Adrenal Insufficiency

Hi Christy, Because I wasn't really familiar with this condition i did a Google and found this: (it's very detailed... I just skimmed through it). I noticed the thyroid link (I have a thyroid problem) so i thought it was interesting. What were your main symptoms? At least your doctor has identified the problem... if not the reason... anyhow here's the article:

Background

Adrenal insufficiency can be classified as primary or secondary.

* Primary adrenal insufficiency occurs when the adrenal gland itself is dysfunctional.
* Secondary adrenal insufficiency, also called central adrenal insufficiency, occurs when a lack of secretion of corticotropin-releasing hormone (CRH) from the hypothalamus or of corticotropic hormone (ACTH) from the pituitary leads to hypofunction of the adrenal cortex.

Adrenal insufficiency can further be classified as congenital or acquired.

Pathophysiology

The adrenal cortex is divided into 3 major anatomic zones: the zona glomerulosa, which produces aldosterone, and the zonae fasciculata and reticularis, which together produce cortisol and adrenal androgens. A fetal zone, unique to primates, produces dehydroepiandrosterone, a precursor of both androgens and estrogens. This zone becomes involuted within the first few months of postnatal life.

Aldosterone secretion is primarily regulated by the renin-angiotensin system. Increased serum potassium concentrations can also stimulate aldosterone secretion. Cortisol secretion is regulated by ACTH, which, in turn, is regulated by CRH from the hypothalamus. Serum cortisol inhibits the secretion of both CRH and ACTH to prevent excessive secretion of cortisol from the adrenal glands.

ACTH partially regulates adrenal androgen secretion; other unknown factors contribute to this regulation as well. ACTH not only stimulates cortisol secretion but also promotes growth of the adrenal cortex in conjunction with growth factors such as insulinlike growth factor (IGF)-1 and IGF-2.

Frequency
United States

Primary adrenal insufficiency is uncommon. By comparison, iatrogenic central adrenal insufficiency is a more frequent cause of morbidity and mortality, though its exact incidence is unknown. Adrenal insufficiency secondary to congenital adrenal hyperplasia occurs in approximately 1 per 16,000 infants.
International

In Great Britain, the prevalence of adrenal insufficiency is 110 cases per million persons of all ages. More than 90% of cases are attributed to autoimmune disease. Willis and Vince (1997) reported data from Coventry County, Great Britain.1

An Italian study provided statistics similar to those observed in Great Britain. The incidence in Italy is estimated to be 117 cases per million persons.2

Worldwide, the most common cause of adrenal insufficiency is tuberculosis (TB). The calculated incidence of adrenal insufficiency caused by TB is approximately 5 or 6 cases per million persons per year.

Mortality/Morbidity

Adrenal insufficiency may be difficult to differentiate from other conditions (eg, chronic fatigue syndrome, depression) if its onset is gradual. Hyperpigmentation may be seen in primary adrenal insufficiency due to ACTH overproduction by the pituitary. The ACTH molecule contains the sequence for alpha-melanocyte-stimulating hormone (MSH), which stimulates melanocytes.

Salt craving is a symptom typical of patients with dysfunction of the zona glomerulosa. Salt craving may be the first sign of autoimmune adrenal destruction.

Patients with chronic adrenal insufficiency often report having fatigue, anorexia, asthenia, weight loss, abdominal pain, nausea, vomiting, and/or weakness. Patients may have hypoglycemia, and most have hypotension. Orthostatic changes in blood pressure and pulse are cardinal signs of adrenal insufficiency.

Hyponatremia with or without hyperkalemia is common in patients with primary adrenal insufficiency, and it is due to deficient aldosterone secretion. Hyponatremia is occasionally found in patients with central or secondary adrenal insufficiency. The presumed cause is water retention due to increased secretion of vasopressin.

Adrenal insufficiency is a potentially fatal disease if it is unrecognized and untreated. Death usually results from hypotension or cardiac arrhythmia secondary to hyperkalemia.

Race

Adrenal insufficiency exhibits no racial predilection.
Sex

* Autoimmune adrenal insufficiency is more common in female individuals than in male individuals.
* Adrenal insufficiency due to adrenoleukodystrophy is limited to male individuals because it is X linked. As a form of congenital adrenal hypoplasia, this condition is called adrenal hypoplasia congenita. Both conditions are relatively rare.
* Secondary adrenal insufficiency due to a deficiency of ACTH or CRH, or a lack of ACTH receptors, is equally common among male and female individuals.

Age

Autoimmune adrenal insufficiency is more common in adults than in children. Congenital causes, such as congenital adrenal hyperplasia, congenital adrenal hypoplasia, and defects in the ACTH receptor, are most commonly recognized in childhood.

CLINICAL
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* Authors and Editors
* Introduction
* Clinical
* Differentials
* Workup
* Treatment
* Medication
* Follow-up
* Miscellaneous
* Multimedia
* References

History

* In infants, acute adrenal insufficiency may occur in the context of serious illness (eg, sepsis), prolonged and difficult labor, or traumatic delivery. Children and adults may also have a history of infectious illness, particularly TB or meningococcemia, though any type of severe sepsis may trigger adrenal insufficiency.
* Adrenal insufficiency may occur without concomitant illnesses when it is due to congenital adrenal hyperplasia or congenital adrenal hypoplasia.
* Antiphospholipid syndrome occasionally results in acute adrenal insufficiency secondary to bilateral adrenal hemorrhage.
* In general, patients present with chronic symptoms (eg, fatigue, anorexia, abdominal pain) if they have autoimmune adrenal insufficiency or adrenal insufficiency due to adrenoleukodystrophy (Online Mendelian Inheritance in Man [OMIM] 300100), chronic infections (eg, HIV infection, TB, fungal infection), or infiltrative lesions. Acute adrenal crisis may exacerbate their symptoms. (See also Adrenal Crisis and Adrenal Insufficiency and Adrenal Crisis.)
* Patients with chronic adrenal insufficiency usually have chronic fatigue, anorexia, nausea, vomiting, loss of appetite, weight loss, recurring abdominal pain, and a lack of energy.
* Symptoms of hypoglycemia are common in small children.
* Altered mental status, even without hypoglycemia, is common in patients with acute adrenal insufficiency.
* Increased skin pigmentation and salt craving are common among individuals with chronic primary adrenal insufficiency.
*
o These symptoms are not noted in patients with secondary or central adrenal insufficiency due to ACTH or CRH deficiency because these conditions do not elevate serum ACTH concentrations.
o Excess MSH activity causes hyperpigmentation.
o If the defect lies in the pituitary or hypothalamus, aldosterone production is not altered because the renin-angiotensin system adequately stimulates the adrenal zona glomerulosa to ensure sufficient aldosterone concentrations and to prevent salt wasting.
* Patients who have recently received long-term pharmacologic doses of glucocorticoids are prone to develop symptoms of adrenal insufficiency when they are stressed because of an illness or trauma.
*
o In this setting, adrenal insufficiency is due to chronic suppression of CRH and ACTH by exogenous glucocorticoids. As a consequence, patients are unable to mount an appropriate cortisol response to stress.
o Patients in this situation do not waste sodium because their renin-angiotensin system maintains aldosterone secretion.
o Recovery of the hypothalamic-pituitary-adrenal axis may take weeks to months and is related to how long the patient was exposed to pharmacologic glucocorticoids.

Physical

* Patients with acute adrenal insufficiency generally present with acute dehydration, hypotension, hypoglycemia, or altered mental status. These signs usually occur in an acutely ill patient with sepsis or disseminated intravascular coagulation or in a patient after a traumatic delivery.
* Patients with chronic adrenal insufficiency may have increased skin pigmentation, particularly in the areolae and genitalia, as well as any scars or moles. Recent scars are typically affected most often. Areas unexposed to sun (eg, palmar creases, axillae, areolae) are often hyperpigmented. The patient also may have pigmentary lines in the gums.
* Signs of weight loss may be evident. If the patient is not frankly hypotensive, he or she may have orthostatic hypotension.
* Some patients lose pubic and axillary hair. However, they may not become totally alopecic because adrenal androgens support growth of body hair in these areas.
* Wolman disease (OMIM 278000) is an autosomal recessive disorder caused by a deficiency of lysosomal acid lipase. In general, Wolman disease is accompanied by hepatosplenomegaly and adrenal calcifications, which may be seen on plain radiographs or CT scans of the adrenal glands.

Causes

Central adrenal insufficiency

Most cases are iatrogenic, caused by long-term administration of glucocorticoids. A mere 2 weeks' exposure to pharmacologic doses of glucocorticoids can suppress the CRH-ACTH-adrenal axis. The suppression can be so great that acute withdrawal or stress may prevent the axis from responding with sufficient cortisol production to prevent an acute adrenal crisis.

Recent treatment with megestrol acetate, an orexigenic agent, has also resulted in iatrogenic adrenal suppression. The mechanism is presumably related to the glucocorticoid properties of megestrol acetate.

Other causes of central adrenal insufficiency include congenital or acquired hypopituitarism and ACTH unresponsiveness. This unresponsiveness may be isolated (as in Familial Glucocorticoid Deficiency, OMIM 202200), or it may be associated with achalasia and alacrima (as in achalasia-addisonism-alacrima syndrome, or triple A syndrome [AAAS], OMIM 231550).

Acquired primary adrenal insufficiency

In developed countries, the most common cause is autoimmune destruction of the adrenal cortex. This disorder may exist in isolation or may be part of a polyglandular autoimmune disorder.

Patients with type 1 autoimmune polyglandular disease (OMIM 240300) present in the first decade of life. Type 1 autoimmune polyglandular disease is transmitted as an autosomal recessive disorder with all or some of the following features:

* Adrenal failure
* Hypoparathyroidism
* Hypothyroidism
* Gonadal failure
* Diabetes mellitus type 1
* Vitiligo
* Alopecia
* Pernicious anemia
* Chronic mucocutaneous candidiasis

Type 2 autoimmune polyglandular disease consists of type 1 diabetes mellitus, autoimmune thyroid disease, and adrenal failure. Individuals with this condition present in the second or third decades of life. Type 2 autoimmune polyglandular disease is transmitted as an autosomal disorder with variable penetrance.

Relatively uncommon causes of adrenal failure are the following:

* Adrenal hemorrhage
* Infections (eg, TB, HIV infection)
* Neoplastic destruction
* Metabolic disorders (eg, various forms of adrenal leukodystrophy, Wolman disease [OMIM 278000], Smith-Lemli-Opitz syndrome)

Hemochromatosis may cause either primary or secondary adrenal insufficiency. Among patients with thalassemia who have received multiple transfusions, iron deposition in the pituitary and/or adrenal glands may also cause adrenal insufficiency.

Congenital primary adrenal insufficiency

Congenital disease may occur as a result of adrenal hypoplasia or hyperplasia.

Inherited as an X-linked disorder, adrenal hypoplasia congenita (OMIM 300200) is caused by deletion of the DAX1 gene on chromosome X. This change is often part of a contiguous gene deletion that involves glycerol kinase deficiency, Duchenne muscular dystrophy, and hypogonadotropic hypogonadism. An alternate form, also X linked, is characterized by intrauterine growth retardation and skeletal and genital anomalies (ie, IMAGE syndrome; OMIM 300290). A third form of adrenal hypoplasia congenita is autosomal recessive (OMIM 240200).

Congenital adrenal hyperplasia results from a deficiency of 1 of several enzymes required for adrenal synthesis of cortisol. Adrenal insufficiency most often develops with combined deficiencies of cortisol and aldosterone. The most prevalent form of congenital adrenal hyperplasia is caused by a deficiency in steroid 21-hydroxylase (OMIM 201910).

Lipoid adrenal hyperplasia is another rare form of adrenal insufficiency caused by a mutation in the steroid acute regulatory protein (ie, STAR protein; OMIM 201710) or a mutation in the cholesterol side-chain cleavage gene (at the cytochrome P450 [CYP] 11A locus; OMIM 118485). This disease causes a defective synthesis of all adrenocortical hormones. In its complete form, the disease is lethal.

Mutations or deletions involving CYP oxidoreductase, a flavoprotein that provides electrons to various enzyme systems, results in combined deficiencies of 17-hydroxylase, 21-hydroxylase, and 17-20 lyase activities. The result is adrenal insufficiency, which is often accompanied by primary hypogonadism.