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Questions and Answers
Which type of Multiple Endocrine Neoplasia syndrome is associated with the MENIN gene mutation?
Which type of Multiple Endocrine Neoplasia syndrome is associated with the MENIN gene mutation?
- MEN 2B/MEN 3
- MEN 2A
- MEN 4
- MEN 1 (correct)
MEN 2A is characterized by an intron inversion causing a base pair deletion.
MEN 2A is characterized by an intron inversion causing a base pair deletion.
False (B)
What is the most common benign tumor associated with MEN 1?
What is the most common benign tumor associated with MEN 1?
Adreno cortical adenoma
The major manifestation of MEN 1 includes collagenoma and ________.
The major manifestation of MEN 1 includes collagenoma and ________.
Match the following types of MEN syndromes with their primary characteristic:
Match the following types of MEN syndromes with their primary characteristic:
What is the initial dosage for Phenoxybenzamine in BP control?
What is the initial dosage for Phenoxybenzamine in BP control?
Metyrosine is commonly used in BP control.
Metyrosine is commonly used in BP control.
What type of blocker is Phenoxybenzamine?
What type of blocker is Phenoxybenzamine?
For HR control, __________ can be administered three days before surgery.
For HR control, __________ can be administered three days before surgery.
Match the following medications with their usage:
Match the following medications with their usage:
What is the primary type of cancer associated with Classical MEN 2A?
What is the primary type of cancer associated with Classical MEN 2A?
Familial medullary thyroid cancer (FMTC) is also known as MEN 2B.
Familial medullary thyroid cancer (FMTC) is also known as MEN 2B.
Name one additional feature associated with MEN 2B besides medullary thyroid cancer.
Name one additional feature associated with MEN 2B besides medullary thyroid cancer.
In MEN 4, a mutation in __________ is typically present.
In MEN 4, a mutation in __________ is typically present.
Match the following types of MEN syndromes with their characteristic features:
Match the following types of MEN syndromes with their characteristic features:
What is the most common type of incidental adrenal mass?
What is the most common type of incidental adrenal mass?
All incidental adrenal masses are malignant.
All incidental adrenal masses are malignant.
Name one alarm sign in non-functioning tumors.
Name one alarm sign in non-functioning tumors.
A malignant, endocrine active tumor that produces cortisol is known as a ______.
A malignant, endocrine active tumor that produces cortisol is known as a ______.
Match the following characteristics with their corresponding type of tumor:
Match the following characteristics with their corresponding type of tumor:
What percentage of total bone mass does cortical/compact bone contribute?
What percentage of total bone mass does cortical/compact bone contribute?
Trabecular bone has a low remodeling rate compared to cortical bone.
Trabecular bone has a low remodeling rate compared to cortical bone.
What term is used to evaluate osteoporosis based on trabecular bone?
What term is used to evaluate osteoporosis based on trabecular bone?
The structural functional unit of cortical bone is called an __________.
The structural functional unit of cortical bone is called an __________.
Match the following features with their respective types of bone:
Match the following features with their respective types of bone:
What is the sensitivity of the Plasma Fractionated Metanephrine/Nm test?
What is the sensitivity of the Plasma Fractionated Metanephrine/Nm test?
MIBG is currently the preferred imaging method for adrenal pheochromocytoma.
MIBG is currently the preferred imaging method for adrenal pheochromocytoma.
What treatment is the standard of care for adrenal pheochromocytoma?
What treatment is the standard of care for adrenal pheochromocytoma?
Gallium DOTATATE PET scan is used if MRI is negative but biochemical tests are positive, indicating a __________.
Gallium DOTATATE PET scan is used if MRI is negative but biochemical tests are positive, indicating a __________.
Match the following imaging techniques with their descriptions:
Match the following imaging techniques with their descriptions:
What is the primary age group affected by APS Type 1 in childhood?
What is the primary age group affected by APS Type 1 in childhood?
In adults, Hashimoto's thyroiditis is more common than Graves' disease in APS Type 1.
In adults, Hashimoto's thyroiditis is more common than Graves' disease in APS Type 1.
Which gene is associated with childhood APS Type 1?
Which gene is associated with childhood APS Type 1?
The autoantibody commonly found in APS Type 1 in adults is __________.
The autoantibody commonly found in APS Type 1 in adults is __________.
Match the following features of APS Type 1 with the correct category:
Match the following features of APS Type 1 with the correct category:
What is the most common cause of death in MEN I?
What is the most common cause of death in MEN I?
Primary hyperparathyroidism is more common in females compared to males.
Primary hyperparathyroidism is more common in females compared to males.
What is the peak age of presentation for sporadic primary hyperparathyroidism?
What is the peak age of presentation for sporadic primary hyperparathyroidism?
The treatment for small multifocal gastrinomas includes _____ and octreotide.
The treatment for small multifocal gastrinomas includes _____ and octreotide.
Match the following neuroendocrine tumors with their respective features:
Match the following neuroendocrine tumors with their respective features:
What is the primary type of collagen found in organic constituents of bone?
What is the primary type of collagen found in organic constituents of bone?
Osteocalcin is one of the non-collagenous proteins found in bone.
Osteocalcin is one of the non-collagenous proteins found in bone.
Name one disorder associated with Type IV collagen.
Name one disorder associated with Type IV collagen.
The primary inorganic constituents of bone include calcium, phosphorous, and __________.
The primary inorganic constituents of bone include calcium, phosphorous, and __________.
Match the collagen types with their associated disorders:
Match the collagen types with their associated disorders:
Which type of collagen is primarily found in the vitreous humor?
Which type of collagen is primarily found in the vitreous humor?
Matrix GLA protein acts as a vascular calcification inhibitor.
Matrix GLA protein acts as a vascular calcification inhibitor.
What are the main types of cells found in bone?
What are the main types of cells found in bone?
Type __________ collagen is mainly found in the basement membrane.
Type __________ collagen is mainly found in the basement membrane.
Which of the following collagen types is primarily found in the vascular system?
Which of the following collagen types is primarily found in the vascular system?
Which of the following syndromes is associated with the VHL gene on chromosome 3?
Which of the following syndromes is associated with the VHL gene on chromosome 3?
McCune-Albright syndrome is inherited in an autosomal dominant pattern.
McCune-Albright syndrome is inherited in an autosomal dominant pattern.
Name one associated feature of Hyper parathyroidism/Jaw tumor syndrome.
Name one associated feature of Hyper parathyroidism/Jaw tumor syndrome.
The gene associated with Couden syndrome is the ____ gene.
The gene associated with Couden syndrome is the ____ gene.
Match the following syndromes with their associated features:
Match the following syndromes with their associated features:
Study Notes
Multiple Endocrine Neoplasia (MEN) Syndromes
- MEN 1: Autosomal dominant inheritance pattern, mutation in MENIN tumor suppressor gene on chromosome 11q.
- Major Manifestations:
- Collagenoma (more common than lipoma)
- Tumors:
- Benign: Adrenal cortical adenoma (most common), Meningioma (most common neurotumor), Pheochromocytoma
- Treatment:
- Start with alpha-blockers:
- Phenoxybenzamine (DOC): 10mg daily, gradually increased to 10mg three times daily. Non-selective, irreversible, long-lasting, non-competitive inhibitor.
- Prazosin (2.5mg daily, increased to 5mg twice daily) and Terazosin also used.
- Calcium Channel Blockers: Amlodipine and Nicardipine if adequate blood pressure control not achieved.
- Metyrosine: Rarely used.
- Start with alpha-blockers:
- Pre-operative Management:
- 3 days before surgery: Beta-blockers for heart rate control (Atenolol: 12.5mg twice daily, increased to 25mg twice daily).
- Intraoperative Hypertensive Crisis: Sodium nitroprusside or Nicardipine.
- Major Manifestations:
MEN 2A:
- RET protooncogene mutation on chromosome 10q.
- Classical MEN 2A:
- Medullary thyroid cancer (100%)
- Pheochromocytoma (50%)
- Parathyroid hyperplasia (25%)
- Variations of MEN 2A:
- MEN 2A + Cutaneous lichen amyloidosis
- MEN 2A + Hirschprung's disease
- Familial medullary Thyroid cancer (FMTC)
MEN 2B/MEN 3:
- RET protooncogene mutation on chromosome 10q.
- Characteristics:
- Medullary thyroid cancer (100%)
- Pheochromocytoma (50%)
- Marfanoid habitus
- Mucosal and intestinal ganglioneuromatosis
- Myelinated corneal nerve fibers
MEN 4:
- Cyclin-Dependent Kinase Inhibitor B (CDKN1B) mutation
- Characteristics:
- Parathyroid hyperplasia (adenoma)
- Pituitary, Renal/adrenal, and Testicular/ovarian tumors
Adrenal Medulla: Part 1
- Incidental Adrenal Mass/Incidentaloma:
- Benign (most common): Endocrine inactive/non-functional tumors.
- Malignant: Endocrine active/functional tumors: Cortisol producing tumors more common than Pheochromocytomas.
- Alarm Signs in Non-Functioning Tumors:
- Tumor size ≥ 4 cm
- CT density > 20 HU
- CT contrast washout
- 24-hour Fractionated Metanephrine/Normetanephrine (Nm) Screening Test:
- Highly sensitive (98%)
- Highly specific (98%)
- Plasma Fractionated Metanephrine/Nm:
- 100% sensitivity
- No false negatives - Used along with 24-hour urine metanephrine/Nm in patients with a strong family history.
- Imaging:
- MRI abdomen: Used for adrenal pheochromocytoma. Shows hyperintensities with hemorrhagic or cystic changes.
- MIBG: Obsolete
- FDG-PET: Obsolete
- Gallium DOTATATE PET scan: Useful for detecting paragangliomas
- Indicated if MRI is negative but biochemical tests are positive.
- DOTA binds to Octreotate, which binds to Somatostatin Receptor Type a (SSTR type 2) on the tumor surface.
- Treatment: Laparoscopic retroperitoneal adrenalectomy (TOC)
- Pre-Operative Preparation: Liberal fluid intake for 10 days before surgery.
Inheritance Patterns
- Hyperparathyroidism/Jaw tumor syndrome: Autosomal dominant. Parafibromin (CDC73) gene mutation. Associated with ossifying fibroma of jaw, atrial myxoma (lepidic pattern).
- VHL syndrome: Autosomal dominant. VHL gene mutation on chromosome 3. Associated with renal cell carcinoma (RCC), cerebellar hemangioblastoma, islet cell tumors of pancreas, papillary cystadenoma of broad ligament of uterus, epididymal cyst, endolymphatic sac tumors.
- Neurofibromatosis type I (NF-1): Autosomal dominant. Neurofibromin gene mutation on chromosome 17. Associated with neurofibromas, pheochromocytoma, optic nerve sheath tumors, meningiomas.
- Cowden syndrome: Autosomal dominant. PTEN gene mutation. Associated with breast cancer, hamartomatous polyps of GIT.
- McCune-Albright syndrome: Not inherited. Polyostotic fibrous dysplasia (PFD), precocious puberty, café au lait spots.
BASICS OF BONE AND MINERAL METABOLISM
- Skeletal system: Highly vascular; receives 10% of total cardiac output.
- Types of Bone:
- Cortical Bone (compact):
- Makes up 80% of total bone mass.
- Found in the diaphysis of long bones.
- Has osteons as its structural functional unit.
- Contains a Haversian system.
- Remodelling rate and metabolic activity are low.
- Low porosity.
- Trabecular Bone (spongy/cancellous):
- Makes up 20% of total bone mass.
- Found epiphyses and vertebrae.
- Has trabeculae as its structural functional unit.
- No Haversian system.
- Remodelling rate and metabolic activity are high.
- High porosity.
- Cortical Bone (compact):
- Key Features of Trabecular Bone:
- Osteoporosis is evaluated based on trabecular bone.
- Bone mineral density (BMD) and Trabecular Bone Score (TBS) are newer investigations used for evaluating trabecular bone.
Primary Hyperparathyroidism:
- Men 1 Associated:
- Occurs at a younger age (< 20 years).
- Equal prevalence in males and females.
- Sporadic:
- Occurs in individuals over 40 years of age, with a peak prevalence at 60 years.
- More common in females.
- Clinical Presentation:
- Both types: Hypercalcemia, recurrent stones, urinary tract infections.
- Men 1 Associated: Acute abdominal pain
- Overall most common symptom of hypercalcemia: Fatigue.
- Treatment: 3 1/2 near-total parathyroidectomy.
Pancreas: Enteropancreatic Neuroendocrine Tumors
- Most common cause of death in MEN 1.
- Most Common Types:
- Gastrinoma (most common)
- Insulinoma
- Glucagonoma
- VIPoma (20-40 years)
- Glucagonoma: Migratory necrolytic erythematous rash.
- VIPoma: Watery diarrhea, hypochlorhydria, acidosis (WDHA) syndrome. Normal anion gap metabolic acidosis (NAGMA).
Gastrinomas:
| Feature | MEN 1 Associated | Sporadic |
|---|---|---|
| Location | Duodenum | Passaro's triangle |
| Size | Small multifocal | Large |
| Risk of malignancy | 50-60% | |
| Spread | Endoscopic ultrasound, lymph nodes | Somatostatin Receptor scintigraphy (SRS) scan, bloodstream |
| Treatment | Streptozocin + octreotide, surgery for tumors >2cm | High-dose PPI |
Pituitary:
- Prolactinoma: Aggressive macroadenomas.
Organic Constituents of Bone: Collagen
- Matrix Composition:
- Organic (30-40%): Primarily type I collagen, non-collagenous proteins (osteopontin, osteocalcin, thrombospondin, matrix GLA protein, fibronectin)
- Inorganic (60-70%): Calcium, phosphorus, magnesium
- Cells (2%): Osteoblasts, osteoclasts, osteocytes
- Distribution of Collagen Types:
- Type I: Bone, connective tissue
- Type V: Cartilage
- Type II: Vitreous humor
- Type III: Vascular system, lungs
- Type IV: Basement membrane
- Type VII: Dermal-epidermal junction (DEJ)
- Type VIII: Endothelium
Disorders Associated with Collagen Types:
| Collagen Type | Associated Disorders |
|---|---|
| Type VII | Ehlers-Danlos syndrome (EDS) (Arthrochalasia type), Osteogenesis imperfecta, Osteoporosis, EDS classical type |
| Type IV | Chondrodysplasia, EDS type IV (vascular type), Alport syndrome, Goodpasture syndrome, Epidermolysis bullosa |
Polyglandular Autoimmune (PGA) Syndrome / Autoimmune Polyendocrine Syndrome (APS)
- APS Type 1:
- Childhood: Males = Females. Autosomal recessive inheritance. APECED gene (Autoimmune Poly Endocrinopathy with candidiasis & Ectodermal dystrophy) / AIRE gene.
- Adulthood: Females > Males. Polygenic inheritance. HLA DR3, HLA DR4 association.
- Clinical Manifestations:
- Childhood:
- Anti-21 hydroxylase antibody (Addison's disease)
- Anti-interferon antibody
- Thyroid: Graves' disease more common than Hashimoto's
- Hypoparathyroidism
- Addison's disease
- Minor Manifestations: Candidiasis, Type 1 DM, Hypogonadism
- Adulthood:
- Anti-21 hydroxylase antibody
- Thyroid: Hashimoto's more common than Graves' disease
- Addison's disease
- Associated with celiac disease
- Childhood:
- Clinical Manifestations:
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Description
This quiz focuses on Multiple Endocrine Neoplasia (MEN) Syndromes, particularly MEN 1. It covers the genetic basis, major manifestations, treatment options, and pre-operative management strategies. Test your knowledge about these critical aspects of MEN syndromes.
