Higher Cortisol Levels Found in Hair of Patients With Adrenal Insufficiency Using Hydrocortisone

Patients on hydrocortisone replacement for adrenal insufficiency appear to have elevated cortisol concentrations in their scalp hair, according to recent findings.

In the cross-sectional study, Nienke R. Biermasz, MD, PhD, of Leiden University Medical Center in the Netherlands, and colleagues evaluated patients treated at the outpatient clinical of the medical center between July 2012 and January 2014. Participants included 132 adults with primary or secondary adrenal insufficiency being treated with hydrocortisone (group 1) and 42 controls with a pituitary disease receiving hydrocortisone (group 2). A third group of 195 healthy controls were also included in the analysis.

The researchers collected locks of roughly 150 hairs cut as close to the scalp as possible. The most proximal 3 cm of hair were used in the analysis to correlate with the most recent 3 months. The researchers extracted cortisol from the hair and used ELISA to measure cortisol concentration.

The researchers found that compared with healthy controls and group 2, group 1 had a higher hair cortisol concentration (P < .001) and hair cortisol concentration was associated with hydrocortisone dose (P = .04).

Male participants in group 1 had higher hair cortisol concentrations compared with women in the group (P < .001).

Compared with healthy controls, group 1 had a higher mean BMI (P < .001) and BMI was associated with hair cortisol concentration in the overall sample. The association between hair cortisol concentration and BMI was especially strong in men.

According to the researchers, further studies are needed to better understand the sex-specific associations between hair cortisol concentrations and hydrocortisone use in this population.

“Intriguingly, this gender effect seems to be specific for hydrocortisone use, since it is not present in controls with an intact [hyptothalamic-pituitary-adrenal axis],” the researchers wrote. “In female patients, higher self-reported hydrocortisone intake was associated with higher [hair cortisol concentration], whereas this association was not found in male patients who demonstrated on average higher [hair cortisol concentration] even in the lower dose range.” – by Jennifer Byrne

Disclosure: The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/online/%7B1d2660eb-3f68-4302-94b2-321f73a4ee89%7D/higher-cortisol-levels-found-in-hair-of-patients-with-adrenal-insufficiency-using-hydrocortisone

Time to Recovery of Adrenal Function After Curative Surgery for Cushing’s Syndrome Depends on Etiology

Address all correspondence and requests for reprints to: Martin Reincke, MD, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstr. 1, D-80336 Munich, Germany. E-mail: .

Successful tumor resection in endogenous Cushing’s syndrome (CS) results in tertiary adrenal insufficiency requiring hydrocortisone replacement therapy.

The aim was to analyze the postsurgical duration of adrenal insufficiency of patients with Cushing’s disease (CD), adrenal CS, and ectopic CS.

We performed a retrospective analysis based on the case records of 230 patients with CS in our tertiary referral center treated from 1983–2014. The mean follow-up time was 8 years.

We included 91 patients of the three subtypes of CS undergoing curative intended surgery and documented followup after excluding cases with persistent disease, pituitary radiation, concurrent adrenostatic or somatostatin analog treatment, and malignant adrenal disease.

The probability of recovering adrenal function within a 5 years followup differed significantly between subtypes (P = .001). It was 82% in ectopic CS, 58% in CD and 38% in adrenal CS. In the total cohort with restored adrenal function (n = 52) the median time to recovery differed between subtypes: 0.6 years (interquartile range [IQR], 0.03–1.1 y) in ectopic CS, 1.4 years (IQR, 0.9–3.4 y) in CD, and 2.5 years (IQR, 1.6–5.4 y) in adrenal CS (P = .002). In CD the Cox proportional-hazards model showed that the probability of recovery was associated with younger age (hazard ratio, 0.896; 95% confidence interval, 0.822–0.976; P = .012), independently of sex, body mass index, duration of symptoms, and basal ACTH and cortisol levels. There was no correlation with length and extend of hypercortisolism or postoperative glucocorticoid replacement doses.

Time to recovery of adrenal function is dependent on the underlying etiology of CS.

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

Diagnosing and Treating Cortisol Excess and Deficiency

From Day 1 of the 16th International Congress of Endocrinology and the Endocrine Society’s 96th Annual Meeting and Expo »

Chicago, IL – June 21, 2014

A phase 2 study of Chronocort®, a modified release formulation of hydrocortisone, in the treatment of adults with classic congenital adrenal hyperplasia

A Mallappa, L-A Daley, N Sinaii, C Van Ryzin, H Huatan, D Digweed, D Eckland, M Whitaker, LK Nieman, RJ Ross, DP Merke

Summary: Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is characterized by cortisol and aldosterone deficiency and androgen excess. Current conventional glucocorticoid therapy is suboptimal as it cannot replace the normal cortisol circadian rhythm and inadequate or inappropriate suppression of adrenal androgens are common. In the preliminary results of a phase 2 study of Chronocort®, a modified release hydrocortisone capsule formulation, researchers found that Chronocort®, a novel modified release hydrocortisone capsule formulation, approximates physiological cortisol secretion, and improves biochemical control of CAH. Further analyses are underway.

Methods:

  • The study objectives were to characterize pharmacokinetics and examine disease control following 6 months dose titration.
  • Serial profiling was obtained at baseline (conventional glucocorticoid) and every 2 months.
  • Twice-daily Chronocort® was initiated: 20 mg at 2300 h, 10 mg at 0700 h.
  • Dose titration was based on clinical status and optimal hormonal ranges (17OHP 300-1200 ng/dL, normal androstenedione (males: 40-150, females: 30-200 ng/dL), with androstenedione prioritized.
  • Chronocort® cortisol pharmacokinetic profile was the primary endpoint.
  • Secondary endpoints included biomarkers of disease control.

Results:

  • A total of 16 adults (8 females; age 29 ±13 years) with classic CAH (12 salt-wasting, 4 simple virilizing) participated.
  • Conventional therapy varied (5 dexamethasone, 7 prednisone, 4 hydrocortisone).
  • Chronocort® cortisol pharmacokinetic profile approximated physiological cortisol secretion.
  • Ten patients required Chronocort® dose adjustments (decrease in 8, increase in 2; mean hydrocortisone equivalent dose conventional vs 6 months: 16.1 ± 6.4 vs 14.7 ± 6.4 mg/m2).
  • Serial androstenedione levels were in the normal range in 8 (50%) of patients on conventional therapy compared with 12 (75%) on Chronocort® at 6 months.
  • The majority of patients on Chronocort® achieved 17O HP levels within the normal range, rather than within the mildly elevated range currently used for management.
  • At 6 months, Chronocort® resulted in lower 24-hr (P=0.02), morning (0700-1500; P=0.008), and afternoon (1500-2300; P=0.03) area-under-the-curve androstenedione compared with conventional therapy.
  • No serious adverse events occurred.
  • Common adverse events were headache, fatigue, early awakening, and anemia.
  • Three patients had unexpected carpal tunnel syndrome, which resolved with wrist splints.

From http://www.mdlinx.com/endocrinology/conference-abstract.cfm/ZZ5BA369FDE9DE4CED82CB6A7CD5BFD1BE/16521/?utm_source=confcoveragenl&utm_medium=newsletter&utm_content=abstract-list&utm_campaign=abstract-ICE/EN2014&nonus=0#

Adrenal Glands

adrenal-glandsAnatomy of the adrenal glands:

Adrenal glands, which are also called suprarenal glands, are small, triangular glands located on top of both kidneys. An adrenal gland is made of two parts: the outer region is called the adrenal cortex and the inner region is called the adrenal medulla.

Function of the adrenal glands:

The adrenal glands work interactively with the hypothalamus and pituitary gland in the following process:

  • the hypothalamus produces corticotropin-releasing hormones, which stimulate the pituitary gland.
  • the pituitary gland, in turn, produces corticotropin hormones, which stimulate the adrenal glands to produce corticosteroid hormones.

Both parts of the adrenal glands — the adrenal cortex and the adrenal medulla — perform very separate functions.

What is the adrenal cortex?

The adrenal cortex, the outer portion of the adrenal gland, secretes hormones that have an effect on the body’s metabolism, on chemicals in the blood, and on certain body characteristics. The adrenal cortex secretes corticosteroids and other hormones directly into the bloodstream. The hormones produced by the adrenal cortex include:

  • corticosteroid hormones
    • hydrocortisone hormone – this hormone, also known as cortisol, controls the body’s use of fats, proteins, and carbohydrates.
    • corticosterone – this hormone, together with hydrocortisone hormones, suppresses inflammatory reactions in the body and also affects the immune system.
  • aldosterone hormone – this hormone inhibits the level of sodium excreted into the urine, maintaining blood volume and blood pressure.
  • androgenic steroids (androgen hormones) – these hormones have minimal effect on the development of male characteristics.

What is the adrenal medulla?

The adrenal medulla, the inner part of the adrenal gland, is not essential to life, but helps a person in coping with physical and emotional stress. The adrenal medulla secretes the following hormones:

  • epinephrine (also called adrenaline) – this hormone increases the heart rate and force of heart contractions, facilitates blood flow to the muscles and brain, causes relaxation of smooth muscles, helps with conversion of glycogen to glucose in the liver, and other activities.
  • norepinephrine (also called noradrenaline) – this hormone has little effect on smooth muscle, metabolic processes, and cardiac output, but has strong vasoconstrictive effects, thus increasing blood pressure.

From: University of Maryland Center for Diabetes and Endocrinology