Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
275 Cards in this Set
- Front
- Back
|
What are multiple endocrine neoplasia syndromes?
|
are group of inherited diseases = proliferative diseases (hyperplasia, adenoma, carcinoma) in multiple endocrine organs
|
|
|
What's Type I MEN (Wermer's) syndrome?
|
11q13 = : Pituitary adenoma, Pancreatic Islet cell Tumor (NOT adenocarcinoma), and Hyperparathyroidism or Parathyroid Adenoma
|
|
|
What's type IIa MEN (Sipple's) syndrome?
|
10q11.2 = pheochromocytoma (in adrenal medulla) , medullary carcinoma of the thyroid, and hyperparathyroidism
|
|
|
What's type IIb MEN syndrome?
|
10q11.2 = pheochromocytoma, medullary carcinoma of the thyroid, and neuroma of the tongue causing glossitis
|
|
|
What does the pituitary's anterior lobe (adenohypophysis) release? (5)
|
Produced by granular cells: PROLACTIN
GH ACTH (MSH) TSH LH & FSH |
|
|
What does the pituitary's posterior lobe (neurohypophysis) release? (2)
|
Produced by hypothalamus, simply distributed by pituitary:
ADH OXYTOCIN |
|
|
Anatomical location of the pituitary and neighboring structures?
|
Sits in the sella turcica. Above sphenoid sinus, internal carotids run on either side, optic chiasm runs right in front of stalk.
|
|
|
Differences in blood flow to the anterior and posterior pituitary?
|
Posterior lobe gets a lot of blood whereas the anterior only gets low-pressure portal flow = 1st to be affected with decreased flow.
|
|
|
What can cause hyperfunction of the anterior pituitary?
|
usually adenomas
less common: hyperplasia, hypothalamic disease, ectopic pituitary hormones |
|
|
What can cause hypofunction of the anterior pituitary?
|
destructive processes
|
|
|
What happens when the pituitary enlarges? (5 things)
|
Radiographic abnorms (enlarged sella turcica)
Visual field abnorms (bitemporal hemianopsia) Elevated ICP (h/a, n/v, sz, obstructive hydrocephalus) Cranial nerve palsy Pituitary apoplexy |
|
|
What's Pituitary apoplexy? What happens with this in the long term?
|
Adenoma hemorrages = rapid expansion = sudden h/a progressing to coma.
Long-term: Hypopituitarism |
|
|
What's Sheehan's syndrome?
|
Post-partum hemorrhage of the pituitary gland (it enlarges during pregnancy, which leads to more blood then rupture)
|
|
|
What are the 2 types of pituitary adenoma?
|
Micro and macro (>1cm).
If hormones are made by the adenoma = sx = early dx = microadenoma |
|
|
Are pituitary adenomas malignant?
|
No but their location causes problems
|
|
|
Histologic appearance of pituitary adenomas?
|
Pituitary's normally a mix of eosinophilic (GH and PL producing), basophilic and chromophobic cells. Adenoma = all one color no reticular network (no nests)
|
|
|
What are null cell adenomas?
|
Non-functional (tend to be bigger = local mass effect sx)
|
|
|
What are prolactinomas?
|
Produce prolactin
|
|
|
What are croticotroph cell adenomas? What do they cause?
|
Produce ACTH = cushing's disease/hypercortisolism or Nelson's syndrome (intractable ACTH adenomas you get from removing the adrenal glands)
|
|
|
What are somatotroph adenomas? What do they cause?
|
Produce growth hormone = gigantism (in kids)/acromegly (in adults, just get thickening since epiphyseal plates are closed)
|
|
|
What are gonadotroph adenomas? What do they cause?
|
Produce FSH and LH = infertility and libido problems (picked up later = usually larger)
|
|
|
What are thyrotroph adenomas? What do they cause?
|
Produce TSH = hyperthyroidism with increased T4 and TSH (if the problem was in the thyroid, you'd have decreased TSH)
|
|
|
What are the symptoms of a prolactinoma? How do you tx it?
|
Galactorrhea
Amenorrhea- infertility Loss of libido Tx = Bromocriptine (hypothalamus negatively controls via DM which blocks PL formation) |
|
|
What are other causes of increased prolactin levels (besides adenoma)?
|
High estrogen states
Pregnancy Renal failure Hypothyroidism Certain drugs (Reserpine, neuroleptic (Inhibit dopamine)) Damage to the pituitary stalk |
|
|
How do cortiotroph cell adenomas cause Cushing's Disease?
|
the tumor releases ACTH which goes to the adrenals and stimulates cortisol release (this normally works as neg feedback for ACTH release but the tumor doesn't care!)
|
|
|
What stimulates the release of ACTH from the anterior pituitary?
|
CRH from the hypothalamus
|
|
|
What stimulates the release of GH from the anterior pituitary? What inhibits it?
|
Stimulated by GHRH from the hypothalamus
Inhibited by Somatostatin from the hypothal and IGF1 (neg feedback from liver/tissues) |
|
|
What's the best way to measure GH levels?
|
Measure IGF-1 (the product of GH stimulation of liver/tissues - has more stable levels than GH)
|
|
|
Characteristic findings in acromegly?
|
Thickened bones (hyperosteosis of thoracic vertebrae, thick calvaria, prominent nose/chin/brow, barrel chest, big hands and feet), degen arthritis, thickened skin, goiter, abnl glucose tolerance, cardiomegly, male sexual dysfunct, peripheral neuropathy
|
|
|
What's the major clinical manifestation of gonadotroph adenoma?
|
Hypogonadism
|
|
|
What stimulates the release of LH and FSH from the anterior pituitary? What inhibits it?
|
Stimulated by GnRH from the hypothalamus
Stim/Inhib by feedback from estradiol and progesterone |
|
|
What stimulates release of TSH from the anterior pituitary? What inhibits it?
|
Stim by TRH from the hypothalamus
Inhib by neg feedback via thyroxine and thriodothronine |
|
|
What are the most common types of pituitary adenomas? What are the least common?
|
Most = GH and prolactin secreting
Least = TSH secreting |
|
|
What's anterior hypopituitarism?
|
75+% loss of the anterior pituitary which leads to hypofunction of the adrenals, thyroid, and gonads
|
|
|
What's the most common etiology of anterior hypopituitarism? What are other possible causes?
|
Most common = adenoma
Other causes = ischemic necrosis, surgery/radiation ablation, empty sella, inflam, hypothalamic RF dysfunction |
|
|
What's empty sella syndrome?
|
Seen in multiparous, obese women = enlarged sella then pituitary hemorrhage or herniation into subarachnoid space
|
|
|
What's sheehan's syndrome?
|
Postpartum infarction of the pituitary
|
|
|
Causes of Sheehan's syndrome?
|
Pregnancy
Others = DIC, hypotension, ICP (compresses vessels), trauma, shock (hypotension) |
|
|
Signs/sx of Sheehan's syndrome?
|
Pallor (due to dec MSH), hypothryoid (dec TSH), *lactation failure (dec prolactin - seen first), adrenal insuff (dec ACTH), and amenorrhea (dec FSH+LH)
|
|
|
What leads to Diabetes Insipidus? What complications arise from this?
|
ADH deficiency = lots of peeing = dehydration, hypernatremia, hyperosmolality, and dilute urine
|
|
|
What are the main causes of ADH deficiency?
|
30% idiopathic
tumors trauma post-hypophysectomy |
|
|
What are the complications from syndrome of inappropriate ADH?
|
hyponatremia, cerebral edema
|
|
|
Causes of SIADH?
|
ectopic ADH (paraneoplastic from small cell lung cancer)
Non-neoplastic lung disease Local injury to hypothalamus or posterior pituitary |
|
|
Where does the thyroid gland develop from?
|
Pharygeal epithelium
|
|
|
What happens when free T4(T3) interacts with cellular receptors?
|
Increase in BMR (inc metabolism of carbs, lipids, and proteins)
Stimulation of calcitonin production in parafollicular/C cells |
|
|
What does calcitonin do?
|
Increases skeletal absorption of calcium
Decreases osteoclast activity |
|
|
4 main blood tests for thyroid function?
|
Free and total T4
Free and total T3 TSH Thyroid Binding Globulin (can mess with amount free to interact with cells) |
|
|
Explain the radioactive iodine uptake test for thyroid function.
|
Normal = diffuse
Graves = excessive diffuse uptake Thyroiditis = little uptake Defect/Cold nodule = hypofunct (can be tumor, cyst, etc) |
|
|
Name the 4 common causes of hyperthyroidism?
|
Graves disease
exogenous thyroid hormone (old weight loss drugs) hyperfunctioning goiter hyperfunctioning adenoma |
|
|
Name the 3 uncommon causes of hyperthyroidism?
|
Thyroiditis
TSH pituitary adenoma Ectopic thyroid (struma ovarii = mature thyroid tissue) |
|
|
Who gets Graves disease?
|
Pts in their 20-40,
7x female predominance Increased incidence with FHx (HLA-DR3, CTLA4) |
|
|
What is Graves disease?
|
Autoimmune disease where there's IgG against the TSH receptor (ab = TG1,TS1, TBII) = overstimulation = hyperthyroid
|
|
|
What are the symptoms of Graves disease?
|
Hyperthyroidism with diffusely enlarged gland (vessels engorged)
Opthalmoplegia Dermatopathy |
|
|
What are the characteristics of a Grave's patient?
|
Fine hair, exopthalmos, goiter, muscle wasting, sweating, tachycardia/high output failure, weight loss, oligomenorrhea, tremor
|
|
|
What causes the bug eyed appearance in Grave's disease?
|
There's deposits in the tissues behind the eye + inflammation, may be irreversible if tx happens too late
|
|
|
Are most cases of hypothyroidism primary or secondary?
|
Primary
|
|
|
Causes of hypothyroidism?
|
Thyroid ablation
Thyroiditis (Hashimotos) Primary idiopathic Creinism Myxedema |
|
|
What's cretinism?
|
Serve hypothyroidism in kids
|
|
|
What's myxedema?
|
Really extreme hypothyroidism in adults
Caused by low iodine (slightly low = compensatory inc TSH = goiter) |
|
|
What will you see in a kid with low thyroid hormone?
|
Coarse facies (boxy)
Umbilical hernias Short stature Low IQ Protruding tongue |
|
|
Clinical features of a patient with myxedema?
|
Muscle weakness
Coarse brittle hair Lose eyebrows Listless attitude, forgetful (Myxedema madness) Peri-orbital edema, puffy face Pallor Larger tongue (due to buildup of aminoglycans) Edema vocal cords, hoarse Bradycardia, cardiomegly gastric atrophy, Constipation Menorrhagia Peripheral edema |
|
|
What's the underlying issue with Diffuse nontoxic, colloid, or multinodular goiter?
|
Impaired thyroid hormone synthesis
|
|
|
What's Plummer's Syndrome?
|
Groups of hyperfunctioning thyoid cells (makes T4 without TSH stimulation)
|
|
|
What happened to multinodular goiter in the long term?
|
You get cysts, fibrosis, calcification, and hemorrhage
|
|
|
Discuss features of subacute lymphocytic thyroiditis? (who gets it, what do you see micro-wise)
|
More common in middle aged females (postpartum)
See mild/no symmetrical enlargement and lymphocytic infultration with follicles - poss autoimmune. Can recur but is benign/self-limiting |
|
|
Characteristic micro finding in Hashimoto's thyroiditis? What else do you see micro-wise?
|
Hurhtle cells (reactive cells = big, granular with nucleoli)
Inflammation, plasma cells, and follicles |
|
|
Gross appearance of Hashimoto's thyroiditis?
|
diffuse enlargement, pale and firm
|
|
|
What's the pathogenesis behind Hashimoto's thyroiditis?
|
cytotox t's destroy the thyroid due to auto ab against thryroglobulin and thyroid peroxidase (IgG's - opposite of graves, this is ab blocking the receptor)
|
|
|
HLA's associated with Hashimoto's thyroiditis? Who gets this disease?
|
HLA-DR5 (and 3)
Presents in 45-60 y/o 10-20x female predominance |
|
|
Clinical signs and sx of hashimoto's?
|
Same as hypothyroid - mild obesity, carpal tunnel, puffy face and eyes, bradycardia, physical and mental slowing, etc
|
|
|
When do you see a subacute, granulomatous/De Quervain's thyroiditis?
|
Pts in 30-50's, more in females
Often following viral URI Less common than Hashimotos |
|
|
Gross and micro findings in subacute, granulomatous/De Quervain's thyroiditis?
|
uni/bilateral englargement - may be painful
Firm and granulomatous with PMNs (inc WBC and sed rate) |
|
|
Prognosis of subacute, granulomatous/De Quervain's thyroiditis?
|
Self-limiting - usually recover in 6-8 weeks
|
|
|
What's Riedel's thyroiditis?
|
Rare fibrotic disease of unknown etiology (can compress trachea + esophagus)
Assoc with fibrosis elsewhere |
|
|
Who gets Riedel's thyroiditis?
|
Middle aged women (3:1)
|
|
|
Who gets infectious thyroiditis?
|
Pretty much just immunocompromised pts (HIV, cancer, etc)
|
|
|
Difference in lab values between primary and secondary hypothryroidism?
|
Primary has an increase in TSH, secondary has a decrease
|
|
|
Are most solitary nodules in the thyroid benign or malignant?
|
Mostly benign (99%) - more often malignant in males
|
|
|
4 examples of benign solitary nodules of the thyroid?
|
nodular hyperplasia/goiter
simple cysts foci of thyroiditis follicular adenomas |
|
|
4 neoplasms of the thyroid?
|
follicular adenoma + carcinoma
papillary carcinoma medullary carcinoma anaplastic carcinoma (atypical, undifferentiated - old people) |
|
|
Clinical exam and RAIU results of a thyroid adenoma?
|
Painless enlargement
"cold nodule" with rare hyperfunctioning |
|
|
Gross appearance of a thyroid adenoma?
|
encapsulated, solitary and grey/red-brown
hemorrhagic, fibrosis, calcification, or cystic change "normaloid follicles" |
|
|
What would you think if you saw a sea of Hurthe cells?
|
Carcinoma or adenoma
|
|
|
What protooncogenes play a part in what types of thyroid carcinomas?
|
Papillary related to PTC oncogene
Medullary ca related to RET protooncogene (growth factor receptor, MEN II) |
|
|
What increases your risk of thyroid cancer?
|
irradiation of neck (Chernobyl)
solitary nodule in male or child hard nodule w/ LAD Family Hx of medullary CA - MEN IIa&b |
|
|
Incidence of follicular carcinoma of the the thyroid?
|
Second most common thyroid ca
More common with goiter |
|
|
Does follicular carcinoma of the the thyroid arise from adenomas? How do you differentiate the 2?
|
Probably not.
Differentiate by capsule invasion and mets (via blood stream) (don't usually see pleomoph/mitosis) |
|
|
What's the most common type of thyroid cancer?
|
Papillary
|
|
|
What's risk factor is strongly associated with papillary carcinoma of the thyroid?
|
Radiation
|
|
|
Gross features of papillary carcinoma of the thyroid?
|
papillary or granular cut surface
Ca++, fibrosis, cystic change papillary or follicular variant |
|
|
Microscopic features of papillary carcinoma of the thyroid?
|
“Orphan Annie eyes” (chromatin pushed to edges w/ cleared out middle)
psammoma bodies (laminated, calclified secretions) |
|
|
Prognosis of papillary carcinoma of the thyroid?
|
Likes to spread to lymph nodes but is indolent with 10 yr survival of 85%
|
|
|
Incidence of medullary carcinoma of the thyroid? Who gets it?
|
Rare - 10% familial assoc with RET protoonc (MEN IIa/IIb) = younger and multiple
Adults in 50-60's |
|
|
Cell origin of medullary carcinoma of the thyroid? Tumor marker?
|
Neuroendocrine = parafollicular cell origin. Calcitonin = tumor marker.
|
|
|
Gross appearance of a medullary carcinoma of the thyroid?
|
hemorrhage and necrosis
extracapsular extension |
|
|
Microscopic appearance of a medullary carcinoma of the thyroid?
|
polygonal, spindled and anaplastic cells
trabecular, nests or follicles Amyloid of altered calcitonin |
|
|
Where do medullary carcinoma of the thyroid like to met?
|
Blood and lymph nodes
|
|
|
What's the prognosis of a medullary carcinoma of the thyroid?
|
Aggressive, 50% 5 year survival
|
|
|
Who normally gets an anaplastic carcinoma of the thyroid?
|
Elderly people in areas of endemic goiter
|
|
|
What's the main microscopic feature of an anaplastic carcinoma of the thyroid?
|
anaplastic cells, of course! (lots of mitoses, hyperchromic, etc)
|
|
|
How does an anaplastic carcinoma of the thyroid behave?
|
aggressive with rapid growth and extension beyond the capsule = invasion of local neck structures. Also does distant mets
|
|
|
What's the prognosis of an anaplastic carcinoma of the thyroid?
|
bad
normally too late by the time you find them - so sad |
|
|
What does PTH do?
|
Increases calcium: Activates osteoclasts, inc renal and GI Ca absorp and phosphate excretion, and increases conversion of dihyrdoxy VitD in the kidney
|
|
|
What controls levels of PTH?
|
Blood calcium levels
|
|
|
What's PTH related peptide?
|
A hormone secreted by paraneoplastic tumors, like increased PTH = high serum calcium.
|
|
|
Who gets hyperparathyroidism?
|
3x female, usually adult
|
|
|
Causes of hyperparathyroidism?
|
Adenomas, primary hyperplasia, or rarely carcinoma (sporatically or with MEN I and IIa)
|
|
|
What are the symptoms of hyperparathyroidism?
|
"stones, bones, abdominal groans and psychic moans" = kidney stones, osteitis fibrosa cystica, peptic ulcers, and emotional disorders. (also pancreatitis, nephrocalcinosis, and muscle atrophy)
|
|
|
What condition, besides hyperparathyroidism, must you rule out in a patient hypercalcemia?
|
Paraneoplastic syndrome due to nonparathyroid malignancy
|
|
|
What do you see with adenomas of the parathyroid? (gross and micro)
|
Compresses normal tissue on edge, other gland's nl/atrophied, and micro = uniform chief cells (oxyphils or clear)
|
|
|
What do you see micro-wise with hyperplasia of the parathyroid? What happens to the other glands?
|
See diffuse/multilobular cheif cell hyperplasia
Variable enlargement of all glands |
|
|
How do you diagnose a carcinoma of the parathyroid?
|
Looking for invasion and mets (just like carcinomas of the thyroid!)
|
|
|
What are the main causes of secondary hyperparathyroid?
|
Conditions that chronically decreases calcium - renal failure, inadequate dietary intake, steatorrhea, Vit D deficency
|
|
|
What are some changes you may see with secondary hyperparathyroid?
|
Bone changes
Metastatic Calicification Non-symmetrical hyperplasia of the parathyroid gland |
|
|
What's tertiary hyperparathyroid?
|
Unregulated (autonomous) parathyroid that can follow long-standing secondary hyperparathyroid.
|
|
|
Which is more common: hyper- or hypo- parathyroid?
|
Hyper
|
|
|
What are the main causes of hypoparathyroid?
|
surgical ablation of thyroid
primary or idiopathic atrophy- (autoimmune) DiGeorge’s syndrome |
|
|
What is Pseudohypoparathyroidism?
|
tissue PTH resistance
|
|
|
What are the clinical manifestations of hypoparathyroidism?
|
Tingling
Neuromuscular irritability Chvostek’s sign (cringe when facial nerve's hit) Trousseau’s sign (hand contracts when BP cuff's inflated) Carpopedal spasm Seizures |
|
|
What is the difference in lab values between parathyroid adenoma and paraneoplastic syndrom with PTHrH?
|
Both have increased calcium and decreased Phosphate but an adenoma would have inc PTH whereas w/ a neoplasm it's dec
|
|
|
What is the difference in lab values between parathyroid adenoma and primary hypoparathyroid?
|
Adenoma has increased Ca/PTH and decreased phosphate
Hypoparathyroid is the opposite |
|
|
What is the difference in lab values between primary hypoparathyroid and secondary hypoparathyroid?
|
Both have decreased calcium and increased phosphate but primary has a dec PTH whereas in secondary it's increased.
|
|
|
What are the 3 major hormones secreted by the adrenal cortex?
|
glucocorticoids- cortisol
mineralocorticoids- aldosterone adrenal cortical androgens |
|
|
What are the 3 major syndromes associated with hyperfunctioning of the adrenal cortex?
|
Cushing’s syndrome
hyperaldosteronism virilizing syndromes |
|
|
What is Cushing's syndrome?
|
ANY condition with increased glucocorticoids
|
|
|
What are the causes of Cushing's syndrome? (4)
|
Exogenous glucocorticoids
Primary hypothalamic/pituitary disease (Cushing’s disease) Primary adrenal cortical hyperplasia or neoplasia Ectopic ACTH by non-endocrine neoplasms |
|
|
Signs and sx of Cushing's syndrome seen in the face, head, bones and skin?
|
Emotional disturb, enlarged sella turcica, moon faces, oseoporosis, purpura, skin ulcers (poor healing), thin/wrinkled skin
|
|
|
Signs and sx of Cushing's syndrome seen in the trunk and muscles?
|
Cardiac hypertrophy and htn, obesity, buffalo hump, adrenal tumor/hyperplasia, abd striae, amenorrhea, muscle weakness
|
|
|
What percent of Cushing's syndrome is caused by Cushing's Disease?
|
50%
|
|
|
Who gets Cushing's Disease?
|
pts in 20-30's
5x female predom |
|
|
What are the causes of Cushing's Disease?
|
mostly corticotroph pituitary adenomas or hyperplasia.
Rarely = hypothalamic stimulation |
|
|
What gross changes do you see with Cushing's Disease?
|
Bilateral adrenal cortical hyperplasia
|
|
|
What are 2 other names for primary cortical hyperplasia/neoplasia of the adrenals?
|
Adrenal Cushing’s syndrome or ACTH independent Cushing’s
|
|
|
What percent of Cushing's syndrome cases are due to primary cortical hyperplasia/neoplasia of the adrenals?
|
15-30%
|
|
|
What are the most common types of primary cortical hyperplasia/neoplasia of the adrenals?
|
Adenomas and Carcinomas
(Hyperplasia = less common, poorly understood) |
|
|
With what cancers do you see paraneoplastic cushing's syndrome?
|
Usually small cell lung cancer
Also: Carcinoid tumors, Islet cell tumors, and medullary carcinomas. |
|
|
What labs would you run if you suspect Cushing's syndrome?
|
Serum ACTH
24hr urine free cortisol Overnight dexamethasone suppression test (high+low dose) |
|
|
In what Cushing's syndrome disorder would ACTH be decreased?
|
Adrenal Cushing's
|
|
|
In what Cushing's syndrome disorder would Overnight dexamethason suppression yeild decreased ACTH?
|
Adrenal cushing's
|
|
|
In what Cushing's syndrome disorder would Overnight dexamethason suppression yeild increased ACTH?
|
Ectopic cushing's
|
|
|
In what Cushing's syndrome disorder would Overnight dexamethason suppression vary based on dose (inc in small, dec in large)?
|
Cushing's disease
Obesity |
|
|
What would the Overnight dexamethason suppression test show in a normal patient?
|
both ACTH and cortisol would be decreased at both the low and high dose.
|
|
|
What are the main causes of primary hyperaldosteronism?
|
Decreased renin due to:
80%- Conn’s syndrome (secreting adenoma) 15%- primary adrenal hyperplasia |
|
|
What are the main causes of secondary hyperaldosteronism?
|
Increased renin caused by overactivation of renin-angiotensin system (CHF and decreased renal perfusion)
|
|
|
What are the direct effects of hyperaldosteronism?
|
Na retention and K excretion = hypertension and hypokalemia
|
|
|
What is Conn's syndrome?
|
Usually an aldosterone secreting solitary adenoma with no surrounding cortical atrophy (no ACTH suppression)
|
|
|
Who get's Conn's syndrome?
|
Middle adult life, 2x females
|
|
|
What's important about htn associated with Conn's syndrome?
|
Less than 1% of HTN, however a surgically correctable form
|
|
|
What do you see (gross morph) with primary adrenocortical hyperplasia?
|
Diffuse, bilateral hyperplasia due to a non-ACTH pituitary glycoprotein?
No surrounding cortical atrophy |
|
|
Who gets primary adrenocortical hyperplasia?
|
Children and young adults
|
|
|
What causes primary adrenocortical hyperplasia?
|
idiopathic
|
|
|
How do you treat primary adrenocortical hyperplasia?
|
Managed with medical therapy
|
|
|
What adrenogential syndromes can cause virilization? (little boys turn to little girls and visa versa)
|
Primary gonadal disorders
Adrenal cortical neoplasms Primary adrenal disorders collectively called “Congenital adrenal hyperplasia” (CAH) |
|
|
What is congenital adrenal hyperplasia?
|
An adrenogenital syndrome with enzyme deficiencies in cortisol synthesis
|
|
|
What are the inherited issues involved with congenital adrenal hyperplasia?
|
95% - 21 hydroxylase def: dec cortisol = inc ACTH w inc virilizing cortisol precursors
17 hydroxylase def.-androgen and glucocorticoid deficiency |
|
|
What are the clinical features congenital adrenal hyperplasia?
|
androgens inc or dec
abnormal sodium metabolism Severe cases glucocorticoid def (tx w exogenous glucocorticoid) |
|
|
What are the gross morphologic changes seen with congenital adrenal hyperplasia?
|
Bilateral adrenal enlargement and pituitary corticotroph hyperplasia
|
|
|
In which varient of congenital adrenal hyperplasia do you not see virilism?
|
17-OH deficiency
|
|
|
Differences between 21OH def and 17OH def (types of congenital adrenal hyperplasia)?
|
21= virilism, salt loser, and inc urine 17KS and preganaetriol
17 = (none of the above changes) + salt retention, htn |
|
|
Name 2 primary causes of adrenal insufficiency.
|
chronic Addison’s disease
acute primary adrenal insufficiency |
|
|
Name 3 secondary causes of adrenal insufficiency.
|
Dec stim by ACTH-hypopituitary:
Sheehan’s syndrome Nonfunctioning pituitary adenomas Hypothalamic/suprasellar lesions |
|
|
What's the first problem you'll see with secondary causes of adrenal insufficiency?
|
Decreased cortisol
|
|
|
What is Addison’s disease?
|
Destruction of ~90% of adrenal cortex
|
|
|
What are the major causes of Addison’s disease?
|
Autoimmune (Ab to 17 or 21 OH)
Tb (granulomas) AIDS metastatic disease |
|
|
What are the minor causes of Addison’s disease?
|
Amyloidosis,
fungi, hemochromatosis, *sarcoidosis* |
|
|
What happens when pts with Addison's disease are stressed? How do you tx that?
|
Adrenal crisis = shock, n/v, coma
Tx with corticosteriods |
|
|
What are the main symptoms of addison's disease?
|
Hypotension (dec Na), Weight loss (v/d, anorexia), weakness, hypoglycemia, hyperpigmentation (ACTH-MSH), Vitiligo
|
|
|
What is vitiligo? What disease is it associated with (endocrine related)?
|
autoimmune against skin melanocytes = irregular white patches
Assoc with autoimmune Addisons |
|
|
What are the 3 main causes of acute primary adrenal cortical insufficiency?
|
Massive adrenal hemorrhage
(Waterhouse-Friderichsen syndrome) Sudden withdrawal from steroid Tx Stress w/ underlying adrenal cortical insufficiency |
|
|
What are the clinical signs/sx of acute primary adrenal cortical insufficiency?
|
Vomiting, abdominal pain, hypotension, vascular collapse, coma, death unless TX with corticosteroids
|
|
|
What is Waterhouse-Friderichsen syndrome? What causes it?
|
Massive adrenal hemorrhage from Nisseria Meningitis endotoxin = vascular injury
|
|
|
How can you tell between a primary and secondary adrenal insufficiency?
|
Primary insufficiencies won't respond to ACTH stimulation and have a more severe hyponatremia with hyperkalemia and metabolic acidosis.
|
|
|
What are the characteristics (gross morph and functioning) of an adrenal adenoma?
|
most nonfunctioning
yellow to yellow brown well circumscribed nodules usually 1-2 cm. |
|
|
Microscopic appearance of an adrenal adenoma?
|
Eosinophilic or vacuolated cytoplasm, +/- pleomorphism
|
|
|
How would you know if an adrenal adenoma is functioning or not? (just by looking at an autopsy pt)
|
If the adenoma was functioning, you would see atrophy of the contra-lateral adrenal gland.
|
|
|
How common are adrenal carcinomas? Who gets them?
|
rare, occur any age
|
|
|
How do adrenal carcinomas behave?
|
They're bad - more likely to be functioning than adenomas with virilism/hyperadrenalism
usually large and invasive |
|
|
How do adrenal carcinomas like to met?
|
lymphatic, blood, adrenal vein and Inf Vena Cava spread
|
|
|
What do adrenal carcinomas look like grossly?
|
usually variegated with cystic change and hemorrhage
|
|
|
What is the prognosis for an adrenal carcinomas?
|
median survival 2 years
|
|
|
Where's the adrenal medulla derived from and what does it do?
|
Derived from neural crest cells (chromaffin cells)
synthesize catecholamines |
|
|
Where do you mostly see neuroblastomas of the adrenal medulla?
|
In kids
|
|
|
What are ganglion cell tumors of the adrenal made of?
|
very mature, neural crest cells (not very aggressive)
|
|
|
What do you call an extra-adrenal pheochromocytoma?
|
Paraganglioma
|
|
|
What are the symptoms of pheochomocytomas?
|
Paroxysmal or sustained HTN wtih h/a, apprehension, inc HR, sweating, tremor, MI, heart failure, renal damage, CVA
|
|
|
What does a pheochomocytoma make?
|
catecholamines
|
|
|
Why are pheochomocytomas the "10% tumor"?
|
10% familial
10% malignant (based on metastases) 10% bilateral* 10% extraadrenal 10% occur in childhood |
|
|
What 4 syndromes are associated with familial pheochomocytomas?
|
MEN II
neurofibromatosis Von Hippel-Lindau disease Sturge-Weber syndrome |
|
|
What do pheochomocytomas look like grossly?
|
Size varies
Yellow-tan potassium dichromate turns tumor brown |
|
|
What is the microscopic appearance of pheochomocytomas?
|
Polygonal to spindled cells in “Zellballen” (nests of cells)
Granular cytoplasm, + with silver stains |
|
|
How do you screen for a pheochomocytoma?
|
24 hr urinary free catecholamines and metabolites (vanillylmandelic acid-VMA and metanephrines - best screen)
|
|
|
What is the treatment for pheochomocytomas?
|
surgical removal and adrenergic (beta) blocking agents
*can bleed into itself = massive catecholamine release |
|
|
What is the incidence of nueroblastomas?
|
Most common extracranial solid tumor of childhood (infants, first 5 years)
|
|
|
Where can neuroblastomas be found?
|
Found anywhere in sympathetic system
75% in abdomen, mostly retroperitoneal picked up due to sx of mass effect |
|
|
Are neuroblastomas sporatic or familial?
|
Usually sporadic, but some familial (m-myc amplification)
|
|
|
What's the typical microscopic appearance of neuroblastomas?
|
Homer Wright rosettes (circles of malignant cells)
|
|
|
What issues do you see with MEN I? (Wermer’s syndrome)
|
Parathyroid problem (Hypercalcemia)
Pancreas (islet tumor - Usually death because of this) Pituitary tumor |
|
|
What do you see with MEN II?
|
100% chance of medullary carcinoma in first 2 decades of life
pheochromocytoma syndrome |
|
|
What do you see with MEN IIa? (Sipple Syndrome)
|
parathyroid hyperplasia
pheochromocytoma Medullary carcinoma |
|
|
What do you see with MEN IIb? (William Syndrome)
|
mucosal neuromas(tongue lumps) marfanoid habitus (tall, thin)
pheochromocytoma Medullary carcinoma |
|
|
What happens with acute pancreatitis?
|
Acute abdominal pain with enzymatic necrosis and inflammation
|
|
|
What is acute hemorrhagic pancreatitis?
|
Damaged blood vessels = bleeding into pancreas = bradykinins and such released = severe hypotension
|
|
|
How do you diagnose acute pancreatitis?
|
Pancreatic enzymes in blood and urine
|
|
|
What happens after acute pancreatitis?
|
The part that was digested/necrosed can fill with fluid, forming a pseudocyst (pseudo = no epithelium)
|
|
|
What are the causes of acute pancreatitis?
|
80% are from either alcoholism and gallstones (fat, forty, female, flatulent)
10-20% unknown |
|
|
What triggers acute pancreatitis?
|
Damaged tissue = releases proenzymes that are then activated setting off a cascade (especially trypsin)
|
|
|
How are the enzymes activated to cause acute pancreatitis?
|
pancreatic obstruction
primary acinar cell injury defective transport of proenzymes in acinar cells |
|
|
What are the clinical presentations of acute pancreatitis?
|
Abdominal pain
Shock Jaundice,hyperglycemia and glucosuria in < 1/2 |
|
|
What are the laboratory results seen with acute pancreatitis?
|
Lowered calcium (binds to lipids: "soap making" from fat necrosis)
Amylase - inc in first 12 hrs, normalizes in 2-3 days Lipase - stays elevated for a little longer (7-10 days) |
|
|
Can you die from acute pancreatitis?
|
Yes, 20-40% do from shock, secondary sepsis, and ARDS
|
|
|
What is chronic pancreatitis?
|
Repeated bouts of inflammation
|
|
|
Who gets chronic pancreatitis?
|
Middle aged men, especially alcoholics. Assoc. with hypercalcemia and hyperlipoproteinemia
|
|
|
What causes chronic pancreatitis?
|
protein plugs
oxidative stress protein calorie malnutrition |
|
|
Is biliary tract disease more important in acute or chronic pancreatitis?
|
More important in acute
|
|
|
What's the relation between chronic pancreatitis and CF?
|
50% have no predisposing factors but 1/3 idiopathic chronic pancreatitis pts have some defect in CFTR (not enough to have abnl sweat chloride and such)
|
|
|
What is the morphology of chronic pancreatitis?
|
Fibrosis (nerves can get stuck = more pain) and chronic inflammation
Islet sparing (severe can = diabetes) Protein plugs and calcium carbonate stones |
|
|
What is the clinical presentations of chronic pancreatitis?
|
Repeated attacks of abd pain
Silent until pancreatic insuff develops (= malabsorption) Can see pleural effusions |
|
|
What lab results are seen in chronic pancreatitis?
|
Slight increased amylase/lipase
Severe = DM and malabsorption |
|
|
Who gets pancreatic cancer?
|
60-80 years, increased incidence in smokers
|
|
|
What's the usual type of pancreatic cancer?
|
Usually exocrine ductal epithelium (islet cell tumors less common)
|
|
|
How long does it take to discover pancreatic cancer?
|
A long time, normally - Tumors of head clinically evident sooner
|
|
|
How does pancreatic cancer spread?
|
Local invasion and metastatic spread (lung, liver, peritoneum - like to met quickly - likes perineural invasion = pain)
|
|
|
What are the clinical signs of pancreatic cancer?
|
Abdominal pain
obstructive jaundice (+painless gallbladder enlargement = "courvoisier" gallbladder) Trousseau’s sign (migratory thrombophlebitis) Weight loss |
|
|
What is the prognosis of pancreatic cancer?
|
Grim prognosis:
1 yr-10% 10 yr- 2.5% |
|
|
What are the serum markers in Pancreatic adenocarcinoma? Are they specific?
|
not specific:
CEA CA 19-9 |
|
|
What are the genetic markers associated with Pancreatic adenocarcinoma?
|
K-RAS AND CDKN2A = 90%
SMAD4 (DPC4) in 50% p53 in >50% ERBB2 (HER2/NEU) >50% |
|
|
What are the products of the islet of Langerhan's (and what kinds of cells make them?
|
beta cells (70%)- insulin
Alpha (5-20%)- glucagon Delta (5-10%)- somatostatin PP- pancreatic polypeptide (exocrine too - stimulates gastrin secretion and inhibs mobility) |
|
|
What is diabetes?
|
A heterogeneous group of disorders of carbohydrate, fat and protein metabolism with a deficient or defective insulin response
|
|
|
What do the different types of diabetes differ in?
|
pattern of inheritance
insulin response origins |
|
|
What are the secondary causes of diabetes? (4)
|
pancreatitis
tumors certain drugs iron overload |
|
|
Name the characteristics (onset, prevalence, risk) of DM type I?
|
juvenile onset (peak = 10/11 but it can be older)
10-20% of diabetes cases 0.5% risk |
|
|
Name the characteristics (onset, risk) of DM type II?
|
adult onset (peak = 55-60, now more younger due to fat kids)
80-90% of diabetes cases 5-7% risk |
|
|
What do DM I and II have in common?
|
The same types of long term consequences, involving blood vessels, kidneys, eyes, and nerves
|
|
|
What stimulates the synthesis and release of insulin?
|
glucose
|
|
|
What stimulates the release but not the synthesis of insulin?
|
cholinergic input
intestinal hormones leucine and arginine sulfonylureas |
|
|
What does insulin do? (5)
|
Anabolic hormone:
1. Transmembrane transport of glucose and AA’s 2. glycogen formation in liver and skeletal muscle 3. conversion of glucose to triglycerides 4. nucleic acid synthesis 5. protein synthesis |
|
|
How does insulin do what it does? (what does it bind to)
|
Binds to tyrosine kinase receptor and transports GLUTs to plasma membrane
|
|
|
Which cells don't bind insulin?
|
Brain
Parts of blood vessels |
|
|
What happens with hyperglycemia?
|
Glycosuria = loss of calories (weight loss and mobilization of fat/protein = nitrogen balance and acidosis) and polyuria with dehydration and lyte imbalance. Can = coma and death.
|
|
|
What's a good way to diagnose DM?
|
Fasting glucose (nl = <100, DM>126)
Glucose tolerance -2hrs after 75gm glucose (nl <140, DM>200) |
|
|
What's the pathogenesis of DM type IA?
|
Lack of insulin and decreased beta cell mass due to autoimmune destruction of beta cells
|
|
|
What's the onset and the risk of DM type IA?
|
Manifests in childhood - dependent on insulin for survival
Risk = Acute ketoacidosis and coma |
|
|
What are the 3 "interlocking mechanisms" of DM 1A?
|
Genetic susceptibility
Autoimmunity Enviro event that alters beta cells |
|
|
What are the characteristics of the Genetic susceptibility assoc with DM 1A?
|
twin studies- 40%, 1st order relatives- 6%
See more in northern europeans and class II MHC- locus IDDM1 (DR3 and 4) |
|
|
What are the characteristics of the autoimmunity assoc with DM 1A?
|
Early intense insulitis with abs to islets
Associated with other autoimmune diseases |
|
|
What are the characteristics of the environmental event which alters beta cells assoc with DM 1A?
|
viral molecular mimicry or mild injury. Assoc with coxsackie B, mumps, measles, rubella, EBV
|
|
|
What's the pathogenesis of DM II?
|
No evidence of autoimmune mechanisms and not linked to HLA but genetic factors more important than type I: twin studies- 60 to 80%, 1st order relatives 20 to 80%
|
|
|
What are the 2 major metabolic defects seen in DM II?
|
Abnormal secretion of insulin
(early abnl pattern with later deficiency) Insulin resistance- major factor |
|
|
What later abnormalities are associated with insulin secretion with DM II?
|
Mild to moderate deficiency with modest reduction of beta cells (chronic hyperglycemia may contribute to dysfunction)
|
|
|
When do you see insulin resistance?
|
obesity (may unmask DM earlier, not really a causative)
pregnancy |
|
|
What happens with insulin resistance?
|
Inability to have direct deposition of glucose
More persistent hyperglycemia Prolonged beta cell stimulation |
|
|
What's the relation of amylin to DM II?
|
Amyloid type change in islets around the beta cells - protein precipitates due to overwork = don't respond as well to glucose
|
|
|
What happens in long term diabetes (4 main things)?
|
Microangiopathy/atherosclerosis
retinopathy nephropathy neuropathy |
|
|
What are the two mechanisms of the chronic complications of diabetes?
|
1. nonenzymatic glycosylation (HbA1c and AGE - dysfunctional protein)
2. intracellular hyperglycemia and polyol pathways (increased sorbitol and fructose = osmotic injury) |
|
|
What do you see in the pancreas after long term DM?
|
Type I = decreased number of islets/islet mass, insulitis, beta cell degranulation
Type II - amyloid/amylin |
|
|
What do you see in the vessels after long term DM?
|
all sizes affected: large and medium sized = accelerated atherosclerosis, hyaline arteriolosclerosis
capillaries = microangiopathy (leaky) |
|
|
What are the 2 most common causes of death in DM pts?
|
MI
Renal failure |
|
|
What are the 3 main lesions you see in the kidneys of DM pts?
|
1. glomerular lesions (nephrotic syndrome, diffuse/nodular glomerulosclerosis, (nodular = Kimmelstiel Wilson lesion)
2. hyaline arteriosclerosis and atherosclerosis 3. pyelonephritis- necrotizing papillitis |
|
|
What are the ocular complications of diabetes?
|
Retinopathy
Cataracts Glaucoma |
|
|
How common is blindness in DM?
|
4th leading cause of blindness in U.S.
|
|
|
What do you see with non-proliferative retinopathy in DM?
|
intra-/preretinal hemorrhages, exudates, microaneurysms, venous dilations, edema, microangiopathy
|
|
|
What do you see with proliferative retinopathy in DM?
|
neovascularity
fibrosis retinal detachment |
|
|
What is the effect of long term DM on the PNS?
|
Peripheral neuropathy (usually lower extremities, motor and sensory. Mononeuropathy- foot drop, CN palsies)
Autonomic neuropathy (bladder, bowel, impotence) |
|
|
What is the effect of long term DM on the CNS?
|
Microangiopathy and neuronal depletion
Infarcts, hemorrhage (due to HTN and atherosclerosis) Spinal cord affected too |
|
|
What the risk of amputation/gangrene with DM?
|
100x the risk of the general population
|
|
|
What skin issues can you see with DM?
|
Infections
Necrobiasis Lipoidica Trophic ulcerations |
|
|
What happens in DKA?
|
Insulin defciency = polyuria (= volume depletion) and FA break dwon to acetoacetic and beta hydroxybutyric acids (ketones) + protein catabolism = acidosis = coma
|
|
|
What happens with DM II decompensation?
|
hyperosmotic non-ketotic coma
|
|
|
What's the incidence of islet cell tumors?
|
Rare compared to exocrine tumors
Neuroendocrine tumors |
|
|
What are the 3 main clinical syndromes assoc with an islet cell tumors?
|
hyperinsulinism/insulinoma
hypergastrinoma/Zollinger-Ellison syndrome multiple endocrine neoplasia syndrome (MEN I) |
|
|
What do you see with insulinomas?
|
Hypoglycemia - Precipitated by fasting or exercise
Neuropsychiatric symptoms nervousness, confusion, stupor |
|
|
What's the gross morph of insulinomas?
|
Usually benign, solitary, and small red-brown nodules
Immunochemistry + for insulin |
|
|
What lab work do you see with insulinomas?
|
high insulin & hypoglycemia
|
|
|
What do you see with gastrinomas?
|
Hypersecretion & peptic ulcers (6:1 duodenum to stomach)
Diarrhea tumor can be in the duodenum |
|
|
How do gastrinomas behave?
|
More than 50% invaded and metastasized by diagnosis
|
