Sandbox:Hannan

Cortex	Product	Clinical manifestations		Dianosis				Gold standard	Other features
		Symptoms	Signs	Blood & Urine	Histopathological	Imaging	Others
Adenoma	Aldosterone	Headache Vision problems Muscle cramps Muscle weakness & cramps Numbness Temporary paralysis Polyuria and polydipsia	Hypertension Refractory hypertension	Hypokalemia Alkalosis ↑ Plasma aldosterone ↓ Plasma Renin ↑ ARR	Single or multiple nodules Encapsulated Abundant clear cytoplasm Uniforming nuclei Histopathology may resemble: ZF (large, lipid-laden clear cells) ZG (small, compact cells with moderate amount of lipid) ZR (lipid-sparse cytoplasm)	Adrenal mass or nodule Unilateral or bilateral adrenal atrophy Hypodense mass (CT) Iso and low FDG uptake compared with liver (FDG PET/CT) Hyperintense on in-phase and hypointense on oppose-phase (MRI)	Fludrocortisone Suppression Testing Oral Sodium Loading Saline Infusion Testing Captopril test Adrenal venous sampling Posture test Genetic testing Immunohistochemical staining	Fludrocortisone Suppression Testing	Glucocorticoid-Remediable Aldosteronism responds to glucocorticoids Higher cardiovascular and cerebrovascular morbidity
	Cortisol	Weight gain Growth retardation Headache Amenorrhea Virilization (rare) Acne Violaceous striae Acanthosis nigricans Sleep disruption Mental changes Muscular weakneness	Hypertension Hirsutism Hypogonadism Growth retardation Facial plethora Acne Striae Bruising Acanthosis nigricans Mental changes Muscular weakneness	↑ Plasma cortisol ↑ 24 Hour urinary cortisol ↓ or inappropriately normal plasma ACTH ↑ Blood glucose	Yellow fat Brown discoloration Large cells with increased lipid contetnt (zona fasciculata) May contain pigment (lipofuscin) Adjacent atrophied cells Hemorrhage and calcification (Pre-malignant lesions)	Adrenal mass or nodule Unilateral or bilateral adrenal atrophy ↑ Fat Hypodense mass (CT) Iso and low FDG uptake compared with liver (FDG PET/CT) Hyperintense on in-phase and hypointense on oppose-phase (MRI)	Diurnal plasma cortisol variation Low dose and high dose dexamethasone suppression test Dexamethasone-CRH test Adrenal venous sampling Genetic testing Immunohistochemical staining Dual-energy X-ray absorptiometry	N/A	Associated with Carney complex Associated with MEN-1 Plasma levels of cortisol and ACTH may show false positive and false negative results due to normal diurnal hormonal variation
	Androgens	Hirsutism Virilization Amenorrhea Precocious puberty Testicular atrophy & diminished libido (male)	Clitorimegaly Male pattern baldness Resistant hypertension Gynecomastia	↑ Serum testosterone ↑ Serum androstenedione ↑ Serum dehydroepiandrosterone sulfate (DHEA-S) ↑ urine 17-ketosteroids ↑ plasma and urine estrogens	Pale tan to brown Pseudocapsule or the fibrous capsule Nesting, alveolar, cords, trabeculae Eosinophilic cytoplasm May see clear, vacuolated cytoplasm	Well-defined Solid mass Homogeneous enhancement (CT contrast) Hyperintense on in-phase and hypointense on oppose-phase (MRI)	FSH, LH, prolactin levels Cortisol levels FDG PET/CT Pelvic Ultrasound Adrenal Venous sampling	N/A	Extremely rare Most androgen secreting adenomas are mixed tumors
	Non-functional	Asymptomatic Abdominal pain Abdominal distenstion Nausea/vomiting Sub-clinical Cushing syndrome Sub-clinical hyperaldosteroism	Asymptomatic Abdominal asymmetry Abdominal mass Sub-clinical Cushing syndrome Sub-clinical hyperaldosteroism	N/L ↓ Adrenal hormones ↑ Serum cortisol (sub-clinical) ↑ Serum aldosterone (sub-clinical) ↑ Serum androgens (sub-clinical)	Well-defined margins Large monomorphic cells Abundant/foamy cytoplasm Typically resemble normal adrenal histology May see hemorrhage & necrosis	Solid, well defined mass (ultrasound) High lipid content and adjacent compression (CT) Hyperintense on in-phase and hypointense on oppose-phase (MRI)	Adrenal hormone levels Blood glucose level Plasma catecholamines and urinary metanephrines ARR Immunohistochemical staining	N/A	2-fold increased risk for Diabetes mellitus in some studies Work up must exclude Cushing syndrome, pheochromocytoma and adrenal carcinoma
Carcinoma	Cortisol Aldosterone Androgens Non-functional Erythropoietin	Symptoms of adrenal hormones as mentioned in adrenal adenomas Constitutional symptoms such as cachexia, night sweats, fever Localized symptoms such as abdominal pain, mass, fullness, early satiety	Hypertension Signs of adrenal hormones as mentioned in adrenal adenomas Constitutional Localized signs such as abdominal mass,abdominal distension	N/L ↑ Serum cortisol ↑ Serum aldosterone ↑ Serum androgens Hypokalemia Alkalosis ↑ ARR ↑ Blood glucose	brown to orange to yellow Necrosis & mitosis Hypercellular & solid and/or diffuse growth pattern Low to high lipid content Nuclear pleomorphism Lymphovascular invasion	Heterogeneous enhancement (CT) Heterogenous hyper-intensity (T2-weighted) and hypo-intensity on (T1-weighted) (MRI) Heterogeneous mass with intense FDG uptake greater than liver ([18F]FDG PET/CT)	Serum ACTH Low dose and high dose dexamethasone suppression test Urinary adrenal metabolites Proton MR spectroscopy [11C]MTO PET Immunohistochemical staining	N/A	May cause hypoglycemia (Anderson's syndrome} May be associated with: hyperreninemic hyperaldosteronism erythropoietin-associated polycythemia leukocytosis
Hyperplasia	Cortisol (most common) Aldosterone Androgens Non-functional	Depending on the product secreted, may present as: Cushing syndrome Hyperaldosteronism Virilization, hirsutism, menstrual irregularities, testicular atrophy & diminished libido Localized symptoms such as abdominal pain, mass, fullness, early satiety	Depending on the product secreted, may present as: Cushing syndrome Hyperaldosteronism Virilization, hirsutism, menstrual irregularities, gynaecomastia and testicular atrophy Localized signs such as abdominal mass,abdominal distension	↑ Serum cortisol ↑ Serum aldosterone ↑ Serum androgens Hypokalemia Alkalosis ↑ ARR ↑ Blood glucose ↑ Serum testosterone ↑ Serum androstenedione ↑ Serum dehydroepiandrosterone sulfate (DHEA-S) ↑ plasma and urine estrogens	Diffuse or nodular enlargement Increased thickness of zona reticularis and fasciculata Large polygonal cells with/without lipid depletion May contain pigment (lipofuscin) endocrine atypia Small micronodules	Adrenal mass Unilateral or bilateral adrenal enlargement or thickening Density and signaling is same as that of normal adrenal gland	Adrenal venous sampling Pelvic & pituitary imaging Genetic testing Fludrocortisone Suppression Testing Saline Infusion Testing Diurnal plasma cortisol variation Low dose and high dose dexamethasone suppression test FSH, LH, prolactin levels Cortisol levels	N/A	Congenital adrenal hyperplasia presents in children/young adults Associated with Carney complex Plasma levels of cortisol and ACTH may show false positive and false negative results due to normal diurnal hormonal variation
Medulla	Product	Clinical manifestations		Dianosis				Gold standard	Other features
		Symptoms	Signs	Blood & Urine	Histopathological	Imaging	Others
Pheochromocytoma	catecholamines	Headaches Palpitations Excessive sweating Anxiety Pallor Pain in chest/abdomen Weakness, fatigue Nausea/vomiting Dizziness Paresthesias Constipation (rarely diarrhea) Visual disturbance	Hypertension Postural hypotension Tachycardia or reflex bradycardia Tremulousness Pallor Flushing (rare) Weight loss Fasting hyperglycaemia Decreased GI motility Pallor ↑ Respiratory rate Psychosis	↑ Plasma and urine catecholamines ↑ Plasma and urine metanephrines ↑ Chromogranin A ↑ Plasma methoxytyramine	Loosely cohesive clusters Scattered tumor cells with prominent anisokaryosis, abundant eosinophilic granular cytoplasm and indistinct cell borders Occasional bi-nucleate cells	Heterogeneous appearance, often with some cystic areas. Calcification or hemorrhage may also be present (CT) T2-bright lesions, with/without cystic or necrotic components (MRI) Cystic or solid with necrotic areas or hemorrhages (U/S)	Genetic testing Provacative glucagon test Clonidine suppression test Metaiodobenzyl-guanidine scintigraphy PET scan Octereoscan	Plasma and urine catecholamines & metanephrines combined with clinical findings	May mimic panic attack May be associated with Von Hippel-Lindau disease, MEN type 2 and Neurofibromatosis type 1. Arise from the chromaffin cells Stains positive for Chromogranin A (CGA) Protein gene product (PGP) 9.5 Synaptophysin (SYN) CD56 (N-CAM) Glial fibrillary acidic protein (GFAP)
Neuroblastoma	catecholamines	Constitutional Failure to thrive Abdominal pain Diarrhea Constipation Dyspnea Prolonged cough Strabismus Proptosis	Abdominal mass Pallor Tachycardia Hypertension Failure to thrive Strabismus Proptosis	N/L Slight elevation in catecholamines ↑ Urinary metanephrines ↓ Hb ↑ Ferritin ↑ LDH Thrombocytosis	Cells may show: Undifferentiation Poor differentiation Differentiating neuroblasts Necrosis Salt and pepper chromatin spindle-like fibers	Large mass extending across the midline (CT) Heterogeneous enhancement (CT) Calcification & hemorrhage (CT & MRI) Non-homogeneous and hyperintense (T2-weighted) Hypointense (T1-weighted)	Immunohistochemical staining PET scan Octereoscan 131I-metaiodobenzylguanidine (MIBG) scintigraphy FISH Genetic testing	Pathological examinations	Stains positive for Chromogranin A (CGA) Protein gene product (PGP) 9.5 Neuron-specific enolase Synaptophysin (SYN) CD56 & CD57 Glial fibrillary acidic protein (GFAP)
Ganglioneuroma	catecholamines VIP Cortisol Androgens	Asymptomatic Abdominal pain Diarrhea	N/L Abdominal mass Hypertension	N/L ↑ plasma and urinary catecholamine ↑ VIP ↑ cortisol and testosterone	Mature type: mature Schwann cells, ganglion cells and perineural cells Maturing type: Schwann cells, ganglion cells and perineural cells with varying maturation	well-defined, Homogeneous (CT) Punctate or discrete calcification (CT) Hypointense (T1-weighted) Varied signal (T2-weighted)	Ultrasound Immunohistochemical staining 18F-2-fluoro-deoxy-D-glucose-positron emission tomography (PET)	Pathological examinations	Stains positive for S100 Synaptophysin Neurofilament (NF) protein Chromogranin A Glial fibrillary acidic protein PGP 9.5 Type IV collagen VIP
Stroma	Product	Clinical manifestations		Dianosis				Gold standard	Other features
		Symptoms	Signs	Blood & Urine	Histopathological	Imaging	Others
Lipoma/Myolipoma	N/A	Asymptomatic Abdominal pain Back pain Fever	N/L Abdominal mass Fever	N/L	Yellow adipose tissue Hemorrhagic foci Islands of hematopoietic cells (myolipoma) and mature fat cells (Lipoma)	Retro-peritoneal mass Well-defined heterogenous enhancement High signal (MRI)	RFTs LFTs Urine analysis Ultrasound	Pathological examinations	Myolipoma: mature adipose tissue and haematopoietic elements Lipoma: mature fat cells
Others	Product	Clinical manifestations		Dianosis				Gold standard	Other features
		Symptoms	Signs	Blood & Urine	Histopathological	Imaging	Others
Tuberculosis	N/A	Weakness Malaise Nausea Fatigue Anorexia Abdominal pain Orthostatic hypotension Constipation Salt craving Adrenal crisis Symptoms of pulmonary TB	Weight loss Hyperpigmentation of the skin Fever Hypotension Adrenal crisis Signs of pulmonary tuberculosis	Anemia Leukocytosis Hyponatremia Hyperkalemia Hypoglycemia Low early morning serum cortisol levels Low basal urinary cortisol ↑ ACTH ↓ Aldosterone ↑ Plasma renin	Enlarged, necrotic adrenal glands Central caseous necrosis Rim of granulomatous inflammatory cells (Langerhans giant cells and lymphocytes) Identifiable acid-fast stain-positive bacteria with Ziehl-Neelsen or fluorescent stains	Enlarged adrenal glands Calcification Hypodense areas (CT scan) Rim enhancement (CT scan) High FDG uptake by adrenal glands (18-FDG PET CT)	Laparoscopic adrenalectomy Chest X-ray Chest CT scan Tuberculin test ACTH stimulation test Insulin induced hypoglycemia Metyrapone stimulation tests	N/A	Majority of the cases are secondary to: Pulmonary TB Genitourinary TB HIV infection May present with shock with severe hypotension and hypoglycemia due to glucocorticoid insufficiency
Histoplasmosis	N/A	No adrenal symptoms Adrenal insufficiency: Weakness & malaise Nausea, fatigue and anorexia Abdominal pain Orthostatic hypotension Constipation Salt craving Symptoms of pulmonary/skin/bone histoplasmosis	Weight loss Hyperpigmentation of the skin Fever Hypotension Adrenal crisis Signs of pulmonary/skin/bone histoplasmosis	Anemia Leukocytosis Hyponatremia Hyperkalemia Hypoglycemia Low early morning serum cortisol levels Low basal urinary cortisol ↑ ACTH ↓ Aldosterone ↑ Plasma renin	Necrotizing granulomatous inflammation similar to tuberculosis Capsulated yeast forms of Histoplasma (Giemsa stain) Histoplasma identification (H&E stain) Focal ovoid bodies with a clear halo (PAS stain)	Enlarged adrenal glands Calcification Heterogeneous enhancement (CT) Isointense adrenal mass (MRI) Abnormal FDG uptake by adrenal glands (18-FDG PET CT)	Laparoscopic adrenalectomy Endoscopic ultrasound Abdominal ultrasound Chest X-ray ACTH stimulation test Metyrapone stimulation tests	Ultrasound-guided fine needle aspiration cytology (USG-FNAC)	Patient may exhibit no clinical manifestations of adrenal involvement Majority of the cases are secondary to: Pulmonary histoplasmosis HIV infection May present with shock with severe hypotension and hypoglycemia due to glucocorticoid insufficiency
Cysts	N/A	Abdominal pain abdominal mass Abdominal fullness Hematuria Infection Symptoms of malignancy (Cystic part of other tumors)	Abdominal mass & assymetry Fever Hypertension (Renal compression) Hypotension (Hemorrhage into cyst) Signs of malignancy (Cystic part of other tumors)	N/L Anemia Leukocytosis	Vascular or endothelial cyst: lined by flattened endothelial cells Epithelial: lined by epithelium Pseudocyst: lined by fibrous tissue Hydatid cyst: 3 layers (germinal layer, laminated membrane and dense fibrovascular tissue)	Homogeneous mass No enhancement Calcification Low density (CT) High signal (MRI) Circumscribed anechoic or hypoechoic mass (Ultrasound)	Complete endocrine panel [18F]FDG PET/CT (if malignancy is suspected) Biopsy (if maligancy is suspected) ACTH stimulation test	Ultrasonography	3 major subtypes Pure cysts (vascular or endothelial cyst, pseudocyst and 'true' epithelial cysts) Parasitic cysts Cystic part of an otherwise solid tumor
Haematoma	N/A	Flank/back pain Weakness Hypovolemic shock Adrenal crisis Adrenal insufficiency (massive hemorrhage) Symptoms of underlying cause	Hypotension Abdominal/flank mass Hypovolemic shock Adrenal crisis Adrenal insufficiency (massive hemorrhage) Signs of underlying cause	Anemia ↓ Serum and urinary adrenal hormones and metabolites Findings related to underlying cause	Pseudocyst: lined by fibrous tissue Findings related to underlying cause	High density (acute hemorrhage on CT) Isointense and low signal (Early hemorrhage on MRI) Hypointense (Late hemorrhage on MRI)	Adrenal ultrasound ACTH stimulation test Tests related to underlying cause	N/A	Majority of the cases in neonantal peiod Majority of the cases caused by trauma
Hemangioma	Cortisol (rare) Aldosterone (rare) Androgens (rare)	Abdominal mass & discomfort Nausea & vomiting Back pain Hypovolemic shock (hemorrhage) Symptoms of hormonal excess (very rare)	Abdominal mass Hypovolemic shock (hemorrhage) Symptoms of hormonal excess (very rare)	N/L ↓ Hb (hemorrhage) ↑ Serum and urinary adrenal hormones and metabolites (very rare)	Most often cavernous Peripheral dilated vascular spaces Monostromatic endothelium Absence of atypia Central necrosis Calcification Hemorrhage	Calcifications Phleboliths Irregular peripheral enhancement (CT) Hyperintensity (T2) hypointensity (T1)(MRI) Peripheral spotty and centripetal enhancement (MRI)	Complete endocrine panel Ultrasound FDG-PET scan Endoscopic ultrasound Post-resection biopsy (if malignancy is suspected)	Histopathology	Majority of the cases diagnosed incidentally Majority of the lesions are non-functional with female pre-dominance
Lymphoma	N/A	Fatigue Loss of appetite Weight loss Pigmentation of skin Flank/abdominal pain Fever Nausea & vomiting	Hypotension Altered mental status Abdominal/flank mass Fever Weight loss	↑ ESR ↑ LDH ↑ Serum ACTH ↓ Serum sodium Low early morning serum cortisol levels Low basal urinary cortisol ↓ Aldosterone	Diffuse growth pattern with large cells ( 5× normal lymphocytes) resembling immunoblasts Extensive necrosis May resemble anaplastic large cell lymphoma or metastatic carcinoma Abundant T-cells	Heterogeneous mass Hemorrhages Necrosis Enlarged retroperitoneal lymph nodes (MRI) Low intensity (T1-MRI) High intensity (T2-MRI))	Complete endocrine panel Ultrasound ACTH stimulation test CT-guided needle biopsy 18F-fluorodeoxyglucose (FDG) positron emission tomography PET/CT	Histopathology	May stain positive for CD3, CD19, CD20, CD22 BCL6+ / CD10+ CD43, CD45 Surface Ig CD68 CD79a LCA Pax.5
Cystic Lymphangioma	N/A	Asymptomatic Flank/back/abdominal pain Abdominal/flank mass GI obstruction	N/L Palpable mass Hypertension Fever	N/L	Cystic channels and spaces Flat endothelial cells Mature lymphoid aggregates	Well-demarcated Low-density Calcification T1 hypointense & T2 hyperintense (MRI)	Complete endocrine panel Ultrasound FDG-PET scan Aspiration & biopsy	Histopathology	Associated with Gorlin-Goltz syndrome Stains positive for CD31, CD34, and D2-40 and negative for cytokeratin
Teratoma	N/A	Asymptomatic Abdominal/back discomfort & pain Abdominal distension Lumbago Nausea, vomiting Local obstructive symptoms	N/L Abdominal distension Abdominal mass Weight loss Urinary retention Lower extremity edema Peritoneal effusion or peritonitis (rupture)	N/L	Fibrous tissue, adipose tissue and muscle fibers stratified squamous epithelium, hair shafts, fat cells, GI and respiratory epithelium Necrosis Calcification	Heterogeneous Mixed echo (U/S) Mixed density elements (CT scan) Egg-shell calcification Mild enhancement Mixed signals (MRI)	Complete endocrine panel 18F-fluorodeoxyglucose (FDG) positron emission tomography PET/CT Post-resection biopsy (if malignancy is suspected)	N/A	Derived from germ layers Majority are benign, but about one forth of adrenal teratomas are malignant lesions
Metastases	Related to the primary tumor	Asymptomatic Adrenal insufficiency Abdominal mass & discomfort Symptoms due to primary tumor that may include: Lung cancer Breast cancer Gastric cancer Liver cancer Pancreatic cancer Renal cell carcinomas Melanoma Lymphoma	Asymptomatic Adrenal insufficiency Abdominal mass Signs due to primary tumor that may include Lung cancer Breast cancer Gastric cancer Liver cancer Pancreatic cancer Renal cell carcinomas Melanoma Lymphoma	Varies depending on the primary tumor N/L If adrenal insufficiency: Hyponatremia Hyperkalemia Hypoglycemia Low early morning serum cortisol levels Low basal urinary cortisol ↑ ACTH ↓ Aldosterone ↑ Plasma renin	Single or multiple firm masses Hemorrhage Necrosis Morphology similar to the primary tumor Compression and atrophy of adjacent adrenal tissue	Calcification Hemorrhage Irregular peripheral enhancement Low signal on T1-weighed MRI and high signal on T2-weighed MRI OR Isointense on T1- and T2-weighed MRI	Blood and urine lab testing Complete endocrine panel Imaging of chest, abdomen, and pelvis Immunohistochemistry Endoscopy MRCP & ERCP 18F-fluorodeoxyglucose (FDG) positron emission tomography PET/CT	N/A	Metastases more common than primary adrenal tumors Adrenal hemorrhage is the most serious complication and may present as adrenal crisis and/or shock