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| __NOTOC__ | | __NOTOC__ |
| '''For patient information, click [[Adrenal atrophy (patient information)|here]]'''
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| {{Adrenal_atrophy}} | | {{Adrenal_atrophy}} |
| {{CMG}} | | {{CMG}}; {{AE}} {{MHP}} |
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| '''Associate Editor-In-Chief:''' {{CZ}}
| | {{SK}} [[Adrenal atrophy]]; [[Adrenal insufficiency]]; [[Adrenal crisis]] |
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| ==[[Adrenal atrophy pathophysiology|Pathophysiology]]== | | ==[[Adrenal atrophy pathophysiology|Pathophysiology]]== |
| ===Pathogenesis===
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| The exact pathogenesis of adrenal atrophy is not fully understood. However, it is thought that adrenal atrophy is caused by direct insult or the lack of stimulation of the gland. As a result, the disease can be categorized as primary or secondary.
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| *Primary Adrenal Atrophy: The primary atrophy is due to direct insult to the adrenal tissue due to:
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| **Infections (TB, CMV, histoplasmosis, paracoccidioidomycosis)
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| **Vascular impairments (hemorrhage from sepsis, adrenal vein thrombosis, HIT)
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| **Deposition disease (hemochromatosis, amyloidosis, sarcoidosis)
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| **Drugs (azole anti-fungals, etomidate (even one dose), rifampin, anticonvulsants)
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| **Cytotoxic agents such as mitotane.
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| *Secondary Adrenal Atrophy
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| The secondary atrophy is mainly due to the loss of ACTH and trophic support of the adrenal cortex, and this may result in deficits in functional capability of the cortex to produce glucocorticoids. This situation occurs in patients who are on prolonged glucocorticoid therapy, which leads to prolonged inhibition of endogenous pituitary ACTH secretion. Removal of the therapy often results in adrenocortical incompetence.
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| Adrenal atrophy may caused by inhibition of pituitary ACTH or hypothalamic function. Compounds such as valproic acid, bromocriptine, cyproheptadine, ketanserin, ritanserin, somatostatin analogs, glucocorticoids, 4′-thio-beta-d-arabinofuranosylcytosine, and hexachlorobenzene have been noted previously to impair hypothalamo-pituitary function through deficits in ACTH or CRH in various species.
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| ===Genetics===
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| The development of adrenal atrophy is the result of multiple genetic and environmental factors, as discussed above. However, the congenital adrenal hypoplasia, a form of adrenal hypotrophy is known as a result of the mutation on the following genes:
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| *An X-linked gene, NROB1, encoding DAX-1 protein
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| *The steroidogenic factor 1 (SF-1) gene, encoded on the 9q33 loci
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| The autosomal recessive ACTH resistance syndromes such as triple-A syndrome and familial glucocorticoid deficiency, are among other genetics disorders yielding to adrenal atrophy.<ref name="pmid31747186">{{cite journal |vauthors=Saleem F, Baradhi KM |title= |journal= |volume= |issue= |pages= |date= |pmid=31747186 |doi= |url=}}</ref><ref name="pmid16597550">{{cite journal |vauthors=Colagiovanni DB, Drolet DW, Dihel L, Meyer DJ, Hart K, Wolf J |title=Safety assessment of 4'-thio-beta-D-arabinofuranosylcytosine in the beagle dog suggests a drug-induced centrally mediated effect on the hypothalamic-pituitary-adrenal axis |journal=Int J Toxicol |volume=25 |issue=2 |pages=119–26 |date=2006 |pmid=16597550 |doi=10.1080/10915810600605898 |url=}}</ref><ref name="pmid34237259">{{cite journal| author=| title=Correction to Lancet Infect Dis 2021; published online June 23. https://doi.org/10.1016/ S1473-3099(21)00330-3. | journal=Lancet Infect Dis | year= 2021 | volume= 21 | issue= 8 | pages= e208 | pmid=34237259 | doi=10.1016/S1473-3099(21)00397-2 | pmc=8318405 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34237259 }} </ref>
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| ==[[Adrenal atrophy causes|Causes]]== | | ==[[Adrenal atrophy causes|Causes]]== |
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| ==[[Adrenal atrophy differential diagnosis|Differentiating Adrenal atrophy from other Diseases]]== | | ==[[Adrenal atrophy differential diagnosis|Differentiating Adrenal atrophy from other Diseases]]== |
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| Adrenal atrophy must be differentiated from other diseases that cause salt wasting and nausea or vomiting and yield to the adrenal hormone imbalance. Among the main diseases are:
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| *Adrenal Crisis
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| *Adrenal Hemorrhage
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| *C-17 Hydroxylase Deficiency
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| *Eosinophilia
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| *Histoplasmosis
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| *Hyperkalemia
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| *Sarcoidosis
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| *Tuberculosis (TB)
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| In addition, hyponatremia and hyperkalemia may result from chronic renal insufficiency due to inadequate production of renin and consequent aldosterone deficiency.<ref name="pmid26981183">{{cite journal |vauthors=Sousa AG, Cabral JV, El-Feghaly WB, de Sousa LS, Nunes AB |title=Hyporeninemic hypoaldosteronism and diabetes mellitus: Pathophysiology assumptions, clinical aspects and implications for management |journal=World J Diabetes |volume=7 |issue=5 |pages=101–11 |date=March 2016 |pmid=26981183 |pmc=4781902 |doi=10.4239/wjd.v7.i5.101 |url=}}</ref><ref name="pmid19500759">{{cite journal |vauthors=Husebye E, Løvås K |title=Pathogenesis of primary adrenal insufficiency |journal=Best Pract Res Clin Endocrinol Metab |volume=23 |issue=2 |pages=147–57 |date=April 2009 |pmid=19500759 |doi=10.1016/j.beem.2008.09.004 |url=}}</ref>
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| ==[[Adrenal atrophy epidemiology and demographics|Epidemiology and Demographics]]== | | ==[[Adrenal atrophy epidemiology and demographics|Epidemiology and Demographics]]== |
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| ===Incidence===
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| It is estimated that the incidence of the disease is 4.4 to 6 new cases per million population, annually.
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| ===Prevalence===
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| The prevalence of primary adrenal atrophy is estimated to be 93 to 144 cases per million population.
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| In addition, secondary adrenal atrophy is more common with estimated prevalence of 150 to 280 cases per million population. Secondary adrenal atrophy is more common among women but is mainly diagnosed in their 60s.
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| Generally, Adrenal atrophy is more prevalent in women and may occur in any age but the clinical manifestations mainly occur in 30s to 50s.
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| ===Mortality===
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| The mortality of the patients with adrenal atrophy is due to the lack of adrenal stress hormones impairs the body's capacity to deal adequately with stressful situations, resulting in life-threatening adrenal crises. It is estimated that one out of 200 patients with adrenal atrophy dies from adrenal crisis each year.<ref name="pmid25905309">{{cite journal |vauthors=Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, Nicolaides NC, Chrousos GP, Charmandari E |title= |journal= |volume= |issue= |pages= |date= |pmid=25905309 |doi= |url=}}</ref><ref name="pmid29716733">{{cite journal |vauthors=Hahner S |title=Acute adrenal crisis and mortality in adrenal insufficiency: Still a concern in 2018! |journal=Ann Endocrinol (Paris) |volume=79 |issue=3 |pages=164–166 |date=June 2018 |pmid=29716733 |doi=10.1016/j.ando.2018.04.015 |url=}}</ref>
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| ==[[Adrenal atrophy risk factors|Risk Factors]]== | | ==[[Adrenal atrophy risk factors|Risk Factors]]== |
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| There are no established risk factors for adrenal atrophy.
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| ==[[Adrenal atrophy screening|Screening]]== | | ==[[Adrenal atrophy screening|Screening]]== |
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| There is insufficient evidence to recommend routine screening for adrenal atrophy. However, the adrenal-hypopituitary axis can be evaluated with sodium, potassium, renin, aldosterone, cortisol, DHEA, ACTH, and CRH levels.<ref name="pmid16287965">{{cite journal |vauthors=Brender E, Lynm C, Glass RM |title=JAMA patient page. Adrenal insufficiency |journal=JAMA |volume=294 |issue=19 |pages=2528 |date=November 2005 |pmid=16287965 |doi=10.1001/jama.294.19.2528 |url=}}</ref>
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| ==[[Adrenal atrophy natural history, complications and prognosis|Natural History, Complications and Prognosis]]== | | ==[[Adrenal atrophy natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| Adrenal atrophy is mainly due to the prolonged malfunction of the adrenal gland. If left untreated, the patients are mainly at risk of a lethal condition, called adrenal crisis.
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| ===Natural History===
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| The onset of clinical manifestations is dependent to the etiology of the atrophy. However, the symptoms of the adrenal atrophy usually develop in patient’s 30s to 50s and in their 60s in the case of secondary adrenal atrophy.
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| If left untreated, the patients are mainly at risk of a lethal condition, called adrenal crisis.
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| ===Complications===
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| Common complications of the adrenal atrophy and its malfunction include hypoglycemia, dehydration, weight loss, and disorientation.
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| Additional signs and symptoms include weakness, tiredness, dizziness, low blood pressure that falls further when standing (orthostatic hypotension), cardiovascular collapse, muscle aches, nausea, vomiting, and diarrhea. These problems may develop gradually and insidiously.
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| ===Prognosis===
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| Prognosis is generally poor, due to the irreversibility of atrophy and the one out of 200 patients with adrenal atrophy dies each year due to the adrenal crisis.<ref name="pmid29716733">{{cite journal |vauthors=Hahner S |title=Acute adrenal crisis and mortality in adrenal insufficiency: Still a concern in 2018! |journal=Ann Endocrinol (Paris) |volume=79 |issue=3 |pages=164–166 |date=June 2018 |pmid=29716733 |doi=10.1016/j.ando.2018.04.015 |url=}}</ref><ref name="pmid16287965">{{cite journal |vauthors=Brender E, Lynm C, Glass RM |title=JAMA patient page. Adrenal insufficiency |journal=JAMA |volume=294 |issue=19 |pages=2528 |date=November 2005 |pmid=16287965 |doi=10.1001/jama.294.19.2528 |url=}}</ref>
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| ==Diagnosis== | | ==Diagnosis== |
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| ==Treatment== | | ==Treatment== |
| | | [[Adrenal atrophy medical therapy|Medical Therapy]] | [[Adrenal atrophy interventions|Interventions]] | [[Adrenal atrophy surgery|Surgery]] | [[Adrenal atrophy primary prevention|Primary Prevention]] | [[Adrenal atrophy secondary prevention|Secondary Prevention]] | [[Adrenal atrophy cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Adrenal atrophy future or investigational therapies|Future or Investigational Therapies]] |
| ===Medical Therapy====
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| Adrenal atrophy is the irreversible damage to the adrenal tissue, due to direct trauma or the secondary causes. As a result, treatment of the adrenal atrophy is a conservative treatment. | |
| For adrenal crisis:
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| *Intravenous fluids
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| *Intravenous steroids
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| The cortisol deficiency is treated by supplementing with cortisol, prednisolone, prednisone, methylprednisolone, and dexamethasone.
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| The mineralocorticoid insufficiency is also cured by the fludrocortisone.
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| ===Primary Prevention===
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| Primary prevention of the adrenal atrophy consists of avoiding overuse of exogenous corticosteroid drugs.
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| ===Secondary Prevention===
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| The secondary prevention of the adrenal atrophy is also known as early diagnosis of any steroid or mineralocorticoid deficiency in the body, as discussed at the causes section, and its early appropriate treatments.<ref name="pmid19500761">{{cite journal |vauthors=Hahner S, Allolio B |title=Therapeutic management of adrenal insufficiency |journal=Best Pract Res Clin Endocrinol Metab |volume=23 |issue=2 |pages=167–79 |date=April 2009 |pmid=19500761 |doi=10.1016/j.beem.2008.09.009 |url=}}</ref><ref name="pmid7170268">{{cite journal |vauthors=Barnett AH, Espiner EA, Donald RA |title=Patients presenting with Addison's disease need not be pigmented |journal=Postgrad Med J |volume=58 |issue=685 |pages=690–2 |date=November 1982 |pmid=7170268 |pmc=2426562 |doi=10.1136/pgmj.58.685.690 |url=}}</ref>
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| ==Case Studies== | | ==Case Studies== |
| | | [[Adrenal atrophy case study one|Case #1]] |
| A 46-year-old man presented to his physician with a 3-month history of generalized weakness and 15-pound unintentional weight loss. He denied sick contacts, specifically exposure to tuberculosis, smoking, alcohol consumption, or the use of illicit substances. Physical examination revealed abdominal distension and free fluid but was otherwise unremarkable. A diagnostic paracentesis revealed an exudative effusion with a positive Ziehl Neelsen stain for acid fast bacilli. The patient was started on treatment.
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| One month after starting antitubercular therapy he presented to the hospital with worsening fatigue, salt craving, vomiting, loss of libido, and erectile dysfunction. On examination, he had low blood pressure and appeared cachectic. In addition, he had bitemporal muscle wasting and hyperpigmentation of skin, oral mucosa, and nails. Laboratory evaluation was significant for hyponatremia, hyperkalemia, and mild hypercalcemia. A random cortisol was 2.5 mcg/dL with an ACTH of 531.2 pcg/mL. The basal and cosyntropin stimulated serum cortisol were, respectively 1.8 mcg/dL and 2.0 mcg/dL, which was consistent with the diagnosis of primary adrenal insufficiency most likely due to tuberculosis.
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| A computed tomography scan of the abdomen with intravenous contrast revealed bilaterally enlarged adrenal glands (4 cm × 3.3 cm on the right, 2.3 cm × 2.1 cm on the left). On review of his prior CT scan of the abdomen, the patient had bilaterally enlarged adrenal glands at the time of his initial presentation as well. A biopsy was obtained from the patient’s right adrenal gland and the findings were in consistent with granulomatosis with caseification necrosis, besides wide cellular disorganization and atrophy and compensatory hypertrophy.
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| He was initially treated with intravenous hydrocortisone and was subsequently discharged on hydrocortisone and fludrocortisone. His symptoms have improved significantly. However, he is requiring slightly higher dose of hydrocortisone, which could be due to CYP 3A4 induction by rifampicin. He is likely to require lifelong treatment for adrenal atrophy, caused by tuberculosis infection.<ref name="pmid25165474">{{cite journal| author=Upadhyay J, Sudhindra P, Abraham G, Trivedi N| title=Tuberculosis of the adrenal gland: a case report and review of the literature of infections of the adrenal gland. | journal=Int J Endocrinol | year= 2014 | volume= 2014 | issue= | pages= 876037 | pmid=25165474 | doi=10.1155/2014/876037 | pmc=4138934 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25165474 }} </ref>
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