www.sciencedirect.com Open in urlscan Pro
162.159.136.70  Public Scan

Form analysis
1 forms found in the DOM

GET /search#submit

<form class="QuickSearch" action="/search#submit" method="get" aria-label="form">
  <div class="search-input">
    <div class="search-input-container search-input-container-no-label"><label class="search-input-label u-hide-visually" for="article-quick-search">Search ScienceDirect</label><input type="search" id="article-quick-search" name="qs" value=""
        class="search-input-field" aria-label="Search ScienceDirect" aria-describedby="article-quick-search-description-message" placeholder="Search ScienceDirect"></div>
    <div class="search-input-message-container">
      <div aria-live="polite" class="search-input-validation-error"></div>
      <div id="article-quick-search-description-message"></div>
    </div>
  </div><button type="submit" class="button small u-margin-xs-left button-primary button-icon-only" aria-disabled="false" aria-label="Submit search"><svg focusable="false" viewBox="0 0 100 128" height="20" width="18.75" class="icon icon-search">
      <path
        d="m19.22 76.91c-5.84-5.84-9.05-13.6-9.05-21.85s3.21-16.01 9.05-21.85c5.84-5.83 13.59-9.05 21.85-9.05 8.25 0 16.01 3.22 21.84 9.05 5.84 5.84 9.05 13.6 9.05 21.85s-3.21 16.01-9.05 21.85c-5.83 5.83-13.59 9.05-21.84 9.05-8.26 0-16.01-3.22-21.85-9.05zm80.33 29.6l-26.32-26.32c5.61-7.15 8.68-15.9 8.68-25.13 0-10.91-4.25-21.17-11.96-28.88-7.72-7.71-17.97-11.96-28.88-11.96s-21.17 4.25-28.88 11.96c-7.72 7.71-11.97 17.97-11.97 28.88s4.25 21.17 11.97 28.88c7.71 7.71 17.97 11.96 28.88 11.96 9.23 0 17.98-3.07 25.13-8.68l26.32 26.32 7.03-7.03">
      </path>
    </svg></button><input type="hidden" name="origin" value="article"><input type="hidden" name="zone" value="qSearch">
</form>

Text Content

JavaScript is disabled on your browser. Please enable JavaScript to use all the
features on this page. Skip to main contentSkip to article
ScienceDirect
 * Journals & Books

 * 
 * Search

RegisterSign in

 * Access through your institution
 * Purchase PDF
 * 
 * Patient Access
 * Other access options

Search ScienceDirect



ARTICLE PREVIEW

 * Abstract
 * Introduction
 * Section snippets
 * References (47)
 * Cited by (33)


BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM

Volume 29, Issue 1, January 2015, Pages 17-24


2
MINERALOCORTICOID SUBSTITUTION AND MONITORING IN PRIMARY ADRENAL INSUFFICIENCY

Author links open overlay panelMarcus Quinkler MD (Prof. Dr. med.) a b, Wolgang
Oelkers MD (Prof. Dr. med.) c, Hanna Remde (cand. med.) b, Bruno Allolio MD
(Prof. Dr. med.) d
Show more
Add to Mendeley
Share
Cite
https://doi.org/10.1016/j.beem.2014.08.008Get rights and content



Patients with primary adrenal insufficiency usually show pronounced impairment
of aldosterone secretion and, therefore, require also mineralocorticoid
replacement for full recovery. Clinical signs of mineralocorticoid deficiency
comprise hypotension, weakness, salt craving and electrolyte disturbances
(hyperkalemia, hyponatremia). Mineralocorticoid deficiency is confirmed by
demonstration of profoundly decreased aldosterone and highly elevated plasma
renin activity (PRA). Standard replacement consists of 9α-fluorocortisol
(fludrocortisone) given once daily as a single oral dose (0.05–0.2 mg).
Monitoring of mineralocorticoid replacement consists of clinical assessment
(well-being, physical examination, blood pressure, electrolyte measurements) and
measurement of PRA aiming at a PRA level in the upper normal range. Current
replacement regimens may often be associated with mild hypovolemia. Dose
adjustments are frequently needed in pregnancy to compensate for the
anti-mineralocorticoid activity of progesterone and in high ambient temperature
to avoid sodium depletion. In arterial hypertension a dose reduction is usually
recommended, but monitoring for hyperkalemia is required.


INTRODUCTION

In secondary adrenal insufficiency (SAI), caused by ACTH deficiency, aldosterone
secretion remains largely intact, as it is mainly under the control of the renin
angiotensin system. In contrast, in primary adrenal insufficiency (PAI)
aldosterone secretion is usually severely impaired due to destruction (e.g. by
an autoimmune adrenalitis) or removal (bilateral adrenalectomy) of the zona
glomerulosa. Thus mineralocorticoid replacement is required to compensate for
the loss of aldosterone secretion causing electrolyte imbalance, hypovolemia and
hypotension. Intriguingly, optimal mineralocorticoid replacement has received
little attention in the last two decades, certainly much less than
glucocorticoid substitution. This may indicate that mineralocorticoid
replacement in PAI poses no or little problems for these patients. However, it
is also conceivable that neglecting optimal mineralocorticoid substitution
contributes to the well-known failure to fully restore the quality of life [3],
[11], [19] to normal in these patients.


SECTION SNIPPETS


CLINICAL PRESENTATION AND DIAGNOSIS OF MINERALOCORTICOID DEFICIENCY

Fatigue and loss of energy are mentioned most often in patients with PAI, e.g.
Addison's disease, as well as unspecific symptoms like weight loss, a loss of
appetite, diarrhea, vomiting and nausea [4]. These unspecific symptoms and
complaints quite often lead to the false diagnosis of psychiatric or
gastrointestinal diseases [1]. In a German cohort, the more specific PAI
symptoms like hypotension (55%), hyperpigmentation of patient's skin (41%) and
salt craving (38%) were less frequently


MINERALOCORTICOID SUBSTITUTION

Desoxycorticosterone (DOC), a mineralocorticoid precursor in aldosterone
synthesis, was identified in 1937 [29] and used since 1939 in oil and pellets in
the treatment of Addison's disease [44]. Aldosterone itself is not suitable for
replacement therapy because of its short half-life and rapid hepatic
inactivation after oral ingestion. In 1954
9α-fluor-11β,17α,21-trihydroxy-pregnen-(4)-dion-(3,20), called
9α-fluorohydrocortison or 9α-fluorocortisol or fludrocortisone, was discovered
and


MONITORING OF MINERALOCORTICOID REPLACEMENT

Mineralocorticoid replacement is evaluated clinically by asking the patient
about salt craving or lightheadedness, measuring blood pressure in the supine
and standing positions to assess orthostatic dysregulation, and by identifying
the presence of peripheral edema [21]. General well-being, electrolytes within
the normal range and normal blood pressure without evidence of postural
hypotension indicate adequate mineralocorticoid replacement. Furthermore, a PRA
in the upper normal range has been


PREGNANCY

Progesterone has anti-mineralocorticoid potency in vitro [38] and in vivo [39],
and is competing with aldosterone or 9α-fluorocortisol for binding to the hMR.
During pregnancy progesterone levels steadily increase and the 9α-fluorocortisol
dose may need to be increased depending on blood pressure and potassium levels.
PRA concentrations are not informative during pregnancy due to the pregnancy
induced increase in renin substrate [10]. Oelkers and other investigators
reported increasing


CONFLICT OF INTEREST

None.


ACKNOWLEDGMENTS

None.

Special issue articlesRecommended articles



REFERENCES (47)

 * B. Bleicken et al.
   
   
   DELAYED DIAGNOSIS OF ADRENAL INSUFFICIENCY IS COMMON: A CROSS-SECTIONAL STUDY
   IN 216 PATIENTS
   
   
   AM J MED SCI
   
   (2010 Jun)
 * T.M. Buckley et al.
   
   
   THE ACUTE EFFECTS OF A MINERALOCORTICOID RECEPTOR (MR) AGONIST ON NOCTURNAL
   HYPOTHALAMIC-ADRENAL-PITUITARY (HPA) AXIS ACTIVITY IN HEALTHY CONTROLS
   
   
   PSYCHONEUROENDOCRINOLOGY
   
   (2007 Sep)
 * J. Fried
   
   
   HUNT FOR AN ECONOMICAL SYNTHESIS OF CORTISOL: DISCOVERY OF THE FLUOROSTEROIDS
   AT SQUIBB (A PERSONAL ACCOUNT)
   
   
   STEROIDS
   
   (1992 Aug)
 * U. Keilholz et al.
   
   
   ADVERSE EFFECT OF PHENYTOIN ON MINERALOCORTICOID REPLACEMENT WITH
   FLUDROCORTISONE IN ADRENAL INSUFFICIENCY
   
   
   AM J MED SCI
   
   (1986 Apr)
 * O. Lekarev et al.
   
   
   ADRENAL DISEASE IN PREGNANCY
   
   
   BEST PRACT RES CLIN ENDOCRINOL METAB
   
   (2011 Dec)
 * H.L. Mason et al.
   
   
   CHEMICAL STUDIES OF THE SUPRARENAL CORTEX: III. THE STRUCTURES OF COMPOUNDS
   A, B, AND H
   
   
   J BIOL CHEM
   
   (1937)
 * W.K.H. Oelkers
   
   
   EFFECTS OF ESTROGENS AND PROGESTOGENS ON THE RENIN-ALDOSTERONE SYSTEM AND
   BLOOD PRESSURE
   
   
   STEROIDS
   
   (1996)
 * M. Ribot et al.
   
   
   HUMAN PLASMA QUANTIFICATION OF FLUDROCORTISONE USING LIQUID CHROMATOGRAPHY
   COUPLED WITH ATMOSPHERIC PRESSURE CHEMICAL IONIZATION MASS SPECTROMETRY AFTER
   LOW-DOSAGE ADMINISTRATION
   
   
   CLIN CHIM ACTA
   
   (2013 May)
 * S.J. Smith et al.
   
   
   EVIDENCE THAT PATIENTS WITH ADDISON'S DISEASE ARE UNDERTREATED WITH
   FLUDROCORTISONE
   
   
   LANCET
   
   (1984 Jan 7)
 * J.R. Stockigt et al.
   
   
   RENIN AND RENIN SUBSTRATE IN PRIMARY ADRENAL INSUFFICIENCY: CONTRASTING
   EFFECTS OF GLUCOCORTICOID AND MINERALOCORTICOID DEFICIENCY
   
   
   AM J MED
   
   (1979 Jun)

B. Allolio et al.


ADDISONIAN CRISIS IN A YOUNG MAN WITH ATYPICAL ANOREXIA NERVOSA


NAT REV ENDOCRINOL

(2011 Feb)
S. Bird


FAILURE TO DIAGNOSE: ADDISON DISEASE


AUST FAM PHYSICIAN

(2007 Oct)
B. Bleicken et al.


IMPAIRED SUBJECTIVE HEALTH STATUS IN CHRONIC ADRENAL INSUFFICIENCY: IMPACT OF
DIFFERENT GLUCOCORTICOID REPLACEMENT REGIMENS


EUR J ENDOCRINOL

(2008 Dec)
J.H. Brown et al.


IN VITRO METABOLISM OF SUBSTITUTED STEROIDS BY RAT LIVER


ENDOCRINOLOGY

(1958 Feb)
E. Charmandari et al.


ADRENAL INSUFFICIENCY


LANCET

(2014 Feb 3)
N. Cohen et al.


ATRIAL NATRIURETIC PEPTIDE AND PLASMA RENIN LEVELS IN ASSESSMENT OF
MINERALOCORTICOID REPLACEMENT IN ADDISON'S DISEASE


J CLIN ENDOCRINOL METAB

(1996 Apr)
C. Cosimo et al.


ADDISON'S DISEASE AND PREGNANCY: CASE REPORT


J PRENAT MED

(2009 Oct)
S. Diederich et al.


THERAPIE DER NEBENNIERENRINDENINSUFFIZIENZ


DTSCH MED WOCHENSCHR

(1994)
M.M. Erichsen et al.


CLINICAL, IMMUNOLOGICAL, AND GENETIC FEATURES OF AUTOIMMUNE PRIMARY ADRENAL
INSUFFICIENCY: OBSERVATIONS FROM A NORWEGIAN REGISTRY


J CLIN ENDOCRINOL METAB

(2009 Dec)
T.M. Flad et al.


THE ROLE OF PLASMA RENIN ACTIVITY IN EVALUATING THE ADEQUACY OF
MINERALOCORTICOID REPLACEMENT IN PRIMARY ADRENAL INSUFFICIENCY


CLIN ENDOCRINOL (OXF)

(1996 Nov)
J. Fried


BIOLOGICAL EFFECTS OF 9-ALPHA-FLUOROHYDROCORTISONE AND RELATED HALOGENATED
STEROIDS IN ANIMALS


ANN N Y ACAD SCI

(1955 May 27)
D.B. Grant et al.


CONGENITAL ADRENAL HYPERPLASIA: RENIN AND STEROID VALUES DURING TREATMENT


EUR J PEDIATR

(1977 Aug 23)
K.D. Griffiths et al.


PLASMA RENIN ACTIVITY IN THE MANAGEMENT OF CONGENITAL ADRENAL HYPERPLASIA


ARCH DIS CHILD

(1984 Apr)
View more references


CITED BY (33)


 * DRUG-INDUCED ENDOCRINE BLOOD PRESSURE ELEVATION
   
   2020, Pharmacological Research
   Citation Excerpt :
   
   Direct stimulation of the MR as is the case for aldosterone, results in
   increased renal sodium retention and potassium excretion, causing hypokalemia
   and hypernatremia, volume expansion and increased blood pressure. The
   synthetic mineralocorticoid fludrocortisone (also known as 9α-fluorocortisol)
   is used, usually in combination with a GR agonist, as replacement therapy in
   adrenal insufficiency, particularly in patients suffering from Addison’s
   disease [132]. The potency of fludrocortisone to activate MR is 200–400 times
   greater than that of cortisol, although both steroids exhibit similar
   receptor biding affinities [133–136].
   
   Show abstract
   
   Patients with uncontrolled hypertension are at risk for cardiovascular
   complications. The majority of them suffers from unidentified forms of
   hypertension and a fraction has so-called secondary hypertension with an
   identifiable cause. The patient’s medications, its use of certain herbal
   supplements and over-the-counter agents represent potential causal factors
   for secondary hypertension that are often overlooked. The current review
   focuses on drugs that are likely to elevate blood pressure by affecting the
   human endocrine system at the level of steroid synthesis or metabolism,
   mineralocorticoid receptor activity, or by affecting the catecholaminergic
   system. Drugs with known adverse effects but where benefits outweigh their
   risks, drug candidates and market withdrawals are reviewed. Finally,
   potential therapeutic strategies are discussed.


 * ADRENAL INSUFFICIENCY OF THE ADULT
   
   2016, Revue de Medecine Interne
   Show abstract
   
   L’insuffisance surrénalienne est une pathologie rare et potentiellement
   mortelle en l’absence de traitement. Les symptômes associent une asthénie, un
   amaigrissement, des troubles digestifs et, dans l’insuffisance surrénalienne
   primitive, une mélanodermie qui est le seul signe spécifique. Le diagnostic,
   compte tenu de la rareté de cette pathologie et de l’absence de spécificité
   de ses signes cliniques, peut être retardé et porté à l’occasion d’une
   insuffisance surrénalienne aiguë qui en fait toute la gravité. L’étiologie
   peut être primitive (maladie d’Addison), principalement d’origine
   auto-immune, ou centrale, secondaire à l’arrêt d’une corticothérapie
   prolongée ou plus rarement à une pathologie hypothalamo-hypophysaire. Les
   doses et l’adaptation du traitement substitutif sont maintenant bien
   codifiées. L’éducation thérapeutique du patient joue un rôle majeur dans
   cette pathologie chronique dont le risque de décompensation aiguë reste
   cependant à l’heure actuelle encore élevé.
   
   Adrenal insufficiency is a rare but life-threatening disorder. Clinical
   manifestations include fatigue, weight loss, gastrointestinal manifestations
   and skin hyperpigmentation, the latter being specific of primary adrenal
   failure. Because of non-specific clinical features of this rare disorder,
   diagnosis can be delayed and adrenal failure be revealed by an acute crisis.
   Adrenal insufficiency can be primary (Addison disease), most frequently
   autoimmune, or secondary, resulting from long term administration of
   exogenous glucocorticoids or more rarely from pituitary disorders. Monitoring
   of substitutive treatment is now well codified. Patient education is very
   important in this chronic disease that remains associated with a persistent
   high risk of adrenal crisis.


 * CLINICAL APPROACH TO ADRENAL INSUFFICIENCY
   
   2024, Postgraduate Medical Journal of Ghana
   
   


 * NOVEL AGENTS TO TREAT ADRENAL INSUFFICIENCY: FINDINGS OF PRECLINICAL AND
   EARLY CLINICAL TRIALS
   
   2024, Expert Opinion on Investigational Drugs
   
   


 * EXTENSIVE EXPERTISE IN ENDOCRINOLOGY: ADRENAL CRISIS IN ASSISTED REPRODUCTION
   AND PREGNANCY
   
   2024, European Journal of Endocrinology
   
   


 * TRANSPLANTATION OF PORCINE ADRENAL SPHEROIDS FOR THE TREATMENT OF ADRENAL
   INSUFFICIENCY
   
   2023, Xenotransplantation
   
   

View all citing articles on Scopus

View full text
Copyright © 2014 Elsevier Ltd. All rights reserved.


SUBSTANCES (1)

Generated by , an expert-curated chemistry database.
 1. 


PART OF SPECIAL ISSUE

Hormone replacement strategies in adult endocrine disease
Edited by
Bruno Allolio


OTHER ARTICLES FROM THIS ISSUE


 * OPTIMAL GLUCOCORTICOID REPLACEMENT IN ADRENAL INSUFFICIENCY
   
   January 2015
   Marianne Øksnes, …, Kristian Løvås
   


 * IS DHEA REPLACEMENT BENEFICIAL IN CHRONIC ADRENAL FAILURE?
   
   January 2015
   Katharina Lang, …, Stefanie Hahner
   


 * SUBSTITUTION THERAPY IN ADULT PATIENTS WITH CONGENITAL ADRENAL HYPERPLASIA
   
   January 2015
   Nicole Reisch
   

View more articles


RECOMMENDED ARTICLES


 * ADHERENCE TO GROWTH HORMONE THERAPY: RESULTS OF A MULTICENTER STUDY
   
   Endocrine Practice, Volume 20, Issue 1, 2014, pp. 46-51
   Banu Küçükemre Aydın, …, Feyza Darendeliler
   


 * SUGAR INTAKE: LOWERING THE BAR
   
   The Lancet Diabetes & Endocrinology, Volume 3, Issue 5, 2015, p. 305
   The Lancet Diabetes & Endocrinology
   


 * THE ROLE OF PASIREOTIDE IN THE TREATMENT OF ACROMEGALY
   
   The Lancet Diabetes & Endocrinology, Volume 2, Issue 11, 2014, pp. 855-856
   Nicholas A Tritos
   


 * IATROGENIC PSEUDOPHEOCHROMOCYTOMA
   
   Annales d'Endocrinologie, Volume 84, Issue 3, 2023, p. 398
   Antoine-Guy Lopez, Hervé Lefebvre
   


 * TREATMENT OF PRIMARY ALDOSTERONISM: CLINICAL PRACTICE GUIDELINES OF THE
   TAIWAN SOCIETY OF ALDOSTERONISM
   
   Journal of the Formosan Medical Association, Volume 123, Supplement 2, 2024,
   pp. S125-S134
   Chi-Shin Tseng, …, Jeff S. Chueh
   


 * DIAGNOSIS AND MANAGEMENT OF ADRENAL INSUFFICIENCY
   
   The Lancet Diabetes & Endocrinology, Volume 3, Issue 3, 2015, pp. 216-226
   Irina Bancos, …, Wiebke Arlt
   

Show 3 more articles


ARTICLE METRICS

Citations
 * Citation Indexes: 33

Captures
 * Readers: 70


View details
 * About ScienceDirect
 * Remote access
 * Shopping cart
 * Advertise
 * Contact and support
 * Terms and conditions
 * Privacy policy

Cookies are used by this site. Cookie Settings

All content on this site: Copyright © 2024 Elsevier B.V., its licensors, and
contributors. All rights are reserved, including those for text and data mining,
AI training, and similar technologies. For all open access content, the Creative
Commons licensing terms apply.






We use cookies that are necessary to make our site work. We may also use
additional cookies to analyze, improve, and personalize our content and your
digital experience. For more information, see ourCookie Policy
Cookie Settings Accept all cookies



COOKIE PREFERENCE CENTER

We use cookies which are necessary to make our site work. We may also use
additional cookies to analyse, improve and personalise our content and your
digital experience. For more information, see our Cookie Policy and the list of
Google Ad-Tech Vendors.

You may choose not to allow some types of cookies. However, blocking some types
may impact your experience of our site and the services we are able to offer.
See the different category headings below to find out more or change your
settings.

Allow all


MANAGE CONSENT PREFERENCES

STRICTLY NECESSARY COOKIES

Always active

These cookies are necessary for the website to function and cannot be switched
off in our systems. They are usually only set in response to actions made by you
which amount to a request for services, such as setting your privacy
preferences, logging in or filling in forms. You can set your browser to block
or alert you about these cookies, but some parts of the site will not then work.
These cookies do not store any personally identifiable information.



Cookie Details List‎

FUNCTIONAL COOKIES

Functional Cookies

These cookies enable the website to provide enhanced functionality and
personalisation. They may be set by us or by third party providers whose
services we have added to our pages. If you do not allow these cookies then some
or all of these services may not function properly.

Cookie Details List‎

PERFORMANCE COOKIES

Performance Cookies

These cookies allow us to count visits and traffic sources so we can measure and
improve the performance of our site. They help us to know which pages are the
most and least popular and see how visitors move around the site.

Cookie Details List‎

TARGETING COOKIES

Targeting Cookies

These cookies may be set through our site by our advertising partners. They may
be used by those companies to build a profile of your interests and show you
relevant adverts on other sites. If you do not allow these cookies, you will
experience less targeted advertising.

Cookie Details List‎
Back Button


COOKIE LIST



Search Icon
Filter Icon

Clear
checkbox label label
Apply Cancel
Consent Leg.Interest
checkbox label label
checkbox label label
checkbox label label

Confirm my choices