Sandbox:Akshun

• In 1563, Bartholomeus Eustachius an anatomy professor at the Collegio della Sapienza in Rome was the first to give a description of the adrenal glands in his publication "glandulae renibus incumbentes"
• In 1586, Piccolomini was the first to name the glands as suprarenals.
• In 1651, Highmore was the first to suggest that the suprarenals act to absorb exudates from the large vessels,
• In 1656, Thomas Wharton was the first to describe the concept of the neuroendocrine function of the adrenal medulla.
• In 1805, Cuvier was the first to give a detailed description of medulla and cortex of adrenal glands
• In 1852, Albert von Kölliker was the first to give a detailed microscopic description of the adrenal glands.

Hypoaldosteronism can be due to adrenal insufficiency, enzyme deficiency (aldosterone synthase, 21 hydroxylase, and 11B hydroxylase), renal disorders (chronic renal failure and diabetic nephropathy) and drugs inhibiting aldosterone effect (NSAID, spironolactone, and triamterene).

Aldosterone Deficiency: Hyporeninemic hypoaldosteronism - Commonly seen in patients with renal insufficiency (diabetic kidney disease, chronic tubulointerstitial disease, or glomerulonephritis) and those that take certain medications (non-steroidal anti-inflammatory drugs, calcineurin inhibitors).[1] Angiotensin inhibitors - angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), direct renin inhibitors Heparin therapy (including low molecular weight heparin) - Heparin has a direct toxic effect on the adrenal zona glomerulosa cells which leads to a reduction in plasma aldosterone concentration.[9] Primary adrenal insufficiency (Addison’s disease) - Associated with the lack of cortisol and aldosterone. This can result from autoimmune adrenalitis, infectious adrenalitis, and other disorders.[14] Critical illness - There is decreased adrenal production of aldosterone and stress-induced hypersecretion of ACTH which can diminish aldosterone synthesis by diverting substrate to the production of cortisol. Congenital isolated hypoaldosteronism - Deficiency of enzymes required for aldosterone synthesis.[14] Pseudohypoaldosteronism type 2 (Gordon’s syndrome or familial hyperkalemic hypertension) - Abnormalities in WNK kinases in the distal nephron increase chloride reabsorption leading to reduced renal potassium secretion. Characterized by hypertension, hyperkalemia, metabolic acidosis, normal renal function, and low or low-normal plasma renin activity and aldosterone concentrations.[14][2] Aldosterone Resistance: Inhibitors of the epithelial sodium channel - Most commonly associated with the administation of potassium-sparing diuretics (spironolactone, eplerenone, amiloride) and certain antibiotics (trimethoprim, pentamidine). Pseudohypoaldosteronism type 1 - Characterized by marked elevations of plasma aldosterone levels. There is an autosomal recessive form, and an autosomal dominant or sporadic form. The autosomal dominant form tends to be associated with milder symptoms

Type of Adrenal insufficiency	Skin Pigmentation	ACTH	Normal ACTH
Addison disease	+	>60 ng/mL	5-30 ng/mL
Secondary / tertiary adrenal insufficiency	-	<5 ng/mL

Addison's disease must be differentiated from other diseases that cause hypotension, skin pigmentation, and abdominal pain such as myopathies, celiac disease, Peutz-Jeghers syndrome ,anorexia nervosa, syndrome of inappropriate anti-diuretic hormone (SIADH), neurofibromatosis, porphyria cutanea tarda, salt-depletion nephritis and bronchogenic carcinoma.

Disease	Differentiating symptoms							Differentiating laboratory findings			Gold standard test
	Hypotension	Abdominal pain	Anorexia/ weight loss	Muscle weakness	Hypoglycemia	Skin pigmentation	Other symptoms	Hyponatremia	Cortisol levels	Other labs
Addison's disease	+	+	+	+	+	+		-	Low		ACTH stimulation test
Myopathies (polymyositis, hereditary myopathies)	-	-	-	+	-	Heliotrope rash and Gottron's sign	Muscle tenderness	-	Normal	-	Muscle biopsy
Celiac disease	-	+	+	-	-	Dermatitis herpetiformis	Greasy stools Increased fecal fat	-	Normal	-	Abnormal small bowel biopsy
Syndrome of inappropriate anti-diuretic hormone (SIADH)	-	-	-	-	-	-	-	+	Normal	Decreased osmolality Euvolemia Sodium in urine typically >20 mEq/L	Water deprivation test
Neurofibromatosis	-	-	+	+	-	Axillary- and inguinal-area freckling	Occasional development of peripheral sarcomas May have overgrowth of subcutaneous tissues	-	-	-	Biopsy of skin tissue
Peutz-Jeghers syndrome		+				+	Melanotic hyperpigmentation of the skin and mucous membranes	-	Normal		Colonic imaging showing the small intestinal polyps
Porphyria cutanea tarda	-	+	-	-	-	Blisters on sun-exposed sites	Associated liver disease (usually hepatitis C) Hypertrichosis	-	Normal or elevated	High level of porphyrins in the urine
Salt-depletion nephritis	+	Flank pain	-	-	-	-	Fever Dysuria Pyuria Oliguria	+	Elevated	<15:1 BUN:CR
Bronchogenic carcinoma	-	-	+	-	-	+	Cough Dyspnea Hemoptysis	-	Elevated	Increased ACTH and Hypokalemia	Cytological or histological evidence of lung cancer in sputum, pleural fluid, or tissue
Anorexia nervosa	+	-	+	+	+	-	Distorted body image Oligomenorrhea	-	Elevated	-	Psychiatric condition