Clinical Associations and Pathoma Endocrine Flashcards
1
Q
Psammoma Bodies: what do they indicate?
A
histological evidence of calcified papillations; found in cancers:
- Papillary carcinoma of thyroid
- Serous cystadenocarcinoma of ovary/serous endometrial carcinoma
- Meningioma
- Mesothelioma
2
Q
Cherry red appearance of skin
A
Carbon Monoxide poisoning
3
Q
Chocolate colored blood
A
Methemoglobinemia:
Fe2+ normally binds O2 in the blood;
Methemoglobinemia is when lots of blood iron is oxidized to Fe3+ and can’t bind O2 anymore
4
Q
Things that can happen after a viral infection
A
- Subacute (deQuervain) Granulomatous Thyroiditis
-
5
Q
Patient presents with a “hard as wood”, non-tender thyroid with dysphagia or respiratory compromise. What’s the differential?
A
= If the patient is a young female => Reidel fibrosing thyroiditis:
- chronic inflam with extensive fibrosis of thyroid; fibrosis extends to local structures
= If the patient is elderly => anaplastic carcinoma:
- undiff malig tumor of thyroid; very poor prognosis; invades local structures leading to dysphagia or resp compromise
6
Q
patient presents with a tender thyroid and transient symptoms of hyperthyroid (hypocholesterolemia, hyperglycemia, tachycard, wt loss with incr apetite, heat intolerance, arrhythmia [elderly], tremor/anxiety, oligomenorrhea, diarrhea with malabs, staring gaze, decreased muscle mass, bone resorption w/ hypercalcemia)
A
Think: subacute (deQuervain) Granulomatous Thyroiditis
- after viral infection
- self-limited; will not progress to hypothyroid
7
Q
what are the symptoms of hyperthyroid?
A
- hypocholesterolemia
- hyperglycemia
- tachycard (w/ incr CO)
- wt loss with incr apetite
- heat intolerance
- arrhythmia [elderly]
- tremor/anxiety
- oligomenorrhea
- diarrhea with malabs
- staring gaze
- decreased muscle mass
- bone resorption w/ hypercalcemia
8
Q
what are the symptoms of hypothyroid?
A
- wt gain with normal appetite
- slow mental activity
- muscle weakness
- cold intol w/ decr sweat
- bradycardia (w/ decr CO)
- oligomenorrhea
- hypercholesterolemia
- constipation
9
Q
patient presents with an anterior neck mass distinct from the thyroid, what could it be?
A
think: Thyroglossal duct cyst
- cystic dilation of thyroglossal duct remnant
10
Q
patient presents with a mass at the base of the tongue, what could it be?
A
think: Lingual thyroid
- thyroid tissue persists at the base of the tongue (recall embryological development)
11
Q
hypothyroid in infant/neonate: what is it, what’s the presentation, and what are causes?
A
think: Cretinism = presents with - mental retardation - short stature/skeletal abnorm - coarse face - big tongue - umbilical hernia = caused by: - maternal hypothyroid early on in pregnancy - thyroid agenesis - dyshormonogenic goiter (can't make thyroid hormone, often due to deficiency of peroxidase enzyme) - iodine deficiency
12
Q
what is it called when you can’t make thyroid hormone?
A
dyshormonogenic goiter:
- can’t make thyroid hormone, often due to deficiency of peroxidase enzyme
13
Q
What does thyroid peroxidase do?
A
- Oxidizes iodide to I or I+
- Organification: incorporates iodine into thyroglobulin molecule
- Coupling of diiodotyrosine and monoiodotyrosine to make T3 and T4
14
Q
female presents with symptoms of hyperthyroid, diffuse goiter, exophthalmos, and pretibial myxedema. What is it?
A
Graves disease:
- IgG Ab stimulation of TSH Recept
- incr synthesis and release of thyroid hormone
- often seen in women of childbearing age
- most common cause of hyperthyroid
Labs:
- incr total and free T4; decr TSH, hypocholesterol, hyperglycemia
Tx:
- beta-blockers, Thioamide (block peroxidase), or radioiodine ablation
Feared complication: Thyroid storm
15
Q
Patient with graves disease presents with arrhythmia, hyperthermia, vomiting, and hypovolemic shock, what is it?
A
Thyroid storm:
- increased catecholamines and hormone excess
Tx:
- PTU (peroxidase inhib AND inhib peripheral conversion of T4->T3)
- beta-blockers
- steroids
16
Q
What is the mechanism of incr basal metabolic rate and sympathetic nervous system in hyperthyroid?
A
BMR -> from increased expression of Na/K ATPase
symp NS -> from incr production of beta1-adrenergic receptor
17
Q
Multinodular goiter
A
- most commonly from iodine deficiency
- usually non-toxic
- toxic goiter: TSH- independent regions
18
Q
hypothyroid in an older child or adult: what is it, what’s the presentation, what are the causes?
A
Myxedema
- features caused by glycosaminoglycans (GAGs) in connective tissue like skin, tongue, and larynx (leading to a deep voice)
causes:
- iodine deficiency (world)
- Hashimoto thyroiditis (developed world)
- drugs (Lithium)
- surgery/radioiodine ablation
19
Q
patient initially presents with hyperthyroid before progressing to hypothyroid with decreased T4 and increased TSH;
what is it an which antibodies will be present?
A
Hashimoto thyroiditis
- autoimmune destruction of thyroid; mediated by HLA-DR5
- antithyroglobin and antimicrosomal antibodies will be present
- increased risk of B-cell lymphoma (marginal zone lymphoma from B-cells in marginal zone)
20
Q
Microscopic examination of thyroid tissue shows chronic inflammation, germinal centers, and Hurthle cells; what is it?
A
Hashimoto thyroiditis
- Hurthle cells have more pink cytoplasm
21
Q
What are the types of thyroid cancer, how is cancer distinguished from other abnormal thyroid tissue?
A
- more likely benign than malignant
- distinguish thyroid CA with radioactive 131I uptake study: there will be increased uptake in Graves of nodular goiter, decreased uptake in adenoma or carcinoma (do FNA biopsy)
- Follicular adenoma (benign)
- carcinoma:
Papillary (80%; good prog)
Follicular (malig; FNA cannot distinguish from follic adenocarc)
Medullary (malig; C cells; Familial: MEN 2A/B)
Anaplastic (malig; elderly; poor prognosis)
22
Q
thyroid follicles surrounded by a dense capsule on microscopy
A
Follicular adenocarcinoma
- benign prolif of follicles (surrounded by fib capsule)
- non-functional; rare secretion of thyroid hormone
23
Q
thyroid on microscopy show orphan annie-eyed nuclei on some cells and a nuclear groove on others, calcifications are noted; what is it?
A
Papillary carcinoma of thyroid
- most common thyroid cancer (80%)
- major risk of development is radiation in childhood (acne tx)
- calcifications on micro are psammoma bodies
- good prognosis, even with spread to cervical lymph nodes
24
Q
What are the four types of carcinoma that tend to spread hematogenously
A
- Renal cell carcinoma -> renal vein
- Hepatocellular carcinoma -> hep vein
- choriocarcinoma
- follicular carcinoma of thyroid
Other carcinomas tend to have lymphatic spread
25
malignant proliferation of thyroid follicular cells; what is it?
Follicular carcinoma
- surrounded by fibrous capsule, but invades through capsule
- FNA CANNOT distinguish follicular carcinoma from adenoma
- hematogenous spread
26
microscopic examination of thyroid FNA shows malignant cells within amyloid stroma; what is it?
Medullary carcinoma of the thyroid
- malignant prolif of C cells;
- hi calcitonin -> hypocalcemia
- calcitonin deposits as amyloid within tumor
- Familial: MEN 2A/B
- assoc with mutation in RET oncogene -> prophylactic thyroidectomy
- 2A: medul carc of thyroid, pheochomocytoma, parathyroid adenoma
- 2B: medul carc of thyroid, pheochomocytoma, ganglion neuroma (esp of oral mucosa)
27
Female presents with galactorrhea and amenorrhea, what might cause this?
Think: prolactinoma (functional tumor of anterior pituitary)
- most common tumor of ant pit
- prolactin inhibits GnRH
- tx: Bromocriptine (DA agonist; recall that dopamine antagonizes the action of prolactin)
28
Male presents with decreased libido and headache, which might cause this?
Think: prolactinoma (functional tumor of anterior pituitary)
- most common tumor of ant pit
- prolactin inhibits GnRH
- tx: Bromocriptine (DA agonist; recall that dopamine antagonizes the action of prolactin)
29
Patient presents with bitemporal hemianopsia, headache, and/or hypopituitarism, what might cause these symptoms
Consider: mass effect - anterior pituitary tumor (could be functional or not)
30
A child presents with gigantism, what might cause this?
Pituitary adenoma of growth hormone
31
An adult presents with coarse facial features, large hands and feet, what other findins might be present and what is this? How is it diagnosed?
Acromegaly
- can also present with enlarged visceral organs: heart and tongue
- cardiac failure is the most common cause of death
- patients can also present with secondary diabetes (recall: GH inhibits cellular uptake of glucose)
- Dx: elevated GH and IGF-1 (IGF produced by liver is actually responsible for growth);
lack of suppression of GH with oral glucose
- Tx: Octreotide (somatostatin analogue; blocks ant pit response to GHRH);
GH receptor antagonist;
Surgery
32
What types of anterior pituitary tumors may arise and what would they cause?
Prolactinoma (most common)
Growth hormone adenoma -> gigantism/acromegaly
ACTH adenoma -> Cushing
TSH, LH, FSH rare
33
What are some complications of pituitary adenoma?
Mass effect/functional adenoma
| apoplexy: bleeding into pit adenoma -> compress and destroy tissue -> hypothyroid
34
What are some causes of hypopituitarism?
- pituitary adenoma (adult)
- apoplexy: bleeding into pit adenoma -> compress and destroy tissue
- craniopharyngioma (child) -> arrises commonly in region of sella and can compress and destroy pituitary
- Sheehan syndrome (common in preg; pit can double in size then infarct; present with poor lactation lost pubic hair
- Empty sella syndrome
- secondary from trauma
- primary from congenital defect leading to herniation of arachnoid and CSF into sella compressing and destroying pituitary
35
A woman presents post-partum with poor lactation and loss of pubic hair, what might be the cause?
Sheehan syndrome
- pituitary infarct is more likely after pregnancy due to increased size without much increase in vascularization
- presents with symptoms of low FSH/LH
36
Name the hormones of the anterior and posterior pituitary
```
Ant pit:
- FSH
- LH
- ACTH
- TSH
- PRL
- Endorphines
- GH
Post pit:
- Oxytocin: uterine contraction and milk release in response to suckling
- ADH: free water regulation at dist tubule and collecting duct
```
37
Patient presents with polyuria and polydipsia. Broadly, what is the disease and how do you distinguish between causes?
Diabetes mellitus
- Type 1: patient is often young and will have high serum glucose, wt loss, low muscle mass, polyphagia, glycosuria
- Type 2: patient will have hyperglycemia; may otherwise be clinically silent
Diabetes insipidus
- patient will have hypernatremia and hi serum osmolality with low urine osmolality
- Central: water deprivation fails to concentrate urine AND there is a response to Desmopressin (ADH analogue)
- Nephrogenic: water deprivation fails to concentrate urine BUT there is NO response to Desmopressin
38
What is central diabetes insipidus and what might cause the condition?
How will it present?
How do you treat?
- ADH deficiency
- might be caused by HTH or Pit pathology like tumor, trauma, infection, inflammation
- present with polyuria and polydipsia with hypernatremia and hi serum osmolality with low urine osmolality
- Tx: Desmopressin (ADH analogue)
39
What is nephrogenic diabetes insipidus and what might cause the condition?
How will it present?
- impaired renal response to ADH
- caused by inherited mutations or drugs (Lithium, demeclocycline)
- present with polyuria and polydipsia with hypernatremia and hi serum osmolality with low urine osmolality
- NO response to desmopressin
40
What is SIADH and what might cause the condition?
How will it present?
How do you treat?
- excess ADH secretion
- causes include ectopic production (eg. small cell carcinoma), CNS trauma, pulmonary infection (like in pts with COPD), drugs (eg. cyclophosphamide)
- hyponatremia, low serum osmolality, mental status changes, seizures (cerebral edema)
- Tx: free water restriction, Demeclocycline
41
Patient presents with hyponatremia, low serum osmolality, mental status changes, and seizures. What might cause this and what is the mechanism of CNS involvement?
Could be caused by SIADH: inappropriate water retention.
| - CNS involvement is secondary to cerebral edema from the water retention
42
what is the embryological origin of the adrenal gland?
there are two:
- adrenal cortex: mesoderm (posterior abdominal wall)
- adrenal medulla: Neural crest-derived chromaffin cells (ectoderm)
43
What are the layers of the adrenal cortex, what does each layer produce? How are the products of the adrenal cortex synthesized?
- Granulosa: makes mineralocorticoids (Aldosterone); regulate salt balance
- Fasciculata: makes glucocorticoids (cortisol)
- Reticularis: makes sex steroids (androgens)
- mneumonics: GFR; it gets sweeter as you go deeper
- hormones are all synthesized from cholesterol, which is why adrenals are yellow in color
44
A patient presents with truncal obesity, muscle weakness, and buffalo hump. What is it? What other findings may be present? How is diagnosis made?
Cushing syndrome
- may also present with thin extremities, moon face, truncal obesity, abdominal striae, HTN, osteoporosis, and immune suppression
- Dx by elevated 24 hr urine cortisol level
45
What are causes of Cushing?
- exogenous corticosteroids (most common): both adrenals atrophic
- primary adrenal adenoma, hyperplasia, or carcinoma: one adrenal big, one atrophic
- ACTH-secreting pit adenoma: both adrenals enlarged
- paraneoplastic ACTH secretion: both adrenals enlarged
- distinguish the later two causes by administering a high dose dexamethasone test (cortisol analogue) -> suppress ACTH production by pit adenoma (cortisol will decrease too); No change in paraneoplastic ACTH production
46
What are the functions of cortisol?
- raise blood sugar: breaks down muscle for gluconeogenesis (in Cushing: leads to hi serum glucose -> excess insulin -> store fat -> buffalo hump, moon face, truncal obesity; muscle breakdown also leads to muscle weakness)
- impaired collagen synthesis (in Cushing: leads to abdominal striae)
- increased alpha1 receptors on arterioles (to maintain vascular tone; in Cushing: HTN)
- immunosuppression
47
What are the mechanisms of immunosuppression from cortisol?
- inhibit Phospholipase A2 (needed to generate arachidonic acid metabolites for inflammatory response)
- inhibit IL-2 (T-cell growth factor)
- inhibit release of histamine from mast cells (needed for vasodilation and increased vascular permeability)
48
Recall: what parts of the nephron does aldosterone work on? What cells are present? What does Aldo induce the cells to do?
- Aldo acts on the late distal tubule and collecting duct
- Principle cell and alpha intercalated cells are acted upon by Aldo; beta-interc cells also present
- Aldo induces overall salt retention (and thus water retension)
- specifically: sodium absorption, potassium secretion, and hydrogen ion secretion
49
Patient presents with HTN and labs significant for hypernatremia, hypokalemia, and metab. alkalosis. What condition might this be and what might cause it? What specific patient demographics might correspond with certain causes?
Hyperaldosteronism
- excess aldo
- primary Hyperaldo
- most commonly from adrenal adenoma (benign); other causes are hyperplasia and carcinoma
- will have HI Aldo and LOW Renin
- secondary Hyperaldo
- activation of Renin-Angiotensin system (fibromuscular dysplasia -> young woman; atherosclerosis -> elderly male)
- JGA -> Renin
- HI Aldo; HI Renin
50
Patient presents with hyponatremia, hyperkalemia, and hypovolemia with severe hypotension. A female pt has clitoral enlargement; a male pt has precocious puberty. What is it? What are causes? What is the mechanism?
Congenital adrenal hyperplasia
- most common cause is 21-hydroxylase deficiency
- less common are deficiency of 11- and 17-hydroxylase
- in 21: only make sex steroids
- in 11: make sex steroids and mineralocorticoids (No salt wasting!)
- in 17: only make mineralocorticoids (excess!)
- all result in no cortisol -> incr ACTH -> adrenal hyperplasia
- Mech: no cortisol: severe hypotension, incr ACTH -> big adrenals; increased sex steroids: clitoromegaly/precocious puberty; no Aldo: salt wasting, hypovolemia
51
Recall: what is the mechanism of steroid synthesis in the adrenal cortex?
Cholesterol -> pregnenolone
preg [17] -> sex steroids
preg [17] -> [21] -> [11] -> cortisol
preg [21] -> mineralocort (weak) -> [11] -> mineralocort
52
Patient presents as a young child with N. meningitidis infection who becomes hypotensive and weak. What is the cause? What other findings may be present?
Acute adrenal insufficiency
- > Waterhouse-Friderichsen sydrome
- also present with DIC and bilateral necrosis of adrenal glands
- hypovolemia
- vomiting and diarrhea
- labs significant for hyponatremia, hyperkalemia
- hyperpigmentation
53
What is the mechanism of hyperpigmentation is adrenal insufficiency?
POMC (ACTH precursor molecule) also makes MSH (melanocyte stimulating hormone)
- ACTH is overactive in an attempt to force adrenal production of cortisol; MSH will also be produced and lead to hyperpig
- especially on oral mucosa and skin
54
Patient presents with hypotension, hypovolemia, weakness, hyperpigmentation, vomiting and diarrhea. What is it? What are causes? What will lab values be significant for?
Adrenal insufficiency
- chronic presentation is due to progressive destruction of adrenals
- causes:
- autoimmune adrenalitis: destruction of adrenals (Addison's; most common in West)
- TB (most common in developing world)
- metastatic carcinoma to both adrenals (think: from lung)
- labs will be significant for hyponatremia and hyperkalemia (due to insufficient mineralocorticoids)
55
What is produced by the adrenal medulla?
Epinephrine and Norepi
56
What is the main pathology associated with the adrenal medulla?
Pheochromocytoma
| recall: rule of 10
57
Gross exam of adrenal medulla presents with a large brown mass, what is it likely to be?
Pheochromocytoma
58
Patient presents with episodic HTN, headache, palpitations, tachycardia, and sweating. What might cause these symptoms? How is this condition diagnosed? What is the treatment?
Pheochromocytoma
- Dx: increased serum metanephrines, increased 24 hour urine metanephrine and VMA
- Tx: surgical excision
* * recall: before tumor removal, must administer phenoxybenzamine: irreversible blockade of alpha receptors -> prevents accidental massive release of Epi/NE during surgery leading to malig HTN
59
recall: what is the biochemical breakdown of Epi and NE?
Epi -> metanephrines -> VMA
NE -> normetanephrines -> VMA
- clinically useful in diagnosis of pheochromocytoma, which will present with increased Epi/NE metabolites in serum and urine
60
What is the rule of 10 for pheochromocytoma?
10% bilateral
10% familial
10% malignant
10% located extra-adrenally (think: bladder wall; episodic HTN with urination)
61
What are associated conditions with Pheochromocytoma and what are complications of those conditions?
- MEN 2A: medullary carcinoma of thyroid, pheo, parathyroid adenoma
- MEN 2B: med carc of thyroid, pheo, mucosal ganglioneuroma (often of oral mucosa)
- MEN 2A/B: med carc of thyroid is killer -> prophylactic thyroid removal with RET mutation
- Von Hippel-Lindau disease (VHL): AD loss of VHL tumor suppressor gene; incr risk of hemangioblastoma of cerebellum, renal cell carc, and pheo
- NF type 1
62
What is constellation of symptoms in MEN 1, 2A, and 2B
- MEN 1: 3Ps: parathyroid hyperplasia, pituitary adenoma, and pancreas endocrine tumor
- MEN 2A: med carc of thyroid, pheo, parathyroid adenoma
- MEN 2B: med carc of thyroid, pheo, mucosal ganglioneuroma (often oral mucosa)
63
Von Hippel-Lindau disease increases risk for what cancer? What is the mechanism?
- AD loss of VHL tumor suppressor gene
- increased risk of
- hemangioblastoma of cerebellum
- renal cell carc
- pheo
64
What is Lynch syndrome?
aka Hereditary nonpolyposis colorectal cancer (HNPCC)
- associated cancers: colon, ovary, endometrium, stomach, small intestine
- Amsterdam criteria for screening:
- 3 family members
- 2 generations
- 1 HNPCC cancer dx under age 50
- FAP ruled out
- Dx with genetic testing
65
Parathyroid. recall: what is the main cell, what does it produce, and what does it regulate?
Chief cell produces PTH (parathyroid hormone)
| - PTH regulates serum free (ionized) Calcium (as opposed to that bound by albumin or phosphate)
66
What are the actions of PTH?
- increased activity of osteoclast (actually activate osteoblast -> activates osteoclast): resorbs bone; incr serum Ca and Phos
- increase small bowel absorption of Ca and Phos (thru vitamin D)
- increase renal Ca reabs AND DECREASE renal phosphate reabs (dump phosphate! ** important for regulating free calcium as opposed to that bound to phosphate)
67
patient presents with lab findings significant for
Hi PTH
Hi serum Calcium
Low serum phosphate
What will other lab findings be and why? What is the condition? What causes it? What are symtoms and mechanisms? what is treatment?
Primary Hyperparathyroid
- excess PTH production from parathyroid pathology
- caused by adenoma (80%), hyperplasia, or carcinoma
- Parathyroid adenoma is a benign neoplasm -> usually of 1 gland
- usually asymptomatic, but if symptoms present, may include:
- nephrolithiasis (Ca oxalate stones)
- nephrocalcinosis (metastatic calcification in kidney tubules -> renal insufficiency with polyuria)
- CNS disturbances (depression, seizures)
- constipation, PUD, and acute pancreatitis (recall: Ca activates panc enzymes -> autodigestion of pancreas)
- osteitis fibrosa cystica (bone resoprtion)
- other lab findings will include
- increased urinary cAMP (activated by PTH action on tubule cells -> Gstim -> AC -> cAMP -> mediate effects of PTH)
- increased serum alk phos (from increased osteoblast activity; alkaline environment necessary to calcify bone)
- treatment is surgical resection
68
Patient presents with lab findings significant for
Hi PTH
Low serum Calcium
High serum phosphate
increased alkaline phosphatase
What is the condition? What causes it? What are symtoms and mechanisms?
Secondary hyperparathyroid
- excess PTH production from disease outside parathyroid
- most common cause is chronic renal failure: decreased phosphate secretion -> incr serum phos -> binds free Ca -> decr free Ca -> stim all 4 parathyroid glands -> incr PTH -> bone resorp
69
Patient presents with numbness and tingling, especially in the peri-oral area, muscle cramps, and has lab values significant for
Low PTH
Low serum Calcium
What is the condition? What are causes?
Hypoparathyroid
- low PTH
- caused by autoimmune disease, surgical excision, and DiGeorge syndrome (failed development of 3rd and 4th pharyngeal pouches)
70
If you suspect a patient has hypoparathyroid, what are some signs that you would test for? How are the signs elicited?
- Chvostek sign: tap on facial nerve (parotid gland) -> facial muscles will spasm
- Trousseau sign: inflate BP cuff on patient's arm greater than systolic for 3 min -> arm spasm will occur
71
Patient presents with labs significant for
Lo Calcium
Hi PTH
What is the condition? What is the cause?
Pseudohypoparathyroidism
- end-organ resistance to PTH (due to defect of Gstim protein)
- Lo Ca with Hi PTH could also be secondary hyperparathyroid, but this is more likely in the setting of a cause like renal insufficiency
- Gstim mutation is Autosomal Dominant and associated with short stature and short 4th and 5th digits
72
What is the composition of the endocrine pancreas? What do insulin and glucagon do?
- alpha cells -> glucagon
- beta cells -> insulin ** Center of the islet
- delta cells -> somatostatin
- PP cells -> pancreatic polypeptide
- insulin is anabolic; it increases GLUT4 receptors on skeletal muscle and adipose tissue
- increases synthesis of lipids, glycogen, and protein
- decreases blood sugar
- drives potassium into cells (anabolism)
- glucagon is catabolic
- increases blood sugar: glycolysis, lipolysis
73
What is the pathophysiology of type 1 Diabetes Mellitus? What's treatment?
- overall insuling deficiency leading to metabolic disorder with hyperglycemia
- type IV hypersensitivity reaction
- T lymphocytes destroy beta cells
- will have inflammation of islets
- assoc with HLA-DR3/4
- autoantibodies against insulin
- Tx is life-long insulin
74
Patient presents with a high anion gap metabolic acidosis and severe hyperglycemia. What is the condition? What are causes? What other symptoms and labs might the patient present with? What is the treatment?
DKA (feared complication of type 1 DM)
- hyperglycemia > 300 mg/dL
- increased serum ketoacids
- provoked by stress (eg. infection) -> Epi -> incr glucagon -> lipolysis -> incr FFA -> ketone bodies (liver): beta-hydroxybuteric acid, acetoacetic acid
- can also present with Kussmal respirations, dehydration, N/V, mental status changes and fruity breath
- labs will be significant for hyperkalemia
1) insulin is not present to drive K into cells
2) acidosis is buffered by exchanging potassium in cells for hydrogen ions outside cells
- there is a high serum potassium, but overall loss of K thru urine
- Tx: fluids, insulin, electrolytes (potassium!)
75
What is anion gap? What defines a normal anion gap? What defines metabolic acidosis? What is the differential dx for a patient with high anion gap metabolic acidosis?
- anion gap is [Na] - [Cl] - [HCO3]
- this is a measurement of how many more unmeasured anions are in serum than unmeasured cations
- normal anion gap is 3-11 mEq/L (high is >11)
- met acidosis is serum pH < 7.4 (or < 7.35) with Low HCO3 and normal/normally decreased pCO2
Diff dx: MUDPILES
- Methanol
- Uremia
- DKA
- Propylene glycol
- Isoniazid
- Lactic acidosis
- Ethylene glycol
- Salicylates
76
What is the pathophysiology of type 2 Diabetes Mellitus? What's diagnosis and treatment?
- end-organ resistance to insulin -> metabolic disorder -> hyperglycemia
- most common type of Diabetes
- classic demographic is a middle-aged, obese adult
- obesity -> decr # insulin receptors
- genetic predisposition (more than type 1 DM)
- increase insulin early in disease -> decr insulin later from beta-cell exhaution
- amyloid in islet cells
- Dx: fasting glucose > 126
- casual glucose > 200
- gluc tol test > 200 after 2 hours
- Tx: wt loss (diet, exercise)
- drug therapy
- insulin
77
Patient presents with obesity, severe hyperglycemia, and severe hypotension. What is the condition? What are causes? What other findings may be present?
Hyperosmolar non-ketotic coma (feared complication of type 2 DM)
- serum glucose > 500 mg/dL
- > leads to life-threatening diuresis
- hypotension can progress to coma
- NO ketones (some circulating insulin prevents ketone formation)
78
What are the two major mechanism by which complications in diabetes arrise?
1) non-enzymatic glycosylation of vascular BM
- NEG of large/medium vessels -> atherosclerosis
- cardiovascular disease (leading cause of death)
- peripheral vascular disease (leading cause of non-traumatic amputation)
- NEG of small vessels -> hyaline arteriolosclerosis (think: kidney)
- preferential efferent involvement -> incr glom pressure -> hyperfilt injury -> microalbuminemia
- mesangial sclerosis -> Kimmelstiel-Wilson nodules
- > ** Nephrotic Syndrome!
- afferent involvement -> decr glom blood supply -> diffuse sclerosis -> chronic renal failure
- NEG of hemoglobin -> HbA1c
2) osmotic damage
- schwann cells: take up sugar without insulin
- Aldose reductase converts glucose to sorbitol -> osmotic damage to cells
- > ** peripheral neuropathy
- pericytes of retinal blood vessels: glucose uptake -> sorbitol -> osmotic dmg -> cell death -> weakened vessel wall -> aneurysm -> rupture -> hemorrhage -> blindness
- > ** diabetic retinopathy
- lens: gluc -> sorbitol -> dmg
- > ** cataracts
79
Recall: what are the main pancreatic endocrine tumors? What are they most likely associated with?
```
Tumors of islet cells:
- Insulinoma
- Gastrinoma
- Somatostatinoma
- VIPoma
Often associated with MEN 1 (along with parathyroid hyperplasia and pituitary adenoma)
```
80
Patient presents with episodic hypotension and mental status changes that are relieved by eating. What is this? What lab values will be present?
Insulinoma
- decr glucose
- incr insulin
- incr C-peptide (produced with insulin -> indicates that high insulin is endogenous)
81
Patient presents with peptic ulcer disease that is resistant to treatment. What is it? what is pathophysiology?
Zollinger-Ellison syndrome (Gastrinoma)
- recall: gastrin secreted by G-cells -> stimulates parietal cells to release acid
- may be multiple and extend to jejunum
82
patient presents with low stomach acid, cholelithiasis, and steatorrhea. What is it? what is pathophysiology?
Somatostatinoma
- recall:
- inhibits gastrin -> achlorhydria (low stomach acid)
- inhibits CCK -> steatorrhea and incr risk of cholelithiasis
83
patient presents with watery diarrhea, hypokalemia and low stomach acid. What is it? What is the pathophysiology?
VIPoma
- excess vasoactive intestinal peptide
- low stomach acid = achlorhydria
84
What are some conditions of the adrenal glands?
```
Medulla: pheochromocytoma
Cortex:
- Cushing
- Hyperaldosteronism
- primary (adenoma: Conn syndrome)
- secondary (eg. fibromuscular dysplasia, atherosclerosis)
- Congenital adrenal hyperplasia
- 21-hydroxylase (11, 17)
- Adrenal insufficiency
- acute (Waterhouse-Friderichsen)
- chronic (Addison's, TB, mets)
```
85
What are some conditions of the pituitary?
```
Anterior:
- Adenoma
- functional vs. mass effect
- prolactinoma
- GH
- Hypopituitarism
Posterior:
- Diabetes insipidus
- central
- nephrogenic
- SIADH
```
86
What are some issues of the thyroid?
- Lingual thyroid
- Thyroglossal duct cyst
- Hyperthyroid
- Graves (thyroid storm)
- Multinodular goiter
- Hypothyroid
- cretinism
- myxedema
- Thyroiditis
- Hashimoto
- subacute DeQuervain Granulomatous Thyroiditis
- Reidel fibrosing thyroiditis
- Thyroid neoplasia
- Adenoma: follicular
- Carcinoma: papillary, follicular, medullary, anaplastic
87
What are some issues of the parathyroid?
- Primary hyperparathyroid
- Secondary hyperparathyroid
- Hypoparathyroid
- Pseudohypoparathyroid
88
What are some issues of the endocrine pancreas?
- Type 1 DM
- DKA
- Type 2 DM
- Hyperosmolar non-ketotic coma
- Pancreatic endocrine tumors
- Insulinoma
- Gastrinoma (Zollinger-Ellison syndrome)
- Somatostatinoma
- VIPoma
