Role of radiosurgery in management of pituitary adenoma-The BNI experience

Posted on May 30, 2016 by MaryO

Screenshot 2016-05-27 13.12.55

 

S Meah, E Youssef, W White

Summary: Researchers conducted this study to determine the efficacy of stereotactic radiosurgery with CyberKnife for the treatment of recurrent pituitary adenoma. They concluded that stereotactic radiosurgery for recurrent/residual pituitary adenomas using CyberKnife appears to be relatively safe and effective when compared to conventional radiotherapy.

Methods:

  • Included in this retrospective study were patients who underwent cyberKnife radiosurgery for recurrent or residual pituitary adenoma at Barrow Neurological Institute (n=48).
  • Patients were followed for an average of 44 months.
  • Thirty-three patients had non-functioning adenomas, 10 had acromegaly, and 5 had Cushing’s disease.
  • Researchers analyzed the change in tumor size, hormonal function, and complication of therapy for each patient.

Results:

  • Tumor resection operation was performed through either the transsphenoidal or transcranial approach before CyberkKnife treatment.
  • All patients had either recurrence or residual mass in the cavernous sinus before CyberKnife treatment.
  • The total irradiation dose ranged from 2100-4000 cGy in an average of 3-5 fractions.
  • Slightly more than half of the patients (n=26, 54.2%) had smaller tumors at follow-up, while 22 (45.8%) had stable tumors.
  • Visual acuity remained unchanged post-treatment.
  • One patient developed radiation-induced temporal lobe necrosis.
  • Four patients (8.3%) required hormonal replacement due to panhypopituitarism.
  • Of the 15 patients with functioning adenoma, hormonal function improved in 12.
  • Treatment failed in 1 patient with acromegaly, 2 patients with Cushing’s disease, and 1 patient with non-functioning adenoma.

From http://www.mdlinx.com/endocrinology/conference-abstract.cfm/ZZFEBE5A85394340E188330278A399E6CF/57978/?utm_source=confcoveragenl&utm_medium=newsletter&utm_content=abstract-list&utm_campaign=abstract-AACE2016&nonus=0

Filed under: Cushing's, Meetings and Conferences, Treatments | Tagged: , , , , , | Leave a comment »

Johns Hopkins surgeon ‘Dr. Q’ to get Hollywood treatment

Posted on March 9, 2016 by MaryO

DrQ

 

Brad Pitt’s production company Plan B has teamed up with Disney to develop a movie based on the life of Alfredo Quiñones-Hinojosa, the head of brain tumor surgery at Johns Hopkins Hospital.

Quiñones-Hinojosa’s path to becoming a physician started in an unlikely place: a cotton field. He had come to the United States in 1987 from his native Mexico at the age of 19, penniless and unable to speak English. Driven to have a better life than the one he would have had in Mexico, he took jobs picking cotton, painting, and welding to pay for his tuition at San Joaquin Delta Community College in Stockton, California.

“These very same hands that now do brain surgery, right around that time they had scars everywhere from pulling weeds. They were bloody,” he told CNN correspondent Sanjay Gupta in a 2012 interview.

After earning his medical degree from Harvard Medical School and training in both general surgery and neurosurgery at the University of California, San Francisco, Quiñones-Hinojosa came to Johns Hopkins in 2005 and became a faculty member and surgeon. He specializes in brain cancer and pituitary tumors. His autobiography Becoming Dr. Q: My Journey from Migrant Farm Worker to Brain Surgeon was published in 2011 and received the International Latino Book Award in 2012.

Feeling like an outsider helped keep Quiñones-Hinojosa focused and “at the top of his game,” he told CNN. In the keynote speech delivered at Johns Hopkins University’s 2013 commencement ceremony, he elaborates, weaving together memories of his own brush with death in a work accident with his experience operating on a patient with a massive brain tumor that unexpectedly ruptured during surgery. Quoting the migrant farm worker and civil rights activist Cesar Chavez, he says, “If you are afraid, you will work like crazy.”

Plan B began developing the project—titled Dr. Q, the nickname for Quiñones-Hinojosa adopted by his patients—in 2007 after hearing a radio broadcast about the doctor and his background.

Matt Lopez, author of the popular Civil War play The Whipping Man and a former staff writer for HBO’s The Newsroom, will write the script.

According to The Hollywood Reporter, Disney expects Dr. Q to be a modestly-budgeted inspirational drama. Plan B executives Pitt, Dede Gardner, and Jeremy Kleiner won Best Picture Oscars two years ago for their production work on 12 Years a Slave and were nominated this year for their work on The Big Short.

From http://hub.jhu.edu/2016/03/07/brad-pitt-disney-dr-q-movie

 

Filed under: Cushing's, Helpful Doctors, pituitary, Rare Diseases, Video | Tagged: , , , , , , , , | Leave a comment »

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/

Filed under: Cushing's, growth hormone, pituitary | Tagged: , , , , , , , , , | Leave a comment »

Cushing’s Disease – Quality of Life, Recurrence and Long-term Morbidity

Posted on September 28, 2015 by MaryO
Isabel Huguet, Georgia Ntali, Ashley Grossman, Niki Karavitaki
European Endocrinology, 2015;11(1):34–8 DOI:10.17925/EE.2015.11.01.34
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Abstract:

Cushing’s disease (CD) is a rare disorder caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. Chronic exposure to hypercortisolism leads to significant morbidities, which may be only partially reversible after remission of the disease, as well as to impairment of the health-related quality of life (HRQoL) and an increase in mortality. Transsphenoidal surgery (TSS) is the treatment of choice, and recurrence rates vary widely, confirming the need for lifelong follow-up. This review summarises the studies performed on HRQoL, recurrence rates and morbidities in patients who have CD.

Keywords: Cushing’s disease, quality of life, recurrence, morbidity
Received: February 18, 2015 Accepted March 16, 2015 CitationEuropean Endocrinology, 2015;11(1):34–8 DOI:10.17925/EE.2015.11.01.34

Correspondence: Isabel Huguet, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Old Rd, Headington, Oxford, OX3 7LJ, UK. E: ihm.huguet@gmail.com

Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit.

Cushing’s disease (CD) is a rare condition caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. Chronic hypercortisolism is associated with the development of several morbidities that impair health-related quality of life (HRQoL) and contribute to an increased mortality rate.1–5 Obesity and metabolic alterations, hypertension and cardio-/ cerebrovascular complications, neuropsychiatric, muscle/skeletal, hypercoagulability/thromboembolism and immune consequences remain the most challenging.

Despite successful treatment of CD, a number of adverse consequences may persist long after cure or may even be irreversible. Moreover, the remission/cure criteria of CD vary between different studies, making comparison of the results difficult.

This paper aims to review and summarise the studies performed on HRQoL, recurrence rates and morbidities during long-term follow-up in patients who have CD.

Materials and Methods
The available literature was evaluated to address questions on HRQoL, recurrence and morbidities in CD. The literature search was conducted in two stages: (1) identification, review and inclusion of all the most relevant articles published in PubMed having the keywords CD, remission, cure, HRQoL and morbidities and (2) additional hand research conducted on the basis of bibliographies of identified articles, with articles referring to paediatric population and case reports excluded and with papers referring to Cushing’s syndrome (CS) reviewed and included only if presenting data on CD.

Quality of LifeHRQoL was initially assessed in CD patients using such generic measures as the Short Form (SF)-366 and the SF-127and measures of specific symptoms associated with the disease, including the Hospital Anxiety and Depression Scale (HADS).8 More recently, two disease-specific measures, the CushingQoL9 and the Tuebingen CD-2510,11 have been developed. Tables 1 and 2 present studies evaluating QoL using various questionnaires in CD patients having active disease or in remission.

Quality of life is significantly impaired not only in patients with active CD,9 but also in those in long-term remission,12,13regardless of the presence of hormonal deficiencies9 or treatment strategies,14,15 and patients who have CS report more negative illness perceptions than do patients who have other acute or chronic conditions.16

Quality of Life Assessed by Generic Questionnaires
Lindholm et al. reported that patients in remission for more than 5 years after initial surgery scored significantly worse in all subscales of SF-36 except for mental health and bodily pain.17 van Aken et al. evaluated patients cured for a mean period of 13.6 years and showed that general perceived well-being was reduced compared with healthy controls for all subscales in SF-36 and the Nottingham Health Profile (NHP). Moreover, such patients scored worse in all subscales of fatigue (Multidimensional Fatigue Inventory [MFI]-20), anxiety and depression (HADS).18 In comparison with subjects having other pituitary adenomas, patients who had CD were the most severely affected in all parameters of the SF-36 questionnaire.8 Sonino et al. studied patients who had CS in remission (the majority of them had CD) for 1 to 3 years and found significantly higher scores in anxiety, depression, anger, hostility and psychotic symptoms in the Symptom Rating Test (SRT) questionnaire in comparison with healthy controls.19 When the Beck Depression Inventory (BDI), SF-36 and the multidimensional body-self relations questionnaire (MBSRQ) were used, patients who had CD demonstrated lower QoL, lower body image perception and higher levels of depression compared with healthy controls, particularly in cases of persistent disease.15

Quality of Life Assessed with Disease-specific Questionnaires
Since 2008, two disease-specific questionnaires have been developed: CushingQoL and Tuebingen CD-25. The CushingQoL questionnaire was evaluated by Webb et al. in a multicentre European study. Active CD was associated with worse scores, but the presence of hypopituitarism or prior pituitary radiotherapy did not determine differences in the scores.9 Similarly, Santos et al. found that active CD patients scored worse on the CushingQoL questionnaire than did cured subjects.20 Wagenmakers et al. found that CD patients in remission without hormonal deficiencies scored significantly better than those having hormone deficiencies but significantly worse thanthe control group on 50 % of the items of the questionnaires.14 The Tuebingen CD-25 also demonstrated significant differences in all subscales and the total score between active CD patients and healthy controls.10,11

The post-operative improvement in HRQoL could be predicted by the presence of pre-operative HRQoL impairment, andyounger patients were more likely to improve. Patients without post-operative pituitary deficiencies improved significantly in the cognition scale.21,22

QoL does not change after short-term biochemical remission induced by medical therapy but may improve after sustained control of the hypercortisolism.23,24

To summarise, most of the results on HRQoL in CD derive from generic questionnaires raising concerns about how appropriate these are for the reliable and accurate assessment of the HRQoL of patients with this rare condition. Interestingly, despite the use of the same type of questionnaire in some studies, the subscales mainly affected show variation among them, suggesting that either CD affects several dimensions in QoL in a heterogeneous way in different patient groups, or these questionnaires are not specific enough. The newly developed questionnaires focus on important disease-specific aspects of the QoL, and their sensitivity in detecting changes renders them a very promising and useful tool in clinical practice.

Recurrence
Transsphenoidal surgery is the treatment of choice in CD, with immediate post-operative remission rates ranging from 59 % to 94 % and recurrence rates from 3 % to 46 %, both depending upon the definition criteria, the duration of follow-up, the number of patients studied and the inclusion of macroadenomas (see Table 3).2,25–29A small number of studies have used undetectable or very low post-operative serum cortisol levels as a strict criterion of remission, but most have defined effective remission as the resolution of clinical features and the reversal of hypercortisolism (in serum or urine), along with the recovery of cortisol suppressibility on dexamethasone administration or a normal cortisol circadian rhythm. Predictors of remission in CD include age at diagnosis, presence of hypertension or diabetes,4,5 response to desmopressin testing,30 identification of tumour at surgery and an adenoma histology positive for ACTH.31–33

Out of concern about recurrence of CD after initial remission, several parameters have been evaluated and are still matter of debate. Factors that have been associated with a low (but not zero) risk of CD recurrence include undetectable or low early morning serum levels of cortisol,33 low plasma levels of ACTH and prolonged requirement for glucocorticoid replacement after pituitary surgery. The effects of serum cortisol levels in the early post-operative period on predicting relapse have been assessed in various studies. No recurrences were found by Trainer et al.34during a median follow-up of 40 months in patients with a postoperative serum cortisol of <50 nmol/l; similar results were reported after a median follow-up of 58 months by McCance et al.35 In contrast to these findings, several series have reported recurrence rates of 11.5 % and 15 % despite a serum cortisol <50 nmol/l post surgery.27,28 Another possible parameter is the length of adrenal insufficiency post-TSS. Thus it has been suggested that patients who have a shorter duration of adrenal insufficiency have a significantly higher risk of relapse.36

Accordingly, after successful treatment of CD, there is no accurate criterion that can ensure lifelong cure, and although the evidence shows a more optimal outcome in patients who achieve severe cortisol deficiency after TSS, lifelong follow-up is mandatory.

Morbidities
CD is associated with significant comorbidities – metabolic and vascular complications, osteoporosis, neuropsychiatric dysfunction and immunosuppression – that increase mortality and affect daily life. A number of these may persist long after cure or may even be permanent.37

Metabolic and Vascular Complications
It is well recognised that CD increases cardiovascular risk, with hypertension and obesity the most common associated risk factors. The cardiovascular complications are part of the metabolic syndrome, but hypertension related to endogenous hypercortisolism is not simply a component of the CS-related metabolic syndrome. The renin–angiotensin system, mineralocorticoid activity, the sympathetic nervous system and the vasoregulatory systems have been reported to be involved in the pathophysiology of hypertension, but the mechanisms are only partially understood.38

The adverse cardiovascular risk profile of patients who have CD39is attributed to metabolic and vascular aberrations, as well as to changes in cardiac structure and function. Patients who have CD have increased leptin,40,41 resistin42 and pro-inflammatory agents, such as tumour necrosis factor-α and interleukin-6, C-reactive protein and low ghrelin levels.40 Moreover, they are characterised by a prothrombotic phenotype attributed to various abnormalities of coagulation and fibrinolysis: these include shortened activated partial thromboplastin time,43 increased factor VIII, von Willebrand factor, fibrinogen and plasminogen activator inhibitor-1,43 decreased fibrinolytic capacity44 and increased α2-antiplasmin.45 Endothelium-dependent flow-mediated vasodilatation is impaired, and several humoral markers of endothelial dysfunction (such as endothelin, homocysteine, vascular endothelial growth factor, osteoprotegerin and cell adhesion molecules) are elevated. Cardiac echocardiograms demonstrate left ventricular hypertrophy, concentric remodelling and diastolic and systolic dysfunction.

Persistent clinical abnormalities have been documented in terms of cardiovascular complications, showing that remission of hypercortisolaemia reduces, but does not completely eliminate them. Colao et al. reported that 27 % of patients having CD in remission for 5 years had persistently atherosclerotic plaques, compared with only 3 % of gender-, age- and body mass index–matched controls.45 Faggiano et al. also found persistence of the metabolic syndrome, vascular damage and atherosclerotic plaques after disease remission.46

Thus it is likely that disease remission does not entirely reverse cardiovascular morbidities affecting long-term survival and that lifelong follow-up is needed, with particular emphasis on cardiovascular risk factors.

Bone
Bone loss is attributed to decreased osteoblastic activity, increased osteoclastic bone resorption and impaired enteral calcium absorption. In the ERCUSYN study, osteopenia at the spine and hip was reported in 40 % and 46 % of patients who had CD, respectively, and osteoporosis at the spine and hip in 22 % and 12 %, respectively.47,48 Bone mineral density (BMD) does not completely recover following remission,49,50 though normalisation in some skeletal sites has been reported in the long-term.51

Glucocorticoid-induced vertebral fractures may develop even in the presence of normal or slightly low BMD. The risk of fractures at comparable BMD values with controls suggests that components of bone strength, not assessed by routine densitometric approaches, are also affected by glucocorticoids (including bone architecture, geometry and remodelling). Methods of assessment other than measurement of BMD are required, because despite the improvement of BMD after correction of hypercortisolism, the quality of the bone likely remains compromised.

Immune System
Hypercortisolism induces reversible immunosuppression. During hypercortisolaemia, autoimmune disorders improve but may worsen during remission and new ones develop.52 There is a high risk of superficial fungal, opportunistic or bacterial infections.

Neuropsychiatric Manifestations
Glucocorticoids are known to influence many functions of the central nervous system. Hypercortisolaemia is associated with depression, disrupted sleep and a wide range of cognitive impairments (derangement of memory – especially short-term – irritability and decreased concentration). High anxiety levels and low externalising behaviour are common emotional disorders.53Smaller hippocampal volumes and generalised brain atrophy have been described.54 Functional magnetic resonance imaging studies in patients having CD have demonstrated emotion-processing difficulties and hyperactivity in the frontal and subcortical regions, similar to major depressive disorders. After remission, hippocampal volumes increase and emotional and cognitive functions improve,53–55 but profound structural alterations in the brain remain such as smaller volumes in the anterior cingulate cortex, a structure involved in cognitive–affective processes and behavioural adaptation.56

The new data on persistent changes in the central nervous system after cure of CD support the hypothesis that psychiatric symptoms and cognitive impairment could be related to structural changes, providing the basis for future research on the neurobiological background of psychological dysfunction in this complex condition.

Conclusions
CD is associated with significant adverse sequelae affecting longterm morbidity, mortality and quality of life. To some extent, the duration and severity of hypercortisolism determine the possibility of reversion of the morbidities, but a number of manifestations may persist long after cure – possibly permanently. Generic questionnaires and disease-specific measures have evaluated many aspects of the quality of life impaired, not only during the active state, but also when in remission.

Despite initial successful treatment, there is a risk of relapse, and post-operative hypocortisolism is the most significant predictor of remission. These long-term and persistent changes are challenging to our understanding of hypercortisolaemia but in a clinical context suggest that long-term follow-up is essential in all patients having CD, even those apparently cured.

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From http://www.touchendocrinology.com/articles/cushing-s-disease-quality-life-recurrence-and-long-term-morbidity/page/1/0

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Hair Analysis Provides a Historical Record of Cortisol Levels in Cushing’s Syndrome

Posted on July 25, 2015 by MaryO
Exp Clin Endocrinol Diabetes. Author manuscript; available in PMC 2010 Sep 24.
Published in final edited form as:
PMCID: PMC2945912
NIHMSID: NIHMS235640
Hair Analysis Provides a Historical Record of Cortisol Levels in Cushing’s Syndrome
S. Thomson,1 G. Koren,1,6 L.-A. Fraser,2 M. Rieder,3 T. C. Friedman,4 and S. H. M. Van Uum5
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Abstract

The severity of Cushing’s Syndrome (CS) depends on the duration and extent of the exposure to excess glucocorticoids. Current measurements of cortisol in serum, saliva and urine reflect systemic cortisol levels at the time of sample collection, but cannot assess past cortisol levels. Hair cortisol levels may be increased in patients with CS, and, as hair grows about 1 cm/month, measurement of hair cortisol may provide historical information on the development of hypercortisolism.

We attempted to measure cortisol in hair in relation to clinical course in six female patients with CS and in 32 healthy volunteers in 1 cm hair sections. Hair cortisol content was measured using a commercially available salivary cortisol immune assay with a protocol modified for use with hair.

Hair cortisol levels were higher in patients with CS than in controls, the medians (ranges) were 679 (279–2500) and 116 (26–204) ng/g respectively (P <0.001). Segmental hair analysis provided information for up to 18 months before time of sampling. Hair cortisol concentrations appeared to vary in accordance with the clinical course.

Based on these data, we suggest that hair cortisol measurement is a novel method for assessing dynamic systemic cortisol exposure and provides unique historical information on variation in cortisol, and that more research is required to fully understand the utility and limits of this technique.

Keywords: glucocorticoids, pituitary adenoma, cancer, adrenal gland, hormones, cushing hair
Read the entire article at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945912/

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