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:

• Anorexia
• Weight loss
• Fatigue
• Muscular weakness
• Hyperpigmentation [4]
• Hypotension
• Syncope
• Hypoglycemia [5]
• Salt cravings
• Nausea and vomiting
• Diarrhea [6]
• Myositis and arthritis
• Irritability 
• Depression
• Alopecia
• Sexual dysfunction in women

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]

• Weakness

  It presents with hyperpigmentation, weakness, hypoglycemia, and seizures. [pedclerk.bsd.uchicago.edu]

  Addison disease is usually caused by your immune system attacking your adrenal glands Symptoms come on slowly You feel weak and tired all the time and may get dizzy when you stand up Your skin may develop dark areas, like an uneven tan Doctors give you [merckmanuals.com]

  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]

  Depends on the course of the disease: acute stage: the patient presents with fever, back pain, hypotension, weakness chronic stage : progressive lethargy, weakness, cutaneous pigmentation, weight loss Laboratory data chemistry: hyponatremia, hyperkalemia [radiopaedia.org]

• Fatigue

  Forty-eight per cent of patients showed abnormal fatigue, while 61% had severe fatigue. The CIS fatigue scores were significantly higher compared to controls (P < 0·01). [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]

• 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]

  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]

  Abstract A 19-yr-old intact female variable flying fox ( Pteropus hypomelanus ) presented with lethargy, behavior changes, and substantial weight loss. [doi.org]

• 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. .. [mh.bmj.com]

• 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

  In major stress (temperatures above 38 degrees C and/or vomiting), the hydrocortisone dose should be increase to three to four times the normal replacement. [pedclerk.bsd.uchicago.edu]

  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]

  New onset Addison's disease is rare in pregnancy but may present with prolonged vomiting and weight loss. Therefore adrenal failure should be included in the differential diagnosis of hyperemesis gravidarum. [ncbi.nlm.nih.gov]

• 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]

• 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]

  If left untreated, Addison's disease can cause severe abdominal pain, weakness, low blood pressure, kidney failure and shock. [ar.childrenshospital.org]

  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]

  Patients with Addison’s Disease may present acutely in Addisonian crisis that involve sudden sharp leg pain, lower back or abdominal pain, nausea, vomiting, hyponatremic dehydration, hyperkalemia, metabolic acidosis, hypotension, hypoglycemia, shock or [pedclerk.bsd.uchicago.edu]

• Loss of Appetite

  Symptoms & Causes The most common symptoms are fatigue, muscle weakness, loss of appetite, weight loss, and abdominal pain. [niddk.nih.gov]

  Symptoms of Addison disease start slowly and usually include: Feeling weak and tired Feeling dizzy when you stand up Loss of appetite Feeling sick to your stomach or throwing up Diarrhea Sometimes you also have: Darkening of your skin Black freckles on [merckmanuals.com]

• 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]

• 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]

  Addisonian (adrenal) crisis: acute complication of adrenal insufficiency (circulatory collapse, dehydration, hypotension, nausea, vomiting, hypoglycemia); usually precipitated by an acute physiologic stressor(s) such as surgery, illness, exacerbation [unboundmedicine.com]

  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]

  Poorly managed or undiagnosed adrenal insufficiency Symptoms Inappropriate fatigue Depression Darkening of the skin Loss of appetite, nausea and/or vomiting Diarrhea Salt craving Orthostatic hypotension (light headedness upon standing) or incredibly low [addisonssupport.com]

  Other symptoms include orthostatic hypotension (a drop in blood pressure when standing, which can cause dizziness or fainting) and skin changes. [diabetesselfmanagement.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]

  Clinical symptoms include ANOREXIA; NAUSEA; WEIGHT LOSS; MUSCLE WEAKNESS; and HYPERPIGMENTATION of the SKIN due to increase in circulating levels of ACTH precursor hormone which stimulates MELANOCYTES. [hon.ch]

• 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]

  Sim ), 이석종 ( Seok Jong Lee ), 이창돈 ( Chang Don Lee ) 발행기관 : 영남대학교 의과대학 간행물 : 영남의대학술지 29권 1호 발행 연도 : 2012 페이지 : pp. 28-30 (3 pages) 다운로드 (기관인증 필요) 초록보기 A 48-year-old male visited the emergency room of the authors` hospital due to nausea, vomiting, and myalgia [kiss.kstudy.com]

  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]

• Hyperpigmentation

  The trusted provider of medical information since 1899 Hyperpigmentation of Addison Disease Hyperpigmentation of Addison Disease Patients with Addison disease have diffuse hyperpigmentation as well as hyperpigmentation on extensor surfaces (here the elbows [msdmanuals.com]

  It presents with hyperpigmentation, weakness, hypoglycemia, and seizures. [pedclerk.bsd.uchicago.edu]

  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]

• Loss of Pubic Hair

  […] sugar level Loss of interest in sex (decreased libido) Irregular or absent menstruation (amenorrhea) Loss of pubic hair and body hair Muscle twitching or seizures. [innerbody.com]

• Loss of Libido

  Loss of libido and recurrent admissions for adrenal crisis may contribute. Osteoporosis. On lower doses of hydrocortisone, this should not be a risk, but may occur when other steroids or regular high doses are required for management. [patient.info]

• 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]

  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]

  […] 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]

  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]

  Addison disease is usually caused by your immune system attacking your adrenal glands Symptoms come on slowly You feel weak and tired all the time and may get dizzy when you stand up Your skin may develop dark areas, like an uneven tan Doctors give you [merckmanuals.com]

  Warning signs include: severe nausea headache dizziness extreme weakness chills or fever confusion. [addisons.org.uk]

• 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 [msdmanuals.com]

• Apathy

  These may be associated with: Abdominal or flank pain Fever with negative cultures and unresponsive to antibiotic therapy Unexplained mental changes (i.e., apathy, depression) Electrolyte abnormalities (hyponatremia, hyperkalemia, hypoglycemia) Neutropenia [clinicaladvisor.com]

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]

  Hyponatremia and hyperkalemia may also result form chronic renal insufficiency. Diagnosis Addison’s requires a high degree of suspicion and investigation. [pedclerk.bsd.uchicago.edu]

  Preparation of such a patient for surgery should include treatment of hypovolemia, hyperkalemia, and hyponatremia. [openanesthesia.org]

• Eosinophils Increased

  Even with treatment, Addison disease may cause a slight increase in mortality. It is not clear whether this increase is due to mistreated adrenal crises or long-term complications of inadvertent over-replacement. [msdmanuals.com]

• Normocytic Anemia

  Laboratory testing showed hyponatremia, hyperkaliemia and severe normocytic anemia. Endocrinological evaluation disclosed low morning cortisol and increased adrenocorticotropic hormone levels. [ncbi.nlm.nih.gov]

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.

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.

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).

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.

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.

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.

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.

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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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.