Hypopituitarism

Panhypopituitarism or partial pituitary failure. Diagnosis usually requires dynamic testing with insulin or glucagon stress to detect deficiency of either one or more anterior or posterior pituitary hormones.

Glucocorticoid deficiency and adequacy of replacement


Has the patient lost weight? 

This may indicate suboptimal glucocorticoid replacement.


Does the patient feel well in themselves? 

General malaise may occur with suboptimal glucocorticoid replacement.


Have they noticed loss of energy or fatigue? 

This may indicate suboptimal glucocorticoid replacement.


Does the patient have a poor appetite or nausea? 

This may indicate suboptimal glucocorticoid replacement.


Does the patient have postural symptoms or dizziness? 

This may indicate suboptimal glucocorticoid replacement.


Does the patient suffer from low energy or tiredness at particular times of the day? 

A drop in energy at particular times of day may suggest inadequate glucocorticoid replacement at that time and may be remedied by splitting or altering the timing of doses.

Symptoms of glucocorticoid over-replacement


Has the patient gained weight? 

This may indicate supraphysiological glucocorticoid replacement.


Has the patient developed hypertension, diabetes or glucose intolerance? 

This may indicate supraphysiological glucocorticoid replacement.


Has the patient developed symptoms suggestive of osteoporosis? 

This may indicate supraphysiological glucocorticoid replacement.


Has the patient noticed changes in their skin? 

Thinning of the skin, redness, acne, easy bruising and new striae may all indicate supraphysiological glucocorticoid replacement.

Thyroid hormone deficiency and adequacy of replacement


Does the patiet feel well in themselves? 

Tiredness and general malaise may occur with suboptimal thyroid hormone replacement.


Have they noticed loss of energy or fatigue or low mood? 

This may indicate suboptimal thyroid hormone replacement.


Has the patient gained weight? 

This may indicate suboptimal thyroid hormone replacement.


Has the patient developed constipation? 

This may indicate suboptimal thyroid hormone replacement.


Has the patient developed menorrhagia?

This may indicate suboptimal thyroid hormone replacement.


Has the patient noticed changes in their skin? 

Doughy, pallid and dry skin may indicate suboptimal thyroid hormone replacement. Diffuse hair loss may also occur.

Symptoms of thyroid hormone over-replacement


Is the patient losing weight?

In a hypopituitary patient on replacement therapy this may be the only symptom to indicate supraphysiological thyroid hormone replacement. Symptoms of frank hyperthyroidism are rare.


Has the patient developed anxiety or tremulousness? 

This may indicate supraphysiological thyroid hormone replacement, though this is rarely seen in hypopituitary patients.


Has the patient developed diarrhoea? 

This may indicate supraphysiological thyroid hormone replacement.


Has the patient developed oligomenorrhoea or scanty periods? 

This may indicate supraphysiological thyroid hormone replacement, though in patients with pituiary disease, this usually indicates loss of gonadotropic function, and will also occur with hyperprolactinaemia.


Has the patient developed symptoms suggestive of osteoporosis? 

This may indicate supraphysiological thyroid hormone replacement or more commonly, supraphysiological glucocorticoid replacement therapy.

Sex hormone deficiency and adequacy of replacement


Has the patient been through the normal sequence of puberty? 

Assess timing of stages of puberty: timing of secondary hair development and rate of change of height in all, breast development and menarche in females, increase in testicular and penile volume, early morning erections and voice breaking in males.


Does the patient feel well in themselves? 

General malaise and lack of energy may indicate gonadotropin deficiency or inadequate replacement, particularly in male patients.


Have they noticed loss of energy, fatigue or enjoyment in life? 

This may indicate gonadotropin deficiency or inadequate replacement.


Does the patient feel their libido is normal or has this changed? 

Loss of libido occurs with gonadotropin deficiency or inadequate replacement.


Has the patient developed hot flushes? 

This may indicate gonadotropin deficiency or inadequate replacement.


Has the patient noticed any change or loss of body hair? 

This may indicate gonadotropin deficiency or inadequate replacement.


Does the patient feel their body shape has changed with loss of, or difficulty building, muscle bulk? Have they developed new or localised adiposity? 

This may indicate gonadotropin deficiency or inadequate replacement.


Female patients: has there been any change in menstrual cycle?

Secondary amenorrhoea occurs with hypogonadism.


Female patients: has the patient previously sought fertility? Has the patient had previous pregnancies and were they able to breast feed? 

If the patient has previously sought fertility without success, this may help time the onset of their disease.

Previous pregnancies imply that gonadotropic function was normal at that time.

Inability to breast feed may suggest Sheehan’s syndrome as the cause of hypopituitarism.


Female patients: could the patient be pregnant now? 

Pregnancy should always be excluded before investigation of amenorrhoea.


Female patients: does the patient describe vaginal dryness or dysparunia? 

These may be secondary to gonadotropin deficiency.


Male patients: does the patient wake with an erection sometimes or often? Has the patient developed erectile dysfunction? 

Erectile dysfunction may be multi-factorial though loss of early morning erections is a more significant sign of hypogonadism.


Male patient: has the patient developed breast swelling or tenderness? 

Gynaecomastia may occur with hypogonadism and in particular with hyperprolactinaemia.


Male patient: does the patient shave? If so, how often and has the frequency changed? 

Frequency of shaving varies widely but is usually constant with an individual adult.

Symptoms of sex hormone over-replacement


Has the patient developed an excessive libido? 

Increase in libido is most often encountered in women with high testosterone levels rather than excessive replacement.


Has the patient become aggressive or irritable? 

This may indicate excessive testosterone replacement. Symptoms of over replacement with estrogen are not usually recognised.

Symptoms of growth hormone deficiency


Does the patient feel well in themselves? 

Multiple, rather non-specific symptoms may occur in the syndrome of adult GH deficiency, though none are diagnostic of it. The QOL-AGHDA disease specific questionnaire has been specifically developed to seek symptoms of adult GH deficiency. Scores above 11/25 are required to qualify for GH replacement therapy according to NICE guidelines.


Do they struggle or take excessive effort to finish things? 

This is a commonly reported feature of adult GH deficiency.


Do they feel tired a lot or need to sleep during the day? 

This is a commonly reported feature of adult GH deficiency, as well as a general lack of energy and concentration.


Do they find it hard to mix with others, or to make friends? 

This may occur in the syndrome of adult GH deficiency, and is most likely to be recognised by completing the QOL-AGHDA questionnaire.


Has the patient noticed difficulty concentrating or remembering things? 

This is a commonly reported feature of adult GH deficiency, as well as a general lack of energy and concentration.


Has the patient developed a low mood or symptoms of depression? 

This may occur in the syndrome of adult GH deficiency, though is obviously not specific to it.


Have they lost confidence or enjoyment in life, or do they struggle to control their emotions? 

This may be detected on close questioning.


Is the patient known to have osteoporosis or do they have symptoms to suggest it? 

Osteoporosis is more common in pituitary patients. It often occurs in the context of supraphysiological glucocorticoid replacement, though is also exacerbated by GH deficiency, or thyroxine excess.


Has the patient gained weight or noticed a change in body shape? 

Increased central adiposity, with loss of lean muscle bulk, may occur with GH deficiency.


Has the patient developed hyperlipidaemia? 

This may improve with GH replacement.

Symptoms of supraphysiological growth hormone replacement


Has the patient developed soft tissue swelling or “puffiness”?

This is a common complaint, particularly during initial dose titration.


Has the patient developed excessive sweating?

This is a symptom of GH excess, but is rare in patients on replacement therapy.


Has the patient developed swelling or tenderness of the joints particularly those of the hands?

This is a commonly encountered side effect of excessive GH replacement therapy, and should prompt dose reduction.

Prolactin deficiency

Prolactin deficiency is usually asymptomatic and is not specifically treated.

Symptoms of prolactin excess

This may occur in multiple pituitary pathologies due to disinhibition of prolactin release. Symptoms are usually easily controlled with dopamine agonist therapy. 

Symptoms of anti-diuretic hormone deficiency or of over-replacement


Does the patient complain of excessive thirst? Do they have frequency or nocturia and, if so, how often? 

Diabetes insipidus is typified by unquenchable thirst for any fluid, with polyuria and nocturia.

Ask specifically whether they take a glass of water to bed with them, how many times they get up at night to pass urine, and when they wake do they drink before or after using the toilet?


Does the thirst occur at any particular times of day? 

In patients on replacement therapy, nasal desmopressin tends to control symptoms for approximately 16 hours. Symptoms occurring before this time require an increase in the size or frequency of desmopressin dose.


Does the patient have any periods of thirst during the day? 

If the patient does not experience at least a short period of thirst during the day they are at risk of over-replacement and water overload.


Does the patient pass urine normally during the day? 

If patients do not pass urine during the day, this indicates a risk of severe over-replacement, and a danger that the patient may develop water overload and hyponatraemia.


Has the patient developed obvious fluid retention or puffiness? 

This may indicate severe over-replacement with hyponatraemia.


Does the patient suffer with spells of headaches or confusion? 

This may indicate severe over-replacement with hyponatraemia.

Is the patient known to have pituitary disease? If so, which treatments have they received in the past?

For the assessment of suspected new pituitary disease, see non functioning pituitary adenomas.

GH is often the first anterior pituitary hormone to be lost following pituitary damage. Radiotherapy is particularly associated with GH deficiency.

Has the patient received any radiotherapy for cranial, or other malignancies, in the past?

Radiotherapy is widely used and highly effective in cancer management, and many more adults are now survivors of previous cancer. However, cranial and craniospinal irradiation for childhood haematological malignancy, bone marrow transplants, or intracranial tumours, does increase the risk of hypopituitarism developing, and GH deficiency tends to be the first manifestation of this.

Has the patient ever sustained a head injury?

Even minor traumatic brain injury may be associated with late onset hypopituitarism. This is unpredictable in timing and severity, and may not correlate to the severity of percieved injury, loss of consciousness or the need for intensive care. Furthermore, this form of hypopituitarism does not respect the typical sequential loss of pituitary hormones seen following other non traumatic causes of hypopituitarism such as radiotherapy.

Are they taking any prescribed or non prescribed medications? 

Estrogen replacement therapy of any preparation will lead to elevations in cortisol binding globulin and so effect serum cortisol results.

Inhaled and topical steroids also affect the hypothalamo-pituitary-adrenal axis, and steroids may occasionally be found in preparations thought by the patient to be 'natural' or 'herbal'.