Medical Management of Cushing’s Syndrome: Current and Emerging Treatments

Hinojosa-Amaya, José Miguel; Cuevas‐Ramos, Daniel; Fleseriu, Maria

doi:10.1007/s40265-019-01128-7

Cited by 36 publications

(35 citation statements)

References 137 publications

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“…Medical therapy is classified into steroidogenesis inhibitors (ketoconazole, metyrapone, mitotane, etomidate), centrally acting agents (cabergoline, pasireotide, pasireotide LAR, temozolomide) and glucocorticoid receptor (GR) antagonists (mifepristone). New treatment options such as oxylodrostat and levoketoconazole (steroidogenesis inhibitors), relacorilant (a glucocorticoid receptor antagonist) and drugs targeting corticotroph adenomas (retinoic acid, epidermal growth factor receptor inhibitors, cyclin-dependent kinases inhibitors, and heat shock protein 90 inhibitors, monoclonal antibodies against ACTH) are also being investigated [59,60]. Medical treatment is promising with current drug studies, consequently, it can also be preferred as an alternative treatment.…”

Section: Gks N ( %)mentioning

confidence: 99%

Efficacy and Safety of Stereotactic Radiotherapy in Cushing’s Disease: A Single Center Experience

Apaydın

Özkaya

Durmaz

et al. 2020

Exp Clin Endocrinol Diabetes

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Objective To determine the efficacy and safety of stereotactic RT in patients with Cushing’s disease (CD). Methods The study included 38 patients [31 patients who received gamma knife radiosurgery (GKS) and 7 patients who received cyberknife hypofractionated RT (HFRT)] with CD. Hormonal remission was considered if the patient had suppressed cortisol levels after low dose dexamethasone, normal 24-hour urinary free cortisol (UFC), and lack or regression of clinical features. Results Biochemical control after RT was observed in 52.6% of the patients with CD and median time to hormonal remission was 15 months. Tumor size control was obtained in all of the patients. There was no significant relationship between remission rate and laboratory, radiological and pathological variables except for preoperative UFC. Remission rate was higher in patients with lower preoperative UFC. Time to remission increased in parallel to postoperative cortisol and 1mg DST level. Although medical therapy before RT did not affect the rate of- and time to remission, medical therapy after RT prolonged the time to hormonal remission. Conclusion In this current single center experience, postoperative cortisol and 1mg DST levels were found as the determinants of time to remission. Although medical therapy before RT did not affect the rate of- and time to remission, medical therapy after RT prolonged the time to biochemical control . This latter finding might suggest a radioprotective effect of cortisol lowering medication use on peri-RT period.

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Section: Gks N ( %)mentioning

confidence: 99%

Efficacy and Safety of Stereotactic Radiotherapy in Cushing’s Disease: A Single Center Experience

Apaydın

Özkaya

Durmaz

et al. 2020

Exp Clin Endocrinol Diabetes

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“…The cost of treatment for patients taking PEG is high [79]; exceeding that of SRLs by 3-4 times [79,80]. A combination of PEG and other medications, however, might allow for cost-effective therapy, due to a reduced PEG dose [7,20,77,[81][82][83][84][85][86][87][88][89][90] (▶ table 3).…”

Section: Acromegalymentioning

confidence: 99%

“…Moreover, up to 35 % of patients in apparent remission will relapse within 10 years or more [119,120]. For patients with persistent disease there are several options [109]: repeat surgery (with lower efficacy of around 60 % of cases), radiotherapy (adenoma-targeted or whole sellar stereotactic radiosurgery), with a 54-75 % efficacy at 5 years and a 20-30 % recurrence rate [41,121], medical treatment [85], a combination of the above or bilateral adrenalectomy (the latter having a 10-30 % risk of inducing Nelson's syndrome) [122].…”

Section: Cushing's Diseasementioning

confidence: 99%

“…Criteria for treatment monitoring Clinical status (not always concordant with UFC) UFC -individual intravariability of 52 %, variability increases when baseline values are high LNSC -repeated assessments are useful if baseline value was high; may be more convenient than UFC collection; lack of concordance between UFC and LNSC in many cases Serum cortisol, ACTH -highly variable; during treatment with mifepristone ACTH and cortisol evaluation are not relevant, only clinical monitoring is available Biochemistry evaluation should correspond to the drug mechanism and potential side-effects UFC: 24 h-Urinary free cortisol; LNSC: Late-night salivary cortisol; ACTH: Adrenocorticotrophic hormone; CD: Cushing's disease. a Adapted from ref [85].…”

Section: Concomitant Medication For Comorbiditiesmentioning

confidence: 99%

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Updates in the Medical Treatment of Pituitary Adenomas

2019

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Pituitary adenomas represent approximately 15% of brain tumors; incidence is significantly on the increase due to widespread use of magnetic resonance imaging. Surgery remains the first-line treatment for most tumors overall. The role of dopaminergic agonists (DAs) and somatostatin receptor ligands (SRLs) in the treatment of pituitary adenomas is quite well established for prolactinomas and growth hormone (GH) excess. However, over the last decade new multi-receptor binding SRLs are increasingly used for treatment of acromegaly and Cushing’s disease. SRLs/DA chimeric compounds seem to have enhanced potency and efficacy when compared to that of individual SRLs or DA receptor agonists according to preclinical data. However, following negative results, more research is needed to determine if this interesting mechanism will translate into positive clinical effects for acromegaly patients. Furthermore, new agents that block adrenal steroidogenesis have been developed in phase III clinical trials for Cushing’s disease and several new compounds working at the pituitary level and/or blocking the glucocorticoid receptor are also in development. Combination therapy of drugs with similar or different mechanisms (possibly synergistic) are also on the increase. A growing awareness regarding all mechanisms involved in both control of pituitary secretion and cellular proliferation might allow for sole medical treatment of pituitary adenomas, especially macroadenomas, rather than surgery and/or radiation therapy, in the future. Moreover, the underlying decision on how to treat patients with pituitary adenomas should be individualized on a case-by-case basis with not only a goal of tumor shrinkage and biochemical control, but also of improving patients’ quality of life.

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“…However, the obvious disadvantage of this procedure is the subsequent permanent hypoadrenalism, which requires lifetime hormone replacement therapy (Chow et al, 2008). Medical therapy plays a secondary role to the previous alternatives in the management of CS, where it is used in severe cases of hypercortisolism to lower anaesthetic risk for a given surgical procedure or to diminish clinical afflictions during the latency period for remission in radiotherapy (Mancini, Porcelli &Giustina, 2010 andHinojosa-Amaya, Cuevas-Ramos, &Fleseriu, 2019).…”

Section: Therapeutic Principles In Cushing's Syndromementioning

confidence: 99%

A Stratified Approach for Cushing’s Syndrome Diagnosis

Chávez-Castillo¹,

Rojas²,

Aguirre³

et al. 2019

GJHS

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Cushing’s syndrome is an endocrine disorder broadly renowned as a diagnostic challenge. From the initial clinical presentation up to the identification of the underlying etiology, it is necessary to adhere to a logical and stratified plan of action, directed to the correlation of signs and symptoms to the physiopathology of the syndrome, in order to accurately establish a diagnosis and adequate treatment. From stages as early as the patient’s first clinical evaluation, the physician should be specially attentive of a constellation of clinical signs which strongly suggest the diagnosis of Cushing’s syndrome, such as the presence of a “moon face”, a “buffalo hump”, cutaneous atrophy, proximal muscle weakness and purplish cutaneous striae, among others. Based off these findings, laboratory analyses are necessary for the detection of hypercortisolism. According to these results, and if physiologic causes are ruled out, pathologic hypercortisolism is confirmed. Lastly, a complex array of diagnostic tests must be navigated to identify the primary origin of the disorder. Thus, the diagnosis of Cushing’s syndrome requires a logically structured algorithm of action, constructed off its pathophysiologic implications, in order to optimize time, resources and the interdisciplinary workgroup required for its consecution, and offer patients the possibility of a better quality of life. It is also important to highlight the need for a stratified approach in patients with metabolic disturbance given that medical professionals may simply treat the patient for obesity not recognizing the presence of the complicating condition Cushing’s syndrome.

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Medical Management of Cushing’s Syndrome: Current and Emerging Treatments

Cited by 36 publications

References 137 publications

Efficacy and Safety of Stereotactic Radiotherapy in Cushing’s Disease: A Single Center Experience

Efficacy and Safety of Stereotactic Radiotherapy in Cushing’s Disease: A Single Center Experience

Updates in the Medical Treatment of Pituitary Adenomas

A Stratified Approach for Cushing’s Syndrome Diagnosis

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