Hypopituitarism and
Non-Functioning Pituitary Adenomas
Non-functioning pituitary adenomas
Non-functioning pituitary adenomas (NFPAs) are bioc cally inert
tumours. They usually present with the physical effects of a pituitary mass
lesion (e.g. visual field loss, headache and hypopituitarism) or, increasingly,
when discovered incidentally on routine brain MRI (‘pituitary incidentalomas’).
Surgical decompression is indicated if there is a visual field defect or if the
lesion is close to the optic chiasm.
The usual route for removal is trans-sphenoidally, although
trans-cranial surgery is occasionally needed. NFPAs can cause hypopituitarism
by compressing the normal gland, which requires endocrine replacement.
Histologically, NFPAs can have positive immunostaining for inactive LH and FSH,
but they do not secret bioactive hormones. Patients with significant
postoperative residual tumour may require radiotherapy.
Hypopituitarism
Causes
Hypopituitarism has several causes, either congenital (from
pituitary transcription factor defects) or acquired. Acquired hypopituitarism
is most commonly caused by the presence of a pituitary tumour. Other acquired
causes include inflammatory and infiltratitive disorders, traumatic brain
injury and radiotherapy (Figure 5.1). In patients with hypopituitarism and a
large empty pituitary fossa on MRI, it is important to enquire about a previous
history of severe headache, as this may reflect missed pituitary apoplexy
(Chapter 36).
Order of anterior pituitary hormone loss
In pituitary tumours, compression of the stalk usually
leads to loss of pituitary hormones in the following order: GH, gonadotrophins,
TSH then ACTH. Of these, ACTH deficiency is the most urgent problem as
secondary hypoadrenalism has significant clinical implications requiring
immediate hydrocortisone replacement. Pituitary stalk compression by NFPAs
leads to mild hyperprolactinaemia, typically <5000 miU/L. Prolactin >5000
miU/L in the context of a large pituitary lesion suggests active prolactin
secretion from a macro- prolactinoma (Chapter 6) rather than NFPA. This is an
important distinction because prolactinomas are managed medically, while NFPAs
are managed surgically. Patients with pituitary adenomas hardly ever develop
diabetes insipidus (in the absence of surgery), hence confirmed diabetes
insipidus should lead to consideration of alternative diagnoses, such as
inflammatory hypophysitis, craniopharyngioma or metastasis as a cause of the
hypopituitarism (Chapter 7).
Clinical presentation
Visualfieldlossfrompituitarytumoursisaspecificdiscriminatory
clinical feature, but hypopituitarism often causes non-specific symptoms
including lethargy, weight gain and sexual dysfunction (Figure 5.1). In adults,
acquired hypopituitarism has often been present for many years prior to
diagnosis, and symptoms can mimic common diseases such as depression.
Hypopituitarism can present as an acute hypoadrenal crisis, with hyponatraemia
and hypotension, which is a medical emergency (Chapter 13). In children, short
stature may be a presenting feature (Chapter 24).
In patients with suspected hypopituitarism, the priority is
assessment of the adrenal axis. Patients with chronic ACTH deficiency (>4
weeks) will have a suboptimal response to Synacthen, as a result of adrenal
atrophy. In acute hypopituitarism (e.g. pituitary apoplexy; Chapter 36), the
Synacthen test is not a reliable test of ACTH reserve as the adrenals will not
have had sufficient time to become atrophic and can give a falsely reassuring
normal cortisol response.
Secondary hypothyroidism
is demonstrated by
a low (or low end of normal) T4 with inappropriately
normal TSH. Secondary hypogonadism is confirmed by low sex hormones with
non-elevated LH and FSH. In postmenopausal females, LH and FSH levels are a
good screening test for hypopituitarism, as gonadotrophins should be elevated
at this stage of life. GH deficiency is suggested by low or low–normal IGF-1
levels; dynamic GH-stimulation tests are required to confirm this before
starting treatment. The imaging investigation of choice in hypopituitarism is
MRI, although CT can give reconstructed views of the pituitary fossa in
patients who cannot undergo MRI.
Patients with ACTH deficiency often feel immediately better
with appropriate hydrocortisone replacement, reporting increased energy and
appetite with a general improvement in symptoms. In the acute situation,
hydrocortisone can be life-saving (Figure 5.1). TSH deficiency is treated with
standard thyroxine replacement, with dosage titrated according to symptomatic
improvement and fT4 levels, as TSH cannot be used as a guide. Patients with gonadotrophin
deficiency need appropriate sex hormone replacement. Men with gonadotrophin
deficiency may benefit from testosterone replacement, both for symptom control
and protection from osteoporosis. Testosterone is given by gel or injection.
Women with oestrogen deficiency are given oestrogen and progesterone
replacement as appropriate, which can be given as the combined contraceptive
pill or hormone replacement therapy (HRT).
Growth hormone deficiency in adults can give rise to
reduced quality of life, reduced muscle and bone mass, and increased fat
masswithanadversecardiovascularprofile. GHdeficiencyshould be considered in all
patients with pituitary disease with impaired quality of life, as replacement
has the potential to improve this significantly. Recombinant GH is administered
as a daily subcutaneous injection. In order to qualify for treatment, GH
deficiency should be established as severe through biochemical testing, and
response to treatment should be documented using Adult Growth Hormone
Deficiency Assessment (AGHDA) rding to National Institute for Health and Care xcellence
(NICE) guidelines.
