Consensus Guideline For The Diagnosis and Management of Pituitary Adenomas in Childhood and Adolescence: Part 1, General Recommendations

nature reviews endocrinology https://doi.org/10.
1038/s41574-023-00948-8
Consensus statement Check for updates
Consensus guideline for the diagnosis

and management of pituitary adenomas
in childhood and adolescence: Part 1,
general recommendations
A list of authors and their affiliations appears at the end of the paper
Abstract Sections
Tumours of the anterior part of the pituitary gland represent just 1% Introduction
of all childhood (aged <15 years) intracranial neoplasms, yet they can Methodology
confer high morbidity and little evidence and guidance is in place Recommendations
for their management. Between 2014 and 2022, a multidisciplinary
Conclusions
expert group systematically developed the first comprehensive clinical
practice consensus guideline for children and young people under the
age 19 years (hereafter referred to as CYP) presenting with a suspected
pituitary adenoma to inform specialist care and improve health
outcomes. Through robust literature searches and a Delphi consensus
exercise with an international Delphi consensus panel of experts, the
available scientific evidence and expert opinions were consolidated
into 74 recommendations. Part 1 of this consensus guideline includes
17 pragmatic management recommendations related to clinical care,
neuroimaging, visual assessment, histopathology, genetics, pituitary
surgery and radiotherapy. While in many aspects the care for CYP is
similar to that of adults, key differences exist, particularly in aetiology
and presentation. CYP with suspected pituitary adenomas require
careful clinical examination, appropriate hormonal work-up, dedicated
pituitary imaging and visual assessment. Consideration should be
given to the potential for syndromic disease and genetic assessment.
Multidisciplinary discussion at both the local and national levels can
be key for management. Surgery should be performed in specialist
centres. The collection of outcome data on novel modalities of medical
treatment, surgical intervention and radiotherapy is essential for
optimal future treatment.
e-mail: [email protected]
Nature Reviews Endocrinology | Volume 20 | May 2024 | 278–289 278

Consensus statement
Introduction clinicians in several disciplines to whom CYP present to optimize the

The diagnosis and management of pituitary adenomas in children and management of suspected pituitary adenomas in CYP and improve
young people under 19 years of age (hereafter referred to as CYP) is the quality of clinical care and, thus, health outcomes. Part 1 of this
challenging owing to the rarity of these tumours in this age group, their consensus guideline provides 17 recommendations regarding neuro
potential to disrupt maturation, as well as their more aggressive nature imaging, visual assessment, histopathology, genetics, pituitary sur-
and increased potential for familial or genetic aetiology in this age group gery and radiotherapy relevant to all pituitary adenomas, whereas
compared with adults1–3. Pituitary adenomas increase in incidence Part 2 contains 57 recommendations for each of the individual pituitary
during late adolescence, from 1% of all intracranial neoplasms before adenoma types16 (Supplementary Table 1).
15 years of age to 18% for patients aged 15–24 years4. These patients can
present, often late, to a range of different paediatric or adult special- Methodology
ists: endocrinologists, ophthalmologists, neuro-oncologists, medical This consensus guideline was commissioned by the British Society
oncologists or neurosurgeons. for Paediatric Endocrinology and Diabetes and the Children’s Cancer
Pituitary adenomas are neoplasms (usually non-malignant) arising and Leukaemia Group (CCLG), and was developed in accordance
from the hormone-secreting cells of the anterior pituitary. In CYP, they with Appraisal of Guidelines Research and Evaluation Instrument II
often secrete hormones in excess but the resulting characteristic signs (AGREE II)17 criteria and the CCLG guideline development standard
and symptoms, such as pubertal delay, amenorrhoea, features of Cush- operating procedure18. Members of the Project Board, GDG and Delphi
ing disease or rapid growth velocity, might be occult or missed during consensus panel (Supplementary Table 2) were selected based on
development, leading to late diagnoses5,6. Pituitary adenomas are clinical and academic experience in pituitary tumour diagnosis and
defined as macroadenomas if they measure ≥1 cm and microadenomas management. The methodology is summarized in Fig. 1. All stages of
if they measure <1 cm, whereas neoplasms of >4 cm in size are referred the development process were appraised by the Quality Improvement
to as giant adenomas. Large pituitary adenomas are more prevalent in Committee of the UK Royal College of Paediatrics and Child Health.
CYP than in adults6. Mass effects are more common at presentation
in CYP than in adults and cause deficits of pituitary hormones, visual Developing the clinical questions
field defects, hypothalamic dysfunction, and even raised intracranial The GDG identified its objectives and summarized these as a series of
pressure or oculo-motor nerve palsy. Of note, the 2022 edition of the 155 Population, Intervention, Comparison, Outcome (PICO) clinical
WHO Classification of Endocrine Tumours and of Central Nervous questions19 that were circulated to stakeholder organizations (listed
System Tumours proposed a pathology-based classification of pitui- later and in the Acknowledgements) for comments and then finalized by
tary adenomas as pituitary neuroendocrine tumours (abbreviated to the GDG. The clinical questions guided the systematic literature search
PitNETs), a term that is currently being debated in the field7–13. (Supplementary Table 3), critical appraisal, and synthesis of evidence
Pituitary adenomas have a high survival rate but might confer and facilitated the development of recommendations by the GDG.
potentially serious, life-changing and life-limiting sequelae. They
increase in incidence with increasing age over childhood and repre- Identifying, reviewing and synthesizing evidence
sent 78% of pituitary fossa lesions in CYP14. Between 1997 and 2016 The GDG screened titles and abstracts published in English since
in the UK, 5 children with pituitary adenoma were diagnosed aged January 1990 and identified by three systematic literature searches
0–4 years, 14 children aged 5–9 years, 78 young people aged 10–14 years conducted on the core data bases Ovid MEDLINE, PubMed, EMBASE
and 282 young people aged 15–19 (ref. 15). As children with pituitary and Cochrane Library in October 2014, February 2021 and April 2022
adenomas can, on average, expect to live for a further 6–7 decades, (Supplementary Fig. 1). Full-text articles relevant to development of
their health-related quality of life is paramount. The treatment of CYP this consensus guideline were reviewed and appraised using the Grad-
with pituitary adenomas is challenging due to the lack of high-quality ing of Recommendations, Assessment, Development and Evaluations
evidence for treatment recommendations for this age group. (GRADE) criteria20. For inclusion and exclusion criteria, search terms,
In order to achieve optimal care, improve quality of life, and reduce and strategies, see Supplementary Box 1. For detailed evidence tables
secondary and long-term health-related morbidity, CYP with pituitary for recommendations in Part 1, see Supplementary Table 4. Given the
adenomas should be treated by a pituitary-specific multidisciplinary rarity of pituitary adenomas in CYP, especially in the youngest devel-
team (MDT), with experts from both paediatric and adult practice. Such oping children aged <15 years, most paediatric evidence was of low
a level of care could also improve and expedite diagnosis (including quality and the authors have often drawn on evidence from the adult
complex endocrine and genetic screening of patients with suspected literature, which is noted where relevant. This is an abbreviated version
familial aetiology), acute decision-making, perioperative care and of the guideline; full-text and additional references will be available on
long-term surveillance. In contrast to oncology care for CYP, which the CCLG website (Rare endocrine tumour guidelines).
is usually well organized with centralized units, a less well-developed
management provision exists for CYP with pituitary neoplasms. The Developing recommendations
UK and many other countries lack a dedicated pituitary MDT for CYP. Where there was sufficient moderate-quality evidence to answer the
Having recognized these challenges, a Guideline Development PICO questions, the GDG originally made 54 recommendations whose
Group (GDG) and an international Delphi panel were formed to develop strength was determined using the GRADE criteria20 by a trade-off
consensus on diagnostic and management recommendations for between benefits and harms given the quality of the underpinning evi-
CYP with pituitary adenomas according to rigorous methodology dence. Where the evidence base was lacking, of low quality, conflicting
approved by the UK National Institute for Health and Care Excellence or largely extrapolated from adult experiences, the GDG formulated
(NICE). The GDG made 74 recommendations that are included in this consensus recommendations and submitted these to experts outside
two-part consensus guideline. This consensus guideline is intended the GDG (the international Delphi consensus panel, Supplementary
to provide an evidence-based and eminence-based document for Table 2) in three rounds of a Delphi consensus process (first round,

Consensus statement
Fig. 1 | Consensus guideline development

The GDG identified guideline objectives
process. Flowchart of the consensus guideline
development process for recommendations for the
diagnosis and management of pituitary adenomas
Objectives were summarized as PICO questions
in children and young people under 19 years of
age. The Guideline Development Group (GDG)
established the objectives and identified and refined
Objectives and PICO questions were reviewed
by guideline stakeholders
recommendations using Population, Intervention,
Two additional PICO Comparison, Outcome (PICO) clinical questions19
questions were formulated to undertake systematic literature reviews. Evidence
based on updated systematic
was graded using Grading of Recommendations,
literature review
A systematic literature review was undertaken Assessment, Development and Evaluations (GRADE)
using PICO questions criteria20. Recommendations supported by
insufficient, low-quality, or conflicting evidence or
evidence that was largely extrapolated from adult
Quality of evidence identified in literature experiences, were reviewed by a Delphi consensus
review was appraised (GRADE)
process. Recommendations that achieved
consensus, alongside those with sufficient evidence
not to require a consensus process, were reviewed,
and this Consensus Guideline was published
Guideline recommendations Guideline recommendations drafted by
following the National Institute for Health and
made for PICO questions were the GDG for PICO questions were not
answered by the identified answered by the identified evidence Care Excellence-approved Appraisal of Guidelines
evidence (33 statements) (55 statements) Research and Evaluation Instrument II (AGREE II)
criteria17.
For further refinement, the Delphi

Recommendations were reviewed by
process was also applied to 13
an expert international Delphi
statements
consensus panel in three rounds (39
statements), the GDG (6) or by both (10)
Recommendations supported by ≥70%

of consensus group respondents were
included in the consensus guideline
The recommendations were reviewed by

the GDG
The recommendations were reviewed by

guideline stakeholders and independent
reviewers
The consensus guideline was published
74 recommendations; second round, 41 recommendations; third limited consensus, 10 of these with additional GDG consensus and 6 based on
round for 1 question; see Supplementary Table 5 for full details of the GDG consensus). We followed a consistent NICE terminology, using the
voting for each recommendation). In some cases, a strong recommen- verbs ‘should’ and ‘offer’ to indicate strong recommendations, whereas
dation was paired with moderate-quality evidence: these recommenda- ‘consider’ was used to indicate moderate or weak recommendations.
tions were based on adult data and strong recommendations in adult The evidence levels are shown as strong, moderate or low quality using
guidelines that are applicable to CYP. High-quality evidence is unlikely GRADE criteria with any Delphi or GDG consensus. Recommendations
to be prospectively generated in the CYP age group in the future due to supported by ≥70% of consensus group respondents are included in
the rarity of these conditions. these guidelines. Areas where the GDG felt that further research was
Following a revised literature review in 2021, the GDG finalized a required have been proposed as research recommendations (Box 1).
total of 74 main recommendations with a total of 89 statements as some As part of the consensus guideline development process, the draft
of the recommendations included 2 or more interrelated statements. Of article was submitted to two paediatric endocrinology international
89 statements, 34 were evidence based (with 13 of these also having experts for external peer review between August and November 2018.
Delphi consensus) and 55 were eminence based (49 based on Delphi A second round of external peer review took place before submission

Consensus statement
for publication in February 2022 by four national and four international • Part 1: R4.2. Offer transfer to adult pituitary services for contin-
experts (three adult endocrinologists, four paediatric endocrinologists ued surveillance at completion of growth and puberty (strong
and one histopathologist). recommendation, low-quality evidence, Delphi 89%).
Stakeholder, patient and public involvement No published evidence is available to guide the organization of
This consensus guideline received scientific comments and endorse- age-specific services for the management of pituitary and other rare
ment from various stakeholders, listed here and in the Acknowledge- endocrine tumours in CYP. All CYP with a suspected pituitary adenoma
ments. Stakeholders were given the opportunity to comment on the PICO or any radiological abnormality in the region of the pituitary fossa
questions, on the first draft of the recommendations (September and and stalk require clinical assessment of growth and puberty and its
December 2016) and on the final draft (November 2021–January 2022). age-appropriate timing. Baseline assessment for pituitary hormone
The following learned societies endorse Parts 1 and 2 (ref. 16) of this
consensus guideline: Society for Endocrinology, Society of British
Neurological Surgeons, British Paediatric Neurosurgical Group, Royal
College of Physicians, British Society for Paediatric Endocrinology
Box 1
and Diabetes, British Society of Paediatric Radiology, Royal College
of Paediatrics and Child Health, British Neuropathology Society, and Research recommendations
the Association for Clinical Biochemistry and Laboratory Medicine.
In addition, views from patients with pituitary adenoma, survivors •• Set up of age-appropriate hypothalamic–pituitary
and their families were sought through various patient organizations multidisciplinary team support (neurosurgery, paediatric
in October and November 2021, including the Association of Multiple oncology, radiation oncology, endocrinology, neuroradiology
Endocrine Neoplastic Disorders (AMEND), Success Charity and the and neuropathology) including, where appropriate, adult
Pituitary Foundation. All feedback was considered by the GDG before pituitary specialists (for example, endocrinologists and skull
the consensus guideline was finalized and submitted for publication. base neurosurgeons) for children and young people under
19 years of age (CYP) with pituitary adenomas.
Implementation and update •• Collection of long-term data in CYP, including local pituitary
To facilitate the implementation of the recommendations in this adenoma control, biochemical control, surgical outcome,
consensus guideline, we strongly recommend cooperative paediat- secondary health effects (for example, endocrine, reproductive,
ric and adult, pituitary-specific multidisciplinary meetings and staff visual, metabolic, joint and neurological effects) as well as
training in nominated specialist centres. Potential barriers to imple- psychosocial and employment health-related quality of life
mentation include lack of funding for novel medical therapies, lack of parameters, should be a mandatory part of the treatment and
paediatric-specific expertise for diagnostic procedures (petrosal sinus follow-up protocol.
sampling) or treatments (surgical expertise or proton beam therapy), •• The choice of radiotherapy modality and timing is unclear for
and lack of access to expert centres due to geography or insurance CYP with pituitary adenomas who are unresponsive to surgical or
restrictions. Our consensus guideline could support health-care provid- medical therapy. Outstanding questions include the following:
ers, patient advocates and policy-makers to overcome these barriers -- The timing of radiotherapy, for example, after the first relapse
and might facilitate these services where they are currently not avail- following the initial treatment modality.
able. The literature will be reviewed again 5 years after the publication -- The comparison of radiotherapy techniques such as
of this consensus guideline; if, prior to this, any new evidence is identi- stereotactic radiosurgery versus conventionally fractionated
fied that notably changes the recommendations, then the update will radiotherapy.
occur sooner. -- The prospective, long-term, endocrine, vascular,
neurocognitive and secondary malignancy outcomes
Recommendations of patients who receive proton beam therapy versus
General statements intensity-modulated radiation therapy.
• Part 1: R1. Offer CYP with suspected or confirmed pituitary
adenoma management in a specialist age-appropriate endo- •• Functional imaging for the diagnosis of pituitary adenomas in
crine and neuro-oncology centre by an MDT working collabora- children, especially corticotroph adenomas that are not visible
tively with appropriate local health-care professionals (strong on state-of-the-art MRI.
recommendation, low-quality evidence, Delphi 100%). •• The use of overnight dexamethasone test in CYP with suspected
• Part 1: R2. Offer all CYP with a pituitary mass growth and puber- Cushing syndrome and the value of measuring serum levels of
tal assessment and baseline pituitary hormone measurements dexamethasone in CYP.
(strong recommendation, high-quality evidence). •• The role and predictive value of the Ki-67 labelling index
• Part 1: R3. Clinicians treating CYP with pituitary adenomas and the role of molecular characterization in CYP with pituitary
should have access to a national paediatric pituitary-specific adenomas should be assessed in a large collaborative study,
advisory panel in order to discuss the management of com- where histological data are correlated with long-term outcomes.
plex patients (strong recommendation, low-quality evidence, •• The aetiology of temporary growth hormone (GH) excess in
Delphi 90%). CYP with optic glioma and the transition of GH excess to GH
• Part 1: R4.1. Report CYP with a confirmed pituitary adenoma deficiency requires further collaborative neuroendocrine
to an appropriate national registry (strong recommendation, oncology study (see Part 2 (ref. 16)).
low-quality evidence, Delphi 90%).

Consensus statement
deficiencies and specific investigations for hormone excess21 should resection rates of adenomas without increasing complication rates34–40.
be performed, coordinated and interpreted by a paediatric endocri- Low-level gadolinium deposits in the dentate nucleus and globus pal-
nologist with expertise in pituitary disorders at a specialist centre. The lidus have unknown neurological impact. Therefore, unenhanced
availability of paediatric pituitary-specific advisory panels is scarce in T1-weighted and T2-weighted MRI sequences should be considered
various countries and setting these up would benefit the management during follow-up in paediatric patients41–43, especially if good quality
of pituitary adenomas in CYP22. Consultation with an adult endocrinolo- enhanced images have been obtained at diagnosis. Macrocyclic or
gist specializing in pituitary adenomas for the interpretation of results newer linear gadolinium-containing contrast agents should be used
is key for care in the majority of patients. Close interaction between in weight-adapted doses. In patients with an estimated glomerular
paediatric and adult endocrine services is required to coordinate filtration rate of <30 ml/min/1.73 m2 or on dialysis, administration
long-term medical care and the transition to adult services. The tim- of gadolinium-containing contrast should be considered individu-
ing of this transition depends on local guidelines but could be variable ally, and alternative imaging modalities utilized whenever possible.
for patients with pituitary adenoma due to potential developmental If gadolinium-containing contrast agents are necessary, macrocyclic
delays. Patient support groups for pituitary patients (for example, or newer linear gadolinium-containing contrast agents could be admin-
the Pituitary Foundation, Child Growth Foundation, AMEND, Success istered with patient or parental consent citing an exceedingly low risk
Charity, Pituitary Network Association and World Alliance of Pituitary (much less than 1%) of developing nephrogenic systemic fibrosis44.
Organizations) offer educational resources and support communities
that highlight the unique challenges affecting this developmental age Visual assessment
group and could provide help for people living with pituitary disease. • Part 1: R7. In CYP with suspected or confirmed pituitary ade-
noma, offer assessment of visual acuity (ideally logarithm of
Neuroimaging the minimum angle of resolution measurement), visual fields
• Part 1: R5. Offer pre-contrast (T1 and T2) and post-contrast- (ideally Goldmann perimetry) and fundoscopy, with or without
enhanced (T1) thin-sliced pituitary MRI, including colour vision (strong recommendation, low-quality evidence,
post-contrast volumetric (gradient (recalled) echo) sequences Delphi 94%).
for increased sensitivity, to CYP presenting with a visual field • Part 1: R8. In CYP with confirmed pituitary adenoma with
defect or with signs and symptoms of pituitary hypersecre- potentially severe acuity or field deficits, consider base-
tion or hyposecretion (strong recommendation, low-quality line optical coherence tomography (weak recommendation,
evidence, Delphi 92%). low-quality evidence, GDG consensus).
• Part 1: R6. Consider 3-Tesla MRI for surgical planning or intra- • Part 1: R9.1. Consider visual assessment (including acuity and
operative MRI as it enhances anatomical definition and might fields if age appropriate) in all CYP with a pituitary macro
improve completeness of resection without altering compli- adenoma within 3 months of first-line therapy (moderate
cation rates (moderate recommendation, low-quality evidence, recommendation, low-quality evidence, Delphi 94% and GDG
Delphi 92%). consensus).
• Part 1: R9.2. Ongoing visual follow-up should be based on indi-
In CYP undergoing investigation for suspected pituitary ade- vidual indications (moderate recommendation, low-quality
noma, a dedicated pituitary MRI before (T1 and T2) and after gado- evidence, Delphi 81% and GDG consensus).
linium contrast enhancement (T1) is the imaging investigation of
choice and should be reported by a neuroradiologist. The standard Pituitary macroadenomas can impinge on the optic chiasm and
pituitary protocol (2 mm slice, spin echo T1-weighted sequences optic nerves. Visual disturbances are more often encountered in CYP
performed before and after contrast, and fast or turbo spin echo with pituitary adenoma than in adult patients. Data on visual function
T2-weighted sequences pre-contrast) can be supplemented by a volu- testing in patients with paediatric pituitary adenomas are scarce.
metric (gradient (recalled) echo) acquisition after contrast, and some Yet, studies of children with other lesions of the sellar or suprasellar
evidence suggests that this strategy could improve the sensitivity for region that affect vision and various other causes of visual impairment
adenoma detection23–28. The differential diagnosis of pituitary fossa suggest that visual acuity, visual field testing and assessment of opti-
lesions in CYP (for example, Rathke cleft cysts or craniopharyngioma) cal nerve integrity as well as fundoscopy can detect abnormalities at
is beyond the scope of this consensus guideline, but these entities diagnosis45–49. Visual acuity is a psychophysical measure that relies
have separate guidelines29,30. on patient cooperation and attention. Qualitative measures of visual
In patients with suspected pituitary adenoma where MRI is nega- acuity are insufficient and subtle and even large changes in visual acuity
tive or equivocal, molecular (functional) imaging might aid neoplasm might not be adequately detected by these methods. Instead, visual
localization31. Specifically, hybrid imaging techniques (for example, acuity should be measured with age-specific tests and recorded as
PET–CT co-registered with MRI or PET–MRI) using ligands such as the internationally recognized logarithm of the minimum angle of
11
C-methionine or 18F-fluoroethyltyrosine have shown promising results resolution measurement50.
in both de novo and recurrent functioning pituitary adenomas; how- Age-appropriate visual field testing is of key importance in patients
ever, the successful use of these imaging modalities has only been with pituitary macroadenomas as well as in those with microadenomas
reported in a small number of CYP to date31,32 and these techniques are after surgery. No data are available on optical coherence tomography
currently in the research stage. in paediatric patients with pituitary adenomas, but optical coherence
The better resolution of a 3-Tesla MRI can improve anatomical tomography can be a surrogate for visual field loss and visual dysfunc-
delineation of pituitary adenomas and might enhance surgical plan- tion as a thinner retinal nerve fibre layer is present in patients with visual
ning but, as yet, there is no evidence of an increased sensitivity for field loss, reduced visual acuity or evidence of optic neuropathy51.
adenoma detection33. Intraoperative MRI might improve complete Although the use of optical coherence tomography is limited by patient

Consensus statement
cooperation, this is required to a lesser extent than in visual field test- Genetics
ing. Despite variability in cooperation among children aged under • Part 1: 11.1. Offer genetic assessment to all CYP with a pitui-
6 years, reliable optical coherence tomography imaging was obtained tary adenoma to inform management and family surveillance
in children from as young as 3 years of age52. No data are available for (strong recommendation, high-quality evidence).
visual evoked potentials (a measure of the electrical signal generated at • Part 1: 11.2. Given the high prevalence of genetic abnormalities
the visual cortex in response to visual stimulation) in CYP with pituitary in somatotroph and lactotroph tumours, offer genetic testing
adenomas. Visual evoked potentials have been used for non-verbal or to all CYP with growth hormone (GH) and prolactin excess
disabled children, where standard visual assessment is difficult, but (strong recommendation, high-quality evidence).
should not be used for long-term surveillance29,53.
If CYP with pituitary adenomas are treated with surgery, further Several genes have been identified in association with pituitary
recovery of visual field deficits is unlikely after the first post-operative adenomas in CYP occurring as isolated pituitary adenomas (familial
month54,55, with age <6 years and the presence of visual symptoms at isolated pituitary adenoma) or as part of a syndromic disease67–71.
diagnosis indicating an increased risk of poor visual outcomes56,57. Although these conditions are rare, the number of identified germline
Monitoring of CYP with pituitary adenomas should be determined on an (and somatic) genetic alterations is expected to increase in the future
individual patient basis, depending on baseline visual assessment and with the implementation of wider genetic testing. This knowledge
MRI appearance. Given the data from adults with pituitary adenoma58 could inform prognosis, treatment and screening for other manifesta-
and from paediatric patients with craniopharyngioma (a neoplasm of tions in the proband, while family members could benefit from genetic
the sellar or suprasellar region that can also affect vision)29, the GDG testing and clinical screening72–76. Genetic testing is available in several
strengthened the visual assessment recommendations (Part 1: R8 laboratories that also support testing for international patients.
and R9). Genetic assessment of potential mutation carriers of known muta-
tions should be performed prior to the typical age at onset of symptoms
Histopathology (variable for different diseases). Some advocate genetic screening from
• Part 1: R10 Offer histopathological assessment of the oper- the age of the youngest known patient (for example, aged 4 years for
ated pituitary adenoma tissue, including immunostaining AIP mutations77), whereas others suggest genetic screening at the point
for pituitary hormones and Ki-67, and additional immuno- where biochemical screening is advised if the patient is a carrier (for
profiling when relevant, to accurately classify the pituitary example, aged 5–10 years for multiple endocrine neoplasia type 1 syn-
neoplasm (strong recommendation, moderate-quality evidence, drome (MEN1)78). Follow-up of gene mutation carriers might include
Delphi 100%). yearly clinical and biochemical follow-up. Timing of pituitary MRI screen-
ing and assessment of other potentially associated features depend on
Data from adult patients with pituitary adenoma who undergo the genetic disease in question. Treatment of pituitary neoplasms of
surgery and the recent WHO guidelines12,59 suggest that Ki-67 staining genetic origin, in general, is similar but might require more treatment
and mitotic activity might help predict clinical outcomes in adults60–62. modalities compared with patients without genetic aetiology72,74.
While available data on the prognostic value of Ki-67 is controversial, If mutations in known genes have been ruled out in a proband with
the 2022 WHO guideline encourages accurate quantification (positive young-onset or familial disease, no clinical assessment is recommended
staining per 500–1,000 neoplastic cells in two hotspots). Therefore, for family members as genetic background is uncertain, penetrance is
prospective evaluation is recommended in CYP to identify correlates probably incomplete and regular long-term screening could lead to
with outcomes (Box 1). anxiety and increased health expenses77.
A paediatric pituitary adenoma surgical series found that 55%
(28/51) of patients had Ki-67 of ≥3%5. Furthermore, data on 42 paedi- GH excess in CYP. Among all pituitary adenomas, childhood-onset
atric pituitary tumours suggested that the combination of ≥3% Ki-67 GH-secreting adenomas (with or without prolactin co-secretion)
and local invasion on imaging predicts a 25% recurrence rate after are most likely to have an identifiable genetic cause79; for example,
surgery63. Recommendations from the European Pituitary Pathology almost 50% of patients with gigantism have an identifiable genetic
Group for standardized reporting of paediatric and adult pituitary alteration79,80. Germline genetic abnormalities in CYP with GH-secreting
neoplasms suggest a multilevel approach, with pituitary hormones, pituitary adenomas have been identified in patients with familial iso-
cytokeratin and Ki-67 as the most basic report64. Transcription fac- lated pituitary adenoma (AIP, GPR101 (female predominance, causing
tors should be added if the sample is immunonegative or has scanty X-linked acrogigantism; X-LAG)) or with syndromic disease (MEN1,
hormonal staining or if there is a plurihormonal or unusual combina- CDKN1B, PRKAR1A, PRKACB, SDHx and MAX). In X-LAG, duplications
tion of hormone staining. In selected cases, chromogranin, soma- in the Xq26.3 region lead to enhanced GPR101 gene expression via
tostatin receptor and p53 staining can be added based on further disruption of the topologically associating domain (TAD) surround-
clinical information64. O6-methylguanine-DNA methyltransferase ing the gene, so X-LAG represents a TADopathy81. Mosaic mutations
immunohistochemistry can be useful if considering temozolomide have been seen in GNAS (McCune–Albright syndrome) and GPR101
therapy for aggressively growing tumours65 as strong staining might (in boys), whereas somatic GNAS mutations restricted to the pituitary
predict a lack of response. Electron microscopy is not routinely used are rare in CYP unlike in adults, where they have been identified in
in molecular pathology of pituitary neoplasms from CYP but might 20–40% of tumour samples82–84. In CYP with GH-secreting adenoma,
assist in selected patients. Several studies have provided data on the AIP mutations (29% of patients with gigantism) and duplication in
molecular pathology of pituitary neoplasms, which might have a GPR101 (10%) occur most frequently, followed by McCune–Albright
role in their future classification61,66. Given data from adult pituitary syndrome (5%), Carney complex (1%), MEN1 (1%)79 and, rarely, MEN1-
adenoma guidelines65 and the recent WHO classifications12,59, the GDG like disease or phaeochromocytoma–paraganglioma-related
strengthened recommendation R10. gene alterations.

Consensus statement
Prolactinomas in CYP. MEN1 and AIP germline abnormalities occur in sphenoid sinuses (strong recommendation, low-quality evidence,
both familial and apparently sporadic forms of prolactinoma73,74,85,86, Delphi 100% and GDG consensus).
while MEN1-like (MEN4 or the recently suggested MEN5 (ref. 87) due to • Part 1: R13. In CYP with pituitary adenoma, consider endo-
MAX variants) or phaeochromocytoma–paraganglioma gene-related scopic rather than microscopic transsphenoidal surgery for its
pituitary disease (also known as the three P Association or 3PA due potentially superior efficacy in preserving pituitary function
to SDHx variants) is rare. In patients with a macroprolactinoma diag- (weak recommendation, low-quality evidence, Delphi 86%).
nosed before their twentieth birthday, 14% have a genetic aetiology • Part 1: R14. In all CYP with pituitary adenoma who undergo
(5% MEN1 and 9% AIP)86, while 34% of patients with MEN1 under 21 years surgery, offer strict fluid and electrolyte balance monitoring
of age have a pituitary adenoma, 70% of these being prolactinomas73. peri-operatively and post-operatively (strong recommendation,
In an AIP mutation-positive patient cohort, 10% had a prolactinoma, moderate-quality evidence, Delphi 100%).
and a third of these had childhood-onset disease74. Of note, patients
with microprolactinomas and AIP mutation have been described in In patients with pituitary adenoma, surgery is often a necessary
a familial setting, but only extremely rarely in a sporadic setting74. primary or secondary intervention. In CYP with pituitary adenoma,
It has been reported that some patients with hyperprolactinaemia transsphenoidal resection by pituitary surgeons in age-appropriate
but no detectable pituitary mass and variable phenotype have pro- neurosurgical units with extensive experience (at least 50 pituitary
lactin receptor mutations; however, none manifested symptoms in operations per year per unit105–107), including in children, is a safe and
childhood88,89. No other gene has been reliably identified in familial effective procedure108–112.
or sporadic childhood-onset prolactinomas. For follow-up of patients In CYP, transsphenoidal surgery by an experienced pituitary sur-
with MEN1 mutations, we refer to the MEN1 guidelines78. geon is the definitive treatment of choice for most pituitary adenomas,
even in children with incompletely pneumatized sinuses; intraop-
Corticotroph pituitary tumours in CYP. Germline mutations are rare erative image guidance might be additionally helpful. In a study of
in CYP with corticotroph adenomas85,90. MEN1 mutations have occa- 66 children with pituitary adenomas113, 17% of patients required drilling
sionally been identified in both microadenomas and macroadenomas of incompletely pneumatized sphenoid sinuses; however, anatomical
(2 of 55 patients with MEN1 aged <21 years)73,91,92. Variants in CABLES1 differences related to patient age or size were not a limiting factor to the
(2 of 146 paediatric patients with corticotrophinomas) and CDKN1B surgical procedure or its outcome. Likewise, further transsphenoidal
(3 of 190 paediatric patients with or without additional MEN1-like surgery, if necessary, was performed with minimal difficulty and with
manifestations) have also been identified90,93. A unique form of Cushing results approaching those in adults undergoing debulking or removal
disease due to infant-onset pituitary blastoma has been associated with of recurrent or residual lesions113.
DICER1 syndrome, with very low penetrance (<1%); pituitary blastoma is Changes in water metabolism and regulation of arginine vasopres-
pathognomic for DICER1 mutations based on the 18 cases published94,95. sin (AVP) are common complications of pituitary surgery114,115. Several
One patient has also been identified with DICER1 syndrome-related patterns have been observed, for example, transient or permanent AVP
pituitary blastoma diagnosed later in childhood96,97. deficiency, biphasic response with signs of AVP deficiency followed by
Somatic mutations of the USP8 deubiquitinase gene have been inappropriate antidiuresis (SIADH), and triphasic pattern with usually
implicated in over a third of childhood98 and adult-onset99–101 corti- permanent AVP deficiency after the two phases of the biphasic pattern.
cotrophinomas, most typically in female patients with corticotroph Patients must be managed in a setting where close observations (includ-
microadenomas. In one case report, developmental delay was asso- ing careful monitoring of fluid input and output) can occur so that any
ciated with a germline USP8 mutation and Cushing disease102. Large concerns can be flagged and raised with an expert endocrinologist at
somatic genomic aberrations in the DNA of paediatric corticotrophino- an early stage116,117. In a retrospective study of 160 children undergoing
mas might indicate a more aggressive neoplasm compared to tumours transsphenoidal surgery for pituitary neoplasms, the post-operative
without large genomic aberrations103. incidence of AVP deficiency (diabetes insipidus) and SIADH was 26%
and 14%, respectively114. Risk factors for AVP deficiency or SIADH were
TSHomas. TSHomas have not been associated with germline genetic female sex, cerebrospinal fluid leak, drain after surgery, invasion of
alterations in CYP, except in one patient with resistance to thyroid the posterior pituitary by the tumour or manipulation of the posterior
hormone due to THRB mutation and a TSHoma104. TSHomas have rarely pituitary during surgery.
been described in adult patients with MEN1 and AIP variants71. In CYP with pituitary apoplexy, the GDG suggests adopting the
recommendations of available adult guidelines118 given the limited case
Non-functioning pituitary adenomas in CYP. Non-functioning pitui- reports and case series in CYP115,119–124. However, paediatric pituitary
tary adenomas (NFPAs) occur in 25% of CYP with MEN1 syndrome. apoplexy can be more severe than in adults and selected patients might
Non-functioning microadenomas, not dissimilar to incidentalomas, benefit from early surgery123.
have been identified as part of clinical screening in MEN1 and AIP Endoscopic over microscopic transsphenoidal techniques are
mutation-positive CYP72–74. In a few AIP mutation-positive CYP, clini- increasingly used in pituitary surgery and are perceived as providing
cally non-functioning but GH and prolactin immunostaining-positive better operative visualization and fewer perioperative complications
macroadenomas have been identified74,85. Functioning gonadotroph and hormone deficiencies125. While further data are needed to show
adenoma in childhood has not been described with a germline mutation. the clear advantage of endoscopic surgery, most adult guidelines
agree that surgeon experience is more important to the outcome than
Pituitary surgery surgical technique (microscopic or endoscopic)126. Endoscopic trans-
• Part 1: R12. If surgery is indicated in CYP with pituitary sphenoidal pituitary surgery in CYP with Cushing disease shows an
adenoma, offer transsphenoidal surgery as the technique excellent efficacy outcome125 and improved safety, reducing surgical
of choice, even in patients with incompletely pneumatized trauma, pain perception, paediatric intensive care unit admissions,

Consensus statement
blood transfusions, anterior pituitary deficiencies and incidence 5 days per week over 25 or 30 days146. This regimen has been demon-
of AVP deficiency125,127,128. Over time, this strategy could become the strated to cure children with Cushing disease147. All regimens should
standard surgical approach in children as is current practice in adults. limit radiation delivery to no more than 1.8 Gy per fraction in keeping
Post-operative high-quality outpatient support for CYP for biochemical with modern paediatric cranial radiation schedules.
assessment can shorten the hospital stay129. Despite the restrictions of cost and availability, modern fraction-
Indications for repeat pituitary surgery in recurrent or progressive ated external beam therapy with protons is increasingly applied to pae-
disease are detailed for each pituitary adenoma type in Part 2 of this diatric neoplasms driven by the expected decrease in late effects148–150.
consensus guideline16. Prospective data collection for long-term endocrine, vascular, second-
ary malignancy and cognitive outcomes for proton beam therapy in
Radiotherapy CYP is ongoing already in the UK and represents one of our research
• Part 1: R15. In CYP with pituitary adenoma, offer radiotherapy recommendations (Box 1).
when the tumour is symptomatic, growing, resistant to medical Stereotactic radiosurgery delivers a single large radiotherapeu-
therapy and surgically inaccessible (strong recommendation, tic fraction to a limited volume with a restricted margin. This tech-
low-quality evidence, Delphi 94%). nique is routinely used for irradiating pituitary neoplasms in adults.
• Part 1: R16. Consider clinical radiation treatment protocols for Single-fraction radiosurgery lacks long-term safety data in CYP and
CYP according to adult guidelines or paediatric regimens concerns have been raised regarding late toxicity, with younger chil-
for similarly located tumours (moderate recommendation, dren, especially under 5 years, possibly being at increased risk of
low-quality evidence, Delphi 94%). vasculopathy and cognitive impairment.
• Part 1: R17. Consider external beam fractionated radiotherapy In CYP with NFPA, radiotherapy might be considered as an adjuvant
at a total dose of 45–50.4 Gy in 1.8 Gy daily fractions to CYP with therapy after subtotal resection or where surgery is contraindicated.
pituitary adenomas indicated for radiotherapy; offer fraction- Radiotherapy might also be considered as second-line therapy for radio
ated radiotherapy as proton beam therapy, where available, or logical progression or recurrence. In CYP with hormone-secreting
as highly conformal photon therapy; single-fraction radiosur- pituitary adenomas, radiotherapy should be considered in patients
gery might be appropriate in older patients in individual cir- with biochemical progression despite maximal surgery and medical
cumstances (moderate recommendation, low-quality evidence, therapy147, although no clear risk–benefit analysis has been performed
Delphi 100% and GDG consensus). to identify the number of times surgery should be attempted before
proceeding to radiotherapy. An age-appropriate pituitary MDT should
The evidence for radiotherapy in CYP with pituitary adenomas determine radiation treatment options on an individual patient basis29,151.
is both limited and inconsistently reported. Some studies consider Risk–benefit outcome data is insufficient to support one radio-
all adenomas108,130–133, while others report on specific tumour types therapy treatment modality over another139,152,153. However, where
separately110,134–139. While focal radiotherapy (photon or proton beam the planned target volume includes the optic chiasm or optic nerves,
therapy) is consistently administered to salvage those CYP with pitui- stereotactic radiosurgery should be avoided and fractionated radio-
tary adenomas who have relapsed following surgery, no standardized therapy should be employed instead as the stereotactic radiosurgery
timing of treatment indication has been developed (for example, num- dose typically exceeds tissue tolerance. On the two Delphi consen-
ber of surgeries offered prior to radiotherapy)140. Moreover, there is a sus rounds performed, individual experts held particularly strong
lack of data on dose fractionation or radiation modality comparisons positions and disagreements occurred, with those who expressed a
that assess effectiveness or risk–benefit outcomes. Thus, few data preference for stereotactic radiosurgery139 against those who have
are available on which to base recommendations regarding conven- concerns about the late effects of high doses per fraction in children.
tional photon radiation versus high-energy proton beam therapy or Both sides agreed that fairly little data exist on important long-term
stereotactic radiosurgery. Even fewer toxicity data exist, particularly health, well-being and cognitive function following single-fraction
regarding cognitive outcomes, vasculopathies, secondary tumours radiation in CYP.
and wider endocrinopathies, especially relevant to CYP.
If radiotherapy is needed, highly conformal radiotherapeutic Radiotherapy: outcomes. Adjuvant radiotherapy after transsphenoi-
techniques should be used according to availability. Options include dal surgery achieves long-term tumour control in over 90% of adult
high-energy photon-based therapy (delivered as intensity-modulated patients with NFPA134,154,155. Endocrinological criteria determining bio-
radiotherapy or conventionally fractionated stereotactic radiother- chemical remission vary across reported series, making it difficult to
apy), proton beam fractionated radiotherapy or hypo-fractionated compare tumour control in functioning pituitary adenomas. Specific
stereotactic radiosurgery. data for Cushing disease can be found in Part 2 data16. Of note, 4 out of
In CYP with pituitary adenomas, the largest clinical experi- 12 CYP with GH excess achieved remission after radiosurgery139.
ence comes from conventionally fractionated external beam pho-
tons. Intensity-modulated radiation therapy (including volumetric Radiotherapy: adverse effects. Hypopituitarism is one of the most
modulated and tomotherapy arc techniques) and stereotactic radio common adverse effects in CYP with pituitary adenomas who undergo
therapy with photons have more conformal coverage than older radiotherapy. GH deficiency could be present at diagnosis due to tumour
3D-conformal radiotherapy techniques, thereby reducing high radia- location and is universally present by 5 years after radiotherapy. Hypopi-
tion doses to organs at risk outside the treated volume141–146, however, tuitarism with multiple hormone deficiencies evolves over time to an inci-
intensity-modulated radiation therapy still exposes surrounding dence of ~20% at 5 years after radiotherapy and 80% at 10–15 years155,156,
normal tissue to a low dose of radiation. although late effects of surgery or the evolving tumour also have a role.
In adults with pituitary adenomas, the total radiation dose recom- In CYP who undergo radiotherapy, follow-up for hypopituitarism needs
mendation is usually 45–50.4 Gy, 1.8 Gy per fractionation, once a day, to be lifelong, with planned transition to specialist adult services.

Consensus statement
The young brain, although more plastic than the adult brain, is also assessment, access to age appropriate expert neuroimaging, visual
more vulnerable to injury; for example, stereotactic radiosurgery might review, histopathology, informed genetic assessment, and evaluation
carry a higher risk of radionecrosis in CYP than standard fractionated by an expert pituitary surgeon working closely with the paediatric endo-
external beam radiotherapy157. Other late effects of concern, particu- crinology, neuro-oncology and radiotherapy teams. Paediatric pitui-
larly in children, include neurocognitive sequelae137, cerebrovascular tary specialist centres offering expertise in diagnosis, treatment and
events and second malignancies158. In a group of 462 patients with follow-up of pituitary adenomas require urgent centralization around
pituitary adenoma (age range 10–83 years), Sattler et al.159 reported major adult pituitary and paediatric neuro-oncology treatment centres
no increased incidence of secondary tumours or mortality in patients as these centres improve the evidence base for treatment and long-term
receiving adjuvant post-operative radiotherapy compared with those patient benefit in such a rare, high survival condition of maturing chil-
treated with surgery alone. By contrast, Minniti et al.160 reported a dren. Multi-professional pituitary expert teams will be best placed to
2.4% risk of secondary brain tumours at 20 years after surgery and meet the specific challenges and complexities of pituitary adenomas in
radiotherapy for pituitary adenoma in adults. However, long-term children, gather the evidence needed to evaluate these consensus treat-
mortality from secondary brain tumours was minimal and mortal- ment recommendations in the future and improve the maturational,
ity predominantly arose from cerebrovascular events of complex reproductive, long-term health and functional outcomes for CYP with
multifactorial aetiology. Thus, these authors concluded that the low these eminently curable neoplasms. Having reviewed the evidence and
incidence of secondary brain tumours should not preclude the use sought consensus opinion on areas where evidence is contradictory or
of radiotherapy as an effective treatment modality in patients with poor, the GDG has suggested some research recommendations (Box 1).
otherwise uncontrolled pituitary adenomas.
In a large cohort of adult patients with GH deficiency from a GH Published online: 9 February 2024
treatment data base, secondary tumour incidence rate ratios for those
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Consensus statement
techniques including dynamic and conformal arcs, shaped beams, and IMRT. Int. J. London, London, UK), Sarah Farndon (Great Ormond Street Hospital for Children, London, UK),
Radiat. Oncol. Biol. Phys. 66, S33–S39 (2006). Mary Dang (Queen Mary University of London, London, UK), Amy Ronaldson (Queen Mary
154. Sheehan, J. P. et al. Stereotactic radiosurgery for pituitary adenomas: an intermediate University of London, London, UK), Rezvan Salehidoost (Queen Mary University of London,
review of its safety, efficacy, and role in the neurosurgical treatment armamentarium. London, UK), Gabriela Mihai (Queen Mary University of London, London, UK) and Benjamin
J. Neurosurg. 102, 678–691 (2005). Loughrey (Queen’s University Belfast, Belfast, UK) for their help in updating the literature
155. Sheehan, J. P. et al. Gamma Knife radiosurgery for the management of nonfunctioning search, grading the papers from the literature search, reviewing the manuscript and providing
pituitary adenomas: a multicenter study. J. Neurosurg. 119, 446–456 (2013). administrative support.
156. Xu, Z., Lee Vance, M., Schlesinger, D. & Sheehan, J. P. Hypopituitarism after stereotactic
radiosurgery for pituitary adenomas. Neurosurgery 72, 630–637 (2013). Author contributions
157. Mitsumori, M. et al. Initial clinical results of LINAC-based stereotactic radiosurgery and All authors researched data for the article. M.K., J.C.B., J.A., J.H.D., M.R.D., J.E., D.F., N.G., C.E.H.,
stereotactic radiotherapy for pituitary adenomas. Int. J. Radiat. Oncol. Biol. Phys. 42, T.S.J., S.S., I.S., N.T., F.M.S., H.L.S. and H.A.S. contributed substantially to discussion of the
573–580 (1998). content. M.K., J.C.B., A.B., J.H.D., J.E., T.S.J., S.S., I.S., N.T., H.L.S. and H.A.S. wrote the article.
158. Brada, M. et al. Cerebrovascular mortality in patients with pituitary adenoma. All authors reviewed and/or edited the manuscript before submission.
Clin. Endocrinol. 57, 713–717 (2002).
159. Sattler, M. G. et al. The incidence of second tumours and mortality in pituitary adenoma Competing interests
patients treated with postoperative radiotherapy versus surgery alone. Radiother. Oncol. M.K. received grant funding or served on the Advisory Board for Pfizer, Crinetics, Novo Nordisk,
104, 125–130 (2012). Recordati, and ONO Pharmaceuticals and honoraria from Ipsen, Corcept, Sandoz and Novo
160. Minniti, G. et al. The long-term efficacy of conventional radiotherapy in patients with Nordisk. J.C.B. has received honoraria, funding and travel bursaries from Novo Nordisk
GH-secreting pituitary adenomas. Clin. Endocrinol. 62, 210–216 (2005). and honoraria from Sandoz and Ipsen. J.H.D. has received travel bursaries from Sandoz,
161. Burman, P., van Beek, A. P., Biller, B. M., Camacho-Hubner, C. & Mattsson, A. F. Radiotherapy, Pfizer, and Novo Nordisk and grant funding from Pfizer. T.S.J. is director and shareholder in
especially at young age, increases the risk for de novo brain tumors in patients treated for Repath Ltd. and Neuropath Ltd. and received an honorarium from Bayer. H.L.S. received grant
pituitary/sellar lesions. J. Clin. Endocrinol. Metab. 102, 1051–1058 (2017). funding from Ipsen and Sandoz and consultancy fees from Novo Nordisk, Pfizer and Springer.
162. Swerdlow, A. J. et al. Risk of meningioma in European patients treated with growth H.A.S. has received honoraria from Ferring and Pfizer and grants from Novo Nordisk and Sandoz.
hormone in childhood: results from the SAGhE cohort. J. Clin. Endocrinol. Metab. 104, The other authors declare no competing interests.
658–664 (2019).
163. Swerdlow, A. J. et al. Cancer risks in patients treated with growth hormone in Additional information
childhood: the SAGhE European Cohort Study. J. Clin. Endocrinol. Metab. 102, Supplementary information The online version contains supplementary material available at
1661–1672 (2017). https://doi.org/10.1038/s41574-023-00948-8.
Acknowledgements Peer review information Nature Reviews Endocrinology thanks Bing Xing and the other,
The development of this consensus guideline was sponsored by unrestricted grants from anonymous, reviewers for their contribution to the peer review of this work.
professional societies (The Society of British Neurosurgical Surgeons, Children’s Cancer and
Leukaemia Group (CCLG) and British Society for Paediatric Endocrinology and Diabetes), Disclaimer Health-care providers need to use clinical judgment, knowledge and expertise
patient support groups (Association of Multiple Endocrine Neoplastic Disorders (AMEND), when deciding whether it is appropriate to apply these guidelines. The recommendations
Success Charity and The Pituitary Foundation) and from Sandoz Pharmaceuticals. All, cited here are a guide and might not be appropriate for use in all situations. The decision
except Sandoz, were stakeholders. Sandoz supported administrative and travel expenses to adopt any of the recommendations cited here is the responsibility of the treating
after the initial seed funding ended and had no role in instigating the endeavour, the clinician and must be made in the light of individual patient circumstances, the wishes of
development of guideline methodology or the final recommendations. The CCLG provided the patient and their family, clinical expertise, and resources.
administrative support throughout the development of these consensus statements and
the Royal College of Paediatrics and Child Health (RCPCH) provided advice and appraisal Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in
to ensure the process met rigorous AGREE II guideline standards. The CCLG, British Society published maps and institutional affiliations.
for Paediatric Endocrinology and Diabetes, AMEND, Success Charity, Society of British
Neurosurgical Surgeons or The Pituitary Foundation did not influence the decisions of the Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this
Guideline Development Group (GDG) or the recommendations other than through their roles article under a publishing agreement with the author(s) or other rightsholder(s); author
as stakeholders, as described in the main text. We would like to thank all of the stakeholders self-archiving of the accepted manuscript version of this article is solely governed by the
who contributed comments to this consensus guideline at various stages of development, terms of such publishing agreement and applicable law.
including members of the Society for Endocrinology, Society of British Neurological
Surgeons, British Paediatric Neurosurgical Group, Royal College of Physicians, British Society
for Paediatric Endocrinology and Diabetes, British Society of Paediatric Radiology, RCPCH, Related links
British Neuropathology Society, and the Association for Clinical Biochemistry and Laboratory AMEND: https://www.amend.org.uk/
Medicine as well as patient organizations AMEND, Success Charity and the Pituitary Child Growth Foundation: https://childgrowthfoundation.org/
Foundation. The GDG would like to thank the Project Board members and Delphi panellists NICE terminology: https://www.nice.org.uk/process/pmg20/chapter/
(Supplementary Table 2) and our external peer reviewers for their input into this consensus glossary#recommendations
guideline. The GDG would also like to thank Rosa Nieto Hernandez (Clinical Guidelines Pituitary Foundation: https://www.pituitary.org.uk/
Manager) and Helen McElroy (Quality Improvement Committee Clinical Lead for Evidence Pituitary Network Association: https://pituitary.org/
Base Medicine and Appraisals), both at the Research and Quality Improvement Directorate Rare endocrine tumour guidelines: https://www.cclg.org.uk/professionals/
of the RCPCH, for their advice and appraisal of this consensus guideline at different stages. rare-endocrine-tumour-guidelines
We also wish to thank Stephen Shalet (University of Manchester, UK), William Drake (Queen Mary Success Charity: https://successcharity.org.uk/
University of London, London, UK), Mark Gurnell (University of Cambridge, Cambridge, UK), World Alliance of Pituitary Organizations: https://www.wapo.org/
Luis Syro (Hospital Pablo Tobon Uribe and Clinica Medellin, Medellin, Colombia), Di Zou (Great
Ormond Street Hospital for Children, London, UK), Lucas Castro (Queen Mary University of © Springer Nature Limited 2024, corrected publication 2024
Márta Korbonits 1 , Joanne C. Blair2, Anna Boguslawska 3, John Ayuk4, Justin H. Davies5, Maralyn R. Druce1,
Jane Evanson6, Daniel Flanagan7, Nigel Glynn1, Claire E. Higham8, Thomas S. Jacques9,10, Saurabh Sinha11, Ian Simmons12,
Nicky Thorp8, Francesca M. Swords13, Helen L. Storr 1 & Helen A. Spoudeas10,14
1
Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London,
London, UK. 2Alder Hey Children’s Hospital, Liverpool, UK. 3Department of Endocrinology, Jagiellonian University Medical College, Krakow, Poland.
4
University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. 5University Hospital Southampton NHS Foundation Trust, Southampton, UK.
6
Neuroradiology, Barts Health NHS Trust, London, UK. 7Plymouth Hospitals NHS Trust, Plymouth, UK. 8The Christie NHS Foundation Trust, Manchester, UK.
9
Great Ormond Street Institute of Child Health, University College London, London, UK. 10Great Ormond Street Hospital for Children NHS Foundation
Trust, London, UK. 11Sheffield Children’s and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK. 12The Leeds Teaching Hospitals NHS Trust,
Leeds, UK. 13Norwich and Norfolk NHS Foundation Trust, Norwich, UK. 14University College London Hospitals NHS Foundation Trust, London, UK.

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nature reviews endocrinology https://doi.org/10.

Consensus statement Check for updates

Consensus guideline for the diagnosis

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Introduction clinicians in several disciplines to whom CYP present to optimize the

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Fig. 1 | Consensus guideline development

For further refinement, the Delphi

Recommendations supported by ≥70%

The recommendations were reviewed by

The recommendations were reviewed by

The consensus guideline was published

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Nature Reviews Endocrinology | Volume 20 | May 2024 | 278–289 289

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