Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The current study is a randomized, open study aimed to compare the effects of conventional glucocorticoid replacement treatment and dual-release hydrocortisone on anthropometric, metabolic, cardiovascular and bone outcomes in treatment-naïve patients with primary adrenal insufficiency and secondary adrenal insufficiency in a 10 year-observation period.
Adrenal insufficiency (AI) can be caused by a disease involving the adrenal gland resulting in inadequate secretion of adrenal cortex hormones, primary adrenal insufficiency (PAI). Secondary adrenal insufficiency (SAI) results from a decreased level of adrenocorticotrophin hormone (ACTH) released from the pituitary gland.
The mainstay of treatment of PAI and SAI is glucocorticoid (GC) replacement therapy. Conventional steroid replacement therapy includes cortisone acetate and hydrocortisone administered 2-3 times a day with the highest dose in the morning and the lowest dose in the afternoon. These dosing regimens have been designed to mimic the peak of cortisol secretion in the morning and avoid overdosing during the night hours, even though a higher risk of developing comorbidities has been shown, notably in patients treated with higher evening doses.
In patients with AI on conventional steroid replacement therapy, mortality remains higher than in the general population, mainly due to non-physiological daily GC overexposure and to inadequate cortisol exposure during stress-related events and illness.
Studies aiming to evaluate the long-term clinical outcomes of patients with AI on conventional steroid replacement therapy clearly showed increased comorbidities, mainly related to the dose used.
By contrast, dual-release hydrocortisone (DR-HC) is characterized by once-daily administration with high release of hydrocortisone immediately after intake and a very low release in the evening and nocturnal hours. The switch from conventional GC therapy to DR-HC has been shown to be associated with improvement in BMI, hepatic, bone and glucometabolic parameters and QoL. However, long-term clinical outcomes of patients treated with DR-HC in patients naïve to steroid treatment are not known.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Conventional steroid treatment | Experimental | Cortisone acetate and hydorocortisone will be administered in two daily doses |
|
| Dual-release hydrocortisone | Experimental | Dual-release hydrocortisone will be administered once daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| dual-release hydrocortisone | Drug | Oral tablets 20-25-30-40 mg/day |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change of body weight | Single outcome measurement of body weight (kg). | 0, 5 years, 10 years |
| Measure | Description | Time Frame |
|---|---|---|
| Change of anthropometric parameters | waist circumference | 0, 5 years and 10 years |
| Change of metabolic parameters | Composite outcome including evaluation of total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides, HbA1c and fasting blood glucose |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39171906 | Derived | Guarnotta V, Di Stefano C, Tomasello L, Maniscalco L, Pizzolanti G, Arnaldi G, Giordano C. Conventional steroids vs. dual-release hydrocortisone on metabolic, cardiovascular, and bone outcomes in adrenal insufficiency: a 10-year study. Eur J Endocrinol. 2024 Aug 30;191(3):300-311. doi: 10.1093/ejendo/lvae107. |
Not provided
Not provided
Study protocol could be available on request
2 years
Send an email to carla.giordano@unipa.it
Not provided
Not provided
| ID | Term |
|---|---|
| D000309 | Adrenal Insufficiency |
| ID | Term |
|---|---|
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D006854 | Hydrocortisone |
| D003348 | Cortisone |
| ID | Term |
|---|---|
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Conventional glucocortidois | Drug | Oral tablets 10-15-20-25-37,5-50-62,5 mg/day |
|
|
| 0, 5 years and 10 years |
| Change of insulin sensitivity parameters | the Isi-Matsuda index | 0, 5 years and 10 years |
| Change of cardiovascular parameters | Measurement of interventricular septum at diastole (IVSd) and the thickness of the posterior wall (PWT) by high-resolution M-B-mode transthoracic echocardiography | 0, 5 years and 10 years |
| Change of bone metabolic parameters | Composite outcome including calcium, phosphorus, Vitamin D, PTH, creatinine (all measured in mg/dL) | 0, 5 years and 10 years |
| Change of bone density | Bone mineral density quantified by Dual X-Ray Absorptiometry (DEXA) | 0, 5 years and 10 years |
| Change of vascular parameters | Measurement carotid intima media thickness by high-resolution M-B-mode echography | 0, 5 years and 10 years |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D015062 | 11-Hydroxycorticosteroids |
| D006889 | Hydroxycorticosteroids |
| D000305 | Adrenal Cortex Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D015065 | 17-Hydroxycorticosteroids |