A successful case of pregnancy in a woman with ACTH-independent Cushing’s syndrome treated with ketoconazole and metyrapone

Zieleniewski, Wojciech; Michalak, Renata

doi:10.1080/09513590.2017.1290070

Cited by 17 publications

(10 citation statements)

References 19 publications

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“…Medical treatment of CS with ketoconazole in pregnant women may permit good control of hypercortisolism and in a limited number of cases was found to be well tolerated both by the mother and the fetus (36). However, it was less frequently used because of potential teratogenicity and increased rate of abortion observed in animal studies (6).…”

Section: Is the Use Of Anticortisolic Drugs Possible During Pregnancy?mentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Management of Cushing’s syndrome during pregnancy: solved and unsolved questions

Brue

Amodru

Castinetti

2018

European Journal of Endocrinology

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With fewer than 200 reported cases, Cushing's syndrome (CS) in pregnancy remains a diagnostic and therapeutic challenge. In normal pregnancies, misleading signs may be observed such as striae or hypokalemia, while plasma cortisol and urinary free cortisol may rise up to 2- to 3-fold. While the dexamethasone suppression test is difficult to use, reference values for salivary cortisol appear valid. Apart from gestational hypertension, differential diagnosis includes pheochromocytoma and primary aldosteronism. The predominant cause is adrenal adenoma (sometimes without decreased ACTH), rather than Cushing's disease. There are considerable imaging pitfalls in Cushing's disease. Aberrant receptors may, in rare cases, lead to increased cortisol production during pregnancy in response to HCG, LHRH, glucagon, vasopressin or after a meal. Adrenocortical carcinoma (ACC) is rare and has poor prognosis. Active CS during pregnancy is associated with a high rate of maternal complications: hypertension or preeclampsia, diabetes, fractures; more rarely, cardiac failure, psychiatric disorders, infection and maternal death. Increased fetal morbidity includes prematurity, intrauterine growth retardation and less prevalently stillbirth, spontaneous abortion, intrauterine death and hypoadrenalism. Therapy is also challenging. Milder cases can be managed conservatively by controlling comorbidities. Pituitary or adrenal surgery should ideally be performed during the second trimester and patients should then be treated for adrenal insufficiency. Experience with anticortisolic drugs is limited. Metyrapone was found to allow control of hypercortisolism, with a risk of worsening hypertension. Cabergoline may be an alternative option. The use of other drugs is not advised because of potential teratogenicity and/or lack of information. Non-hormonal (mechanical) contraception is recommended until sustained biological remission is obtained.

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Section: Is the Use Of Anticortisolic Drugs Possible During Pregnancy?mentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Management of Cushing’s syndrome during pregnancy: solved and unsolved questions

Brue

Amodru

Castinetti

2018

European Journal of Endocrinology

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“…Use in pregnant women and in women of childbearing potential not using contraception is not recommended unless clearly necessary; monitor blood pressure in pregnant women receiving metyrapone and manage hypertension as needed Limited data in pregnant women (20 pregnancies in 17 women [6,13,[28][29][30][31][32][33][34][35][36][37][38][39][40][41])…”

Section: Breastfeedingmentioning

confidence: 99%

Metyrapone in Cushing’s syndrome: a profile of its use

Al-Salama

2021

Drugs Ther Perspect

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Metyrapone (Metopirone ® ), a pyridine derivative, is a useful treatment option for the management of patients with endogenous Cushing's syndrome, based on evidence from more than six decades of its use in clinical practice, prospective and retrospective studies, as well as case reports. Metyrapone is associated with a rapid onset of action and is effective in reducing cortisol levels and improving clinical and/or biochemical features and cortisol-related comorbidities of Cushing's syndrome. The efficacy of metyrapone was demonstrated in all aetiologies of the condition, when used in a range of clinical settings (including presurgery treatment and when used in combination with other drugs) and in the short and long term. Metyrapone is generally well tolerated when used in the treatment of patients with endogenous Cushing's syndrome, with gastrointestinal adverse events being the most commonly reported. Plain Language SummaryEndogenous Cushing's syndrome is a rare disease, resulting from cortisol hypersecretion, and is associated with substantial morbidity and mortality. Surgery is the mainstay treatment for the majority of patients with Cushing's syndrome; however, medical therapy is increasingly being used, particularly when surgery is not indicated or is unsuccessful, or while waiting for radiotherapy to be effective. Oral metyrapone (Metopirone ® ), a pyridine derivative, is approved for the management of endogenous Cushing's syndrome in the EU. Evidence for the efficacy of metyrapone in the treatment of Cushing's syndrome has been demonstrated in prospective and retrospective studies. Metyrapone has a rapid onset of action (≈ 2 h), reduces cortisol levels, improves the clinical and/or biochemical features and cortisol-related comorbidities of the disease, and demonstrates sustained efficacy in the long term; the efficacy of metyrapone is evident in a range of clinical settings. Metyrapone is generally well tolerated in patients with endogenous Cushing's syndrome. Given its efficacy and tolerability profile, metyrapone is a useful treatment option for the management of patients with endogenous Cushing's syndrome.

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“…Metyrapone, 31,35,70,[74][75][76][77][78] ketoconazole, 70,74,[79][80][81] cabergoline, 80,[82][83][84] mitotane, 85,86 cyproheptadine, [87][88][89] and aminogluthemide 5,6 have all been used in the management of patients with CS during pregnancy. Each is discussed in turn, along with their benefits and limitations, in Table 3.…”

Section: Medical Therapymentioning

confidence: 99%

“…92,93 Even with the application of strict definition criteria (mean serum cortisol level between 150-300 nmol L À1 assessed serially on a cortisol day curve), over 50% of patients with CS achieve target cortisol levels with metyrapone monotherapy. 94 The evidence for use during pregnancy is limited to a small number of case reports, 31,35,70,[74][75][76][77][78] but has been the medical treatment most commonly used in pregnancy. 30 Of particular benefit, onset of action is rapid, with normalisation of urinary cortisol within the first few weeks.…”

Section: Metyraponementioning

confidence: 99%

The diagnosis and management of Cushing's syndrome in pregnancy

Hamblin

Coulden

Fountas

et al. 2022

J Neuroendocrinology

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Endogenous Cushing's syndrome (CS) is rarely encountered during pregnancy. Clinical and biochemical changes in healthy pregnancy overlap with those seen in pregnancy complicated by CS; the diagnosis is therefore challenging and can be delayed. During normal gestation, adrenocorticotrophic hormone, corticotrophin‐releasing hormone, cortisol, and urinary free cortisol levels rise. Dexamethasone administration fails to fully suppress cortisol in pregnant women without CS. Localisation may be hindered by non‐suppressed adrenocorticotrophic hormone levels in a large proportion of those with adrenal CS; smaller corticotroph adenomas may go undetected as a result of a lack of contrast administration or the presence of pituitary hyperplasia; and inferior petrosal sinus sampling is not recommended given the risk of radiation and thrombosis. Yet, diagnosis is essential; active disease is associated with multiple insults to both maternal and foetal health, and those cured may normalise the risk of maternal–foetal complications. The published literature consists mostly of case reports or small case series affected by publication bias, heterogeneous definitions of maternal or foetal outcomes or lack of detail on severity of hypercortisolism. Consequently, conclusive recommendations, or a standardised management approach for all, cannot be made. Management is highly individualised: the decision for surgery, medical control of hypercortisolism or adoption of a conservative approach is dependent on the timing of diagnosis (respective to stage of gestation), the ability to localise the tumour, severity of CS, pre‐existing maternal comorbidity, and, ultimately, patient choice. Close communication is a necessity with the patient placed at the centre of all decisions, with risks, benefits, and uncertainties around any investigation and management carefully discussed. Care should be delivered by an experienced, multidisciplinary team, with the resources and expertise available to manage such a rare and challenging condition during pregnancy.

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A successful case of pregnancy in a woman with ACTH-independent Cushing’s syndrome treated with ketoconazole and metyrapone

Cited by 17 publications

References 19 publications

MANAGEMENT OF ENDOCRINE DISEASE: Management of Cushing’s syndrome during pregnancy: solved and unsolved questions

MANAGEMENT OF ENDOCRINE DISEASE: Management of Cushing’s syndrome during pregnancy: solved and unsolved questions

Metyrapone in Cushing’s syndrome: a profile of its use

The diagnosis and management of Cushing's syndrome in pregnancy

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