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Cortisol Pills can cure Arachnophobia by Peter Warmingham

According to a recent report in the Daily Mail, tests in Switzerland have shown that a two-week course of a cortisol-based pill can help people halve their fears of spiders.  Researchers at the University of Zurich believe that with further treatment plus counselling, people could overcome their fears of spiders completely.

The researchers looked at the effects of Cortisol on twenty men and women who were afraid of spiders. Half of them were given cortisol tablets and the rest took dummy pills.  They were then forced to look at a colour photograph of a large spider and asked to gauge how scared they were on a scale of one to ten while researchers noted if they were sweating or trembling.  The procedure was repeated six times over the course of two weeks.

Those taking the cortisol were noticeably less fearful than the others and by the fourth treatment their fear levels had dropped by 45%.  The effects were also lasting, with the volunteers still feeling brave two days after their last cortisol pill.
A second experiment on volunteers with a fear of public speaking had a similar result.

The researchers believe that cortisol, by cutting the blood flow to the part of the brain that retrieves memories, leaves people unable to remember their phobia.  The hormone is also thought to boost the formation of new memories so that people treated with it store information about their newfound bravery over images of their previous fear.

Dr Cosmo Hallstrom, a fellow of the Royal College of Psychiatrists and a Phobia Expert, said “Cortisol is the hormone released during stress, so this suggests that giving lots of cortisol can reduce the impact of stress.  A lot of people are tormented by fear and their lives are ruined by it.  But cortisol is a powerful drug.  One has to be careful that the treatment is not as bad as the condition”.

On reflection, it seems somewhat ironic that cortisol should be offered to healthy people to overcome irrational fears but not to sick people suffering from both thyroid and adrenal insufficiency who desperately need it to regain their health.  But then, people who maintain that they continue to have symptoms after their blood tests come back normal are, as we know, all too often referred to a psychologist.  The best way of obtaining treatment for adrenal insufficiency may perhaps be to convince your doctor that you have a life-ruining phobia of some kind!

Eur J Pharmacol. 2008 Apr 7;583(2-3):365-71. Epub 2008 Jan 24.
Glucocorticoids for the treatment of post-traumatic stress disorder and phobias: a novel therapeutic approach.

de Quervain DJ, Margraf J.

Division of Psychiatry Research, University of Zürich, Lenggstr. 31, 8032 Zürich, Switzerland. quervain@bli.unizh.ch



Comparison of the Low Dose Short Synacthen Test (1µg), the Conventional Dose Short Synacthen Test (250µg), and the Insulin Tolerance Test for Assessment of the Hypothalamo-Pituitary-Adrenal Axis in Patients with Pituitary Disease

T.A.M. Abdu, T.A. Elhadd, R. Neary and R.N. Clayton
Department of Endocrinology, North Staffordshire Hospitals, and School of Postgraduate Medicine, Keele University, Stoke on Trent, United Kingdom.
J Clin Endocrinol Metab. 1999 Mar;84(3):838-43


The researchers of this study stated that, “There is still uncertainty about what is the most appropriate test for assessment of the integrity of the hypothalamo-pituitary-adrenal (HPA) axis. Many advocate the insulin tolerance test (ITT), but this is unpleasant and resource intensive, and may occasionally give misleading results.  The conventional 250 µg tetracosactrin, ACTH-(1-24) short synacthen test (SST) has been used as a simple alternative to the ITT, but it has produced some falsely reassuring results with potentially serious consequences.”  They tell us that the low dose short synacthen test using 1µg tetracosactrin has been thought of as a more reliable and safer alternative to ITT.

They studied 64 patients with suspected or proven pituitary disease.  All the patients had both the short synacthen test and the insulin tolerance test. 42 patients underwent the insulin tolerance test alone. 

They found that the Low Dose Short Synacthen Test was 100% correct with no falsely reassuring results, the short synacthen test produced 2 false results and the insulin tolerance test produced 1 false result.

They suggested that although the short synacthen test and the insulin tolerance test were “sufficient for the purpose of clinical decision making with regard to steroid replacement therapy in patients with pituitary disease” the low dose short synacthen test should replace the short synacthen test and the insulin tolerance test for initial diagnosis of pituitary disease.

They suggested the use of 1µg tetracosactrin, iv, with sampling at 0, 20 and 30 minutes.

Lyn Mynott: The Society for Endocrinology has informed one of our members that should an ACTH test result be "normal" and the patient still has symptoms of adrenal insufficiency, then more "dynamic" testing should take place, such as an insulin stress test or the glucagon stimulation test, as some patients have been found to be severely deficient.

Shortcomings in the Low-Dose (1 μg) ACTH Test for the Diagnosis of ACTH Deficiency States

David H. P. Streeten
Professor Emeritus of Medicine SUNY Health Science Center Syracuse, New York 13210

March 1999

Severe and long-standing hypocortisolism may result from primary or secondary adrenocortical failure to secrete sufficient cortisol to sustain normal health either in the absence or in the presence of stress. In patients with primarily adrenal failure the diagnosis can be made reliably, quickly, and relatively inexpensively by measurement of the serum cortisol response to a single injection (250 μg) of ACTH1–24 (cosyntropin, tetracosatrin, Cortrosyn (Organon, W. Orange, NJ), or Synacthen (Novartis, Basel, Switzerland): all identical products), administered either i.v. or i.m. as an out-patient procedure. This diagnosis can even be made in many patients by measuring plasma concentrations of endogenous adrenocorticotropin (ACTH) and cortisol in a single blood sample (1). There is also no doubt that profound ACTH deficiency that has been present for more than a few weeks will, by causing severe adrenocortical atrophy or impairment of cortisol secretion, almost always result in a subnormal response in serum cortisol concentration to the "short ACTH test" (2).

However, it has been recognized for several years that, in some patients who had adrenal insufficiency secondary to hypothalamic or pituitary failure, the normal result of the short ACTH test with 250μ g did not necessarily indicate normal function of the entire hypothalamic-pituitary-adrenal (HPA) system.

Full text of this article:

Lyn Mynott: The Society for Endocrinology has informed one of our members that should an ACTH test result be "normal" and the patient still has symptoms of adrenal insufficiency, then more "dynamic" testing should take place, such as an insulin stress test or the glucagon stimulation test, as some patients have been found to be severely deficient.


Diagnosis of Adrenal Insufficiency

Richard I. Dorin, MD; Clifford R. Qualls, PhD; and Lawrence M. Crapo, MD, PhD
August 5, 2003
vol. 139 no. 3 194-204


Background: The cosyntropin stimulation test is the initial endocrine evaluation of suspected primary or secondary adrenal insufficiency.

Purpose: To critically review the utility of the cosyntropin stimulation test for evaluating adrenal insufficiency.

Data Sources: The MEDLINE database was searched from 1966 to 2002 for all English-language papers related to the diagnosis of adrenal insufficiency.

Study Selection: Studies with fewer than 5 persons with primary or secondary adrenal insufficiency or with fewer than 10 persons as normal controls were excluded. For secondary adrenal insufficiency, only studies that stratified participants by integrated tests of adrenal function were included.

Data Extraction: Summary receiver-operating characteristic (ROC) curves were generated from all studies that provided sensitivity and specificity data for 250-µg and 1-µg cosyntropin tests; these curves were then compared by using area under the curve (AUC) methods. All estimated values are given with 95% CIs.

Data Synthesis: At a specificity of 95%, sensitivities were 97%, 57%, and 61% for summary ROC curves in tests for primary adrenal insufficiency (250-µg cosyntropin test), secondary adrenal insufficiency (250-µg cosyntropin test), and secondary adrenal insufficiency (1-µg cosyntropin test), respectively. The area under the curve for primary adrenal insufficiency was significantly greater than the AUC for secondary adrenal insufficiency for the high-dose cosyntropin test (P < 0.001), but AUCs for the 250-µg and 1-µg cosyntropin tests did not differ significantly (P > 0.5) for secondary adrenal insufficiency. At a specificity of 95%, summary ROC analysis for the 250-µg cosyntropin test yielded a positive likelihood ratio of 11.5 (95% CI, 8.7 to 14.2) and a negative likelihood ratio of 0.45 (CI, 0.30 to 0.60) for the diagnosis of secondary adrenal insufficiency.

Conclusions: Cortisol response to cosyntropin varies considerably among healthy persons. The cosyntropin test performs well in patients with primary adrenal insufficiency, but the lower sensitivity in patients with secondary adrenal insufficiency necessitates use of tests involving stimulation of the hypothalamus if the pretest probability is sufficiently high. The operating characteristics of the 250-µg and 1-µg cosyntropin tests are similar.


Lyn Mynott: The Society for Endocrinology has informed one of our members that should an ACTH test result be "normal" and the patient still has symptoms of adrenal insufficiency, then more "dynamic" testing should take place, such as an insulin stress test or the glucagon stimulation test, as some patients have been found to be severely deficient.



Chronic Stress at work and the metabolic syndrome: prospective study

BMJ,doi:10.1136/bmj.38693.435301.80 (pub 20 Jan 2006) Tarani Chandola, Eric Brunner, Michael Marmot

What is metabolic syndrome?

Metabolic syndrome (also called syndrome X) is a group of risk factors for heart disease. Many people who have type 2 Diabetes also have metabolic syndrome. The website www.familydoctor.org states, “You have metabolic syndrome if at least three of the following are true:

  • You are overweight or obese and you carry the weight around your middle. For men, this means waist greater than 40 inches . For women, it means a waist measures greater than 35 inches .
  • You have high blood pressure (130/85 mm Hg or greater).
  • You have high amount of sugar in your blood (a fasting blood sugar of 110 mg/dL or greater).
  • You have a high amount of fat in your blood (a level of 150 mg/dL or greater). You have low HDL cholesterol (the "good" cholesterol). For men, this an HDL level less than 40 mg/dL; for women, less than 50 mg/dL.
  • The more of these risk factors you have, the higher your risk of heart disease. Even if your cholesterol level is normal, you still may be at risk for a heart attack or stroke.” 1

Why do people develop metabolic syndrome?

A Suffolk diabetes group tells us, “This is probably due to a combination of genetic predisposition and lifestyle factors. The mechanisms surrounding this condition are complex, though a high fat diet and physical inactivity are thought to be key contributors.”2 and this is what is generally known about the condition.
However, a study published in the BMJ3 last year showed “dose-response (The Dose-response relationship describes the change in effect on – in this case -  a person caused by differing levels of exposure to stress) relation was found between exposure to work stressors over 14 years and risk of the metabolic syndrome, independent of other relevant risk factors. Employees with chronic work stress (three or more exposures) were more than twice as likely to have the syndrome than those without work stress.

The researchers concluded, “Stress at work is an important risk factor for the metabolic syndrome. The study provides evidence for the biological plausibility of the link between psychosocial stressors from everyday life and heart disease.”
Since many people I talk to with thyroid and adrenal problems tell me their problems started after more than one stressor at the same time, it makes you wonder if metabolic syndrome is, in fact, thyroid disease which has been undiagnosed!

1. http://familydoctor.org/826.xml
2. http://www.diabetesuffolk.com/Complications/Metabolic%20Syndrome.asp
3. BMJ,doi:10.1136/bmj.38693.435301.80 (pub 20 Jan 2006)


Small adrenal glands in chronic fatigue syndrome:
a preliminary computer tomography study.

Scott LV, Teh J, Reznek R, Martin A, Sohaib A, Dinan TG. Psychoneuroendocrinology. 1999 Oct;24(7):759-68.
Department of Psychiatry, Trinity College Dublin Medical School, St. James's, Hospital, Ireland.

No inclusive or satisfactory biomedical explanation for chronic fatigue syndrome (CFS) has as yet been forwarded. Recent research suggests that a dysregulated hypothalamic-pituitary-adrenal axis (HPA) may be contributory, and in particular that there may be diminished forward drive and adrenal under-stimulation. In this preliminary study we wished to examine a cohort of CFS patients in whom evidence for such hypofunctioning was found. Our aim was to establish whether these patients had altered adrenal gland size. Patients were recruited from a fatigue clinic. Those who fulfilled the Centre for Disease Control and Prevention (CDC) criteria underwent a 1 microgram adrenocorticotropin (ACTH) stimulation test, a test of adrenal gland functioning. Eight subjects (five females, three males) with a subnormal response to this test underwent a computer tomography (CT) adrenal gland assessment. Measurements were compared with those from a group of 55 healthy subjects. The right and left adrenal gland bodies were reduced by over 50% in the CFS subjects indicative of significant adrenal atrophy in a group of CFS patients with abnormal endocrine parameters. This is the first study to use imaging methods to measure adrenal gland size in CFS. It is a limitation of this study that a selected CFS sample was employed. A future larger study would optimally employ an unselected cohort of CFS patients. This study has implications not only for the elucidation of CFS pathophysiology, but also for possible therapeutic strategies.

PMID: 10451910 [PubMed - indexed for MEDLINE]

Combination therapy with hydrocortisone and fludrocortisone does not improve symptoms in chronic fatigue syndrome:
a randomized, placebo-controlled, double-blind, crossover study

Daniel Blockmans, Philippe Persoons , Boudewijn Van Houdenhove , Marina Lejeune and Herman Bobbaers
American Journal of Medicine - 15 June 2003, Volume 114, Issue 9 Pages 736-741


Purpose - Chronic fatigue syndrome has been associated with decreased function of the hypothalamic-pituitary-adrenal axis. Although neurally mediated hypotension occurs more frequently in patients with chronic fatigue syndrome than in controls, attempts to alleviate symptoms by administration of hydrocortisone or fludrocortisone have not been successful. The purpose of this study was to investigate the effect of combination therapy (5 mg/d of hydrocortisone and 50 μg/d of 9-alfa-fludrocortisone) on fatigue and well-being in chronic fatigue syndrome.

We performed a 6-month, randomized, placebo-controlled, double-blind, crossover study in 100 patients who fulfilled the 1994 Centers for Disease Control and Prevention criteria for chronic fatigue syndrome. Between-group differences (placebo minus treatment) were calculated on a 10-point visual analog scale.

Results - Eighty patients completed the 3 months of placebo and 3 months of active treatment in a double-blind fashion. There were no differences between treatment and placebo in patient-reported fatigue (mean difference, 0.1; 95% confidence interval [CI]: −0.3 to 0.6) or well-being (mean difference, −0.4; 95% CI: −1.0 to 0.1). There were also no between-group differences in fatigue measured with the Abbreviated Fatigue Questionnaire, the Short Form-36 Mental or Physical Factor scores, or in the Hospital Anxiety and Depression Scale.

Conclusion - Low-dose combination therapy of hydrocortisone and fludrocortisone was not effective in patients with chronic fatigue syndrome.



Misinterpretation of serum cortisol in a patient with hyponatraemia - Jamike C Smith, H Siddique, R J M Corrall - Dept. of Medicine, Bristol Royal Infirmary

We all know, don’t we, that in many cases of thyroid disease, particularly, the undiagnosed variety, that the adrenals have been compromised and therefore many of us actually have adrenal problems as well as thyroid problems.  Unfortunately, doctors don’t test for the adrenals very often and this is the case mentioned in the “Lesson of the Week”, on 24th January 2004 in the BMJ.

A 93 year old man had been admitted to hospital complaining of weight loss, nausea and vomiting.  He had been unwell for some 18 months and on admission he was found to have a problem with his oesophagus and was treated for this.  However, he continued to be unwell and was admitted again two months later with the same symptoms.  He was diagnosed with dehydration and pneumonia.  He was found also to have hyponatraemia (low sodium levels), a symptom of adrenal insufficiency.

In a study from a UK teaching hospital, only one case of adrenal insufficiency was excluded out of 47 cases of severe lack of sodium in the blood.

These findings show that doctors are not checking for low sodium levels as part of their diagnostic assessments. The Lesson informs, “ Rather, adrenal insufficiency should be considered in any hyponatraemic patient in whom an alternative precipitating cause for hyponatraemia is not apparent.”

So if you feel you have symptoms of adrenal insufficiency, such as dizziness on standing and dark circles under the eyes,  it might be a good idea to ask for a sodium test as well as a cortisol test.  Be aware though, that as in thyroid hormone testing, there is a range and you may well be told you are “normal” even if you are only just inside the range.

Is there a Thyroid-Cortisol-Depression Axis?

Frank King Thompson, Director, Fallbrook Medical Research Foundation. 2414 Via La Orilla, Fallbrook, CA 92028, USA

Summarised from: Thyroid Science 2(10)1, 2007

Frank Thompson informs us that the association between thyroid insufficiency and depression was recognized over a century ago and that evidence of a significant relationship is compelling.

There is a high rate of hypothyroidism - over 50% - in patients with difficult-to-treat depression and some studies have found that in people with severe hypothyroidism, there is 100% rate of depression.

Thompson tells us that subclinical hypothyroidism has been found  in four times as many people with depression and that thyroid hormone has been used to treat depression for 50 years or more and resolution of depression after thyroid hormone treatment has been reported in studies. T3 is currently used along with antidepressants as a treatment for depression - antidepressants are thought to be helpful because they impact on the thyroid hormone in the brain.

Recent studies report a thyroid hormone effect on the neurotransmitters serotonin and norepinephrine - T3 can increase the activity of serotonin in the brain while serotonin has been shown to inhibit thyroid function.

Although a link has been recognized and examined of the interaction between thyroid hormone and neurotransmitters, no clear-cut explanation for the effect of thyroid hormone on depression has emerged.

High cortisol levels are common findings in depression and have been shown to inhibit the activity of neurotransmitters in the brain.  Also resolution of depression following normalization of cortisol levels has been shown.

Thompson wrote, “It has long been recognized that an increase in thyroid hormone levels enhances the metabolic clearance of cortisol. So effective is this action, that it poses a risk of adrenal crisis to thyroid hormone users who lack adequate cortisol reserves. Perhaps, then, a thyroid hormone-induced drop in cortisol, and subsequent potentiation of neurotransmitters, is the mechanism by which thyroid hormone relieves certain cases of depression.”
“If selective serotonin and norepinephrine reuptake inhibiting drugs affect thyroid hormone as well as neurotransmitters in the brain, could part of their activity be due to a thyroid hormone effect on brain cortisol levels? Further studies are needed to examine these possibilities.”