pasireotide and Hypertension

The aim of this study was to review the literature published and the most important papers presented to meetings on Cushing's disease from October 2011 to September 2012. The selection has been performed according to the authors' criteria. Articles have been classified into five groups: quality of life and perception of the disease, clinical features and pathophysiology, comorbidity conditions, diagnosis, and treatment. The results and conclusions of each publication are discussed.

Topics: ACTH-Secreting Pituitary Adenoma; Deamino Arginine Vasopressin; Endomyocardial Fibrosis; Humans; Hyperglycemia; Hypertension; Hypoglycemic Agents; Hypophysectomy; Neoplasm Proteins; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Prognosis; Quality of Life; Somatostatin; Thrombophilia

Epidemiological data of rare diseases are important for understanding disease burden, improving treatment, and planning healthcare systems. However, those of acromegaly in Japan are not well known. Our study aimed to describe the prevalence, incidence, prediagnostic comorbidities, and treatment patterns of patients with acromegaly in Japan. Using the National Database of Health Insurance Claims and Specific Health Checkups of Japan, we retrospectively identified 12,713 patients with acromegaly aged ≥20 years between January 2014 and December 2017 (the prevalence cohort), 2,552 newly diagnosed patients between January 2013 and December 2017 (the incidence and comorbidity cohort), and 2,125 patients enrolled in the database at least 365 days after the diagnosis (the treatment-pattern cohort). The average annual prevalence in 2015-2017 was 9.2 cases per 100,000 in the prevalence cohort, and the average annual incidence in 2013-2017 was 0.49 cases per 100,000 in the incidence and comorbidity cohort. The most common prediagnostic comorbidities included hypertension (43%), diabetes (37%), and hyperlipidemia (27%). In the treatment-pattern cohort, 54% and 45% of patients received surgery and medical treatment as the primary treatment, respectively. Between the first surgery and 365 days after diagnosis, 15% of the patients in this cohort received medical treatment as the secondary treatment, mostly with somatostatin analogs (83%). Of the 1,569 patients who underwent surgery, 29% received medical treatment before surgery. The prevalence and incidence of acromegaly in Japan were similar to those in other countries. This epidemiological study provides the basis for better management of acromegaly nationwide.

Topics: Acromegaly; Adenoma; Adult; Aged; Antineoplastic Agents, Hormonal; Bromocriptine; Cabergoline; Comorbidity; Dopamine Agonists; Female; Growth Hormone-Secreting Pituitary Adenoma; Human Growth Hormone; Humans; Hyperlipidemias; Hypertension; Incidence; Japan; Male; Middle Aged; Neurosurgical Procedures; Octreotide; Peptides, Cyclic; Prevalence; Radiosurgery; Radiotherapy, Intensity-Modulated; Retrospective Studies; Somatostatin; Young Adult

Cushing disease (CD) results from excessive exposure to glucocorticoids caused by an adrenocorticotropic hormone-secreting pituitary tumor. Inadequately treated CD is associated with significant morbidity and elevated mortality. Multicenter data on CD patients treated in routine clinical practice are needed to assess treatment outcomes in this rare disorder. The study purpose was to describe the burden of illness and treatment outcomes for CD patients.. Eight pituitary centers in four U.S. regions participated in this multicenter retrospective chart review study. Subjects were CD patients diagnosed at ≥18 years of age within the past 20 years. Descriptive statistical analyses were conducted to examine presenting signs, symptoms, comorbidities, and treatment outcomes.. Of 230 patients, 79% were female (median age at diagnosis, 39 years; range, 18 to 78 years). Length of follow-up was 0 to 27.5 years (median, 1.9 years). Pituitary adenomas were 0 to 51 mm. The most common presenting comorbidities included hypertension (67.3%), polycystic ovary syndrome (43.5%), and hyperlipidemia (41.5%). Biochemical control was achieved with initial pituitary surgery in 41.4% patients (91 of 220), not achieved in 50.0% of patients (110 of 220), and undetermined in 8.6% of patients (19 of 220). At the end of follow-up, control had been achieved with a variety of treatment methods in 49.1% of patients (110 of 224), not achieved in 29.9% of patients (67 of 224), and undetermined in 21.0% of patients (47 of 224).. Despite multiple treatments, at the end of follow-up, biochemical control was still not achieved in up to 30% of patients. These multicenter data demonstrate that in routine clinical practice, initial and long-term control is not achieved in a substantial number of patients with CD.. BLA = bilateral adrenalectomy CD = Cushing disease CS = Cushing syndrome eCRF = electronic case report form MRI = magnetic resonance imaging PCOS = polycystic ovary syndrome.

Topics: 14-alpha Demethylase Inhibitors; ACTH-Secreting Pituitary Adenoma; Adenoma; Adolescent; Adrenalectomy; Adult; Aged; Antineoplastic Agents; Cabergoline; Comorbidity; Enzyme Inhibitors; Ergolines; Female; Follow-Up Studies; Hirsutism; Hormone Antagonists; Hormones; Humans; Hyperlipidemias; Hypertension; Hypoglycemic Agents; Ketoconazole; Male; Metyrapone; Middle Aged; Mifepristone; Muscle Weakness; Muscular Atrophy; Neurosurgical Procedures; Obesity, Abdominal; Pituitary ACTH Hypersecretion; Pituitary Irradiation; Polycystic Ovary Syndrome; Retrospective Studies; Rosiglitazone; Somatostatin; Striae Distensae; Thiazolidinediones; Treatment Outcome; Tumor Burden; Young Adult

Cushing's disease (CD) is often accompanied by hypertension. CD can be treated surgically and, given the expression of somatostatin subtype 5 and dopamine 2 receptors by corticotroph pituitary adenomas, pharmacologically. Indeed, we recently observed that stepwise medical combination therapy with the somatostatin-analog pasireotide, the dopamine-agonist cabergoline, and ketoconazole (which directly suppresses steroidogenesis) biochemically controlled CD patients and lowered their blood pressure after 80 days. Glucocorticoids (GC) modulate the renin-angiotensin-aldosterone system (RAAS) among others by increasing hepatic angiotensinogen expression and stimulating mineralocorticoid receptors (MR). This study therefore evaluated plasma RAAS components in CD patients before and after drug therapy. In addition, we studied whether cabergoline/pasireotide have direct relaxant effects in angiotensin II (Ang II)-constricted iliac arteries of spontaneously hypertensive rats, with and without concomitant GR/MR stimulation with dexamethasone or hydrocortisone.. Baseline concentrations of angiotensinogen were elevated, while renin and aldosterone were low and suppressed, respectively, even in patients treated with RAAS-blockers. This pattern did not change after 80 days of treatment, despite blood pressure normalization, nor after 4 years of remission. In the presence of dexamethasone, pasireotide inhibited Ang II-mediated vasoconstriction.. The low plasma renin concentrations, even under RAAS blockade, in CD may be the consequence of increased GC-mediated MR stimulation and/or the elevated angiotensinogen levels in such patients. The lack of change in RAAS-parameters despite blood pressure and cortisol normalization suggests persisting consequences of long-term exposure to cortisol excess. Finally, pasireotide may have a direct vasodilating effect contributing to blood pressure lowering.

Topics: Adult; Aged; Aldosterone; Angiotensinogen; Animals; Cabergoline; Ergolines; Female; Humans; Hypertension; Iliac Artery; In Vitro Techniques; Male; Middle Aged; Pituitary ACTH Hypersecretion; Rats; Renin; Renin-Angiotensin System; Somatostatin; Vasoconstriction