Long Term Management of Patients After Successful Pituitary Surgery for Cushings Disease

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Many patients will have undetectable (<50 nmol/L or 1.8 Mg/dL) early morning cortisol concentrations after pituitary surgery. Once cure has been established, replacement glucocorticoids should be initiated and titrated to ensure satisfactory clinical response and biochemical levels. Many centers favor the use of hydrocortisone or cortisone acetate, facilitating measurement of cortisol concentrations to monitor therapy. Most patients receive divided doses, typically three times a day, taken before rising in the morning, at midday and in the early evening, allowing for circadian dynamics close to those seen in the healthy population. A hydrocortisone day curve (HCDC) allows measurement of this pattern (see "Endocrine Protocols", Appendix 1, p. 201). All patients should receive a "steroid card" and instruction on management of glucocorticoid replacement during periods of illness, while specialist centers may also provide an "emergency pack" for parenteral (usually intramuscular) hydrocortisone administration during severe illness.

Spontaneous recovery of preserved corticotrophs usually occurs within 2 yr in most cases of successful cure of CD, but recovery may be delayed considerably beyond this time (19). After assessment of pituitary function and establishment of glucocorticoid replacement, patients should be periodically reassessed to determine recovery of the ACTH-adrenal axis. We favor re-admission for assessment initially after a 3- to 6-month interval, with subsequent reassessments at 6- to 12 month intervals. The reassessment after successful cure of CD includes successive daily measurements of early morning serum cortisol concentrations for 72 h after discontinuation of glucocorticoid. If values remain undetectable, replacement is reinitiated and the patient discharged to be evaluated at a later date. In those with detectable cortisol concentrations, particularly >100 nmol/L (3.6 Mg/dL), a provocative test of ACTH reserve is performed, either in the form of the insulin-hypoglycemia test or a glucagon stimulation test (see "Endocrine Protocols", Appendix 1, pp. 197-198). Other centers may perform outpatient assessment of hypothalamic-pituitary-adrenal axis activity.

In those patients achieving satisfactory responses, glucocorticoid replacement can be discontinued. An intermediary response (>200 nmol/L [7.3 Mg/dL] and <550 nmol/L [20 ^g/dL]) is frequently observed and in such a case a clinical judgment is made whether glucocorticoid replacement is necessary and at what dosing regimen.

Periodic reassessment should be continued, and generally the lowest dose considered clinically safe is chosen, with the availability of an emergency sup ply. In those with reemerging ACTH-adrenal secretion, identification of normal circadian dynamics and exclusion of recurrence of CD is undertaken during these assessments. Once measurable serum cortisol levels are evident, the circadian pattern may be evaluated during 48 h with measurement of cortisol levels at 9 am, 6 pm, and 12 am, the last value ideally with the patient asleep for the most accurate interpretation. The low dose dexamethasone suppression test (see Appendix 1, p. 200) should be performed to further exclude recurrent CD.

All patients with CD require life-long endocrine surveillance, and attention should be paid to body composition, psychologic health, blood pressure, carbohydrate tolerance, lipid status, and bone mineral density (BMD). At least yearly clinic attendances are required, with periodic assessment to exclude recurrence of disease. Established associated conditions should be aggressively treated, and BMD measured using dual-energy X-ray absorptiometry (DXA). BMD will increase in time with cure of CD; however, if there is a severe persistent deficiency, bisphosphonates may be used; however, the effects of the agents in human pregnancy are not yet established. Recent evidence indicates that reversible GH-deficiency (GHD) may persist for as long as 2 yr after successful treatment of CD. It has been recommended that definitive assessment of GH status in adults with cured CD be delayed for this period (20). In addition, the possibility of delayed hypopituitarism should be considered and measurement of basal pituitary function performed. If necessary, a provocative test of ACTH and GH reserve can be carried out and occasionally, a water deprivation test if cranial diabetes insipidus (DI) persists after surgery (see Appendix 1, pp. 198-199).

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