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Dosing regimens used to administer a total daily dose of 20 mg of hydrocortisone. BID, twice daily; HC, hydrocortisone; QD, once daily; QID, four times daily; TID, three times daily. a Data were available for 412 patients in total. b Two further QD, three further BID regimens and five further TID regimens were used by one patient each.
Source publication
Context and objective:
Treatment for adrenal insufficiency (AI) remains suboptimal. Despite glucocorticoid replacement, patients with AI have reduced life expectancy and quality of life. This study aimed to describe the spectrum of management of glucocorticoid replacement in patients with AI enrolled in the European Adrenal Insufficiency Registry...
Context in source publication
Context 1
... was recorded. Using these data, we examined the variation in how a daily hydrocorti- sone dose of 20 mg was delivered. Twenty-five different regi- mens were being used to deliver a daily dose of 20 mg hydrocortisone; the most common regimen (used by 28Á2% of patients) was 10 mg administered in the morning, 5 mg at mid- day and 5 mg in the evening (Fig. 4). The second most frequent regimen was use of hydrocortisone as a twice-daily regime: 10 mg in the morning and a further 10 mg at midday (18Á0%). The third most common regimen was 10 mg administered in the morning, 5 mg at midday and 5 mg in the afternoon (17Á2%), differing only from the most common regimen by tak- ing the last ...
Citations
... Patients with adrenal insufficiency (AI) despite appropriate steroid hormone replacement therapy [3] are at increased risk of infection, hospitalisation and life-threatening adrenal crises [4,5]. Infections are the most frequent cause of adrenal crises, however emotional and physical stresses are additional recognised precipitants [4,6]. ...
Background
A proportion of patients with adrenal insufficiency (AI) require increases in their maintenance glucocorticoids following the Covid-19 vaccine as a result of vaccine-related symptoms or development of incipient or frank adrenal crisis. In a large cohort of AI patients, we aim to characterise symptoms, changes in glucocorticoid dosage, occurrence of adrenal crises and whether there are differences between the mRNA and adenovirus vector vaccines.
Patients and methods
Patients with AI of any aetiology were invited to complete a short, structured questionnaire of their experience of the Covid-19 vaccination.
Results
279 of the 290 patients enrolled to this study fully completed the questionnaires. 176, 100 and 3 received the Astra Zeneca (AZ), Pfizer-BioNTech (PB) and Moderna (MD) as initial vaccine respectively; and for the second vaccine, 170, 99 and 10 received AZ, PB and MD respectively. Moderate to severe symptoms occurred in 44.8 and 39.7% after the first and second vaccines respectively, were of early onset (6.0 h, IQR 2–12 &. 6.0 h, IQR 2–24 h) and short duration (24 h, IQR 12–72 h & 26 h, IQR 12–72 h). 34.4 and 29.7% increased their maintenance glucocorticoid dose.
Discussion
The Covid-19 vaccines appear well-tolerated in patients with AI, with similar frequency of symptoms to that reported in the background population. The AZ vaccine leads to slightly greater post-vaccination symptom burden and need to increase glucocorticoid dosage, but this does not translate to greater adverse outcomes.
... In PAI, patients need replacement of both glucocorticoids and mineralocorticoids (2,17). The standard medication of glucocorticoid treatment for patients with AI (primary and secondary) is hydrocortisone or cortisone acetate (6,18,19). Patients with primary AI additionally take fludrocortisone treatment for mineralocorticoid deficiency. Unrestricted sodium intake and avoiding salt craving are also parts of the mineralocorticoid substitution therapy. ...
The adrenal glands are small endocrine glands located on top of each kidney, producing hormones regulating important functions in our body like metabolism and stress. There are several underlying causes for adrenal insufficiency, where an autoimmune attack by the immune system is the most common cause. A number of genes are known to confer early onset adrenal disease in monogenic inheritance patterns, usually genetic encoding enzymes of adrenal steroidogenesis. Autoimmune primary adrenal insufficiency is usually a polygenic disease where our information recently has increased due to genome association studies. In this review, we go through the physiology of the adrenals before explaining the different reasons for adrenal insufficiency with a particular focus on autoimmune primary adrenal insufficiency. We will give a clinical overview including diagnosis and current treatment, before giving an overview of the genetic causes including monogenetic reasons for adrenal insufficiency and the polygenic background and inheritance pattern in autoimmune adrenal insufficiency. We will then look at the autoimmune mechanisms underlying autoimmune adrenal insufficiency and how autoantibodies are important for diagnosis. We end with a discussion on how to move the field forward emphasizing on the clinical workup, early identification, and potential targeted treatment of autoimmune PAI.
... Глюкокортикоиды блокируют синтез широкого спектра провоспалительных медиаторов [ 16 ] . Однако при этом глюкокортикоиды подавляют экспрессию белка β1-интегрина на мембране остеобластов, что, в свою очередь, приводит к снижению способности остеобластов прикрепляться к белкам костного матрикса, ослаблению минерализации и, вероятно, к снижению синтеза коллагена 1-го типа [ 17 ] . Кроме того, имеются данные о способности глюкокортикоидов влиять на активность и образование остеокластов. ...
Вероятно, системные гипервоспалительные проявления можно считать общим патогенетическим звеном между COVID-19 и заболеваниями пародонта, взаимно ухудшающим совместное течение двух заболеваний. Цель — изучить направленность изменения пародонтального статуса у больных хроническим генерализованным пародонтитом (ХГП) после перенесенной коронавирусной инфекции и установить влияние лекарственной терапии COVID-19 на течение воспалительных заболеваний пародонта. Материалы и методы. В исследование включены 155 больных ХГП средней и тяжелой степени тяжести после перенесенного COVID-19 и длительностью постковидного этапа 3—6 месяцев (основная группа), а также 89 пациентов с ХГП при отсутствии коронавирусной инфекции в анамнезе (контрольная группа). Все 244 пациента за 6—12 месяцев до обострения ХГП были обследованы стоматологом в рамках стоматологического мониторинга. Результаты. Разработана оптимизированная анкета для сбора информации о пародонтальном статусе больного и об анамнестических особенностях. В основной группе прогредиентное течение установлено в 41,3% случаев, а в контрольной группе — в 18%. Среди больных основной группы с прогрессированием ХГП в 89,1% случаев наблюдали системную воспалительную реакцию в виде «цитокинового шторма», а у больных со стабильным течением ХГП системное повышение IL-6 встречалось в 53,8%. При стабильном течении ХГП применение антибактериальной терапии было чаще по сравнению с пациентами, у которых ХГП прогрессировал (84,6 против 40,6%, p
... Принципы заместительной гормональной терапии (ЗГТ) при НН в разных странах существенно отличаются, наиболее широко используется режим приема гидрокортизона 2-3 раза в день [19]. ...
Adrenal insufficiency (AI) is a life-threatening disease characterized by a decrease in the production of hormones by the adrenal cortex and requires lifelong replacement therapy with glucocorticoids (GCs) and, in some cases, mineralocorticoids (MCs). The number of individuals with primary and secondary AI in Europe is estimated at 20-50 per 100 thousand people, the increase in the number of cases of this disease in the world may be partly due to the rapid increase in the frequency of use of GC in various clinical strategies, including in oncological diseases.
In AI, hormone replacement therapy is vital, but long-term use of GC may be associated with various adverse effects, especially at non-physiological concentrations of GC. This review provides a brief overview of the current therapeutic possibilities of AI hormone therapy, which contributes to the prevention of the development of adrenal crises, as well as promising opportunities for more effective imitation of the physiological profile of cortisol, aimed at preventing the development of undesirable effects of therapy. Several different forms of AI are currently available, differing in profile, duration of action, and route of administration. The most preferred currently in the treatment of AI are GCs with a short half-life, which provides a more manageable action profile and a lower risk of side effects. Promising substitution therapy options include modified-release hydrocortisone preparations, as well as new methods of drug administration using an insulin pump, which will better mimic the physiological effects of endogenous cortisol.
... Despite adequate treatment, patients with AI have an increased mortality risk and report fatigue in addition to reduced quality of life (QoL), questioning the quality of current treatment regimens [2][3][4][5]. Te conventional replacement therapy shows heterogeneity across Europe, but the most frequently used is oral hydrocortisone (OHC) administered twice or thrice daily, with the highest dose administered in the morning [6]. Under normal physiological conditions, the circulating levels of cortisol follow a distinct circadian rhythm with the lowest concentration in the evening and during the night, replaced by rising levels in the early morning. ...
Objective:
Despite appropriate oral glucocorticoid replacement therapy, patients with hypocortisolism often suffer from impaired health and frequent hospitalizations. Continuous subcutaneous hydrocortisone infusion (CSHI) has been developed as an attempt to improve the health status of these patients. The objective of this study was to compare the effects of CSHI to conventional oral treatment on hospitalizations, glucocorticoid doses, and subjective health status. Patients. Nine Danish patients (males: 4 and females: 5) with adrenal insufficiency (AI) were included, with a median age of 48 years, due to Addison (n = 4), congenital adrenal hyperplasia (n = 1), steroid induced secondary adrenal insufficiency (n = 2), morphine induced secondary adrenal insufficiency (n = 1), and Sheehan's syndrome (n = 1). Only patients with severe symptoms of cortisol deficit on oral treatment were selected for CSHI. Their usual oral hydrocortisone doses varied from 25-80 mg per day. The duration of follow-up depended on when the treatment was changed. The first patient started CSHI in 2009 and the last in 2021.
Design:
A retrospective case series comparing hospitalizations and glucocorticoid doses before and after treatment with CSHI. In addition, patients were retrospectively interviewed about their health-related quality of life (HRQoL) after the change of treatment modality.
Results:
Patients significantly reduced their daily dose of glucocorticoids by 16.1 mg (p = 0.02) after changing to CSHI. The number of hospital admission due to adrenal crisis decreased by 1.3 per year on CSHI, which was a 50% reduction (p = 0.04). All patients found it easier to handle an adrenal crisis with CSHI, and almost all patients found it easier to overcome everyday activities and had fewer symptoms of cortisol deficit such as abdominal pain and nausea (7-8 out of 9 patients).
Conclusions:
The change of treatment from conventional oral hydrocortisone to CSHI resulted in a reduced daily dose of glucocorticoids and a reduced number of hospitalizations. Patients reported regain of energy, achievement of better disease control, and better handling of adrenal crisis.
... Thus some of our patients were prescribed unusual doses such as 13mg hydrocortisone, which may afford flexibility to reduce the doses taken by patients. 97.5% of our patients were prescribed glucocorticoid therapy with hydrocortisone as per guidelines, which compares favourably with other studies where this figure ranges from 26.5% in Korea (18) to 87% in the EU-AIR study (24). ...
Objective:
Primary Adrenal Insufficiency (PAI) is a rare disease with an increasing prevalence, which may be complicated by life-threatening adrenal crisis (AC). Good quality epidemiological data remain scarce. We performed a Belgian survey to describe the aetiology, clinical characteristics, treatment regimens, comorbidities and frequency of AC in PAI.
Methods:
A nationwide multicentre study involving 10 major university hospitals in Belgium collected data from adult patients with known PAI.
Results:
200 patients were included in this survey. Median age at diagnosis was 38 years (IQR 25-48) with a higher female prevalence (F/M sex ratio=1.53). Median disease duration was 13 years (IQR 7-25). Autoimmune disease was the most common aetiology (62.5%) followed by bilateral adrenalectomy (23.5%) and genetic variations (8.5%). The majority (96%) of patients were treated with hydrocortisone at a mean daily dose of 24.5±7.0 mg, whereas 87.5% of patients also received fludrocortisone. About one third of patients experienced one or more AC over the follow-up period, giving an incidence of 3.2 crises per 100 patient years. There was no association between the incidence of AC and maintenance dose of hydrocortisone. 27.5% of patients were hypertensive, 17.5% had diabetes and 17.5% had a diagnosis of osteoporosis.
Conclusion:
This study provides the first information on the management of PAI in large clinical centres in Belgium, showing an increased frequency of postsurgical PAI, a nearly normal prevalence of several comorbidities, and an overall good quality of care with a low incidence of adrenal crises, compared with data from other registries.
... The management of AI in the patients in this series were reflective of UK practice. 14,15 All the individuals were on appropriate HC replacement regimens, had undergone regular education as to 'sick day' rules for managing their HC during intercurrent illness and stresses, had IM HC for emergency usage, and had been taught how to administer this. ...
Background:
Patients with adrenal insufficiency (AI) have excess mortality, in part due to the occurrence of life-threatening adrenal crises. Infective processes, including that of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are recognised as the major precipitant of adrenal crises. Adverse reactions to the ChAdOx1 SARS-CoV-2 vaccine occur in a significant proportion of individuals, however, are mild-moderate in the majority of cases.
Design:
Case series.
Patients & Results:
We describe five cases where more severe adverse reactions to the ChAdOx1 SARS-CoV-2 vaccine led to actual or incipient adrenal crises requiring parenteral hydrocortisone within 24 h of receiving the first ChAdOx1 SARS-CoV-2 vaccination.
Conclusion:
In individuals with adrenal insufficiency, adverse reactions to the initial dose of the ChAdOx1 SARS-CoV-2 vaccination can precipitate adrenal crises. We recommend that patients with AI should immediately increase their maintenance glucocorticoid dosage 2–3 fold on experiencing any symptoms in the initial 24 h following vaccination.
... related to cryptorchidism) may cause failure. The need to wear an infusion pump or attend for regular intramuscular injections over many months is clearly a disadvantage, but self-administration of low doses of gonadotrophins subcutaneously may also be successful in both induction of fertility and increase in testicular size (28). When pregnancy is achieved spermatogenesis may occasionally be maintained by testosterone replacement alone although usually continued or repeated gonadotrophin therapy is required. ...
Hypopituitarism is the consequence of diseases or interventions resulting in deficiency of pituitary hormones. Pituitary hormone replacement is one of the most frequent clinical interventions in pituitary disease, yet is rarely been the subject of rigorous scientific evaluation. With the exception of growth hormone, anterior pituitary hormones are replaced with target hormones (sex steroids, cortisol, and thyroxine), in preference to pituitary trophic hormones, as the former have longer half-lives allowing for oral administration. The precise reason for increased morbidity and mortality associated with hypopituitarism is unclear, but underlines the importance of replacing hormones close to physiological patterns. In an era of ‘evidence-based’ medicine, recommendations are frequently based on clinical experience, consensus guidelines, and retrospective reviews rather than on randomized trials. Within these limitations, this chapter will attempt to give a balanced view on current best practice for replacement therapy in adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), and gonadotrophin deficiency.
... Hydrocortisone has a structure identical to endogenous cortisol and is commonly used for replacement (1,2). As hydrocortisone possesses a short duration of action and needs to be taken twice or thrice daily in an attempt to replicate physiology, prednisolone which has a longer duration of action has been recommended as an alternative (3,4). ...
Context
Prednisolone has been recommended rather than hydrocortisone for glucocorticoid replacement in adrenal insufficiency due its longer duration of action and lower cost.
Objective
To determine mortality rates with prednisolone versus hydrocortisone.
Design
Observational study.
Setting
A UK primary care database (Clinical Practice Research Datalink).
Participants
Patients with primary and secondary adrenal insufficiency, treated with either prednisolone or hydrocortisone, and controls individually matched for age, sex, period and place of follow-up.
Interventions
Nil
Outcomes
Mortality relative to individually matched controls.
Results
As expected, mortality in adrenal insufficiency irrespective of cause was increased, based on 5478 patients (4228 on hydrocortisone; 1250 on prednisolone) and 54314 controls (41934 and 12380, respectively). Overall, the adjusted hazard ratio (HR) was similar with the two treatments (prednisolone, 1.76 [95% CI, 1.54-2.01] vs. hydrocortisone 1.69 [1.57-1.82]; p=0.65). This was also the case for secondary adrenal insufficiency. In primary disease (1405 on hydrocortisone vs. 137 on prednisolone:13965 and 1347 controls, respectively), prednisolone-users were older, more likely to have another autoimmune disease and malignancy, and less likely to have mineralocorticoid replacement. Nevertheless, after adjustment, the HR for prednisolone-treated patients remained higher than for those taking hydrocortisone (2.92 [2.19-3.91] vs. 1.90 [1.66-2.16]; p=0.0020).
Conclusions
In primary but not in secondary adrenal insufficiency mortality was higher with prednisolone. The study was large, but the number of prednisolone-treated patients was small, and they had greater risk factors. Nonetheless the increased mortality associated with prednisolone persisted despite statistical adjustment. Further evidence is needed regarding the long-term safety of prednisolone as routine replacement.
... Таким образом, применявшиеся ранее схемы со среднесуточной дозой гидрокортизона более 30 мг избыточны и приводят к хронической передозировке ГК [25]. Однако необходимо отметить, что в настоящее время, в попытке минимизировать риски адреналового криза при всех вариантах НН, а также с целью подавления избыточной секреции надпочечниковых андрогенов при ВДКН в клинической практике нередко назначаются супрафизиологические дозы ГК [26,27]. ...
Adrenal insufficiency (AI) is a syndrome caused by disturbance in the synthesis and secretion of hormones of the adrenal cortex, which ensure the vital activity, energy and water-salt homeostasis. The widest hormonal deficiency is observed in primary hypocorticism, when the synthesis of not only glucocorticoids (GC) and adrenal androgens, but also mineralocorticoids is disrupted. Lifelong replacement therapy with GCs for this pathology may be associated with a risk of bone loss and osteoporosis. However, at present, there are no clear guidelines for diagnosis of bone condition, including and bone mineral density (BMD) monitoring during treatment with GCs in patients with AI. This review summarizes collected data on the key pathogenetic links of glucocorticoid-induced osteoporosis, incidence of decreased BMD and fractures in patients with AI. In this review factors that influence bone metabolism in this cohort of patients are considered: the type and the dose of prescribed GCs, the type (primary, secondary, HH in congenital adrenal cortex dysfunction) and the duration of AI, age, gender, and the presence of concomitant endocrine disorders (hypogonadism, growth hormone (GH) deficiency). In addition, the review presents data on the effect of adrenal androgen replacement therapy and recombinant GH therapy on bone metabolism in secondary AI.
