Differentiating Secondary adrenal insufficiency from other diseases

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Secondary adrenal insufficiency must be differentiated from primary adrenal insufficiency, acute adrenal insufficiency/adrenal crisis, adrenal hemorrhage,congenital adrenal hyperplasia and salt losing nephropathy.

Adrenal Insufficiency

Acute/ Chronic	Disease	Clinical history/findings							Causes	Laboratory findings				Medical therapy
	Disease	Hypotension	Skin pigmentation/ findings	Fatigue	Anorexia/ weightloss	Abdominal pain	Muscle weakness	Other history findings	Causes	Hypo natremia	Cortisol levels	Gold Standard	Other	Medical therapy
	Differentiating amongst adrenal insufficiencies
Chronic	Primary adrenal insufficiency/ Addison's disease	+	+	+	+	+	+	Nausea and Vomiting Hypoglycemia	Autoimmune/idiopathic Infections- Tuberculosis^[1]^[2], histoplasmosis^[3]^[4]	+	Low	Cosyntropin/ ACTH stimulation test	Hyperkalemia	Hydrocortisone -15 to 25 mg PO q daily in 2 to 3 divided doses Fludrocortisone - 0.1 to 0.2 mg PO q daily
Chronic	Secondary adrenal insufficiency	±	–	+	+	–	±	Hypoglycemia (more than primary adrenal insufficiency) Signs of pituitary tumor- headache, visual field defects (bitemporal hemianopsia)	Hypopituitarism- Tumors, infections, hemorrhage/trauma Drugs- Chronic steroid therapy and its withdrawal, opiates^[5] Genetic- Combined pituitary hormone deficiency (CPHD), POMC (proopiomelanocortin) gene deficiency	–	Normal	Cosyntropin/ ACTH stimulation test	CT scan/ MRI scan showing pituitary causes	Hydrocortisone -15 to 25 mg PO daily in 2 to 3 divided doses
Acute	Acute adrenal insufficiency/ Acute adrenal crisis	++	±	+	+	+	±	Signs of shock Altered mental status/ Loss of consciousness/ Coma Fever Nausea/ vomiting	Infection Trauma Surgery Anesthesia (etomidate)	+	Normal to Low	Cosyntropin/ ACTH stimulation test	ECG (electrocardiogram) CBC (complete blood count) BUN (blood urea nitrogen) Creatinine	I/V 0.9% saline 1-3 liters within 12-24 hours I/V Dexamethasone 4 mg bolus, or, I/V hydrocortisone 50 mg bolus Fludrocortisone - 0.1 to 0.2 mg PO q daily after initial stabilization
Differentiating Adrenal Insufficiency from other diseases
	Adrenal hemorrhage/ Waterhouse Friderichsen syndrome	orthostatic	±	+	±	+	–	Fever Tachycardia Dizziness Nausea/ vomiting Diarrhea	Infection Sepsis- pneumonia Waterhouse Friderichsen syndrome- meningococcemia Cardiac- Congestive heart failure (CHF), myocardial infarction Gastrointestinal- Acute pancreatitis, cirrhosis Bleeding situations- Spontaneous abortions, thrombocytopenia, anticoagulants use, surgery, heparin-induced thrombocytopenia Trauma Thrombotic phenomenon- pulmonary embolus, deep venous thrombosis, antiphospholipid antibody syndrome Tumors- Adrenal adenomas, pheochromocytoma	+	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]	–	–	–	–	Female- Ambiguous genitalia/ virilization, infertility Male- Normal or enlarged phallus Short stature	21-hydroxylase deficiency 17α hydroxylase deficiency 11 β hydroxylase deficiency	±	Low	Cosyntropin/ ACTH stimulation test	Serum 17-hydroxyprogesterone Hyperkalemia	Hydrocortisone -15 to 25 mg PO daily in 2 to 3 divided doses Fludrocortisone - 0.1 to 0.2 mg PO q daily
	Syndrome of inappropriate antidiuretic hormone (SIADH)	–	–	–	–	–	–	Nausea/vomiting Cramps Depressed mood Irritability Confusion Hallucinations Seizures, stupor or coma	Head trauma-subarachnoid hemorrhage Tumors- metastasis Infections- Brain abscess Drugs- chlorpropamide, cyclophosphamide, carbamazepine, selective serotonin reuptake inhibitors, methylenedioxymethamphetamine (MDMA, commonly called Ecstasy)	+	Normal	Water deprivation test	Decreased osmolality Euvolemia Sodium in urine typically >20 mEq/	Mild- Fluid restriction Moderate- Loop diuretics Severe Hypertonic (3%) saline
	Salt-depletion nephritis/ Salt losing nephropathy	+	–	–	–	+ Flank pain	–	Fever Dysuria Pyuria Oliguria	Chronic renal failure Bartter syndrome^[7] Gitelman syndrome Drugs- Tacrolimus^[8]	++^[9]	High	Genetic study	<15:1 BUN:CR	Fludrocortisone - 0.05 to 0.2 mg PO q daily
	Anorexia nervosa	+	–	+	+	–	+	Distorted body image Hypoglycemia Amenorrhoea/ oligomenorrhoea Osteoporosis Refeeding syndrome	Genetic Hormonal- Low dopamine and serotonin Psychological	–	High	Psychiatric condition	–	Nutritional replacement Psychotherapy- e.g. Cognitive behavioral therapy For refeeding syndrome-hospitalization and replacements of potassium, phosphate and magnesium

References

↑ Patnaik MM, Deshpande AK (2008). "Diagnosis--Addison's disease secondary to tuberculosis of the adrenal glands". Clin Med Res. 6 (1): 29. doi:10.3121/cmr.2007.754a. PMC 2442022. PMID 18591375.
↑ Bhattacharjee R, Sharma A, Rays A, Thakur I, Sarkar D, Mandal B, Mookerjee SK, Chatterjee SK, Chowdhury PR (2013). "Addison's disease presenting with muscle spasm". J Assoc Physicians India. 61 (9): 675–6. PMID 24772716.
↑ Ray A, Sanyal D (2016). "A rare case of Addison's disease due to bilateral adrenal histoplasmosis presenting with hypoglycaemia". J Assoc Physicians India. 64 (1): 45–46. PMID 27727656.
↑ Choudhary N, Aggarwal I, Dutta D, Ghosh AG, Chatterjee G, Chowdhury S (2013). "Acquired perforating dermatosis and Addison's disease due to disseminated histoplasmosis: Presentation and clinical outcomes". Dermatoendocrinol. 5 (2): 305–8. doi:10.4161/derm.22677. PMC 3772918. PMID 24194970.
↑ Schimke KE, Greminger P, Brändle M (2009). "Secondary adrenal insufficiency due to opiate therapy - another differential diagnosis worth consideration". Exp. Clin. Endocrinol. Diabetes. 117 (10): 649–51. doi:10.1055/s-0029-1202851. PMID 19373753.
↑ 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.
↑ 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.
↑ 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.
↑ 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.

Template:WikiDoc Sources

[pmid18591375-1] Patnaik MM, Deshpande AK (2008). "Diagnosis--Addison's disease secondary to tuberculosis of the adrenal glands". Clin Med Res. 6 (1): 29. doi:10.3121/cmr.2007.754a. PMC 2442022. PMID 18591375.

[pmid24772716-2] Bhattacharjee R, Sharma A, Rays A, Thakur I, Sarkar D, Mandal B, Mookerjee SK, Chatterjee SK, Chowdhury PR (2013). "Addison's disease presenting with muscle spasm". J Assoc Physicians India. 61 (9): 675–6. PMID 24772716.

[pmid27727656-3] Ray A, Sanyal D (2016). "A rare case of Addison's disease due to bilateral adrenal histoplasmosis presenting with hypoglycaemia". J Assoc Physicians India. 64 (1): 45–46. PMID 27727656.

[pmid24194970-4] Choudhary N, Aggarwal I, Dutta D, Ghosh AG, Chatterjee G, Chowdhury S (2013). "Acquired perforating dermatosis and Addison's disease due to disseminated histoplasmosis: Presentation and clinical outcomes". Dermatoendocrinol. 5 (2): 305–8. doi:10.4161/derm.22677. PMC 3772918. PMID 24194970.

[pmid19373753-5] Schimke KE, Greminger P, Brändle M (2009). "Secondary adrenal insufficiency due to opiate therapy - another differential diagnosis worth consideration". Exp. Clin. Endocrinol. Diabetes. 117 (10): 649–51. doi:10.1055/s-0029-1202851. PMID 19373753.

[pmid27072733-6] 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.

[pmid26178649-7] 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.

[pmid27500237-8] 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.

[pmid19888422-9] 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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Differentiating Secondary adrenal insufficiency from other diseases

Overview

Adrenal Insufficiency

References

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