; Nakhleh et al. 2016; Sek et al. 2017). Medical treatment with anticortisolic drugs could be reserved for special cases, with Metyrapone being the safest option. These drugs should be used with extreme caution in view of the low number of patients reported and limited experience with its use (Brue et al. 2018).
Retroperitoneal laparoscopic resection of adrenal tumor in pregnant woman with cushing’s syndrome
Published in Gynecological Endocrinology, 2020
Zhenquan Lu, Bingfeng Luo, Yuan Yuan, Xiang Yi, Tuo Liang, Lin Xiong, Yi Jiang, Richard Lo
Therapeutic options of CS include surgical treatment, conservative management, medical treatment, and delay of surgery after delivery [6,9]. Active management of patients with CS in gestation can reduce the maternal and fetal complications. Surgical treatment is reported to be the mainstay of treatment in pregnancy with CS. Some authors [15–19] demonstrated that adrenalectomy for this patients with adrenal tumor is the most successful treatment option, and live birth rate after surgery is up to 87%. In our case, the decision about the patient’s treatment was made by a multidisciplinary team, consisting of urologists, perinatologists, obstetricians, endocrinologists, cardiologist, anesthesiologists and other relevant clinical specialists. Retroperitoneal laparoscopic resection of left adrenal tumor was recommended as the first choice for this patient in her second trimester, with medical treatment as a second choice. When surgical treatment is contraindicated, medical therapy can be used to treat these pregnant patients [8], including metyrapone, ketoconazole, cyproheptadine and aminoglutethimide. However, there are risks for the fetal and maternal adverse effects.
N-acetyltransferase: the practical consequences of polymorphic activity in man
Published in Xenobiotica, 2020
The related antihypertensives, dihydralazine and endralazine, owing to their structural similarity to hydralazine, have been shown to undergo polymorphic N-acetylation but there was only a slight dissimilarity between the phenotypes with no significant differences in half-life (Reece et al., 1982; Waller et al., 1979). Endrazaline metabolism has been stated as being largely independent of the patient’s acetylator status (Quyyumi et al., 1983) but toxicity may be mediated via Phase I metabolites (Bourdi et al., 1994). Aminoglutethimide was introduced into medical usage as an anticonvulsant in the 1960s but was withdrawn a few years later owing to toxicity. A major metabolite is an N-acetylated derivative (Coombes et al., 1982; Goss et al., 1985) but acetylation does not appear to be associated with adverse events.