HYPOTHALAMIC-PITUITARY (HP) AXIS PROBLEMS

Evidence-based recommendation for surveillance of hypothalamic-pituitary (HP) axis problems (IGHGa) b, c

This page is part of the PanCare follow-up recommendations for surveillance of late effects. Click here, for more information on these recommendations.

On this page you can find:

Click here, to read this recommendation in PLAIN language.

Who is at risk for HP axis problems?

CAYA cancer survivors treated with or with a history of

  • radiotherapy to a volume exposing the HP region, including TBI
  • surgery near or within the HP region
  • CNS tumours near or within the HP region
  • hydrocephalus or cerebrospinal fluid shunt d

What HP axis problems might occur?

  • Growth hormone deficiency (GHD)

  • TSH deficiency (TSHD)
  • LH/FSH deficiency (LH/FSHD)
  • ACTH deficiency (ACTHD)

Who should be referred directly to a (paediatric) endocrinologist or seen in a multidisciplinary team?

CAYA cancer survivors treated with or with a history of

  • suprasellar and sellar tumours
  • surgery near or within the HP region
  • ≥ 30 Gy radiotherapy exposing the HP region

When should surveillance for HP axis problems be initiated?

For survivors treated with radiotherapy to a volume exposing the HP region, including TBI:

  • Initiate surveillance for any HP axis problem at ≥ 6 months from the end of radiotherapy, even in the absence of symptoms e

For survivors with a history of hydrocephalus or cerebrospinal fluid shunt:

  • Initiate surveillance for GHD from occurrence of hydrocephalus or cerebrospinal fluid shunt

For survivors treated with prolonged periods of steroids:

  • Initiate surveillance for ACTHD according to country specific guidelines

What surveillance modality should be used and at what frequency should it be performed?

Pre-pubertal and peri-pubertal survivors:

  • Height velocity (height, expressed as standard deviation and plotted on a growth chart) in relation to parental height
  • Tanner stage f (pubertal development and pubertal progression)
    every 6 months

Pre-pubertal and peri-pubertal survivors:

  • Relevant clinical history for HP axis problems
  • Physical examination for symptoms and signs suggestive of HP axis problems
  • Laboratory surveillance
    • fT4, TSH, morning cortisol

every year

Post-pubertal survivors:

  • Relevant clinical history for HP axis problems
  • Evaluation of menstrual cycle in females
  • Physical examination for symptoms and signs suggestive of HP axis problems
  • Laboratory surveillance
    • fT4, TSH, morning cortisol, IGF-I g
    • Morning

For how long should surveillance for HP axis problems be performed?

Surveillance should be continued for at least 15 years from radiotherapy exposure or after diagnosis. However, HP axis problems may still occur after 15 years. Continuation of surveillance should be a shared decision between survivor and HCP considering available healthcare resources. If the decision is made to stop surveillance, the survivor should be educated about possible signs and symptoms of HP axis problems.

What should be done if abnormalities are identified?

  • Refer to a (paediatric) endocrinologist
    • All CAYA cancer survivors with clinical symptoms or laboratory results suggestive for HP axis problems
    • Pre- and peri-pubertal CAYA cancer survivors experiencing decline in height velocity or lack of acceleration of growth velocity in case of signs of puberty or a height SDS below their target height range SDS, which cannot be explained by other causes
  • Refer directly to a (paediatric) endocrinologist in case of a low morning cortisol h
  • Counsel survivors with (a suspicion for) HP axis problems regarding the benefits of hormonal replacement therapy on overall health, as well as the risks associated with untreated HP axis problems, and assist them with coordinating and obtaining an early referral when appropriate i

Disclaimer

While PanCare strives to provide accurate and complete information that is up-to-date as of the date of publication, we acknowledge that the sequence of referral and diagnostic tests might vary according to the local and national healthcare system logistics.

It is recognised that survivors and their healthcare professionals have the final responsibility for making decisions concerning their long-term follow-up care. As such, they may choose to either adopt these recommendations or not to do so after individual informed discussion. It is good practice to document this decision.

In addition to regular surveillance, real-time awareness and prompt reporting of new symptoms and signs is essential to the early detection and timely treatment of late effects.

No warranty or representation, expressed or implied, is made concerning the accuracy, reliability, completeness, relevance, or timeliness of this information.

The PanCare materials are free to use for anyone aiming to inform about late effects and long-term survivorship care. However, no financial advantage may be achieved. All communication should reference PanCare and link to the PanCare website.

a This recommendation reflects the recommendations of the preliminary evidence-based IGHG Hypothalamic-pituitary dysfunction guideline. The guideline will be published in a peer-reviewed journal soon.

b Further recommendations regarding height are specified in the Consensus-based recommendation for health promotion.

c Further recommendations regarding male fertility and male sexual dysfunction are specified in the Evidence-based recommendation for male fertility problems and sexual dysfunction.

d Risk factor for growth hormone deficiency.

e Monitoring height and pubertal status at six months from the end of radiotherapy is desirable, as interpretation of growth and pubertal development requires multiple measurements over time. Oncology and primary care clinicians involved in the follow-up care of CAYA cancer survivors should be aware that growth hormone deficiency may already present in the first year after radiotherapy exposure.

f Boys exposed to gonadotoxic therapy (e.g. alkylating agents and radiotherapy to the testes) may have testes small for pubertal stage while in puberty.

g Measure IGF-I with the understanding that an IGF-I level up to 0 SDS does not rule out the diagnosis of growth hormone deficiency.

h These survivors should be counselled regarding the risks associated with untreated ACTH deficiency. A hydrocortisone stress scheme should be provided in case of doubt of an adequate functioning ACTH axis.

i Thyroid hormone treatment should be started only after evaluation and approval of function of the ACTH axis.