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244 Cards in this Set
- Front
- Back
What can cause Cushing syndrome? |
Excess cortisol due to a variety of causes:
- Exogenous steroids - Primary adrenal adenoma, hyperplasia, or carcinoma - ACTH-secreting pituitary adenoma |
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What is the number one cause of Cushing syndrome? Characteristics?
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Exogenous corticosteroids: results in ↓ ACTH and bilateral adrenal atrophy
|
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What causes of Cushing syndrome result in ↓ ACTH? Effect on adrenals?
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- Exogenous steroids - bilateral adrenal atrophy
- Primary adrenal adenoma, hyperplasia, or carcinoma - atrophy of uninvolved adrenal gland |
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What can primary adrenal adenoma / hyperplasia / carcinoma produce?
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- ↑ Cortisol (= Cushing Syndrome)
OR - ↑ Aldosterone (1° Aldosteronism = Conn Syndrome) |
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What is Conn Syndrome?
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1° Aldosteronism (due to primary adrenal adenoma, hyperplasia, or carcinoma)
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What causes of Cushing syndrome result in ↑ ACTH? Effect on adrenals?
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ACTH-secreting pituitary adenoma (Cushing disease)
- Paraneoplastic ACTH secretion: small cell lung cancer, bronchial carcinoids - Bilateral adrenal hyperplasia |
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What is responsible for the majority of the endogenous cases of Cushing Syndrome?
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Cushing Disease
- ACTH-secreting pituitary adenoma - Paraneoplastic ACTH secretion: small cell lung cancer, bronchial carcinoids |
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What are the findings associated with Cushing Syndrome?
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- Hypertension
- Weight gain - Moon facies - Truncal obesity - Buffalo hump - Hyperglycemia (insulin resistance) - Skin changes (thinning, striae) - Osteoporosis - Amenorrhea - Immune suppression |
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How do you screen for Cushing Syndrome?
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** Measure serum ACTH **
You can also evaluate: - ↑ Free cortisol on 24-hr urinalysis - Midnight salivary cortisol - Overnight low-dose dexamethasone suppression test (measure serum ACTH) |
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What should you suspect / do if a patient you suspect of having Cushing Syndrome has a low ACTH (<5 pg/mL)?
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Suspect ACTH-independent Cushing Syndrome (primary adrenal adenoma, hyperplasia, or carcinoma)
* Order MRI to confirm adrenal tumor |
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What should you suspect / do if a patient you suspect of having Cushing Syndrome has a high ACTH (>20 pg/mL)?
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Suspect ACTH-dependent Cushing Syndrome
* Order high-dose dexamethasone suppression test * Order CRH stimulation test |
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What diagnosis does a patient you suspect of having Cushing Syndrome, with an elevated ACTH, and adequate suppression via high-dose dexamethasone suppression test?
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Cushing Disease (ACTH-secreting pituitary adenoma)
|
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What diagnosis does a patient you suspect of having Cushing Syndrome, with an elevated ACTH, and no suppression via high-dose dexamethasone suppression test?
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Ectopic ACTH secretion (paraneoplastic syndrome: small cell lung cancer or bronchial carcinoids)
- Ectopic secretion will not decrease with dexamethasone because the source is resistant to negative feedback |
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What diagnosis does a patient you suspect of having Cushing Syndrome, with an elevated ACTH, and after after a CRH stimulation test there was ↑ ACTH and cortisol?
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Cushing Disease (ACTH-secreting pituitary adenoma)
|
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What diagnosis does a patient you suspect of having Cushing Syndrome, with an elevated ACTH, and after after a CRH stimulation test there was no increase in ACTH and cortisol?
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Ectopic ACTH secretion
- Ectopic secretion will not increase with CRH because pituitary ACTH is suppressed |
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What are the causes of primary hyperaldosteronism?
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- Adrenal hyperplasia
- Aldosterone secreting adrenal adenoma (Conn syndrome) (May be unilateral or bilateral) |
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What are the consequences of adrenal hyperplasia or aldosterone-secreting adrenal adenoma?
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Primary Hyperaldosteronism:
- Hypertension - Hypokalemia - Metabolic alkalosis - Low plasma renin - Normal Na+ due to aldosterone escape → no edema |
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How do you treat primary hyperaldosteronism?
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Surgery to remove the tumor and/or spironolactone (K+ sparing diuretic that acts as an aldosterone antagonist)
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What are the causes of secondary hyperaldosteronism?
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- Renal artery stenosis
- Congestive Heart Failure - Cirrhosis - Nephrotic Syndrome |
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What are the consequences of renal artery stenosis, CHF, cirrhosis, or nephrotic syndrome?
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Secondary Hyperaldosteronism
- Renal perception of low intravascular volume → over-active renin-angiotensin system - Associated with high plasma renin |
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How do you treat secondary hyperaldosteronism?
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Spironolactone (K+ sparing diuretic that acts as an aldosterone antagonist)
|
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What form of hyperaldosteronism is associated with a high plasma renin?
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Secondary Hyperaldosteronism
- In primary, there is negative feedback to decrease renin - In secondary, the high renin is what is causing the high aldosterone |
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What are the causes of primary adrenal insufficiency?
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Addison Disease - CHRONIC process
- Atrophy of adrenals - Destruction by disease: auto-immune, TB, metastasis Waterhouse-Friderichsen Syndrome - ACUTE process - Adrenal hemorrhage associated with Neisseria meningitidis, septicemia, DIC, and endotoxic shock |
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What are the implications of Addison Disease?
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- Deficiency of aldosterone and cortisol
- Hypotension (hyponatremic volume contraction) - Hyperkalemia - Acidosis - Skin and mucosal hyperpigmentation |
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What causes the skin hyperpigmentation in Addison Disease?
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MSH (melanocyte stimulating hormone): by-product of ↑ ACTH production from pro-opiomelanocortin (POMC)
|
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How is Addison Disease characterized?
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- Adrenal Atrophy
- Absence of hormone production, involving all three cortical divisions (but spares medulla) |
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How do you distinguish primary adrenal insufficiency from secondary?
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Secondary adrenal insufficiency would have:
- ↓ Pituitary ACTH production - No skin/mucosal hyperpigmentation - No hyperkalemia |
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What are the electrolyte and acid/base balance changes in primary adrenal insufficiency?
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- Hyponatremia
- Hyperkalemia - Acidosis |
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What is the name of the syndrome causing ACUTE 1° adrenal insufficiency? Cause?
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Waterhouse-Friderichsen Syndrome
- Adrenal hemorrhage associated with Neisseria meningitidis septicemia, DIC, and endotoxic shock |
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What is the most common tumor of the adrenal medulla in children? When specifically?
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Neuroblastoma
- Usually <4 years old |
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What is the origin of a neuroblastoma?
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Neural crest cells
|
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Where can a neuroblastoma appear?
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Occurs anywhere along the sympathetic chain
|
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What is the most common presentation of Neuroblastoma?
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- Abdominal distension
- Firm, irregular mass that can CROSS THE MIDLINE - Usually in children < 4 years old - Less likely to develop hypertension |
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When you have a firm, irregular mass that crosses the midline of a young child, what diagnosis should you think of?
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Neuroblastoma
|
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When you have a smooth mass that does not cross the midline of a young child, what diagnosis should you think of?
|
Wilms tumor (nephroblastoma)
- Most common renal malignancy of early childhood (ages 2-4) |
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What lab studies are associated with a Neuroblastoma?
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- Homovanillic acid (HVA), a breakdown product of dopamine, is increased in urine
- Bombesin (+) - LM: rosettes (arrow) and classic small, round, blue/purple nuclei |
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What genetic change is associated with Neuroblastoma?
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Over-expression of the N-myc oncogene
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What is the most common tumor of the adrenal medulla in adults?
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Pheochromocytoma
|
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What is a pheochromocytoma derived from?
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Chromaffin cells (arise from neural crest)
|
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What rule can you use to remember characteristics of a pheochromocytoma?
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Rule of 10s:
- 10% malignant - 10% bilateral - 10% extra-adrenal - 10% calcify - 10% in kids |
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What does a pheochromocytoma do?
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Most tumors secrete epinephrine, norepinephrine, and dopamine → episodic hypertension
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What genetic change is pheochromocytoma associated with?
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- Von Hippel-Lindau disease
- MEN 2A - MEN 2B |
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What symptoms are typical of pheochromocytoma?
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Symptoms occur in "spells" - relapse and remit:
Episodic hyperadrenergic symptoms (5 P's): - Pressure (↑ BP) - Pain (headache) - Perspiration - Palpitations (tachycardia) - Pallor |
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What are the lab findings associated with a pheochromocytoma?
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- ↑ Urinary VMA (breakdown product of NE and Epi)
- ↑ Plasma catecholamines (NE, Epi, etc) |
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How do you treat pheochromocytoma?
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1. Irreversible α-antagonist (phenoxybenzamine)
2. β-blockers 3. Tumor resection ** α-blockade must be achieved before giving β-blockers to avoid a hypertensive crisis ** |
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For what diagnosis must you treat the patient first with α-antagonists before β-blockers? Why?
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For treatment of Pheochromocytoma:
This is necessary to avoid a hypertensive crisis |
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What are the characteristic signs / symptoms of hypothyroidism?
|
- Cold intolerance (↓ heat production)
- Weight gain, ↓ appetite - Hypoactivity, lethargy, fatigue, weakness - Constipation - ↓ Reflexes - Myxedema (facial / periorbital) - Dry, cool skin with coarse, brittle hair - Bradycardia, dyspnea on exertion |
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What are the characteristic signs / symptoms of hyperthyroidism?
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- Heat intolerance (↑ heat production)
- Weight loss, ↑ appetite - Hyperactivity - Diarrhea - ↑ Reflexes - Pretibial myxedema (Graves disease), periorbital edema - Warm, moist skin with fine hair - Chest pain, palpitations, arrhythmias, ↑ number and sensitivity of β-adrenergic receptors |
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How do patients with hypothyroidism vs hyperthyroidism compare in terms of their bowel habits?
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- Hypothyroidism: constipation
- Hyperthyroidism: diarrhea |
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How do patients with hypothyroidism vs hyperthyroidism compare in terms of their reflexes?
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- Hypothyroidism: decreased reflexes
- Hyperthyroidism: increased reflexes |
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How do patients with hypothyroidism vs hyperthyroidism compare in terms of myxedema (swelling of the skin and underlying tissues giving a waxy consistency)?
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- Hypothyroidism: facial and periorbital myxedema
- Hyperthyroidism: pretibial myxedema (Graves disease), periorbital edema |
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How do patients with hypothyroidism vs hyperthyroidism compare in terms of their skin and hair?
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- Hypothyroidism: dry, cool skin with coarse, brittle hair
- Hyperthyroidism: warm, moist skin with fine hair |
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How do patients with hypothyroidism vs hyperthyroidism compare in terms of cardiac symptoms?
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- Hypothyroidism: bradycardia and dyspnea on exertion
- Hyperthyroidism: chest pain, palpitations, arrhythmias, ↑ number and sensitivity of β-adrenergic receptors |
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Why do patients with hyperthyroidism sometimes have chest pain, palpitations, and arrhythmias?
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↑ number and sensitivity of β-adrenergic receptors
|
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What are the lab findings associated with hypothyroidism?
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- ↑ TSH (sensitive for 1° hypothyroidism)
- ↓ free T3 and T4 - Hypercholesterolemia (due to ↓ LDL receptor expression) |
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What are the lab findings associated with hyperthyroidism?
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- ↓ TSH (if 1°)
- ↑ free or total T3 and T4 - Hypocholesterolemia (due to ↑ LDL receptor expression) |
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How do thyroid disorders affect cholesterol? Mechanism?
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- Hypothyroidism: hypercholesterolemia due to ↓ LDL receptor expression
- Hyperthyroidism: hypocholesterolemia due to ↑ LDL receptor expression |
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What is the most common cause of hypothyroidism in iodine-sufficient regions?
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Hashimoto Thyroiditis
|
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What causes Hashimoto Thyroiditis?
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Auto-immune disorder
- Anti-thyroid peroxidase and anti-thyroglobulin antibodies - Associated with HLA-DR5 |
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What is there increased risk of in patients with Hashimoto Thyroiditis?
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Non-Hodgkin Lymphoma
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What may be an early, contradictory finding seen in patients with Hashimoto Thyroiditis?
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May be hyperthyroid early in course due to thyrotoxicosis during follicular rupture
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What are the histologic findings of Hashimoto Thyroiditis?
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Hürthle cells, lymphoid aggregate with germinal centers
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What does this histology indicate?
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Hürthle cells, lymphoid aggregate with germinal centers → Hashimoto Thyroiditis
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What are the expected thyroid findings on physical exam in a patient with Hashimoto Thyroiditis?
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Moderately enlarged, non-tender
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The presence of Hürthle cells should make you think of what?
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Hashimoto Thyroiditis
|
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What can cause severe fetal hypothyroidism (congenital hypothyroidism)?
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- Maternal hypothyroidism
- Thyroid agenesis - Thyroid dysgenesis (most common cause in US) - Iodine deficiency - Dyshormonogenic goiter |
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What are the findings of a patient with congenital hypothyroidism?
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6 P's:
- Pot-bellied - Pale - Puffy-faced child - Protruding umbilicus - Protuberant tongue - Poor brain development |
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What is cretinism?
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Congenital hypothyroidism
|
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What is the most common cause of congenital hypothyroidism in the US?
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Thyroid Dysgenesis
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What is wrong with the child on the left (before) and after treatment on the right?
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Congenital hypothyroidism
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What is the term for the self-limited hypothyroidism often following a flu-like illness?
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Subacute Thyroiditis (de Quervain)
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What happens in Subacute Thyroiditis (de Quervain)?
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- May be hyperthyroid early in course
- Self-limited hypothyroidism often following a flu-like illness |
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What is the appearance of the thyroid histologically in Subacute Thyroiditis (de Quervain)?
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Granulomatous inflammation
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What cause of hypothyroidism is associated with a very tender / painful thyroid?
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Subacute Thyroiditis (de Quervain)
*de QuerVAIN is associated with PAIN* |
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What are the findings in Subacute Thyroiditis (de Quervain)?
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- ↑ ESR
- Jaw pain - Early inflammation - Very tender thyroid - Granulomatous inflammation of thyroid |
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What causes granulomatous inflammation of the thyroid?
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Subacute Thyroiditis (de Quervain)
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What disease causes the thyroid to be replaced with fibrous tissue? What does this cause?
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Riedel Thyroiditis - causes hypothyroidism
|
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What happens in Riedel Thyroiditis?
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- Thyroid replaced by fibrous tissue (hypothyroid)
- Fibrosis may extend to local structures (eg, airway), mimicking anaplastic carcinoma |
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What is Riedel Thyroiditis considered a manifestatoin of?
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Manifestation of IgG4-related systemic disease
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What are the findings of a patient's thyroid in Riedel Thyroiditis on physical exam?
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- Fixed
- Hard (rock-like) - Painless goiter |
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What are some other causes of hypothyroidism?
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- Iodine deficiency
- Goitrogens - Wolff-Chaikoff effect - Painless thyroiditis |
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What are the causes of hyperthyroidism?
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- Toxic multinodular goiter
- Graves disease - Thyroid storm |
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What pathology is associated with focal patches of hyper-functioning follicular cells that work independently of TSH due to a mutation in the TSH receptor?
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Toxic Multinodular Goiter
|
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What is wrong in Toxic Multinodular Goiter?
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- Focal patches of hyper-functioning follicular cells
- Work independently of TSH due to mutation in TSH receptor - ↑ Release of T3 and T4 |
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What does this histologic image of the thyroid show?
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Toxic Multinodular Goiter
- Follicles of various sizes distended with colloid (black arrows) - Follicles are lined by flattened epithelium with areas of fibrosis and hemorrhage (blue arrows) - Nodules are rarely malignant |
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What is the term for thyrotoxicosis when a patient with iodine deficiency suddenly is made iodine replete?
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Jod-Basedow Phenomenon
|
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What happens in the Jod-Basedow Phenomenon?
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Thyrotoxicosis if a patient with iodine deficiency goiter is made iodine replete
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What is the most common cause of hyperthyroidism?
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Graves disease
|
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What is the underlying pathophysiology responsible for Graves disease?
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Auto-antibodies (IgG) stimulate TSH receptors on thyroid, retro-orbital fibroblasts, and dermal fibroblasts
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What kind of antibodies are associated with Graves disease? Hashimoto Thyroiditis?
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- Graves disease: IgG auto-Abs that stimulate TSH receptors
- Hashimoto Thyroiditis: anti-thyroid peroxidase and anti-thyroglobulin auto-Abs |
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What are the implications of auto-antibodies (IgG) stimulating the TSH receptors on the thyroid?
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- Hyperthyroidism
- Diffuse goiter |
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What are the implications of auto-antibodies (IgG) stimulating the TSH receptors on retro-orbital fibroblasts?
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Exophthalmos: proptosis, extraocular muscle swelling
|
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What are the implications of auto-antibodies (IgG) stimulating the TSH receptors on dermal fibroblasts?
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Pretibial myxedema
|
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When does Graves disease often present?
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During stress (eg, childbirth)
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What is the name for the stress-induced catecholamine surge seen as a serious complication of Graves disease and other hyperthyroid disorders?
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Thyroid Storm
|
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What causes a Thyroid Storm?
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Stress-induced catecholamine surge seen as a serious complication of Graves disease and other hyperthyroid disorders
|
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What are the symptoms of a Thyroid Storm?
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- Agitation
- Delirium - Fever - Diarrhea - Coma - Tachyarrhythmia (cause of death) |
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What lab value is possibly elevated in Thyroid Storm? Why?
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↑ ALP due to ↑ bone turnover
|
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How do you treat Thyroid Storm?
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Treat with the 3 P's:
- β-blockers (eg, Propranolol) - Propylthiouracil - Corticosteroids (eg, Prednisolone) |
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What are the indications for thyroidectomy?
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Treatment option for thyroid cancers and hyperthyroidism
|
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What are the potential complications of thyroid cancer?
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- Hoarseness: due to recurrent laryngeal nerve damage
- Hypocalcemia: due to removal of parathyroid glands - Transection of inferior thyroid artery |
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What are the types of thyroid cancers?
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- Papillary carcinoma
- Follicular carcinoma - Medullary carcinoma - Undifferentiated / anaplastic carcinoma - Lymphoma |
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If you see this on a sample of the thyroid, what diagnosis do you need to think of?
|
Papillary Carcinoma of the thyroid
- Empty appearing nuclei ("Orphan Annie" eyes) |
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What is the most common type of thyroid cancer? Associations?
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- Empty-appearing nuclei (Orphan Annie eyes), psamomma bodies, nuclear grooves
- Increased risk with RET and BRAF mutations and childhood irradiation - Excellent prognosis |
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What are the histologic findings of Papillary Carcinoma of the thyroid?
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- Empty-appearning nuclei ("Orphan Annie" eyes)
- Psammoma bodies - Nuclear grooves |
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What can increase your risk of getting Papillary Carcinoma of the Thyroid?
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- RET mutations
- BRAF mutations - Childhood irradiation |
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Which types of thyroid cancer are associated with a good prognosis?
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- Papillary Carcinoma (excellent prognosis, most common type)
- Follicular Carcinoma (good prognosis) |
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Which type of thyroid cancer has a very poor prognosis?
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Undifferentiated / Anaplastic Carcinoma of thyroid
|
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What are the characteristics of a Follicular Carcinoma of the thyroid?
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- Good prognosis
- Invades thyroid capsule (unlike follicular adenoma) - Uniform follicles |
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What type of thyroid cancer arises from parafollicular "C cells"?
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Medullary Carcinoma of the thyroid
|
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What is the origin of Medullary Carcinoma of the thyroid? What does it produce?
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- From parafollicular "C cells"
- Produces calcitonin |
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If you see this on a sample of the thyroid, what diagnosis do you need to think of?
|
Medullary Carcinoma of the thyroid
- Solid sheets of cells with amyloid deposition (arrow) - Amyloid stroma |
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What is Medullary Carcinoma of the thyroid associated with?
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- MEN 2A and 2B
- RET mutations |
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What type of thyroid cancer is more common in older patients?
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Undifferentiated / Anaplastic Carcinoma of thyroid
|
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What are the characteristics of Undifferentiated / Anaplastic Carcinoma of thyroid?
|
- Affects older patients
- Invades local structures - Very poor prognosis |
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Which type of thyroid cancer is associated with Hashimoto thyroiditis?
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Lymphoma
|
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What are the types of hyperparathyroidism? Levels of Calcium in each?
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- Primary: hypercalcemia
- Secondary: hypocalcemia - Tertiary: hypercalcemia |
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What is the most common cause of primary hyperparathyroidism?
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Parathyroid Adenoma
|
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How are hormones / electrolytes affected by Primary Hyperparathyroidism?
|
- ↑ Ca2+: hypercalcemia and hypercalciuria
- ↓ PO4-: Hypophosphatemia - ↑ PTH - ↑ ALP - ↑ cAMP in urine |
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What are the most common symptoms of Primary Hyperparathyroidism?
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- Most often asymptomatic
- May present with symptoms of hypercalcemia: weakness and constipation ("groans"), abdominal / flank pain (kidney "stones", or acute pancreatitis), depression ("psychiatric overtones") |
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What mnemonic helps you remember the symptoms of hypercalcemia?
|
"Stones, bones, groans, and psychiatric overtones"
- Renal stones → abdominal / flank pain - Bones → osteitis fibrosa cystica (cystic bone spaces filled with brown fibrous tissue causing bone pain) - Groans → weakness and constipation - Psychiatric overtones → depression |
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What happens in Osteitis Fibrosa Cystica? Cause?
|
- Cystic bone spaces are filled with brown fibrous tissue → bone pain
- Caused by hyperparathyroidism |
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What causes Secondary Hyperparathyroidism?
|
- Secondary hyperplasia due to ↓ gut Ca2+ absorption and ↑ PO4(3-)
- Most often in chronic renal disease (causes hypovitaminosis D → ↓ Ca2+ absorption) |
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What are the hormone / electrolyte findings in Secondary Hyperparathyroidism?
|
- ↓ Ca2+: hypocalcemia
- ↑ PO4-: hyperphosphatemia in chronic renal failure, although most other causes have hypophosphatemia - ↑ ALP - ↑ PTH |
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How are the bones affected by Secondary Hyperparathyroidism or Tertiary Hyperparathyroidism?
|
Bone lesions occur in 2° or 3° hyperparathyroidism due in turn to renal disease = Renal Osteodystrophy
|
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What causes Tertiary Hyperparathyroidism?
|
Refractory (autonomous) hyperparathyroidism resulting from chronic renal disease
|
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What are the hormone / electrolyte findings in Tertiary Hyperparathyroidism?
|
- ↑ Ca2+
- ↑↑ PTH |
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What is the difference between secondary and tertiary hyperparathyroidism?
|
Both commonly due to chronic renal disease
- 2°: ↓ Ca2+ and ↑ PTH - 3°: ↑ Ca2+ and ↑↑ PTH Both associated with renal osteodystrophy (bone lesions) |
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What are the most common causes of hypoparathyroidism?
|
Hypoparathyroidism:
- Accidental surgical excision of parathyroid glands - Auto-immune destruction - DiGeorge syndrome Pseudohypoparathyroidism (Albright Hereditary Osteodystrophy) - Autosomal dominant unresponsiveness of kidney to PTH |
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What are the findings associated with hypoparathyroidism?
|
- Hypocalcemia
- Tetany - Chvostek sign - Trousseau sign |
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How do you check for a Chvostek sign? What does it indicate if it is positive?
|
- Tap the facial nerve (tap the cheek)
- Positive: contraction of facial muscles - Sign of hypoparathyroidism |
|
How do you check for a Trousseau sign? What does it indicate if it is positive?
|
- Occlusion of brachial artery with BP cuff (cuff the TRiceps)
- Positive: carpal spasm - Sign of hypoparathyroidism |
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What is the other name for pseudohypoparathyroidism? Cause?
|
Albright Hereditary Osteodystrophy
- Autosomal dominant unresponsiveness of kidney to PTH |
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What are the symptoms of Albright Hereditary Osteodystrophy? Cause?
|
- Hypocalcemia, shortened 4th/5th digits, and short sature
- Caused by autosomal dominant unresponsiveness of kidney to PTH (pseudo-hypoparathyroidism) |
|
Which PTH / Calcium pathology is associated with a low Ca2+ and a low PTH? Cause?
|
Hypoparathyroidism:
- Surgical removal - Autoimmune destruction |
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Which PTH / Calcium pathology is associated with a low Ca2+ and a high PTH? Cause?
|
2° Hyperparathyroidism
- Vitamin D deficiency - Chronic renal failure |
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Which PTH / Calcium pathology is associated with a high Ca2+ and a low PTH? Cause?
|
PTH-independent hypercalcemia:
- Excess Ca2+ ingestion - Cancer |
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Which PTH / Calcium pathology is associated with a high Ca2+ and a high PTH? Cause?
|
1° Hyperparathyroidism:
- Hyperplasia - Adenoma - Carcinoma |
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What is the most common form of pituitary adenoma? Symptoms?
|
Prolactinoma
- Amenorrhea - Galactorrhea - Low libido - Infertility |
|
How do you treat a prolactinoma (pituitary adenoma)?
|
Dopamine agonists:
- Bromocriptine - Cabergoline |
|
What are the types of pituitary adenomas?
|
- Functional (hormone producing, eg, prolactinoma)
- Non-functional (silent, present with mass effect) |
|
What is most likely wrong in a patient with amenorrhea, galactorrhea, low libido, and infertility?
|
Prolactinoma (type of functioning pituitary adenoma)
|
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What is most likely wrong in a patient with bitemporal hemianopia, hypopituitarism, and a headache?
|
Non-functional pituitary adenoma, causing problems due to mass effect
|
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What are the symptoms of a non-functional pituitary adenoma with mass effect?
|
- Bitemporal hemianopia
- Hypopituitarism - Headache |
|
What are the symptoms of a somatotropic pituitary adenoma?
|
Acromegaly
|
|
What is the cause of acromegaly?
|
Excess GH in adults, typically caused by a pituitary adenoma
|
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What are the characteristic findings in a patient with Acromegaly?
|
- Large tongue with deep furrows
- Deep voice - Large hands and feet - Coarse facial features - Impaired glucose tolerance (insulin resistance) |
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What is the name of the syndrome caused by increased GH in children? Symptoms? Cause of death?
|
Gigantism
- ↑ Linear bone growth - Cardiac failure most common cause of death |
|
How do you confirm a diagnosis of Acromegaly?
|
- ↑ Serum IGF-1
- Failure to suppress serum GH following oral glucose tolerance test - Pituitary mass seen on brain MRI |
|
How do treat a patient with Acromegaly?
|
- Pituitary adenoma resection
- If not cured, treat with Octreotide (somatostatin analog) or Pegvisomant (GH receptor antagonist |
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What drug is a GH receptor antagonist?
|
Pegvisomant
|
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What drug is a somatostatin analog?
|
Octreotide
|
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What drugs are dopamine agonists?
|
- Bromocriptine
- Cabergoline |
|
If you have a patient with intense thirst, polyuria, and inability to concentrate urine, what diagnosis should you think of?
|
Diabetes Insipidus
|
|
What are the types of Diabetes Insipidus? Basic issue?
|
- Central DI: lack of ADH
- Nephrogenic DI: insensitivity to ADH |
|
What are possible causes of Central Diabetes Insipidus?
|
- Pituitary tumor
- Auto-immune process - Trauma - Surgery - Ischemic encephalopathy - Idiopathic |
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What are possible causes of Nephrogenic Diabetes Insipidus?
|
- Hereditary (ADH receptor mutation)
-2° to hypercalcemia, lithium, demeclocycline (ADH antagonist) |
|
If you have a patient with intense thirst, polyuria, and inability to concentrate urine, and you get the following lab results, what diagnosis should you make?
- ↓ ADH - Urine specific gravity <1.006 - Serum osmolarity >290 mOsm/L - Hyperosmotic volume contraction |
Central Diabetes Insipidus
* Only way to distinguish from Nephrogenic is based on ↓ ADH |
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If you have a patient with intense thirst, polyuria, and inability to concentrate urine, and you get the following lab results, what diagnosis should you make?
- Normal ADH - Urine specific gravity <1.006 - Serum osmolarity >290 mOsm/L - Hyperosmotic volume contraction |
Nephrogenic Diabetes Insipidus
* Only way to distinguish from Central is based on normal ADH |
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What are the following values in diabetes insipidus:
- ADH level - Urine specific gravity - Serum osmolarity - Type of volume contraction |
- ADH: ↓ if central or normal if nephrogenic
- Urine specific gravity: < 1.006 (dilute) - Serum osmolarity >290 mOsm/L (concentrated) - Hyperosmotic volume contraction |
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How do you diagnose Central Diabetes Insipidus?
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Water restriction test:
- No water intake for 2-3 hours - Followed by hourly measurements of urine volume / osmolarity and plasma Na+ concentration / osmolarity * Central: >50% ↑ in urine osmolarity * Nephrogenic: no change in urine osmolarity |
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What should you do if after a water restriction test normal values are not clearly reached?
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Give DDAVP (ADH analog) - this will improve central diabetes insipidus
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How do you treat central diabetes insipidus?
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- Intranasal DDAVP (ADH analog)
- Hydration |
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How do you treat nephrogenic diabetes insipidus?
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- HCTZ, indomethacin, amiloride
- Hydration |
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What can cause excessive water retention, hyponatremia, urinary Na+ excretion, and urine osmolarity > serum osmolarity?
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SIADH: Syndrome of Inappropriate Anti-Diuretic Hormone
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What are the findings of SIADH?
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- Excessive water retention
- Hyponatremia w/ continued urinary Na+ exretion - Urine osmolarity > serum osmolarity |
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How does the body normally respond to water retention?
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↓ Aldosterone (hyponatremia) to maintain near-normal volume status
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What are the possible consequences of the hyponatremia in SIADH?
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Can lead to cerebral edema and seizures
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When correcting hyponatremia in SIADH, what do you need to do? Why?
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Correct hyponatremia slowly to prevent central pontine myelinolysis
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What are the possible causes of SIADH?
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- Ectopic ADH (small cell lung cancer)
- CNS disorders / head trauma - Pulmonary disease - Drugs (eg, cyclophosphamide) |
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How do you treat SIADH?
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- Fluid restriction
- IV hypertonic saline - Conivaptan (ADH inhibitor) - Tolvaptan (ADH receptor antagonist) - Demeclocycline (ADH antagonist) |
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What can cause under-secretion of pituitary hormones (hypo-pituitarism)?
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- Non-secreting pituitary adenoma, craniopharyngioma
- Sheehan syndrome - Empty sella syndrome - Brain injury, hemorrhage - Radiation |
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What tumors can cause hypo-pituitarism?
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- Non-secreting pituitary adenoma
- Craniopharyngioma |
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What is Sheehan syndrome?
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Ischemic infarct of pituitary following post-partum bleeding, usually presents with a failure to lactate (no prolactin being released because of pituitary damage)
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What causes empty sella syndrome? Effect?
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- Atrophy or compression of pituitary, often idiopathic
- Common in obese women - Leads to hypopituitarism |
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What kind of brain injury can cause hypo-pituitarism?
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- Hemorrhage (pituitary apoplexy)
- General brain trauma - Radiation |
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How do you treat hypo-pituitarism?
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Hormone replacement therapy:
- Corticosteroids - Thyroxine - Sex steroids - Human growth hormone |
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What cause of hypo-pituitarism is common in obese women?
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Empty Sella Syndrome
- Atrophy or compression of pituitary, often idiopathic |
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What are the acute manifestations of diabetes mellitus?
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- Polydipsia
- Polyuria - Polyphagia - Weight loss - DKA (diabetic ketoacidosis) (type 1) - Hyperosmolar coma (type 2) |
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What can, although rarely, cause Diabetes Mellitus?
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Unopposed secretion of GH and Epinephrine
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What are the immediate consequences of an insulin deficiency (and glucagon excess)?
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- Decreased glucose uptake
- Increased protein catabolism - Increased lipolysis |
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What is the effect of decreased glucose uptake (due to insulin deficiency / glucagon excess)?
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- Hyperglycemia
- Glycosuria (excess of sugar in the urine) - Osmotic diuresis - Electrolyte depletion |
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What is the effect of increased protein catabolism (due to insulin deficiency / glucagon excess)?
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- Increased plasma amino acids
- Nitrogen loss in urine |
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What is the effect of increased lipolysis (due to insulin deficiency / glucagon excess)?
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- Increased plasma FFAs
- Ketogenesis - Ketonuria - Ketonemia |
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What is the combined effect of decreased glucose uptake, increased protein catabolism, and increased lipolysis (due to insulin deficiency / glucagon excess)?
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Dehydration and acidosis, which can cause coma or death
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What are the types of damage due to chronic diabetes?
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- Non-enzymatic glycosylation: small vessel and large vessel disease
- Osmotic damage: neuropathy, cataracts |
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What are the manifestations of non-enzymatic glycosylation on small vessels in patients with chronic diabetes?
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Diffuse thickening of basement membrane of small vessels leads to:
- Retinopathy - Glaucoma - Nephropathy |
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How are the eyes of patients with chronic diabetes affected?
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Small vessel disease due to diffuse thickening of basement membrane via non-enzymatic glycosylation:
- Retinopathy (picture): hemorrhage, exudates, microaneurysms, vessel proliferation - Glaucoma |
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How are the kidneys of patients with chronic diabetes affected?
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Small vessel disease (diffuse thickening of basement membrane) via non-enzymatic glycosylation:
- Nephropathy: nodular sclerosis, progressive proteinuria, chronic renal failure, arteriolosclerosis leading to HTN, Kimmelstiel-Wilson nodules) |
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What are the manifestations of retinopathy in chronic diabetes mellitus?
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- Hemorrhage
- Exudates - Microaneurysms - Vessel proliferation |
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What are the manifestations of nephropathy in chronic diabetes mellitus?
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- Nodular sclerosis
- Progressive proteinuria - Chronic renal failure - Arteriolosclerosis leading to HTN - Kimmelstiel-Wilson nodules |
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What are the manifestations of non-enzymatic glycosylation on large vessels in patients with chronic diabetes?
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- Large vessel atherosclerosis → cerebrovascular disease
- CAD → MI (most common cause of death) - Peripheral vascular occlusive disease - Gangrene → limb loss |
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What is the most common cause of death in patients with Diabetes Mellitus?
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Myocardial Infarction
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What causes osmotic damage in patients with chronic diabetes?
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Sorbitol accumulates in organs with aldose reductase and ↓ or absent sorbitol dehydrogenase
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What are the manifestations of osmotic damage in patients with chronic diabetes?
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- Neuropathy: motor, sensory, and autonomic degeneration
- Cataracts |
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What tests can be used to assess a patient's diabetes mellitus?
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- Fasting serum glucose
- Oral glucose tolerance test - HbA1c (reflects average blood glucose over prior 3 months) |
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What is the primary defect in T1DM vs T2DM?
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- T1DM: auto-immune destruction of β cells
- T2DM: ↑ resistance to insulin, progressive pancreatic β-cell failure |
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Is insulin necessary in treatment of T1DM and T2DM?
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- T1DM: always
- T2DM: sometimes |
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What is the typical age of onset for patients with T1DM vs T2DM?
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- T1DM: <30 years
- T2DM: >40 years *Exceptions commonly occur |
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What is the association with obesity for T1DM vs T2DM?
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- T1DM: none
- T2DM: associated |
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Is there a genetic predisposition for T1DM vs T2DM?
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- T1DM: relatively weak (50% concordance in identical twins), polygenic
- T2DM: relatively strong (90% concordance in identical twins), polygenic |
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What is the association with HLA system for T1DM vs T2DM?
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- T1DM: associated with HLA-DR3 and -DR4
- T2DM: no association |
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What is the relative glucose intolerance in T1DM vs T2DM?
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- T1DM: severe
- T2DM: mild to moderate |
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What is the relative insulin sensitivity in T1DM vs T2DM?
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- T1DM: high
- T2DM: low |
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How common is ketoacidosis in T1DM vs T2DM?
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- T1DM: common
- T2DM: rare |
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How many β-cells are there in the islets relatively in T1DM vs T2DM?
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- T1DM: ↓ β-cell numbers
- T2DM: variable (with amyloid deposits) |
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What is the relative serum insulin level in T1DM vs T2DM?
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- T1DM: ↓
- T2DM: Variable |
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Are the classic symptoms of polyuria, polydipsia, polyphagia, and weight loss seen in T1DM vs T2DM?
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- T1DM: common
- T2DM: sometimes |
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What is the histologic appearance of the Islets of Langerhans in T1DM vs T2DM?
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- T1DM: islet leukocytic infiltrate (auto-immune process)
- T2DM: islet amyloid polypeptide (IAPP) deposits |
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What is one of the most important complications of diabetes (usually type 1)?
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Diabetic Ketoacidosis
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What causes diabetic ketoacidosis?
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- Complication of diabetes (usually type 1)
- Usually due to ↑ insulin requirements from ↑ stress (eg, infection) - Excess fat breakdown and ↑ ketogenesis from ↑ FFAs, when are converted into ketone bodies |
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What are the types of ketone bodies? Which is more common in diabetic ketoacidosis?
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β-Hydroxybutyrate > Acetoacetate
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What are the signs / symptoms of diabetic ketoacidosis?
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- Kussmaul respirations (rapid / deep breathing)
- Nausea / vomiting - Abdominal pain - Psychosis / delirium - Dehydration - Fruity breath odor (due to exhaled acetone) |
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What are Kussmaul respirations? Sign of?
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- Rapid / deep breathing
- Sign of diabetic ketoacidosis |
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What causes the fruity breath odor in diabetics?
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Diabetic ketoacidosis → exhaled acetone
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What are the lab findings associated with diabetic ketoacidosis?
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- Hyperglycemia
- ↑ H+ and ↓ HCO3- (anion gap metabolic acidosis) - ↑ Blood ketone levels - Leukocytosis - Hyperkalemia, but depleted intracellular K+ d/t transcellular shift from ↓ insulin |
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What kind of acid/base disturbance occurs with diabetic ketoacidosis?
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Anion gap metabolic acidosis
- ↑ H+ - ↓ HCO3- |
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How are WBCs affected in diabetic ketoacidosis?
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Leukocytosis
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How is K+ balance affected in diabetic ketoacidosis?
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- Hyperkalemia
- Depleted intracellular K+ because of transcellular shift from ↓ insulin |
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What are the potenial complications of diabetic ketoacidosis?
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- Life-threatening mucormycosis (usually caused by Rhizopus infection)
- Cerebral edema - Cardiac arrhythmias - Heart failure |
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How do you treat diabetic ketoacidosis?
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- IV fluids
- IV insulin - K+ (to replete intracellular stores) - Glucose if necessary to prevent hypoglycemia |
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What is the source of an insulinoma? What is its effect?
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- Tumor of β cells of pancreas
- Over-produces insulin → hypoglycemia |
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What are the common symptoms with an insulinoma?
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Whipple triad of episodic CNS symptoms:
- Lethargy - Syncope - Diplopia |
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What lab values are associated with insulinoma?
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- ↓ Blood glucose
- ↑ C-peptide (vs exogenenous insulin use which would cause similar findings but have low/normal C-peptide) |
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How do you treat an insulinoma?
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Surgical resection of tumor in pancreas
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What is the most common malignancy in the small intestine?
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Carcinoid Syndrome
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What causes Carcinoid Syndrome?
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Rare syndrome caused by carcinoid tumors (neuroendocrine cells), especially metastatic small bowel tumors, which secrete high levels of serotonin (5-HT)
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What is necessary for a carcinoid tumor of the small intestine to cause Carcinoid Syndrome?
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- Tumor secretes high levels of serotonin (5-HT)
- Tumor must not be restricted to the GI tract because 5-HT undergoes first pass metabolism in the liver |
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What are the symptoms of Carcinoid Syndrome?
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- Recurrent diarrhea
- Cutaneous flushing - Asthmatic wheezing - Right sided valvular disease |
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What are the lab changes associated with Carcinoid Syndrome?
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- ↑ 5-hydroxyindoleacetic acid (5-HIAA) in urine
- Niacin deficiency (pellagra - diarrhea, dementia, dermatitis) |
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How do you treat Carcinoid Syndrome?
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- Resection of carcinoid tumor
- Somatostatin analog (eg, octreotide) |
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What is the rule of 1/3 for Carcinoid Syndrome?
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- 1/3 metastasize
- 1/3 present with 2nd malignancy - 1/3 are multiple |
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What causes Zollinger-Ellison Syndrome?
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- Gastrin-secreting tumor of pancreas or duodenum
- Leads to acid hyper-secretion → recurrent ulcers in distal duodenum and jejunum |
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Zollinger-Ellison Syndrome leads to ulcers where?
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Distal duodenum and jejunum
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What symptoms does a patient with Zollinger-Ellison Syndrome typically present with?
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- Abdominal pain (peptic ulcer disease, distal ulcers)
- Diarrhea (malabsorption) |
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What may Zollinger-Ellison Syndrome be associated with?
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MEN 1
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What are the types of Multiple Endocrine Neoplasias?
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- MEN 1 (Wermer syndrome)
- MEN 2A (Sipple syndrome) - MEN 2B |
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What kind of tumors are associated with MEN 1?
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MEN 1 = 3 P's (diamond):
- Pituitary tumors (prolactin or GH) - Parathyroid tumors - Pancreatic endocrine tumors (Zollinger Ellison syndrome, insulinomas, VIPomas, glucagonomas-rare) |
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Besides pituitary tumors, parathyroid tumors, and pancreatic endocrine tumors, what else is associated with MEN 1?
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- Kidney stones
- Stomach ulcers |
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What kind of tumors are associated with MEN 2A?
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MEN 2A: 2 P's (square):
- Parathyroid (hyperplasia) - Pheochromocytoma (adrenals) - Medullary Thyroid Carcinoma (secretes calcitonin) |
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Besides medullary thyroid carcinoma, pheochromocytoma, and parathyroid hyperplasia, what else is associated with MEN 2A?
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Associated with RET gene mutations
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What kind of tumors are associated with MEN 2B?
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MEN 2B: 1 P (triangle):
- Pheochromocytoma (adrenals) - Oral / intestinal ganglioneuromatosis (mucosal neuromas) - Medullary Thyroid Carcinoma (secretes calcitonin) |
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Besides medullary thyroid carcinoma, pheochromocytoma, and oral/intestinal ganglioneuromatosis (mucosal neuromas), what else is associated with MEN 2B?
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Marfanoid habitus
- Resembling symptoms of Marfan Syndrome - Long limbs, arachnodactyly, and hyperlaxity - Arm span is greater than the height of the individual Associated with RET gene mutation |
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How are MEN syndromes inherited? Other associated genetic changes?
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- All are autosomal dominant (think "MEN are dominant" - or so they think)
- Associated with RET gene mutation in MEN 2A and 2B |