2.

X Pathophysiology
Addisons disease only affects the cortex portion of the adrenal glands; it
causes deficiency of hormone that is produced there, including
mineralocorticoid (aldosterone), glucocorticoid (cortisol), and adrenal
androgen.
a. Mineralocorticoid (Aldosterone)
Ninety percent of mineralocorticoid activity that is secreted by adrenal
cortex is aldosterone. It has function mainly to maintain electrolyte
balance by increasing natrium and chloride reabsorption and also
increasing kalium secretion in renal tubules epithelium. Deficiency of
aldosterone causes hyponatremia that followed by hyperkalemia in
extracellular fluid significantly. Decreasing extracellular fluid total
volume leads to low plasma volume and hypotension. Circulation
shock will present when cardiac output decreases. In severe
hyperkalemic condition (60-100% above normal), cardiac contraction
weakness and arrhythmia can be clearly seen.[1]
Aldosterone also stimulates hydrogen secretion that will be changed
with natrium in renal. Increasing hydrogen concentration in
extracellular fluid can cause mild acidosis. Another function of
aldosterone is increasing natrium absorption in intestine, mainly in
colon. Failure of this function will be followed by failure of kalium,
another anion, and water absorption; the patient will suffers from
diarrhea and so will presents sign of dehydration.[1]
b. Glucocorticoid (Cortisol)
The main glucocorticoid hormone produced by adrenal cortex is
cortisol, which contributes ninety-five percent of all glucocorticoid
activity. Cortisol plays a role in carbohydrate, protein, and lipid
metabolism.

In

carbohydrate

metabolism,

cortisol

stimulates

gluconeogenesis in the liver by increasing enzymes that is needed to

this process and transporting amino acid from extrahepatic tissue,

especially from muscles. It also reduces cellular glucose usage by

unknown mechanism. In protein metabolism, cortisol increases level
of liver protein and plasma protein by suppressing amino acid
mobilization into extrahepatic tissue. It reduces protein synthesize, but
protein catabolism continues inside the cell, so tissue protein deposit
will decrease. In lipid metabolism, cortisol helps in increasing fatty
acid mobilization from adipose tissue. So, suppression of many
metabolism functions will be happened in Addisons disease.[1]
In the correlation of metabolism, patient with Addisons disease may
presents with hypoglycemic, weight loss, and muscle weakness.
Decreasing cortisol secretion reduces blood glucose, thus will cause
hypoglycemic. Low blood glucose triggers insulin secretion to drop.
Beside its function in glucose uptake, insulin can also stimulates
triglyceride storage, so the patient will experienced weight loss.
Muscle weakness is resulted from lack of ATP because of low glucose.
Cortisol is one of orexigenic substance or appetite stimulant; it
correlates with complain of loss of appetite from patient with
Addisons disease.[1][2]
Cortisol is important in managing the body to react with stress,
including trauma, infection, surgery, emotional, etc. It has antiinflammation features: (1) stabilizing lyzosome membrane which can
reduce the release of proteolytic enzyme, (2) preventing leukocyte
migration to affected area by reducing prostaglandin and leukotrien
formation, (3) reducing IL-1 release to prevent fever, (4) suppressing
lymphocyte reproduction, and (5) promoting healing process. In
cortisol deficiency, the patient with extreme stressful events may
present with severe illnesses. Cortisol is also found to stimulates
erythrocyte production by unknown mechanism; the patient will show
anemia signs in Addisons disease.[1]
When Adrenocorticotropin Hormone (ACTH) was secreted from
anterior hypophysis gland, another hormone that has same chemical

characteristics, such as Melanocyte Stimulating Hormone (MSH), will

also be secreted too because those hormones have same precursor. In
normal condition, MSH did not give significant effect on human body
because it was secreted only in small amount. If ACTH is rapidly
secreted because of low level plasma cortisol, secretion of MSH will
be increased too. This condition leads to overstimulation of melanin
dformation or hyperpigmentation in skin and mucous membrane.[1][3][4]
c. Adrenal Androgen
Besides mineralocorticoid and glucocorticoid, adrenal cortex also
secretes sex hormone--adrenal androgen, which has same effects with
testosterone. Because it secreted in small amount, deficiency in this
hormone did not produce significant features. Women may have loss
of androgen-stimulated hair, such as pubic and axillary hair, and
irregular or absent menstrual periods. Men do not have hair loss
because male androgen is produced primarily in testes.[1][2][5]

Summary
Deficiency of aldosterone causes hyponatremia, hyperkalemia, low plasma
volume, mild acidosis, and diarrhea. Deficiency of cortisol causes hypoglycemic,
weight loss, muscle weakness, loss of appetite, failure to react with stress, anemia,
and hyperpigmentation. Deficiency of adrenal androgen causes less significant
effects.

References
1. Guyton AC, Hall JE. Buku Ajar Fisiologi Kedokteran. Edisi 11. Translated by:
Irawati, et al. Jakarta: EGC; 2007. p992-1009.
2. Chakera AJ, Vaidya B. Addison Disease in Adults: Diagnosis and Management.
The American Journal of Medicine. 2010;123(5):409-13.
3. Piliang S. Penyakit Korteks Adrenal Lainnya. In: Sudoyo AW, et al. Buku Ajar
Ilmu Penyakit Dalam. Jilid III Edisi V. Jakarta: Interna Publishing; 2009.
p2069-73.
4. Shah SS, Oh CH, Coffin SE, Yan AC. Addisonian Pigmentation of the Oral
Mucosa. Cutis. 2005;76(2):97-9.
5. Erichsen MM, Husebye ES, Michelsen TM, Dahl AA, Lovas K. Sexuality and

Fertility in Women with Addisons Disease. J Clin Endocrinol Metab.

2010;95(9):4354-60.