Endocrine Disease Flashcards
1
Q
Identify this concept
- Secretion of a stimulating hormone inhibited by increased activity of target organ/tissue
- Examples
- Decreased secretion of pituitary hormones with increased levels of target hormone
- Decreased secretion of parathyroid hormone (PTH) with increased calcium levels
- The opposite is also true-decreased activity of target organ causes increased secretion of stimulating hormone.
A
Feedback Inhibition
2
Q
What is the morphology of neuroendocrine tumors?
A
- “Salt and Pepper” nuclear chromatin
- Immunohistochemical markers
- Neuron-specific enolase (NSE)
- Chromogranin
-
Synaptophysin
- if we find these markers we know there is a neuroendocrine tumor
- CD56
- Ultrastructure
- Neurosecretory granules
3
Q
What kind of neuroendocrine tumors are these an example of: Benign, Low grade malignant or High grade malignant?
- Paraganglioma, pheochromocytoma, some islet
cell tumors
A
Benign
4
Q
What kind of neuroendocrine tumors are these an example of: Benign, Low grade malignant or High grade malignant?
• Carcinoid tumor
A
Low grade malignant
5
Q
What kind of neuroendocrine tumors are these an example of: Benign, Low grade malignant or High grade malignant?
- Large cell neuroendocrine carcinoma
- Small cell carcinoma
A
High grade malignant
6
Q
What type of endocrine gland malfunction is this?
- Diffuse or nodular; usually involves entire gland(s)
- localized overgrowth
- multinodular–more than one node!
- May be primary or secondary (driven by stimulating hormone)
A
Endocrine Hyperplasia
7
Q
What type of endocrine gland malfunction is this?
• Usually solitary; often nonfunctional
A
Endocrine Adenoma
8
Q
What type of endocrine gland malfunction is this?
- Less common than corresponding adenoma
- Often well differentiated
- Demonstration of tumor invasion or metastasis required for diagnosis
A
Carcinoma
9
Q
What are some hormones produced by anterior pituitary?
A
- Thyroid Stimulating Hormone (TSH)
- Adrenocorticotrophic Hormone (ACTH)
- Melanocyte Stimulating Hormone (MSH)
- Follicle Stimulating Hormone (FSH)
- Luteinizing Hormone (LH)
- Prolactin, Growth Hormone
- these two have direct physical effects
10
Q
Identify:
- The most common cause of pituitary hyperfunction; usually in anterior lobe
- 25% are nonfunctional
- Most functional ones produce one hormone
- Peak age-middle age adults (30-60)
- Mass effects
- Imaging-expansion of sella
- Visual disturbances (pressure on optic chiasm)
- Increased intracranial pressure (headache, nausea)
- Hormonal effects
A
Pituitary Adenoma
11
Q
What is this type of functioning pituitary adenoma?
- MOST COMMON
- Symptoms: Galactorrhea, amenorrhea, infertility
- Symptoms most prominent in childbearing age women
A
Prolactinoma
Excess prolactin
12
Q
What is this type of functioning pituitary adenoma?
- SECOND most common
- Growth disturbances (gigantism, acromegaly)
- Diabetes-like metabolic effects
A
Growth Hormone (somatotroph) adenoma
13
Q
What is this symptom of excess growth hormone?
- Growth hormone excess onset before closure of epiphyses
- General increase in body size with increased limb length
A
Gigantism
14
Q
What is this symptom of excess growth hormone?
- Growth hormone excess onset or continuance after closure of epiphysis
- Coarsening of facial features and hands
- Soft tissue/visceral effects
A
Acromegaly
15
Q
Identify this functioning pituitary adeonma:
- Cushing’s Disease
- Hyperpigmentation (concomitant increase of MSH)
A
Corticotroph Adenoma
16
Q
What are hormones produced by posterior pituitary?
A
- Antidiuretic hormone (ADH)
- Promotes retention of water by renal tubules
- Oxytocin (vasopressin)
- Uterine and breast smooth muscle stimulation
17
Q
What are the causes of diabetes insipidus?
A
- Decreased or absent ADH secretion
- Increase in urine output because lack of ADH
- Other causes of hypopituitarism
- Idiopathic
- May be caused by renal tubular dysfunction (nephrogenic DI)
- Clinical
- Polyuria, polydipsia
- Dilute urine (low specific gravity)
- Life-threatening dehydration if water not replaced
18
Q
Identify:
- Increased ADH usually due to ectopic production by malignant tumor
- Most common is small cell carcinoma of lung
- Kidneys retain too much water
- Hyponatremia
- Cerebral edema
A
Syndrome of Inappropriate ADH Secretion (SIADH)
19
Q
What are these indications of?
- Deficiency of all anterior pituitary hormones
- These are the potential causes this:
- Neoplasms (mass effect; usually nonfunctioning adenoma)
- Ischemic necrosis
- Postpartum (Sheehan’s syndrome)
- Iatrogenic (surgery, radiation)
- Clinical effects
- Most important ones due to TSH and ACTH deficiency
A
Panhypopituitarism
20
Q
What are the hormones produced by the adrenal CORTEX?
A
Hormones
- Glucocorticoids
- Mineralocorticoids
- Sex steroids
21
Q
What is produced by the adrenal medulla?
A
Catecholamines
22
Q
What type of adrneal hormone is this:
- Metabolic effects
- Catabolic hormone, principally carbohydrates
- break down of carbs and proteins!
- Other effects
-
Anti-inflammatory/immunosuppressive
- use this for drug therapy!
- Inhibit bone formation and calcium absorption
-
Anti-inflammatory/immunosuppressive
A
Glucocorticoids
- Cortisol
23
Q
What type of adrneal hormone is this:
Effects: sodium (and water) retention, potassium excretion
A
Mineralocorticoids
- Aldosterone
24
Q
What type of adrneal hormone is this:
• Major source of androgens in females and in males with nonfunctional testes
A
Sex steroids
- Androgens
25
What type of adrneal hormone is this:
Modulates “fight or flight” response, including increase in blood pressure
Catecholamines
* Epinephrine, norepinephrine
26
Identify illness:
* Excess in glucocorticoids
* when ACTH is specifically causing hyperplasia
* Causes
* **Iatrogenic (steroid therapy)-MOST COMMON**
* Primary adrenal disease
* Hyperplasia or functioning adenoma
* Hypersecretion of ACTH
* Pituitary adenoma (\_\_\_\_\_\_\_)
* Ectopic ACTH secretion (usually lung cancer)
Cushing's Syndrome
Clinical:
* Impaired glucose tolerance/diabetes
* Weight gain/hypertension
* Axial redistribution of fat
* Moon facies
* “Buffalo hump”
* Truncal obesity
* Bone resorption
* brittle bones
* Skin fragility (striae)
* Susceptibility to infection
* Virilization (hirsutism, menstrual abnormalities)
* Mental disturbances
* Skin pigmentation (ACTH hypersecretion causes only)
27
Identify:
* Excess in mineralocorticoids
* Excess sodium/hypertension
* Hypokalemia
* Causes
* Primary adrenal
* Aldosterone-secreting adenoma (Conn’s syndrome)
* Adrenal hyperplasia
* Secondary (activation of renin-angiotensin system)
Hyperaldosteronism
28
Identify:
* Excessive secretion of adrenal androgens
* Effects
* Virilization (hirsutism, menstrual abnormalities,etc., **primarily in females)**
* Causes
* ACTH hypersecretion--\> pituitary gland
* Adrenal cortical adenoma/carcinoma
* Congenital adrenal hyperplasia
* Primarily **21-hydroxylase deficiency**
Adrenogenital Syndromes
* When we have a block in 21-hydroxylase we have a decrease in minealcorticoids and glucocorticoids, BUT sex steroids are still good
29
Identify adrenal problem:
* Usually solitary--not multiple nodes
* Size usually 1.5-6 cm
* Usually nonfunctional
* Well-circumscribed; may not have capsule
* can be benign or malignant
Adrenal Cortical Adenoma
30
* Malignant, very large, locally invasive
* Uncommon (incidence 1 per 1 million)
* Metastasis in 70-90%
* Liver, lung, retroperitoneum, regional nodes
* Criteria for malignancy
* Vascular invasion or local spread
* Size/weight
* Marked pleomorphism
* Tumor necrosis
* Weight loss
Adrenal Cortical Carcinoma
31
Identify this adrenal disease:
* Progressive destruction of adrenal cortex
* Causes
* Autoimmune
* Most common
* May be isolated or associated with other autoimmune disease
* Infections
* Mycobacterial/fungal
* May be associated with HIV, immunodeficiency states
* Metastatic malignancy
Chronic Primary Adrenal Insufficiency (Addison’s Disease)
Clinical Features of Addisons:
* Fatigue, weakness
* Gastrointestinal symptoms
* Nausea, vomiting, weight loss, diarrhea
* Hyponatremia, hyperkalemia, volume depletion
* Hyperpigmentation
* decrease in glucocorticoids = increase in ACTH
* because of the feedback inhibition loop
* so result is hyperpigmentation
32
Identify this adrenal problem:
* **Clinical EMERGENCY**
* Intractable vomiting, abdominal pain
* Hypotension, vascular collapse, coma
* Causes
* **Sudden withdrawal** of long-term steroid therapy
* you need to take people off steroids gradually
* Adrenal hemorrhage
* Coagulopathy
* Sepsis (Waterhouse-Friedrichsen syndrome)
* Acute stress in chronic adrenal insufficiency (Addisonian crisis)
Acute Adrenocortical Insufficiency
33
* Neoplastic hypersecretion
* Neuroendocrine tumor, nodular
* Arises from **chromaffin cells** of adrenal medulla
* Usually secrete **catecholamines**; **hypertension** is usual symptom
* “The 10 percent tumor”
* 10 percent bilateral
* 10 percent malignant
* 10 percent extra-adrenal
* 10 percent in children
Pheochromocytoma
34
Identify this hormone:
* Polypeptide hormone; 84 amino acids
* Effects: **Increase** serum calcium, **decrease** serum phosphate
* Increase in osteoclast activity
* Promotes renal tubule retention of calcium and GI absorption of calcium
* Promotes renal phosphate excretion
* Promotes renal activation of vitamin D
* Secretion of this is stimulated by **low** ionized calcium and inhibited by increased ionized calcium
Parathyroid Hormone (PTH)
35
Identify:
* Increase in PTH
* Primary-- actual problem in the parathyroid gland
* Parathyroid hyperplasia or neoplasia
* Hypercalcemia, hypophosphatemia
* Clinical effects:
* Skeletal abnormalities (“painful bones”)
* “Renal stones”
* Gastrointestinal problems (“abdominal groans”)
* Depression, lethargy (“psychic moans”)
* Neuromuscular (weakness, hypotonia)
* Secondary
* Increased PTH due to hypocalcemia; most common cause is chronic renal failure
Hyperparathyroidism
36
What is this **second** most common cause of primary hyperparathyroidism?
* 15-20% of primary hyperparathyroidism cases
* Usually all four glands **similarly enlarged-symetrical**
* Occasionally asymmetrical (pseudoadenomatous) gland enlargement
* Functional parathyroid
Parathyroid Hyperplasia/neoplasia
37
What is this **most common cause** of hyperparathyroidism?
* About 80% of cases of primary hyperparathyroidism
* One gland enlarged, the other three normal to atrophic
* Limited to one gland
* Surgeon can just remove the one gland and the pt is cured
* functional parathyroid
Parathyroid Adenoma
38
What is this **least common cause** of hyperparathyrodism?
* Rare (less than 5% of cases of primary hyperparathyroidism)
* PTH levels may be **massively elevated**
* ****over 10,000
* Diagnostic criteria:
* Invasion of adjacent tissue
* Difficult surgical dissection
* because it is invading surrounding tissues
* Fibrosis
* Mitotic activity
* Functional parathyroid
Parathyroid Carcinoma
39
What are some causes decreased PTH?
* Feedback inhibition by non-PTH causes of hypercalcemia
* Most common is malignancy-associated hypercalcemia
* Hypoparathyroidism
* Hypocalcemia and hyperphosphatemia due to decreased PTH
* Cause: **usually surgical removal of parathyroid glands**-iatrogenic
* Treatment of parathyroid hyperplasia
* Complication of thyroidectomy
* Effects
* Muscle hypertonia (spasms, tetany, tingling)
* Cardiac arrythmias
40
What are the thyroid gland hormones?
* Thyroid Hormones
* Thyroxine (T4)
* Main thyroid hormone in blood
* Triiodothyronine (T3)
* Lesser amounts inblood than T4
* More active than T4
* Calcitonin
* Synthesized by parafollicular cells (C cells)
* Regulates calcium metabolism
* Inhibits osteoclast activity
* Promotes calcium uptake by bone
41
What are the thyroid-associated proteins?
* Thyroid binding globulin (TBG)
* **Protein transport**; most serum T4 and T3 bound to TBG
* Only unbound (free) hormone (FT4 or FT3) is biologically active
* Thyroglobulin
* **Storage** form of thyroid hormone in thyroid gland
* Main component of colloid
42
What are thyroid hormone effects?
* Speeds everything up!!
* Increase of basal metabolic rate
* Increase of carbohydrate and lipid catabolism
* Stimulation of protein synthesis
* Stimulation of glucose absorption
* Increase in cardiac output
* Growth effects
43
What are these clinical effects of?
* General
* Heat intolerance
* Weight loss/increased appetite
* Cardiac
* Palpitations/tachycardia
* Arrythmias
* Gastrointestinal
* Hypermotility
* Malabsorption, diarrhea
* Skin
* Warm, moist skin
* Sweating
* Neuromuscular
* Nervousness, irritability
* Tremor
* Muscle weakness
Hyperthyroidism --things are going to fast
44
How do you diagnosis Hyperthyroidism?
* Decreased TSH (primary)
* because its not enough to inhibit the TH
* Increased FT4
* T3 toxicosis-decreased FT4, increased T3
These tests tell us what type
* Radioactive iodine uptake (RAIU)
* Diffuse increase-Graves disease
* Focal/nodular uptake-toxic goiter/adenoma (“hot nodule”)--locally
* Decreased uptake-thyroiditis (early stage), factitious (pt taking TH medication and its too much)
45
What is this **most common cause** of hyperthyroidism?
* Typically young to middle aged women
* Etiology: autoimmune
* Clinical features:
* Hyperthyroidism--\>increase in TH secretion
* Opthalmapathy
* proptosis--due to increased retrorbital tissue
* Dermopathy
* skin manifestation which are least common
Graves Disease
46
How do you treat Grave's Disease?
* Surgery-thyroidectomy
* Life long thyroid replacement therapy
* Radioactive iodine treatment
* Drugs
* Beta blockers (propranolol, etc)
* Antithyroid drugs
* Propylthiouracil (PTU)
* Methimazole (tapazole)
47
Identify:
* Acute, **severe** hyperthyroidism
* Most commonly a complication of Graves disease
* **MEDICAL EMERGENCY!**
* Death from cardiac arrythmia or cardiac failure
* Usually markedly **elevated T4**
Thyroid Storm
48
What are some clinical effects of hypothyroidism?
* General
* Cold intolerance
* Listlessness
* Weight gain
* Cardiac
* Bradycardia
* Pericardial effusion
* Skin
* Dry skin/decreased sweating
* Brittle hair
* Mucopolysaccharide accumulation (myxedema)
* Neuromuscular
* Slow reflexes
* Gastrointestinal
* Decreased motility/constipation
49
What are these causes of?
* **Primary**
* Therapeutic ablation (thyroidectomy, radioactive iodine)--iatrogenic
* Hashimoto’s thyroiditis
* Dietary iodine deficiency--then we cant make TH
* Cretinism-development of hypothyroidism in utero or infancy/childhood
* Dyshormonogenetic goiter
* Drugs (lithium, p-aminosalicylic acid)
* **Secondary** (hypopituitarism)
Hypothyroidism
50
How do you diagnosis and treat Hypothyroidism?
* Diagnosis
* Increased **TSH-most sensitive test!!!**
* Decreased T4
* Treatment-thyroxine
* We will see increase in TSH before we see decrease in T4
51
What is thyroid problem?
* Autoimmune destruction of gland
* inflammation of thyroid gland that eventually takes over the gland
* Common cause of hypothyroidism
* May have transient hyperthyroidism initially
* Typically middle aged to elderly women
* Morphology
* Diffuse (occasionally nodular) enlargement of gland
* Marked lymphocytic infiltration with hurthle cells
* Diagnosis: antithyroid antibodies--specific Igs we measue when we suspect this disease
* Complications
* Lymphoma
* Papillary carcinoma
Chronic Lymphocytic Thyroiditis (Hashimoto’s)
52
What is this type of Thyroiditis?
* Probably viral infection
* Symptoms: pain, ENLARGED AND PAINFUL
* self-resolving
* Euthyroid; usually resolves in several weeks
Subacute--DeQuervain's
53
What is this type of thyroiditis?
* Destruction of gland by cellular fibrous tissue
* Clinically, hard mass; often mimics tumor
* Autoimmune etiology; rare
Fibrosing (Riedel’s)
--he didnt really talk about this
54
What is the MOST COMMON ENLARGEMENT of the thyroid gland?
* Endemic—in areas of iodine **deficiency**
* Sporadic—most common cause of thyroid enlargement
* `3-5% incidence
* Euthyroid-normal
* `Multiple nodules, varying sizes
* “Dominant” nodule
* one that is significantly bigger than other ones
* Marked variation in follicle size
* Nodules without fibrous capsule
* Secondary changes
* Hemorrhage
* Fibrosis
* Calcification
* Cystic degeneration
Nodular Hyperplasia (“Goiter”)
55
What is the MOST COMMON THYROID TUMOR?
* Usually nonfunctional
* “cold” or “warm” on iodine scan
* cold on iodine scan because not functional
* “Hot” nodules rarely malignant
* Usually solitary nodule with thin fibrous capsule
* Entirely bounded by fibrous capsule
Follicular Adenoma
56
What is this cancer of the thyroid?
* Incidence—5-15% of all thyroid malignancies
* More common in iodine- deficient areas
* Minimally invasive or widely invasive
* **Metastases**—usually bloodborne (lung, bones)
* Ras point mutation in about 50%
* Histology-same as adenoma, with capsular/vascular invasion--\>inorder to diagnosis this you have to be able to see the vascular invasion because it looks so simalr to an adenoma
Follicular Carcinoma
57
What is this tumor of the thyroid?
* “Follicular tumor with oncocytic features”
* \>75% oncocytes
* large cell with a lot of cytoplasma, and cytoplasm is granular = lots of mitochondria
* Gross-brown color
* Adenoma/carcinoma differential diagnosis same as for follicular tumors
* if this is malignant than it is considered 20% of all follicular carcinomas
Hurthle Cell Tumors
58
What is the **most common malignant tumor** of the thyroid?
* 65-80% of all thyroid cancers in U.S.
* \>90% in children
* Gross-usually ill-defined, unencapsulated
* Spread and metastasis
* Extrathyroid local spread
* Cervical lymph nodes
* spread via lymphatics!
* Distant metastasis very **uncommon**
* Nuclear abnormalities
* Optically clear (**“Orphan Annie”**) nuclei
* Nuclear grooves
* **Intranuclear cytoplasmic inclusions (INCIs)**
* Psammoma bodies
* Oncogenes
* RET/PTC (chromosome 10)
* BRAF (chromosome 7)
Papillary Carcinoma
Can be a Cystic Papillary Carcinoma
* About 10% of all PCT have marked cystic change
* Node metastases may be cystic
* Differential diagnosis is cystic goiter
59
What is this **Highly malignant tumor** of they thyroid?
* rapid growth and wide invasion
* Elderly patients (\>50 yrs)
* May have squamous, sarcomatoid, or giant cell appearance
* **Often coexist with (arise from) better differentiated thyroid tumors**
* Very **poor** prognosis
* most thyroid tumors have good prognosis except this one
Undifferentiated (Anaplastic) Carcinoma
60
What is this tumor of the thyroid?
* Tumor of parafollicular cells (C cells-secrete calcitonin)
* Two types
* Sporadic—70-80% of cases, usually \>45 yrs
* nodes are solitary
* Familial—younger age group, better prognosis, associated with C cell hyperplasia
* nodes are multiple or solitary
* Associated with:
* MEN IIA or IIB
* Germline mutations of RET oncogene
* Overall 5 year survival 70-80%
* See Amyloid
* To diagnosis look for calcitonin, CEA, neuroendocrine markers
* frequently mets to cervical nodes and may show distant mets
Medullary Carcinoma (MCT)
61
What is this thyroid tumor?
* Highly associated with lymphocytic thyroiditis (80%)
* Most are large B-cell lymphomas
* Other common types—low grade follicular, marginal zone
* Clinical—rapid enlargement of thyroid, often in patient with history of thyroiditis
Thyroid Lymphoma
62
What is this thyroid tumor?
* A group of familial syndromes characterized by tumors or hyperplasia in multiple endocrine organs
* Autosomal dominant
* Associated with described chromosomal abnormality
* _____ compared to non-\_\_\_\_\_\_ tumors:
* Younger age
* Multifocal
* Tumors often preceded by hyperplasia
Multiple Endocrine Neoplasia (MEN)
