Management of acromegaly

Acromegaly is caused by hypersecretion of growth hormone and resultant overproduction of insulin-like growth factor-1 and is associated with increased mortality and morbidity. Successful treatment modalities have been developed and are used in a multistep approach allowing normal life expectancy as well as improved quality of life in an increasing number of patients

Clinical and genetic aspects of familial isolated pituitary adenomas

Pituitary adenomas represent a group of functionally diverse neoplasms with relatively high prevalence in the general population. Most occur sporadically, but inherited genetic predisposing factors are increasingly recognized. Familial isolated pituitary adenoma is a recently defined clinical entity, and is characterized by hereditary presentation of pituitary adenomas in the absence of clinical and genetic features of syndromic disease such as multiple endocrine neoplasia type 1 and Carney complex. Familial isolated pituitary adenoma is inherited in an autosomal dominant manner and accounted for approximately 2–3% of pituitary tumors in some series. Germline mutations in the aryl-hydrocarbon interacting protein gene are identified in around 25% of familial isolated pituitary adenoma kindreds. Pituitary adenomas with mutations of the aryl-hydrocarbon interacting protein gene are predominantly somatotropinomas and prolactinomas, but non-functioning adenomas, Cushing disease, and thyrotropinoma may also occur. These tumors may present as macroadenomas in young patients and are often relatively difficult to control. Furthermore, recent evidence indicates that aryl-hydrocarbon interacting protein gene mutations occur in >10% of patients with sporadic macroadenomas that occur before 30 years of age, and in >20% of children with macroadenomas. Genetic screening for aryl-hydrocarbon interacting protein gene mutations is warranted in selected high-risk patients who may benefit from early recognition and follow-up

Levoketoconazole: a novel treatment for endogenous Cushing's syndrome.

Introduction: Endogenous Cushing's syndrome (CS) is a rare, life-threatening endocrine disorder that is caused by chronic exposure to cortisol overproduction. Levoketoconazole (Recorlev), a 2S, 4R stereoisomer of ketoconazole, is a steroidogenesis inhibitor under investigation for the treatment of CS. Areas covered: This review covers the pharmacology, efficacy, and safety of levoketoconazole for the treatment of patients with endogenous CS. Expert opinion: Based on the preclinical and clinical pharmacology findings, levoketoconazole appears to be the relevant enantiomer of ketoconazole for inhibition of steroidogenesis, with more potent inhibition of both cortisol and androgen synthesis relative to ketoconazole racemate and the 2R, 4S stereoisomer dextroketoconazole. Results from the phase III SONICS study showed that levoketoconazole was effective in normalizing cortisol levels and improving biomarkers of cardiovascular risk in a significant percentage of patients. In addition, treatment with levoketoconazole showed improvements in subjective clinical assessments of clinician-rated CS clinical signs and symptoms, patient-reported quality of life, and depression symptom severity. Testosterone levels decreased significantly in women. Levoketoconazole had an acceptable safety profile with no unexpected safety signals. The favorable pharmacology, efficacy, and safety profile of levoketoconazole supports its use as medical therapy for CS, if approved

Corticotroph tumor progression after bilateral adrenalectomy (Nelson’s syndrome):systematic review and expert consensus recommendations

Corticotroph tumor progression (CTP) leading to Nelson's syndrome (NS) is a severe and difficult-to-treat complication subsequent to bilateral adrenalectomy (BADX) for Cushing's disease. Its characteristics are not well described, and consensus recommendations for diagnosis and treatment are missing

Time to diagnosis in Cushing’s syndrome: A meta-analysis based on 5367 patients

The time from first symptom to diagnosis of Cushing's syndrome is considered relevant for the severity of phenotype at presentation and long-term outcome. We therefore performed a systematic literature search to investigate relevant factors associated with a short time to diagnosis. The meta-analysis of 45 studies with 5560 patients showed significant differences for adrenal Cushing’s syndrome, Cushing’s disease and the ectopic Cushing’s syndrome. We did not find difference for gender, age or time of publication

Acromegaly at diagnosis in 3173 patients from the Liège Acromegaly Survey (LAS) Database

Acromegaly is a rare disorder caused by chronic growth hormone (GH) hypersecretion. While diagnostic and therapeutic methods have advanced, little information exists on trends in acromegaly characteristics over time. The Liège Acromegaly Survey (LAS) Database, a relational database, is designed to assess the profile of acromegaly patients at diagnosis and during long-term follow-up at multiple treatment centers. The following results were obtained at diagnosis. The study population consisted of 3173 acromegaly patients from ten countries; 54.5% were female. Males were significantly younger at diagnosis than females (43.5 vs 46.4 years; P 3100 patients is the largest international acromegaly database and shows clinically relevant trends in the characteristics of acromegaly at diagnosis

Clinical and Molecular Update on Genetic Causes of Pituitary Adenomas.

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MANAGEMENT OF ENDOCRINE DISEASE: Pituitary "incidentaloma": Neuroradiological assessment and differential diagnosis.

Pituitary incidentalomas are a by-product of modern imaging technology. The term ‘incidentaloma’ is neither a distinct diagnosis nor a pathological entity. Rather, it is a collective designation for different entities that are discovered fortuitously, requiring a working diagnosis based on the input of the radiologist, endocrinologist and often a neurosurgeon. In addition to pathological conditions affecting the pituitary gland, a thorough knowledge of the radiological characteristics of normal variants and technical artifacts is required to arrive at an accurate differential diagnosis. After careful radiological and hormonal evaluation, the vast majority of pituitary incidentalomas turn out to be non-functioning pituitary microadenomas and Rathke’s cleft cysts (RCCs). Based on the low growth potential of non-functioning pituitary microadenomas and RCCs, periodic MRI surveillance is currently considered the optimal management strategy. Stricter follow-up is required for macroadenomas, as increases in size occur more frequently.</jats:p