Adrenal incidentalomas

Quick tip; They may not sound exciting on a scan report, but please refer patients with adrenal incidentalomas to endocrinology for work up to exclude subtle hormone excess and even malignancy.

‘Incidentalomas’ in endocrinology are unexpected lesions picked up on a scan done for other reasons and are now very common. It has been estimated that ~5% of people have adrenal nodularity as they age, and whilst this is usually benign and indolent, some can cause long term harm through hormone excess and it is important to identify malignant features.

The European Society for Endocrinology has published guidance on adrenal incidentalomas (AIs) – see link below for more info. Your local departments may have adapted this for their use. It is now generally recommended to only investigate lesions ≥ 1cm, unless there are risk factors for malignancy (inc age under 40 yrs) or relevant symptoms, so clinicians should use their judgement.

Causes;

ESE guidelines report the following:

~80% of AIs represent benign adrenal adenomas, of which 15-30% may secrete hormones
8% primary adrenal cancer (adrenocortical carcinoma)
7% phaeochromocytoma

5% metastasis from extra-adrenal source

Workup;

Consider referral to endocrinology for further Ix of incidental adrenal lesions ≥1cm (or if < 1cm with other concerns or in young patients i.e. <40yrs)

Referral may not be appropriate for patients with limited prognosis for other reasons

Refer rapidly (under cancer pathway) if imaging report suggestive of adrenal malignancy (e.g. large size, evidence of local invasion)
Identify features from history/general examination suggestive of adrenal hormone excess
Identify features from history/general examination consistent with malignancy

Clinical Evaluation:

Hypertension (esp if treatment resistant) – may be in keeping with aldosterone, cortisol or catecholamine excess
Cushingoid features – e.g. diabetes, osteoporosis, myopathy
Adrenal androgen excess – hirsuitism (male distribution of hair in a female), deepening of voice, cliteromegaly, cessation of periods
Catecholamine excess (phaeochromocytoma) – hypertension (may be paroxysmal), headaches, palpitations, anxiety
Malignant features – weight loss, fatigue etc

Tumours that metastasize to adrenals commonly include lung, breast, bowel, pancreas and many other sites.

In patients with bulky bilateral adrenal lesions check for signs/symptoms of adrenal insufficiency which can occur due to malignant (or other) infiltration – e.g. pigmentation, postural hypotension, weight loss, fatigue, hyponatraemia etc.

Please include a detailed drug history with referral – some medications can interfere with interpretation of endocrine tests (esp for measurement of catecholamines and aldosterone).

Biochemical/endocrine evaluation:

Endocrine testing is not usually necessary before referral, but U&Es and HbA1c/glucose can be helpful to include.

Patients with AIs will require (usually in secondary care)

Assessment for cortisol excess (overnight 1mg dexamethasone test or 24h urinary cortisol collection plus ACTH assessment)
Assessment for catecholamine excess (plasma or urine metanephrines)

Assessment for androgen excess (plasma androgens – testosterone with sex hormone binding globulin, DHEA-S, androstenedione)
Assessment for aldosterone excess (aldosterone-renin ratio ARR) (if hypertensive)*
Exclusion of malignancy on imaging criteria**

*may require a temporary change to medications as many BP medications can interfere with ARR

** preferred test is a plain (non-contrast) adrenal CT to assess the density of the glands (measured in Hounsfield units – HU). Adrenal glands are usually rich in fat so appear dark (low density, traditionally <10HU) on CT. Malignant lesions have higher density and may be heterogenous in appearance. MRI of adrenals is an alternative test in younger patients.

Further endocrine or imaging tests may then be arranged if hormone hypersecretion or malignancy is suspected.

It is recommended that cases are discussed at a formal adrenal MDT meeting where malignancy or hormone excess is suspected.

NB – adrenal biopsy is rarely carried out and should first be discussed at MDT due to risks of disrupting a phaeochromocytoma, and of seeding malignancy.

Ref:

European Society of Endocrinology guideline (2016): https://eje.bioscientifica.com/view/journals/eje/175/2/G1.xml

Adrenal insufficiency

Quick tip; It is vital not to delay initiation of treatment in unwell patients if adrenal insufficiency suspected – the diagnosis can always be established later

The adrenal cortex secretes cortisol and androgens (under control of pituitary ACTH) as well as aldosterone (under control of the renin-angiotensin-aldosterone system).

Adrenal insufficiency may be primary (due to destruction/dysfunction of the adrenal gland itself), secondary (due to inadequate ACTH from the pituitary) or tertiary (due to pituitary suppression from exogenous steroids).

Primary adrenal insufficiency causes deficiency of cortisol, androgens and aldosterone; secondary and tertiary insufficiency cause deficiency of cortisol and androgens alone.

Causes of adrenal insufficiency

Primary – autoimmune, malignant infiltration, TB, enzyme abnormalities e.g. congenital adrenal hyperplasia, adrenal haemorrhage, drugs like ketoconazole
- ACTH and renin high, cortisol and aldosterone low
Secondary – pituitary adenomas, infiltration or surgery
- ACTH low, cortisol low, renin/aldosterone normal
Tertiary – exogenous steroid therapy (topical, oral, injected, inhaled), hypothalamic tumours/injury
- ACTH low, cortisol low, renin/aldosterone normal

Symptoms of adrenal insufficiency are non-specific include

Fatigue
Weight loss
Dizziness
Abdominal pain/vomiting
Leg cramps

Clinical findings

Adrenal crisis is a life-threatening manifestation of adrenal insufficiency characterised by shock.

Dehydration
Pigmentation (primary insufficiency only; secondary insufficiency associated with pallor)
Postural hypotension
If severe may be shocked, drowsy, comatose

Investigations

U+Es – hyponatraemia, hyperkalaemia (primary only), raised urea +/- creatinine
Glucose – may be low (more common in childhood)
FBC – normocytic anaemia, mild eosinophilia can occur
Cortisol – not required if diagnosis already established – see guidance on cortisol interpretation if suspected new case. Never delay hydrocortisone treatment in suspected adrenal crisis
ECG (in case of hyperkalaemia)
Other investigations to determine cause of adrenal failure usually initiated by specialist later in new cases
- E.g. ACTH to confirm primary/secondary, imaging, adrenal antibodies

Management of adrenal crisis

Follow guidelines from Society for Endocrinology (link below):
- IV hydration with saline
- IV or IM parenteral glucocorticoid either as initial bolus followed by boluses 4-6hrly, or by continuous IV infusion
- Management of hyperkalaemia in usual way if needed (calcium gluconate, insulin etc)
- Monitor BP, glucose, fluid balance
- Consider admission to HDU/ITU in case of shock
- Investigate and manage any precipitating cause e.g. sepsis

Prevention of adrenal crisis

Sick day rule 1 - Patients with adrenal insufficiency (including patients on long term low dose maintenance steroids for any reason) will require an increase in usual glucocorticoid dose at times of illness (at least double, and if on prednisolone increased to at least 10mg)
Mineralocorticoid dose should not be changed during illness
Sick day rule 2 - steroids should be administered IV/IM if not tolerated orally or patient is nil by mouth
- Tip – if patient has administered their own emergency dose at home prior to admission, try to replace this for discharge
See the Working Party guidance below for advice on peri-operative steroid replacement

References:

SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Emergency management of acute adrenal insufficiency (adrenal crisis) in adult patients (2016) URL: https://ec.bioscientifica.com/view/journals/ec/5/5/G1.xml

Guidelines for the management of glucocorticoids during the peri‐operative period for patients with adrenal insufficiency

Guidelines from the Association of Anaesthetists, the Royal College of Physicians and the Society for Endocrinology UK (2020) URL: https://onlinelibrary.wiley.com/doi/full/10.1111/anae.14963

Serum cortisol tests

Quick tip; never hold back hydrocortisone treatment in an emergency in order to secure a diagnosis of adrenal insufficiency. That can always be done later. A blood sample taken before hydrocortisone can be analysed afterwards for cortisol (and ideally ACTH).

Cortisol is the main glucocorticoid hormone. It circulates >95% bound to CBG (cortisol binding globulin), however it is the free unbound hormone that is active.

We measure total serum cortisol levels rather than the free active component as this is very difficult to do outside the research setting.

There are many caveats with measuring plasma cortisol levels and a single random cortisol measurement may not be helpful in proving sufficiency or insufficiency. Patients with cortisol deficiency or excess may have a cortisol level within the “normal range” at certain times of the day. It is for these reasons that we usually investigate suspected cortisol disorders with dynamic function testing (e.g. synacthen test, dexamethasone suppression test) to determine if cortisol levels are appropriate to the circumstance (section on DFTs to follow).

The main usefulness of a plasma cortisol measurement in the hospital setting is in excluding adrenal insufficiency. We might think about this in the investigation of unexplained hyponatraemia or weight loss, for instance, or in a hypotensive patient in a sample taken before we administer empirical hydrocortisone.

Random plasma levels of cortisol have no real use if cortisol excess is suspected (including patients with features of glucocorticoid excess such as obesity and diabetes, or in patients with adrenal or pituitary masses).

Factors influencing cortisol levels:

Timing – cortisol exhibits circadian (24h) and ultradian (hourly) variation. In normal individuals, morning cortisol levels range roughly from 275-555 nmol/L; in late afternoon may be 85-275 nmol/L; and may be <140 nmol/L at midnight but there is great inter-individual variation and no absolute cut-offs.

Cortisol insufficiency suspected – a morning level is most helpful
Cortisol excess suspected – a midnight level is most helpful

Type of assay –measured by immunoassay (antibodies). There may be overlap in reactivity for other steroids (endogenous and exogenous). Different assays have different specificities for cortisol so you should consult local reference ranges as they may differ significantly. There is no cross-reactivity with dexamethasone (hence why we use it for suppression tests), but there is with hydrocortisone and potentially with prednisolone.

Cortisol binding globulin – since 95% of the cortisol measured is bound to CBG, variations in CBG levels may have dramatic effects on total cortisol but free cortisol levels remain normal.

High CBG = high total cortisol – usually due to oestrogens, e.g. pregnancy, OCP, HRT use therefore a “normal” cortisol may be inappropriately low
Low CBG = low total cortisol e.g. nephrotic syndrome, liver failure or sepsis therefore a “low”(ish) cortisol may actually be normal

If cortisol insufficiency suspected:

On basis of symptoms (e.g. weight loss, fatigue, dizziness) or biochemistry (hyponatraemia, hyperkalaemia) an early morning (<9am) cortisol is helpful. NB – if patient is unwell then treatment should not be delayed – further testing can be done later.
- If very low (e.g. <50 nmol/L) then further dynamic testing may not be required and you should liaise with endocrinology urgently to institute replacement. Ensure no recent exogenous steroids (oral, inhaled, topical, parenteral).
- If in the mid-upper range of normal and no oestrogen excess, then adrenal insufficiency can usually be ruled out e.g. virtually all patients with cortisol >415 nmol/L have a normal response to synacthen
- Levels in the low-mid normal range for morning will usually require dynamic testing – usually with a short synacthen test.
- In critically unwell patients in hospital, there is no agreed cut off for normal cortisol – liaise with specialist if suspected

If cortisol insufficiency confirmed:

Exclude interfering agents (e.g. recent steroids)
Check baseline (i.e. pre-synacthen or pre-steroid) ACTH, renin and aldosterone
- High ACTH, high renin, low aldosterone suggests primary adrenal insufficiency
  - Usually Addison’s disease – check adrenal antibodies. If negative consider adrenal imaging.
- Low/normal ACTH, normal renin, normal aldosterone suggests secondary adrenal insufficiency
  - Most commonly due to exogenous suppression (e.g. steroid inhalers). Liaise with endocrinology re imaging and screen for other pituitary hormone defects (LH, FSH with oestradiol/testosterone, IGF1, TSH with T4, prolactin)
You should involve endocrinology urgently in any case of cortisol insufficiency

Cortisol excess suspected:

Plasma cortisol on its own not useful - most patients with Cushing’s disease do not have a high random cortisol
A high midnight plasma cortisol (e.g. >140 nmol/L) is indicative, but not a convenient test in most settings
Suggest involve the local endocrine team to arrange dynamic function tests

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Privacy Policy of Buku Haematology

This Application collects some Personal Data from its Users.

This document can be printed for reference by using the print command in the settings of any browser.

Owner and Data Controller

Buku Haematology - Newcastle - United Kingdom

Owner contact email: bukuhaem@gmail.com

Types of Data collected

Buku Haematology (The Owner) records no personally identifiable data. The following usage data are collected by default by the host of our App, AppYourself GmbH. This data is then managed as per their privacy policy below.

System Version
Smartphone model
Hardware ID (https://help.pushwoosh.com/hc/en-us/articles/360000365023-What-is-a-HWID-)
Opening of each module together with the time of the action
Date of register

Data will only be shared by AppYourself in accordance with their Privacy Policy.

Buku Haematology (owned by Buku Tech Ltd) retain none of this data. We can see our user traffic, country of access and modules accessed. Unique identifiers are generated for each user by the AppYourself system to show the number of times the App is accessed and which modules are viewed by individuals. No further information about the individual is given.

AppYourself privacy policy

We (Buku Haematology) have removed those elements that we have chosen not to include in the App (such as Facebook integration for example). Please contact privacy@appyourself.net if you have any questions about personal data storage.

Among the types of Personal Data that this Application collects, by itself or through third parties, there are: Cookies; Usage Data; various types of Data; unique device identifiers for advertising (Google Advertiser ID or IDFA, for example); Storage permission; geographic position.

Complete details on each type of Personal Data collected are provided in the dedicated sections of this privacy policy or by specific explanation texts displayed prior to the Data collection.

Personal Data may be freely provided by the User, or, in case of Usage Data, collected automatically when using this Application.

Unless specified otherwise, all Data requested by this Application is mandatory and failure to provide this Data may make it impossible for this Application to provide its services. In cases where this Application specifically states that some Data is not mandatory, Users are free not to communicate this Data without consequences to the availability or the functioning of the Service.

Any use of Cookies – or of other tracking tools – by this Application or by the owners of third-party services used by this Application serves the purpose of providing the Service required by the User, in addition to any other purposes described in the present document and in the Cookie Policy, if available.

Mode and place of processing the Data

Methods of processing

In some cases, the Data may be accessible to certain types of persons in charge, involved with the operation of this Application (administration, sales, marketing, legal, system administration) or external parties (such as third-party technical service providers, mail carriers, hosting providers, IT companies, communications agencies) appointed, if necessary, as Data Processors by the Owner. The updated list of these parties may be requested from the Owner at any time.

Legal basis of processing

The Owner may process Personal Data relating to Users if one of the following applies:

Users have given their consent for one or more specific purposes. Note: Under some legislations the Owner may be allowed to process Personal Data until the User objects to such processing (“opt-out”), without having to rely on consent or any other of the following legal bases. This, however, does not apply, whenever the processing of Personal Data is subject to European data protection law;
provision of Data is necessary for the performance of an agreement with the User and/or for any pre-contractual obligations thereof;
processing is necessary for compliance with a legal obligation to which the Owner is subject;
processing is related to a task that is carried out in the public interest or in the exercise of official authority vested in the Owner;
processing is necessary for the purposes of the legitimate interests pursued by the Owner or by a third party.

In any case, the Owner will gladly help to clarify the specific legal basis that applies to the processing, and in particular whether the provision of Personal Data is a statutory or contractual requirement, or a requirement necessary to enter into a contract.

Retention time

Personal Data shall be processed and stored for as long as required by the purpose they have been collected for.

The Owner records no personal data, and therefore usage data is the only data retained, and this is retained by AppYourself.

Once the retention period expires, Personal Data shall be deleted. Therefore, the right to access, the right to erasure, the right to rectification and the right to data portability cannot be enforced after expiration of the retention period.

The purposes of processing

The Data concerning the User is collected for the following purposes: Analytics, Hosting and backend infrastructure, Data transfer outside the EU, Device permissions for Personal Data access, Displaying content from external platforms, Infrastructure monitoring, Registration and authentication, and Location-based interactions.

For specific information about the Personal Data used for each purpose, the User may refer to the section “Detailed information on the processing of Personal Data”.

Detailed information on the processing of Personal Data

Key facts about data control by AppYourself;

The servers used by AppYourself are located in Europe (and thus protected by GDPR) and the US.
The data is hosted on AWS infrastructure, but AWS does not store any user-related data. User-related data is stored by AppYourself in Google Firebase. The storage is located in USA.
Although the Google Firebase server (based in the US) is not secured by GDPR they operate under the EU-US privacy shield. For more information about cloud-sided encryption see; https://firebase.google.com/support/privacy#data_encryption. Google Firebase is also compliant with ISO27001. For more information see; https://firebase.google.com/support/privacy#firebase_is_certified_under_major_privacy_and_security_standards
User data is stored for up to 90 days after App subscription is terminated. Furthermore, users have the right to delete their profile at any time. By doing so, their account is irretrievably deleted.
In case of a data breach by AppYourself, this can be reported via https://iapp.org/resources/article/how-to-notify-your-dpa-of-a-data-breach/

Personal Data is collected for the following purposes and using the following services:

Analytics

The services contained in this section enable the Owner to monitor and analyze web traffic and can be used to keep track of User behavior.

Google Analytics for Firebase (Google LLC)

Google Analytics for Firebase or Firebase Analytics is an analytics service provided by Google LLC.

In order to understand Google's use of Data, consult Google's partner policy.

Firebase Analytics may share Data with other tools provided by Firebase, such as Crash Reporting, Authentication, Remote Config or Notifications. The User may check this privacy policy to find a detailed explanation about the other tools used by the Owner.

This Application uses identifiers for mobile devices and technologies similar to cookies to run the Firebase Analytics service.

Users may opt-out of certain Firebase features through applicable device settings, such as the device advertising settings for mobile phones or by following the instructions in other Firebase related sections of this privacy policy, if available.

Personal Data processed: Cookies; unique device identifiers for advertising (Google Advertiser ID or IDFA, for example); Usage Data.

Place of processing: United States – Privacy Policy. Privacy Shield participant.

Data transfer outside the EU

Any data collected by AppYourself is transferred in keeping with these statements.

The Google Firebase services used to store and transfer data provide HTTPS encryption during information transit. Data encryption is also provided for cloud data storage. See https://firebase.google.com/support/privacy#data_encryption for more information.

Data transfer from the EU and/or Switzerland to the U.S based on Privacy Shield (this Application)

If this is the legal basis, the transfer of Personal Data from the EU or Switzerland to the US is carried out according to the EU - U.S. and Swiss - U.S. Privacy Shield.

In particular, Personal Data is transferred to services that self-certify under the Privacy Shield framework and therefore guarantee an adequate level of protection of such transferred Data. All services are listed within the relevant section of this document and those that adhere to Privacy Shield can be singled out by checking their privacy policy and possibly also by specifically checking for Privacy Shield adherence in the official Privacy Shield List. Privacy Shield also specifically guarantees rights to Users which can be found in its most current form on the website run by the US Department of Commerce.

Personal Data may be transferred from within the EU or Switzerland to the U.S. to services that are not, or not anymore, part of Privacy Shield, only based on other valid legal grounds. Users can ask the Owner to learn about such legal grounds.

Personal Data processed: various types of Data.

Data transfer to countries that guarantee European standards (this Application)

If this is the legal basis, the transfer of Personal Data from the EU to third countries is carried out according to an adequacy decision of the European Commission.

The European Commission adopts adequacy decisions for specific countries whenever it considers that country to possess and provide Personal Data protection standards comparable to those set forth by EU data protection legislation. Users can find an updated list of all adequacy decisions issued on the European Commission's website.

Personal Data processed: various types of Data.

Device permissions for Personal Data access

This Application requests certain permissions from Users that allow it to access the User's device Data as described below.

Device permissions for Personal Data access (this Application)

This Application requests certain permissions from Users that allow it to access the User's device Data as summarized here and described within this document.

Personal Data processed: Storage permission.

Hosting and backend infrastructure

This type of service has the purpose of hosting Data and files that enable this Application to run and be distributed as well as to provide a ready-made infrastructure to run specific features or parts of this Application. Some of these services work through geographically distributed servers, making it difficult to determine the actual location where the Personal Data are stored.

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Firebase Cloud Functions is a hosting and backend service provided by Google LLC.

Personal Data processed: Usage Data; various types of Data as specified in the privacy policy of the service.

Place of processing: United States – Privacy Policy. Privacy Shield participant.

Firebase Cloud Firestore (Google LLC)

Firebase Cloud Firestore is a hosting and backend service provided by Google LLC.

Personal Data processed: Usage Data; various types of Data as specified in the privacy policy of the service.

Place of processing: United States – Privacy Policy. Privacy Shield participant.

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Personal Data processed: Usage Data; various types of Data as specified in the privacy policy of the service.

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Firebase Cloud Storage is a hosting service provided by Google LLC.

Personal Data processed: Usage Data; various types of Data as specified in the privacy policy of the service.

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Interoute (Interoute Communications Limited.)

Interoute is a hosting service provided by Interoute Communications Limited.

Personal Data processed: various types of Data as specified in the privacy policy of the service.

Place of processing: United Kingdom – Privacy Policy.

Infrastructure monitoring

This type of service allows this Application to monitor the use and behavior of its components so its performance, operation, maintenance and troubleshooting can be improved.

Which Personal Data are processed depends on the characteristics and mode of implementation of these services, whose function is to filter the activities of this Application.

Sentry (Functional Software, Inc. )

Sentry is a monitoring service provided by Functional Software, Inc. .

Personal Data processed: various types of Data as specified in the privacy policy of the service.

Place of processing: United States – Privacy Policy.

Managing contacts and sending messages

This type of service makes it possible to manage a database of email contacts, phone contacts or any other contact information to communicate with the User.

These services may also collect data concerning the date and time when the message was viewed by the User, as well as when the User interacted with it, such as by clicking on links included in the message.

Firebase Cloud Messaging (Google Inc.)

Firebase Cloud Messaging is a message sending service provided by Google, Inc. Firebase Cloud Messaging allows the Owner to send messages and notifications to Users across platforms such as Android, iOS, and the web. Messages can be sent to single devices, groups of devices, or specific topics or User segments.

Personal Data processed: various types of Data as specified in the privacy policy of the service.

Place of processing: United States – Privacy Policy. Privacy Shield participant.

Further information about Personal Data

Push notifications

This Application may send push notifications to the User.

Unique device identification

This Application may track Users by storing a unique identifier of their device, for analytics purposes or for storing Users' preferences.

The rights of Users

Users may exercise certain rights regarding their Data processed by AppYourself.

In particular, Users have the right to do the following:

Withdraw their consent at any time. Users have the right to withdraw consent where they have previously given their consent to the processing of their Personal Data.
Object to processing of their Data. Users have the right to object to the processing of their Data if the processing is carried out on a legal basis other than consent. Further details are provided in the dedicated section below.
Access their Data. Users have the right to learn if Data is being processed by the Owner, obtain disclosure regarding certain aspects of the processing and obtain a copy of the Data undergoing processing.
Verify and seek rectification. Users have the right to verify the accuracy of their Data and ask for it to be updated or corrected.
Restrict the processing of their Data. Users have the right, under certain circumstances, to restrict the processing of their Data. In this case, the Owner will not process their Data for any purpose other than storing it.
Have their Personal Data deleted or otherwise removed. Users have the right, under certain circumstances, to obtain the erasure of their Data from the Owner.
Receive their Data and have it transferred to another controller. Users have the right to receive their Data in a structured, commonly used and machine readable format and, if technically feasible, to have it transmitted to another controller without any hindrance. This provision is applicable provided that the Data is processed by automated means and that the processing is based on the User's consent, on a contract which the User is part of or on pre-contractual obligations thereof.
Lodge a complaint. Users have the right to bring a claim before their competent data protection authority.

Cookie Policy

This Application uses Cookies and other Identifiers. To learn more, the User may consult the Cookie Policy.

Additional information about Data collection and processing

Legal action

The User's Personal Data may be used for legal purposes by the Owner in Court or in the stages leading to possible legal action arising from improper use of this Application or the related Services.

The User declares to be aware that the Owner may be required to reveal personal data upon request of public authorities.

Additional information about User's Personal Data

In addition to the information contained in this privacy policy, this Application may provide the User with additional and contextual information concerning particular Services or the collection and processing of Personal Data upon request.

System logs and maintenance

For operation and maintenance purposes, this Application and any third-party services may collect files that record interaction with this Application (System logs) use other Personal Data (such as the IP Address) for this purpose.

Information not contained in this policy

More details concerning the collection or processing of Personal Data may be requested from the Owner at any time. Please see the contact information at the beginning of this document.

How “Do Not Track” requests are handled

This Application does not support “Do Not Track” requests.

To determine whether any of the third-party services it uses honor the “Do Not Track” requests, please read their privacy policies.

Changes to this privacy policy

The Owner reserves the right to make changes to this privacy policy at any time by notifying its Users on this page and possibly within this Application and/or - as far as technically and legally feasible - sending a notice to Users via any contact information available to the Owner. It is strongly recommended to check this page often, referring to the date of the last modification listed at the bottom.

Should the changes affect processing activities performed on the basis of the User’s consent, the Owner shall collect new consent from the User, where required.

Definitions and legal references

Personal Data (or Data)

Any information that directly, indirectly, or in connection with other information — including a personal identification number — allows for the identification or identifiability of a natural person.

Usage Data

Information collected automatically through this Application (or third-party services employed in this Application), which can include: the IP addresses or domain names of the computers utilized by the Users who use this Application, the URI addresses (Uniform Resource Identifier), the time of the request, the method utilized to submit the request to the server, the size of the file received in response, the numerical code indicating the status of the server's answer (successful outcome, error, etc.), the country of origin, the features of the browser and the operating system utilized by the User, the various time details per visit (e.g., the time spent on each page within the Application) and the details about the path followed within the Application with special reference to the sequence of pages visited, and other parameters about the device operating system and/or the User's IT environment.

User

The individual using this Application who, unless otherwise specified, coincides with the Data Subject.

Data Subject

The natural person to whom the Personal Data refers.

Data Processor (or Data Supervisor)

The natural or legal person, public authority, agency or other body which processes Personal Data on behalf of the Controller, as described in this privacy policy.

Data Controller (or Owner)

The natural or legal person, public authority, agency or other body which, alone or jointly with others, determines the purposes and means of the processing of Personal Data, including the security measures concerning the operation and use of this Application. The Data Controller, unless otherwise specified, is the Owner of this Application.

This Application

The means by which the Personal Data of the User is collected and processed.

Service

The service provided by this Application as described in the relative terms (if available) and on this site/application.

European Union (or EU)

Unless otherwise specified, all references made within this document to the European Union include all current member states to the European Union and the European Economic Area.

Cookies

Small sets of data stored in the User's device.

Legal information

This privacy statement has been prepared based on provisions of multiple legislations, including Art. 13/14 of Regulation (EU) 2016/679 (General Data Protection Regulation).

This privacy policy relates solely to this Application, if not stated otherwise within this document.

Latest update: May 17, 2018

Cookie Policy of Buku Haematology

Cookies and other Identifiers consist of portions of code placed on the User’s device that assist the Owner in providing the Service according to the purposes described.

Some of the purposes for which Identifiers are used may also require the User's consent. Whenever consent is given, it can be freely withdrawn at any time following the instructions provided in this document.

Activities strictly necessary for the operation of this Application and delivery of the Service

This Application uses Cookies or other Identifiers to carry out activities that are strictly necessary for the operation or delivery of the Service and, therefore, do not require Users to consent. Users can disable such Identifiers by modifying their browser or device settings as described in more detail within this document, but this may affect core operational functions or result in the unavailability of the Service.

Other activities

Experience enhancement

This Application uses Cookies or other Identifiers to provide a personalized user experience by improving the quality of preference management options, and by enabling interaction with external networks and platforms.

Measurement

This Application uses Cookies or other Identifiers to measure traffic and analyze User behavior with the goal of improving the Service.

Analytics

The services contained in this section enable the Owner to monitor and analyze web traffic and can be used to keep track of User behavior.

Google Analytics for Firebase (Google LLC)

Google Analytics for Firebase or Firebase Analytics is an analytics service provided by Google LLC.

In order to understand Google's use of Data, consult Google's partner policy.

This Application uses identifiers for mobile devices and technologies similar to cookies to run the Firebase Analytics service.

Personal Data processed: Cookies, unique device identifiers for advertising (Google Advertiser ID or IDFA, for example) and Usage Data.

Place of processing: United States – Privacy Policy. Privacy Shield participant.

How to provide or withdraw consent

Users can provide or withdraw consent to the use of Cookies and other Identifiers by setting their preferences within the cookie notice or by updating such preferences via the relevant consent-preferences widget accordingly, if available.

Additionally, Users can manage preferences regarding Identifiers directly from within their own device settings and prevent – for example – the storing of third-party Identifiers. It is also possible, via relevant browser or device features, to delete previously stored Identifiers, including those used to remember the User’s initial consent. Users can, for example, find information about how to manage Identifiers in the most commonly used browsers at the following addresses: Google Chrome, Mozilla Firefox, Apple Safari and Microsoft Internet Explorer.

With regard to any Identifiers stored by third parties, Users can manage their preferences and withdraw their consent by clicking the related opt-out link (where provided), by using the means indicated in the third party's privacy policy, or by contacting the third party.

Notwithstanding the above, Users are hereby informed that they may follow the instructions provided by YourOnlineChoices (EU), the Network Advertising Initiative (US) and the Digital Advertising Alliance (US), DAAC (Canada), DDAI (Japan) or other similar services. Such initiatives allow Users to select their tracking preferences for most of the advertising tools. The Owner thus recommends that Users make use of these resources in addition to the information provided in this document.

Owner and Data Controller

Buku Haematology - Newcastle - United Kingdom

Owner contact email: bukuhaem@gmail.com

Since the storing of third-party Cookies and other Identifiers through the services used within this Application cannot be technically controlled by the Owner, any specific references to Identifiers stored by third parties are to be considered indicative. In order to obtain complete information, the User is kindly requested to consult the privacy policies of the respective third-party services listed in this document.

Given the objective complexity surrounding technologies related to Cookies and other Identifiers, Users are encouraged to contact the Owner should they wish to receive any further information on the use of such Identifiers by this Application.

Definitions and legal references

Personal Data (or Data)

Usage Data

User

The individual using this Application who, unless otherwise specified, coincides with the Data Subject.

Data Subject

The natural person to whom the Personal Data refers.

Data Processor (or Data Supervisor)

The natural or legal person, public authority, agency or other body which processes Personal Data on behalf of the Controller, as described in this privacy policy.

Data Controller (or Owner)

This Application

The means by which the Personal Data of the User is collected and processed.

Service

The service provided by this Application as described in the relative terms (if available) and on this site/application.

European Union (or EU)

Unless otherwise specified, all references made within this document to the European Union include all current member states to the European Union and the European Economic Area.

Cookie

Cookies are Identifiers consisting of small sets of data stored in the User's browser.

Identifier

Any technology - including Cookies - that allows for the storing of information, or the accessing of already-stored information, on the User’s device.

Legal information

This privacy statement has been prepared based on provisions of multiple legislations, including Art. 13/14 of Regulation (EU) 2016/679 (General Data Protection Regulation).

This privacy policy relates solely to this Application, if not stated otherwise within this document.

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