4.2 Review

Long-term follow-up and predictors of recurrence of Cushing's disease

Related references

Note: Only part of the references are listed.
Review Endocrinology & Metabolism

Glucose and lipid metabolism abnormalities in Cushing's syndrome

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Summary: Prolonged excess of glucocorticoids can lead to metabolic alterations, including increased gluconeogenesis, reduced insulin sensitivity, inhibited insulin secretion, and increased fat tissue and free fatty acid levels. These metabolic changes can have negative impacts on health and mortality, highlighting the importance of long-term monitoring.

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Summary: Radiotherapy, particularly Gamma Knife radiosurgery (GKRS), is a useful adjuvant treatment for patients with persistent or recurrent Cushing's disease. The most common side effect is hypopituitarism, while severe neurological complications are rare in radiation-naive patients.

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Summary: This study presents data on the clinical presentation at diagnosis in 1564 patients with Cushing's syndrome. The most frequent symptoms were weight gain, hypertension, skin alterations, and myopathy. Men were more likely to experience reduced libido and bone fractures, while women were more likely to have skin alterations and menstrual irregularities. Patients had poor quality of life at diagnosis, and there was a delay of 2 years between symptom onset and diagnosis. It is important to develop strategies to shorten the time to diagnosis and start treatment promptly to reduce the burden on patients' psychophysical health.

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Long-term morbidity and mortality in patients with Cushing's syndrome

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Summary: Patients with Cushing's syndrome have increased multisystem morbidity and mortality, presenting clinical problems such as hypertension, diabetes, overweight, and myopathy. Mortality is particularly high during active disease and within the first year after diagnosis.

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Long-term effects of glucocorticoid excess on the brain

Alies J. Dekkers et al.

Summary: The clinical manifestations of metabolism and cardiovascular system in patients with Cushing's syndrome are well-known. However, recent studies have shown that hypercortisolism, both endogenous and exogenous, affects brain functioning at different time scales. This review discusses the effects of hypercortisolism on the brain, the prevalence of cognitive and neuropsychological deficits, and their course after remission. Possible underlying neuronal changes are also proposed based on experimental models and in vitro studies. Recommendations for future studies are provided.

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Hypothalamic-pituitary-adrenal axis recovery after treatment of Cushing's syndrome

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Summary: Secondary adrenal insufficiency develops after successful treatment for Cushing's syndrome. Glucocorticoid replacement therapy is necessary until the recovery of the HPA axis. Patients often experience symptoms of glucocorticoid withdrawal syndrome after cure. Individualized treatment is needed to avoid overtreatment or undertreatment.

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Distinguishing Cushing's disease from the ectopic ACTH syndrome: Needles in a haystack or hiding in plain sight?

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Summary: In the context of ACTH-dependent Cushing's syndrome, ectopic ACTH secretion from a neuroendocrine tumour needs to be differentiated carefully from pituitary-dependent Cushing's syndrome, Cushing's disease, for optimal therapy. Diagnosis may be difficult as clinical and biochemical tests may overlap with Cushing's disease. Imaging is essential and should be interpreted considering both anatomical and functional imaging modalities.

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Aggressive corticotroph tumors and carcinomas

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Summary: Pituitary tumors are usually benign, but aggressive pituitary tumors and carcinomas are rare and challenging to treat, with high mortality rates. Most of these are corticotroph tumors, which have special prognoses. Current clinical, pathological, and molecular prognostic markers are limited, making early management difficult. Temozolomide is the first-line treatment, with immune checkpoint inhibitors as alternative options for temozolomide treatment failure.

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The diagnosis and management of Cushing's syndrome in pregnancy

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Summary: Endogenous Cushing's syndrome (CS) is rarely encountered during pregnancy and the diagnosis is challenging. Conclusive recommendations or a standardized management approach for all patients with CS in pregnancy cannot be made due to the lack of comprehensive literature. Management decisions, including surgery, medical control, or conservative approach, should be highly individualized and consider various factors such as stage of gestation, tumor localization, severity of CS, maternal comorbidity, and patient choice.

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Jean-Francois Bonneville et al.

Summary: Pituitary MRI is essential for the diagnosis of ACTH-dependent Cushing's syndrome, but its results can vary. The expertise of the neuroradiologist, the use of a Tesla 3.0 MRI, and the choice of sequences are important factors. T2 and 3D gradient echo sequences after gadolinium injection are the most informative and can detect most macro- and microadenomas. However, diagnosing picoadenomas (<3-4 mm) remains challenging.

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Julia Simon et al.

Summary: Corticotroph tumours are sporadic monoclonal neoplasms, with USP8 gene mutations found in around half of cases. TP53 and ATXR mutations may indicate transition to a more aggressive tumour phenotype. The role and importance of other genomic alterations remain to be elucidated.

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Diagnostic workup of Cushing's syndrome

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Summary: Cushing's syndrome is a rare but detrimental endocrine disorder, and early diagnosis and prompt treatment are crucial. The diagnostic approach involves a stepwise process of screening, confirming the diagnosis, and establishing the etiology.

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Medical management of Cushing's disease: When and how?

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Summary: Transsphenoidal surgery is the first-line treatment for Cushing's disease, but medical treatment is also an option in certain cases, such as severe hypercortisolism, short-term treatment before surgery, long-term treatment after failed surgery, or while waiting for the full effect of radiation therapy. The approach to medical treatment varies depending on the severity of hypercortisolism, with a block and replace approach for severe cases and a titration approach for mild cases.

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Summary: Transsphenoidal surgery (TSS) is the preferred initial treatment for Cushing's disease (CD), with microscopic TSS and endoscopic TSS being the two available surgical techniques. Repeat TSS can achieve remission rates of over 70% for microadenomas. Early postoperative assessment of remission status and a steroid-sparing protocol are recommended for postoperative management. Prophylactic antithrombotic measures can significantly reduce the risk of postoperative thromboembolic events. Prevention or successful treatment of cortisol withdrawal syndrome remains a challenge. The development of functional imaging holds promise for improved preoperative detection of microadenomas. Intraoperative identification of microadenomas using specific fluorescent targeting is a promising future avenue.

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