Endocrine 2 Flashcards
(113 cards)
1
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Normal Endocrine Pancreas
2
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Normal Endocrine Pancreas
Antibody staining for glucagon in alpha-cells
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Normal Endocrine Pancreas
Antibody staining for insulin in beta-cells
4
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Diabetes Mellitus Type 1
Autoimmune destruction of islets.
Inflammation and infiltration by T lymphocytes (dark cells) = insulinitis
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Diabetes Mellitus Type 1
Deposits of extracellular amyloid composed of amylin, which is co-secreted with insulin
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Diabetes Mellitus Type 1
Congo red stain of amyloid
7
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Diabetes Mellitus Type 1
Amyloid deposits
8
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Diabetes Complications (Picture 1)
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9
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Diabetes Complications (Picture 2)
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10
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Pancreatic Endocrine Neoplasm
(Islet Cell Tumor)
Circumscribed/encapuslated.
In pancreas or region around pancreas.
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Pancreatic Endocrine Neoplasm
(Islet Cell Tumor - on the left)
Circumscribed/encapuslated.
In pancreas or region around pancreas.
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Pancreatic Endocrine Neoplasm
(Islet Cell Tumor - arranged in groups)
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Pancreatic Endocrine Neoplasm
(Islet Cell Tumor - cells are well-differentiated)
14
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Insulinoma
15
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-omas
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16
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Necrolytic Migratory Erythema
(Glucagonoma)
17
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Gastrinoma Triangle
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18
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Normal Parathyroid Gland
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Acini of cheif cells; granular cells = oxyphil cells
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Parathyroid Hyperplasia
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PT Hyperplasia
22
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Manifestations of Parathyroid Adenoma
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23
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Parathyroid Hyperplasia
Sestamibi Scan
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Parathyroid Adenoma
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Parathyroid Adenoma
Solid sheets of cells.
Adenomas have compressed non-neoplastic tissue at edges.
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Parathyroid Adenoma
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Parathyroid Adenoma
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Parathyroid Adenoma
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Parathyroid Carcinoma
Very uncommon.
Tend to have higher Ca++ levels because they're larger.
Invasive to soft tissues of the neck.
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Parathyroid Carcinoma.
Bands of fibrous tissue.
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Normal Adrenal Gland
Cortex is yellowish.
Medulla is reddish-brown.
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Adrenal Gland
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Cortex
Zona Glomerulosa
Zona Fasciculata
Zona Reticularis
Medulla
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Cortex
Zona Glomerulosa
Zona Fasciculata
Zona Reticularis
Medulla
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Left: Zona Fasciculata
Right: Zona Reticularis
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Waterhouse-Friderichsen Syndrome purpura
Acute adrenal insufficiency due to DIC/hemorrhage caused by Neiserria meningititides infection.
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Waterhouse-Friderichsen Syndrome
Hemorrhagic necrosis of adrenal glands.
Acute adrenal insufficiency due to DIC/hemorrhage caused by Neiserria meningititides infection.
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Waterhouse-Friderichsen Syndrome
Hemorrhage in adrenal glands.
Acute adrenal insufficiency due to DIC/hemorrhage caused by Neiserria meningititides infection.
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Waterhouse-Friderichsen Syndrome
Acute adrenal insufficiency due to DIC/hemorrhage caused by Neiserria meningititides infection.
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Waterhouse-Friderichsen Syndrome
Hemorrhagic necrosis of adrenal glands.
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Adrenal Tuberculosis
Caseous Necrosis
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Adrenal Tuberculosis
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Adrenal Tuberculosis
Histiocytes or macrophages
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Adrenal Tuberculosis
Activated T cells
Langhans nucleated cells
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Adrenal Tuberculosis
Acid Fast Bacilli
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Adrenal Cortical Adenoma
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Adrenal Cortical Adenoma
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Adrenal Cortical Adenoma
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Adrenal Cortical Adenoma
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Adrenal Cortical Adeonoma
Left: tumor
Right: Residual normal adrenal tissue
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Adrenal Cortical Adenoma
Right: tumor, often with much lipid
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Adrenal Cortical Adenoma
Uniform, arranged in nests.
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Adrenal Cortical Carcinoma
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Adrenal Cortical Carcinoma
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Adrenal Cortical Carcinoma
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Adrenal Cortical Carcinoma
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Adrenal Cortical Carcinoma
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Adrenal Cortical Carcinoma
More mitotically active.
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Adrenal Cortical Carcinoma
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Adrenal Cortical Carcinoma
Vascular invasion, metastasis = malignancy
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Pheochromocytoma
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Pheochromocytoma
Adrenal medulla turns dark brown in a solution of chromium salts (oxidizes cathecholamines)
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Pheochromocytoma
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Pheochromocytoma
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Pheochromocytoma
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Pheochromocytoma
Secretory granules with catecholamines
Present with HTN intermittently
Can measure urinary metanephrines/VMA
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Neuroblastoma
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Neuroblastoma
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Neuroblastoma
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Neuroblastoma
Tumor cells form rosettes around a central anucleated zone.
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Neuroblastoma
Left: area of necrosis
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Multiple Endocrine Neoplasia
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Multiple Endocrine Neoplasia 2B
Mucosal neuromas
Have C cell hyperplasia nodules
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Multiple Endocrine Neoplasia 2B
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Islets of Langerhans
Clusters of uniform cells scattred within exorine pancreas
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4 major and 2 minor cells types of endocrine pancreas and their hormones
1. Beta cell: insulin
2. Alpha cell: glucagon
3. delta cell: somatostain
4. PP cell: pancreatic polypeptide
5. D1 cell: vasoactive intestinal polypeptide
6. Enterochromafiin cell: serotonin
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Gross findings of DM pancreas
Pancreas may be small, atropic
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Microscopic findings in DM pancreas (Types 1, 2)
Type 1: reduction in number and size of islets;
leukocytic infiltration of islets ("insulinitis")
Type 2: hyalinization/fibrosis of islets;
amyloid deposition (compose of amylin - cosecreted with insulin)
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Comparison of Type 1 and Type 2 Diabetes Mellitus
80
Pancreatic Endocrine Neoplasm:
Epidemiology
Area of pancreas that is affected
Functional?
Histology
Epi: much less common than tumor of exocrine pancreas; adults primarily affected; single or multiple; benign or malignant
Area: Usually body or tail of pancreas
Functional: 60% secrete one or several peptide hormones
Histo: uniform cells with round/oval nuclei, fine chromatin, and pale granular cytoplasm
81
Presentation of Insulinoma
Most common functioning islet cell tumor.
Presents with episodic hypoglycemic attacks, low blood glucose, symptoms precipitated by fasting or exercise, symptoms relieved by glucose.
High plasma insulin levels, increased insulin:glucose.
90% are solitary tumors, may be small and require special imaging.
Only 10% are malignant.
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Presentation of Glucagonoma
Mainly adult females (perimenopausal or postmenopausal).
Associated with glucagonoma synrome: mild glucose intolerance, anemia, skin rash "necrolytic migratory erythema", weight loss, glossitis/stomatitis
High plasma glucagon levels
Overall 60-70% malignant
Usually malignant if associated with glucagonoma syndrome, otherwise benign
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Zollinger-Ellison syndrome
Gastrinoma, acid hypersecretion, peptic ulcers
Associated with gastrinoma
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Presentation of Gastrinoma
75% located in pancreas, peripancreatic region, 23% in duodenum, and rare in stomach
70-90% are malignant
Usually solitary and malignant if not associated with other endocrine abnormalities
Usually multiple and benign in a component of MEN
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Normal Parathyroid Gland
Four glands (variable)
Mixture of chief cells (pale cytoplasm) and oxyphil cells (eosinophilic cytoplasm)
Variable amounts of adipose tissue (increases with age)
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Presentation of Parathyroid Adenoma
Women \> men, 3:1
Usually too small to be palpated
Presentation related to hypercalcemia due to PTH secretion (80% asymptomatic)
Encapsulated, cellular neoplasm
Usually chief cells predominate, other cell types may be present
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Etiology of Hyperparathyroidism
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Layers of Adrenal Gland
Outer yellow cortex and red brown medulla (10:1)
Zona glomerulosa (10-15%): mineralocorticoids
Zona Fasciculata (60-70%): glucocorticoids
Zona Reticularis (20-30%): androgens
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Etiology of Hypoadrenalism
Adrenocortical Insufficiency
Primary: chronic (Addison's) or acute (Waterhouse-Friderichsen)
Secondary: Pituitary insufficiency or exogenous corticosteroids
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Etiology of Hypercortisolism
Cushing's Syndrome
Pituitary (Cushing's Disease): 60-70%
Adrenal: 20-25%
Ectopic: 10-15%
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Presentation of Cushing's Syndrome
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Presentation of Conn's Syndrome
Primary hyperaldosteronism due to adrenal cortical adenoma.
HTN, neuromuscular symptoms (weakness, paresthesias), potassium wasting, increased aldosterone with typically decreased renin levels.
Almost invariabley caused by an adrenocortical adenoma.
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What is Waterhouse-Friderichsen Syndrome?
Hemorrhagic destruction of adrenals related to severe bacterial infection: Meningococcus, pneumococci, Staphylococci, Pseudomonas, Haemophilus
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Presentation of Waterhouse: Friderichsen Syndrome
Rapidly progressive hypotension leading to shock
DIC with purpura
Pathology: Bilateral adrenal hemorrhage and necrosis
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Presentation of Adrenal Tuberculosis
Infection of adrenal glands by Mycobacterium tuberculosis
Formely the most comon cause of chronic adrenal insufficiency
Granulomatous inflammation: epitheliod histiocytes, giant cells, and acid-fast bacilli
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Adrenal Cortical Adenoma gross and microscopic findings
Gross: Bright yellow or yellow-brown tumors, usually \<5cm and \<40-60gm
Microscopic: Usually composed of clear-pale cells resembling adrenal cortical cells, may have pleomorphism of cells, mitotic activity is usually low
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Diagnosis of Adrenal Cortical Carcinoma
May have hemorrhage and necrosis
May appear encapsulated or circumscribed
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Adrenal Cortical Adenoma
Microscopic findings
Features of malignancy
Median survival
Microscopy: May be frankly anaplatic or resemble tumor cells of adrenal cortical adenoma
Malignancy: vascular invasion or metastasis
Survival: ~2 years
99
Pheochromoctyoma Rule of 10
10% extra-adrenal (paraganglioma)
10% multiple (sporadic cases)
10% malignant
10% occur in children
10% familial (MEN2A/2B, NF-1, VHL)
100
Pheochromocytoma Clinical Presentation
Severe or episodic HTN, palpitations, tachycardia, anxiety, and excessive sweating
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Pheochromocytoma Diagnosis
Elevated urine metanephrines and vanillylmandelic acid (VMA), which are metabolites of cathecholamines
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Pheochromocytoma Gross and Microscopic findings
Indicator of malignancy
Gross: well demarcated, very vascular, pale grey to light brown tumors; tumor turns dark brown in chromium salt solution (Zenker's solution); "pheochrome" refers to affinity for chromium salts
Microscopy: Large cells with basophilic granular cytoplasm, arranged in small nests separated by capillaries; may have nuclear pleomorphism and mitotic activty
Malignancy: metastatis
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Neuroblastoma Epi
7-10% of all childhood malignancies
2nd most common childhood solid malignancy
80% occur in children \< 5yo
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Neuroblastoma Gross and Microscopic Findings
Gross: Large tumors (6-8cm avg.), sof, white, with areas of hemorrhage, necrosis, or calcification
Microscopic: Small blue cell tumor arranged in diffuse sheets (may see Homer Wright rosettes)
90% produce catecholamines (urinary metanephrines/VMA elevated)
105
MEN-1: Wermer's Syndrome
Mutation in MEN-1 gene (11q13)
Parathyroid hyperplasia/adenoma
Pituitary adenoma
Pancreatic (or duodenal) islet cell tumor (symptomatic tumors are commonly gastrinoma or insulinoma)
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MEN-2A: Sipple's Syndrome
Mutation in RET oncogene (10q11)
Medullary carcinoma of thyroid
Pheochromocytoma of adrenal medulla
Parathyroid hyperplasia
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MEN-2B: Gorlin's Syndrome
Mutation in RET oncogene
Medullary carcinoma of thyroid
Pheochromocytoma of adrenal gland
Mucosal neuromas (oral cavity, GI tract, etc.)
Marfanoid appearance
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Multiple Endocrine Neoplasia (MEN) Syndromes
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MEN-1 vs. MEN-2
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RET Protooncogene mutations in MEN type 2
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How can you differentiate between hypoglycemia caused by beta-cell tumors and self-induction by insulin/sulfonylureas?
Beta-cell tumors are accompanied by high serum levels of C peptide.
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What is the Whipple triad?
1. Sx of hypoglycemia are present (esp. confusion, stupor, loss of consciousness)
2. Hypoglycemia is present, typically glucose less than 50 mg/dL
3. Attacks are precipitated by fasting or exercise and are promptly relieved by administration of glucose
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What are the common causes of hypoadrenalism?
Autoimmune adrenalitis
Granulomatous infections of the adrenal gland
Anterior Pituitary failure
