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.
Urgent serum prolactin and urgent 9am cortisol must be assessed immediately in all patients, and hydrocortisone replacement therapy instituted immediately if rapid assessment is not possible.
Hormone replacement therapy should be started immediately.
Specific education regarding steroid replacement therapy, a steroid instructions card and emergency identification need to be discussed with all patients.
Cortisone acetate has been largely superseded by the biologically active hydrocortisone for glucocorticoid replacement.
Typical modern doses of hydrocortisone are 10mg on waking, 5mg approximately five hours after waking, and 5mg approximately 10 hours after waking.
Doses should then be adjusted according to clinical response, for example if the patient feels very tired at certain times of the day, the previous dose may be increased, or the next dose brought forward. A hydrocortisone day curve may be useful during the initial period of dose adjustment as in Addison's disease and post adrenalectomy patients.
Patients with residual ACTH reserve as indicated by 9am cortisols >250nmol/l, or with a suboptimal response to insulin tolerance test, may require lower 'top-up' doses. Asymptomatic patients with suboptimal reserve may not require daily replacement therapy, though all need thorough education and will need hydrocortisone therapy in the case of intercurrent illness and emergencies.
If the treatment dose appears to be excessive clinically, a hydrocortisone day curve may be repeated to confirm the safety of dose reduction, although routine repetition of a day curve is unlikely to alter management.
In most patients, a starting dose of 50mcg thyroxine is appropriate, with dose titrated according to serum thyroxine levels taken after approximately six weeks treatment.
In patients with cardiac disease, and those with profound hypothyroidism, it may be appropriate to start with lower doses or in the presence of unstable cardiac disease with low doses of short acting liothyronine.
Serum thyroxine should be monitored annually in patients taking stable doses. Dose adjustments should be made according to symptoms, aiming for levels between the median and the upper end of the reference range.
Estrogen deficiency should be treated in most women below 50, particularly those with a low bone mineral density.
Patches, depot injections, and oral hormone replacement therapy should all be discussed.
When GH is being considered, it is usual to switch to trans-dermal estrogen as this allows lower doses of GH to be administered to achieve the same serum IGF-I level.
The presence or absence of a uterus, personal and family history of cardiovascular, cerebrovascular and thromboembolic disease and the desire or not for a withdrawal bleed should all inform treatment choice.
Treatment is usually continued until the age of the natural menopause approximately 50 years.
Testosterone replacement should be discussed in all patients with profound biochemical deficiency and particularly those with a low bone mineral density.
Intermittent intra-muscular, topical gel and depot preparations should be discussed in all patients.
Potential effects on libido and mood must be discussed prior to treatment initiation, particularly in those with long standing and profound biochemical deficiency.
Testosterone, SHBG, PSA, FBC and LFTs should be assessed annually in all patients to aid dose adjustment in conjunction with symptoms and to detect potential treatment complications.
Dynamic testing of GH reserve with either insulin tolerance, arginine-GHRH or glucagon testing is necessary to confirm the need for GH replacement. NICE guidelines also dictate that GH therapy should only be considered in patients with confirmed pituitary diseaase, and once all other axes of the pituitary have been assessed and treated if necessary. AGHDA or other validated quality of life score should be then be assessed with a minimum score of >11/25 necessary for NICE approval of GH treatment in the UK.
MRI scan, DEXA bone scan, waist hip ratio, fasting glucose and lipids and IGF-I should all be documented prior to starting treatment. It is also worth considering switching from oral to transdermal estrogen replacement therapy prior to treatment, to reduce GH dose requirements.
The practicalities of GH replacement therapy should be discussed and the delivery methods demonstrated and then taught to the patient prior to treatment.
IGF-I levels are initially tested monthly to guide treatment dose with dose adjustment according to symptoms, adverse effects and serum IGF-I level, aiming for a level between the median and the upper limit of the age and gender related reference range.
IGF-I and AGHDA score should be reassessed after six months to determine whether it is appropriate to continue treatment - a drop of 6 points is deemed an appropriate response according to NICE guidelines.
Hydrocortisone and thyroxine doses should also be assessed three months after starting GH as serum levels may fall requiring up-titration in a minority of cases.
Repeat MRI scan after one year of treatment, and then according to multidisciplinary team discussion. Further assessments of serum IGF-I should then be made after six months and then on an annual basis.
Symptoms of DI are profound and require treatment immediately whenever this occurs, for example after the initiation of hydrocortisone therapy.
Emergency treatment of DI is with subcutaneous doses of desmopressin (typical dose 1mcg). Urea and electrolytes, and paired urine and serum osmolalities should be performed daily in the acute phase to confirm the need for ongoing treatment, and to prevent over-treatment.
Long term treatment is usually given as an intranasal spray (typical dose 1 x 10mcg inhalation on retiring). Mild cases may be controlled with oral DDAVP (typical dose 100-300mcg on retiring), and top up oral doses may also be added during the day in those whose symptoms are not fully controlled with once daily treatment.
In patients with a normal thirst mechanism, treatment aims to relieve nocturia and extreme thirst, while allowing a short period of polyuria and thirst just before a dose to prevent water overload developing, and maintain normal serum biochemistry. However, in patients with hypothalamic damage and loss of thirst, it may be necessary to calculate a fixed oral intake and desmopressin dose.
Long term monitoring of urea and electrolytes is the usually all that is required according to symptoms. Hyponatraemia indicates excessive replacement, prompting discussion of dose reduction.
Clinical assessment of pituitary status should be performed annually to ensure that new deficiencies are not emerging and to detect clinical under or over-replacement. Blood pressure, weight, waist hip ratio and BMI should also be documented.
Aggressive treatment of diabetes and cardiovascular risk should be undertaken.
Bone mineral density should have been assessed at baseline and treatment considered accordingly. Repeat DEXA scans may then be considered in some cases.
The minimum monitoring performed in all hypopituitary patients prior to annual review in our unit includes: full blood count, urea and electrolytes, liver function test, HbA1c, fasting glucose and lipid profile, HbA1c, thyroxine, 9am cortisol (unless on hydrocortisone replacement), IGF-I, LH and FSH. In male patients testosterone, SHBG and PSA are also performed, and in female patients estrodiol may also be checked in patients not already on replacement.
AGHDA score is also completed in most patients, and MRI scanning is repeated when indicated by previous MDT discussion.
Dynamic pituitary function is tested every two years in patients who have previously received pituitary irradiation, and who are not currently on replacement therapy, and according to baseline results in other patients.