Edit concept Question Editor Create issue ticket

Addison's Disease

Addisons 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.


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:

Fatigue
  • The patient noted a marked symptomatic improvement in morning symptoms, but with persistent fatigue during the day.[ncbi.nlm.nih.gov]
  • Health Diseases Adrenal Fatigue Addison’s Disease and Adrenal Fatigue Adrenal insufficiency, also known as Addison’s disease, is an autoimmune condition. Though the features overlap, it is different than adrenal fatigue.[dummies.com]
Weakness
  • Classically, patients affected with Addison's disease develop weakness, anorexia, electrolyte imbalances: decreased sodium and chloride with increased serum potassium resulting in hypotension, and hyperpigmentation of the skin and mucous membranes.[ncbi.nlm.nih.gov]
  • Aldosterone deficiency Hypotension Hyponatremia Hyperkalemia Acidosis "Salt appetite" Cortisol deficiency Sensation of weakness Nausea and vomiting Weight loss Hypoglycemia Increased ACTH secretion Hyperpigmentation of the skin, caused by the release[flexikon.doccheck.com]
Weight Loss
  • On review of history, the cause of vomiting and weight loss was questioned and combined with subsequent biochemical testing a diagnosis of Addison's disease was made.[ncbi.nlm.nih.gov]
Fever
  • Orthostatic hypotension, fever, and hypoglycemia characterize acute adrenal crisis, whereas chronic primary adrenal insufficiency presents with a more insidious history of malaise, anorexia, diarrhea, weight loss, joint, and back pain.[ncbi.nlm.nih.gov]
  • This cyclic pattern of fever, known as the Pel-Ebstein fever, is “a classic clinical sign in Hodgkin’s disease. ..[dx.doi.org]
Anorexia
  • Classically, patients affected with Addison's disease develop weakness, anorexia, electrolyte imbalances: decreased sodium and chloride with increased serum potassium resulting in hypotension, and hyperpigmentation of the skin and mucous membranes.[ncbi.nlm.nih.gov]
Vomiting
  • On review of history, the cause of vomiting and weight loss was questioned and combined with subsequent biochemical testing a diagnosis of Addison's disease was made.[ncbi.nlm.nih.gov]
  • Excessive diarrhea and vomiting among patients may also benefit from the sodium supplementations. Addison’s disease presenting with significant adrenal hormone insufficiency can be life threatening if left untreated.[symptoma.com]
Nausea
  • Hyperpigmentation was observed in 76%, nausea and vomiting occurred in more than 40%, and weight loss was noted in 25%.[ncbi.nlm.nih.gov]
Diarrhea
  • Excessive diarrhea and vomiting among patients may also benefit from the sodium supplementations. Addison’s disease presenting with significant adrenal hormone insufficiency can be life threatening if left untreated.[symptoma.com]
  • Orthostatic hypotension, fever, and hypoglycemia characterize acute adrenal crisis, whereas chronic primary adrenal insufficiency presents with a more insidious history of malaise, anorexia, diarrhea, weight loss, joint, and back pain.[ncbi.nlm.nih.gov]
  • Get medical care for your child right away if he or she has vomiting or diarrhea or other illness.[urmc.rochester.edu]
  • Severe vomiting and diarrhea. Sudden, deep pain in the lower back, belly, or legs. Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission.[my.clevelandclinic.org]
Abdominal Pain
  • After initial improvement with antimicrobial therapy, new symptoms appeared, consisting of persistent vomits, abdominal pain and hypotension, which led to the diagnosis of Addison's disease.[ncbi.nlm.nih.gov]
  • Symptoms & Causes The most common symptoms are fatigue, muscle weakness, loss of appetite, weight loss, and abdominal pain.[niddk.nih.gov]
  • Seek emergency medical treatment if you experience the following signs and symptoms: Severe weakness Confusion Pain in your lower back or legs Severe abdominal pain, vomiting and diarrhea, leading to dehydration Reduced consciousness or delirium In an[mayoclinic.org]
  • If left untreated, Addison's disease can cause severe abdominal pain, weakness, low blood pressure, kidney failure and shock.[ar.childrenshospital.org]
  • Common symptoms include: weakness fatigue abdominal pain nausea weight loss low blood pressure darkened skin (in the case of Addison’s disease) salt craving (in the case of Addison’s disease) dizziness upon standing depression However, there are different[endocrineweb.com]
Loss of Appetite
  • Symptoms & Causes The most common symptoms are fatigue, muscle weakness, loss of appetite, weight loss, and abdominal pain.[niddk.nih.gov]
  • You may experience: lack of energy or motivation (fatigue) muscle weakness low mood loss of appetite and unintentional weight loss increased thirst Over time, these problems may become more severe and you may experience further symptoms, such as dizziness[nhs.uk]
  • Loss of appetite. Low blood glucose. Low blood pressure. Muscle weakness. Nausea. Patches of dark skin, especially around scars, skin folds, and joints. Sensitivity to cold. Unexplained weight loss. Vomiting. Worsening fatigue (extreme tiredness).[my.clevelandclinic.org]
Hypotension
  • As hypotension may be one of the few situations, in which NAAION may be treatable and the visual loss reversible, it is important to recognize and treat sustained episodes of hypotension in these individuals.[ncbi.nlm.nih.gov]
  • Hypotension. Postural hypotension. Other situations which should provoke consideration of Addison's disease include: People with hypothyroidism in whom symptoms get worse when thyroxine treatment is commenced.[patient.info]
Orthostatic Hypotension
  • Orthostatic hypotension, fever, and hypoglycemia characterize acute adrenal crisis, whereas chronic primary adrenal insufficiency presents with a more insidious history of malaise, anorexia, diarrhea, weight loss, joint, and back pain.[ncbi.nlm.nih.gov]
  • Here are some key symptoms that can suggest Addison’s disease: When this condition first begins, you may experience fatigue, lightheadedness, and orthostatic hypotension (a drop in blood pressure when moving from lying down to either a sitting or standing[dummies.com]
  • Other symptoms include orthostatic hypotension (a drop in blood pressure when standing, which can cause dizziness or fainting) and skin changes.[diabetesselfmanagement.com]
  • hypotension ) darkening (hyperpigmentation) of the skin, in most cases, including areas not exposed to the sun (characteristic sites are skin creases (e.g. of the hands), nipples, and the inside of the cheek (buccal mucosa), also old scars may darken[web.archive.org]
Oral Pigmentation
  • The patient presented with oral pigmented lesions, which were hypothesized to be mucosal pigmentation associated with Addison's disease.[ncbi.nlm.nih.gov]
Hyperpigmentation
  • Herein this case report, we focus on the subtle findings of diffuse hyperpigmentation and intermittent but repetitive "flu-like" symptoms in two patients to correctly identify the diagnosis of Addison's disease effectively and efficiently.[ncbi.nlm.nih.gov]
  • This potentially fatal disease may result in hyperpigmentation, hypotension, and cardiovascular collapse.[symptoma.com]
Alopecia
  • A young Marshallese woman presented with the insidious development of fever, cough, fatigue, profound weakness, massive weight loss, cachexia, alopecia, amenorrhea, and periumbilical hyperpigmentation.[ncbi.nlm.nih.gov]
  • […] usually presented by patients with primary adrenal insufficiency: Anorexia Weight loss Fatigue Muscular weakness Hyperpigmentation Hypotension Syncope Hypoglycemia Salt cravings Nausea and vomiting Diarrhea Myositis and arthritis Irritability Depression Alopecia[symptoma.com]
  • Autoimmune thyroid disease • TSH; check free T4 and anti TPO antibodies if TSH outside reference range Type 1 diabetes • Fasting glucose/HbA1c Autoimmune parathyroid disease • Bone profile — check PTH if low calcium Vitiligo • Physical examination only Alopecia[bjgp.org]
  • Common autoimmune diseases associated with Addison’s Disease are: Chronic thyroiditis Graves’ disease Testicular dysfunction Hypopituitarism Hypoparathyroidism Type 1 diabetes Alopecia areata Hypogonadism Sjogren’s syndrome Vitiligo Pernicious anemia[dovemed.com]
Loss of Pubic Hair
  • […] of pubic hair and body hair Muscle twitching or seizures.[innerbody.com]
Muscle Weakness
  • The physical examination was completely normal except for muscle weakness, hyperpigmentation on labial mucosa and skin in a patient. The laboratory tests revealed anemia and hypoglycemia.[ncbi.nlm.nih.gov]
  • Symptoms & Causes The most common symptoms are fatigue, muscle weakness, loss of appetite, weight loss, and abdominal pain.[niddk.nih.gov]
  • A medical condition in which the adrenal glands do not produce enough cortisol or, in some cases, aldosterone, causing such problems as weight loss, muscle weakness, fatigue, low blood pressure, and sometimes darkened patches of skin.[diabetesselfmanagement.com]
  • The disease is characterized by weight loss, muscle weakness, fatigue, low blood pressure, and sometimes darkening of the skin in both exposed and non-exposed parts of the body. Addison disease affects about 1 in 100,000 people.[web.archive.org]
  • Symptoms of Addison's disease begin gradually and include chronic, worsening fatigue, muscle weakness, loss of appetite, and weight loss.[medicinenet.com]
Myalgia
  • We present a 51-year-old male patient, who underwent hemodialysis therapy for 8 years, diagnosed with Addison's disease after having myalgia, skin hyperpigmentation, weight loss, sweating, and nausea for the past few weeks.[ncbi.nlm.nih.gov]
  • Chronic Addison's disease Typically, chronic primary adrenal insufficiency has an insidious onset and presents with many non-specific symptoms and signs: - Weakness and fatigability (99%), anorexia (99%), nausea/vomiting, abdominal pain, myalgias/arthralgias[clinicaladvisor.com]
  • Myalgias and flaccid muscle paralysis may occur due to hyperkalemia. Patients may have a history of using medications known to affect adrenocortical function or to increase cortisol metabolism.[web.archive.org]
Muscle Cramp
  • Muscle cramps and joint pains. Syncope or dizziness (due to hypotension). Confusion. Personality change. Irritability. Loss of pubic or axillary hair in women, delayed puberty in children.[patient.info]
  • Symptoms of adrenal insufficiency include fatigue, nausea, anorexia, postural dizziness and muscle cramps. A history of weight loss, reduced strength and salt craving may also be found.[em-consulte.com]
Arthralgia
  • Chronic Addison's disease Typically, chronic primary adrenal insufficiency has an insidious onset and presents with many non-specific symptoms and signs: - Weakness and fatigability (99%), anorexia (99%), nausea/vomiting, abdominal pain, myalgias/arthralgias[clinicaladvisor.com]
Muscular Atrophy
  • Spontaneous resolution is rare, and the disease may be aggressive with soft-tissue sclerosis and muscular atrophy, bone involvement with resorptive osteolysis, or loss of the distal parts of fingers or toes.[dermatologyadvisor.com]
Decreased Libido
  • libido) Irregular or absent menstruation (amenorrhea) Loss of pubic hair and body hair Muscle twitching or seizures.[innerbody.com]
  • . - Orthostatic hypotension (90%) - Electrolyte abnormalities: hyponatremia (88%), hyperkalemia (64%), hypercalcemia (6%) - Hyperpigmented skin and mucosa - Sparse axillary hair (more common in women), amenorrhea, decreased libido (both men and women)[clinicaladvisor.com]
  • Impotence and decreased libido may occur in male patients, especially in those with compromised or borderline testicular function.[web.archive.org]
Amenorrhea
  • A young Marshallese woman presented with the insidious development of fever, cough, fatigue, profound weakness, massive weight loss, cachexia, alopecia, amenorrhea, and periumbilical hyperpigmentation.[ncbi.nlm.nih.gov]
  • […] weakness Low blood pressure Dizziness Darkening of the skin and mucous membranes (hyperpigmentation) Nausea and vomiting Craving salt Headache Sweating Low blood sugar level Loss of interest in sex (decreased libido) Irregular or absent menstruation (amenorrhea[innerbody.com]
  • Measuring serum calcium, phosphorus, glucose and thyrotropin Measure serum PTH if patient has hypocalcemia Hypogonadism should be investigated in post-menarchal female adolescents presenting in oligomenorrhea or amenorrhea by measuring FSH and LH.[pedclerk.bsd.uchicago.edu]
  • Steroid-responsive hyperprolactinemia may contribute to the impairment of gonadal function and to the amenorrhea.[web.archive.org]
Oligomenorrhea
  • Measuring serum calcium, phosphorus, glucose and thyrotropin Measure serum PTH if patient has hypocalcemia Hypogonadism should be investigated in post-menarchal female adolescents presenting in oligomenorrhea or amenorrhea by measuring FSH and LH.[pedclerk.bsd.uchicago.edu]
Dizziness
  • She presented with a four-week history of decreased energy, malaise and postural dizziness. Our patient described an unusual diet of liquorice sticks and soy sauce, consuming around 46 g of salt per week.[ncbi.nlm.nih.gov]
  • Common symptoms include: weakness fatigue abdominal pain nausea weight loss low blood pressure darkened skin (in the case of Addison’s disease) salt craving (in the case of Addison’s disease) dizziness upon standing depression However, there are different[endocrineweb.com]
  • Symptoms of Addison disease include: Chronic diarrhea, nausea, and vomiting Darkening of the skin in some places Dehydration Dizziness when standing up Low-grade fever Extreme weakness, fatigue, and slow, sluggish movement Darker skin on the inside of[medlineplus.gov]
Asthenia
  • Adrenal crisis is characterized by Profound asthenia (weakness) Severe pain in the abdomen, lower back, or legs Peripheral vascular collapse Renal shutdown with azotemia Body temperature may be low, although severe fever often occurs, particularly when[merckmanuals.com]
Apathy
  • ., apathy, depression) Electrolyte abnormalities (hyponatremia, hyperkalemia, hypoglycemia) Neutropenia, eosinophilia B.[clinicaladvisor.com]

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.
Hyponatremia
  • Based on the findings of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), we had considered that the cause of the hyponatremia was syndrome of inappropriate secretion of antidiuretic hormone (SIADH) due to active extrapulmonary tuberculosis[ncbi.nlm.nih.gov]
  • Preparation of such a patient for surgery should include treatment of hypovolemia, hyperkalemia, and hyponatremia.[openanesthesia.org]
Eosinophils Increased
  • Increased Imaging X-ray or CT Evidence of Calcification in adrenal area Renal TB Pulmonary TB Hyperpigmentation can result from bronchogenic carcinoma, ingestion of heavy metals (eg, iron, silver), chronic skin conditions, or hemochromatosis.[merckmanuals.com]

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.

References

Article

  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.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2019-07-11 21:43