Further Outpatient Care
Patients on steroid replacement therapy need to be closely monitored by their primary care physician and by an endocrinologist.
Close monitoring for any signs of inadequate replacement (eg, morning headaches, weakness, and dizziness) and any signs of over-replacement (eg, cushingoid features) should prompt appropriate dosage adjustment. A periodic bone dual-energy radiographic absorptiometry scan may be useful in detecting early osteoporosis in patients who are inadvertently over-replaced with maintenance steroids.
Additional concerns may include hypothyroidism, pregnancy, and bone loss.
Hypothyroidism
Hypothyroidism occurring in association with Addison disease may be steroid-responsive and may not require thyroxine replacement. Some patients who have symptoms of hypothyroidism may need only temporary levothyroxine replacement during the symptomatic phase. Therefore, holding off or delaying levothyroxine replacement may be prudent in asymptomatic patients until a variable period on steroid replacement has passed before committing them to unnecessary lifelong thyroxine replacement. [49]
Patients who require thyroxine replacement need periodic monitoring to assess the recovery of thyroid function. Levothyroxine should be withheld for 6-8 weeks or longer until further clinical evaluation and repeat TSH testing is performed. Additionally, if it has not already been done, steroid replacement should be given before thyroid replacement is instituted. If a question about adrenal insufficiency remains and thyroid replacement must be instituted urgently (ie, profound hypothyroidism), corticosteroids should be given and the adrenal status should be sorted out later.
Pregnancy
In pregnancy, the usual steroid replacement doses should be maintained. Occasionally, dose adjustments may need to be made depending on the patient's well being and the presence or absence of symptoms of adrenal insufficiency.
Pregnancy increases the production of cortisol-binding globulins (CBGs) and, therefore, cortisol binding. Free cortisol is proportionately increased so no dose adjustments should be needed.
In labor and delivery, vaginal or caesarean, parenteral stress-dose steroid coverage should be used as at other times of major stress. Stress-dose steroids also may be needed during the stress related to hyperemesis gravidarum.
The preferred mode of steroid administration is by continuous IV infusion and then rapid dose-tapering to the usual maintenance doses when the clinical situation allows.
Bone loss
A cross-sectional study by Lovas et al of 293 patients with Addison disease indicated that the dosage of glucocorticoids administered to individuals with this condition, a higher level than would be delivered through normal endogenous production, reduces bone mineral density in the femoral neck and lumbar spine. [53] In addition, the authors stated that, according to blood sample findings in their study, individuals who have a common polymorphism in the efflux transporter P-glycoprotein may be particularly susceptible to glucocorticoid-induced osteoporosis. The investigators indicated that, based on their results, patients may benefit if hydrocortisone dosages conventionally administered for Addison disease are lowered.
A prospective study by Schulz et al indicated that in patients with primary adrenal insufficiency or congenital adrenal hyperplasia undergoing glucocorticoid replacement therapy, a reduction in daily hydrocortisone equivalent doses (from 25.2 mg to 21.4 mg) increases bone mineral density, with the investigators finding a significant rise in lumber spine and hip Z-scores. It was reported that dose reduction did not lead to an increased adrenal crisis risk. [54]
Further Inpatient Care
With the exception of treatable causes such as TB, where adequate and timely treatment may allow recovery of normal adrenal function, patients need glucocorticoid and mineralocorticoid replacement for life. [8]
Fludrocortisone replacement therapy
Some patients may not need fludrocortisone replacement, or they may need it only in hot weather.
The fludrocortisone daily replacement dose should be titrated to maintain normal blood pressure and normal sodium and potassium levels. No dose adjustment is needed in stressful situations.
Periodic monitoring is needed to assess general well being, weight, blood pressure, electrolytes, the presence or absence of pedal edema, and the presence of cushingoid features.
Hydrocortisone replacement therapy
The usual daily replacement dose of hydrocortisone should be given in a way that mimics the circadian rhythm and keeps with the daily basal cortisol production rate of 8-12 mg/m2/d.
Patients who are thin may require smaller doses, whereas patients who are obese may require larger doses.
Patients on medications that induce the action of the cytochrome P450 enzyme require higher replacement doses. Patients with decreased cortisol clearance, as in liver disease, may require lower replacement doses.
The individual daily hydrocortisone or prednisone replacement dose should be titrated to the patient's general well being and the presence or absence of symptoms of adrenal insufficiency.
The intermediate-acting steroids, such as prednisone or prednisolone, may be used for daily replacement therapy in place of hydrocortisone. The equivalent daily replacement dose is 5-7.5 mg. A study by Chandy and Bhatia, however, indicated that prednisolone therapy in male patients with primary adrenal insufficiency can result in a small, but significant, reduction in bone mineral density. [55]
Patient Education
Patients should wear an emergency medical alert bracelet.
Patients should be instructed to double or triple their steroid replacement doses in stressful situations, such as a common cold or tooth extraction.
Patients should be instructed to contact their regular physician or to go to the emergency department in case of illness.
Patients should be instructed on how to give themselves IM injections. They should be given a prescription for parenteral hydrocortisone for use on occasions when oral intake may not be possible or when marked vomiting or diarrhea occurs. No adjustment needs to be made on the mineralocorticoid replacement dose in stressful situations.
