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Adrenal failure (Addison's disease) is recognized, while fatigue is not. The adrenal gland secretes epinephrine (adrenaline),
norepinephrine, and corticosteroids.
How can we test for adrenal fatigue?
J Endocrinol Invest. 2004 Jan;27(1):42-6. Related Articles, Links
Investigation of the hypothalamo-pituitary-adrenal axis (HPA) by 1 microg ACTH test and metyrapone test in patients with
primary fibromyalgia syndrome.
Calis M, Gokce C, Ates F, Ulker S, Izgi HB, Demir H, Kirnap M, Sofuoglu S, Durak AC, Tutus A, Kelestimur F.
Division of Physical Medicine and Rehabilitation, Department of Medical Sciences, University of Erciyes, Kayseri, Turkey.
Primary fibromyalgia syndrome (PFS) is characterized by widespread chronic pain that affects the musculoskeletal system,
fatigue, anxiety, sleep disturbance, headache and postural hypotension. The pathophysiology of PFS is unknown. The hypothalamic-pituitary-adrenal
(HPA) axis seems to play an important role in PFS. Both hyperactivity and hypoactivity of the HPA axis have been reported
in patients with PFS. In this study we assessed the HPA axis by 1 microg ACTH stimulation test and metyrapone test in 22 patients
with PFS and in 15 age-, sex-, and body mass index (BMI)- matched controls. Metyrapone (30 mg/kg) was administered orally
at 23:00 h and blood was sampled at 08:30 h the following morning for 11-deoxycortisol. ACTH stimulation test was carried
out by using 1 microg (iv) ACTH as a bolus injection after an overnight fast, and blood samples were drawn at 0, 30 and 60
min. Peak cortisol level (659.4 +/- 207.2 nmol/l) was lower in the patients with PFS than peak cortisol level (838.7 +/- 129.6
nmol/l) in the control subjects (p < 0.05). Ten patients (45%) with PFS had peak cortisol responses to 1 microg ACTH test
lower than the lowest peak cortisol detected in healthy controls. After metyrapone test 11-deoxycortisol level was 123.7 +/-
26 nmol/l in patients with PFS and 184.2 +/- 17.3 nmol/l in the controls (p < 0.05). Ninety five percent of the patients
with PFS had lower 11-deoxycortisol level after metyrapone than the lowest 11-deoxycortisol level after metyrapone detected
in healthy controls. We also compared the adrenal size of the patients with that of the healthy subjects and we found that
the adrenal size between the groups was similar. This study clearly shows that HPA axis is underactivated in PFS, rather than
overactivated.
Publication Types:
Clinical Trial
Controlled Clinical Trial
PMID: 15053242 [PubMed - indexed for MEDLINE]
Trends Endocrinol Metab. 2004 Mar;15(2):55-9. Related Articles, Links
The HPA axis and the genesis of chronic fatigue syndrome.
Cleare AJ.
Section of Neurobiology of Mood Disorders, Division of Psychological Medicine, The Institute of Psychiatry, London, SE5
8AF, UK. a.cleare@iop.kcl.ac.uk
Many studies of patients with long-standing chronic fatigue syndrome (CFS) have found alterations to the hypothalamo-pituitary-adrenal
(HPA) axis, including mild hypocortisolism, heightened negative feedback and blunted responses to challenge. However, recent
prospective studies of high-risk cohorts suggest that there are no HPA axis changes present during the early stages of the
genesis of fatiguing illnesses. Moreover, HPA axis changes can be reversed by modifying behavioural features of the illness,
such as inactivity, deconditioning and sleep disturbance. Nevertheless, raising levels of cortisol pharmacologically can temporarily
alleviate symptoms of fatigue. This article presents the case that there is no specific change to the HPA axis in CFS and
that the observed changes are of multifactorial aetiology, with some factors occurring as a consequence of the illness. Nevertheless,
the HPA axis might play a role in exacerbating or perpetuating symptoms late on in the course of the illness.
Publication Types:
Review
Review, Tutorial
PMID: 15036250 [PubMed - indexed for MEDLINE]
J Endocrinol Invest. 2003;26(7 Suppl):74-82. Related Articles, Links
Dynamic evaluation of adrenal hypofunction.
Nieman LK.
Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes
of Health, Bethesda, MD 20892-1583, USA. NiemanL@nih.gov
The diagnosis of adrenal hypofunction is suggested by clinical features and confirmed by biochemical testing. The characteristic
features of acute primary adrenal insufficiency include orthostatic hypotension, fever, and hypoglycemia. By contrast, patients
with chronic primary adrenal insufficiency have a longer history of malaise, as well as fatigue, anorexia, diarrhea, weight
loss, joint and back pain, and darkening of the skin. While the clinical presentation of secondary adrenal insufficiency is
similar to that of primary adrenal insufficiency, there is no hyperpigmentation, and hypotension and orthostasis are less
pronounced. As a result, patients often present with vague, non-specific symptoms and the diagnosis may not be entertained.
There is considerable debate regarding the best dynamic test for the diagnosis of adrenal hypofunction. Optimally, a screening
test would be economic, convenient and safe. It would have high sensitivity and specificity based on consensus criteria for
interpretation. Unfortunately, to date no test meets all of these criteria. Measurement of basal cortisol is an inexpensive
and convenient screening test that can include (< 3 microg/dl; 83 nmol/l) or exclude (> 19 microg/dl; 524 nmol/l) adrenal
insufficiency. However, most patients will have intermediate values and will require dynamic testing. This review discusses
the use of metyrapone, insulin, CRH and synthetic ACTH 1-24 as provocative agents for cortisol secretion. Although the insulin
and metyrapone stimulation tests have the advantage of testing the entire hypothalamic-pituitary-adrenal axis, they are cumbersome
and carry more risk than the other tests. The 250 microg ACTH test works well to identify primary adrenal hypofunction, but
can only detect secondary adrenal hypofunction when there is sufficient time for the glands to atrophy because of reduced
endogenous ACTH stimulation. The 1 microg ACTH test has been advocated in the setting of possible secondary adrenal insufficiency,
but its widespread use has been mitigated by the lack of a commercial preparation of this small dose and controversy regarding
diagnostic criteria. Ultimately, the choice of test should be individualized for each patient, with knowledge of the available
reference assays and the vagaries of each test.
Publication Types:
Review
Review, Tutorial
PMID: 14604069 [PubMed - indexed for MEDLINE]
Should we take steroids for adrenal fatigue?
Pediatrics. 2004 Dec;114(6):1649-57. Related Articles, Links
Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial.
Watterberg KL, Gerdes JS, Cole CH, Aucott SW, Thilo EH, Mammel MC, Couser RJ, Garland JS, Rozycki HJ, Leach CL, Backstrom
C, Shaffer ML.
Division of Neonatology, Department of Pediatrics/Neonatology, University of New Mexico School of Medicine, MSC10 5590,
Albuquerque, NM 87131-0001, USA. kwatterberg@salud.unm.edu
BACKGROUND: Infants developing bronchopulmonary dysplasia (BPD) show decreased cortisol response to adrenocorticotropic
hormone. A pilot study of low-dose hydrocortisone therapy for prophylaxis of early adrenal insufficiency showed improved survival
without BPD at 36 weeks' postmenstrual age, particularly in infants exposed to histologic chorioamnionitis. METHODS: Mechanically
ventilated infants with birth weights of 500 to 999 g were enrolled into this multicenter, randomized, masked trial between
12 and 48 hours of life. Patients received placebo or hydrocortisone, 1 mg/kg per day for 12 days, then 0.5 mg/kg per day
for 3 days. BPD at 36 weeks' postmenstrual age was defined clinically (receiving supplemental oxygen) and physiologically
(supplemental oxygen required for O2 saturation > or =90%). RESULTS: Patient enrollment was stopped at 360 patients because
of an increase in spontaneous gastrointestinal perforation in the hydrocortisone-treated group. Survival without BPD was similar,
defined clinically or physiologically, as were mortality, head circumference, and weight at 36 weeks. For patients exposed
to histologic chorioamnionitis (n = 149), hydrocortisone treatment significantly decreased mortality and increased survival
without BPD, defined clinically or physiologically. After treatment, cortisol values and response to adrenocorticotropic hormone
were similar between groups. Hydrocortisone-treated infants receiving indomethacin had more gastrointestinal perforations
than placebo-treated infants receiving indomethacin, suggesting an interactive effect. CONCLUSIONS: Prophylaxis of early adrenal
insufficiency did not improve survival without BPD in the overall study population; however, treatment of chorioamnionitis-exposed
infants significantly decreased mortality and improved survival without BPD. Low-dose hydrocortisone therapy did not suppress
adrenal function or compromise short-term growth. The combination of indomethacin and hydrocortisone should be avoided.
PMID: 15574629 [PubMed - in process]
Anesth Analg. 2004 Dec;99(6):1813-4, table of contents. Related Articles, Links
Acute adrenal insufficiency after large-dose glucocorticoids for spinal cord injury.
Lecamwasam HS, Baboolal HA, Dunn PF.
Department of Anesthesia and Critical Care, GRB 04-424, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114,
USA.
A 24- to 48-h course of large-dose glucocorticoid therapy is often used in the acute management of spinal cord injury.
We describe a patient who developed adrenal insufficiency (AI) after this protocol. Although a definitive causal relationship
between the steroids and AI was not established, their temporal association and the exclusion of other possible etiologies
led us to postulate that AI was a complication of the steroid protocol. Clinicians should, therefore, consider AI in patients
with spinal cord injury receiving glucocorticoids, a population in whom it may otherwise go undiagnosed and untreated.
PMID: 15562077 [PubMed - in process]
Wien Klin Wochenschr. 2002;114 Suppl 1:9-19. Related Articles, Links
[Cortisol in critically ill patients with sepsis--physiological functions and therapeutic implications]
[Article in German]
Briegel J.
Klinik fur Anaesthesiologie, Klinikum der Universitat Munchen, Deutschland. josef.briegel@ana.med.uni-muenchen.de
Modern immunology reveals that cortisol interacts with the immune response at virtually all levels exerting suppressive
and permissive effects. A prerequisite for the defense of severe infections is the functional integrity of the hypothalamic-pituitary-adrenal
axis (HPAA) resulting in adequate cortisol production. There is increasing evidence that cortisol physiology and regulation
substantially change in the course of septic shock. Patients with septic shock may suffer from relative adrenocortical insufficiency
resulting in a relative deficiency of cortisol. In addition, the number and the affinity of cellular glucocorticoid receptors
are decreased which may reduce the cortisol action at the cellular level. Since septic shock and adrenal insufficiency are
sharing hemodynamic abnormalities such as hyperdynamic shock and peripheral vasodilation, the administration of stress doses
of hydrocortisone appears to be a rational therapeutic approach in patients with septic shock. Controlled studies reveal that
stress doses of hydrocortisone attenuate the systemic inflammatory response. Recently, two double-blind studies demonstrated
that stress doses of hydrocortisone given in patients with septic shock reduce the time to shock reversal. The most important
hemodynamic effect was an increase in the systemic vascular resistance. The earlier weaning from vasopressor therapy was associated
with a trend towards improvements in organ dysfunction and mortality, respectively. Large-scale trials are on the way to investigate
the benefit of stress doses of hydrocortisone on mortality of septic shock. This paper will focus on changes in glucocorticoid
physiology and regulation during septic shock and will discuss the effects of stress doses of hydrocortisone on immune response
and vascular tone in the course of septic shock.
PMID: 15503552 [PubMed - in process]
What causes adrenal fatigue?
J Paediatr Child Health. 2004 Nov;40(11):596-9. Related Articles, Links
Primary adrenal insufficiency in childhood and adolescence: advances in diagnosis and management.
Simm PJ, McDonnell CM, Zacharin MR.
Department of Endocrinology and Diabetes, Royal Children's Hospital, Melbourne, Victoria, Australia.
OBJECTIVES: Primary adrenal insufficiency occurring in childhood and adolescence is due to abnormalities of gland development,
gland responsiveness, and steroid biosynthesis or target organ response. Causes include autoimmune Addison's disease, tuberculosis,
HIV, adrenoleukodystrophy, adrenal hypoplasia congenita and syndromes including triple A and IMAGe. We aimed to define the
causes of adrenal insufficiency for a cohort of children in Melbourne. METHODS: We reviewed the frequency and variety of presentation
of primary adrenal insufficiency to the Royal Children's Hospital over the past 10 years through an audit of patient records,
collating demographic information, presentation and investigations. RESULTS: Sixteen cases (13 male, 3 female) of primary
adrenal insufficiency were diagnosed at this hospital between January 1993 and July 2003. Median age at presentation was 7.7
years (range: birth to 14.8 years). Symptoms at presentation included weakness, increased pigmentation, abdominal pain, nausea,
developmental delay or a reduction in school performance. Four patients presented with adrenal crisis. Median adrenocorticotrophic
hormone (ACTH) at diagnosis was 246 pmol/L (range 30-969 pmol/L). Autoantibodies were positive in five patients. Five patients
had elevation of very long chain fatty acids. Five patients were diagnosed with autoimmune adrenal insufficiency, five with
adrenal hypoplasia congenita, five with adrenoleukodystrophy and one with IMAGe syndrome. CONCLUSIONS: A high index of suspicion
results in earlier detection and possible prevention of adrenal crisis with a reduction in associated morbidities. Definitive
diagnosis is now possible for almost all cases of primary adrenal insufficiency using technologies for screening autoimmunity,
adrenoleukodystrophy (ALD) and genetic screening.
PMID: 15469526 [PubMed - in process]
Seishin Shinkeigaku Zasshi. 2004;106(9):1110-6. Related Articles, Links
[A case of Addison's disease presented with depression as a first symptom]
[Article in Japanese]
Iwata M, Hazama GI, Shirayama Y, Ueta T, Yoshioka S, Kawahara R.
Division of Neuropsychiatry, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University.
This report describes a 52-year-old male patient with idiopathic Addison's disease presenting depression as a first symptom.
His psychomotor inhibition, depressive mood, sleep disturbances, general fatigue, muscular pain, and arthralgia were considered
to be due to intense work in a stressful environment. Neither his physician nor his orthopedist found any physical disease.
Therefore, he was diagnosed with endogenous depression by a psychiatric clinic, and antidepressants were prescribed. Antidepressants
were not sufficient for improving his symptoms, and he was admitted to our hospital. Endocrine blood examination revealed
primary adrenocortical insufficiency. Treatment with glucocorticoid induced rapid improvement in both the psychiatric and
physical symptoms. It is well known that psychiatric symptoms occur in the progressive stage of Addison's disease. At present,
however, the occurrence of psychiatric symptoms is very rare, mainly because of a decrease in the incidence of this disease
or an increase in mild cases. In addition, Addison's disease presenting with psychiatric features in the early stage has the
tendency to be overlooked and misdiagnosed. Thus, we suggest the necessity of blood work for ACTH and cortisol in the field
of psychiatry.
PMID: 15580869 [PubMed - in process]
Endocr Pract. 1995;1(1):14-7. Related Articles, Links
Autoimmune addison's disease after treatment with interleukin-2 and tumor-infiltrating lymphocytes.
Wahle M D JS, Hanson M D JP, Shaker M D JL, Findling M D JW.
Departments of Medicine of Medical College of Wisconsin and of St., Luke's Medical Center,Milwaukee, WI.
Autoimmune thyroiditis with hypothyroidism is a well-known complication of immunotherapy with inter-leukin-2 (IL-2) with
or without lymphokine-activated killer (LAK) cells. To date, however, no cases of IL-2/LAK-induced autoimmune adrenalitis
with adrenal insufficiency have been reported. We describe a patient who developed primary adrenal insufficiency following
IL-2/tumor-infiltrating lymphocytes (TIL) immunotherapy for renal cell carcinoma. A 64-year-old male with renal cell carcinoma
metastatic to bone, skin, lung, and the central nervous system presented for IL-2/TIL treatment. Nine months earlier, he had
undergone a right nephrectomy and adrenalectomy. He had already received two courses of IL-2 and one course of IL-4 following
surgery. Dynamic studies of adrenal function performed prior to IL-2/TIL immunotherapy demonstrated intact cortisol and aldosterone
responses to ACTH as well as negative adrenal antibodies. One week after IL-2/TIL therapy, the patient developed a nonanion
gap metabolic acidosis, hypotension and hypoglycemia. Adrenocortical function was re-evaluated demonstrating blunted cortisol
and aldosterone responses to ACTH with an elevated plasma ACTH confirming the presence of primary adrenal insufficiency. Adrenal
antibodies were now positive. Hydrocortisone and fludrocortisone were given with a good clinical response. We suggest immunotherapy
with IL-2/TIL may cause adrenal insufficiency by activating autoimmune adrenalitis.
PMID: 15251609 [PubMed - in process]
Expert Opin Pharmacother. 2003 Dec;4(12):2145-9. Related Articles, Links
Erratum in:
Expert Opin Pharmacother. 2004 Feb;5(2):485. Correction of dosage error in abstract.
Replacement therapy in Addison's disease.
Lovas K, Husebye ES.
Addison's disease or primary adrenal insufficiency is a rare disease, which is usually caused by autoimmune destruction
of the adrenal cortex. The clinical picture is caused by deficiency of cortisol and aldosterone. These deficiencies are accompanied
by adrenal androgen depletion of yet unknown significance. The current therapy is the replacement of glucocorticoids and mineralocorticoids,
but the available drugs do not restore the normal diurnal variations in serum hormone levels. The clinical consequences of
the grossly unphysiological replacement therapy are largely unknown. Many patients with Addison's disease on standard replacement
therapy complain of fatigue, weariness, and reduced stress tolerance. One particular concern has been negative effects on
both bone metabolism due to over-replacement of glucocorticoids and androgen depletion. This review discusses the evidence
for the current drug and dosage recommendations. Current recommended daily starting dose for hydrocortisone and cortisone
acetate are 20 and 25 mg, respectively, divided into two or preferably three doses. The mineralocorticoid depletion should
be treated with fludrocortisone 0.05-2.0 mg/day [corrected]. Replacement of dehydroepiandrosterone 20-50 mg has been advocated
in adrenal failure, but the evidence for benefit is weak.
Publication Types:
Editorial
Review
Review, Tutorial
PMID: 14640913 [PubMed - indexed for MEDLINE]
Eur J Clin Invest. 2003 Dec;33(12):1029-31. Related Articles, Links
Comment in:
Eur J Clin Invest. 2004 Apr;34(4):317; author reply 318-9.
Chronic fatigue syndrome: an endocrine disease off limits for endocrinologists?
Baschetti R.
Retired Medical Inspector of the Italian State Railways, Fortaleza, Brazil. baschetti@baydenet.com.br
Endocrinologists were not included in the multidisciplinary working groups that prepared two recent reports on chronic
fatigue syndrome, despite its unequalled clinical overlap with Addison's disease, which is a classic endocrine disorder. The
failure to include at least one endocrinologist in those panels may explain why in their extensive reports there is not a
single word about the 42 clinical features that chronic fatigue syndrome shares with Addison's disease, including all the
signs and symptoms listed in the case definition of this syndrome.
Publication Types:
Review
Review, Tutorial
PMID: 14636284 [PubMed - indexed for MEDLINE]
South Med J. 2003 Aug;96(8):824-7. Related Articles, Links
Comment in:
South Med J. 2004 Apr;97(4):424.
Addisonian crisis precipitated by thyroxine therapy: a complication of type 2 autoimmune polyglandular syndrome.
Graves L 3rd, Klein RM, Walling AD.
Division of Metabolism, Endocrinology and Genetics, Department of Internal Medicine, University of Kansas Medical Center,
Kansas City, Kansas 66160, USA. lgraves@kumc.edu
Hypothyroidism is a common condition. Rarely, it may occur in combination with autoimmune failure of other endocrine glands
(autoimmune polyendocrinopathy syndrome type 2, previously known as Schmidt's syndrome). In such cases, restoring normal thyroid
function may precipitate adrenal failure. Clinicians should have a high index of suspicion for this condition in patients
with Addison's disease, those with a family history of autoimmune endocrine gland failure, patients with one autoimmune endocrine
disease who develop nonspecific or serious illness, and patients with type 1 diabetes mellitus whose insulin requirements
drop without obvious explanation.
Publication Types:
Case Reports
PMID: 14515930 [PubMed - indexed for MEDLINE]
South Med J. 2003 Sep;96(9):888-90. Related Articles, Links
Infectious causes of adrenal insufficiency.
Alevritis EM, Sarubbi FA, Jordan RM, Peiris AN.
Division of Infectious Diseases , Department of Medicine, James H. Quillen Veterans Affairs Medical Center, Johnson City,
TN 37614, USA.
More than 150 years ago, Thomas Addison first described the clinical features and pathogenesis of adrenal insufficiency.
At that time, tuberculosis was the most common cause of this disease. The pathway to diagnosis and treatment of Addison's
disease has been well described. However, determining the cause of the disorder remains a challenge. It is important to consider
recently described infectious agents in the pathogenesis of Addison's disease. Mycobacterial, bacterial, viral, and fungal
infections may lead to the development of adrenal insufficiency. Skin, pulmonary, and imaging findings can aid the clinician
in making a prompt diagnosis of specific infections, which is crucial because early identification of infectious causes of
Addison's disease may enable recovery of adrenal function. This review describes the clinical presentations of the multiple
infectious causes of adrenal insufficiency.
Publication Types:
Review
Review, Tutorial
PMID: 14513986 [PubMed - indexed for MEDLINE]
J Clin Endocrinol Metab. 2003 Jul;88(7):2983-92. Related Articles, Links
Polyglandular autoimmune syndromes: immunogenetics and long-term follow-up.
Dittmar M, Kahaly GJ.
Department of Medicine I, Gutenberg University, Mainz, Germany 55101, USA.
Polyglandular autoimmune syndromes (PAS) are rare polyendocrinopathies characterized by the failure of several endocrine
glands as well as nonendocrine organs, caused by an immune-mediated destruction of endocrine tissues. This article summarizes
extensive clinical, epidemiological, serological, and genetic data of a large collective of patients with PAS (n = 360). Since
1988, more than 15,000 adult patients with endocrine diseases have been screened at the endocrine center of the Mainz University,
and 151 of 360 patients with PAS have regularly been followed. Type 1 diabetes, Graves' disease, Hashimoto thyroiditis, Addison's
disease, vitiligo, alopecia, hypogonadism, and pernicious anemia were observed in 61%, 33%, 33%, 19%, 20%, 6%, 5%, and 5%,
respectively. The most common disease combination was type 1 diabetes and autoimmune thyroid disease. In most patients, type
1 diabetes was the first manifestation of PAS (48%). The longest time intervals between manifestations of the first and second
immune endocrinopathies occurred between type 1 diabetes and thyroid disease (13.3 +/- 11.8 yr) and between vitiligo and thyroid
disease (16.3 +/- 13.3 yr), but a shorter time interval was observed between Addison's and thyroid diseases. Of the 471 patients
with type 1 diabetes screened, 83 (17.6%) were positive for PAS. Subsequently, sera of 126 patients with PAS, 287 with type
1 diabetes, and 303 matched controls were compared for human leukocyte antigens. Patients with PAS had significantly higher
frequencies of the human leukocyte antigens A24, A31, B8, B51, B62, DR3, and DR4 (relative risk, 2.35, 2.74, 2.47, 7.17, 2.22,
1.94, and 2.46) vs. controls, and for A31, B15, B52, B55, DR2, DR11, and DR13 (relative risk, 2.51, 7.96, 3.99, 5.36, 4.46,
2.89, and 3.26) vs. type 1 diabetes patients without PAS. In conclusion, patients with autoimmune endocrine disease should
be followed on a regular basis. In subjects at risk for PAS, functional screening every 3 yr is warranted. If clinical disease
is present, serological measurement of organ-specific antibodies should follow.
PMID: 12843130 [PubMed - indexed for MEDLINE]
Am J Clin Dermatol. 2003;4(5):315-31. Related Articles, Links
Cutaneous manifestations of endocrine disorders: a guide for dermatologists.
Jabbour SA.
Division of Endocrinology, Diabetes and Metabolism, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
serge.jabbour@mail.tju.edu
Dermatologists may commonly see skin lesions that reflect an underlying endocrine disorder. Identifying the endocrinopathy
is very important, so that patients can receive corrective rather than symptomatic treatment. Skin diseases with underlying
endocrine pathology include: thyrotoxicosis; hypothyroidism; Cushing syndrome; Addison disease; acromegaly; hyperandrogenism;
hypopituitarism; primary hyperparathyroidism; hypoparathyroidism; pseudohypoparathyroidism and manifestations of diabetes
mellitus.Thyrotoxicosis may lead to multiple cutaneous manifestations, including hair loss, pretibial myxedema, onycholysis
and acropachy. In patients with hypothyroidism, there is hair loss, the skin is cold and pale, with myxedematous changes,
mainly in the hands and in the periorbital region.The striking features of Cushing syndrome are centripetal obesity, moon
facies, buffalo hump, supraclavicular fat pads, and abdominal striae. In Addison disease, the skin is hyperpigmented, mostly
on the face, neck and back of the hands.Virtually all patients with acromegaly have acral and soft tissue overgrowth, with
characteristic findings, like macrognathia and enlarged hands and feet. The skin is thickened, and facial features are coarser.Conditions
leading to hyperandrogenism in females present as acne, hirsutism and signs of virilization (temporal balding, clitoromegaly).A
prominent feature of hypopituitarism is a pallor of the skin with a yellowish tinge. The skin is also thinner, resulting in
fine wrinkling around the eyes and mouth, making the patient look older.Primary hyperparathyroidism is rarely associated with
pruritus and chronic urticaria. In hypoparathyroidism, the skin is dry, scaly and puffy. Nails become brittle and hair is
coarse and sparse. Pseudohypoparathyroidism may have a special somatic phenotype known as Albright osteodystrophy. This consists
of short stature, short neck, brachydactyly and subcutaneous calcifications.Some of the cutaneous manifestations of diabetes
mellitus include necrobiosis lipoidica diabeticorum, diabetic dermopathy, scleredema adultorum and acanthosis nigricans.
Publication Types:
Review
Review, Tutorial
PMID: 12688837 [PubMed - indexed for MEDLINE] Endocr Rev. 2002 Aug;23(4):464-83. Related Articles, Links
Endocrinological disorders and celiac disease.
Collin P, Kaukinen K, Valimaki M, Salmi J.
Department of Medicine, Tampere University Hospital and University of Tampere, 33014 Tampere, Finland. pekka.collin@uta.fi
Celiac disease is a permanent intolerance to dietary gluten. Its well known features are abdominal symptoms, malabsorption
of nutrients, and small-bowel mucosal inflammation with villous atrophy, which recover on a gluten-free diet. Diagnosis is
challenging in that patients often suffer from subtle, if any, symptoms. The risk of clinically silent celiac disease is increased
in various autoimmune conditions. The endocrinologist, especially, should maintain high suspicion and alertness to celiac
disease, which is to be found in 2-5% of patients with insulin-dependent diabetes mellitus or autoimmune thyroid disease.
Patients with multiple endocrine disorders, Addison's disease, alopecia, or hypophysitis may also have concomitant celiac
disease. Similar heredity and proneness to autoimmune conditions are considered to be explanations for these associations.
A gluten-free diet is essential to prevent celiac complications such as anemia, osteoporosis, and infertility. The diet may
also be beneficial in the treatment of the underlying endocrinological disease; prolonged gluten exposure may even contribute
to the development of autoimmune diseases. The diagnosis of celiac disease requires endoscopic biopsy, but serological screening
with antiendomysial and antitissue transglutaminase antibody assays is an easy method for preliminary case finding. Celiac
disease will be increasingly detected provided the close association with autoimmune endocrinological diseases is recognized.
Publication Types:
Review
Review, Tutorial
PMID: 12202461 [PubMed - indexed for MEDLINE]
J Endocrinol Invest. 1999 May;22(5):390-4. Related Articles, Links
Unusual association of thyroiditis, Addison's disease, ovarian failure and celiac disease in a young woman.
Valentino R, Savastano S, Tommaselli AP, Dorato M, Scarpitta MT, Gigante M, Lombardi G, Troncone R.
Centro di Endocrinologia e Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare
L. Califano, Italy.
The coexistence of autoimmune endocrine diseases, particularly autoimmune thyroid disease and celiac disease (CD), has
recently been reported. We here present a 23-year-old woman with a diagnosis of hypothyroidism due to Hashimoto's thyroiditis,
autoimmune Addison's disease, and kariotypically normal spontaneous premature ovarian failure. Considering the close association
between autoimmune diseases and CD, we decided to search for IgA anti-endomysium antibodies (EmA) in the serum. The positivity
of EmA and the presence of total villous atrophy at jejunal biopsy allowed the diagnosis of CD. On a gluten-free diet the
patient showed a marked clinical improvement accompanied, over a 3-month period, by a progressive decrease in the need for
thyroid and adrenal replacement therapies. After 6 months, serum EmA became negative and after 12 months a new jejunal biopsy
showed complete mucosal recovery. After 18 months on gluten-free diet, the anti-thyroid antibodies titre decreased significantly,
and we could discontinue thyroid substitutive therapy. This case emphasizes the association between autoimmune polyglandular
disease and CD; the precocious identification of these cases is clinically relevant not only for the high risk of complications
(e.g. lymphoma) inherent to untreated CD, but also because CD is one of the causes for the failure of substitute hormonal
therapy in patients with autoimmune thyroid disease.
Publication Types:
Case Reports
PMID: 10401714 [PubMed - indexed for MEDLINE]
Am J Med. 1983 May;74(5):829-36. Related Articles, Links
Cardiac failure in Addison's disease.
Knowlton AI, Baer L.
In an average 30 years of follow-up study, seven of 22 patients with primary adrenal insufficiency have had cardiac failure.
Comparison of these seven with the 15 who remain free of this complication revealed that the former group were somewhat older
and had higher incidences of unrelated cardiac disease and of nonsteroid-dependent hypertension, but that their replacement
regimens, with respect to sodium supplementation and sodium-retaining steroids, were identical with the latter. Coincident
with the appearance of cardiac failure, all seven patients had a decrease in sodium requirements. Adequate control of the
adrenal disease was subsequently possible with elimination of mineralocorticoid support in one of the six who had initially
required this therapy and a reduction in dosage in the other five. In all seven, dietary sodium supplements were no longer
required. In three patients with severe failure, sodium restriction was imposed and diuretics were added, although the latter
therapy has required close monitoring to avoid sodium depletion.
PMID: 6837606 [PubMed - indexed for MEDLINE]
What can we do about adrenal fatigue?
Horm Res. 1999;52(5):253-5. Related Articles, Links
Liquorice, growth retardation and Addison's disease.
Doeker BM, Andler W.
Department of Endocrinology, Vestische Kinderklinik Datteln, University of Witten-Herdecke, Germany. Beate_Maria_Doeker@yahoo.com
An 11-year-old boy had hypoparathyroidism and Addison's disease. During treatment with calcitriol, calcium, hydrocortisone
and 9-alpha-fluorocortisol, he developed an apparent mineralocorticoid excess and growth retardation. Pseudohyperaldosteronism
even persisted after treatment with 9-alpha-fluorocortisol was stopped and hydrocortisone was reduced to 6 mg/m(2). The boy
reported an excessive daily intake of 300-400 g liquorice corresponding to 600-800 mg glycyrrhizic acid because of salt craving.
After complete withdrawal of liquorice all symptoms of hypermineralocorticoidism diminished and growth velocity increased.
We hypothesise that inhibition of 11beta-hydroxysteroid dehydrogenase by liquorice caused hypermineralocorticoidism and growth
retardation via increased levels of free cortisol in this patient. We conclude that self-medication with liquorice in children
with Addison's disease should be considered during treatment. Copyright 2000 S. Karger AG, Basel
Publication Types:
Case Reports
PMID: 10844416 [PubMed - indexed for MEDLINE]
Baron JH. Related Articles, Links Glycyrrhizophilia.
Lancet. 1973 Feb 17;1(7799):383. No abstract available.
PMID: 4121988 [PubMed - indexed for MEDLINE]
Cotterill JA, Cunliffe WJ. Related Articles, Links
Self-medication with liquorice in a patient with Addison's disease.
Lancet. 1973 Feb 10;1(7798):294-5. No abstract available.
PMID: 4119173 [PubMed - indexed for MEDLINE]
Acta Endocrinol (Copenh). 1983 Aug;103(4):469-72. Related Articles, Links
Suppression of electroacupuncture(EA)-induced beta-endorphin and ACTH release by hydrocortisone in man. Absence of effects
on EA-induced anaesthesia.
Masala A, Satta G, Alagna S, Zolo TA, Rovasio PP, Rassu S.
Auricular electroacupuncture (EA) increased plasma ACTH and beta-endorphin levels significantly in 10 patients receiving
EA as an analgesic aid during surgery. Pre-treatment with iv hydrocortisone (200 mg) completely suppressed both ACTH and beta-endorphin
release in response to EA without significantly affecting EA anaesthesia in 6 other patients and in a patient with Addison's
disease.
PMID: 6310920 [PubMed - indexed for MEDLINE]
Rev Med Suisse Romande. 2001 Sep;121(9):649-54. Related Articles, Links
[Is there an indication for dehydroepiandrosterone (DHEA) treatment in elderly women with Addison disease? Beneficial
and adverse effects of DHEA]
[Article in French]
Martin-Du Pan RC.
DHEA is a cetosteroid secreted by the adrenal gland. Serum levels of DHEA decline by an average of 10% per decade whereas
cortisol levels remain stable. The relative lack of DHEA secretion in elderly people has been called adrenopause. The daily
administration of 50 mg of DHEA to women over 60 years old results in a two-fold increase in serum level of testosterone and
androstenedione and in a 10% increase of estradiol in men. A 10 to 20% increase of IGF-1 is observed in both sexes. In women
over 70 years old treated by 50 mg/day of DHEA for 6 months an improvement of bone turnover and of skin status was observed
as well as an increase of overall well-being and of libido. These beneficial psychological effects have also been observed
in younger men and women with adrenal insufficiency. In men 50 to 65 years old, 100 mg/day of DHEA for 6 months could slightly
increase the lean body mass and the muscle strength. Moreover DHEA could increase immune function and NK cell activity. As
there are no actual data about cardio-vascular and oncological risks of a prolonged treatment with DHEA, the administration
of this steroid must still be considered experimental. Previous or present cancer of the breast or of the prostate is an absolute
contraindication to DHEA treatment.
Publication Types:
Review
Review, Tutorial
PMID: 11723706 [PubMed - indexed for MEDLINE]
Ann Endocrinol (Paris). 2001 Apr;62(2):212-6. Related Articles, Links
Therapeutic strategies in adrenal insufficiency.
Oelkers W, Diederich S, Bahr V.
Division of Endocrinology, Klinikum Benjamin Franklin, Freie Universitat Berlin Hindenburgdamm 30, 12200 Berlin, Germany.
Severe chronic adrenal insufficiency (primary or secondary) is a potentially lethal disorder, unless the patient is regularly
substituted with glucocorticoids, usually with hydrocortisone (15-25 mg/day) and with 9 alpha-fluor-hydrocortisone (0.05-0.2
mg/day) in addition in patients with the primary adrenal disorder (Addison's disease). In stressful situations and in febrile
disorders, the glucocorticoid dosage must be increased prophylactically in order to prevent an "adrenal crisis".
Most women with adrenal insufficiency will profit from the additional substitution of dehydroepiandrosterone (DHEA) with regard
to well-being and sexual function. A patient with acute adrenal insufficiency will die if the diagnosis is missed and high-dose
glucocorticoid treatment is not instituted immediately. Acute adrenal insufficiency developing de novo in an intensive care
patient (e.g. from adrenal hemorrhage or adrenal vein thrombosis) is a most challenging diagnosis. In these patients, however,
survival not only depends on glucocorticoid substitution but also on the underlying disease.
Publication Types:
Review
Review, Tutorial
PMID: 11353897 [PubMed - indexed for MEDLINE]
J Clin Endocrinol Metab. 2000 Dec;85(12):4650-6. Related Articles, Links
Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison's disease in a randomized, double
blind trial.
Hunt PJ, Gurnell EM, Huppert FA, Richards C, Prevost AT, Wass JA, Herbert J, Chatterjee VK.
Department of Endocrinology, University of Oxford, Radcliffe Infirmary, Oxford, United Kingdom.
Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are adrenal precursors of steroid biosynthesis and centrally acting
neurosteroids. Glucocorticoid and mineralocorticoid deficiencies in Addison's disease require life-long hormone replacement,
but the associated failure of DHEA synthesis is not corrected. We conducted a randomized, double blind study in which 39 patients
with Addison's disease received either 50 mg oral DHEA daily for 12 weeks, followed by a 4-week washout period, then 12 weeks
of placebo, or vice versa. After DHEA treatment, levels of DHEAS and Delta(4)-androstenedione rose from subnormal to within
the adult physiological range. Total testosterone increased from subnormal to low normal with a fall in serum sex hormone-binding
globulin in females, but with no change in either parameter in males. In both sexes, psychological assessment showed significant
enhancement of self-esteem with a tendency for improved overall well-being. Mood and fatigue also improved significantly,
with benefit being evident in the evenings. No effects on cognitive or sexual function, body composition, lipids, or bone
mineral density were observed. Our results indicate that DHEA replacement corrects this steroid deficiency effectively and
improves some aspects of psychological function. Beneficial effects in males, independent of circulating testosterone levels,
suggest that it may act directly on the central nervous system rather than by augmenting peripheral androgen biosynthesis.
These positive effects, in the absence of significant adverse events, suggest a role for DHEA replacement therapy in the treatment
of Addison's disease.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 11134123 [PubMed - indexed for MEDLINE]
J Psychosom Res. 2004 Oct;57(4):391-8. Related Articles, Links
The effect of brief exercise cessation on pain, fatigue, and mood symptom development in healthy, fit individuals.
Glass JM, Lyden AK, Petzke F, Stein P, Whalen G, Ambrose K, Chrousos G, Clauw DJ.
Department of Psychiatry and Institute for Social Research, University of Michigan, Ann Arbor, MI, USA. jglass@umich.edu
OBJECTIVE: Abnormalities of the biological stress response (hypothalamic-pituitary-adrenal axis and the autonomic nervous
system) have been identified in both fibromyalgia (FM) and chronic fatigue syndrome (CFS). Although these changes have been
considered to be partly responsible for symptom expression, we examine an alternative hypothesis that these HPA and autonomic
changes can be found in subsets of healthy individuals in the general population who may be at risk of developing these conditions.
Exposure to "stressors" (e.g., infections, trauma, etc.) may lead to symptom expression (pain, fatigue, and other
somatic symptoms) in part by precipitating lifestyle changes. In particular, we focus on the effect of deprivation of routine
aerobic exercise on the development of somatic symptoms. METHODS: Eighteen regularly exercising (>/=4 h/week) asymptomatic,
healthy adults refrained from physical activity for 1 week. We predicted that a subset of these individuals would develop
symptoms of FM/CFS with exercise deprivation, and this manuscript focuses on the baseline HPA axis, immune, and autonomic
function measures that may predict the development of symptoms. RESULTS: Eight of the subjects reported a 10% increase in
one or more symptoms (pain, fatigue, mood) after 1 week of exercise deprivation. These symptomatic subjects had lower HPA
axis (baseline cortisol prior to VO2max testing), immune (NK cell responsiveness to venipuncture), and autonomic function
(measured by heart rate variability) at baseline (prior to cessation of exercise) when compared to the subjects who did not
develop symptoms. CONCLUSIONS: A subset of subjects developed symptoms of pain, fatigue, or mood changes after exercise deprivation.
This cohort was different from the individuals who did not develop symptoms in baseline measures of HPA axis, immune, and
autonomic function. We speculate that a subset of healthy individuals who have hypoactive function of the biological stress
response systems unknowingly exercise regularly to augment the function of these systems and thus suppress symptoms. These
individuals may be at risk for developing chronic multisymptom illnesses (CMIs) (e.g., FM or CFS among others) when a "stressor"
leads to lifestyle changes that disrupt regular exercise.
PMID: 15518675 [PubMed - in process]
What else are people using?
J Pharmacol Sci. 2004 Jun;95(2):140-4. Related Articles, Links
Proof of the mysterious efficacy of ginseng: basic and clinical trials: suppression of adrenal medullary function in vitro
by ginseng.
Tachikawa E, Kudo K.
Department of Pharmacology, School of Medicine, Iwate Medical University. etachika@iwate-med.ac.jp
The root of Panax ginseng C.A. MEYER has been reported to have an anti-stress action. Therefore, the effects of ginseng
components on functions of adrenal medulla, which is one of the most important organs responsive to stress, were investigated
in vitro. First, the components of ginseng were mainly divided into two fractions, that is, the saponin-rich and non-saponin
fractions. The saponin-rich fraction greatly reduced the secretion of catecholamines from bovine adrenal chromaffin cells
stimulated by acetylcholine (ACh), whereas the non-saponin fraction did not affect it at all. The protopanaxatriol-type saponins
inhibited the ACh-evoked secretion much more strongly than the protopanaxadiol-type. On the other hand, the oleanane-type
saponin, ginsenoside-Ro, had no such effect. Recent reports have demonstrated that the saponins in ginseng are metabolized
and absorbed in digestive tracts following oral administration of ginseng. All of the saponin metabolites greatly reduced
the ACh-evoked secretion. M4 was the most effective inhibitor among the metabolites. M4 blocked ACh-induced Na(+) influx and
ion inward current into the chromaffin cells and into the Xenopus oocytes expressing human alpha3beta4 nicotinic ACh receptors,
respectively, suggesting that the saponin metabolites modulate nicotinic ACh receptors followed by the reduction of catecholamine
secretion. It is highly possible that these effects of ginsenosides and their metabolites are associated with the anti-stress
action of ginseng.
PMID: 15215636 [PubMed - in process]
Indian J Exp Biol. 2001 Apr;39(4):344-9. Related Articles, Links
Anti-stress activity of Indian Hypericum perforatum L.
Kumar V, Singh PN, Bhattacharya SK.
Department of Pharmaceutics, Banaras Hindu University, Varanasi, India.
Indian Hypericum perforatum (IHp) was investigated on a 14-day mild, unpredictable and inescapable foot shock stress (FSS)
induced perturbations in behaviour (depression), suppressed male sexual behaviour and cognitive dysfunction in albino rats.
Gastric ulceration, and adrenal gland and spleen weights, were also used as the stress indices. Panax ginseng (PG) was used
as the standard adaptogenic agent for comparison. FSS induced marked gastric ulceration, significant increase in adrenal gland
weight with concomitant decrease in spleen weight. Chronic stress also suppressed male sexual behaviour, induced behavioural
depression (Porsolt's swim despair test and learned helplessness test) and cognitive dysfunction (attenuated retention of
learning in active and passive avoidance tests). All these FSS induced perturbations were attenuated dose dependently by IHp
(100 and 200 mg/kg, po) and PG (100 mg/kg, po). The results indicate that IHp has significant anti-stress activity, qualitatively
comparable to PG, against a variety of behavioural and physiological perturbations induced by chronic stress, which has been
proposed to be a better indicator of clinical stress than acute stress, and may indicate adaptogenic activity.
PMID: 11491579 [PubMed - indexed for MEDLINE]
Phytother Res. 2001 Jun;15(4):311-8. Related Articles, Links
Adaptogenic activity of a novel, withanolide-free aqueous fraction from the roots of Withania somnifera Dun.
Singh B, Saxena AK, Chandan BK, Gupta DK, Bhutani KK, Anand KK.
Departments of Pharmacology and Natural Products Chemistry, Regional Research Laboratory, Canal Road, Jammu--Tawi 180
001, India. rrlj@nde.vsnl.net.in
The practitioners of the traditional Indian system of medicine regard Withania somnifera Dun. as the 'Indian ginseng'.
A new withanolide-free aqueous fraction was isolated from the roots of this plant and was evaluated for putative antistress
activity against a battery of tests such as hypoxia time, antifatigue effect, swimming performance time, swimming induced
gastric ulceration and hypothermia, immobilization induced gastric ulceration, autoanalgesia and biochemical changes in the
adrenal glands. This bioactive fraction exhibited significant antistress activity in a dose-related manner in all the parameters
studied. The extract of Withania somnifera root (a commercial preparation available locally) was used to compare the results.
A preliminary acute toxicity study in mice showed a good margin of safety. Copyright 2001 John Wiley & Sons, Ltd.
PMID: 11406854 [PubMed - indexed for MEDLINE]
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