Addison's Disease

Addison’s disease is a chronic clinical disease characterized by the progressive decline in the function of the adrenal glands. This potentially fatal disease may result in hyperpigmentation, hypotension, and cardiovascular collapse. Addison’s disease is easily diagnosed clinically and by the use of hormonal assays that reveal an elevated adrenocorticotropic hormone (ACTH) with a low plasma cortisol level.

This disorder is the result of endocrine processes. The incidence of this disorder is established as approximately 1 / 100.000.

Presentation

Addison’s disease has a typical insidious and chronic onset which may take several months. The following signs and symptoms are usually presented by patients with primary adrenal insufficiency:

On occasions, the symptomatology of Addison’s disease may appear acutely or abruptly. The acute onset of adrenal insufficiency symptoms is clinically referred to as Addisonian crisis. The following signs and symptoms are typically observed in acute adrenal failure:

  • Lower back pain
  • Abdominal pain
  • Leg pain
  • Severe diarrhea with dehydration
  • Incessant vomiting
  • Loss of consciousness
  • Low blood pressure
  • Hyperkalemia [7]

Workup

Addison’s disease is primarily investigated by means of an extensive clinical history taking followed by a careful review of the presenting signs and symptoms. When the patients are suspected of having Addison’s disease the following confirmatory tests may be done to ascertain the diagnosis:

  • Serum electrolytes: This blood test will determine the present level of sodium and potassium in the serum because these electrolytes are usually affected in Addison’s disease.
  • Hormonal assays: The hormonal levels of ACTH and cortisol are likewise determined to support the suspicion of Addison’s disease.
  • ACTH stimulation test: This hormonal test monitors the level of cortisol produced in the body after the injection of a synthetic ACTH hormone [8]. A damaged adrenal cortex may not respond to ACTH stimulation at all.
  • Insulin-induced hypoglycemia test: This will test for secondary adrenal insufficiency or those caused by a pituitary dysfunction. This test measures the levels of blood glucose and cortisol levels at the different time intervals after the introduction of synthetic insulin. The normal response of the body is to decrease the glucose level and increase the cortisol level.
  • Imaging: Computed tomography (CT scan) of the abdomen can elucidate the size and pathology of the adrenal gland at the suprarenal region [9]. Magnetic resonance imaging (MRI) may demonstrate the conditions of the pituitary gland in the skull to rule out secondary causes of adrenal insufficiency.

Treatment

The main goal in the treatment of Addison’s disease is to replace the deficient hormones in the right levels of steroid hormones that the adrenal glands are incapable of maintaining. The following are options used in the treatment of Addison’s disease:

  • Oral corticosteroids: Patients may be given oral hydrocortisone, prednisone, or cortisone acetate to replace the deficient cortisol hormone. In the same way, fludrocortisone may be given to replace the aldosterone deficiency.
  • Injectable corticosteroids: This steroid is given for the same indications. This option is resorted by patients if they are unable to tolerate oral corticosteroids [10].
  • Androgen replacement therapy: This regimen is given to women with low androgen levels. The oral dehydroepiandrosterone is preferentially used to address problems of libido and sexual satisfaction in women.
  • Sodium supplementations: Sodium may be amply given during activities that incurs heavy perspiration like exercises. Excessive diarrhea and vomiting among patients may also benefit from the sodium supplementations.

Prognosis

Addison’s disease presenting with significant adrenal hormone insufficiency can be life threatening if left untreated. Patients undergoing hormone replacement therapy with the deficient mineralocorticoid and glucocorticoid may live a normal life.

Etiology

The greater majority of cases of Addison’s disease or primary adrenal insufficiency is caused by the idiopathic atrophy of the adrenals, accounting for almost 70% of all cases. The leading theory postulated for the idiopathic atrophy of the adrenals points to an autoimmune origin. There are however, some less common causes of adrenal destruction which include granuloma, tuberculosis, histoplasmosis, amyloidosis, inflammatory necrosis, hemorrhage and tumorous growths. The most common cause of Addison’s disease among children is congenital adrenal hyperplasia (CAH).

Epidemiology

In the United States, the recent prevalence rate of Addison’s disease is up to 60 cases per one million population. Addison’s disease is relatively rare internationally. The increase in the mortality and morbidity rates is usually due to the delay in the replacement therapy of the mineralocorticoid and glucocorticoid hormones [2]. Although, primary adrenal insufficiency is already considered serious and potentially life threatening, concomitant illnesses like malignancies, cardiovascular diseases, and infectious diseases influences greatly the increased mortality rate among these patients [3].

The primary idiopathic and autoimmune form of Addison’s disease is more commonly seen in children and females. There is no racial predilection to Addison’s disease. The mean age of onset is 30 to 50 years old but may present earlier among the infantile cases of congenital adrenal hyperplasia.

Sex distribution
Age distribution

Pathophysiology

The pathogenesis of Addison’s disease or adrenal insufficiency is primarily due to the destruction of the adrenal cortex. Cortical destruction may either be inflammatory, necrotic, neoplastic, infectious, or hemorrhagic in nature. Signs and symptoms of adrenal insufficient usually present clinically when 90% or more of the adrenal cortex has been rendered dysfunctional or destroyed. The main systemic pathology is brought about by the lack of glucocorticoid and mineralocorticoid hormone secretion that is essential to the body.

Prevention

The congenital form of primary adrenal insufficiency cannot be prevented, although; new born screening may detect congenital adrenal hyperplasia in the first two days of life. The prompt diagnosis and hormone replacement therapy of Addison’s disease can prevent untoward complications and death.

Summary

Addison’s disease is a serious disorder that occurs when the adrenal glands are unable to produce sufficient hormones needed for proper metabolism. In this disorder, the hormones aldosterone and cortisol are insufficiently secreted from the suprarenal glands. For this reason, Addison’s disease is also referred to as primary adrenal insufficiency [1]. Hormonal treatment is the standard approach to this disease to mimic the natural function of the deficient adrenal hormone.

Patient Information

Definition

Addison’s disease is a serious disorder that occurs when the adrenal glands is unable to produce sufficient mineralocorticoid and glucocorticoid hormones needed for normal functioning.

Cause

The most common cause of Addison’s disease is idiopathic autoimmune adrenal atrophy. The other causes include granuloma, tuberculosis, histoplasmosis, amyloidosis, inflammatory necrosis, hemorrhage and tumors.

Symptoms

Patients usually present with anorexia, nausea and vomiting. Muscular fatigue and weakness are fairly common with hyperpigmentation of the skin. Signs of hypotension and hypoglycemia may also be observable.

Diagnosis

Diagnostics for Addison’s disease starts with blood test of electrolytes and hormones. ACTH stimulation tests and Insulin-induced hypoglycemia tests, imaging studies with CT scan and MRI may follow.

Treatment and follow-up

The cornerstone in the treatment of Addison’s disease is the active hormonal replacement of the deficient hormones. Glucocorticoids are replaced with oral and injectable steroids, mineralocorticoids are replace by fludrocortisone. Androgen replacement therapy for afflicted women can allay the signs of androgen deficiency.

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References

  1. Addison T. On the Constitutional and Local Effects of Disease of the Supra-renal Capsules. London, UK: Samuel Highley; 1855.
  2. White K, Arlt W. Adrenal crisis in treated Addison's disease: a predictable but under-managed event. Eur J Endocrinol. Jan 2010; 162(1):115-20.
  3. Kyriazopoulou V. Glucocorticoid replacement therapy in patients with Addison's disease. Expert Opin Pharmacother. Apr 2007; 8(6):725-9.
  4. Bergthorsdottir R, Leonsson-Zachrisson M, Oden A, et al. Premature mortality in patients with Addison's disease: a population-based study. J Clin Endocrinol Metab. Dec 2006; 91(12):4849-53.
  5. McBrien DJ. Steatorrhea in Addison's disease. Lancet. 1963; Vol I: 25-6.
  6. Barnett AH, Espiner EA, Donald RA. Patients presenting with Addison's disease need not be pigmented.Postgrad Med J. Nov 1982; 58(685):690-2.
  7. McBrien DJ. Steatorrhea in Addison's disease. Lancet. 1963; Vol I: 25-6.
  8. Kyriazopoulou V, Parparousi O, Vagenakis AG. Rifampicin-induced adrenal crisis in addisonian patients receiving corticosteroid replacement therapy. J Clin Endocrinol Metab. Dec 1984; 59(6):1204-6.
  9. Likhari T, Magzoub S, Griffiths MJ, et al. Screening for Addison's disease in patients with type 1 diabetes mellitus and recurrent hypoglycaemia. Postgrad Med J. Jun 2007; 83(980):420-1.
  10. Ma ES, Yang ZG, Li Y, et al. Tuberculous Addison's disease: morphological and quantitative evaluation with multidetector-row CT. Eur J Radiol. Jun 2007; 62(3):352-8.

  • Fatigue in neurological disorders - A Chaudhuri, PO Behan - The Lancet, 2004 - Elsevier
  • Permissive effect of glucocorticoids on vascular tone: Perturbations of this mechanism contribute to pathogenesis of Cushing's syndrome and Addison's disease - L Axelrod - The Lancet, 1983 - Elsevier
  • Addison's disease 2001 - S Ten, M New, N Maclaren - Journal of Clinical Endocrinology & , 2001 - Endocrine Soc
  • Adverse effects of medications for rhinitis - H Milgrom, B Bender - Annals of Allergy, Asthma & Immunology, 1997 - Elsevier
  • Deterioration of symptoms after start of thyroid hormone replacement - JS Murray, R Jayarajasingh, P Perros - BMJ, 2001 - bmj.com
  • Chronic fatigue syndrome: A disease of the hypothalamic-pituitary-adrenal axis? - MA Demitrack - Annals of medicine, 1994 - informahealthcare.com
  • 1 Aetiology and pathogenesis of hormonal and metabolic disorders in HIV infection - SK Grinspoon, DS Donovan, JP Bilezikian - clinical endocrinology and , 1994 - Elsevier
  • Addison's disease 2001 - S Ten, M New, N Maclaren - Journal of Clinical Endocrinology & , 2001 - Endocrine Soc
  • Carbohydrate metabolism in Addison's disease - GW Thorn, GF Koepf, RA Lewis - Journal of Clinical , 1940 - ncbi.nlm.nih.gov
  • Addison's disease, vitiligo and multiple autoantibodies. - CJ Burns-Cox, JE Pearson - Postgraduate Medical Journal, 1972 - ncbi.nlm.nih.gov
  • A possible autoimmune basis for Addison's disease in three siblings, one with idiopathic hypoparathyroidism, pernicious anemia and superficial moniliasis - W Hung, CJ Migeon, RH Parrott - New England Journal of , 1963 - Mass Medical Soc
  • Chronic fatigue syndrome: a form of Addison's disease - R Baschetti - Journal of Internal Medicine, 2001 - Wiley Online Library
  • Autoantibodies to steroidogenic enzymes in patients with premature ovarian failure with and without Addison's disease - C Dal Pra, S Chen, J Furmaniak, BR Smith - European journal of , 2003 - EFES
  • Addison's disease and pregnancy - F Brent - The American Journal of Surgery, 1950 - Elsevier
  • Familial Addison's disease: case reports of two sisters with corticoid deficiency unassociated with hypoaldosteronism - TH SHEPARD, BH LANDING - Archives of Pediatrics & , 1959 - Am Med Assoc
  • Adrenal insufficiency - W Arlt, B Allolio - The Lancet, 2003 - Elsevier
  • Addison's disease - LK Nieman, ML Chanco Turner - Clinics in dermatology, 2006 - Elsevier
  • Addison's disease 2001 - S Ten, M New, N Maclaren - Journal of Clinical Endocrinology & , 2001 - Endocrine Soc
  • Addison's disease with renal microangiopathy and renal failure (a new syndrome) - Y Sachdev, AR Morley, R Wilkinson, R Hall - QJM, 1977 - Oxford Univ Press
  • Addison's disease 2001 - S Ten, M New, N Maclaren - Journal of Clinical Endocrinology & , 2001 - Endocrine Soc
  • ACTH-producing tumor of the pituitary gland - DH Nelson, JW Meakin, JB Dealy Jr - England Journal of , 1958 - Mass Medical Soc
  • A possible autoimmune basis for Addison's disease in three siblings, one with idiopathic hypoparathyroidism, pernicious anemia and superficial moniliasis - W Hung, CJ Migeon, RH Parrott - New England Journal of , 1963 - Mass Medical Soc
  • A neurological syndrome associated with orthostatic hypotension: a clinical-pathologic study - GM SHY, GA DRAGER - Archives of neurology, 1960 - Am Med Assoc
  • A syndrome of immunoglobulin A deficiency, diabetes mellitus, malabsorption, a common HLA haplotype. Immunologic and genetic studies of forty-three family - DH Van Thiel, WI Smith Jr, BS Rabin - Annals of internal , 1977 - ncbi.nlm.nih.gov
  • A possible autoimmune basis for Addison's disease in three siblings, one with idiopathic hypoparathyroidism, pernicious anemia and superficial moniliasis - W Hung, CJ Migeon, RH Parrott - New England Journal of , 1963 - Mass Medical Soc
  • A clinical and immunological study of adrenocortical insufficiency (Addison's disease) - WJ Irvine, AG Stewart, L Scarth - Clinical and experimental , 1967 - ncbi.nlm.nih.gov
  • Addison's disease in Africa—a teaching hospital experience - S Soule - Clinical endocrinology, 2001 - Wiley Online Library
  • 17 Pericardial Diseases Bernhard Maisch, Jordi Soler-Soler, Liv Hatle - AD Ristic - mstwente.nl
  • Autoimmune polyglandular syndromes - M Neufeld, N Maclaren, R Blizzard - Pediatr Ann, 1980 - pathology2.jhu.edu
  • A possible autoimmune basis for Addison's disease in three siblings, one with idiopathic hypoparathyroidism, pernicious anemia and superficial moniliasis - W Hung, CJ Migeon, RH Parrott - New England Journal of , 1963 - Mass Medical Soc
  • A challenging case: Severe hypercalcemia in a puppy with hypoadrenocorticism - TL Goodson, SC Randell - 2009 - veterinarymedicine.dvm360.com
  • A comparison of the adrenal responses to hypoglycemia, metyrapone and ACTH. - JC Nelson, DJ Tindall Jr - The American journal of the medical , 1978 - ukpmc.ac.uk
  • Acute renal failure in accidental hypothermia of cold water immersion - Y Yoshitomi, S Kojima, M Ogi, M Kuramochi - American journal of kidney , 1998 - Elsevier
  • Addison's disease and Addisonian anemia: A case report - SJ KRA, AW BARILE - Archives of Internal Medicine, 1964 - Am Med Assoc
  • Autism and autoimmune disease: a family study - J Money, NA Bobrow, FC Clarke - Journal of Autism and Developmental , 1971 - Springer
  • Addison's disease 2001 - S Ten, M New, N Maclaren - Journal of Clinical Endocrinology & , 2001 - Endocrine Soc
  • Addison's disease 2001 - S Ten, M New, N Maclaren - Journal of Clinical Endocrinology & , 2001 - Endocrine Soc
  • Autoimmune/Inflammatory and Other Diseases Associated with Vitiligo - I Mollet, N van Geel, J Lambert - Vitiligo, 2010 - books.google.com
  • 21-Hydroxylase, a major autoantigen in idiopathic Addison's disease - O Winqvist, FA Karlsson, O Kämpe - The Lancet, 1992 - Elsevier
  • Addison's disease and pregnancy - E Albert, K Dalaker, R Jorde - Acta Obstetricia et , 1989 - Wiley Online Library
  • ACTH IN ASTHMA - B Rose, JAP Pare, K Pump - Canadian Medical , 1950 - ncbi.nlm.nih.gov
  • Asymptomatic hyponatremia in pulmonary tuberculosis - EAH Sims, LG Welt, J Orloff - Journal of Clinical , 1950 - ncbi.nlm.nih.gov
  • Addison's disease 2001 - S Ten, M New, N Maclaren - Journal of Clinical Endocrinology & , 2001 - Endocrine Soc
  • Autoimmune thyroiditis, adrenalitis and oophoritis - M Edmonds, L Lamki, DW Killinger, R Volpé - The American journal of , 1973 - Elsevier
  • Abdominal tuberculosis--a disease revived. - NV Addison - Annals of the Royal College of Surgeons of England, 1983 - ncbi.nlm.nih.gov
  • A clinical correlation between encephalopathy and papilloedema in Addison's disease - A Jefferson - Journal of neurology, neurosurgery, and psychiatry, 1956 - ncbi.nlm.nih.gov
  • A test for adrenal cortical insufficiency - GW Thorn, PH Forsham, FTG Prunty - Journal of the American , 1948 - Am Med Assoc
  • Addison's disease 2001 - S Ten, M New, N Maclaren - Journal of Clinical Endocrinology & , 2001 - Endocrine Soc
  • A brief history of testosterone - ER Freeman, DA Bloom, EJ McGUIRE - The Journal of urology, 2001 - Elsevier
  • Amelioration of metabolic acidosis with fludrocortisone therapy in hyporeninemic hypoaldosteronism - A Sebastian, M Schambelan - England Journal of , 1977 - Mass Medical Soc
  • Anti-adrenal cellular hypersensitivity in Addison's disease. II. Correlation with clinical and serological findings - J Nerup, G Bendixen - Clinical and experimental immunology, 1969 - ncbi.nlm.nih.gov
  • Permissive effect of glucocorticoids on vascular tone: Perturbations of this mechanism contribute to pathogenesis of Cushing's syndrome and Addison's disease - L Axelrod - The Lancet, 1983 - Elsevier
  • Acute adrenal insufficiency in the burn intensive care unit - RL Sheridan, CM Ryan, RG Tompkins - Burns, 1993 - Elsevier
  • Cranial Nerve I: The Olfactory Nerve - HK Walker, WD Hall, JW Hurst, HK Walker - 1990 - ncbi.nlm.nih.gov
  • Atypical amyloid disease, with observations on a new silver stain for amyloid - LS King - The American journal of pathology, 1948 - ncbi.nlm.nih.gov
  • Addison's disease presenting as depression. - ML Kaushik, RC Sharma - Indian journal of medical sciences, 2003 - Medknow
  • A test for adrenal cortical insufficiency - GW Thorn, PH Forsham, FTG Prunty - Journal of the American , 1948 - Am Med Assoc
  • Corticotropin levels in Addison's disease are not associated with increased plasma arginine vasopressin and corticotropin-releasing factor concentrations in peripheral - GA Wittert, JH Livesey, C Florkowski, HK Or - Journal of Clinical , 1993 - Endocrine Soc
  • Addison's Disease in Two Brothers - JN Briggs, JF Goodwin, A Wilson - British Medical Journal, 1951 - bmj.com
  • Cortex and steroid 21-hydroxylase autoantibodies in adult patients with organ-specific autoimmune diseases: markers of low progression to clinical Addison's disease - C Betterle, M Volpato, BR Smith - Journal of Clinical , 1997 - Endocrine Soc
  • Acute change in extracellular fluids associated with major surgical procedures - T Shires, J Williams, F Brown - Annals of surgery, 1961 - ncbi.nlm.nih.gov
  • , FSH, and LH with stages of puberty and bone age in normal boys and girls and in patients with Addison's disease or hypogonadism or with premature or late - PC SIZONENKO, LUC PAUNIER - Journal of Clinical Endocrinology , 1975 - Endocrine Soc
  • Adaptive reaction to stress - H Selye, C Fortier - Psychosomatic Medicine, 1950 - Am Psychosomatic Soc
  • Atrophy of the adrenals associated with Addison's disease - W Susman - The Journal of Pathology and Bacteriology, 1930 - Wiley Online Library
  • A STANDARD TEST FOR MEASURING THE VARIABILITY OF BLOOD PRESSURE: ITS SIGNIFICANCE AS AN INDEX OF THE PREHYPERTENSIVE STATE* - EA HINES JR, GE BROWN - Annals of Internal Medicine, 1933 - Am Coll Physicians
  • Addison's disease in children - JC Jaudon - The Journal of pediatrics, 1946 - Elsevier
  • Causes of chronic orthostatic hypotension - D Robertson, RM Robertson - Archives of internal medicine, 1994 - Am Med Assoc
  • Classification of the cerebral edemas with reference to hydrocephalus and pseudotumor cerebri - TH Milhorat - Child's Nervous System, 1992 - Springer
  • Acute large-bowel pseudo-obstruction - AM Gilchrist, JOM Mills, CFJ Russell - Clinical radiology, 1985 - Elsevier
  • AND 17‐HYDROXYPROGESTERONE ON BLOOD PRESSURE RESPONSES OF NORMAL AND ADRENALECTOMIZED RATS DURING HYPOVOLAEMIC SHOCK - BAK Khalid, P Moral, Z Merican - Clinical and experimental , 1987 - Wiley Online Library
  • Acute focal edema of the brain in children with head injuries - W Pickles - New England Journal of Medicine, 1949 - Mass Medical Soc
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