Adrenal atrophy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]
Overview
Adrenal glands, also known as suprarenal glands, are small, triangular-shaped glands located on top of both kidneys. They produce hormones that help regulate your metabolism, immune system, blood pressure, response to stress and other essential functions. Adrenal atrophy may be caused by loss of ACTH and trophic support of the adrenal cortex (due to exogenous corticosteroid overuse) or direct damage to the tissue caused by infections (TB, CMV, histoplasmosis, paracoccidioidomycosis), vascular impairments (hemorrhage from sepsis, adrenal vein thrombosis, HIT), deposition disease (hemochromatosis, amyloidosis, sarcoidosis), or drugs (azole anti-fungals, etomidate, rifampin, anticonvulsants) or cytotoxic agents such as mitotane. 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. Common complications of the adrenal atrophy and its malfunction include hypoglycemia, dehydration, weight loss, and disorientation. Prognosis is generally poor, due to the irreversibility of atrophy and the one out of 200 patients with adrenal atrophy die each year due to the adrenal crisis. As the disease consists of the irreversible atrophy of the adrenal gland treatment of the adrenal atrophy is a conservative treatment, including hormone replacement therapy and managing the adrenal crisis state.
Historical Perspective
There is limited information about the historical perspective of adrenal atrophy.
Famous Cases
The following are a few famous cases of adrenal atrophy:
- President John F. Kennedy was diagnosed with Addison’s disease after his election in 1960, due to an autoimmune disease, attacking the adrenal tissue.
- The King Henry VIII was known as a domineering, philanderer king, who became bloated and significantly obese after 35 years of being in power. Historian Robert Hutchinson has theorized that he has had Cushing’s Syndrome.
Classification
There is no established system for the classification of adrenal atrophy.
However, adrenal insufficiency may be classified into three subtypes based on its cause:
- Primary adrenal insufficiency due to impairment of the adrenal glands. Causes:
- Autoimmune disease in 80% of the cases.
- Congenital adrenal hyperplasia or an adenoma (tumor) of the adrenal gland.
- Infections (TB, CMV, histoplasmosis, paracoccidioidomycosis).
- Vascular (hemorrhage from sepsis, adrenal vein thrombosis, HIT).
- Deposition disease (hemochromatosis, amyloidosis, sarcoidosis).
- Drugs (azole anti-fungals, etomidate (even one dose), rifampin, anticonvulsants).
- Secondary adrenal insufficiency is caused by impairment of the pituitary gland. Causes:
- Pituitary adenoma (which can suppress production of adrenocorticotropic hormone (ACTH) and lead to adrenal deficiency unless the endogenous hormones are replaced).
- Sheehan's syndrome.
- Tertiary adrenal insufficiency is due to hypothalamic disease and a decrease in the release of corticotropin releasing hormone (CRH). Causes:
- Sudden withdrawal from long-term exogenous steroid use (which is the most common cause overall).
- Brain tumor.
Adrenal cortical atrophy may be focal or diffuse. Compared with the normal adrenal cortex, the atrophic cortex is characterized by reduced thickness of the one or more of the cortical layers due to a decrease in cell size or a loss of cells. The zonae fasciculata and reticularis are more often affected than the zona glomerulosa. There is variably decreased overall size of the gland, often with distortion of the gland outline. The glandular capsule may be thickened due to fibrosis.[1][2]
Pathophysiology
Physiology
The normal physiology of adrenal atrophy can be understood as follows:
Adrenal glands produce hormones that help regulate your metabolism, immune system, blood pressure, response to stress and other essential functions. The glands are composed of two parts:
- The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones.
- The adrenal medulla is located inside the adrenal cortex in the center of an adrenal gland. It produces “stress hormones,” including epinephrine.
Pathogenesis
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.
- Primary Adrenal Atrophy: The primary atrophy is due to direct insult to the adrenal tissue due to:
- Infections (TB, CMV, histoplasmosis, paracoccidioidomycosis)
- Vascular impairments (hemorrhage from sepsis, adrenal vein thrombosis, HIT)
- Deposition disease (hemochromatosis, amyloidosis, sarcoidosis)
- Drugs (azole anti-fungals, etomidate (even one dose), rifampin, anticonvulsants)
- Cytotoxic agents such as mitotane.
- Secondary Adrenal Atrophy
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. 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.
Genetics
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: 1.An X-linked gene, NROB1, encoding DAX-1 protein 2.The steroidogenic factor 1 (SF-1) gene, encoded on the 9q33 loci The autosomal recessive ACTH resistance syndromes such as triple-A syndrome and familial glucocorticoid deficiency, are among other genetics disorders yielding to adrenal atrophy.[3]
Causes
Differentiating Adrenal atrophy from other Diseases
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:
- Adrenal Crisis
- Adrenal Hemorrhage
- C-17 Hydroxylase Deficiency
- Eosinophilia
- Histoplasmosis
- Hyperkalemia
- Sarcoidosis
- Tuberculosis (TB)
In addition, hyponatremia and hyperkalemia may result from chronic renal insufficiency due to inadequate production of renin and consequent aldosterone deficiency.[4][5]
Epidemiology and Demographics
Incidence
It is estimated that the incidence of the disease is 4.4 to 6 new cases per million population, annually.
Prevalence
The prevalence of primary adrenal atrophy is estimated to be 93 to 144 cases per million population. 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.
Generally, Adrenal atrophy is more prevalent in women and may occur in any age but the clinical manifestations mainly occur in 30s to 50s.
Mortality
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.[6][7]
Risk Factors
There are no established risk factors for adrenal atrophy.
Screening
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.[8]
Natural History, Complications and Prognosis
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.
Natural History
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. If left untreated, the patients are mainly at risk of a lethal condition, called adrenal crisis.
Complications
Common complications of the adrenal atrophy and its malfunction include hypoglycemia, dehydration, weight loss, and disorientation. 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.
Prognosis
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.[7][8]
Diagnosis
History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | X Ray | CT | MRI | Ultrasound | Other Imaging Findings | Other Diagnostic Studies
Treatment
Medical Therapy=
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:
- Intravenous fluids
- Intravenous steroids
The cortisol deficiency is treated by supplementing with cortisol, prednisolone, prednisone, methylprednisolone, and dexamethasone. The mineralocorticoid insufficiency is also cured by the fludrocortisone.
Primary Prevention
Primary prevention of the adrenal atrophy consists of avoiding overuse of exogenous corticosteroid drugs.
Secondary Prevention
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.
Case Studies
- ↑ Conran RM, Nickerson PA (June 1982). "Atrophy of the zona fasciculata in the adrenal cortex of thyroparathyroidectomized rats: a quantitative study". Am J Anat. 164 (2): 133–43. doi:10.1002/aja.1001640204. PMID 6285687.
- ↑ Grossman AB (November 2010). "Clinical Review#: The diagnosis and management of central hypoadrenalism". J Clin Endocrinol Metab. 95 (11): 4855–63. doi:10.1210/jc.2010-0982. PMID 20719838.
- ↑ Saleem F, Baradhi KM. PMID 31747186. Missing or empty
|title=(help) - ↑ Sousa AG, Cabral JV, El-Feghaly WB, de Sousa LS, Nunes AB (March 2016). "Hyporeninemic hypoaldosteronism and diabetes mellitus: Pathophysiology assumptions, clinical aspects and implications for management". World J Diabetes. 7 (5): 101–11. doi:10.4239/wjd.v7.i5.101. PMC 4781902. PMID 26981183.
- ↑ Husebye E, Løvås K (April 2009). "Pathogenesis of primary adrenal insufficiency". Best Pract Res Clin Endocrinol Metab. 23 (2): 147–57. doi:10.1016/j.beem.2008.09.004. PMID 19500759.
- ↑ 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. PMID 25905309. Missing or empty
|title=(help) - ↑ 7.0 7.1 Hahner S (June 2018). "Acute adrenal crisis and mortality in adrenal insufficiency: Still a concern in 2018!". Ann Endocrinol (Paris). 79 (3): 164–166. doi:10.1016/j.ando.2018.04.015. PMID 29716733.
- ↑ 8.0 8.1 Brender E, Lynm C, Glass RM (November 2005). "JAMA patient page. Adrenal insufficiency". JAMA. 294 (19): 2528. doi:10.1001/jama.294.19.2528. PMID 16287965.