Sandbox:Akshun

Disease	Signs and Symptoms								Barium esophagogram	Endoscopy	Other imaging findings	Gold Standard
	Onset	Dysphagia			Weight loss	Heartburn	Other findings	Mental status
		Solids	Liquids	Type
Plummer-Vinson syndrome	Gradual	+	-	Non progressive	+/-	-	Glossitis Koilonychia	Normal	Thin projections on the anterior esophageal wall Multiple upper (cervical) esophageal constrictions consistent with esophageal webs.	Direct visualization of esophageal webs Superior to esophagogram	Videofluoroscopy:	Triad of Iron deficiency anemia Esophageal webs Glossitis
Esophageal stricture	Gradual Sudden onset	+	-	Progressive	+/-	+/-	Odynophagia Cough Chest pain	Normal	Sacculations Fixed transverse folds Esoophageal intramural pseudodiverticula	Mucosal edema Circumferential thickening in GERD Pale mucosa with white exudate in lymphocytic esophagitis Swelling and hemorrhagic congestion in caustic ingestion	Ct scan for staging malignant strictures Manometry in cases of esophageal stricture due to dysmotility Chest radiography PA and lateral for esophageal stricture due to extrinsic compression	Barium esophagogram
Diffuse esophageal spasm	Onset	+	+	Non progressive	+	+	Chest pain	Normal	Nonperistaltic and nonpropulsive contractions Corkscrew or rosary bead esophagus	Inconclusive	Manometry shows high-amplitude esophageal contractions CT scan may show show hypertrophy of esophageal muscle wall	Manometry
Achalasia	Gradual	+	+	Non progressive	+/-	-	Regurgitation of undigested food Chest pain	Normal	"Bird's beak image" or "rat tail" appearance due to narrowing of esophagus at gastroesophageal junction. Dilated esophageal body Air fluid level due to absent peristalsis Absence of an intragastric air bubble In advanced achalasia - sigmoid appearance.	Dilated esophagus. Residual food fragments. Normal mucosa. Occasionaly there is candidiasis (due to the prolonged stasis).	Residual pressure of LES > 10 mmHg. Incomplete relaxation of the LES. Increased resting tone of LES Aperistalsis – contractions may be absent, diffuse and not coordinated, and/or ‘vigorous’.	History of dysphagia for both solids and liquids. Endoscopy showing dilated esophagus and residual undigested food. Manometry shows increased tone of the lower esophageal sphincter with failure to relax with swallowing.
Systemic sclerosis	Gradual	+	+	Progressive	+/-	+	Muscle and joint pain Raynaud's phenomenon Skin changes (rash, skin thickening)	Normal	Dysmotility Patulous esophagus	Mucosal damage Peptic stricture (advanced cases)	Positive serology for Antinuclear antibodies Rheumatoid factor Creatine kinase ESR	Skin biospy
Zenker's diverticulum	Gradual	+	-	----	+/-	-	Food regurgitation Halitosis Coughing Hoarseness Aspiration pneumonia	Normal	Thin projections on the anterior esophageal wall over the Killian's triangle	Not routinely done due to risk of perforation Exclude the presence of SCC
Esophageal carcinoma				Progressive	+
Stroke (Cerebral hemorrhage)	Sudden	+	+	Progressive	+	+/-	Dysarthria Limb weakness Fatigue	Impaired	Pooling of contrast in the pharynx Aspiration of barium contrast into the airway	Reduced opening of upper esophageal sphincter Reduced larynx elevation	CT without contrast is the best initial test to differentiate between ischemic and hemorrhagic stroke MRI is more specific and sensitive than a CT scan but is more time consuming	CT without contrast
Motor disorders (Myasthenia gravis)		+	+	Progressive	+/-			Normal	hesitancy in initiation of deglutition, slow and inefficient movement of tongue and measurable delay in clearing mouth and oropharynx. stasis in pharynx and pooling in pharyngeal recesses.
GERD	Gradual Sudden onset	+	-	Progressive	+/-	+		Normal	Free acid reflux Oesophagitis with scarring Strictures Barrett oesophagus
Esophageal web	Gradual	+	+/-	Progressive	-	+/-	Findings of the underlying cause such as iron deficiency anemia or bullous pemphigoid.	Normal	Symmetrical narrowing of the esophagus.	Esophageal webs appear as a smooth membrane that is not encircling the whole lumen.	-	Barium esophagogram

polyglandular autoimmune syndrome polyendocrine autoimmune syndrome

tryptophan hydroxylase presenting with malabsorption

• • • Tyrosine hydroxylase presenting with alopecia areata
    • Liver presenting with autoimmune liver disease and chronic active hepatitis
    • Steroidal hormone–producing cell presenting with hypogonadism.

X linked polyendocrinopathy, immune dysfunction and diarrhea. This condition is very rare and generally presents in neonatal period with diabetes and malabsorption. Unlike type 1 and type 2 autoimmune polyglandular syndromes there is no association with HLA genotype. Mutation in FOXP3 gene is inherited as X linked and leads to loss of regulatory T cells and autoimmunity.

The term “polyendocrine” itself is a misnomer, in that not all patients have multiple endocrine disorders, and many have nonendocrine autoimmune diseases. Nevertheless, the recognition that patients in whom multiple autoimmune disorders are diagnosed may have a specific genetic syndrome, may be at increased risk for multiple autoimmune disorders, and may have relatives who have an increased risk should spur clinicians toward early diagnosis and treatment.

In the simplest hypothesis for understanding organ-specific autoimmunity, the initial step is the loss of immunologic tolerance to a peptide within a specific molecule found in the target organ. Clones of the CD4 T cells that recognize the peptide then expand, and the specific cytokines produced by the clonal CD4 T cells favor inflammation (as when type 1 helper T [Th1]–cell clones produce cytokines such as interferon-γ) or favor autoantibody-mediated disease (as is the case predominantly with type 2 helper T [Th2]–cell clones).9 The probability of T-cell autoreactivity is determined both in the thymus (the site of central tolerance) and in the periphery (the site of peripheral tolerance) and is strongly influenced by specific HLA alleles

TYPE 1 APS Mutations in the AIRE gene cause many autoimmune diseases, and affected patients are at risk for the development of multiple additional autoimmune diseases over time, including type 1A diabetes, hypothyroidism, pernicious anemia, alopecia, vitiligo, hepatitis, ovarian atrophy, and keratitis. Affected patients may also have diarrhea or obstipation that may be related to the destruction of gastrointestinal endocrine cells (enterochromaffin and enterochromaffin-like cells).39 Knockout of the AIRE gene in the mouse produces widespread autoimmunity, but the phenotype is relatively mild. SYMPTOMS TYPE1 Addison's disease develops in 80 percent of patients with autoimmune polyendocrine syndrome type I, and type 1A diabetes develops in 18 percent

PROGNOSISI TYPE 1 After diagnosis, patients with autoimmune polyendocrine syndrome type I require close monitoring. Monitoring can help prevent illness associated with delayed diagnosis of additional autoimmune diseases (e.g., Addison's disease and hypoparathyroidism, which can develop during adulthood) as well as oral cancer, which may develop if candidiasis is not treated aggressively, and infection due to asplenism, which is present in a subgroup of patients.

• In patients with autoimmune polyendocrine syndromes who have a single disorder such as Addison's disease or type 1A diabetes, the prevalence of additional autoimmune disorders is 30 to 50 times that in the general population.60,61 The concurrence of more than one endocrinopathy presumably results from shared genetic susceptibility leading to loss of tolerance to multiple tissues

TYPE 2 Autoimmune polyendocrine syndrome type II (also called Schmidt's syndrome with Addison's disease plus hypothyroidism) is much more common and more varied in its manifestations than autoimmune polyendocrine syndrome type I.

TYpe 3 X-Linked Polyendocrinopathy, Immune Dysfunction, and Diarrhea. The syndrome of X-linked polyendocrinopathy, immune dysfunction, and diarrhea (known as XPID) is an extremely rare disorder characterized by fulminant, widespread autoimmunity and type 1A diabetes, which usually develops in neonates; it is often fatal. The disorder is also known as XLAAD (X-linked autoimmunity and allergic dysregulation) and IPEX (immune dysfunction, polyendocrinopathy, and enteropathy, X-linked)

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