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244 Cards in this Set

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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
What is the number one cause of Cushing syndrome? Characteristics?
Exogenous corticosteroids: results in ↓ ACTH and bilateral adrenal atrophy
What causes of Cushing syndrome result in ↓ ACTH? Effect on adrenals?
- Exogenous steroids - bilateral adrenal atrophy
- Primary adrenal adenoma, hyperplasia, or carcinoma - atrophy of uninvolved adrenal gland
What can primary adrenal adenoma / hyperplasia / carcinoma produce?
- ↑ Cortisol (= Cushing Syndrome)
OR
- ↑ Aldosterone (1° Aldosteronism = Conn Syndrome)
What is Conn Syndrome?
1° Aldosteronism (due to primary adrenal adenoma, hyperplasia, or carcinoma)
What causes of Cushing syndrome result in ↑ ACTH? Effect on adrenals?
ACTH-secreting pituitary adenoma (Cushing disease)
- Paraneoplastic ACTH secretion: small cell lung cancer, bronchial carcinoids
- Bilateral adrenal hyperplasia
What is responsible for the majority of the endogenous cases of Cushing Syndrome?
Cushing Disease
- ACTH-secreting pituitary adenoma
- Paraneoplastic ACTH secretion: small cell lung cancer, bronchial carcinoids
Cushing Disease
- ACTH-secreting pituitary adenoma
- Paraneoplastic ACTH secretion: small cell lung cancer, bronchial carcinoids
What are the findings associated with Cushing Syndrome?
- Hypertension 
- Weight gain
- Moon facies
- Truncal obesity
- Buffalo hump
- Hyperglycemia (insulin resistance)
- Skin changes (thinning, striae)
- Osteoporosis
- Amenorrhea
- Immune suppression
- Hypertension
- Weight gain
- Moon facies
- Truncal obesity
- Buffalo hump
- Hyperglycemia (insulin resistance)
- Skin changes (thinning, striae)
- Osteoporosis
- Amenorrhea
- Immune suppression
How do you screen for Cushing Syndrome?
** 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)
** 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)
What should you suspect / do if a patient you suspect of having Cushing Syndrome has a low ACTH (<5 pg/mL)?
Suspect ACTH-independent Cushing Syndrome (primary adrenal adenoma, hyperplasia, or carcinoma)

* Order MRI to confirm adrenal tumor
Suspect ACTH-independent Cushing Syndrome (primary adrenal adenoma, hyperplasia, or carcinoma)

* Order MRI to confirm adrenal tumor
What should you suspect / do if a patient you suspect of having Cushing Syndrome has a high ACTH (>20 pg/mL)?
Suspect ACTH-dependent Cushing Syndrome

* Order high-dose dexamethasone suppression test
* Order CRH stimulation test
Suspect ACTH-dependent Cushing Syndrome

* Order high-dose dexamethasone suppression test
* Order CRH stimulation test
What diagnosis does a patient you suspect of having Cushing Syndrome, with an elevated ACTH, and adequate suppression via high-dose dexamethasone suppression test?
Cushing Disease (ACTH-secreting pituitary adenoma)
Cushing Disease (ACTH-secreting pituitary adenoma)
What diagnosis does a patient you suspect of having Cushing Syndrome, with an elevated ACTH, and no suppression via high-dose dexamethasone suppression test?
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
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
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?
Cushing Disease (ACTH-secreting pituitary adenoma)
Cushing Disease (ACTH-secreting pituitary adenoma)
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?
Ectopic ACTH secretion

- Ectopic secretion will not increase with CRH because pituitary ACTH is suppressed
Ectopic ACTH secretion

- Ectopic secretion will not increase with CRH because pituitary ACTH is suppressed
What are the causes of primary hyperaldosteronism?
- Adrenal hyperplasia
- Aldosterone secreting adrenal adenoma (Conn syndrome)

(May be unilateral or bilateral)
What are the consequences of adrenal hyperplasia or aldosterone-secreting adrenal adenoma?
Primary Hyperaldosteronism:
- Hypertension
- Hypokalemia
- Metabolic alkalosis
- Low plasma renin
- Normal Na+ due to aldosterone escape → no edema
How do you treat primary hyperaldosteronism?
Surgery to remove the tumor and/or spironolactone (K+ sparing diuretic that acts as an aldosterone antagonist)
What are the causes of secondary hyperaldosteronism?
- Renal artery stenosis
- Congestive Heart Failure
- Cirrhosis
- Nephrotic Syndrome
What are the consequences of renal artery stenosis, CHF, cirrhosis, or nephrotic syndrome?
Secondary Hyperaldosteronism
- Renal perception of low intravascular volume → over-active renin-angiotensin system
- Associated with high plasma renin
How do you treat secondary hyperaldosteronism?
Spironolactone (K+ sparing diuretic that acts as an aldosterone antagonist)
What form of hyperaldosteronism is associated with a high plasma renin?
Secondary Hyperaldosteronism

- In primary, there is negative feedback to decrease renin
- In secondary, the high renin is what is causing the high aldosterone
What are the causes of primary adrenal insufficiency?
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
What are the implications of Addison Disease?
- Deficiency of aldosterone and cortisol
- Hypotension (hyponatremic volume contraction)
- Hyperkalemia
- Acidosis
- Skin and mucosal hyperpigmentation
What causes the skin hyperpigmentation in Addison Disease?
What causes the skin hyperpigmentation in Addison Disease?
MSH (melanocyte stimulating hormone): by-product of ↑ ACTH production from pro-opiomelanocortin (POMC)
MSH (melanocyte stimulating hormone): by-product of ↑ ACTH production from pro-opiomelanocortin (POMC)
How is Addison Disease characterized?
- Adrenal Atrophy
- Absence of hormone production, involving all three cortical divisions (but spares medulla)
How do you distinguish primary adrenal insufficiency from secondary?
Secondary adrenal insufficiency would have:
- ↓ Pituitary ACTH production
- No skin/mucosal hyperpigmentation
- No hyperkalemia
What are the electrolyte and acid/base balance changes in primary adrenal insufficiency?
- Hyponatremia
- Hyperkalemia
- Acidosis
What is the name of the syndrome causing ACUTE 1° adrenal insufficiency? Cause?
Waterhouse-Friderichsen Syndrome
- Adrenal hemorrhage associated with Neisseria meningitidis septicemia, DIC, and endotoxic shock
What is the most common tumor of the adrenal medulla in children? When specifically?
Neuroblastoma
- Usually <4 years old
What is the origin of a neuroblastoma?
Neural crest cells
Where can a neuroblastoma appear?
Occurs anywhere along the sympathetic chain
What is the most common presentation of Neuroblastoma?
- Abdominal distension
- Firm, irregular mass that can CROSS THE MIDLINE
- Usually in children < 4 years old
- Less likely to develop hypertension
When you have a firm, irregular mass that crosses the midline of a young child, what diagnosis should you think of?
Neuroblastoma
Neuroblastoma
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)
What lab studies are associated with a Neuroblastoma?
- Homovanillic acid (HVA), a breakdown product of dopamine, is increased in urine
- Bombesin (+)
- LM: rosettes (arrow) and classic small, round, blue/purple nuclei
- Homovanillic acid (HVA), a breakdown product of dopamine, is increased in urine
- Bombesin (+)
- LM: rosettes (arrow) and classic small, round, blue/purple nuclei
What genetic change is associated with Neuroblastoma?
Over-expression of the N-myc oncogene
What is the most common tumor of the adrenal medulla in adults?
Pheochromocytoma
Pheochromocytoma
What is a pheochromocytoma derived from?
Chromaffin cells (arise from neural crest)
Chromaffin cells (arise from neural crest)
What rule can you use to remember characteristics of a pheochromocytoma?
Rule of 10s:
- 10% malignant
- 10% bilateral
- 10% extra-adrenal
- 10% calcify
- 10% in kids
What does a pheochromocytoma do?
Most tumors secrete epinephrine, norepinephrine, and dopamine → episodic hypertension
What genetic change is pheochromocytoma associated with?
- Von Hippel-Lindau disease
- MEN 2A
- MEN 2B
What symptoms are typical of pheochromocytoma?
Symptoms occur in "spells" - relapse and remit:

Episodic hyperadrenergic symptoms (5 P's):
- Pressure (↑ BP)
- Pain (headache)
- Perspiration
- Palpitations (tachycardia)
- Pallor
What are the lab findings associated with a pheochromocytoma?
- ↑ Urinary VMA (breakdown product of NE and Epi)
- ↑ Plasma catecholamines (NE, Epi, etc)
How do you treat pheochromocytoma?
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 **
For what diagnosis must you treat the patient first with α-antagonists before β-blockers? Why?
For treatment of Pheochromocytoma:

This is necessary to avoid a hypertensive crisis
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
What are the characteristic signs / symptoms of hyperthyroidism?
- 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
How do patients with hypothyroidism vs hyperthyroidism compare in terms of their bowel habits?
- Hypothyroidism: constipation
- Hyperthyroidism: diarrhea
How do patients with hypothyroidism vs hyperthyroidism compare in terms of their reflexes?
- Hypothyroidism: decreased reflexes
- Hyperthyroidism: increased reflexes
How do patients with hypothyroidism vs hyperthyroidism compare in terms of myxedema (swelling of the skin and underlying tissues giving a waxy consistency)?
- Hypothyroidism: facial and periorbital myxedema
- Hyperthyroidism: pretibial myxedema (Graves disease), periorbital edema
How do patients with hypothyroidism vs hyperthyroidism compare in terms of their skin and hair?
- Hypothyroidism: dry, cool skin with coarse, brittle hair
- Hyperthyroidism: warm, moist skin with fine hair
How do patients with hypothyroidism vs hyperthyroidism compare in terms of cardiac symptoms?
- Hypothyroidism: bradycardia and dyspnea on exertion
- Hyperthyroidism: chest pain, palpitations, arrhythmias, ↑ number and sensitivity of β-adrenergic receptors
Why do patients with hyperthyroidism sometimes have chest pain, palpitations, and arrhythmias?
↑ number and sensitivity of β-adrenergic receptors
What are the lab findings associated with hypothyroidism?
- ↑ TSH (sensitive for 1° hypothyroidism)
- ↓ free T3 and T4
- Hypercholesterolemia (due to ↓ LDL receptor expression)
What are the lab findings associated with hyperthyroidism?
- ↓ TSH (if 1°)
- ↑ free or total T3 and T4
- Hypocholesterolemia (due to ↑ LDL receptor expression)
How do thyroid disorders affect cholesterol? Mechanism?
- Hypothyroidism: hypercholesterolemia due to ↓ LDL receptor expression
- Hyperthyroidism: hypocholesterolemia due to ↑ LDL receptor expression
What is the most common cause of hypothyroidism in iodine-sufficient regions?
Hashimoto Thyroiditis
What causes Hashimoto Thyroiditis?
Auto-immune disorder
- Anti-thyroid peroxidase and anti-thyroglobulin antibodies
- Associated with HLA-DR5
What is there increased risk of in patients with Hashimoto Thyroiditis?
Non-Hodgkin Lymphoma
What may be an early, contradictory finding seen in patients with Hashimoto Thyroiditis?
May be hyperthyroid early in course due to thyrotoxicosis during follicular rupture
What are the histologic findings of Hashimoto Thyroiditis?
Hürthle cells, lymphoid aggregate with germinal centers
Hürthle cells, lymphoid aggregate with germinal centers
What does this histology indicate?
What does this histology indicate?
Hürthle cells, lymphoid aggregate with germinal centers → Hashimoto Thyroiditis
What are the expected thyroid findings on physical exam in a patient with Hashimoto Thyroiditis?
Moderately enlarged, non-tender
The presence of Hürthle cells should make you think of what?
Hashimoto Thyroiditis
Hashimoto Thyroiditis
What can cause severe fetal hypothyroidism (congenital hypothyroidism)?
- Maternal hypothyroidism
- Thyroid agenesis
- Thyroid dysgenesis (most common cause in US)
- Iodine deficiency
- Dyshormonogenic goiter
What are the findings of a patient with congenital hypothyroidism?
6 P's:
- Pot-bellied
- Pale
- Puffy-faced child
- Protruding umbilicus
- Protuberant tongue
- Poor brain development
6 P's:
- Pot-bellied
- Pale
- Puffy-faced child
- Protruding umbilicus
- Protuberant tongue
- Poor brain development
What is cretinism?
Congenital hypothyroidism
What is the most common cause of congenital hypothyroidism in the US?
Thyroid Dysgenesis
What is wrong with the child on the left (before) and after treatment on the right?
What is wrong with the child on the left (before) and after treatment on the right?
Congenital hypothyroidism
Congenital hypothyroidism
What is the term for the self-limited hypothyroidism often following a flu-like illness?
Subacute Thyroiditis (de Quervain)
What happens in Subacute Thyroiditis (de Quervain)?
- May be hyperthyroid early in course
- Self-limited hypothyroidism often following a flu-like illness
What is the appearance of the thyroid histologically in Subacute Thyroiditis (de Quervain)?
Granulomatous inflammation
What cause of hypothyroidism is associated with a very tender / painful thyroid?
Subacute Thyroiditis (de Quervain)
*de QuerVAIN is associated with PAIN*
What are the findings in Subacute Thyroiditis (de Quervain)?
- ↑ ESR
- Jaw pain
- Early inflammation
- Very tender thyroid
- Granulomatous inflammation of thyroid
What causes granulomatous inflammation of the thyroid?
Subacute Thyroiditis (de Quervain)
What disease causes the thyroid to be replaced with fibrous tissue? What does this cause?
Riedel Thyroiditis - causes hypothyroidism
What happens in Riedel Thyroiditis?
- Thyroid replaced by fibrous tissue (hypothyroid)
- Fibrosis may extend to local structures (eg, airway), mimicking anaplastic carcinoma
What is Riedel Thyroiditis considered a manifestatoin of?
Manifestation of IgG4-related systemic disease
What are the findings of a patient's thyroid in Riedel Thyroiditis on physical exam?
- Fixed
- Hard (rock-like)
- Painless goiter
What are some other causes of hypothyroidism?
- Iodine deficiency
- Goitrogens
- Wolff-Chaikoff effect
- Painless thyroiditis
What are the causes of hyperthyroidism?
- Toxic multinodular goiter
- Graves disease
- Thyroid storm
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?
Toxic Multinodular Goiter
Toxic Multinodular Goiter
What is wrong in Toxic Multinodular Goiter?
- Focal patches of hyper-functioning follicular cells
- Work independently of TSH due to mutation in TSH receptor
- ↑ Release of T3 and T4
- Focal patches of hyper-functioning follicular cells
- Work independently of TSH due to mutation in TSH receptor
- ↑ Release of T3 and T4
What does this histologic image of the thyroid show?
What does this histologic image of the thyroid show?
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
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
What is the term for thyrotoxicosis when a patient with iodine deficiency suddenly is made iodine replete?
Jod-Basedow Phenomenon
What happens in the Jod-Basedow Phenomenon?
Thyrotoxicosis if a patient with iodine deficiency goiter is made iodine replete
What is the most common cause of hyperthyroidism?
Graves disease
What is the underlying pathophysiology responsible for Graves disease?
Auto-antibodies (IgG) stimulate TSH receptors on thyroid, retro-orbital fibroblasts, and dermal fibroblasts
What kind of antibodies are associated with Graves disease? Hashimoto Thyroiditis?
- Graves disease: IgG auto-Abs that stimulate TSH receptors
- Hashimoto Thyroiditis: anti-thyroid peroxidase and anti-thyroglobulin auto-Abs
What are the implications of auto-antibodies (IgG) stimulating the TSH receptors on the thyroid?
- Hyperthyroidism
- Diffuse goiter
What are the implications of auto-antibodies (IgG) stimulating the TSH receptors on retro-orbital fibroblasts?
Exophthalmos: proptosis, extraocular muscle swelling
Exophthalmos: proptosis, extraocular muscle swelling
What are the implications of auto-antibodies (IgG) stimulating the TSH receptors on dermal fibroblasts?
Pretibial myxedema
When does Graves disease often present?
During stress (eg, childbirth)
What is the name for the stress-induced catecholamine surge seen as a serious complication of Graves disease and other hyperthyroid disorders?
Thyroid Storm
What causes a Thyroid Storm?
Stress-induced catecholamine surge seen as a serious complication of Graves disease and other hyperthyroid disorders
What are the symptoms of a Thyroid Storm?
- Agitation
- Delirium
- Fever
- Diarrhea
- Coma
- Tachyarrhythmia (cause of death)
What lab value is possibly elevated in Thyroid Storm? Why?
↑ ALP due to ↑ bone turnover
How do you treat Thyroid Storm?
Treat with the 3 P's:
- β-blockers (eg, Propranolol)
- Propylthiouracil
- Corticosteroids (eg, Prednisolone)
What are the indications for thyroidectomy?
Treatment option for thyroid cancers and hyperthyroidism
What are the potential complications of thyroid cancer?
- Hoarseness: due to recurrent laryngeal nerve damage
- Hypocalcemia: due to removal of parathyroid glands
- Transection of inferior thyroid artery
What are the types of thyroid cancers?
- Papillary carcinoma
- Follicular carcinoma
- Medullary carcinoma
- Undifferentiated / anaplastic carcinoma
- Lymphoma
If you see this on a sample of the thyroid, what diagnosis do you need to think of?
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)
Papillary Carcinoma of the thyroid
- Empty appearing nuclei ("Orphan Annie" eyes)
What is the most common type of thyroid cancer? Associations?
- Empty-appearing nuclei (Orphan Annie eyes), psamomma bodies, nuclear grooves
- Increased risk with RET and BRAF mutations and childhood irradiation
- Excellent prognosis
What are the histologic findings of Papillary Carcinoma of the thyroid?
- Empty-appearning nuclei ("Orphan Annie" eyes)
- Psammoma bodies
- Nuclear grooves
- Empty-appearning nuclei ("Orphan Annie" eyes)
- Psammoma bodies
- Nuclear grooves
What can increase your risk of getting Papillary Carcinoma of the Thyroid?
- RET mutations
- BRAF mutations
- Childhood irradiation
Which types of thyroid cancer are associated with a good prognosis?
- Papillary Carcinoma (excellent prognosis, most common type)
- Follicular Carcinoma (good prognosis)
Which type of thyroid cancer has a very poor prognosis?
Undifferentiated / Anaplastic Carcinoma of thyroid
What are the characteristics of a Follicular Carcinoma of the thyroid?
- Good prognosis
- Invades thyroid capsule (unlike follicular adenoma)
- Uniform follicles
What type of thyroid cancer arises from parafollicular "C cells"?
Medullary Carcinoma of the thyroid
What is the origin of Medullary Carcinoma of the thyroid? What does it produce?
- From parafollicular "C cells"
- Produces calcitonin
If you see this on a sample of the thyroid, what diagnosis do you need to think of?
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
Medullary Carcinoma of the thyroid
- Solid sheets of cells with amyloid deposition (arrow)
- Amyloid stroma
What is Medullary Carcinoma of the thyroid associated with?
- MEN 2A and 2B
- RET mutations
What type of thyroid cancer is more common in older patients?
Undifferentiated / Anaplastic Carcinoma of thyroid
What are the characteristics of Undifferentiated / Anaplastic Carcinoma of thyroid?
- Affects older patients
- Invades local structures
- Very poor prognosis
Which type of thyroid cancer is associated with Hashimoto thyroiditis?
Lymphoma
What are the types of hyperparathyroidism? Levels of Calcium in each?
- Primary: hypercalcemia
- Secondary: hypocalcemia
- Tertiary: hypercalcemia
What is the most common cause of primary hyperparathyroidism?
Parathyroid Adenoma
How are hormones / electrolytes affected by Primary Hyperparathyroidism?
- ↑ Ca2+: hypercalcemia and hypercalciuria
- ↓ PO4-: Hypophosphatemia
- ↑ PTH
- ↑ ALP
- ↑ cAMP in urine
What are the most common symptoms of Primary Hyperparathyroidism?
- Most often asymptomatic
- May present with symptoms of hypercalcemia: weakness and constipation ("groans"), abdominal / flank pain (kidney "stones", or acute pancreatitis), depression ("psychiatric overtones")
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
What happens in Osteitis Fibrosa Cystica? Cause?
- Cystic bone spaces are filled with brown fibrous tissue → bone pain
- Caused by hyperparathyroidism
- Cystic bone spaces are filled with brown fibrous tissue → bone pain
- Caused by hyperparathyroidism
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)
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
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
What causes Tertiary Hyperparathyroidism?
Refractory (autonomous) hyperparathyroidism resulting from chronic renal disease
What are the hormone / electrolyte findings in Tertiary Hyperparathyroidism?
- ↑ Ca2+
- ↑↑ PTH
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)
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
What are the findings associated with hypoparathyroidism?
- Hypocalcemia
- Tetany
- Chvostek sign
- Trousseau sign
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
What is the other name for pseudohypoparathyroidism? Cause?
Albright Hereditary Osteodystrophy
- Autosomal dominant unresponsiveness of kidney to PTH
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
Hypoparathyroidism:
- Surgical removal
- Autoimmune destruction
Which PTH / Calcium pathology is associated with a low Ca2+ and a high PTH? Cause?
2° Hyperparathyroidism
- Vitamin D deficiency
- Chronic renal failure
2° Hyperparathyroidism
- Vitamin D deficiency
- Chronic renal failure
Which PTH / Calcium pathology is associated with a high Ca2+ and a low PTH? Cause?
PTH-independent hypercalcemia:
- Excess Ca2+ ingestion
- Cancer
PTH-independent hypercalcemia:
- Excess Ca2+ ingestion
- Cancer
Which PTH / Calcium pathology is associated with a high Ca2+ and a high PTH? Cause?
1° Hyperparathyroidism:
- Hyperplasia
- Adenoma
- Carcinoma
1° Hyperparathyroidism:
- Hyperplasia
- Adenoma
- Carcinoma
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)
- 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)
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
Non-functional pituitary adenoma, causing problems due to mass effect
What are the symptoms of a non-functional pituitary adenoma with mass effect?
- Bitemporal hemianopia
- Hypopituitarism
- Headache
- 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
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)
- Large tongue with deep furrows
- Deep voice
- Large hands and feet
- Coarse facial features
- Impaired glucose tolerance (insulin resistance)
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
What drug is a GH receptor antagonist?
Pegvisomant
What drug is a somatostatin analog?
Octreotide
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
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
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
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
How do you diagnose Central Diabetes Insipidus?
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
What should you do if after a water restriction test normal values are not clearly reached?
Give DDAVP (ADH analog) - this will improve central diabetes insipidus
How do you treat central diabetes insipidus?
- Intranasal DDAVP (ADH analog)
- Hydration
How do you treat nephrogenic diabetes insipidus?
- HCTZ, indomethacin, amiloride
- Hydration
What can cause excessive water retention, hyponatremia, urinary Na+ excretion, and urine osmolarity > serum osmolarity?
SIADH: Syndrome of Inappropriate Anti-Diuretic Hormone
What are the findings of SIADH?
- Excessive water retention
- Hyponatremia w/ continued urinary Na+ exretion
- Urine osmolarity > serum osmolarity
How does the body normally respond to water retention?
↓ Aldosterone (hyponatremia) to maintain near-normal volume status
What are the possible consequences of the hyponatremia in SIADH?
Can lead to cerebral edema and seizures
When correcting hyponatremia in SIADH, what do you need to do? Why?
Correct hyponatremia slowly to prevent central pontine myelinolysis
What are the possible causes of SIADH?
- Ectopic ADH (small cell lung cancer)
- CNS disorders / head trauma
- Pulmonary disease
- Drugs (eg, cyclophosphamide)
How do you treat SIADH?
- Fluid restriction
- IV hypertonic saline
- Conivaptan (ADH inhibitor)
- Tolvaptan (ADH receptor antagonist)
- Demeclocycline (ADH antagonist)
What can cause under-secretion of pituitary hormones (hypo-pituitarism)?
- Non-secreting pituitary adenoma, craniopharyngioma
- Sheehan syndrome
- Empty sella syndrome
- Brain injury, hemorrhage
- Radiation
What tumors can cause hypo-pituitarism?
- Non-secreting pituitary adenoma
- Craniopharyngioma
What is Sheehan syndrome?
Ischemic infarct of pituitary following post-partum bleeding, usually presents with a failure to lactate (no prolactin being released because of pituitary damage)
What causes empty sella syndrome? Effect?
- Atrophy or compression of pituitary, often idiopathic
- Common in obese women
- Leads to hypopituitarism
What kind of brain injury can cause hypo-pituitarism?
- Hemorrhage (pituitary apoplexy)
- General brain trauma
- Radiation
How do you treat hypo-pituitarism?
Hormone replacement therapy:
- Corticosteroids
- Thyroxine
- Sex steroids
- Human growth hormone
What cause of hypo-pituitarism is common in obese women?
Empty Sella Syndrome
- Atrophy or compression of pituitary, often idiopathic
What are the acute manifestations of diabetes mellitus?
- Polydipsia
- Polyuria
- Polyphagia
- Weight loss
- DKA (diabetic ketoacidosis) (type 1)
- Hyperosmolar coma (type 2)
What can, although rarely, cause Diabetes Mellitus?
Unopposed secretion of GH and Epinephrine
What are the immediate consequences of an insulin deficiency (and glucagon excess)?
- Decreased glucose uptake
- Increased protein catabolism
- Increased lipolysis
- Decreased glucose uptake
- Increased protein catabolism
- Increased lipolysis
What is the effect of decreased glucose uptake (due to insulin deficiency / glucagon excess)?
- Hyperglycemia
- Glycosuria (excess of sugar in the urine)
- Osmotic diuresis
- Electrolyte depletion
- Hyperglycemia
- Glycosuria (excess of sugar in the urine)
- Osmotic diuresis
- Electrolyte depletion
What is the effect of increased protein catabolism (due to insulin deficiency / glucagon excess)?
- Increased plasma amino acids
- Nitrogen loss in urine
- Increased plasma amino acids
- Nitrogen loss in urine
What is the effect of increased lipolysis (due to insulin deficiency / glucagon excess)?
- Increased plasma FFAs
- Ketogenesis
- Ketonuria
- Ketonemia
- Increased plasma FFAs
- Ketogenesis
- Ketonuria
- Ketonemia
What is the combined effect of decreased glucose uptake, increased protein catabolism, and increased lipolysis (due to insulin deficiency / glucagon excess)?
Dehydration and acidosis, which can cause coma or death
Dehydration and acidosis, which can cause coma or death
What are the types of damage due to chronic diabetes?
- Non-enzymatic glycosylation: small vessel and large vessel disease
- Osmotic damage: neuropathy, cataracts
What are the manifestations of non-enzymatic glycosylation on small vessels in patients with chronic diabetes?
Diffuse thickening of basement membrane of small vessels leads to:
- Retinopathy
- Glaucoma
- Nephropathy
How are the eyes of patients with chronic diabetes affected?
Small vessel disease due to diffuse thickening of basement membrane via non-enzymatic glycosylation:
- Retinopathy (picture): hemorrhage, exudates, microaneurysms, vessel proliferation
- Glaucoma
Small vessel disease due to diffuse thickening of basement membrane via non-enzymatic glycosylation:
- Retinopathy (picture): hemorrhage, exudates, microaneurysms, vessel proliferation
- Glaucoma
How are the kidneys of patients with chronic diabetes affected?
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)
What are the manifestations of retinopathy in chronic diabetes mellitus?
- Hemorrhage
- Exudates
- Microaneurysms
- Vessel proliferation
What are the manifestations of nephropathy in chronic diabetes mellitus?
- Nodular sclerosis
- Progressive proteinuria
- Chronic renal failure
- Arteriolosclerosis leading to HTN
- Kimmelstiel-Wilson nodules
What are the manifestations of non-enzymatic glycosylation on large vessels in patients with chronic diabetes?
- Large vessel atherosclerosis → cerebrovascular disease
- CAD → MI (most common cause of death)
- Peripheral vascular occlusive disease
- Gangrene → limb loss
What is the most common cause of death in patients with Diabetes Mellitus?
Myocardial Infarction
What causes osmotic damage in patients with chronic diabetes?
Sorbitol accumulates in organs with aldose reductase and ↓ or absent sorbitol dehydrogenase
What are the manifestations of osmotic damage in patients with chronic diabetes?
- Neuropathy: motor, sensory, and autonomic degeneration
- Cataracts
What tests can be used to assess a patient's diabetes mellitus?
- Fasting serum glucose
- Oral glucose tolerance test
- HbA1c (reflects average blood glucose over prior 3 months)
What is the primary defect in T1DM vs T2DM?
- T1DM: auto-immune destruction of β cells
- T2DM: ↑ resistance to insulin, progressive pancreatic β-cell failure
Is insulin necessary in treatment of T1DM and T2DM?
- T1DM: always
- T2DM: sometimes
What is the typical age of onset for patients with T1DM vs T2DM?
- T1DM: <30 years
- T2DM: >40 years

*Exceptions commonly occur
What is the association with obesity for T1DM vs T2DM?
- T1DM: none
- T2DM: associated
Is there a genetic predisposition for T1DM vs T2DM?
- T1DM: relatively weak (50% concordance in identical twins), polygenic
- T2DM: relatively strong (90% concordance in identical twins), polygenic
What is the association with HLA system for T1DM vs T2DM?
- T1DM: associated with HLA-DR3 and -DR4
- T2DM: no association
What is the relative glucose intolerance in T1DM vs T2DM?
- T1DM: severe
- T2DM: mild to moderate
What is the relative insulin sensitivity in T1DM vs T2DM?
- T1DM: high
- T2DM: low
How common is ketoacidosis in T1DM vs T2DM?
- T1DM: common
- T2DM: rare
How many β-cells are there in the islets relatively in T1DM vs T2DM?
- T1DM: ↓ β-cell numbers
- T2DM: variable (with amyloid deposits)
What is the relative serum insulin level in T1DM vs T2DM?
- T1DM: ↓
- T2DM: Variable
Are the classic symptoms of polyuria, polydipsia, polyphagia, and weight loss seen in T1DM vs T2DM?
- T1DM: common
- T2DM: sometimes
What is the histologic appearance of the Islets of Langerhans in T1DM vs T2DM?
- T1DM: islet leukocytic infiltrate (auto-immune process)
- T2DM: islet amyloid polypeptide (IAPP) deposits
What is one of the most important complications of diabetes (usually type 1)?
Diabetic Ketoacidosis
What causes diabetic ketoacidosis?
- 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
What are the types of ketone bodies? Which is more common in diabetic ketoacidosis?
β-Hydroxybutyrate > Acetoacetate
What are the signs / symptoms of diabetic ketoacidosis?
- Kussmaul respirations (rapid / deep breathing)
- Nausea / vomiting
- Abdominal pain
- Psychosis / delirium
- Dehydration
- Fruity breath odor (due to exhaled acetone)
What are Kussmaul respirations? Sign of?
- Rapid / deep breathing
- Sign of diabetic ketoacidosis
What causes the fruity breath odor in diabetics?
Diabetic ketoacidosis → exhaled acetone
What are the lab findings associated with diabetic ketoacidosis?
- Hyperglycemia
- ↑ H+ and ↓ HCO3- (anion gap metabolic acidosis)
- ↑ Blood ketone levels
- Leukocytosis
- Hyperkalemia, but depleted intracellular K+ d/t transcellular shift from ↓ insulin
What kind of acid/base disturbance occurs with diabetic ketoacidosis?
Anion gap metabolic acidosis
- ↑ H+
- ↓ HCO3-
How are WBCs affected in diabetic ketoacidosis?
Leukocytosis
How is K+ balance affected in diabetic ketoacidosis?
- Hyperkalemia
- Depleted intracellular K+ because of transcellular shift from ↓ insulin
What are the potenial complications of diabetic ketoacidosis?
- Life-threatening mucormycosis (usually caused by Rhizopus infection)
- Cerebral edema
- Cardiac arrhythmias
- Heart failure
How do you treat diabetic ketoacidosis?
- IV fluids
- IV insulin
- K+ (to replete intracellular stores)
- Glucose if necessary to prevent hypoglycemia
What is the source of an insulinoma? What is its effect?
- Tumor of β cells of pancreas
- Over-produces insulin → hypoglycemia
What are the common symptoms with an insulinoma?
Whipple triad of episodic CNS symptoms:
- Lethargy
- Syncope
- Diplopia
What lab values are associated with insulinoma?
- ↓ Blood glucose
- ↑ C-peptide (vs exogenenous insulin use which would cause similar findings but have low/normal C-peptide)
How do you treat an insulinoma?
Surgical resection of tumor in pancreas
What is the most common malignancy in the small intestine?
Carcinoid Syndrome
What causes Carcinoid Syndrome?
Rare syndrome caused by carcinoid tumors (neuroendocrine cells), especially metastatic small bowel tumors, which secrete high levels of serotonin (5-HT)
What is necessary for a carcinoid tumor of the small intestine to cause Carcinoid Syndrome?
- 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
What are the symptoms of Carcinoid Syndrome?
- Recurrent diarrhea
- Cutaneous flushing
- Asthmatic wheezing
- Right sided valvular disease
What are the lab changes associated with Carcinoid Syndrome?
- ↑ 5-hydroxyindoleacetic acid (5-HIAA) in urine
- Niacin deficiency (pellagra - diarrhea, dementia, dermatitis)
How do you treat Carcinoid Syndrome?
- Resection of carcinoid tumor
- Somatostatin analog (eg, octreotide)
What is the rule of 1/3 for Carcinoid Syndrome?
- 1/3 metastasize
- 1/3 present with 2nd malignancy
- 1/3 are multiple
What causes Zollinger-Ellison Syndrome?
- Gastrin-secreting tumor of pancreas or duodenum
- Leads to acid hyper-secretion → recurrent ulcers in distal duodenum and jejunum
Zollinger-Ellison Syndrome leads to ulcers where?
Distal duodenum and jejunum
What symptoms does a patient with Zollinger-Ellison Syndrome typically present with?
- Abdominal pain (peptic ulcer disease, distal ulcers)
- Diarrhea (malabsorption)
What may Zollinger-Ellison Syndrome be associated with?
MEN 1
What are the types of Multiple Endocrine Neoplasias?
- MEN 1 (Wermer syndrome)
- MEN 2A (Sipple syndrome)
- MEN 2B
What kind of tumors are associated with MEN 1?
MEN 1 = 3 P's (diamond):
- Pituitary tumors (prolactin or GH)
- Parathyroid tumors 
- Pancreatic endocrine tumors (Zollinger Ellison syndrome, insulinomas, VIPomas, glucagonomas-rare)
MEN 1 = 3 P's (diamond):
- Pituitary tumors (prolactin or GH)
- Parathyroid tumors
- Pancreatic endocrine tumors (Zollinger Ellison syndrome, insulinomas, VIPomas, glucagonomas-rare)
Besides pituitary tumors, parathyroid tumors, and pancreatic endocrine tumors, what else is associated with MEN 1?
- Kidney stones
- Stomach ulcers
What kind of tumors are associated with MEN 2A?
MEN 2A: 2 P's (square):
- Parathyroid (hyperplasia)
- Pheochromocytoma (adrenals)

- Medullary Thyroid Carcinoma (secretes calcitonin)
MEN 2A: 2 P's (square):
- Parathyroid (hyperplasia)
- Pheochromocytoma (adrenals)

- Medullary Thyroid Carcinoma (secretes calcitonin)
Besides medullary thyroid carcinoma, pheochromocytoma, and parathyroid hyperplasia, what else is associated with MEN 2A?
Associated with RET gene mutations
What kind of tumors are associated with MEN 2B?
MEN 2B: 1 P (triangle):
- Pheochromocytoma (adrenals)

- Oral / intestinal ganglioneuromatosis (mucosal neuromas)
- Medullary Thyroid Carcinoma (secretes calcitonin)
MEN 2B: 1 P (triangle):
- Pheochromocytoma (adrenals)

- Oral / intestinal ganglioneuromatosis (mucosal neuromas)
- Medullary Thyroid Carcinoma (secretes calcitonin)
Besides medullary thyroid carcinoma, pheochromocytoma, and oral/intestinal ganglioneuromatosis (mucosal neuromas), what else is associated with MEN 2B?
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
How are MEN syndromes inherited? Other associated genetic changes?
- All are autosomal dominant (think "MEN are dominant" - or so they think)
- Associated with RET gene mutation in MEN 2A and 2B