Consensus statement on the diagnosis, treatment and follow‐up of patients with primary adrenal insufficiency

Husebye, Eystein S.; Allolio, Bruno; Arlt, Wiebke; Badenhoop, Klaus; Bensing, Sophie; Betterle, Corrado; Falorni, Alberto; Gan, Earn H; Hulting, Anna‐Lena; Kasperlik-Załuska, A; Kämpe, Olle; Løvås, Kristian; Meyer, Gesine; Pearce, Simon H. S.

doi:10.1111/joim.12162

Cited by 339 publications

(312 citation statements)

References 37 publications

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“…Based on studies showing that normal cortisol production rate in humans corresponds to w15-20 mg HC/day (24), prescription of generally lower GC doses is currently recommended (23,25,26,27). The results from our study, together with previous findings showing that high GC doses are associated with increased cardiovascular risk (11), osteoporosis (12,13) and mortality (14), support this approach.…”

Section: Discussionsupporting

confidence: 74%

The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients

Ragnarsson

Mattsson

Monson

et al. 2014

European Journal of Endocrinology

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Objective: Quality of life (QoL) is impaired in hypopituitary patients and patients with primary adrenal insufficiency. The aim of this study was to analyse the impact of glucocorticoid (GC) replacement on QoL. The main hypothesis was that ACTHinsufficient patients experience a dose-dependent deterioration in QoL. Design, patients and methods: This was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database). Data from 2737 adult GH-deficient (GHD) hypopituitary patients were eligible for analysis. Thirty-six per cent were ACTH sufficient and 64% ACTH insufficient receiving a meanGS.D. hydrocortisone equivalent (HCeq) dose of 22.3G8.7 mg (median 20.0). QoL at baseline and 1 year after commencement of GH replacement was assessed by the QoL-assessment of GHD in adults. Results: At baseline, no significant difference in QoL was observed between ACTH-sufficient and -insufficient patients. Increasing HCeq dose was associated with worse QoL. Patients on HCeq %10 mg had the best and patients receiving R25 mg demonstrated the poorest QoL. At 1 year of GH replacement, the improvement in QoL did not differ between ACTH-sufficient and -insufficient patients, and no association was observed between HCeq dose and QoL improvement. Conclusion: Adult hypopituitary patients with untreated GHD receiving GC replacement have similar QoL as ACTH-sufficient patients. Among ACTH-insufficient patients, there is a dose-dependent association between increasing dose and impaired QoL. This association may be explained by supraphysiological GC exposure although it remains plausible that clinicians may have increased GC doses in order to address otherwise unexplained QoL deficits.

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Section: Discussionsupporting

confidence: 74%

The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients

Ragnarsson

Mattsson

Monson

et al. 2014

European Journal of Endocrinology

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“…7 With subsequent tapering of the doses, fludrocortisone should be started in patients with primary adrenal insufficiency, with a dose of 50-200 mg per day sufficient in most patients. 33 …”

Section: Management Of Adrenal Crisismentioning

confidence: 99%

“…46 For physicians who are less familiar with this uncommon condition, it is prudent to listen to patients and their families who often do know best, and in times of uncertainty, heed patients' requests for more hydrocortisone. 47 Increased 33 ‡Ensure patients are given the same "first on the list" priority for scheduled surgery as patients with insulin-dependent diabetes. §Ensure the proposed steroid-cover regime has been agreed by the patient's endocrinologist, with specific assessment of the potential for interactions from any drugs for comorbidities.…”

Section: Emergency Helpmentioning

confidence: 99%

“…One liter of saline 0.9% should be given over the first hour, and further replacement fluids should be guided by frequent hemodynamic monitoring and measurement of serum electrolytes. 7,33 Cortisol replacement can induce water diuresis and suppress antidiuretic hormone (in secondary adrenal insufficiency), which together with sodium replacement can lead to rapid correction of hyponatremia, and osmotic demyelination syndrome. Hence, caution has to be exercised to correct sodium by <10 mEq over the first 24 hours.…”

Section: Management Of Adrenal Crisismentioning

confidence: 99%

See 1 more Smart Citation

Adrenal Crisis: Still a Deadly Event in the 21st Century

Puar

Stikkelbroeck

Smans

et al. 2016

The American Journal of Medicine

144

140

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Adrenal crisis is a life-threatening medical emergency, associated with a high mortality unless it is appropriately recognized and early treatment is rendered. Despite it being a treatable condition for almost 70 years, failure of adequate preventive measures or delayed treatment has often led to unnecessary deaths. Gastrointestinal illness is the most common precipitant for an adrenal crisis. Although most patients are educated about "sick day rules," patients, and physicians too, are often reluctant to increase their glucocorticoid doses or switch to parenteral injections, and thereby fail to avert the rapid deterioration of the patients' condition. Therefore, more can be done to prevent an adrenal crisis, as well as to ensure that adequate acute medical care is instituted after a crisis has occurred. There is generally a paucity of studies on adrenal crisis. Hence, we will review the current literature, while also focusing on the incidence, presentation, treatment, prevention strategies, and latest recommendations in terms of steroid dosing in stress situations.

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“…primary aldosteronism | aldosterone | adrenal | somatic mutations | aldosterone-producing cell cluster P rimary aldosteronism (PA) accounts for 8% of hypertension and is the most common adrenal disease (1)(2)(3)(4). PA patients can be classified into those with aldosterone-producing adenomas (APAs), idiopathic hyperaldosteronism, or familial hyperaldosteronism (FH), which is further divided into FH types 1-3 (FHI-FHIII) (5).…”

mentioning

confidence: 99%

Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands

Nishimoto

Tomlins

Kuick

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

269

273

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Primary aldosteronism (PA) represents the most common cause of secondary hypertension, but little is known regarding its adrenal cellular origins. Recently, aldosterone-producing cell clusters (APCCs) with high expression of aldosterone synthase (CYP11B2) were found in both normal and PA adrenal tissue. PA-causing aldosteroneproducing adenomas (APAs) harbor mutations in genes encoding ion channels/pumps that alter intracellular calcium homeostasis and cause renin-independent aldosterone production through increased CYP11B2 expression. Herein, we hypothesized that APCCs have APArelated aldosterone-stimulating somatic gene mutations. APCCs were studied in 42 normal adrenals from kidney donors. To clarify APCC molecular characteristics, we used microarrays to compare the APCC transcriptome with conventional adrenocortical zones [zona glomerulosa (ZG), zona fasciculata, and zona reticularis]. The APCC transcriptome was most similar to ZG but with an enhanced capacity to produce aldosterone. To determine if APCCs harbored APA-related mutations, we performed targeted next generation sequencing of DNA from 23 APCCs and adjacent normal adrenal tissue isolated from both formalin-fixed, paraffin-embedded, and frozen tissues. Known aldosterone driver mutations were identified in 8 of 23 (35%) APCCs, including mutations in calcium channel, voltage-dependent, L-type, α1D-subunit (CACNA1D; 6 of 23 APCCs) and ATPase, Na + /K + transporting, α1-polypeptide (ATP1A1; 2 of 23 APCCs), which were not observed in the adjacent normal adrenal tissue. Overall, we show three major findings: (i) APCCs are common in normal adrenals, (ii) APCCs harbor somatic mutations known to cause excess aldosterone production, and (iii) the mutation spectrum of aldosteronedriving mutations is different in APCCs from that seen in APA. These results provide molecular support for APCC as a precursor of PA.primary aldosteronism | aldosterone | adrenal | somatic mutations | aldosterone-producing cell cluster P rimary aldosteronism (PA) accounts for 8% of hypertension and is the most common adrenal disease (1-4). PA patients can be classified into those with aldosterone-producing adenomas (APAs), idiopathic hyperaldosteronism, or familial hyperaldosteronism (FH), which is further divided into FH types 1-3 (FHI-FHIII) (5). In 1992, FHI was shown to result from a gene fusion of cytochrome P450, family 11, subfamily B, polypeptide 2 (CYP11B2: aldosterone synthase) and cytochrome P450, family 11, subfamily B, polypeptide 1 (CYP11B1; cortisol synthase) that resulted in zona fasciculata (ZF) expression of CYP11B2 and excess aldosterone production (6). For almost two decades after the original report, no other genetic abnormalities were identified in the other forms of PA.First reported in 2011, exome sequencing identified a series of germ-line and somatic mutations in genes that altered adrenal cell intracellular Ca 2+ in PA. The most common mutations are somatic mutations of the gene encoding the potassium inwardly rectifying channel, subfamily J, member 5 (KCNJ5)...

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Consensus statement on the diagnosis, treatment and follow‐up of patients with primary adrenal insufficiency

Abstract: Abstract. Husebye ES,

Cited by 339 publications

References 37 publications

The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients

The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients

Adrenal Crisis: Still a Deadly Event in the 21st Century

Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands

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