Differentiating Secondary adrenal insufficiency from other diseases

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


Secondary adrenal insufficiency must be differentiated from primary adrenal insufficiency, acute adrenal insufficiency/adrenal crisis, adrenal hemorrhage, congenital adrenal hyperplasia and salt losing nephropathy based on clinical features, such as fatigue and weight loss and laboratory findings.

Secondary Adrenal Insufficiency

Secondary adrenal insufficiency must be differentiated from other diseases that may cause hypotension, fatigue, and skin pigmentation.



Disease Clinical history/findings Causes Laboratory findings Medical therapy
Hypotension Skin



Fatigue Anorexia/


Abdominal pain Muscle


Other history




Cortisol levels Gold Standard Other
Differentiating amongst adrenal insufficiencies
Chronic Primary adrenal

insufficiency/ Addison's disease

+ + + + + + + Low Cosyntropin/ ACTH stimulation test
Chronic Secondary adrenal


± + + ± Normal Cosyntropin/ ACTH stimulation test
  • CT scan/ MRI scan showing pituitary causes
Acute Acute adrenal insufficiency/ Acute adrenal crisis ++ ± + + + ± + "Normal to Low "Cosyntropin/ ACTH stimulation test
Differentiating Adrenal Insufficiency from other diseases
Adrenal hemorrhage/ Waterhouse Friderichsen syndrome Orthostatic ± + ± +
  • Infection
  1. Sepsis- pneumonia
  2. Waterhouse Friderichsen syndrome- meningococcemia
+ Normal to low Cosyntropin/ ACTH stimulation test
  • CBC (Complete blood count)
  • CT scan
  • Stabilize the patient
  • Treat the underlying cause
Congenital adrenal hyperplasia (CAH) Normal to hypertension ±

(can be indicator of Uncontrolled CAH)[6]

± Low Cosyntropin/ ACTH stimulation test
Syndrome of inappropriate antidiuretic hormone (SIADH) + Normal Water deprivation test
  • Decreased osmolality
  • Euvolemia
  • Sodium in urine typically >20 mEq/
Salt-depletion nephritis/ Salt losing nephropathy + + Flank pain ++[9] High Genetic study <15:1 BUN:CR
Anorexia nervosa + + + + High Psychiatric condition

Adrenal insufficiency must be differentiated from other causes of headache, polyuria and polydypsia.

Disease Causes Symptoms Diagnosis and treatment
SIADH SIADH is a syndrome characterized by excessive release of antidiuretic hormone (ADH or vasopressin) from the posterior pituitary gland or another source. The result is hyponatremia, and sometimes fluid overload
  • Urine sodium concentration>40mmol/litre
Cerebral salt wasting syndrome Cerebral salt wasting syndrome is defined as therenal loss of sodium during intracranial disease leading to hyponatremia and a decrease in extracellular fluid volume The patient is Treatment is
Adrenal insufficiency Adrenal insufficiency

Adrenal insufficiency can be

Common causes of primary adrenal insufficiency:

Chronic disease is characterized by

Acute addisonian crisis is characterized by:

The diagnosis of Addisons disease is made through rapid ACTH administration and measurement of cortisol.

The definitive diagnosis is the cosyntropin or ACTH stimulation test. Acortisol level is obtained before and after administering ACTH. A normal person should show a brisk rise in cortisol level after ACTH administration.

Management: The management of Addison disease involves:

Adrenal crisis:

Hypopituitarism Abnormality in anterior pituitary function

Etiology is as follows:

Signs and symptoms ofhypopituitarism vary, depending on the deficient

hormone and severity of the disorder,some of the symptoms may be as follows:

The treatment of permanent hypopituitarism consists of replacement of the peripheral hormones

Hypothyroidism Hypofunctioning of the thyroid gland due to multifactorial etiology ranging from congenital to autoimmune causes described below: Diagnosis of hypothyroidism is based on blood tests:
Psychogenic polydipsia Also called as primary polydipsia is characterized bypolyuria and polydipsia. Causes are: Evaluation ofpsychiatric patients with polydipsia requires an evaluation for other medical causes of polydipsia, polyuria,hyponatremia, and the syndrome of inappropriate secretion of antidiuretic hormone.
  • The management strategy inpsychiatric patients should include:


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  6. Patel FB, Newman SA, Norton SA (2016). "Addisonian-Like Hyperpigmentation as an Indicator of Uncontrolled Congenital Adrenal Hyperplasia". Skinmed. 14 (1): 53–4. PMID 27072733.
  7. Seyberth HW (2016). "Pathophysiology and clinical presentations of salt-losing tubulopathies". Pediatr. Nephrol. 31 (3): 407–18. doi:10.1007/s00467-015-3143-1. PMID 26178649.
  8. Sayin B (2015). "Tacrolimus-Induced Salt Losing Nephropathy Resolved After Conversion to Everolimus". Transplant Direct. 1 (9): e37. doi:10.1097/TXD.0000000000000538. PMC 4946484. PMID 27500237.
  9. Yoshioka K, Nishio M, Sano S, Sakurai K, Yamagami K, Yamashita Y (2009). "Development of Severe Hyponatremia due to Salt-Losing Nephropathy after Esophagectomy for Esophageal Cancer". Case Rep Med. 2009: 241283. doi:10.1155/2009/241283. PMC 2771150. PMID 19888422.


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