Familial isolated pituitary adenoma (AIP study)

Posted on February 29, 2016 by MaryO

Professor Márta Korbonits is the Chief Investigator for the NIHR Clinical Research Network supported familial pituitary adenomas study (AIP) which is investigating the cause, the clinical characteristics and family screening of this relatively recently established disease group.

Please tell us about the condition in layman’s terms?
Pituitary adenomas are benign tumours of the master gland of the body, the pituitary gland. It is found at the base of the brain. The most commonly identified adenoma type causing familial disease makes excess amounts of growth hormone, and if this starts in childhood the patient have accelerated growth leading them to become much taller than their peers. This condition is known as gigantism.

How rare is this condition?
Pituitary adenomas cause disease in 1 in a 1000 person of the general population. About five to seven percent of these cases are familial pituitary adenomas.

How it is normally diagnosed?
There are different types of pituitary adenomas causing quite varied diseases. Gigantism and its adult counterpart acromegaly is usually diagnosed due to rapid growth, headaches, joint pains, sweating, high blood pressure and visual problems. Pituitary adenomas grow slowly and it usually takes 2-10 years before they get diagnosed. The diagnosis finally is made by blood tests measuring hormones, such as growth hormone, and doing an MRI scan of the pituitary area.

What is the study aiming to find out?
The fact that pituitary adenomas can occur in families relatively commonly was not recognised until recently. Our study introduced testing for gene alterations in the AIP (Aryl Hydrocarbon Receptor Interacting Protein) gene in the UK, and identified until now 38 families with 160 gene carriers via screening. We also aim to identify the disease-causing genes in our other families as well.

How will it benefit patients?
The screening and early treatment of patients can have a huge benefit to patients as earlier treatment will lead to less complications and better chance to recovery. We hope we can stop the abnormal growth spurts therefore avoiding gigantism. Patients that are screened will find out if they carry the AIP gene and whether they are likely to pass on the gene to their families. For most patients, knowing they have a gene abnormality also helps them to understand and accept their condition.

How will it change practice?
As knowledge of the condition becomes more understood, genetic testing of patients to screen for AIP changes should be more commonplace. Patients can be treated knowing they have this condition, and family members who are carriers of the gene can benefit from MRI scans to monitor their pituitary gland and annual hormone tests.

How did the NIHR CRN support the study?
The familial pituitary adenoma study is on the NIHR CRN Portfolio. The study’s association with NIHR has allowed the widespread assessment of the patients, has incentivised referrals from clinicians and raised awareness of both our study and the familial pituitary adenoma condition itself.

For more information contact NIHR CRN Communications Officer, Damian Wilcock on 020 3328 6705  or email damian.wilcock@nihr.ac.uk

From https://www.crn.nihr.ac.uk/blog/case_study/national-rare-disease-day-2016-familial-isolated-pituitary-adenoma-aip-study/

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Osilodrostat for Cushing’s

Posted on November 12, 2015 by MaryO

The study looked at a drug to treat Cushing’s disease. The article, in the journal Pituitary, is called Osilodrostat, a potent oral 11β-hydroxylase inhibitor: 22-week, prospective, Phase II study in Cushing’s disease.
Fleseriu M, Pivonello R, Young J, Hamrahian AH, Molitch ME, Shimizu C, Tanaka T, Shimatsu A, White T, Hilliard A, Tian C, Sauter N, Biller BM, Bertagna X.
Pituitary. 2015 Nov 5. [Epub ahead of print]

Abstract

PURPOSE:
In a 10-week proof-of-concept study (LINC 1), the potent oral 11β-hydroxylase inhibitor osilodrostat (LCI699) normalized urinary free cortisol (UFC) in 11/12 patients with Cushing’s disease. The current 22-week study (LINC 2; NCT01331239) further evaluated osilodrostat in patients with Cushing’s disease.

METHODS:
Phase II, open-label, prospective study of two patient cohorts. Follow-up cohort: 4/12 patients previously enrolled in LINC 1, offered re-enrollment if baseline mean UFC was above ULN. Expansion cohort: 15 newly enrolled patients with baseline UFC > 1.5 × ULN. In the follow-up cohort, patients initiated osilodrostat twice daily at the penultimate efficacious/tolerable dose in LINC 1; dose was adjusted as needed. In the expansion cohort, osilodrostat was initiated at 4 mg/day (10 mg/day if baseline UFC > 3 × ULN), with dose escalated every 2 weeks to 10, 20, 40, and 60 mg/day until UFC ≤ ULN. Main efficacy endpoint was the proportion of responders (UFC ≤ ULN or ≥50 % decrease from baseline) at weeks 10 and 22.

RESULTS:
Overall response rate was 89.5 % (n/N = 17/19) at 10 weeks and 78.9 % (n/N = 15/19) at 22 weeks; at week 22, all responding patients had UFC ≤ ULN. The most common AEs observed during osilodrostat treatment were nausea, diarrhea, asthenia, and adrenal insufficiency (n = 6 for each). New or worsening hirsutism (n = 2) and/or acne (n = 3) were reported among four female patients, all of whom had increased testosterone levels.

CONCLUSIONS:
Osilodrostat treatment reduced UFC in all patients; 78.9 % (n/N = 15/19) had normal UFC at week 22. Treatment with osilodrostat was generally well tolerated.

KEYWORDS:
11β-hydroxylase; Cortisol; Cushing’s; LCI699; Osilodrostat

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Pituicytoma and Cushing’s Disease in a 7-Year-Old Girl: A Mere Coincidence?

Posted on November 9, 2015 by MaryO

Paola Cambiaso, Donato Amodio, Emidio Procaccini, Daniela Longo, Stefania Galassi, Francesca Diomedi Camassei, Marco Cappa

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Abstract

Pituicytoma is a tumor extremely rare in childhood, with only 4 cases reported in literature. It is thought to arise from the specialized glial elements called “pituicytes.” The association of pituicytoma and Cushing’s disease (CD) has been described only once so far, in an adult patient.

A 7-year-old girl was referred for clinical signs of hypercortisolism, and a diagnosis of CD was made. MRI revealed 2 pathologic areas in the pituitary gland. The patient underwent surgery, with microscopic transsphenoidal approach, and a well-circumscribed area of pathologic tissue was identified and removed. Surprisingly, histologic and immunohistochemical study provided unequivocal evidence of pituicytoma. No pituitary adenoma could be identified.

For persistent hypercortisolism, the patient necessitated transsphenoidal endoscopic reintervention and 2 other lesions were removed. By immunohistological examination, these lesions were confirmed to be corticotropin-secreting adenoma. Unfortunately, there was no postoperative decrease in corticotropin and cortisol levels, and the patient underwent bilateral laparoscopic adrenalectomy.

Considering that we report a second case of association of pituicytoma and corticotropin-secreting adenoma, that CD is infrequent, and pituicytoma is extremely rare in childhood, the coexistence of these 2 tumors should not be considered a mere coincidence. To date, there is no conclusive evidence about the origin of these different subtypes of pituitary tumors. This case supports the hypothesis that these tumors share a common progenitor cell, which could be the folliculostellate cell.

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Low Immediate Postoperative Serum-Cortisol Nadir Predicts The Short-Term, But Not Long-Term, Remission After Pituitary Surgery For Cushing’s Disease

Posted on October 26, 2015 by MaryO

Cushing’s disease is an ACTH-producing pituitary adenoma, and the primary treatment is microscopic or endoscopic transsphenoidal selective adenectomy. The aims of the present study were to evaluate whether the early postoperative S-cortisol level can serve as a prognostic marker for short- and long-term remission, and retrospectively review our own short and long term results after surgery for Cushing’s disease.

Methods: This single centre, retrospective study consists of 19 consecutive patients with Cushing’s disease who underwent transsphenoidal surgery.

S-cortisol was measured every 6 h after the operation without any glucocorticoid replacement. We have follow-up on all patients, with a mean follow-up of 68 months.

Results: At the three-month follow-up, 16 patients (84 %) were in remission; at 12 months, 18 (95 %) were in remission and at the final follow-up (mean 68 months), 13 (68 %) were in remission.

Five-years recurrence rate was 26 %. The mean postoperative S-cortisol nadir was significantly lower in the group of patients in remission than in the non-remission group at 3 months, but there was no difference between those in long-term remission compared to those in long-term non-remission.

The optimal cut-off value for classifying 3-month remission was 74 nmol/l.

Conclusion: We achieved a 95 % 1-year remission rate with transsphenoidal surgery for Cushing’s disease in this series of consecutive patients. However, the 5-year recurrence rate was 26 %, showing the need for regular clinical and biochemical controls in this patient group.

The mean postoperative serum-cortisol nadir was significantly lower in patients in remission at 3 months compared to patients not in remission at 3 months, but a low postoperative S-cortisol did not predict long-term remission.

Author: Jon Ramm-Pettersen Helene Halvorsen Johan EvangPål Rønning Per Hol Jens Bollers levJon Berg-Johnsen Eirik Helseth
Credits/Source: BMC Endocrine Disorders 2015, 15:62

Published on: 2015-10-26

Copyright by the authors listed above – made available via BioMedCentral (Open Access). Please make sure to read our disclaimer prior to contacting 7thSpace Interactive. To contact our editors, visit our online helpdesk. If you wish submit your own press release, click here.
From http://7thspace.com/headlines/519336/low_immediate_postoperative_serum_cortisol_nadir_predicts_the_short_term_but_not_long_term_remission_after_pituitary_surgery_for_cushings_disease.html

Filed under: Cushing's, Diagnostic Testing, pituitary, Treatments | Tagged: , , , , , , , , | Leave a comment »

Global Cushing’s Syndrome Market Size 2015

Posted on October 19, 2015 by MaryO

Cushing’s as money makers for drug companies 😦

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Steroidogenesis inhibitors were responsible for approximately 28% of total drug sales in the 6MM in 2013, equating to around $50m. As a consequence of this trend, GlobalData expects overall revenues generated by this drug class to increase by approximately 390% to reach around $247m, encompassing 49% of total drug sales in the 6MM in 2018.

The expansion in this segment of the CS market is fuelled by the introduction of premium-priced pharmacological agents such as Novartis’ LCI699 and Cortendo AB’s NormoCort (COR-003) in the US, as well as the arrival of HRA Pharma’s Ketoconazole HRA (ketoconazole) to the European CS stage. One of the greatest unmet needs in this indication is a lack of effective drugs directed against the underlying cause of Cushing’s disease (the pituitary tumor).

Despite this demand, pharmaceutical companies are continuing to adopt a strategy that simply targets the adrenal glands. As a result, there is a vast amount of room for new or existing players to penetrate the market and capture considerable patient share.

Highlights

Key Questions Answered

Although the current standard of care (ketoconazole) is cheap and reasonably effective in most CS patients, it possesses worrying safety profiles, inconvenient dosing schedules, is difficult to obtain and can display waning efficacy over time. Newer medical treatments, for example, Novartis’ Signifor (pasireotide) and Corcept Therapeutics’ Korlym (mifepristone) address only some of these issues; yet, present their own limitations. The CS market is still marked by the existence of a multitude of unmet needs. What are the main unmet needs in this market? Will the drugs under development fulfil the unmet needs of the CS market?

The late-stage CS pipeline is sparsely populated; however, those drugs in development will be a strong driver of CS market growth. Which of these drugs will attain high sales revenues during 2013-2018? Which of these drugs will have the highest peak sales at the highest CAGR, and why?

Key Findings

One of the main drivers influencing growth in the Cushing’s syndrome market will be the introduction of second-generation steroidogenesis inhibitors, LCI699 and NormoCort (COR-003), in the US, which will rival existing standard of care medical treatments.

Another strong driver will be the arrival of Corcept Therapeutics’ Korlym (mifepristone) and HRA Pharma’s Ketoconazole HRA (ketoconazole) to the European CS market. Both drugs will stimulate significant growth here.

The launch of Novartis’ Signifor LAR (pasireotide) in the 6MM will equip physicians with a less frequently administered formulation of Signifor.

Reasons for inadequate CS treatment include poor physician awareness of the condition, delayed diagnosis, a lack of efficacious drugs for individuals suffering from severe hypersecretion, and a shortage of effective medicines targeting the source of Cushing’s disease.

Scope

Overview of Cushing’s syndrome, including epidemiology, etiology, pathophysiology, symptoms, diagnosis, and treatment guidelines.

Annualized Cushing’s syndrome therapeutics market revenues, annual cost of therapies and treatment usage pattern data from 2013 and forecast for five years to 2018.

Key topics covered include strategic competitor assessment, market characterization, unmet needs, clinical trial mapping and implications for the Cushing’s syndrome therapeutics market.

Pipeline analysis: comprehensive data split across different phases, emerging novel trends under development, and detailed analysis of late-stage pipeline drugs.

Analysis of the current and future market competition in the global Cushing’s syndrome therapeutics market. Insightful review of the key industry drivers, restraints and challenges. Each trend is independently researched to provide qualitative analysis of its implications.

Reasons to buy

Develop and design your in-licensing and out-licensing strategies through a review of pipeline products and technologies, and by identifying the companies with the most robust pipeline. Additionally a list of acquisition targets included in the pipeline product company list.

Develop business strategies by understanding the trends shaping and driving the Cushing’s syndrome therapeutics market.

Drive revenues by understanding the key trends, innovative products and technologies, market segments, and companies likely to impact the Cushing’s syndrome therapeutics market in the future.

Formulate effective sales and marketing strategies by understanding the competitive landscape and by analysing the performance of various competitors.

Identify emerging players with potentially strong product portfolios and create effective counter-strategies to gain a competitive advantage.

Track drug sales in the 6MM Cushing’s syndrome therapeutics market from 2013-2018.

Organize your sales and marketing efforts by identifying the market categories and segments that present maximum opportunities for consolidations, investments and strategic partnerships.

From http://www.medgadget.com/2015/10/global-cushings-syndrome-market-size-2015-share-trend-analysis-price-research-report-forecast.html

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