40 mg/day is not a standard replacement dose
Numerous peer reviewed articles would argue strongly that 40 mg is way too much for long term use (15-20 is the typical replacement dose for someone with primary or secondary adrenal insufficiency - caused by pituitary dysfunction or ironically by overuse of steroids). You also need to think about natural circadian patterns of ACTH release.
At the least, excessive long-term dosing carries the risk of bone density depletion, suppression of existing (residual?) adrenal capacity, GH problems and immuno-suppression. Hip fractures (and poor healing due to osteoporosis) are common with excessive long term use of HC. Forty mg/day is a "stress dose" that should not be used for more than a few days, when someone with primary or secondary adrenal insufficiency has an infection, is vomiting, or has sustained an injury.
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Correction of cortisol overreplacement ameliorates morbidities in patients with hypopituitarism: a pilot study.
[FONT="]Danilowicz K, Bruno OD, Manavela M, Gomez RM, Barkan A.[/FONT]
Division of Endocrinology, Hospital de Clnicas, Avenida Crdoba 2351, 5 degrees piso, 1120, Ciudad Autnoma de Buenos Aires, Argentina.
Abstract
CONTEXT: Hypopituitarism in adults is known to be associated with deleterious effects on body composition, lipid profile and quality of life (QoL). This was attributed to GH deficiency. The potential role of glucocorticoid overreplacement had never been investigated. OBJECTIVE: To investigate whether reduction in glucocorticoid replacement dose to more physiological one could ameliorate the "AO-GHD"-attributed symptomatology in patients with hypopituitarism. Design Eleven patients with panhypopituitarism taking 20-30 mg/day of hydrocortisone, but on no GH replacement were switched to 10-15 mg of hydrocortisone daily. Both basally and 6-12 months later, their body mass index, body composition by dual-energy X-ray absorptiometry, lipid profile, and the score of quality of life, QOL-AGHDA were measured. RESULTS: Within 6-12 months of lower hydrocortisone dose, subjects lost an average of 7.1 kg of total body fat and 4.1 kg of abdominal fat. No changes were seen in lean body mass, bone mineral content and HOMA-IR. Plasma total cholesterol and triglyceride concentrations decreased significantly (< 0.05) and the QoL improved (P = 0.018). CONCLUSIONS: Our pilot study suggests that decreasing the glucocorticoid replacement dose to approximately 15 mg/day is beneficial in terms of patients' body composition, lipid profile and quality of life.
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[FONT="]J Clin Endocrinol Metab. 2006[/FONT] Oct;91(10):3954-61. Epub 2006 Aug 8.
The impact of glucocorticoid replacement regimens on metabolic outcome and comorbidity in hypopituitary patients.
[FONT="]Filipsson H, Monson JP, Koltowska-Hggstrm M, Mattsson A, Johannsson G.
Department of Endocrinology, Grna Strket 8, Sahlgrenska University Hospital, S-413 45 Gteborg, Sweden.[/FONT]
Abstract
BACKGROUND: Hypopituitary patients with untreated GH deficiency and patients on inappropriately high doses of glucocorticoid (GC) share certain clinical features. OBJECTIVE: The aim of the study was to examine the influence of GC substitution on clinical characteristics in hypopituitary patients before and after GH replacement therapy. METHOD: A total of 2424 hypopituitary patients within the KIMS (Pfizer International Metabolic Database) were grouped according to ACTH status. Comparisons were performed between subjects on hydrocortisone (HC) (n = 1186), cortisone acetate (CA) (n = 487), and prednisolone/dexamethasone (n = 52), and ACTH-sufficient patients (AS) (n = 717) before and after 1 yr of GH treatment in terms of body mass index, waist and hip circumference, blood pressure, glucose, glycosylated hemoglobin (HbA1c), serum lipids, IGF-I, and comorbidity. Hydrocortisone equivalent (HCeq) doses were calculated, and measurements were adjusted for sex and age. RESULTS: At baseline, the HC group had increased total cholesterol, triglycerides, waist circumference, and HbA1c, and the prednisolone/dexamethasone group had increased waist/hip ratio as compared with AS. After HCeq dose adjustment, the HC group retained higher HbA1c than the CA group. GC-treated patients showed a dose-related increase in serum IGF-I, body mass index, triglycerides, low-density lipoprotein cholesterol and total cholesterol levels. Subjects with HCeq doses less than 20 mg/d (n = 328) at baseline did not differ from AS in metabolic endpoints. The 1-yr metabolic response to GH was similar in all GC groups and dose categories. All new cases of diabetes (n = 12), stroke (n = 8), and myocardial infarction (n = 3) during GH treatment occurred in GC-treated subjects. CONCLUSION: HCeq doses of at least 20 mg/d in adults with hypopituitarism are associated with an unfavorable metabolic profile. CA replacement may have metabolic advantages compared with other GCs.
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[FONT="]J Endocrinol Invest. 2005[/FONT] Jul-Aug;28(7):632-7.
Comparison of different regimens of glucocorticoid replacement therapy in patients with hypoadrenalism.
[FONT="]Barbetta L, Dall'Asta C, Re T, Lib R, Costa E, Ambrosi B.[/FONT]
Endocrinology Unit, Department of Medical and Surgical Sciences, Istituto Policlinico San Donato, University of Milano, Milano, Italy.
Abstract
Since the optimal glucocorticoid replacement needs to avoid over and under treatment, the adequacy of different daily cortisone acetate (CA) doses was assessed in 34 patients with primary and central hypoadrenalism. The conventional twice CA 37.5 mg/day dose was administered to all patients (A regimen: 25 mg at 07:00 h, 12.5 mg at 15:00 h), while in 2 subgroups of 12 patients the dose was shifted on 2 thrice daily regimens (B: 25 mg at 07:00, 6.25 mg at 12: 00, 6.25 mg at 17:00; C: 12.5 mg, 12.5 mg, 12.5 mg). In other 12 patients the conventional dose was reduced to a thrice 25 mg/day administration (D regimen: 12.5 mg, 6.25 mg, 6.25 mg). In all patients, urinary free cortisol (UFC) excretion and cortisol day curves were evaluated. During the CA 37.5 mg administration, nadir cortisol levels were significantly higher with the thrice daily regimens (143 +/- 31 on B and 151 +/- 34 nmol/l on C) than with the conventional twice (85 +/- 16 nmol/l). Moreover, UFC, morning cortisol levels and mean cortisol day curves were similar in each group. Finally, during D regimen nadir cortisol levels were higher than in A and similar to B and C regimens. No difference in UFC and in cortisol day curves by reducing the CA dose was found. In conclusion, the thrice daily cortisone regimens, in which more physiological cortisol levels are achieved, perform better as replacement therapy. The administration of 25 mg/day CA confirms that replacement therapy is more adequate with a lower dose, particularly in patients with central hypoadrenalism.
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[FONT="]Clin Endocrinol (Oxf). 2004 Jun;60(6):688-93.[/FONT]
Conventional glucocorticoid replacement overtreats adult hypopituitary patients with partial ACTH deficiency.
[FONT="]Agha A, Liew A, Finucane F, Baker L, O'Kelly P, Tormey W, Thompson CJ.[/FONT]
Department of Endocrinology, Beaumont Hospital, Dublin, Ireland.
Abstract
BACKGROUND: Glucocorticoid therapy is associated with potentially serious side-effects, but there is no information available regarding glucocorticoid requirement in adult hypopituitary patients with partial ACTH deficiency. SUBJECTS: Ten male adult hypopituitary patients with partial ACTH deficiency, baseline plasma cortisol > 200 nmol/l but a peak stimulated cortisol < 500 nmol/l and 10 matched healthy male control volunteers participated. DESIGN: Patients were assigned, in a random order, to a cross-over protocol of treatment for 1 week with full dose hydrocortisone (10 mg twice daily), half-dose hydrocortisone (5 mg twice daily), or no treatment. All patients completed all three of the treatment limbs. MEASUREMENTS: Following each treatment schedule, patients underwent an 11-h cortisol day curve (CDC), and the results were compared with those from the 10 control volunteers on no glucocorticoid treatment. RESULTS: The integrated CDC values were significantly higher in patients taking a full dose of hydrocortisone compared to controls (P < 0.001). There was no significant difference in the integrated CDC between patients on half-dose (P = 0.37) or no hydrocortisone treatment (P = 0.13), compared to control subjects. Peak postabsorption cortisol values were higher in patients receiving full-dose hydrocortisone treatment compared to controls (P < 0.001). There was no significant difference in plasma sodium concentration, blood pressure or corticosteroid-binding globulin between patients on any treatment schedule and controls. CONCLUSION: Adult patients with pituitary disease and partial ACTH deficiency have a cortisol secretory pattern comparable to that of healthy controls. Conventional full-dose replacement with 10 mg twice daily of hydrocortisone produces hypercortisolaemia, whereas half-dose produces a CDC that is not statistically different from that of healthy controls. The results suggest that current conventional glucocorticoid replacement overtreats patients with partial ACTH deficiency under normal unstressed physiological conditions.