Endocrine pathology Flashcards
1
Q
Prolactinoma
A
- Most common pituitary tumor (30% of pituitary tumors) - functional benign tumor
- Hyperprolactinemia
- Staining - chromophobic
- Wakly acidophilic cells
- Distrofic calcification (small psammoma bodies)
- Woman: amenorrhea and galactorrhea
- Men: decreased libido and headache
- Cause by hypothalamic lesions or by medications that interfere with dopamine (decrease in dopamine)
- Can be associated with estrogen therapy
2
Q
Somatotropic adenoma
A
- Hypersecretion of growth hormone
- Second most common pituitary tumor
- Acidophilic staining - acidophilic or chromophobic cells
- Causes secondary hyperproduction of somatomedins (IGF-1, insulin-like growth factor 1) by the liver
- Childre: gigantism
- Adults: acromegaly - overgrowth of heart, liver, jaws, face, hands and feet. Asymmetrical changes. “Sausage-like” fingers
3
Q
Corticotropic adenoma
A
- Hypersecretion of adrenocorticotropic hormone (ACTH)
- Hypercorticism
- Basophilic cells
- This condition is called Cushing syndrome or Cushing disease
4
Q
Cushing disease
A
- Hypercorticism due to a corticotropic adenoma of the pituitary
- Most often a basophilic adenoma
5
Q
Cushing syndrome
A
- Increased glucocorticoids, primarily cortisol
- Causes: Exogenous corticosteroid medication (most common), hyperproduction of ACTH, adrenal cortical adenoma or adrenal carcinoma
- Most often pituitary and less often adrenal origin
- May also be caused by ectopic ACTH production by various tumors (esp. small cell carcinoma of lung)
- Clinical: muscle weakness with thin extremities, moon facies, buffalo hump, truncal obesity, abdominal stria, HTN, osteoporosis
- Dexamethasone suppression - useful diagnostic measures
6
Q
Hypopituitarism
A
- Pituitary cachexia - destruction of pituitary:
- Caused by: Pituitary tumors, disease of hypothalamus, postpartum pituitary necrosis (Sheehan syndrome)
- > 75% of anterior pituitary is lost
- Adults: Pituitary adenoma
- Children: craniopharyngioma
7
Q
Syndrome of inappropriate ADH (SIADH)
A
- Most commonly caused by ectopic production of ADH by various tumors (esp. small cell lung carcinoma)
- Results in retention of water –> hyponatremia, reduced serum osmolality, cerebral edema, neurologic dysfunction, and inability to dilute the urine
8
Q
Nephrogenic diabetes insipidus
A
- Deficiency of ADH
- Characterized by polyuria, with consequent dehydration and insatiable thirst
- Causes: tumors, trauma, inflammatory processes, lipid starage disorders, and other conditions characterized by damage to the neurohypophysis or hypothalamus
9
Q
Craniopharyngioma
A
- Nonfunctioning pituitary tumor
- Benign chilhood tumor derived from remnants of the Rathke pouch
- Similar to ameloblastoma of the jaw
- Nests and cords of squamous or columnar cells in a loose stroma
- Often cystic
10
Q
Empty sella syndrome
A
- Pituitary hypofunction - pituitary gland is destroyed, sella turcica is enlarged
- Caused by conditions that destroy all or part of the pituitary: Hernia of sella diaphragm, removed mass (adenoma) or spontaneous necrosis of adenoma
11
Q
Nelson syndrome
A
- Pituitary hypofunction
- Development of large pituitary adenomas following bilateral adrenalectomy
- Due to loss of feedback inhibition on growth of preexisting pituitary microadenomas
12
Q
Thyroglossal duct cyst
A
- Most common thyroid anomaly
- Cystic dilation of thyroglossal duct remnant
- Presents as anterior neck mass
13
Q
Ectopic thyroid tissue
A
- May be found anywhere along the course of the thyroglossal duct
- Lingual thyroid: Thyroid tissue at base of tongue
14
Q
Myxedema
A
- Hypothyroidism in adults
- Causes: Therapy for hyperthyroidism with surgery, irradiation, or drugs; Hashimoto thyroiditis; idiopathic; iodine deficiency
- Clinical: Insidious onset, cold intolerance, weight gain despite normal appetite, mental and physical slowness, menorrhagia, constipation, puffiness of face, eyelids and hands, dry skin, hair loss
15
Q
Cretinism
A
- Hypothyroidism in infancy or early childhood
- Causes: Iodine deficiency, deficiency of enzymes, maternal hypothyroidism, thyroid agenesis
- Clinical: Severe mental retardation, short stature with skeletal abnormalities, large tongue, umbilical hernia, coarse facial features
16
Q
Graves disease
A
- Most common cause of hyperthyroidism
- Occurs more frequently in women than in men
- Increased incidence in HLA-DR3 and HLA-B8 positive individuals
- Cause: Autoantibody; TSI (thyroid-stimulation Ig) - (IgG) reacts with TSH receptors and stimulates TH production. TGSI (thyroid growth-stimulation Ig)
- Clinical: hyperthyroidism, diffuse goiter (enlarged thyroid), exophthalmos/ophthalmopathy (protrusion of the eyes), and pretibial myxedema
- Risk for other autoimmune diseases: lupus erythematous, pernicious anemia, type 1 DM, Addison disease
17
Q
Plummer disease
A
- Combination of hyperthyroidism, nodular goiter, and absence of exophthalmos
18
Q
Hashimoto thyroiditis
A
- Autoimmune disorder
- 90-95% in women
- Most common cause of hypothyroidism (may initially present with hyperthyroidism) in iodine-sufficient areas. Most common cause of non endemic goiter in children
- Massive infiltrates of lymphocytes with germinal center formation
- Associated with various autoantibodies; antithyroglobulin, antithyroid peroxidase, anti-TSH receptor, and anti-iodine receptor antibodies
- May coexist with MALT lymphomas of GI tract, other B cell lymphomas
- Increased incidence in HLA-DR5 and HLA-B5 positive individuals
19
Q
Subacute (de Quervain, granulomatous) thyroiditis
A
- Focal destruction of thyroid tissue and granulomatous inflammation
- Most common cause of thyroid pain
- Causes: viral infections such as measles, mumps, adenovirus, upper respiratory infection, influenza, or coxsackievirus
- Damage by lymphocytes T
- Self-limited course of several weeks’ duration consisting of flu-like illness along with pain and tenderness of the thyroid, may present with hyperthyroidism
20
Q
Riedel thyroiditis
A
- Chronic inflammation - thyroid replacement by fibrous tissue
- Unknown etiology
- Presents as hypothyroidism with “hard as wood”, contender thyroid gland
21
Q
Thyroid benign tumors
A
- Most often solitary
- Present clinically as nodules, cold nodule
- Most often nonfunctional, can cause hyperthyroidism
- Folicullar adenoma - proliferation of follicles surrounded by a fibrous capsule, nonfunctional, not forerunner to carcinoma
- Hürthle cell
22
Q
Papillary carcinoma (Thyroid)
A
- Most common thyroid cancer (85%)
- Papillary projections into gland-like spaces; tumor cells have characteristic “ground-glass” (“Orphan Annie”) nuclei
- Risk factors: ionizing radiation, post-Chernobyl, Hashimoto’s thyriditis, FAP
- Better prognosis than other forms of thyroid cancer; even though it often spreads to cervical nodes - 20 year survival is 90%
- Can be associated with changes in chromosome 10, or translocation between chromosome 10 and 17
- Mutations in B-type ras kinase (BRAF) are also common
23
Q
Follicular carcinoma (Thyroid)
A
- 15% of thyroid carcinomas
- Malignant proliferation of follicles
- Surrounded by a fibrous capsule with invasion through capsule (‘invasion’ differentiate carcinoma from adenoma)
- Usually solitary and “cold” on radionuclide scan
- Risk factors: radiation exposure, iodine deficiency, older age
- Metastasis –> generally occurs hematogenously (via veins), to lungs, liver, bone, brain
24
Q
Medullary carcinoma (Thyroid)
A
- 5% of thyroid carcinomas
- Malignant proliferation of parafollicular C cells of neural crest
- Produces calcitonin, a calcium-lowering hormone –> may produce hypocalcemia
- Sheets of tumor cells in an amyloid-containing stroma
- Most are sporadic (80%)
- Familial; Can be associated with MEN syndrome IIa and IIb in 20% of cases
- Associated with RET mutations
- 5 year survival: 86%
25
Q
Anaplastic carcinoma (Thyroid)
A
- Undifferentiated malignant tumor of thyroid
- Usually seen in elderly
- 50% have prior multinodular goiter
- Arises as transformation of cancer
- Often invades local structures leading to dysphagia or respiratory compromise
- Poor prognosis
26
Q
Primary hyperparathyroidism
A
- Most often due to parathyroid adenoma (>80% of cases)
- Other causes: parathyroid hyperplasia, production of PTH-like hormone by nonparathyroid malignant tumors
- Can occur as a part of MEN I and MEN IIa
- Lab: Hypercalcemia and hypercalciuria, decreased serum phosphorus, increased serum alkaline phosphatase, increased serum PTH
- Clinical/consequences: Osteitis fibrosa cystica, nephrocalcinosis, renal calculi, peptic duodenal ulcer, CNS disturbances, constipation, actue pancreatitis
27
Q
Secondary hyperparathyroidism
A
- Parathyroid hyperplasia occurs in response to decreased concentration of serum ionized calcium
- Most common cause is chronic renal failure –> decreased intestinal absorption of calcium, and increased serum phosphorus causes reciprocal decrease in serum calcium
- Decreased serum calcium, increased serum phosphorus, increased serum alkaline phosphatase, and increased PTH.
28
Q
Hypoparathyroidism
A
- Most common caused by accidental surgical excision during thyroidectomy
- May also be associated with DiGeorge syndrome
- Present with numbness and tingling, muscle spasm (tetany), decreased PTH and decreased serum calcium
29
Q
Pseudohypoparathyroidism
A
- Multihormone resistance involving PTH, TSH, luteinizing hormone, and FSH.
- End-organ unresponsiveness of the kidney to PTH
- Shortened forth and fifth metacarpals and metatarsals, short stature, and other skeletal abnormalities
30
Q
Hyperaldosteronism
A
- Excess aldosterone
- Clinical: hypernatremia, hypokalemia, metabolic alkalosis, HTN
- Primary: Most commonly (80%) due to adrenal adenoma. High aldosterone and low renin
- Secondary: Renal ischemia, renal tumors, or edema –> activation of renin-angiotensin system. High aldosterone and high renin
31
Q
Adrenal virilism
A
- Excess sex-steroids with hyperplasia of both adrenal glands
- Causes:
- Congenital enzyme defects lead to diminished cortisol production and compensatory increased ACTH
1) 21-hydroxylase deficiency is most common (90%)
2) 11- hydroxylase deficiency - Tumors and the adrenal cortex
1) Adrenocortical adenomas
2) Adrenocortical carcinomas - Clinical: salt wasting with hyponatremia, hyperkalemia, hypovolemia
32
Q
Addison disease
A
- Hypocorticism (chronic adrenocortical indufficiency)
- Most commonly due to idiopathic adrenal atrophy
- Can also be caused by tuberculosis, metastatic tumor, and various infections
- More than 90% of cortex destructed
- Clinical: Hypotension, increased pigmentation of skin; hyponatremia; decreased chloride, glucose, and bicarbonate; hyperkalemia; weakness, nausea, vomiting, diarrhea
33
Q
Waterhouse-Friderichsen syndrome
A
- Acute adrenal insufficiency and vascular collapse - hypotension leading to shock
- Due to hemorrhagic necrosis of the adrenal cortex
- Often associated with disseminated intravascular coagulation
- Characteristically due to meningococcemia, often in association with meningococcal meningitis
34
Q
Pheochromocytoma
A
- Tumor derived from chromaffin cells of the adrenal medulla - chromaffin cells clustered in small nests (“Zellballen”)
- Most often benign
- Clinical: episodic HTN (result from hyper production of catecholamines), headaches, palpitations, tachycardia, and sweating
- Increased urinary excretion of catecholamines and their metabolites - metanephrine, normetanephrine, and vanillylmandelic acid
- Associated with MEN IIa and IIb, von Hippel-Lindau disease, and neurofibromatosis type I
- Rules of 10s –> 10% bilateral, 10% familial, 10% malignant, 10% located outside of adrenal medulla (bladder wall), 10% without HTN, 10% in children
35
Q
Neuroblastoma (Adrenal)
A
- Highly malignant catecholamine-producing tumor (Pheochromocytoma in children)
- Occur in early childhood - most common solid tumor in children before age 1
- Comprised of small round blue cells which form characteristic rosette-like structures
- Urinary catecholamines and their metabolites are same as in pheochromocytoma
- Rarely causes HTN
- Often presents as a large abdominal mass
- Characterized by amplification of the N-myc oncogene
36
Q
Type 1 Diabetes mellitus
A
- Often begins early in life
- Less common than type 2 DM
- Due to failure of insulin synthesis by beta cells of the pancreatic islets
- May be a genetic predisposition complicated by autoimmune inflammation of islets triggered by a viral infection or environmental factors
- Incidence increased in individuals with point mutation in the HLA-DQ gene; and in HLA-DR3 and HLA-DR4 positive individuals
- Hyperglycemia, leading to polyuria, polydipsia, wight loss despite increased appetite, ketoacidosis, coma, and death
37
Q
Type 2 Diabetes mellitus
A
- Much more common than type 1 DM
- Begins most often in middle-age
- Positive family history is more frequent than in type 1 DM
- Due to increased insulin resistance
- May also be associated with impaired processing of proinsulin to insulin, decreased sensing of glucose by beta cells, or impaired function of intracellular carrier proteins
- Most often associated with mild to moderate obesity
- Ketoacidosis is unusual
38
Q
Maturity-onset diabetes mellitus of the young (MODY)
A
- Autosomal dominant syndrome
- Characterized by mild hyperglycemia and hyposecretion of insulin but no loss of beta cells
- Earlier onset than type 2 DM
- Caused by a diverse group of single gene defects
39
Q
Hereditary hemochromatosis
A
- Secondary DM
- Characteristics include excess iron absorption and parenchymal deposition of hemosiderin, with reactive fibrosis in various organs (esp. pancreas, liver, and heart)
40
Q
Pancreatitis
A
- Characterized by hyperglycemia
- Chronic pancreatitis may result in islet cell destruction and secondary DM
41
Q
Insulinoma
A
- Most common islet cell tumor
- Can be benign or malignant
- Characterized by greatly increased secretion of insulin
- Increase in circulating C-peptide
- Whipple triad: Episodic hyperinsulinemia and hypoglycemia, CNS dysfunction, and dramatic reversal of CNS abnormalities by glucose administration
42
Q
Gastrinoma
A
- Often malignant and sometimes occur in extrapancreatic sites
- Gastrin hypersecretion and hypergastrinemia
- Associated with the Zollinger-Ellison syndrome
43
Q
Glucagonoma
A
- Rare tumor
- Endocrine tumor that results in secondary DM
- Causes a characteristic skin lesion called necrolytic migratory erythema
44
Q
VIPoma
A
- Rare tumor
- Endocrine tumor marked by secretion of vasoactive intestinal peptide (VIP)
- Associated with WDHA syndrome: Watery Diarrhea, Hypokalemia, and Achlorhydria
45
Q
MEN I (Wermer syndrome)
A
- Hyperplasias or tumors of (3Ps):
- Pituitary gland - (prolactinoma)
- Parathyroid - (hyperparathyroidism)
- Pancreatic islets - (gastrinoma, insulinoma)
- May also cause hyperplasias or tumors of the thyroid or adrenal cortex
- Mutations in MEN I gene
- Clinical: Hypoglycemia, peptic ulcers, nephrolithiasis, prolactism
46
Q
MEN IIa (Sipple syndrome)
A
- Include:
- Pheochromocytoma
- Medullary carcinoma of the thyroid
- Hyperparathyroidism
- Mutations in the RET oncogene
47
Q
MEN IIb (MEN III)
A
- Includes:
- Pheochromocytoma
- Medullary carcinoma of thyroid
- Multiple mucocutaneous neuromas or ganglioneuromas
- Linked to different mutations in the RET oncogene compared with MEN IIa
