Abstract:ObjectiveThis study aimed at comparing precursors of endogenous corticosteroid production in patients with primary adrenal insufficiency and in secondary adrenal insufficiency.DesignTwenty patients with primary adrenal insufficiency and matched controls and 19 patients with secondary adrenal insufficiency participated in this ancillary analysis of two different studies.Patients and measurementsPatients with primary adrenal insufficiency were on stable hydrocortisone and fludrocortisone therapy. Patients with s… Show more
“…17 These studies have recently been extended by 3 different groups using mass spectrometric steroid metabolome assays in a further 249 individuals with established AAD (Table 1). [18][19][20] In summary, these three additional studies have used more sensitive assays to establish beyond doubt that AAD patients are heterogeneous in terms of adrenal function, with around 30% having some low level, residual adrenal steroidogenesis for many years following diagnosis. In the two largest studies around 10% had detectable serum cortisol concentration ≥100 nmol/l and 5% had concentrations ≥150nmol/l.…”
Section: What Is Residual Adrenal Function?mentioning
confidence: 99%
“…All studies found that the glucocorticoid precursor 11deoxycortisol, either in serum or urine, correlated strongly with serum cortisol concentration, making it a potentially useful marker of residual adrenal steroidogenesis that might be ascertained in patients who continued to take their regular medications. [18][19][20] Interestingly, six of 84 participants with residual function had AAD for 20 or more years, 19,20 suggesting that it is a durable state in some patients, although overall residual steroidogenesis was commoner in patients with shorter disease duration. One patient had originally been studied in 2012, 4 years after presentation with AAD when she had a peak stimulated serum cortisol of 184 nmol/L (6.7 ug/dL); repeat measurement in 2016 showed a concentration of 252 nmol/L (9.1 ug/dL).…”
Section: What Is Residual Adrenal Function?mentioning
confidence: 99%
“…36 This rate of residual adrenal function is greater than that found spontaneously in the observational studies, where only 10% of individuals had serum cortisol concentrations ≥100nmol/l. [17][18][19][20] Could adrenal steroidogenesis be salvageable further into the course of the disease? With this question in mind, we administered high dose synacthen to 13 unselected patients with AAD established for more than a year.…”
Section: Residual Adrenal Function In Context Of Autoimmunitymentioning
confidence: 99%
“…While none of these patients had a normal cortisol response, 10 (37%) did show detectable serum cortisol concentrations, with one patient having a peak value of 100 nmol/L (3.62 µg/dL), suggesting that low level, residual adrenal function might not be uncommon ( 17 ). These studies have recently been extended by three different groups using mass spectrometric steroid metabolome assays in a further 249 individuals with established AAD ( Table 1 ) ( 18 , 19 , 20 ).…”
Section: What Is Residual Adrenal Function?mentioning
confidence: 99%
“…In contrast, preserved adrenal androgen secretion was not frequent, and indeed because of preserved gonadal steroid secretion, was technically more difficult to evaluate. All studies found that the glucocorticoid precursor 11-deoxycortisol, either in serum or urine, correlated strongly with serum cortisol concentration, making it a potentially useful marker of residual adrenal steroidogenesis that might be ascertained in patients who continued to take their regular medications ( 18 , 19 , 20 ). Interestingly, 6 of 84 participants with residual function had AAD for 20 or more years ( 19 , 20 ), suggesting that it is a durable state in some patients, although overall residual steroidogenesis was commoner in patients with shorter disease duration.…”
Section: What Is Residual Adrenal Function?mentioning
Over the last 10 years, evidence has accumulated that autoimmune Addison’s disease (AAD) is a heterogeneous disease. Residual adrenal function, characterised by persistent secretion of cortisol, other glucocorticoids and mineralocorticoids is present in around 30% of patients with established AAD, and appears commoner in men. This persistent steroidogenesis is present in some patients with AAD for more than 20 years, but it is commoner in people with shorter disease duration. The clinical significance of residual adrenal function is not fully clear at the moment, but as it signifies an intact adrenocortical stem cell population, it opens up the possibility of regeneration of adrenal steroidogenesis and improvement in adrenal failure for some patients.
“…17 These studies have recently been extended by 3 different groups using mass spectrometric steroid metabolome assays in a further 249 individuals with established AAD (Table 1). [18][19][20] In summary, these three additional studies have used more sensitive assays to establish beyond doubt that AAD patients are heterogeneous in terms of adrenal function, with around 30% having some low level, residual adrenal steroidogenesis for many years following diagnosis. In the two largest studies around 10% had detectable serum cortisol concentration ≥100 nmol/l and 5% had concentrations ≥150nmol/l.…”
Section: What Is Residual Adrenal Function?mentioning
confidence: 99%
“…All studies found that the glucocorticoid precursor 11deoxycortisol, either in serum or urine, correlated strongly with serum cortisol concentration, making it a potentially useful marker of residual adrenal steroidogenesis that might be ascertained in patients who continued to take their regular medications. [18][19][20] Interestingly, six of 84 participants with residual function had AAD for 20 or more years, 19,20 suggesting that it is a durable state in some patients, although overall residual steroidogenesis was commoner in patients with shorter disease duration. One patient had originally been studied in 2012, 4 years after presentation with AAD when she had a peak stimulated serum cortisol of 184 nmol/L (6.7 ug/dL); repeat measurement in 2016 showed a concentration of 252 nmol/L (9.1 ug/dL).…”
Section: What Is Residual Adrenal Function?mentioning
confidence: 99%
“…36 This rate of residual adrenal function is greater than that found spontaneously in the observational studies, where only 10% of individuals had serum cortisol concentrations ≥100nmol/l. [17][18][19][20] Could adrenal steroidogenesis be salvageable further into the course of the disease? With this question in mind, we administered high dose synacthen to 13 unselected patients with AAD established for more than a year.…”
Section: Residual Adrenal Function In Context Of Autoimmunitymentioning
confidence: 99%
“…While none of these patients had a normal cortisol response, 10 (37%) did show detectable serum cortisol concentrations, with one patient having a peak value of 100 nmol/L (3.62 µg/dL), suggesting that low level, residual adrenal function might not be uncommon ( 17 ). These studies have recently been extended by three different groups using mass spectrometric steroid metabolome assays in a further 249 individuals with established AAD ( Table 1 ) ( 18 , 19 , 20 ).…”
Section: What Is Residual Adrenal Function?mentioning
confidence: 99%
“…In contrast, preserved adrenal androgen secretion was not frequent, and indeed because of preserved gonadal steroid secretion, was technically more difficult to evaluate. All studies found that the glucocorticoid precursor 11-deoxycortisol, either in serum or urine, correlated strongly with serum cortisol concentration, making it a potentially useful marker of residual adrenal steroidogenesis that might be ascertained in patients who continued to take their regular medications ( 18 , 19 , 20 ). Interestingly, 6 of 84 participants with residual function had AAD for 20 or more years ( 19 , 20 ), suggesting that it is a durable state in some patients, although overall residual steroidogenesis was commoner in patients with shorter disease duration.…”
Section: What Is Residual Adrenal Function?mentioning
Over the last 10 years, evidence has accumulated that autoimmune Addison’s disease (AAD) is a heterogeneous disease. Residual adrenal function, characterised by persistent secretion of cortisol, other glucocorticoids and mineralocorticoids is present in around 30% of patients with established AAD, and appears commoner in men. This persistent steroidogenesis is present in some patients with AAD for more than 20 years, but it is commoner in people with shorter disease duration. The clinical significance of residual adrenal function is not fully clear at the moment, but as it signifies an intact adrenocortical stem cell population, it opens up the possibility of regeneration of adrenal steroidogenesis and improvement in adrenal failure for some patients.
Purpose The impact of patient's characteristics on glucocorticoid (GC) replacement therapy in adrenal insufficiency (AI) is poorly evaluated. Aims of this study were to assess the influence of sex and body weight on GC dosing and to describe the choice of GC in AI of different etiologies. Methods We retrospectively evaluated hydrocortisone (HC) equivalent total daily dose (HC-TDD) and per-kg-daily dose (HC-KDD) in 203 patients (104 primary AI [pAI], 99 secondary AI [sAI]) followed up for ≥ 12 months. They were treated with HC, modified-release HC (MRHC) or cortisone acetate (CA) and fludrocortisone acetate (FCA) in pAI. Results At baseline, CA was preferred both in pAI and sAI; at last visit, MRHC was most used in pAI (49%) and CA in sAI (73.7%). Comparing the last visit with baseline, in pAI, HC-TDD and HC-KDD were significantly lower (p = 0.04 and p = 0.006, respectively), while FCA doses increased during follow-up (p = 0.02). The reduction of HC-TDD and HC-KDD was particularly relevant for pAI women (p = 0.04 and p = 0.002, respectively). In sAI patients, no change of HC-KDD and HC-TDD was observed, and we found a correlation between weight and HC-TDD in males (r 0.35, p = 0.02). Conclusions Our real-life study demonstrated the influence of etiology of AI on the type of GC used, a weight-based tailoring in sAI, a likely overdosage of GC treatment in pAI women at the start of treatment and the possibility to successfully increase FCA avoiding GC over-treatment. These observations could inform the usual clinical practice.
Context
Fludrocortisone (FC) is the mineralocorticoid (MC) replacement treatment for patients with primary adrenal insufficiency (PAI).
Objective
To explore the dose of FC treatment and its relationship with glucocorticoid therapy, sodium, potassium, renin and clinical parameters.
Setting
Monocentric cohort.
Patients
Data of 193 patients with PAI (130 autoimmune) were collected during baseline (T0), intermediate (T1) and last follow-up visit (T2, respectively, after a mean of 38 and 72 months).
Main outcome measure
Utility of endocrine and clinical parameters to titrate FC dose.
Results
FC dose (50–75 μg/daily) was stable in the follow-up in half patients. The MC activity of FC was dose-dependent: we observed a reduced but significant positive linear correlation between FC dose and sodium (r = 0.132) and negative linear correlation between FC and potassium (r = − 0.162) or renin (r = − 0.131, all p < 0.01). An overall reduction in the FC dose was observed at T2 in the group with longer follow-up (> 60 months, p < 0.05). Higher doses of FC were observed in patients with low-normal renin, especially in autoimmune PAI (86 vs 65 μg/daily, p < 0.05). On the contrary, reduced sodium and increased potassium levels were observed in patients with high renin at T2. The number of cardiovascular events (15 in the whole cohort) was similar in patients sorted by renin levels or FC dose.
Conclusions
Renin and electrolytes can indicate the MC activity of FC treatment: they should be routinely evaluated and used to titrate its dose that can be reduced in the long-term follow-up.
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