Adrenal atrophy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maryam Hadipour, M.D.[2]

Adrenal atrophy is the shrinkage of adrenal gland due to reduce in size and number of adrenal gland cells.

We have had many famous cases of adrenal atrophy like president John F. Kennedy, king Henry VIII.

There is no established system for the classification of adrenal atrophy. However, some authors have classified it by causes.

The adrenal glands produce hormones that help regulate your metabolism, immune system, blood pressure, response to stress and other essential functions. Adrenal atrophy may be caused by a loss of ACTH and trophic support of the adrenal cortex or direct damage to the tissue due to exogenous corticosteroid overuse or an endocrine disease, affecting the glands.

Adrenal atrophy may be caused by a loss of ACTH and trophic support of the adrenal cortex or direct damage to the tissue.

There are some conditions that cause salt wasting, nausea, vomiting, hyponatremia, hyperkalemia and finally adrenal hormone imbalance which should be differentiated from adrenal atrophy.

Generally, secondary adrenal atrophy is more common than primary adrenal atrophy and is more common in women. Clinical manifestations occur in 30s to 50s in primary and in 60s in secondary adrenal atrophy.

There are no established risk factors for adrenal atrophy.

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.

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. 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.

The most common signs and symptoms of adrenal atrophy are fatigue, weight loss, salt craving, abdominal pain and myalgia.

In the physical examination the patients may have hypotension, hyperpigmentation, depigmentation in autoimmune cases.

The labs include random cortisol, serum ACTH, aldosterone and renin, potassium and sodium, ACTH stimulation test and CRH stimulation test.

There are no specific ECG changes due to adrenal atrophy. However it consequences such as hyperkalemia may change ECG.

There are no x-ray findings associated with adrenal atrophy.

The adrenal glands can be studied in ultrasound imaging and each abdominal ultrasound. Any new incidental mass, larger than 1cm should be evaluated with CT-scan or MRI.

A CT of the adrenal glands can be used to check for structural abnormalities of the adrenal glands.

An MRI of the pituitary can be used to check for structural abnormalities of the pituitary.

There are no other imaging findings associated with adrenal atrophy.

There are no other diagnostic studies associated with adrenal atrophy.

Treatment of adrenal atrophy is conservative. In case of adrenal crisis IV fluid and steroid are recommended. For long-term management supplementing with steroid and mineralocorticoid is necessary.

Surgery can be done in case of micro or macro adenomas of brain or other glandular tumors that may lead to adrenal atrophy.

Primary prevention of the adrenal atrophy consists of avoiding overuse of exogenous corticosteroid drugs.

The secondary prevention of the adrenal atrophy is also known as early diagnosis of any steroid or mineralocorticoid deficiency in the body and its early appropriate treatments.

There is no cost-effectiveness of therapy for adrenal atrophy.

There are no future or investigational therapies for adrenal atrophy.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Maryam Hadipour, M.D.[2]

We have had many famous cases of adrenal atrophy like president John F. Kennedy, king Henry VIII.

There is limited information about the historical perspective of adrenal atrophy.

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.^[1][2][3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maryam Hadipour, M.D.[2]

There is no established system for the classification of adrenal atrophy. However, some authors have classified it by causes.

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 zona fasciculata and zona 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]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Maryam Hadipour, M.D.[2]

The adrenal glands produce hormones that help regulate your metabolism, immune system, blood pressure, response to stress and other essential functions. Adrenal atrophy may be caused by a loss of ACTH and trophic support of the adrenal cortex or direct damage to the tissue due to exogenous corticosteroid overuse or an endocrine disease, affecting the glands.

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.

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.

The development of adrenal atrophy is the result of multiple genetic and environmental factors, as discussed above. However, the congenital adrenal hyperplasia, a form of adrenal hypotrophy is known as a result of the mutation on the following genes:

• An X-linked gene, NROB1, encoding DAX-1 protein
• 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.^[1][2][3]

On gross pathology we expect shrunken adrenal gland.

On microscopic histopathological analysis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maryam Hadipour, M.D.[2]

Adrenal atrophy may be caused by a loss of ACTH and trophic support of the adrenal cortex or direct damage to the tissue.

• Adrenal atrophy may be caused by prolonged glucocorticoid therapy or a functional adrenocortical neoplasm in the same or contralateral gland, which secondarily results in decreased adrenocorticotropic hormone (ACTH) levels.
• Atrophy can also result from more direct ACTH deficiency, such as abnormal pituitary function.
• Cortical atrophy can also be a direct effect of exogenous toxicants that interfere with normal adrenocortical steroidogenesis and/or the physiologic effects of the renin-angiotensin system on the adrenal.
• Because of the complex physiologic interactions of hypothalamus, pituitary, thyroid, and gonads with the adrenal gland, other exogenous toxicants and experimental manipulations that directly damage these tissues or modulate their secretory functions can result in secondary effects in the adrenal cortex, including atrophy.^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Maryam Hadipour, M.D.[2]

There are some conditions that cause salt wasting, nausea, vomiting, hyponatremia, hyperkalemia and finally adrenal hormone imbalance which should be differentiated from adrenal atrophy.

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.^[1][2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maryam Hadipour, M.D.[2]

Generally, secondary adrenal atrophy is more common than primary adrenal atrophy and is more common in women. Clinical manifestations occur in 30s to 50s in primary and in 60s in secondary adrenal atrophy.

It is estimated that the incidence of the disease is 4.4 to 6 new cases per million population, annually.

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.

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.^[1][2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maryam Hadipour, M.D.[2]

There are no established risk factors for adrenal atrophy.

There are no established risk factors for adrenal atrophy.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maryam Hadipour, M.D.[2]

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.

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.^[1]

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maryam Hadipour, M.D.[2]

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. 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.

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. Symptoms include low blood pressure, profound weakness, high fever, nausea and vomiting, dehydration, confusion and coma.

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 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.^[1][2]

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