Hypopituitarism

Hypopituitarism is the partial or complete deficiency of pituitary hormones. If untreated, this can result in increased morbidity and mortality particularly from cardiovascular disease.

Recognition
Recognition of this condition is therefore important as an underlying pathology may need to be rectified and appropriate hormones may require replacement. The importance of adequate glucocorticoid replacement should be emphasised to the physician and the patient. Knowledge of dose alterations and administration during illness, Medic-Alert bracelets and steroid cards could be life-saving.

Aetiology
Hypopituitarism may be congenital or acquired.

Kallmann's syndrome is a congenital cause of hypopituitarism that manifests as congenital hypogonadotropic hypogonadism and anosmia. The development of hypopituitarism tends to follow a characteristic order.

Growth hormone (GH) is affected first, followed by gonadotrophins, then thyroid stimulating hormone (TSH) and adrenocorticotrophic hormone (ACTH).

Prolactin deficiency is rare, except in Sheehans's syndrome which is represented by haemorrhagic infarction of the pituitary gland following blood loss after postpartum haemorrhage. Antidiuretic hormone (ADH) deficiency is rare with anterior pituitary tumours.

Epidemiology
The incidence of some degree of hypopituitarism has been reported as about 1 per 10,000 of the UK population.

There is no racial predilection, and the prevalence is higher in women. This is probably because of post-partum hypopituitarism.

2.DIAGNOSIS

Clinical features
The clinical features are similar to those occurring when there is target gland hormone insufficiency. An additional clinical feature is the amelioration of diabetes mellitus in patients with hypopituitarism due to a reduction in counter-regulatory hormones. This is known as the Houssay phenomenon.

Anterior pituitary function
To test anterior pituitary function, both pituitary hormone and target organ hormone concentrations should be measured. These include LH, FSH and testosterone or oestradiol, TSH and thyroxine, 9am cortisol, PRL and IGF-1.

Dynamic tests, such as the insulin tolerance test, are used to assess cortisol and GH reserve. The short synacthen test measures ACTH reserve.

Posterior pituitary function
To test posterior pituitary function, plasma and urine osmolalities should be measured. 

These may indicate the presence of diabetes insipidus, and a water deprivation test can diagnose it formally.

Glucocorticoids must be replaced prior to assessing posterior pituitary function as ACTH deficiency leads to reduced GFR and the inability to excrete a water load, which may mask diabetes insipidus.

Investigation of the cause may include pituitary imaging (MRI), ferritin (haemochromatosis), serum and CSF ACE (sarcoidosis). A visual field check should also be carried out.

Adapted from Oxford Handbook of Endocrinolgy and Diabetes, 2006

3. MANAGEMENT

Treatment involves replacement of the target hormone rather than the deficient pituitary or hypothalamic hormone, except for GH replacement and for fertility induction ( see table).

Glucocorticoids
Monitoring of glucocorticoid replacement is essential. Over-replacement is associated with increased BP, increased glucose level and reduced bone mineral density. Under-replacement leads to symptoms seen in Addison's disease.

Monitoring involves both clinical assessment and biochemical measurement of urine and plasma cortisol. Urinary free cortisol (UFC) should be kept to <220nmol/24 hours.

The aim is to keep the plasma level between 150 and 300nmol/l, avoiding nadirs of <50nmol/l pre-dose.

Patients should wear a Medic-Alert bracelet to indicate cortisol deficiency and they should keep a vial of parenteral hydrocortisone at home for administration during emergency situations.

Thyroid hormone replacement
Replacement is with thyroxine, as in primary hypothyroidism. In younger patients, the starting dose is 100µg once daily, and in older patients with a history of ischaemic heart disease, an initial dose is 25-50µg with an increase in 25µg increments at four week intervals with the aim of getting T4 into the upper normal range.

Monitoring is carried out by clinical assessment and measurement of free thyroid hormone concentrations.

Oestrogen/progestogen
Oestrogen and progestogen preparations must be used in non-hysterectomised women to avoid endometrial hyperplasia. Administration can be oral, transdermal patch or gel or subcutaneous implant.

Before oestrogen replacement, patients must be assessed for risk factors for breast and endometrial cancer, thromboembolic disease and acute liver disease.

Androgen replacement
Several preparations of testosterone are available. Administration can be IM, transdermal, oral or a subcutaneous implant. Androgen replacement in women is indicated when there is poor well-being and libido despite HRT. Subcutaneous testosterone implants are the only preparation available for women.

Monitoring is required at three months and then six and 12 monthly. It involves clinical assessment, rectal examination of the prostate, serum testosterone, PSA (if  over 45 years), haemoglobin and serum lipids.

GH replacement
All patients with GH deficiency should be considered for hormone replacement, especially those with impaired well-being, reduced exercise capacity, increased central adiposity, reduced bone mineral density and adverse cardiovascular risk profile.

Current recommendations are a starting dose of 0.1-0.4mg/day and maintenance dose of 0.2-0.6mg/day. The dose in women is often higher than for age-matched men. A common side effect is fluid retention. GH replacement should be avoided in patients with active malignancy and benign intracranial hypertension.

Monitoring involves clinical examination focusing on body weight and BP. Biochemical monitoring includes IGF-1 which should be monitored every one to two months during dose titration and then annually.