Sandbox: Dr.Reddy

http://www.aafp.org/afp/2011/0615/p1403.html

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• Types of Pancreatic Intraepithelial Neoplasia (PanIN):

Types of Pancreatic Intraepithelial Neoplasia (PanIN)
PanIN 1 (low grade)
Minimal degree of atypia
Subclassified into PanIN 1A: absence of micropapillary infoldings of the epithelium; and 1B, presence of micropapillary infoldings of the epithelium
PanIN 2 (intermediate grade)
Moderate degree of atypia, including loss of polarity, nuclear crowding, enlarged nuclei, pseudostratification, and hyperchromatism
Mitoses are rarely seen
PanIN 3 (high grade/carcinoma in situ)
Severe atypia, with varying degrees of cribriforming, luminal necrosis, and atypical mitoses
Contained within the basement membrane

• Risk factors for Pancreatic Cancers:

Risk factors for Pancreatic Cancer
Risk factors
Smoking
Alcohol
Increased BMI
Diabetes mellitus
Chronic pancreatitis
Family history of pancreatic cancer
Familial Cancer Syndromes
BRCA1, BRCA2
Familial adenomatous polyposis (FAP)
Peutz-Jeghers syndrome
Familial atypical multiple mole melanoma syndrome (FAMMM)
Lynch syndrome
von Hippel-Lindau syndrome
Multiple endocrine neoplasia type 1
Gardner syndrome
Other medical conditions
Inflammatory bowel disease
Periodontal disease
Peptic ulcer disease

• Risk Factors and Inherited Syndromes associated with Pancreatic Cancer:

Risk Factors and Inherited Syndromes associated with Pancreatic Cancer
Risk Factor	Approximate Risk
Smoking	2-3 %
Long-standing Diabetes mellitus	2 %
Nonhereditery and Chronic Pancreatitis	2-6 %
Obesity, Inactivity or both	2 %
Non O Blood Group	1-2 %
Genetic SYndrome and Associated Gene or Genes
Hereditary pancreatitis (PRSS1, SPINK1)	50 %
Familial atypical multiple mole and melanoma syndrome (p16)	10-20 %
Hereditary breast and ovarian cancer syndromes (BRCA1, BRCA2, PALB2)	1-2 %
Peutz-Jeghers syndrome (STK11 [LKB1])	30-40 %
Hereditary nonpolyposis colon cancer (Lynch syndrome) (MLH1, MSH2, MSH6)	4 %
Ataxia-telangiectasia (ATM)	Unknown
Li-Fraumeni syndrome (P53)	Unknown

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Functional Pancreatic Neuroendocrine Tumors and their Characteristics
Tumor type and syndrome	Location in pancreas	Signs and symptoms	Circulating biomarkers
Insulinoma (Whipple’s triad)	Head, body, tail (evenly distributed)	Hypoglycemia, dizziness, sweating, tachycardia, tremulousness, confusion, seizure	CgA and CgB, insulin inappropriate for blood glucose level, proinsulin, C-peptide
Gastrinoma (Zollinger–Ellison)	Gastrinoma triangle Often extrapancreatic (duodenal); can be found anywhere in gland	Gastric acid hypersecretion, peptic ulcer, diarrhea, esophagitis, epigastric pain	CgA, gastrin, PP (35%)
VIPoma (Verner– Morrison syndrome, WDHA)	Distal pancreas (body and tail) Often spread outside pancreas	Watery diarrhea, hypokalemia, achlorhydria (or acidosis)	CgA, VIP
Glucagonoma	Body and tail of pancreas Often large and spread outside pancreas	Diabetes (hyperglycemia), necrolytic migratory erythema, stomatitis, glossitis, angular cheilitis	CgA, glucagon, glycentin
Somatostatinoma	Pancreatoduodenal groove, ampullary, periampullary	Gallstones, diabetes (hyperglycemia), steatorrhea	CgA, somatostatin
Ppoma	Head of pancreas	None	CgA, PP

Gastritis staging in clinical practice: The OLGA staging system
Atrophy Score		Corpus
		No Atrophy (Score: 0)	Mild Atrophy (Score: 1)	Moderate Atrophy (Score: 2)	Severe Atrophy (Score: 3)
A N T R U M	No Atrophy (Score: 0) (including incisura angularis)	STAGE 0	STAGE I	STAGE II	STAGE II
	Mild Atrophy (Score: 1) (including incisura angularis)	STAGE I	STAGE I	STAGE II	STAGE III
	Moderate Atrophy (Score: 2) (including incisura angularis)	STAGE II	STAGE II	STAGE III	STAGE IV
	Severe Atrophy (Score: 3) (including incisura angularis)	STAGE III	STAGE III	STAGE IV	STAGE IV

Sydney system for grading of chronic gastritis

Sydney system for grading of chronic gastritis
Feature	Definition	Grading guidelines
Chronic inflammation	Increased lymphocytes and plasma cells in lamina propria	Mild, moderate or severe increase in density
Activity	Neutrophilic infiltrates of the lamina propria, pits or surface epithelium	Mild: less than one-third of pits and surface infiltrated Moderate: one-third to two-thirds Severe: more than two-thirds
Atrophy	Loss of specialized glands from either antrum or corpus	Mild, moderate, or severe loss
Helicobacter pylori	H. pylori density	Mild colonization: scattered organisms covering less than one-third of the surface Moderate colonization: intermediate numbers Severe colonization: large clusters or a continuous layer over two-thirds of surface
Intestinal Metaplasia	Intestinal metaplasia of the epithelium	Mild: less than one-third of mucosa involved Moderate: one-third to two-thirds Severe: more than two-thirds

Feature	Non-atrophic Helicobacter	Atrophic Helicobacter	Autoimmune
Inflammation pattern	Antral or diffuse	Antrum & corpus, mild inflammation	Corpus only
Atrophy & metaplasia	Nil	Atrophy present, metaplasia at incisura	Corpus only

Antral predominant gastritis	Corpus predominant gastritis
More predominant in antrum in developed countries	Less predominant in developed countries
High acid output	Low acid output
Associated with duodenal ulceration

Classification Gastritis

Classification and grading of Gastritis: Updated Sydney System
Type of Gastritis		Etiology	Gastritis synonyms
Non-atrophic		Helicobacter pylori Other factors	Superficial Diffuse antral gastritis (DAG) Chronic antral gastritis (CAG) Interstitial - follicular Hypersecretory Type B*
Atrophic	Autoimmune	Autoimmunity	Type A* Diffuse corporal Pernicious anemia-associated
	Multifocal atrophic	Helicobacter pylori	Type B*, type AB*
		Dietary	Environmental
		Environmental factors	Metaplastic
Special forms	Chemical	Chemical irritation	Reactive
		Bile	Reflux
		NSAIDs	NSAID
		Other agents	Type C
	Radiation	Radiation injury
	Lymphocytic	Idiopathic? Immune mechanisms	Varioliform (endoscopic)
		Gluten	Celiac disease-associated
		Drug (ticlopidine)
		H. pylori
	Noninfectious granulomatous	Crohn's disease
		Sarcoidosis
		Granulomatosis with polyangiitis and other vasculitides
		Foreign substances
		Idiopathic	Isolated granulomatous
	Eosinophilic	Food sensitivity	Allergic
		Other allergies
	Other infectious gastritides	Bacteria (other than H. pylori)	Phlegmonous
		Viruses Fungi Parasites

Classification and grading of gastritis: Updated Sydney System
Type of gastritis		Etiologic factors	Gastritis synonyms
Nonatrophic	Helicobacter pylori Other factors	Superficial Diffuse antral gastritis (DAG) Chronic antral gastritis (CAG) Interstitial - follicular Hypersecretory Type B*

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• The table below differentiates Gastritis from other conditions

Differential Diagnosis

Disease

Cause

Symptoms

Diagnosis

Other findings

Pain

Nausea & Vomiting

Heartburn

Belching or Bloating

Weight loss

Loss of Appetite

Stools

Endoscopy findings

Location

Aggravating Factors

Alleviating Factors

Acute gastritis

H. pylori NSAIDS Corticosteroids Alcohol Spicy food Viral infections Crohn's disease Autoimmune diseases Bile reflux Cocaine use Breathing machine or ventilator Ingestion of corrosives

Epigastric pain

Food

Antacids

✔

✔

✔

-

✔

Black stools

Pangastritis or antral gastritis Erosive (Superficial, deep, hemorrhagic) Nonerosive (H. pylori)

-

Chronic gastritis

H. pylori Alcohol Medications Autoimmune diseases Chronic stress

Epigastric pain

Food

Antacids

✔

✔

✔

✔

✔

-

H. pylori gastritis Atrophy Intestinal metaplasia Lymphocytic gastritis Enlarged folds Aphthoid erosions

-

Atrophic gastritis

H. pylori Autoimmune disease

Epigastric pain

-

-

✔

-

✔

✔

-

H. pylori Mucosal atrophy Autoimmune Mucosal atrophy

Iron deficiency anemia Autoimmune gastritis diagnosis includes: Antiparietal and anti-IF antibodies Achlorhydria and hypergastrinemia Low serum cobalamine

Crohn's disease

Autoimmune disease

Abdominal pain

-

-

-

-

-

✔

✔

Chronic diarrhea often bloody with pus or mucus Rectal bleeding

Mucosal nodularity with cobblestoning Multiple aphthous ulcers Linier or serpiginous ulcerations Thickened antral folds Antral narrowing Hypoperistalsis Duodenal strictures

Fever Fatigue Anemia (pernicious anemia)

GERD

Lower esophageal sphincter abnormalities Hiatal hernia Abnormal esophageal contractions Prolonged emptying of stomach Gastrinomas

Epigastric pain

Spicy food Tight fitting clothing

Antacids Head elevation during sleep

✔ (Suspect delayed gastric emptying)

✔

-

-

-

-

Esophagitis Barrette esophagus Strictures

Other symptoms: Dysphagia Regurgitation Nocturnal cough Hoarseness Complications Esophagitis Strictures Barrette esophagus

Peptic ulcer disease

H. pylori Smoking Alcohol Radiation therapy Medications Zollinger-ellison syndrome

Epigastric pain sometimes extending to back Right upper quadrant pain

Duodenal ulcer Pain aggravates with empty stomach Gastric ulcer Pain aggravates with food

Antacids Duodenal ulcer Pain alleviates with food

✔

✔

-

-

-

Black stools

Gastric ulcers Discrete mucosal lesions with a punched-out smooth ulcer base with whitish fibrinoid base Most ulcers are at the junction of fundus and antrum 0.5-2.5cm Duodenal ulcers Well-demarcated break in the mucosa that may extend into the muscularis propria of the duodenum Found in the first part of duodenum <1cm

Other diagnostic tests Serum gastrin levels Secretin stimulation test Biopsy

Gastrinoma

Associated with MEN type 1

Abdominal pain

-

-

✔ (suspect gastric outlet obstruction)

✔

-

-

-

Black stools

Useful in collecting the tissue for biopsy

May present with symptoms of GERD or peptic ulcer disease Associated with MEN type 1 Diagnostic tests Serum gastrin levels Somatostatin receptor scintigraphy CT and MRI

Gastric Adenocarcinoma

H. pylori infection Smoked and salted food

Abdominal pain

-

-

✔

✔

✔

✔

✔

Black stools, or blood in stools

Esophagogastroduodenoscopy Multiple biopsies are taken to establish the diagnosis

Other symptoms Dysphagia Early satiety Frequent burping

Primary gastric lymphoma

H. pylori infection

Abdominal pain Chest pain

-

-

-

-

-

✔

-

-

Useful in collecting the tissue for biopsy

Other symptoms Painless swollen lymph nodes in neck and armpit Night sweats Fatigue Fever Cough or trouble breathing

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Chronology of Yersinia pestis infection Outbreaks("WHO | Plague".)
Date	Region Affected	Suspected, Probable & Confirmed Cases	Deaths	Details
15 October 2017	Seychelles - Suspected Plague (Ex- Madagascar)	1	0	On 10 October 2017, the Seychellois Ministry of Health notified WHO of a probable case of pneumonic plague The probable case is a 34-year-old man who had visited Madagascar and returned to Seychelles on 6 October 2017. He developed symptoms on 9 October 2017 and presented to a local health centre(pneumonic plague infection suspected, isolated and treated) 11 October, rapid diagnostic test (RDT) preformed, sputum sample was weakly positive. October 9 to 11 2017, eight of his contacts developed mild symptoms and have been isolated October 13 was the last day of monitoring of over 320 contact persons of the probable case Contact tracing is done thoroughly and 577 children and 63 teachers in potential contact with one of the individual identified by contact tracing were given antibiotics.
2 October 2017	Madagascar	73	17	The outbreak started following the death of a 31-year-old male from Ankazobe District in the Central Highlands (Hauts-Plateaux), a plague-endemic area. Since then, the Ministry of Public Health of Madagascar enhanced field investigations, contact tracing, surveillance, and monitoring all close contacts As of 30 September, 10 cities have reported pneumonic plague cases and the three most affected districts include: the capital city and suburbs of Antananarivo (27 cases, 7 deaths), Toamasina (18 cases, 5 deaths), and Faratshio (13 cases, 1 death) In addition to the 73 cases of pneumonic plague, from 1 August to 30 September, 58 cases of bubonic plague including seven deaths have been reported. One additional case of septicaemic plague has also been reported, and one case where the type is not specified
29 September 2017	Madagascar	51	12	On 23 August 2017, a 31-year-old male from Tamatave, visiting Ankazobe District in central highlands, developed malaria-like symptoms. On 27 August, he developed respiratory symptoms during his journey in a shared public taxi from Ankazobe District to Tamatave (via Antananarivo). His condition worsened and he died. In addition to the 51 suspected, probable and confirmed cases of pneumonic plague, and during the same period another 53 cases of bubonic plague including seven deaths have been reported throughout the country. One case of septicaemic plague has also been identified and they were not directly linked to the outbreak. Additionally, 31 people who came into contact with this case either through direct contact with the primary case or had other epidemiological links, became ill, and four cases of them died The outbreak was detected on 11 September, following the death of a 47-year-old woman from Antananarivo, who was admitted to a hospital with respiratory failure caused by pneumonic plague
9 January 2017	Madagascar	62 cases (6 confirmed, 5 probable, 51 suspected)	26 (case fatality rate of 42%)	Of the 11 samples tested, 5 were positive for plague on rapid diagnostic test and 6 are now confirmed at Institut Pasteur laboratory. Of the total reported cases, 5 are classified as pneumonic plague cases and the remaining as bubonic plague Retrospective investigations carried out in those two districts showed that it is possible that the outbreak might have started in mid-August 2016. The investigation in neighbouring villages is still ongoing. On 29 December, an investigation carried out within 25 km of the initial foci in Befotaka district has reported three deaths and is being investigated further for possible linkage to the outbreak
6 September 2015	Madagascar	14	10	The Ministry of Health of Madagascar has notified WHO of an outbreak of plague. The first case was identified on 17 August in a rural township in Moramanga district. The case passed away on 19 August All confirmed cases are of the pneumonic form. Since 27 August, no new cases have been reported from the affected or neighbouring districts
21 November 2014	Madagascar	119	40	On 4 November 2014, WHO was notified by the Ministry of Health of Madagascar of an outbreak of plague. The first case, a male from Soamahatamana village in the district of Tsiroanomandidy, was identified on 31 August. The patient died on 3 September Only 2% of reported cases are of the pneumonic form Cases have been reported in 16 districts of seven regions. Antananarivo, the capital and largest city in Madagascar, has also been affected with 2 recorded cases of plague, including 1 death. There is now a risk of a rapid spread of the disease due to the city’s high population density and the weakness of the healthcare system. The situation is further complicated by the high level of resistance to deltamethrin (an insecticide used to control fleas) that has been observed in the country
10 August 2010	Peru	17	-	As of 30 July 2010, the Ministry of Health in Peru confirmed a total of 17 cases of plague in Ascope province of Department La Libertad. Of these, four are pneumonic plague, 12 are bubonic plague and one was septicemic plague. The onset of symptoms for the last reported case of pneumonic plague was on 11 July 2010. During the investigations, 10 strains of Y. pestis were isolated from humans, rodents and domestic cats
11 August 2009	China	12	3	On 1 August 2009, a cluster outbreak of pulmonary plague cases in the remote town of Ziketan, Qinghai province was reported by the Ministry of Health (MoH), China. On 26th July 2009, the first case was a 32 year old male herdsman, who developed fever and hemoptysis was reported. He died enroute to hospital. On 30 July, 11 people who had close contact with the case (mainly relatives who attended the funeral) were all hospitalized as they developed fever and cough. They were all tested positive for plague. On 2 August 2009, 2 people who helped to bury the corpse, 64 year old father-in-law of the first case and a 37 year old male neighbour of the first case also died. On August 6 2009, the local health authority isolated 332 close contacts for further medical observation, and implemented traffic control around affected area. Preventive measures were taken to stop teh spread. Epidemiological investigation showed that the source of this outbreak was a wild marmot, which had contact with the dog of the index case.
7 November 2006	Democratic Republic of the Congo	1174	50	As of 29 September 2006, WHO received reports of a suspected pneumonic plague outbreak in 4 health zones in Haut-Uele district, Oriental province in the north-eastern part of the country. More than 50 samples have been collected and analysed; however, the diagnosis of plague has not been finally laboratory confirmed.
13 October 2006	Democratic Republic of the Congo	626	42	WHO has received reports of a suspected pneumonic plague outbreak in 2 health zones in Haut-Uele district, the majority reported from Wamba health zone in Oriental province in the northern part of the country However, the low case fatality ratio is unusual for pneumonic plague which suggests that the number of suspected cases may be an overestimation Preliminary results from a rapid diagnosis test in the field found three samples positive, out of eight
14 June 2006	Democratic Republic of the Congo	100	19	Suspected cases of bubonic plague have also been reported but the total number is not known at this time. Preliminary results from rapid diagnostic tests in the area confirm pneumonic plague. Ituri is known to be the most active focus of human plague worldwide, reporting around 1000 cases a year. The first cases in this outbreak occurred in a rural area, in the Zone de Santé of Linga, in mid-May
15 March 2005	Plague in the Democratic Republic of the Congo - update 4	130	57	Reported in Zobia, Bas-Uélé district, Oriental province No cases of bubonic plague have been detected
9 March 2005	Plague in the Democratic Republic of the Congo - update 3	114 cases (110 suspect cases, 4 probable cases)	54	Reported in Zobia, Bas-Uélé district, Oriental province
4 March 2005	Plague in the Democratic Republic of the Congo - update 2	57 cases (54 suspect cases, 3 probable cases)	16	Reported in Zobia, Bas-Uélé district, Oriental province
1 March 2005	Plague in the Democratic Republic of the Congo - update	4 probable cases and 4 suspect cases	1	Reported in Zobia, Bas-Uélé district, Oriental province
18 February 2005	Plague in the Democratic Republic of the Congo	-	61	Reported in Bas-Uele district, Oriental province Preliminary results from rapid diagnostic tests in the area confirm pneumonic plague, and the cases had clinical features compatible with this disease Cases have occurred in workers in a diamond mine in Zobia where c. 7000 people work. The mine was re-opened on 16 December 2004 and the first case occurred on 20 December
10 July 2003	Plague in Algeria - Update 2	10 laboratory confirmed cases and 1 probable case	-	Reported in oran district
3 July 2003	Plague in Algeria - Update	10 cases of which 8 have been laboratory confirmed	-	Reported by Ministry of Health, Algeria 8 cases of bubonic plague and 2 of septicemic plague, of which one was fatal
24 June 2003	Plague in Algeria	10 cases, 8 cases of bubonic plague and 2 of septicemic plague	one fatal case reported	Reported by the Ministry of Health, Algeria in Tafraoui, on the outskirts of Oran
5 June 2002	2002 - Plague in Malawi	71	-	Reported by the Malawian Ministry of Health 71 cases of bubonic plague in the district of Nsanje since the onset of the outbreak on 16 April 2002 Outbreak has so far affected 26 villages, 23 in the Ndamera area, 2 in Chimombo and 1 village in neighbouring Mozambique
20 February 2002	2002 - Plague in India	16 cases of pneumonic plague	4 deaths in Hat Koti village	Reported by the Ministry of Health, India
26 March 2001	2001 - Plague in Zambia	23 hospitalized cases	3 deaths in Petauke district, Eastern Province	The last case reported was 15 March 2001

Chronology of Marburg Hemorrhagic Fever Outbreaks ("Marburg Hemorrhagic Fever". Center for Disease Control and Prevention. Center for Disease Control and Prevention (CDC).)

Years	Country	Apparent or suspected origin	Reported number of human cases	Reported number (%) of deaths among cases	Situation
2014	Uganda	Uganda	1	1 (100%)	Ninety-nine individuals were quarantined after a 30-year-old male health-worker died of Marburg hemorrhagic fever on the 28th of September.
2012	Uganda	Kabale	15	4 (27%)	Testing at CDC/UVRI identified a Marburg virus disease outbreak in the districts of Kabale, Ibanda, Mbarara, and Kampala over a 3 week time period
2008	Netherlands ex Uganda	Cave in Maramagambo forest in Uganda, at the southern edge of Queen Elizabeth National Park	1	1 (100%)	A 40-year-old Dutch woman with a recent history of travel to Uganda was admitted to hospital in the Netherlands. Three days prior to hospitalization, the first symptoms (fever, chills) occurred, followed by rapid clinical deterioration. The woman died on the 10th day of the illness.
2007	Uganda	Lead and gold mine in Kamwenge District, Uganda	4	1 (25%)	Small outbreak, with 4 cases in young males working in a mine. To date, there have been no additional cases identified
2004-2005	Angola	Uige Province, Angola	252	227 (90%)	Outbreak believed to have begun in Uige Province in October 2004. Most cases detected in other provinces have been linked directly to the outbreak in Uige
1998-2000	Democratic Republic of Congo (DRC)	Durba, DRC	154	128 (83%)	Most cases occurred in young male workers at a gold mine in Durba, in the north-eastern part of the country, which proved to be the epicenter of the outbreak. Cases were subsequently detected in the neighboring village of Watsa.
1990	Russia	Russia	1	1 (100%)	Laboratory contamination.
1987	Kenya	Kenya	1	1 (100%)	A 15-year-old Danish boy was hospitalized with a 3-day history of headache, malaise, fever, and vomiting. Nine days prior to symptom onset, he had visited Kitum Cave in Mount Elgon National Park. Despite aggressive supportive therapy, the patient died on the 11th day of illness. No further cases were detected
1980	Kenya	Kenya	2	1 (50%)	A man with a recent travel history to Kitum Cave in Kenya's Mount Elgon National Park. Despite specialized care in Nairobi, the male patient died. A doctor who attempted resuscitation developed symptoms 9 days later but recovered
1975	Johannesburg, South Africa	Zimbabwe	3	1 (33%)	A man with a recent travel history to Zimbabwe was admitted to hospital in South Africa. Infection spread from the man to his traveling companion and a nurse at the hospital. The man died, but both women were given vigorous supportive treatment and eventually recovered.
1967	Germany and Yugoslavia	Uganda	31	7 (23%)	Simultaneous outbreaks occurred in laboratory workers handling African green monkeys imported from Uganda. In addition to the 31 reported cases, an additional primary case was retrospectively diagnosed by serology.

Marburg hemorrhagic fever: Symptoms and Disease Progression
Generalisation Phase (Day 1 to Day 5)	Fever Headache Chills Myalgia Malaise Fatigue Nausea Vomiting Diarrhoea Abdominal Pain Conjunctivitis Rash Pharyngitis
Early Organ Phase (Day 6 to Day 13)	Fever Bloody Diarrhoea(Malena) Hematemesis Exanthema Petechiae?Ecchymoses Muscosal hemorrhage Visceral hemorrhage Dyspnea Conjunctival injection Edema Apathy/Depression Irritability/aggression
Late Organ or Convalescence Phase (Day 14 to Day 21)	Fever Obtundation Dementia Coma Convulsions Diffuse coagulopathy Metabolic disturbances Shock Myalgia Arthralgia Hepatitis Asthenia Ocular disease Psychosis Social separation

Disease	Gene	Chromosome	Differentiating Features	Components of MEN			Diagnosis
				Parathyroid	Pitutary	Pancreas
von Hippel-Lindau syndrome	Von Hippel–Lindau tumor suppressor	3p25.3	Angiomatosis,  Hemangioblastomas, Pheochromocytoma,  Renal cell carcinoma, Pancreatic cysts (pancreatic serous cystadenoma) Endolymphatic sac tumor, Bilateral papillary cystadenomas of the epididymis (men) or broad ligament of the uterus (women)	-	-	+	Clinical diagnosis In hereditary VHL, disease techniques such as Southern blotting and gene sequencing can be used to analyse DNA and identify mutations.
Carney complex	PRKAR1A	17q23-q24	Myxomas of the heart Hyperpigmentation of the skin (lentiginosis) Endocrine (ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease)	-	-	-	Clinical diagnosis
Neurofibromatosis type 1	RAS	17	Scoliosis Learning disabilities Vision disorders Cutaneous lesions Epilepsy.	-	-	-	Prenatal Chorionic villus sampling or amniocentesis can be used to detect NF-1 in the fetus. Postnatal Cardinal Clinical Features" are required for positive diagnosis. Six or more café-au-lait spots over 5 mm in greatest diameter in pre-pubertal individuals and over 15 mm in greatest diameter in post-pubertal individuals. Two or more neurofibromas of any type or 1 plexiform neurofibroma Freckling in the axillary (Crowe sign) or inguinal regions Optic glioma Two or more Lisch nodules (pigmented iris hamartomas) A distinctive osseous lesion such as sphenoid dysplasia, or thinning of the long bone cortex with or without pseudarthrosis.
Li-Fraumeni syndrome	TP53	17	Early onset of diverse amount of cancers such as Sarcoma Cancers of Breast Brain Adrenal glands	-	-	-	Criteria Sarcoma at a young age (below 45) A first-degree relative diagnosed with any cancer at a young age (below 45) A first or second degree relative with any cancer diagnosed before age 60.
Gardner's syndrome	APC	5q21	Multiple polyps in the colon  Osteomas of the skull Thyroid cancer, Epidermoid cysts, Fibromas Desmoid tumors	-	-	-	Clinical diagnosis Colonoscopy
Multiple endocrine neoplasia type 2	RET	-	Medullary thyroid carcinoma (MTC) Pheochromocytoma Primary hyperparathyroidism	+	-	-	Hypercalcemia Hypophosphatemia, Elevated parathyroid hormone, Elevated norepinephrine Criteria Two or more specific endocrine tumors Medullary thyroid carcinoma Pheochromocytoma Parathyroid hyperplasia
Cowden syndrome	PTEN	-	Hamartomas	-	-	-	PTEN mutation probability risk calculator
Acromegaly/gigantism	-	-	Enlargement of the hands, feet, nose, lips and ears, and a general thickening of the skin Hypertrichosis Hyperpigmentation Hyperhidrosis Carpal tunnel syndrome.	-	+	-	An elevated concentration of serum growth hormone (GH) and insulin-like growth factor 1(IGF-1) levels is diagnostic of acromegaly.
Pituitary adenoma	-	-	Visual field defects classically bitemporal hemianopsia Increased intracranial pressure Migraine Lateral rectus palsy	-	+	-	Elevated serum level of prolactin Elevated or decreased serum level of adrenocorticotropic hormone (ACTH) Elevated or decreased serum level of growth hormone (GH) Elevated or decreased serum level of thyroid-stimulating hormone (TSH) Elevated or decreased serum level of follicle-stimulating hormone (FSH) Elevated or decreased serum level of luteinizing hormone (LH)
Hyperparathyroidism	-	-	- Kidney stones Hypercalcemia, Constipation Peptic ulcers Depression	+	-	-	An elevated concentration of serum calcium with elevated parathyroid hormone level is diagnostic of primary hyperparathyroidism. Most consistent laboratory findings associated with the diagnosis of secondary hyperparathyroidism include elevated serum parathyroid hormone level and low to normal serum calcium. An elevated concentration of serum calcium with elevated parathyroid hormone level in post renal transplant patients is diagnostic of tertiary hyperparathyoidism.
Pheochromocytoma/paraganglioma	VHL RET NF1   SDHB  SDHD	-	Characterized by Episodic hypertension Palpitations Anxiety Diaphoresis Weight loss	-	-	-	Increased catecholamines and metanephrines in plasma (blood) or through a 24-hour urine collection.
Adrenocortical carcinoma	p53 Retinoblastoma h19 Insulin-like growth factor II (IGF-II) p57kip2	17p, 13q	Cushing syndrome (cortisol hypersecretion) Conn syndrome (aldosterone hypersecretion) virilization (testosterone hypersecretion)	-	-	-	Increased serum glucose Increased urine cortisol Serum androstenedione and dehydroepiandrosterone Low serum potassium Low plasma renin activity High serum aldosterone. Excess serum estrogen.
Adapted from Toledo SP, Lourenço DM, Toledo RA. A differential diagnosis of inherited endocrine tumors and their tumor counterparts, journal=Clinics (Sao Paulo), volume= 68, issue= 7, 07/24/2013

Disease	Definition
von Hippel-Lindau syndrome	An autosomal dominant genetic disorder causing abnormal growth of blood vessels in different parts of the body.
Tuberous sclerosis	A rare multi-system genetic disease that causes benign tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin.
Carney complex	An autosomal dominant condition comprising myxomas of the heart and skin, hyperpigmentation of the skin (lentiginosis), and endocrine overactivity.
Neurofibromatosis type 1	An autosomal dominant tumor disorder of central nervous system due to germline mutations in neurofibromin manifesting as scoliosis (curvature of the spine), learning disabilities, vision disorders, cutaneous lesions and epilepsy.
Li-Fraumeni syndrome	An autosomal dominant rare disorder due to germline mutations of the TP53 tumor suppressor gene characterized by early onset of diverse amount of cancers such as sarcoma, cancers of the breast, brain and adrenal glands.
Gardner's syndrome	Familial colorectal polyposis is an autosomal dominant form of polyposis characterized by the presence of multiple polyps in the colon together with tumors outside the colon .
Multiple endocrine neoplasia type 2	An autosomal dominant disorder characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and primary hyperparathyroidism.
Cowden syndrome	A rare autosomal dominant disorder due to germline mutation of PTEN, a tumor suppressor gene characterized by multiple tumor-like growths called hamartomas.
Cushing's syndrome	A disorder due to prolonged exposure to cortisol characterized by hypertension, abdominal obesity but with thin arms and legs, purple abdominal striae, moon facies, buffalo lump, weak muscles, weak bones, acne, and fragile skin that heals poorly.
Acromegaly/gigantism	A rare syndrome due to excess growth hormone characterized by enlargement of the hands, feet, nose, lips and ears, and a general thickening of the skin, hypertrichosis, hyperpigmentation and hyperhidrosis and carpal tunnel syndrome.
Hyperaldosteronism	A disorder due to excess production of the aldosterone by the adrenal glands characterized by hypertension, muscular weakness, muscle spasms, tingling sensations and excessive urination.
Pituitary adenoma	A tumor in pituitary gland characterized by visual field defects, classically bitemporal hemianopsia, increased intracranial pressure, migraine and lateral rectus palsy.
Hyperparathyroidism	A disorder due to excess production of parathyroid hormone characterized by kidney stones, hypercalcemia, constipation, peptic ulcers and depression.
Thyroid carcinoma	A tumor of the thyroid gland characterized by signs and symptoms of hyperthryroidism or hypothyroidism.
Pheochromocytoma/paraganglioma	A neuroendocrine tumor of the medulla of the adrenal glands characterized by episodic hypertension, palpitations, anxiety, diaphoresis and weight loss.
Adrenocortical carcinoma	An aggressive cancer originating in the cortex of the adrenal gland that may either by non-secretory (asymptomatic) or secretory with signs and symptoms of Cushing syndrome (cortisol hypersecretion), Conn syndrome (aldosterone hypersecretion), virilization (testosterone hypersecretion)
Adapted from Toledo SP, Lourenço DM, Toledo RA. A differential diagnosis of inherited endocrine tumors and their tumor counterparts, journal=Clinics (Sao Paulo), volume= 68, issue= 7, 07/24/2013

Risk factors of VTE may be categorized in to modifiable, non-modifiable, temporary and other risk factors.

Modifiable Risk Factors	Non-Modifiable Risk Factors	Temporary Risk Factors	Other Risk Factors
❑ Modifiable risk factors are reversible based upon lifestyle/behavior modification. ❑ Obesity is defined as a body-mass index (BMI) above 30 kg/m2. ❑ Smoking: Smoking significantly increases the risk of DVT, particularly among women who are taking oral contraceptive pills as well as among obese people. ❑ Use of oral contraceptives ❑ Hyperhomocysteinemia: Hyperhomocysteinemia can be reduced with vitamin B supplementation.	❑ Advanced age ❑ Heart failure ❑ Thrombophilia or hypercoagulable state ❑ Polycythemia vera ❑ Factor V Leiden ❑ Prothrombin G20210A mutation ❑ Protein C deficiency ❑ Protein S deficiency ❑ Activated protein C resistance ❑ Antithrombin III deficiency ❑ Factor VIII mutation ❑ Antiphospholipid syndrome ❑ Heparin induced thrombocytopenia ❑ Nephrotic syndrome ❑ Paroxysmal nocturnal hemoglobinuria	❑ Pregnancy and the peri-partum period ❑ Active cancer ❑ Central venous catheter	❑ Other possible factors associated with VTE include: ❑ Nutrition low in fish ❑ Psychological stress ❑ Cardiovascular risk factors such as diabetes and hypercholesterolemia

Functional (Nuclear) Imaging for Thyrotoxicosis
Diagnosis	Degree of Thyrotoxicosis	Radioactive iodine Uptake	Scintigraphy Image
Toxic multinodular goiter	+/++	Normal or +/++	Enlarged gland with multiple "hot" or "cold" nodules
Grave's disease	++++	++++	Enlarged gland with homogenous uptake
Thyrotoxic phase of subacute thyroiditis	++++	<1% at 4 or 24 hr.	Absent isotope uptake
Toxic adenoma	+/++	Normal or +/++	Dominant "hot" nodule with low or absent uptake in the surrounding normal gland.

Multiple Endocrine Neoplasia-1 (MEN-1) Syndrome Tumors
Enteropancreatic tumor	Gastrinoma Insulinoma Glucagonoma Nonfunctioning and PPoma VIPoma
Pituitary adenoma	Prolactinoma Somatotrophinoma Corticotropinoma Nonfunctioning
Associated tumors	Adrenal cortical tumor Pheochromocytoma Bronchopulmonary NET Thymic NET Gastric NET Lipomas Angiofibromas Collagenomas Meningiomas
Parathyroid adenoma	-

|- ! colspan="1" style="background: #4479BA; padding: 5px 5px;" | Parathyroid adenoma | style="padding: 5px 5px; background: #F5F5F5;" | Parathyroid adenoma

Laboratory Findings of Familial Hypocalciuric Hypercalcemia
Condition	PTH	Serum Calcium	Serum phosphate	Urine Calcium	Urine Calcium/Serum Creatinine Ratio
Familial Hypocalciuric Hypercalcemia	Normal	Normal or ↑	Normal	↓	↓
Primary Hyperparathyroidism	↑	↑	↓	Normal	↑

Cause of dementia	Characteristics and clinical and cognitive features
Alzheimer's disease	Brain disease that encompasses predementia and dementia phases. Memory changes and AD biomarker evidence required for diagnosis of probable AD. Slow cognitive and functional decline with early loss of awareness. Amnestic and nonamnestic phenotypes
Lewy body dementia	Spectrum of disorders with movement, cognitive, autonomic changes. Includes dementia with Lewy bodies and Parkinson's disease dementia. Early visual hallucinations, muscle rigidity, sleep disturbance. α-synuclein deposits present in neurons
Frontotemporal lobar degeneration	Focal atrophy of frontal and temporal lobes; knife-edge atrophy noted on MRI. Younger onset, changes in personality and behavior, language impairment, strong familial component.
Vascular dementia	Stepwise progression and focal neurologic signs (also known as multi-infarct dementia or poststroke dementia). Dysexecutive syndrome, slowed processing speed, retrieval difficulties, depression, mild motor signs in subcortical vascular dementia. Symptoms overlap with alzheimer's disease.

Causes of Hypergastrinemia
Appropriate hypergastrinemia	Atrophic gastritis with or without pernicious anemia Antisecretory therapy (PPIs or high-dose histamine H2-receptor antagonist) Chronic renal failure H pylori pangastritis Vagotomy
Inappropriate hypergastrinemia	ZES (sporadic or associated with MEN-1) Antral-predominant H pylori infection Retained-antrum syndrome Gastric-outlet obstruction Small-bowel resection
Spurious hypergastrinemia	Nonfasting patient Inaccurate assay

Cause of dementia	Characteristics and clinical and cognitive features
AD	Brain disease that encompasses predementia and dementia phases. Memory changes and AD biomarker evidence required for diagnosis of probable AD. Slow cognitive and functional decline with early loss of awareness. Amnestic and nonamnestic phenotypes
Lewy body dementia	Spectrum of disorders with movement, cognitive, autonomic changes. Includes dementia with Lewy bodies and Parkinson's disease dementia. Early visual hallucinations, muscle rigidity, sleep disturbance. α-synuclein deposits present in neurons
Frontotemporal lobar degeneration	Focal atrophy of frontal and temporal lobes; knife-edge atrophy noted on MRI. Younger onset, changes in personality and behavior, language impairment, strong familial component
VaD	Stepwise progression and focal neurologic signs (also known as multi-infarct dementia or poststroke dementia). Dysexecutive syndrome, slowed processing speed, retrieval difficulties, depression, mild motor signs in subcortical VaD. Symptoms overlap with AD

Cause of dementia	Characteristics and clinical and cognitive features
AD	Brain disease that encompasses predementia and dementia phases. Memory changes and AD biomarker evidence required for diagnosis of probable AD. Slow cognitive and functional decline with early loss of awareness. Amnestic and nonamnestic phenotypes
Lewy body dementia	Spectrum of disorders with movement, cognitive, autonomic changes. Includes dementia with Lewy bodies and Parkinson's disease dementia. Early visual hallucinations, muscle rigidity, sleep disturbance. α-synuclein deposits present in neurons
Frontotemporal lobar degeneration	Focal atrophy of frontal and temporal lobes; knife-edge atrophy noted on MRI. Younger onset, changes in personality and behavior, language impairment, strong familial component
VaD	Stepwise progression and focal neurologic signs (also known as multi-infarct dementia or poststroke dementia). Dysexecutive syndrome, slowed processing speed, retrieval difficulties, depression, mild motor signs in subcortical VaD. Symptoms overlap with AD

Clinical Dementia Rating
Based on the severity of Impairment
Criteria	Minimal	Questionable	Mild	Moderate	Severe
Memory	No memory loss or slight inconsistent forgetfulness	Consistent slight forgetfulness; partial recollection of events; “benign” forgetfulness	Moderate memory loss; more marked for recent events; defect interferes with everyday activities	Severe memory loss; only highly learned material retained; new material rapidly lost	Severe memory loss; only fragments remain
Orientation	Fully oriented	Fully oriented except for slight difficulty with time relationships	Moderate difficulty with time relationships; oriented for place at examination; may have geographic disorientation elsewhere	Severe difficulty with time relationships; usually disoriented to time, often to place	Oriented to person only
Judgment and problem solving	Solves everyday problems and handles business and financial affairs well; judgment good in relation to past performance	Slight impairment in solving problems, determining similarities and differences	Moderate difficulty in solving problems, determining similarities and differences; social judgment usually maintained	Severely impaired in solving problems, determining similarities and differences; social judgment usually impaired	Unable to make judgments or solve problems
Community affairs	Independent function at usual level in job, shopping, and volunteer and social groups	Slight impairment in these activities	Unable to function independently at these activities, although may still be engaged in some; appears normal to casual inspection	No pretense of independent function outside of home; appears well enough to be taken to functions outside a family home	No pretense of independent function outside of home; appears too ill to be taken to functions outside a family home
Home and hobbies	Life at home, hobbies, and intellectual interests well maintained	Life at home, hobbies, and intellectual interests slightly impaired	Mild but definite impairment of function at home; more difficult chores abandoned; more complicated hobbies and interests abandoned	Only simple chores preserved; interests very restricted and poorly maintained	No significant function in home
Personal care	Fully capable of self-care	Fully capable of self-care	Needs prompting	Requires assistance in dressing, hygiene, keeping of personal effects	Requires much help with personal care; frequent incontinence

Sandbox: Dr.Reddy
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{| class="wikitable"

!Condition !T3 !T4 !TSH |- |Thyrotoxicosis |Increased |Increased |Supressed |- |T3 Toxicosis |2X (Increased Twice) |Normal |Supressed |- |Hypothyroidism |Low/Normal |Low |Increased |} ↓ β

Differentiating Thyroid adenoma from other Diseases

The table below summarizes the findings that differentiate thyroid adenoma from other conditions that cause neck swelling.

Disease	Findings
Multinodular goiter	Multinodular goiter is the multinodular enlargement of the thyroid gland. They are large nodules of more than 1 cm that produces symptoms of hyperthyroidism.
Grave's disease	Grave's disease is an autoimmune disease that affects the thyroid. It frequently results in hyperthyroidism and an enlarged thyroid. Pretibial myxedema and ophthalmopathy are some of the findings of grave's disease.
Hashimoto's disease	Hashimoto's disease is an autoimmune disease in which the thyroid gland is attacked by a variety of cell-mediated and antibody-mediated immune processes, causing primary hypothyroidism.
Medullary thyroid carcinoma	Medullary thyroid carcinoma is a form of thyroid carcinoma which originates from the parafollicular cells (C cells), which produce the hormone calcitonin.
Thyroid lymphoma	Thyroid lymphoma is a rare malignant tumor which manifests as rapidly enlarging neck mass causing respiratory difficulty.
De Quervain's thyroiditis	De Quervain's thyroiditis is a subacute granulomatous thyroiditis preceded by an upper respiratory tract infection.
Acute suppurative thyroiditis	Acute suppurative thyroiditis is an uncommon thyroid disorder usually caused by bacterial infection.

Thyroid adenoma must be differentiated from other causes of hyperthyroidism such as Grave's disease and toxic nodular goiter.

Cause of thyrotoxicosis	TSH receptor antibodies	Thyroid US	Color flow Doppler	Radioactive iodine uptake/Scan	Other features
Graves' disease	+	Hypoechoic pattern	?	?	Ophthalmopathy, dermopathy, acropachy
Toxic nodular goiter	-	Multiple nodules	-	Hot nodules at thyroid scan	-
Toxic adenoma	-	Single nodule	-	Hot nodule	-
Subacute thyroiditis	-	Heterogeneous hypoechoic areas	Reduced/absent flow	?	Neck pain, fever, and elevated inflammatory index
Painless thyroiditis	-	Hypoechoic pattern	Reduced/absent flow	?	-
Amiodarone induced thyroiditis-Type 1	-	Diffuse or nodular goiter	?/Normal/?	? but higher than in Type 2	High urinary iodine
Amiodarone induced thyroiditis-Type 2	-	Normal	Absent	?/absent	High urinary iodine
Central hyperthyroidism	-	Diffuse or nodular goiter	Normal/?	?	Inappropriately normal or high TSH
Trophoblastic disease	-	Diffuse or nodular goiter	Normal/?	?	-
Factitious thyrotoxicosis	-	Variable	Reduced/absent flow	?	? Serum thyroglobulin
Struma ovarii	-	Variable	Reduced/absent flow	?	Abdominal RAIU

Disease		Findings
Thyroiditis	Direct chemical toxicity with inflammation	Amiodarone, sunitinib, pazopanib, axitinib, and other tyrosine kinase inhibitors may also be associated with a destructive thyroiditis.
	Radiation thyroiditis	Patients treated with radioiodine may develop thyroid pain and tenderness 5 to 10 days later, due to radiation-induced injury and necrosis of thyroid follicular cells and associated inflammation.
	Drugs that interfere with the immune system	Interferon-alfa is a well-known cause of thyroid abnormality. It mostly leads to the development of de novo antithyroid antibodies.
	Lithium	Patients treated with lithium are at a high risk of developing painless thyroiditis and Graves' disease.
	Palpation thyroiditis	Manipulation of the thyroid gland during thyroid biopsy or neck surgery and vigorous palpation during the physical examination may cause transient hyperthyroidism.
Exogenous and ectopic hyperthyroidism	Factitious ingestion of thyroid hormone	The diagnosis is based on the clinical features, laboratory findings, and 24-hour radioiodine uptake.
	Acute hyperthyroidism from a levothyroxine overdose	The diagnosis is based on the clinical features, laboratory findings, and 24-hour radioiodine uptake.
	Struma ovarii	Functioning thyroid tissue is present in an ovarian neoplasm.
	Functional thyroid cancer metastases	Large bony metastases from widely metastatic follicular thyroid cancer cause symptomatic hyperthyroidism.
Hashitoxicosis		It is an autoimmune thyroid disease that initially presents with hyperthyroidism and a high radioiodine uptake caused by TSH-receptor antibodies similar to Graves' disease. It is then followed by the development of hypothyroidism due to the infiltration of the thyroid gland with lymphocytes and the resultant autoimmune-mediated destruction of thyroid tissue, similar to chronic lymphocytic thyroiditis.
Toxic adenoma and toxic multinodular goiter		Toxic adenoma and toxic multinodular goiter are results of focal/diffuse hyperplasia of thyroid follicular cells independent of TSH regulation. Findings of single or multiple nodules are seen on physical examination or thyroid scan.
Iodine-induced hyperthyroidism		It is uncommon but can develop after an iodine load, such as administration of contrast agents used for angiography or computed tomography (CT), or iodine-rich drugs such as amiodarone.
Trophoblastic disease and germ cell tumors		Thyroid-stimulating hormone and HCG have a common alpha-subunit and a beta-subunit with considerable homology. As a result, HCG has weak thyroid-stimulating activity and high titer HCG may mimic hyperthyroidism.

Sandbox: Dr.Reddy

Diagnostic accuracy of imaging for localization of gastrinoma
CT	50%	Tumors enhance on early arterial phase because of high vascularity; sensitivity decreases for tumors <2cm
MRI

Diagnostic accuracy of imaging for localization of gastrinoma
Modality	Sensitivity	Comments
CT MRI SRS EUS Angiography / Arterial Stimulation	50% 25-50% 80% 70% 40-60%	Tumors enhance on early arterial phase because of high vascularity; sensitivity decreases for tumors <2cm Low T1 and high T2 signal intensity. Additional ability to detect extra abdominal metastatic lesions; enhanced sensitivity when combined with single photon emission computed tomography (SPECT) Much higher sensitivity for pancreatic compared with duodenal lesions; can guide needle biopsy to obtain tissue diagnosis. Contrast administered into GDA and inferior pancreaticoduodenal artery; may be performed intraoperatively

Sporadic and MEN-1-associated ZES
Factors	Sopradic ZES	MEN-1 ZES
Prevalence Family History Other Endocrinopathies Gastrinoma Size Number of tumors Most Common Tumor Location Lymph Node Primary Surgical Cure Rate Malignant Potential	80% No No >2cm Single Pancreas 10% 60% High	20% Yes Yes <2cm Multiple Duodenum No Rare Low

Causes of Hypergastrinemia
Appropriate hypergastrinemia	Atrophic gastritis with or without pernicious anemia Antisecretory therapy (PPIs or high-dose histamine H2-receptor antagonist) Chronic renal failure H pylori pangastritis Vagotomy
Inappropriate hypergastrinemia	ZES (sporadic or associated with MEN-1) Antral-predominant H pylori infection Retained-antrum syndrome Gastric-outlet obstruction Small-bowel resection
Spurious hypergastrinemia	Nonfasting patient Inaccurate assay

Surgical approach to gastrinoma in sporadic ZES and ZES associated with MEN-1
	sporadic ZES	MEN-1 ZES
ABCD	abcd	1234

Surgical approach to gastrinoma in sporadic ZES and ZES associated with MEN-1
	sporadic ZES	MEN-1 ZES
ABCD	abcd	1234

Classification of Androgen Insensitivity Syndrome Phenotypes
Type	External Genitalia	Findings
CAIS - (Complete androgen insensitivity syndrome)	Female (“testicular feminization”)	Absent OR rudimentary wolffian duct derivatives. Absence or presence of epididymides and/or vas deferens. Inguinal, labial, or abdominal testes. Short blind-ending vagina. Scant OR absent pubic AND/OR axillary hair.
Predominantly female (“incomplete AIS”)	Inguinal OR labial testes. Clitoromegaly and labial fusion. Distinct urethral and vaginal openings OR a urogenital sinus.
PAIS - (Partial androgen insensitivity syndrome)	Ambiguous	Microphallus (<1 cm) with clitoris-like underdeveloped glans; labia majora-like bifid scrotum. Descended OR undescended testes. Perineoscrotal hypospadias OR urogenital sinus. Gynecomastia (development of breasts) in puberty.
Predominantly male	Simple (glandular or penile) OR severe (perineal) “isolated” hypospadias with a normal-sized penis and descended testes OR severe hypospadias with micropenis, bifid scrotum, and either descended OR undescended testes. Gynecomastia in puberty.
MAIS - (Mild androgen insensitivity syndrome)	Male (“undervirilized male syndrome”)	Impaired spermatogenesis AND/OR impaired pubertal virilization. Gynecomastia in puberty.

Template:Topic Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: