Safety of DR-HC for adrenal insufficiency

Conventional treatment of adrenal insufficiency involves cortisol replacement therapy with twice- or thrice-daily oral hydrocortisone. Recently dual-release hydrocortisone (DR-HC) administered once daily to provide high levels of cortisol during the morning, followed by a gradual decrease throughout the day is being used. This results in considerably lower cortisol exposure during the afternoon and evening compared with immediate-release thrice-daily hydrocortisone, thereby mimicking normal cortisol secretion more closely than conventional therapy.

Nilsson et al. conducted a study to evaluate the long-term safety of DR-HC and whether the difference in the incidence of adverse events persisted over time and if it was related to different levels of exposure to cortisol. They conducted a randomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden. The results of the study of the newly developed DR-HC showed that long-term maintenance treatment and rescue therapy was well tolerated up to 27 months of continuous treatment.

Read full article titled ‘Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency’ by Nilsson et al., European Journal of Endocrinology 171 pp 369 – 377, DOI: 10.1530/EJE-14-0327

Cushing’s Awareness Challenge, Day 4

Another idea I borrowed from Robin – using a Wordle as inspiration for today’s post.
Even though I’m “in remission” since 1987, I’m still way too fatigued, napping every afternoon for several hours.  People think I should be normal since my pituitary surgery was so long ago.  Well, no.
me-tired
Just a few days ago, I posted this abstract on Severe fatigue in patients with adrenal insufficiency.  I don’t think that they needed to do this study at all.  Just ask any Cushie!

Abstract

BACKGROUND:

Fatigue is a frequently experienced complaint in patients with adrenal insufficiency (AI) and may be influenced by cortisol levels.

AIM:

The objective of this study was to determine the prevalence of severe fatigue in adrenal insufficiency (AI) patients, to assess which dimensions contribute to fatigue severity and to determine the association between salivary cortisol levels and momentary fatigue.

SUBJECTS AND METHODS:

We performed a cross-sectional study in the outpatient department of a university hospital. Included were 27 patients with congenital adrenal hyperplasia (CAH), 26 patients with primary AI (PAI), 24 patients with secondary AI (SAI) and 31 patients with adrenal insufficiency after treatment for Cushing’s syndrome (Cush-AI). Measurements included computerised questionnaires to determine fatigue severity and physical and psychosocial contributors. Patients took four saliva samples at home, in which cortisol levels were measured.

RESULTS:

Severe fatigue was experienced by 41 % of the CAH patients, 42 % of the PAI patients, 50 % of the SAI patients and 42 % of the Cush-AI patients. Psychological distress, functional impairment, sleep disturbance, physical activity, concentration problems and social functioning contributed to the subjective experience of fatigue. Salivary cortisol levels were not correlated with momentary fatigue.

CONCLUSIONS:

A considerable proportion of AI patients experience severe fatigue. Salivary cortisol level is not a significant predictor for momentary fatigue in AI patients.

PMID:
24615365
[PubMed – in process]

From http://www.ncbi.nlm.nih.gov/pubmed/24615365

 

Back to my nap now…

maryo colorful zebra

Severe fatigue in patients with adrenal insufficiency: physical, psychosocial and endocrine determinants

Abstract

BACKGROUND:

Fatigue is a frequently experienced complaint in patients with adrenal insufficiency (AI) and may be influenced by cortisol levels.

AIM:

The objective of this study was to determine the prevalence of severe fatigue in adrenal insufficiency (AI) patients, to assess which dimensions contribute to fatigue severity and to determine the association between salivary cortisol levels and momentary fatigue.

SUBJECTS AND METHODS:

We performed a cross-sectional study in the outpatient department of a university hospital. Included were 27 patients with congenital adrenal hyperplasia (CAH), 26 patients with primary AI (PAI), 24 patients with secondary AI (SAI) and 31 patients with adrenal insufficiency after treatment for Cushing’s syndrome (Cush-AI). Measurements included computerised questionnaires to determine fatigue severity and physical and psychosocial contributors. Patients took four saliva samples at home, in which cortisol levels were measured.

RESULTS:

Severe fatigue was experienced by 41 % of the CAH patients, 42 % of the PAI patients, 50 % of the SAI patients and 42 % of the Cush-AI patients. Psychological distress, functional impairment, sleep disturbance, physical activity, concentration problems and social functioning contributed to the subjective experience of fatigue. Salivary cortisol levels were not correlated with momentary fatigue.

CONCLUSIONS:

A considerable proportion of AI patients experience severe fatigue. Salivary cortisol level is not a significant predictor for momentary fatigue in AI patients.

PMID:
24615365
[PubMed – in process]

From http://www.ncbi.nlm.nih.gov/pubmed/24615365

Perspectives on the management of adrenal insufficiency

Source

Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Headington, Oxford OX3 7EJ, UK.

Abstract

BACKGROUND:

Conventional glucocorticoid (GC) replacement for patients with adrenal insufficiency (AI) is inadequate. Patients with AI continue to have increased mortality and morbidity and compromised quality of life despite treatment and monitoring.

OBJECTIVES:

i) To review current management of AI and the unmet medical need based on literature and treatment experience and ii) to offer practical advice for managing AI in specific clinical situations.

METHODS:

The review considers the most urgent questions endocrinologists face in managing AI and presents generalised patient cases with suggested strategies for treatment.

RESULTS:

Optimisation and individualisation of GC replacement remain a challenge because available therapies do not mimic physiological cortisol patterns. While increased mortality and morbidity appear related to inadequate GC replacement, there are no objective measures to guide dose selection and optimisation. Physicians must rely on experience to recognise the clinical signs, which are not unique to AI, of inadequate treatment. The increased demand for corticosteroids during periods of stress can result in a life-threatening adrenal crisis (AC) in a patient with AI. Education is paramount for patients and their caregivers to anticipate, recognise and provide proper early treatment to prevent or reduce the occurrence of ACs.

CONCLUSIONS:

This review highlights and offers suggestions to address the challenges endocrinologists encounter in treating patients with AI. New preparations are being developed to better mimic normal physiological cortisol levels with convenient, once-daily dosing which may improve treatment outcomes.

PMID:
24031090
[PubMed – in process] 
PMCID:
PMC3805018
 [Available on 2013/12/1]

From http://www.mdlinx.com/endocrinology/newsl-article.cfm/4829245/ZZ4747461521296427210947/?news_id=2364&newsdt=110713&subspec_id=1509&utm_source=Focus-On&utm_medium=newsletter&utm_content=Top-New-Article&utm_campaign=article-section

Hyperthyroidism due to thyroid stimulating hormone secretion after surgery for Cushing’s syndrome: A novel cause of the syndrome of inappropriate secretion of thyroid stimulating hormone

Overview of the thyroid system (See Wikipedia:...

Overview of the thyroid system (See Wikipedia:Thyroid). To discuss image, please see Talk:Human body diagrams (Photo credit: Wikipedia)

  1. Daisuke Tamada, MD1,
  2. Toshiharu Onodera, MD1,
  3. Tetsuhiro Kitamura, MD, PhD1,
  4. Yuichi Yamamoto, MD1,
  5. Yoshitaka Hayashi, MD, PhD2,
  6. Yoshiharu Murata, MD, PhD2,
  7. Michio Otsuki, MD, PhD1 and
  8. Iichiro Shimomura, MD, PhD1

Author Affiliations


  1. 1Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan

  2. 2Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
  1. Address all correspondence and requests for reprints to: Michio Otsuki, MD, PhD, Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2–2 Yamada-oka, Suita, Osaka 565-0871, Japan, Telephone: +81-6-6879-3732. Fax: +81-6-6879-3739, E-mail: otsuki@endmet.med.osaka-u.ac.jp.

Abstract

Context: Hyperthyroidism with the syndrome of inappropriate secretion of thyroid stimulating hormone (TSH) (SITSH) occurred by a decrease in hydrocortisone dose after surgery for Cushing’s syndrome. This is a novel cause of SITSH.

Objective: The aim of this study was to describe and discuss the two cases of SITSH patients who were found after surgery for Cushing’s syndrome. We also checked whether SITSH occurred in the consecutive 7 patients with Cushing’s syndrome after surgery.

Patients and Methods: A 45-year-old Japanese woman with adrenocorticotropin (ACTH)-independent Cushing’s syndrome and a 37-year-old Japanese man with ACTH-dependent Cushing’s syndrome presented SITSH caused by insufficient replacement of hydrocortisone for postoperative adrenal insufficiency. When the dose of hydrocortisone was reduced to less than 20 mg/day within 18 days after operation, SITSH occurred in both cases. We examined whether the change of the hydrocortisone dose induced the secretion of TSH. Free T3 and TSH were normalized by the hydrocortisone dose increase of 30 mg/day and these were elevated by the dose decrease of 10 mg/day. We also checked TSH and thyroid hormone the consecutive 7 patients with Cushing’s syndrome after surgery. Six (66.6 %) of nine patients showed SITSH.

Conclusions: This is the first report that insufficient replacement of hydrocortisone after the surgery of Cushing’s syndrome caused SITSH. Hyperthyroidism by SITSH as well as adrenal insufficiency can contribute to withdrawal symptoms of hydrocortisone replacement. So we need to consider the possibility of SITSH for the pathological evaluation of withdrawal syndrome of hydrocortisone replacement.

  • Received May 4, 2013.
  • Accepted May 8, 2013.
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