Endocrine - Step Up To Medicine

Front 1

Causes of hyperthyroidism

Back 1

1. Grave's disease - diffuse toxic goiter) - most common cause
2. Plummer's disease - multinodular toxic goiter
3. Toxic thyroid adenoma (single nodule) - 2% of all cases
4. Hashimoto's thyroiditis and subacute (granulomatous) thyroiditis - both can cause transient hyperthyroidism
5. other causes- post- partum thyroiditis (transient hyperthyroidism), and iodine-induce hyperthyroidism, excessive doses of levothyroxine (iatrogenic by physician or self admin for weight loss)

Front 2

Grave's disease (diffuse toxic goiter)
1. etiology
2.. who is most often affected?
3. what would a radioiodide scan show?

Back 2

1. The most common cause of hyperthyroidism - 80% of all cases.
- Autoimmune disorder: thyroid simulating immunoglobulin (IgG) antibodies bind to the TSH receptors on the surface cells of the
2. seen most often in younger women. Commonly associated with autoimmune disorders
3. A radioiodide scan would show diffuse uptake because every thyroid cell is hyperfunctioning

Front 3

Plummer's disease (multinodular toxic goiter)
1. etiology/pathophysiology
2. thyroid scan appearance
3. who is most often affected?

Back 3

1. 15% of all cases. Characterized by hyperfunctioning areas that produce high T4 and T3 levels, thereby decreasing TSH levels. As a result, the rest of the thyroid is not functioning/atrophic due to dec TSH
2. Patchy uptake on thyroid scan
3. more common in elderly patients and more common in women than men

Front 4

Clinical features of hyperthyroidism

Back 4

1. nervousness, insomnia, irritability
2. hand tremor, hyperactivity, tremulousness
3. excessive sweating, heat intolerance
4. weight loss despite increase appetite
5. diarrhea, frequent defecation
6. palpitations
7. muscle weakness

Front 5

Signs of hyperthyroidism on exam
1. thyroid - a. Graves, b. subacute thyroiditis, c. Plummer's disease, d. toxic adenoma
2. extrathyroid signs
a. eyes, b. CV, c. skin, d. neuro

Back 5

1. Thyroid gland
a. Grave's disease- diffusely enlarged (symmetric), nontender thyroid gland, a bruit may be present
b. Subacute thyroiditis- an exquisitely tender, diffusely enlarged gland (with a viral illness)
c. Plummer's disease and Hashimoto's thyroiditis- if multinodularity is present then gland is bumpy, irregular and assymetric
d. Toxic adenoma- single nodule with otherwise atrophic gland
2. Extrathyroid signs
a. eyes: proptosis, due to edema of the extraocular muscles and retro-orbital tissue-- hallmark of grave's (but not always present). Irritation and excessive tearing are common due to corneal exposure. Lid retraction may be the only sign in milder disease. Lid lad may be present.
b. CV - arrhythmias (sinus tachycardia, atrial fibrillation, and PVCs), elevated BP
c. Skin changes- warm and moist, pretibial myxedema (edema over tibial surface dye to dermal accumulation of mucopolysaccharides
d. neuro - brisk DTRs, tremor

Front 6

Proptosis

Back 6

- bulging of the eyes- exopthlamous- due to edema of the extraocular muscles and retro-orbital tissue-- hallmark of grave's (but not always present). Irritation and excessive tearing are common due to corneal exposure. Lid retraction may be the only sign in milder disease. Lid lad may be present.

Front 7

Diagnosis of hyperthryroidism

Back 7

1. Serum TSH level (low) - initial test of choice. If TSH is normal or high then hyperthyroidism is unlikely as it should decrease in response to high T3 or T4. TSH- induced hyperthyroidism is quite uncommon.
2. Next order thyroid hormone levels: T4 level should be elevated. Consider a free T4 level assay.
3. Testing the T3 level is usually unnecessary but may be helpful if TSH level is low and T4 is not elevated, because excess T3 alone can cause hyperthyroidism
4. Other tests
a. Radioactive T3 uptake
b. Free Thyroxine Index (FTI)

Front 8

Interpretation of Radioactive T3 uptake test

Back 8

a. Radioactive T3 uptake- gives information regarding the status of thyroid binding globulin (TBG)
b. Radioactive T3 can bind either to TBG of to "resin" that has been given (binds to resin only if there is no "space" on TBG as in hyperthyroidism when T4 is bound to TBG
c. The importance of this test is that it helps differentiate between elevation in thyroid hormones due to increased TBG from true hyperthyroidism (due to an increase in Free T4)
d. consider hyperthyroidism when the thyroid gland is producing excess T4. In this cases, all the binding sites on TBG will be bound to T4, so radioactive T3 uptake will increase.
e. Consider pregnancy when there is a high TBG. There are more binding sites for radioactive T3, so radioactive T3 uptake decreases. Therefore, high TBG production leads to low radioactive T3 uptake.

Front 9

Free Thyroxine Index (FTI)

Back 9

1. FTI = (radioactive T3 uptake x serum total T4)/100
2. FTI = (patient's radioactive T3 uptake/normal radioactive T3 uptake) 3 total T4
3. Normal FTI values are 4-11. FTI should not change (as T4 decreases, radioactive T3 uptake increases and vice versa)
4. FTI is proportional to actual free T4 concentration

Front 10

Treatment of hyperthyroidism (3 options)

Back 10

1. Pharmacologic (thionamides-e.g. methimazole, b-blockers, sodium ipodate, etc)
2. radioiodine ablation- 131 Radioiodine
3. Surgical- subtotal thyroidectomy

Front 11

Pharmacologic Treatment of Hyperthyroidism

Back 11

1. Thionamides- Methimazole and Propylthiouracil (PTU) inhibits thyroid hormone synthesis, and PTU also inhibits conversion of T4 to T3 in the periphery. Treatment with thionamides results in long-term remission in the minority of patients, a major serious side effect is agranulocytosis. (Methimazole should not be used in pregnancy as it can cause aplasia cutis- congenital lack of skin)
2. beta-blockers- for acute management of symptoms such as palpitations, tremors, anxiety, tachycardia, sweating, and muscle weakness
3. Sodium ipodate or iopanoic acid- lowers serum T3 and T4 levels and causes rapid improvement in hyperthyroidism. Appropriate for acute management of severe hyperthyroidism that is not responding to conventional therapy

Front 12

Radioiodine 131 Treatment of Hyperthyroidism

Back 12

- causes destruction of thyroid follicular cells
- most common therapy in the US for Grave's hyperthyroidism
- main complication is hypothyroidism and occurs in majority of patients
- If the first dose does not control the hyperthyroidism within 6-12 months, then administer another dose
- Contraindicated in pregnancy and breastfeeding due to risk of cretinism (destroys baby's thyroid too)

Front 13

Surgical Treatment of hyperthyroidism

Back 13

Subtotal thyroidectomy
- very effective, but only 1% of patients with hyperthyroidism are treated with surgery due the following side effects : permanent hypothyroidism (30%), recurrence of hyperthyroidism (10%), recurrent laryngeal nerve palsy (1%), permanent hypoparathyroidism (1%)
- Often reserved for patients with very large goiters (more common in Toxic Multinodular Goiter), those who are allergic to anti-thyroid drugs, or patients who prefer surgery over meds
- Watch for hypocalcemia after surgery that may not return to normal due to parathyroid inflammation or accidental removal

Front 14

Treatment of hyperthyroidism
1. Immediate control of adrenergic symptoms
2. nonpregnant patients with Grave's disease
3. Pregnant patients with Grave's disease
4. radioactive Iodine ablation

Back 14

1. Beta-blocker (propanolol)
2. Start methimazole (in addition to beta-blocker), taper beta blocker after 4-8 weeks (once methimazole takes effect). Continue for 1-2 years. Measure thyroid stimulating antibodies at 12 months. If it is absent then discontinue therapy. If relapse occurs then resume for 1 more year or consider radioiodine therapy
3. Endo consult before treatment, PTU preferred
4. leads to hypothyroidism over time in many patients. Consider for the following patients (elderly with grave's, patients with solitary toxic nodule, patients with grave's who therapy with anti-thyroid drugs fail- due to relapse or agranulocytosis)

Front 15

Thyroid storm
1. frequency
2. cause
3. mortality
4. clinical manifestations

Back 15

RARE, but life-threatening complication of thyrotoxicosis characterized by an acute exacerbation of the manifestations of hyperthyroidism
- there is usually a precipitating factor, such as infection, DKA, or stress (e.g. severe trauma, surgery, illness, childbirth)
- High mortality rate: up to 20% of patients enter a coma or die
- Clinical manifestations include marked fever, tachycardia, agitation, or psychosis, confusion, and GI symptoms (n/v, diarrhea)

Front 16

Treatment of thyroid storm

Back 16

1. provide supportive therapy with IV fluids, cooling blankets, and glucose
2. Give anti-thyroid agents (PTU every 2 hours). Follow with iodine to inhibit thyroid hormone release
3. administer beta-blockers for control of heart rate. Give dexamethasone to impair peripheral generation of T3 from T4 and to provide adrenal support (T3 is more active than T4-- higher affinity for receptors)

Front 17

Cretinism

Back 17

congenital thyroid hormone deficiency
- pot belly, large tongue, MR, and protruding umbilicus

Front 18

Hypothyroidism
1. clinical course

Back 18

1. Onset of symptoms is usually insidious, and the condition may go undetected for years
- Sometimes the diagnosis made solely on laboratory evidence in an asymptomatic patient

Front 19

Causes of hypothyroidism
1. Primary
2. Secondary and Tertiary

Back 19

1. Primary- failure of the throid gland to produce sufficient thyroid hormone. This accounts for 95% of all cases. High TSH should be seen
a. Hashimoto's disease- chronic thyroiditis- most common cause of primary hypothyroidism
b. Iatrogenic- second most common cause of primary hypothyroidism; results from prior treatments of hyperthyroidism, including: radioiodine ablation, thyroidectomy, medications (e.g. lithium)
2. Secondary- due to pituitary insufficiency-- dec TSH and tertiary hypothyroidism- due to hypothalamic disease (i.e. deficiency of TRH)- accounts for less than 5% of cases. Both are associated with low free T4 and a low TSH level

Front 20

Clinical features/symptoms of hypothyroidism

Back 20

1. fatigue, weakness, lethargy
2. heavy menstrual periods (menorrhagia), slight weight gain (10-30 lbs)-- patients are NOT typically obese
3. cold intolerance
4. constipation
5. slow mentation, inability to concentrate (mild at first, then in later stages-- dementia)
6. muscle weakness, arthralgias
7. depression
8. diminished hearing

Front 21

Signs of hypothyroidism on physical exam

Back 21

1. dry skin, coarse hair, thickened, puffy features
2. hoarseness
3. non-pitting edema (edema is due to glycosaminoglycan in the interstitial tissues, not water and salt
4. carpal tunnel syndrome
5. slow relaxation of DTRs
6. Loss of lateral portion of eyebrows
7. bradycardia
8. goiter (hashimoto's disease-- goiter is rubber, non-tender and even nodular; subacute thyroiditis-- goiter is very tender and enlarged although not always symmetrically)
9. History of upper respiratory infection an fever (subacute thyroiditis)

Front 22

What is Hashimoto's thyroiditis associated with and what are these patients at an increased risk of developing?

Back 22

1. Associated with other autoimmune disorders (e.g. lupus, pernicious anemia)
2. Increased risk of thyroid carcinoma and thyroid lymphoma

Front 23

Diagnosis of hypothryoidism
1. most sensitive test
2. What is increased in Hashimoto's specifically?
3. Other lab value abnormalities

Back 23

1. TSH. A high TSH level is most sensitive indicator of primary hypothyroidism. A low TSH level indicates either secondary or tertiary hypothyroidism
- Low free T4 level (or free T4 index) in patients with clinically overt hypothyroidism. Free T4 may be normal in subclinical cases.
2. Increased anti-microsomal antibodies
3. Elevated LDL and decreased HDL levels.
- Anemia- mild normocytic anemia is the most common

Front 24

Treatment of hypothyroidism

Back 24

1. Levothyroxine (T4) is the treatment of choice
- effect is evident in 2-4 weeks: highly effective in achieving euthyroid state
- convenient once-daily morning dose
- Treatment is continued indefinitely
- Monitor TSH level and clinical state periodically

Front 25

Subacute (viral) thyroiditis (subacute granulomatous thyroiditis)

Back 25

1. Causes- usually follows a viral illness; associated with HLA-B35
2. Clinical features- prodromal phases of a few weeks (fever, flu-like illness). It can cause transient hyperthyroidism due to leakage of hormone from the inflamed thyroid gland. This is followed by a euthyroid state and then a hypothyroid state (as hormones are depleted)
3. Diagnosis
- Radioiodine uptake is low because thyroid follicular cells are damaged and cannot trap iodine
- Low TSH secondary to suppression by increased T4 and T3 levels; high ESR
4. Treatment- use NSAIDs and aspirin for mild symptoms; corticosteroids, if the pain is more severe
- most patients have recovery of thyroid function within a few months to 1 year

Front 26

Subacute Lymphocytic Thyroiditis

Back 26

- painless thyroiditis, silent thryoiditis
1. A transient thyrotoxic phase of 2-5 months may be followed by a hypothyroid phase, which is usually self-limited and may be the only manifestation of this disease if the hyperthyroid phase is brief.
2. Low radioactive iodine uptake- differentiates it from Grave's disease during thyrotoxic phase
3. Similar to subacute (viral) thyroiditis, only without pain or tenderness of the thyroid gland

Front 27

Chronic lymphocytic thyroiditis
1. prevalence
2. Causes
3. clinical manifestations
4. Diagnosis
5. Treatment

Back 27

- Hashimoto's thyroiditis, lymphocytic thyroiditis)
- Most common cause of autoimmune thyroid disorder. More common in women.
2. Causes- Genetic component - family history is common. Antithyroid antibodies are present in the majority of patients.
3. Clinical manifestations- Goiter is the most common feature. Slow decline in thyroid function is common. Hypothyroidism is present in 20% of cases when first diagnosed but often occurs later in disease
4. Diagnosis- thyroid function studies are normal (unless hypothyroidism is present). Antithyroid antibodies: antiperoxidase antibodies (anti-TPO antibodies) - present in in 90% of patients, anti-thyroglobulin antibodies (present in 50%)
5. Treatment - thyroid hormone (to achieve euthyroid state)

Front 28

Fibrous thyroiditis (Riedel's thyroiditis)
1. Pathophysiology
2. treatment

Back 28

1. Fibrous tissue replaces thyroid tissue, leading to a firm thyroid.
2. Surgery may be necessary if complications occur
3. Patients may be hypothyroid as well, in which case thyroid hormone should be prescribed

Front 29

Thyroid Nodules
1. cancerous?
2. solitary nodule
3. most important function of physical exam
4. how big must it be to detect it on exam
5. What suggests malignancy?

Back 29

1. Cancer is found in 4-10% of nodules that are investigated
2. A solitary nodule can either be thyroid cancel or a benign ademona. However, multinodular conditions may cause confusion because only one of these nodules may be palpable
3. the most important function of physical exam is the detection of the nodule, not determining whether it is benign or malignant
4. To be detectable on palpation, a nodule must be at least 1 cm in diameter
5. Malignancy is suggested by the following:
a. If the nodule is fixed in placed and no movement occurs on swallowing
b. unusually firm consistency or irregularity of the nodule
c. if the nodule is solitary
d. history of radiation therapy to the neck
e. history of rapid development
f. vocal cord paralysis (recurrent laryngeal nerve paralysis)
g. cervical adenopathy

Front 30

Diagnosis of a thyroid nodule

Back 30

1. Fine Needle Aspiration (FNA) biopsy
2. Thyroid Scan (radioactive iodine)
3. Thyroid Ultrasound

Front 31

Fine Needle Aspiration of Thyroid Nodule

Back 31

- test of choice for initial evaluation of a thyroid nodule- often combined with US guidance for better diagnostic utility
- Accuracy- FNA has sensitivity of 95% and specificity of 95%. Therefore, if FNA shows a benign nodule, the nodule is most likely to be benign.
- However, FNA biopsies have 5% false-negative results, so follow-up with periodic FNA if thyroid nodularity persists. Benign lesions should continue to show consistently benign cytology
- FNA is reliable for all cancers (papillary, medullary, anaplastic), EXCEPT follicular

Front 32

Thyroid Scan (radioactive iodine) - role in assessing a thyroid nodule

Back 32

1. Thyroid scans play a supplemental role to FNA. It is performed if the FNA biopsy is indeterminate. It is also performed in patients with a low TSH, as these patients are more likely to have a hyperfunctioning nodule.
2. It gives graphic representations of the distribution of radioactive iodine in the gland. Useful in identifying whether thyroid nodules show decreased ("cold") or increased ("hot") accumulation of radioactive iodine compared with normal paranodular tissue. Nodules are classified as "cold" (hypofunctional), "warm" (normally functioning), or "hot" (hyperfunctional).
- It should be limited to patients whose FNA biopsy suggests a neoplasm. It is not cost effective to scan all patients with thyroid nodules. When such lesions are "cold" on scan, thyroid lobectomy is recommended

Front 33

Thyroid Ultrasound

Back 33

1. Differentiates a solid from a cystic nodule; most cancers are solid
2. Can identify nodules 1-3 mm in diameter
3. Cystic masses larger than 4 cm in diameter are likely not malignant
4. Cannot distinguish between benign and malignant thyroid nodules

Front 34

Thyroid Cancer
1. risk factors
2. types

Back 34

1. Head and neck radiation (during childhood), Gardener's syndrome and Cowden's syndrome for papillary cancer, MEN II for medullary cancer
2. Papillary carcinoma
- Follicular carcinoma
- Medullar carcinoma
- Anaplastic carcinoma

Front 35

Papillary Thyroid Cancer

Back 35

1. accounts for 70-80% of all thyroid cancers
2. least aggressive thryoid cancer- slow growth and slow spreading
3. Most important risk factor is a history of radiation to the head/neck
4. spreads via the lymphatics in the neck. Frequently metastasizes to the cervical lymph nodes - distant mets are rare
5. positive iodine uptake
6. histology shows "orphan annie nuclei"

Front 36

Follicular Carcinoma of the thyroid

Back 36

1. Accounts for 15% of all thyroid cancers, avidly absorbs iodine
2. Prognosis is worse than for papillary cancer. It spreads early via a hematogenous route (brain, lung, bone, liver). Distant mets occur in 20% of patients. Lymph node involvement is uncommon
3. may be associated with iodine deficiency
4. tumor extension through the tumor capsule or vascular invasion distinguishes it from a benign adenoma. A tissue sample is therefore needed for diagnosis
5. more malignant than papillary cancer, but these are slow growing
6. one variant is the hurthle cell carcinoma- characteristic cells contain abundant cytoplasm, tightly packed mitochondria, and oval nuclei with prominent nucleoli. These tumors are radioiodine resistant.

Front 37

Hurthle Cell Variant of Follicular Thyroid Cancer

Back 37

- more aggressive than normal follicular thyroid cancer
- spread by lymphatics ( as opposed to hematogenous spread)
- does not take up iodine
- Treatment - total thyroidectomy

Front 38

Medullary Carcinoma of the thyroid

Back 38

- accounts for 2-3% of all thyroid cancers
- 1/3 sporadic, 1/3 familial, and 1/3 associated with Multiple Endocrine Neoplasia type II (MEN II) - always screen for pheochromocytoma
- Arises from the parafollicular C cells- produces calitonin
- More malignant than follicular cancer but less so than anaplastic cancer- survival of approximately 10 years

Front 39

Anaplastic Carcinoma

Back 39

- accounts for 5% of all thyroid cancers: mostly seen in elderly patients
- highly malignant
- may arise from longstanding follicular or papillary thyroid carcinoma
- prognosis is grim- death typically occurs within a few months. Mortality is due to invasion of adjacent organs (trachea, neck vessels)

Front 40

Diagnosis of thyroid cancer

Back 40

1. thyroid hormone level
2. calcitonin level (if medullary carcinoma)
3. Same diagnostic approach for thyroid nodule-- FNA is first choice

Front 41

What is the most common type of thyroid cancer to develop after history of head/neck radiation exposure

Back 41

Papillary carcinoma-- accounts for 80-90% of post-radiation cancers of the thyroid

Front 42

Treatment of thyroid cancer by subtype
1. papillary
2. follicular
3. medullary
4. anaplastic

Back 42

1. Papillary carcinoma- a. lobectomy with isthmusectomy, b. total thyroidectomy if tumor is > 3 cm, tumor is bilateral, tumor is advanced or distant mets are present, c. adjuvant treatment: TSH suppression therapy, radioiodine therapy for large tumors
2. Follicular- total thyroidectomy with postoperative iodine ablation
3. medullary carcinoma- total thyroidectomy, radioiodine therapy, usually unsuccessful. Modified radical neck dissection is also indicated when there is lymph node involvement- most cases
4. anaplastic- chemo and radiation may provide a modest improvement in survival. Palliative surgery for airway compromised may be needed.

Front 43

Pituitary Adenomas
1. general characteristics
(what % of intracranial neoplasms, malignancy, size)

Back 43

- account for 10% of all intracranial neoplasms
- almost all pituitary tumors are benign but they may grow in any direction causing "parasellar" signs and symptoms
- Size- microadenoma (diameter </= 10 mm), macroadenoma (diameter >/= 11 mm)

Front 44

Clinical features of pituitary adenomas

Back 44

1. hormonal effects occur due to hypersecretion of one or more of the following hormones: Prolactin, GH, ACTH, TSH
2. hypopituitarism- compression of hypothalamic-pituitary stalk, GH deficiency and hypogonadotropic hypogonadism are the most common problems
3. Mass effects- headaches and visual defects-- bitemporal hemianopsia (due to compression of the optic chiasm) is the most common finding, but it depends on the size and symmetry of the tumor

Front 45

Diagnosis of pituitary ademonas

Back 45

1. MRI is the imaging study of choice
2. pituitary hormone levels

Front 46

Treatment of pituitary adenoma

Back 46

1. transphenoidal surgery is indicated in most patients (except with prolactinomas as medication should be tried first - bromocriptine)
2. radiation therapy and medical therapy are adjuncts in most patients

Front 47

Hyperprolactinemia
1. causes

Back 47

1. Prolactinoma- most common cause, most common type of pituitary adenoma
2. medications- psychiatric medications, H2 blockers, metoclopramide, verapamil, estrogen)
3. Pregnancy
4. Renal failure
5. Suprasellar mass lesions (can compress hypothalamus or pituitary stalk)
6. hypothyroidism
7. idiopathic

Front 48

Clinical features of hyperprolactinemia
1. in men
2. in women

Back 48

1. men - hypogonadism, decreased libido, infertility, impotence, galactorrhea or gynecomastia (uncommon), parasellar signs and symptoms (visual field defects and headaches)
2. women- premenopausal- menstrual irregularities, oligomenorrrhea or amenorrhea, anovulation and infertility, decreased libido, dyspareunia, vaginal dryness, risk of osteoporosis, and galactorrhea
postmenopausal- parasellar signs and symptoms- (less common in men)

Front 49

Diagnosis of hyperprolactinemia

Back 49

1. Elevated serum prolactin level
2. order a pregnancy test and TSH level because both pregnancy and primary hypothyroidism are on the differential for hyperprolactinemia
3. CT scan or MRI to identify any mass lesions

Front 50

Treatment of hyperprolactinemia
1. for all causes
2. for prolactinoma
3. if medical treatment fails

Back 50

1. Treat the underlying cause (e.g. stop medication, treat hypothyroidism)
2. If prolactinoma is the cause and the patient is symptomatic, treat with bromocriptine- a dopamine agonist that secondarily diminishes the production and release of prolactin. Continue to treatment for approximately 2 years before attempting cessation. Carbergoline (dopamine agonist) may be better tolerated than bromocriptine.
3. consider surgical intervention if symptoms progress despite appropriate medical therapy. However, the recurrence rate after surgery is high

Front 51

Acromegaly
1. general characteristics
2. cause and prevalence

Back 51

1. broadening of the skeleton, which results from excess secretion of pituitary GH after epiphyseal closure (if before epiphyseal closure, gigantism (excessive height) results)
2. It is almost always caused by a GH-secreting pituitary adenoma (represents 10% of pituitary adenomas)

Front 52

Clinical features of acromegaly

Back 52

1. growth promotion - soft tissue and skeleton overgrowth, coarsening of facial features, abnormally large hand and foot size (ask about increasing glove/ring/shoe/hat size), organomegaly, arthralgia due to joint tissue overgrowth, hypertrophic cardiomyopathy, enlarged jaw (macrognathia)
2. Metabolic disturbances- glucose intolerance and DM in 10-25% of patients, hyperhidrosis
3. parasellar manifestations- headache, superior growth leads to compression of optic chiasm--> bitemporal hemianopsia, lateral growth leads to cavernous sinus compression, inferior growth leads to sphenoid sinus invasion), HTN, sleep apnea

Front 53

Diagnosis of acromegaly

Back 53

1. IGF-1, also known as somatomedin C, should be significantly elevated in acromegaly
2. oral glucose suppression test- glucose load fails to suppress GH (as it should in healthy individuals). This confirms the diagnosis if the IGF-1 level is equivocal.
3. MRI of the pituitary
4. a random GH level is not useful because there is a wide physiologic fluctuation of GH levels

Front 54

Treatment of acromegaly

Back 54

1. Transphenoidal resection of pituitary adenoma- treatment of choice
2. radiation therapy if IGF-1 levels remain elevated after surgery
3. octreotide or other somatostatin analog to suppress GH secretion

Front 55

Craniopharyngioma
1. embryologic remnant of what
2. prevalence
3. clinical features
4. diagnosis
5. endocrine abnormalities
6. treatment

Back 55

1. tumors of the suprasellar region arising from embryologic remnants of Rathke's pouch
2. These tumors comprise 20-25% of all pituitary mass lesions (pituitary adenoma is the most common)
3. They result in visual field defects (bitemporal hemianopsia) due to compression of the optic chiasm and may also cause headaches, papilledema and changes in mentation.
4. Diagnosed by brain MRI
5. they may cause hyperprolactinemia, diabetes insidus, or panhypopituitarism
6. Treatment is surgical excision (total or partial resection) with or without radiation therapy

Front 56

Hypopituitarism

Back 56

1. All or some of the hormones released from the anterior pituitary are absent (FSH, LH, ACTH, TSH, Prolactin, GH)
2. loss of hormones is unpredictable, but LH, FSH and GH are usually lost before TSH and ACTH
3. Clinical manifestations depend on which hormones are lost

Front 57

Causes of hypopituitarism

Back 57

1. hypothalamic or pituitary tumor is the most common cause
2. other causes: radiation therapy, Sheehan's syndrome, infiltrative process (e.g. sarcoidosis, hemachromatosis), head trauma, cavernous sinus thrombosis, surgery

Front 58

Clinical features of hypopituitarism by hormone affected

Back 58

1. reduced GH - growth failure (decreased muscle mass in adults), increased LDL, and inc risk of heart disease
2. reduced prolactin- failure to lactate
3. reduced ACTH- adrenal insufficiency
4. reduced TSH- hypothyroidism
5. reduced gonadotropins (LH and FSH): infertility, amenorrhea, loss of secondary sex characteristics, diminished libido
6. reduced antidiuretic hormone (ADH) - if hypothalamic lesion- diabetes insipidus
7. reduced melanocyte-stimulating hormone- decreased skin and hair pigmentation

Front 59

Diagnosis of hypopituitarism

Back 59

1. low levels of target hormones with low or normal levels of trophic hormones (it is the suppression of the trophic hormones that is important, although the absolute level may be in the normal reference range)
2. MRI of the brain

Front 60

Treatment of hypopituitarism

Back 60

1. Replacement of appropriate hormones
2. women who want to conceive should be referred to an endocrinologist

Front 61

Diabetes Insipidus- Two forms and causes of each

Back 61

1. Central Diabetes Insipidus - most common form - due to low ADH secretion by the posterior pituitary
a. idiopathic in 50% of all cases
b. trauma- surgery, head trauma
c. other destructive processes involving the hypothalamus, including tumors, sarcoidosis, tuberculosis, syphilis, Hand-Shuller-Christian Disease, eosinophilic granuloma, encephalitis
2. Nephrogenic Diabetes Insipidus- ADH secretion is normal but tubules cannot respond to ADH
a. most common cause in adults is chronic lithium use
b. other causes- hypercalcemia, pyelonephritis, and demeclocycline use. It may also be congenital, caused by mutations in the ADH receptor gene or the aquaporin-2 gene

Front 62

clinical features of diabetes insipidus

Back 62

1. Polyuria is a hallmark finding: 5 to 15 L daily, urine is colorless as it is dilute
2. Thirst and polydipsia- hydration is maintained if the patient is conscious and has access to water
3. Hypernatremia is usually mild unless the patient has an impaired thirst drive

Front 63

Diagnosis of diabetes insipidus

Back 63

1. Urine- low specific gravity and low osmolality indicate DI
2. Plasma osmlality - Normal: 250-290 mOsm/kg, Primary polydipsia- 255-280 mOsm/kg, DI - 280 to 310 mOsm/kg (more concentrated)
3. Water deprivation test- required for diagnosis. Procedure- withhold fluids, and measure urine osmolality ever hour. When urine osmolality is stable (<30mOsm/kg hourly increase for 3 hours), inject 2 g desmopressin subQ. Measure urine osmolality 1 hour later. Normal patients will have more concentrated urine with water deprivation, but patients with DI will not. If the cause is central then there will be a response to desmopressin (ADH), but not if it is nephrogenic
4. ADH level- not test of choice as it takes awhile. Low in central DI, and normal or elevated in nephrogenic DI

Front 64

Treatment of central diabetes insipidus

Back 64

1. Desmopressin (DDAVP) is the primary therapy and can be given by nasal spray, orally or by injection
2. Chlorproramide increases ADH secretion and enhances the effect of ADH
3. Treat the underlying cause

Front 65

Treatment of nephrogenic diabetes insipidus

Back 65

1. Sodium restriction and thiazide diuretics
- these deplete the body of sodium, which leads to increased reabsorption of sodium and water in the proximal tubules
- the reabsorption of sodium and water in the proximal tubules means that less reaches the distal tubules (where ADH exerts its effect), leading to decreased urine volume

Front 66

Syndrome of Inappropriate Secretion of ADH (SIADH)- pathophysiology

Back 66

1. Excess ADH is secreted from the posterior pituitary or an ectopic source. Elevated levels lead to water retention and excretion of concentrated urine, which has two major effects: hyponatremia and volume expansion
2. despite volume expansion, edema is NOT seen in SIADH- this is because natriuresis (excretion of excess sodium in urine) occurs despite hyponatremia
- reasons for natriuresis - volume expansion causes an increase in atrial natriuretic peptide (ANP) - increases urine sodium excretion
- volume expansion leads to a decrease in proximal tubular sodium absorption
- the renin-angiotensin aldosterone (RAAS) system is inhibited

Front 67

Causes of SIADH

Back 67

1. neoplasms (e.g. lung, pancreas, prostate, bladder), lymphomas, leukemia
2. CNS disorders (e.g. stroke, head trauma, infection)
3. Pulmonary disorders (e.g. pneumonia, tuberculosis)
4. Ventilators with positive pressure
5. Medication (vincristine, SSRIs, chlorpropramide, oxytocin, morphine, desmopressin)
6. Post-operative state (e.g. result of anesthesia, pain)

Front 68

Clinical features of SIADH - acute vs chronic

Back 68

1. Acute hyponatremia- signs and symptoms are secondary to brain swelling (osmotic water shifts, leading to increased ICF volume) and are primarily neurologic. Lethargy, somnolence, weakness. Can lead to seizures, coma, or death if untreated
2. Chronic hyponatremia- may be asymptomatic, or may have anorexia, nausea, and vomiting. CNS symptoms are less common because chronic loss of sodium and potassium from brain cells decreases brain edema (due to secondary water shifts from ICF to ECF)

Front 69

Diagnosis of SIADH

Back 69

1. SIADH is a diagnosis of exclusion (after other causes of hyponatremia have been ruled out). The following help in supporting the diagnosis
a. hyponatremia and inappropriately concentrated urine, plasma osmolality, 270 mmol/kg
b. low serum uric acid level
c. low BUN and creatinine - because of dilution
d. Normal thyroid and adrenal function, as well as renal, cardiac, and liver function
e. measurement of plasma and urine ADH level
f. absence of significant hypervolemia

Front 70

Treatment of SIADH

Back 70

1. correct the underlying cause, if known
2. For asymptomatic patients- water restriction is usually sufficient. Use normal saline in combination with a loop diuretic if faster results are desired. Lithium carbonate or demeclocycline are other options (with side effects) - both inhibit the effect of ADH in the kidney
3. Symptomatic patients
- restrict water intake
- give isotonic saline. Hypertonic saline may occasionally be indicated in severe cases

Front 71

Hyponatremia pearls - volume status and presence or absence of edema

Back 71

1. hypovolemic hyponatremia- volume contacted
2. hypervolemic hyponatremia- volume expanded with edema
3. SIADH- volume expanded without edema
4. Do NOT raise the serum sodium concentraion too quickly. Rapid flux of water into the ECF can result in central pontine myelinosis (demyelination syndrome may result). A general guideline is that the rate of sodium replacement should not exceed 0.5 mEq/L per hour

Front 72

Hypoparathryoidism
1. Causes

Back 72

1. Head and neck surgery account for the majority of cases- thyroidectomy, parathyroidectomy, radical surgery for head and neck cancers
2. non-surgical hypoparathyroidism is rare

Front 73

Clinical features of hypoparathyroidism

Back 73

1. cardiac arrhythmias
2. rickets and osteomalacia
3. Increased neuromuscular irritability due to hypocalcemia-
a. numbness/tingling- circumoral, fingers and toes
b. Tetany - hyperactive DTRs, Chvostek's sign- tapping the facial nerve elicits contraction of facial muscles. Trousseau's sign- Inflating the BP cuff to pressure higher that the patients SBP for 3 minutes elicits carpal spasms
c. grand mal seizures
4. basal ganglia calcifications
5. prolonged QT interval on ECG- hypocalcemia should always be in the differential
6. cataracts

Front 74

What should always be in the differential for prolonged QT interval?

Back 74

hypocalcemia

Front 75

Diagnosis of hypoparathyroidism

Back 75

1. low serum calcium
2. high serum phosphate - PTH = parthyroid hormone = phosphate trashing hormone
3. serum PTH inappropriately low
4. low urine cAMP

Front 76

Treatment of hypoparathyroidism

Back 76

1. IV calcium gluconate in SEVERE cases, oral calcium in mild to moderate cases
2. Vitamin D supplementation (calcitriol)
3. Note that Vitamin D and calcium replacement can increase urinary calcium excretion, precipitating kidney stones. Therefore, administer with caution to avoid hypercalciuria (the goal is to keep sodium at 8.0 to 8.5 mg/dL)

Front 77

Primary Hyperparathyroidism
1. cause
2. relative prevalence as a cause for hypercalcemia

Back 77

1. One or more glands produce inappropriately high amounts of PTH relative to serum calcium level.
2. Most common cause of hypercalcemia in the outpatient setting

Front 78

Causes of primary hyperparathyroidism

Back 78

1. Adenoma (80% of cases) - majority involve only one gland
2. Hyperplasia (15-20% of cases) - all four glands are usually affected
3. Carcinoma (< 1% of cases)

Front 79

Clinical features of hyperparathyroidism

Back 79

1. Stones - nephrolithiasis, nephrocalcinosis
2. Bones - bone aches and pains. Osteitis fibrosa cystica - "brown tumors" - predisposes patient to pathologic fractures
3. Groans - muscle pain and weakness, pancreatitis, peptic ulcer disease, gout, constipation
4. Psychiatric overtones- depression, fatigue, anorexia, sleep disturbances, anxiety, lethargy
5. Other symptoms- polydipsia, polyuria, HTN, shortened QT interval, weight loss

Front 80

Diagnosis of primary hyperparathyroidism
1. lab
2. radiograph

Back 80

1. a. calcium levels (hypercalcemia) - when calculating calcium levels, be aware of albumin levels. Calculate the ionized fraction or get an ionized calcium level
b. PTH levels- should be elevated relative to serum calcium level. Note that in the presence of hypercalcemia, a normal PTH level is "abnormal" because high calcium levels should suppress PTH secretion
c. Hypophosphatemia
d. hypercalciuria
e. urine cAMP is elevated
f. Chloride/phosphorus ratio > 33 is diagnostic of primary hyperparathyroidsm (33-to-1 rule). Chloride is high secondary to renal bicarbonate wasting (direct effect of PTH)
2. Radiographs- subperiostial bone resorption (usually on the radial aspect of the 2nd and 3rd phalanges), osteopenia

Front 81

Treatment of primary hyperparathyroidism
1. All patients
2. due to hyperplasia
3. due to adenoma
4. due to carcinoma

Back 81

1. surgery is the only definitive treatment, but not all patients require it. If the patient is over 50 years of age and is asymptomatic (with normal bone mass and renal function), surgery may not be needed
a. primary hyperparathyroidism to hyperplasia- all the four glands are removed and a small amount of one of them is placed in the forearm muscle (prevents the need for re-exploration of the neck if hyperplasia recurs post-op) to retain parathyroid function
b. primary hyperparathyroidism due to adenoma- surgical removal of the adenoma is curative
c. primary hyperparathyroidism due to carcinoma- remove the tumor, ipsilateral thyroid lobe and all enlarged lymph nodes
d. medical- encourage fluids. Give diuretics (furosemide) to enhance calcium excretion if hypercalcemia is severe (Loops Lose Calcium) - Do not give thiazide diuretics as they can exacerbate hypercalcemia

Front 82

Relative indications for surgery in primary hyperparathyroidism

Back 82

1. Age < 50 years old
2. marked decrease in bone mass
3. Nephrolithiasis, renal insufficiency
4. markedly elevated serum calcium level or episode of severe hypercalcemia
5. urine calcium > 400 mg in 24 hours

Front 83

Secondary hyperparathyroidism

Back 83

- characterized by an elevated concentration of PTH and a low or low normal serum calcium level
- caused by chronic renal failure (most commonly), as well as Vitamin D deficiency and renal hypercalciuria
- Treatments depend on the cause: if give Vitamin D deficiency- give Vitamin D, if renal failure- give calcitriol (activated vitamin D) and oral calcium supplements plus dietary phosphorus restriction

Front 84

Pseudohypoparathyroidism
- what is it and what are the characteristic lab findings?

Back 84

- End-organ resistance to action of PTH
- Lab value findings : low calcium, high phosphorus, high PTH, low urinary cAMP

Front 85

Cushing syndrome vs cushing's disease

Back 85

Cushing's syndrome- excessive levels of glucocorticoids due to any cause

Cushing's disease- pituitary Cushing's syndrome (pituitary adenoma)

Front 86

Causes of cushing's syndrome

Back 86

1. Iatrogenic cushing's syndrome is the most common causes. It is due to prescribed prednisone or other steroids. Androgen excess is absent (because exogenous steroid suppresses androgen production by the adrenals)
2. ACTH-secreting adenoma of the pituitary (Cushing's disease) is the second most common cause and leads to bilateral adrenal hyperplasia. Androgen excess is common.
3. Adrenal adenomas and carcinomas (10-15%)
4. Ectopic ACTH production (10-15%) - ACTH-secreting tumor stimulates the cortisol release from the adrenal glands without the normal negative feedback loop (because the source of the ACTH is outside the pituitary gland). More than 2/3 are small cell carcinomas of the lung. Bronchial carcinoid and thymoma may be the cause.

Front 87

Clinical features of cushing's syndrome

Back 87

1. Changes in appearance- central obesity, hirsuitism, moon facies, "buffalo hump", purple striae on abdomen, lanugo hair, acne, easy bruising
2. HTN
3. decreased glucose tolerance (diabetes)
4. Hypogonadiam- menstrual irregularity and infertility
5. Masculinization in females (androgen excess)-- only seen in ACTH-dependent forms
6. Musculoskeletal- proximal muscle wasting and weakness (due to protein catabolism), osteoporosis, aseptic necrosis of the femoral head may occur (especially with exogenous steroid use)
7. Psychiatric disturbances (depression, mania)
8. Increased likelihood of infections (due to impaired immunity)

Front 88

Diagnosis of cushing's syndrome- initial screening

Back 88

a. overnight (low-dose) dexamethason suppression test is the initial screening test. Give the patient 1 mg of dexamethasone at 11 pm. Measure the serum cortisol level at 8am. If the serum cortisol is <5, cushing's syndrome can be excluded (this test is very sensitive)
- If the serum cortisol is >5 (and often >10), the patient has Cushing's syndrome. Order a high-dose dexamethasone suppression test to determine the cause (cushing's disease versus adrenal tumor vs ectopic ACTH production)
b. The 24-hour urinary free cortisol level is another excellent screening test; values greater than 4 times normal are rare except in Cushing's syndrome

Front 89

Significance of ACTH level in Cushing's syndrome
- high vs low

Back 89

Once you establish the diagnosis of Cushing's syndrome, measure the ACTH level. If it is low, the cause of high cortisol levels is likely an adrenal tumor or hyperplasia, NOT a pituitary disease or an ectopic ACTH-producing tumor

Front 90

Findings on High-dose dexamethasone suppression test
a. suppression occurs
b. NO suppression

Back 90

a. Cushing's disease - decrease in cortisol levels (greater than 50% suppression occurs)
b. cortisol suppression does NOT occur, plasma ACTH levels are still high, then ectopic ACTH-producing tumor is the likely diagnosis

Front 91

Corticotropin Releasing Hormone (CRH) stimulation test

Back 91

CRH is administered intravenously
a. If ACTH/cortisol levels increase (deemed a "response" then Cushing's disease is the diagnosis
b. If ACTH/cortisol levels do NOT increase (deemed "no response") then the patient either has ectopic ACTH secretion or an adrenal tumor

Front 92

Once the side of disease has been established in Cushing's syndrome, what imaging should be done?

Back 92

CT scan or MRI of the appropriate area (adrenal glands or pituitary)

Front 93

Treatment of Cushing's syndrome

Back 93

1. Iatrogenic Cushing's syndrome- tapering of glucocorticoid
2. Pituitary Cushing's syndrome- surgery (transphenoidal ablation of pituitary adenoma) -- usually safe and effective
3. Adrenal adenoma or carcinoma - surgery (adrenalectomy)

Front 94

Pheochromocytoma- general characteristics

Back 94

1. Rare tumors that produce, store and secrete catecholamine
2. 90% found in the adrenal medulla (10% extra-adrenal)
3. Curable if diagnosed and treated, by may be fatal if undiagnosed
4. Arise from the chromaffin cells of the adrenal medulla or from the sympathetic ganglia if extra-adrenal

Front 95

Pheochromocytoma - Rule of 10s

Back 95

10% are familial
10% are bilateral (suspect MEN II)
10% are malignant
10% are multiple
10% occur in children
10% are extra-adrenal (more often malignant)- the most common site is the organ of Zuckerkandl, which is located at the aortic bifurcation

Front 96

Clinical features of Pheochromocytoma

Back 96

1. HTN- BP is persistently high, with episodes of sever HTN (paroxysmal)
2. Severe pounding headache
3. Inappropriate severe sweating
4. Tachycardia
5. Palpitations, with sudden severe HTN
6. Anxiety
7. Feeling of impending doom
8. Lab findings- hyperglycemia, hyperlipidemia, hypokalemia

Front 97

Diagnosis of pheochromocytoma

Back 97

1. urine screen- test for the presence of the following breakdown products of cathecholamines: a. metanephrine, b. vanillylmandelic acid, homovanilli acid, normetanephrine
2. Plasma metanephrines have been proposed by some investigators as a superior test to urine metanepherines, especially when clinical suspicion is high
3. urine/serum epinepherine and norepinepherine levels- If the epinepherine level is elevated then the tumor much be adrenal or near the adrenal gland (organ of Zuckerkandl) because nonadrenal tumors cannot methylate norepinepherine to epinepherine
4. Tumor localization tests- CT, MRI

Front 98

Treatment of pheochromocytoma
- iatrogenic cushing's
- pituitary cushing's syndrome
- adrenal adenoma or carcinoma

Back 98

1. Surgical tumor resection with early ligation of venous drainage is the treatment of choice. Ligation lowers the possibility of catecholamine release/crisis by tying off drainage
- patients should be treated with alpha-blockage (phenoxybenzamine) for 10-14 days prior to surgery as well as beta-blockade (i.e. propanolol) for 2-3 days prior to surgery. The alpha-blockae is used to control BP, and the beta-blockade is used to decrease tachycardia.
- laparoscopic adrenalectomy can be safely performed for most small to medium-sized pheochromocytomas

Front 99

Response to diagnostic test in cushing's syndrome - healthy patient

Back 99

- normal cortisol/normal ACTH
- suppression with low-dose dexamethasone
- suppression with high-dose dexamethasone
- mild increase with CRH test

Front 100

Response to diagnostic test in cushing's syndrome - Cushing's disease

Back 100

- high cortisol/high ACTH
- no suppression with low-dose dexamethasone
- suppression with high-dose dexamethasone
- great increase in cortisol with CRH test

Front 101

Response to diagnostic test in cushing's syndrome - Adrenal tumor

Back 101

- high cortisol/low ACTH
- no suppression with low dose dexamethasone
- suppression with high dose dexamethasone
- no change after CRH test

Front 102

Response to diagnostic test in cushing's syndrome - ectopic ACTH-producing tumor

Back 102

- high cortisol/high ACTH
- no suppression with low dose dexamethasone
- no suppression with high dose dexamethasone
- No change after CRH test

Front 103

What should always be tested along with a 24 urine collection of metanepherines and catecholamines for pheochromocytoma

Back 103

- test the amount of urine creatinine to determine if the patient has provided an appropriate sample

Front 104

If ALL of the following symptoms are present, what is the diagnosis until proven otherwise:
- headache
- profuse sweating
- palpitations
- tachycardia
- apprehension or sense of impending doom

Back 104

pheochromocytoma

Front 105

Multiple Endocrine Neoplasia (MEN) Syndrome- what is it and what are the types?

Back 105

- inherited condition: propensity to develop multiple endocrine tumors
- autosomal dominant inheritance pattern with incomplete penetrance
Types: MEN type I (Wermer's syndrome), MEN type IIa (sipple's syndrome), MEN type IIb

Front 106

MEN type I (Wermer's syndrome)

Back 106

3 P's
- parathyroid hyperplasia (in 90% of patients with MEN type I)
- Pancreatic islet cell tumors (in 2/3 of patients with MEN I)- Zollinger Ellison syndrome (50%), insulinoma (20%)
- Pituitary tumors (in 2/3 of patients with MEN I)

Front 107

MEN type IIA (sipple's syndrome)

Back 107

MPH
- medullary thyroid cancer (in 100% of patients with MEN IIa)
- pheochromocytoma (in more than 1/3 of patients with MEN IIa)
- Hyperparathyroidism- in 50% of the patients with MEN IIa

Front 108

MEN type IIB

Back 108

MMMP
- mucosal neuromas (in 100% of the patients with MEN IIB) - in the nasopharynx, oropharynx, larynx, and conjunctiva
- medullary thyroid cancer (in 85% of patients with MEN IIB) - more aggressive than in MEN IIa
- marfanoid body habitus (long/lanky)
- pheochromocytoma

Front 109

What should you always suspect in a hypertensive patient with hypokalemia who is not on a diuretic

Back 109

hyperaldosteronism

Front 110

General characteristics of hyperaldosteronism

Back 110

- excessive production of aldosterone by the adrenal glands independent of regulation of by the renin-angiotensin-aldosterone system
- excessive mineralocorticoids increase the activity of the Na/K pumps in the cortical collecting tubules. - leads to sodium retention- causing ECF volume expansion and HTN
- potassium loss- resulting in hypokalemia
- excess aldosterone also increases the secretion of hydrogen ions into the lumen of the medullary collecting tubules: resulting in metabolic alkalosis

Front 111

Causes of hyperaldosteronism

Back 111

- Adrenal adenoma (in 2/3 of the cases) - aldosterone producing adenoma (conn's syndrome)
- Adrenal hyperplasia (in 1/3 of the cases) - almost always bilateral
- Adrenal carcinoma (in < 1% of cases)

Front 112

Clinical features of hyperaldosteronism

Back 112

1. HTN
2. Headache, fatigue, weakness
3. polydipsia, nocturnal polyuria (due to hypokalemia)
4. ABSENCE of Peripheral Edema

Front 113

Diagnosis of hyperaldosteronism
1. screening
2. definitive diagnosis

Back 113

1. Ratio of plasma aldosterone level to plasma renin - a screening test in primary hyperaldosteronism reveals inappropriately elevated levels of plasma aldosterone with co-existent decreased plasma renin activity. Therefore, if the plasma aldosterone-to-renin ratio > 30, evaluate further
2. For definitive diagnosis, one of two tests is usually performed
a. saline infusion test- infusion of saline will decrease aldosterone levels in normal patients, but not those with primary hyperaldosteronism. If aldosterone levels are <8.5 ng/dL after saline infusion, the diagnosis can be ruled out
b. oral sodium loading- the patient is given a high salt diet for 3 days. Serum and urine electrolytes, aldosterone, and creatinine are measured on the third day. High urine aldosterone in the setting of high urine sodium (to document appropriate sodium loading) confirms the diagnosis

Front 114

Diagnosis of the CAUSE of primary hyperaldosteronism

Back 114

1. Adrenal venous sampling of aldosterone levels
2. Renin-aldosterone stimulation test
3. Imaging tests

Front 115

Primary Adrenal Insufficiency (Addison's disease)- cause

Back 115

1. Idiopathic (though to be an autoimmune disease)- most common type in the industrialized world
2. Infectious diseases- including tuberculosis (most common cause worldwide) and fungal infections. Causes also include CMV, cryptococcus, toxoplasmosis, and pneumocystis
3. iatrogenic- for example, bilateral adrenalectomy
4. metastatic disease - from lung or breast cancer

Front 116

Secondary adrenal insufficiency - causes

Back 116

1. patients on long-term steroid therapy - the most common cause of adrenal insufficiency today. When the patients develop a serious illness or undergo trauma, they cannot release an appropriate amount of cortisol because of chronic suppression of CRH and ACTH by the exogenous steroids. Therefore, symptoms of adrenal insufficiency result.
2. hypopituitarism (rare) - due to a variety of insults
3. Tertiary adrenal insufficiency- hypothalamic disease

Front 117

Clinical features of adrenal insufficiency - symptoms due to low cortisol

Back 117

1. GI symptoms - nausea/vomiting, vague abdominal pain, weight loss
2. Mental symptoms- lethargy, confusion, psychosis
3. hypoglycemia- cortisol is a gluconeogenic hormone
4. hyperpigmentation - this is a common finding in primary adrenal insufficiency that is NOT seen in secondary adrenal insufficiency because in secondary adrenal insufficiency ACTH levels are low, not high. Low cortisol levels stimulate ACTH and melanocyte stimulating hormone secretion
5. intolerance to physiologic stress is a feared complication

Front 118

Clinical features of adrenal insufficiency - symptoms due to low aldosterone

Back 118

ONLY seen in primary adrenal insufficiency because aldosterone depends on the renin-angiotensin system, not ACTH
- sodium loss, causing hyponatremia and hypovolemia, which may lead to hypotension, decreased cardiac output, and decreased renal perfusion, weakness, shock and syncope
- hyperkalemia (due to potassium retention)

Front 119

Diagnosis of adrenal insufficiency

Back 119

1. decreased plasma cortisol level
2. Plasma ACTH level - if low, this implies secondary adrenal insufficiency (ACTH-dependent cause).
3. Standard ACTH test- This is the definitive test for primary adrenal insufficiency. Give an IV infusion of synthetic ACTH, and measure plasma cortisol at the end of the infusion. In primary adrenal insufficiency, cortisol does NOT increase sufficiently. In secondary adrenal insufficiency, cortisol fails to respond to ACTH infusion initially, a the adrenals are not used to being stimulated, so they do not respond right away). However, if the test is repeated in 4-5 days the adrenals eventually respond normally
4. Perform imaging tests (MRI of brain - pituitary/hypothalamus) if secondary or tertiary adrenal insufficiency is diagnosed

Front 120

Treatment of adrenal insufficiency

Back 120

1. primary adrenal insufficiency- daily oral glucocorticoid (hydrocortisone or prednisone) and daily fludrocortisone (mineralocorticoid to replace aldosterone)
2. Secondary adrenal insufficiency- same as in primary, except that the fludrocortisone is not necessary

* All of these patients need a stress dose of steroids when they get sick as they are not able to respond as they normally should

Front 121

Congenital Adrenal Hyperplasia (CAH)
1. inheritance pattern
2. most common cause

Back 121

1. Autosomal recessive disease
2. 90% of the cases are due to 21-hydroxylase deficiency (11-hydroxylase deficiency is the next most common cause)

Front 122

Clinical features of 21-hydroxylase deficiency (most common type of congenital adrenal hyperplasia)

Back 122

1. Decreased cortisol and aldosterone production are the main events. Increased ACTH secretion (due to lack of negative feedback) causes adrenal hyperplasia.
2. As precursors of cortisol and aldosterone build up, they are shunted toward the synthesis of androgens (e.g. DHEA, testosterone) causing virilization.
3. Virilization features-- female infants are born with ambiguous external genitalia but normal female ovaries and uterus. Male infants have no genital abnormalities
4. Salt-wasting form- more severe form of disease- emesis, dehydration, hypotension, and shock-- can develop within the first 2-4 weeks of life. Hyponatremia and hyperkalemia- due to lack of aldosterone. Hypoglycemia- due to lack of cortisol.

Front 123

Diagnosis of congenital adrenal hyperplasia

Back 123

High levels of 17-hydroxyprogesterone in the serum. Neonatal screening for 21-hydroxylase deficiency is approved in all 50 states, leading to early diagnosis in most cases

Front 124

Treatment of congenital adrenal hyperplasia

Back 124

1. Medically- use cortisol and mineralocorticoid, this shuts off excess ACTH secretion (via negative feedback). Beware of undertreatment and overtreatment.
2. Surgically- early correction of female genital abnormalities is generally recommended
-- this is a very treatable condition. Affected female patients will be fertile if treated early

Front 125

Classification of Diabetes Mellitus - Two Types and impaired fasting glucose

Back 125

1. Type I - Insulin Dependent Diabetes Mellitus- approximately 5% of all diabetic patients. This is characterized by a severe insulin deficiency. Patients require insulin to live. The onset is typically in youth (before age 20), but can occur at any age. NOT related to obesity.
2. Type II- Non-insulin dependent diabetes mellitus- 90% of all diabetic patients. Insulin levels are usually normal to high but may diminish over many years of having diabetes. Insulin resistance (due to obesity) plays a major role. It often goes undiagnosed for many years.
3. Impaired glucose tolerance- fasting glucose between 110-125 mg/dL or a 2-hour post-prandial glucose between 140-199 mg/dL
- 1-5% annual increase in risk of developing type II diabetes. Increased risk for CV disease

Front 126

Pathogenesis of Type I diabetes

Back 126

1. An auto-immune disease- the immune system mediates the destruction of beta-islet cells of the pancreas
2. It develops in genetically susceptible individuals who are exposed to an environmental factor that triggers the autoimmune response. Beta-cell destruction ensues. Overt IDDM does not appear until 90% of the beta-islet cells are destroyed

Front 127

Pathogenesis of Type II Diabetes
a. risk factors
b. role of obesity
c. lack of compensation in type II diabetics

Back 127

a. obesity, genetics, age (insulin production decreases with age)
b. obesity plays a major role- obesity is associated with increased plasma levels of free fatty acids, which make muscles more insulin resistant, reducing glucose uptake. Therefore, obesity exacerbates insulin resistance. In the liver, free fatty acids increase the production of glucose
c. In normal individuals, the pancreas secretes more insulin in response to free fatty acids, thus neutralizing excess glucose
- in type II diabetics, free fatty acids fail to stimulate the pancreas to release insulin. Therefore, compensation does not occur and hyperglycemia develops. Beta-cells become desensitized to glucose, leading to decreased insulin secretion.

Front 128

Most common clinical findings in adrenal insufficiency

Back 128

- weight loss
- weakness
- skin hyperpigmentation
- anorexia
- nausea
- postural hypotension
- abdominal pain
- hypoglycemia

Front 129

What is the most common cause of Addison's disease
a. worldwide
b. in the Western World

What is the most common cause of adrenal insufficiency (99% of all cases)

Back 129

1. most common causes of Addison's - primary adrenal insufficiency
a. tuberculosis - worldwide
b. autoimmune disease- western world

Most common cause of adrenal insufficiency-- secondary to abrupt cessation of exogenous glucocorticoids!

Front 130

Dawn vs Somogyi Effect

Back 130

- Both cause early morning hyperglycemia
- The dawn phenomenon is probably due to an increase in the nocturnal secretion of growth hormone and is independent of the Somogyi effect
- The Somogyi effect is a rebound response to noctural hypoglycemia-- i.e. counterregulatory systems are activated in response to hypoglycemia, leading to morning hyperglycemia
- If morning hyperglycemia is present, check the glucose level at 3am. If the glucose is elevated, the patient has the dawn phenomenon and his or her evening insulin should be increased to provide additional coverage in the overnight hours. If the glucose is low, the patient has the Somogyi effect and his or her evening insulin should be decreased to avoid nocturnal hypoglycemia

Front 131

What is the characteristic lipid profile for patients with insulin resistance and poorly controlled diabetes?

Back 131

Hypertriglyceridemia with HDL depletion

Front 132

Diagnosis of Diabetes Mellitus

Back 132

One of the following criteria must be met:
1. Two fasting glucose measurements greater than 126 mg/dL
2. Single glucose level > 200 mg/dL with symptoms
3. 2 hour post-prandial glucose > 200 mg/dL
4. Hemoglobin A1c > 6.5%

Front 133

Testing recommendations for Diabetes Mellitus

Back 133

1. Screen ALL adults over age 45 every 3 years
2. For patients with risk factors for DM (obesity, family history, history of gestational DM), start screening earlier. Some recommend earlier screening for African and Native Americans
3. Test everyone with signs and symptoms of DM

Front 134

What is the preferred test for diagnosing diabetes mellitus?

Back 134

Perform a fasting glucose test on 2 separate days.

- A fasting glucose > 126 mg/dL is the criteria for dx
- If fasting level is between 100-126mg/dL then perform a 75 mg glucose tolerance test (GTT)--although this is rarely done or recheck a fasting glucose

- an Oral GTT is considered positive if the glucose level is > 200 mg/dL 2 hours or more after 75g glucose load

Front 135

Clinical presentation of type I diabetes mellitus

Back 135

1. symptoms develop quickly over days to weeks
2. sometimes symptoms appear after an illness
3. patients often present in acute DKA (anion gap metabolic acidosis)

Front 136

Clinical presentation of type II diabetes mellitus

Back 136

1. This is usually discovered on screening urinalysis or blood sugar measurement. Sometimes the diagnosis is made during the evaluation for other diseases
2. Symptomatic patients may present with polyuria, polydipsia, polyphagia, fatigue, blurred vision, weight loss and/or candidal vaginitis
3. Patients who have not routinely sought medical attention may present with complications such as myocardial ischemia, stroke, intermittent claudication, impotence, peripheral neuropathy, proteinuria, or retinopathy

Front 137

What should you focus on during the physical exam of a patient with diabetes mellitus?

Back 137

1. The feet - sores that are not healing
2. Vascular disease (CAD, PVD)
3. neurologic disease (neuropathies)
4. Eyes (retinopathy)
5. renal disease
6. infectious disease

Front 138

Symptoms of DM and why they occur

Back 138

1. Polyuria- glucose in renal tubule causes osmotic retention of water, leading to diuresis
2. polydipsia- a physiologic response to diuresis to maintain plasma volume
3. Fatigue- unknown mechanism
4. Weight loss - due to loss of anabolic effects of insulin
5. Blurred vision- swelling of lens due to osmosis
6. Fungal infections of mouth and vagina- Candida albicans thrives under increased glucose conditions
7. numbness, tingling in hands and feet - neuropathies: mononeuropathy (due to microscopic vasculitis leading to axonal ischemia), polyneuropathy (multifactorial)

Front 139

General Principles of outpatient management and monitoring in all diabetic patients
1. Hemoglobin A1c
2. daily measurements
3. kidney disease screening
4. eyes
5. feet
6. cholesterol
7. BP
8. What meds should they be taking and what vaccines should they get?

Back 139

1. Monitor hemoglobin A1c level every 3 months. Keeping Hemoglobin A1c < 7.0 is the objective (although difficult to achieve) because it is associated with a marked reduction in risk of microvascular complications
2. Patients on insulin therapy should measure their blood glucose before meals and at bedtime. Also, measuring glucose 90-120 minutes after meals enables better control of post-prandial hyperglycemia
3. Screen for microalbuminuria at least once a year, and check BUN and Creatinine at the same time
4. yearly opthalmalogic eval to check for diabetic retinopathy
5. check feet at every visit. Refer high risk patients to podiatry. Patients should regularly check their own feet for ulcers and neuropathy
6. Check cholesterol once per year. Give statin if >100 mg/dL
7. BP at every visit. Give ACE-I or ARB if greater than 130/80 mmHg
8. Daily aspirin in all diabetics over 30 years old. Pneumococcal vaccine

Front 140

Sulfonylureas
1. MOA
2. Site of action
3. Advantages
4. Side effects

Back 140

1. Stimulate pancreas to produce more insulin
2. pancreas
3. inexpensive and effective
4. hypoglycemia and weight gain

Front 141

Metformin
1. MOA
2. Site of action
3. Advantages
4. Side effects

Back 141

1. Enhances insulin sensitivity
2. Liver
3. May cause mild weight loss, does not cause hypoglycemia (insulin levels do not increase)
4. GI upset (diarrhea, nausea, abdominal pain), lactic acidosis, and metallic taste

Serum creatinine > 1.5 in men or 1.4 in women is contraindication to metformin

Front 142

Acarbose
1. MOA
2. Site of action
3. Advantages
4. Side effects

Back 142

1. Reduces glucose absorption from the gut, thereby reducing calorie intake
2. GI tract
3. low risk (no significant toxicity)
4. GI upset (diarrhea, abdominal cramping, flatulence)

Front 143

Thiazolidinediones (e.g rosiglitazone, and pioglitazone)
1. MOA
2. Site of action
3. Advantages
4. Side effects

Back 143

1. reduce insulin resistance (PPAR-gamma)
2. fat, and muscle
3. reduce insulin levels
4. hepatoxicity - monitor LFTs

Front 144

Optimal treatment for type II diabetic patients

Back 144

- glycemic control
- BP control -- goal is <130/85 (the lower the better as long as it is tolerated)
- optimization of serum lipids- goals: LDL < 100, HDL > 40
- smoking cessation
- daily aspirin as long as not CI
* start with diet and exercise, then move to oral hypoglycemics if unsuccessful. If still not controlled, move to insulin therapy quickly to optimize Hgb A1c

Front 145

Insulin vs oral hypoglycemics in type II diabetics

Back 145

- If the patient has severe hyperglycemia (fasting glucose > 240 mg/dL), insulin is typically the agent of choice (whether type I or type II)
- Oral hypoglycemic agents are effective in type II disease with moderate hyperglycemia (fasting glucose between 140-240 mg/dL)

Front 146

What is the initial drug of choice when diet and exercise fail to control type II DM?

Back 146

Metformin (CI in renal failure)-- however since it acts by increasing sensitivity to insulin there is no risk of hypoglycemia

Front 147

How much insulin is usually required per day in a patient with type I DM?

Back 147

0.5-1.0 unit/kg per day.

- start with a conservative dose and then adjust upwards to optimize control

Front 148

Intensive Insulin Therapy

Back 148

- long-acting insulin is given once daily in the evening. Regular insulin is given 30-45 minutes before each meal and should be adjusted according to pre-prandial home glucose measurements
- serious risk of hypoglycemia
- or you could use SubQ infusion of insulin via a pump-- however preprandial boluses are still needed in addition the basal level

Front 149

If a patient is unable or unwilling to carry out an intensive insulin regimen, what is the next most appropriate option and how does it work?

Back 149

70/30 regimen.

Calculate mg/kg per day. Give 70% of this in the morning and 30% of this in the evening. 70% should be intermediate-acting NPH and 30% should be short-acting regular insulin

Adjust doses according to fasting and 4pm glucose levels

Front 150

How do you manage blood sugars of a diabetic patient when they are admitted to the hospital?

Back 150

- An insulin sliding scale (SSI) of regular insulin doses is given according to bedside finger-stick glucose measurements.
- This should be used IN ADDITION to a regimen of intermediate-acting insulin.
- Monitor blood glucose QID. Before meals and at bedtime.
- Take the whole number of units of regular insulin that a patient required in 1 day while on SSI and give 2/3 as pre-breakfast dose (70%NPH/30% regular) and 1/3 before dinner

Front 151

How must you modify insulin dosing with:
a. physical activity
b. patients undergoing surgery

Back 151

a. depends on the intensity of the exercise-- but decrease dose by 1-2 units per 20-30 minutes of exercise
b. patients should only get 1/3 to 1/2 their normal daily dosage. Frequent monitoring should be done

Front 152

What is the main chronic complication of DM?

Back 152

Macrovascular complications due to accelerated atherosclerosis. This leads to an increased risk of stroke, MI, and CHF (thus the need for lower target BP and cholesterol)

Front 153

What is the most common cause of death in diabetic patients?

Back 153

Coronary Artery Disease

Front 154

What are the clinical manifestations of accelerated atherosclerosis in diabetic patients?

Back 154

1. CAD - risk is 2-4 x greater in diabetic patients. Silent MIs are common.
2. PVD- in up to 60% of diabetics
3. cerebrovascular disease (strokes)

Front 155

What is the most common/important cause of end-stage renal disease in the western world?

Back 155

Diabetic nephropathy

Front 156

Pathologic types of diabetic nephropathy

Back 156

1. Nodular glomerular sclerosis (Kimmelstiel-Wilson syndrome)-- hyaline deposition in one area of glomerulus = pathognomonic for DM
2. Diffuse glomerular sclerosis - hyaline deposition is global-- also occurs in HTN
3. Isolated glomerular basement membrane thickening

Front 157

Progression of kidney disease in diabetic patients

Back 157

1. Microalbuminuria/proteinuria- the first sign microalbuminuria. With tight glycemic control you can prevent the progression to proteinuria. HTN usually develops during the transition between microalbuminuria and proteinuria
2. Persistent HTN and proteinuria cause a decrease in GFR leading to ESRD if untreated
3. HTN increases the risk of progression of diabetic nephropathy to ESRD. Control BP aggressively.
4. Initiate ACE-I and ARB immediately

Front 158

What is the screening test for diabetic nephropathy?

Back 158

Monitor microalbumin levels.
- Microalbuminuria means levels of albumin between 30-300 mg in 24 hours. But a urine dipstick for protein will not be positive until > 300 mg
- It usually takes 1-5 years for microalbuminuria to progress to full blown proteinuria, however with BP control this can be prolonged
** Once diabetic nephropathy has progressed to the stage of proteinuria or early renal failure- glycemic control does not significantly affect its course. At this point you need ACE-I and dietary protein restriction

Front 159

Diabetic retinopathy
1. prevalence
2. proliferative vs non-proliferative retinopathy

Back 159

1. approx 75% after 20 years of diabetes. Annual screening by an ophthalmologist is recommended.
2. Background/nonproliferative retinopathy accounts for the majority of cases. Fundoscopic exam shows hemorrhages, exudates, microaneurysms and venous dilation. Patients are usually asx unless retinal edema or ischemia involves the macula. HTN and fluid retention exacerbate this.
- Proliferative retinopathy- key characteristics are new vessel formation (neovascularization) and scarring. Two serious complications are vitreal hemorrhage and retinal detachment. Can lead to blindness. Laser photocoagulation is necessary.

Front 160

Diabetic retinopathy - peripheral neuropathy

Back 160

1. usually affects sensory nerves in a "stocking glove pattern"-- usually begins in the feet and later involves the hands. The longest nerves are affected first. Numbness and paresthesias are common.
2. Loss of sensation leads to the following: ulcer formation (patients do not shift their weight) and subsequent ischemia of pressure point areas; charcot joints
3. Painful diabetic neuropathy- hypersensitivity to light touch. Severe "burning" pain especially at night that can be difficult to tolerate. Treat with gabapentin, tricyclics or pregabalin

Front 161

Diabetic neuropathy - CN complications

Back 161

- occurs secondary to nerve infarction
- most often involves CN III (oculomotor n) but may also involve CN VI and IV
- diabetic third nerve palsy - eye pain, diplopia, ptosis (eye-opening is controlled by CNIII), inability to adduct the eye. Pupils are spared.

Front 162

Diabetic neuropathy- mononeuropathies

Back 162

- occurs secondary to nerve infarction
- median nerve neuropathy, ulnar neuropathy, common peroneal/fibular neuropathy
- diabetic lumbrosacral plexopathy - severe, deep pain in the thigh, atrophy and weakness in thigh and hip muscles. Recovery takes weeks to months
- diabetic truncal neuropathy- pain in the distribution of one of the intercostal nerves

Front 163

Diabetic neuropathy - autonomic neuropathy

Back 163

1. impotence in men (most common presentation)
2. Neurogenic bladder (retention and incontinence)
3. gastroparesis - chronic n/v, early satiety
4. constipation and diarrhea (alternating)
5. postural hypotension

Front 164

Diabetic foot

Back 164

- caused by a combination of artery disease (ischemia) and nerve disease (neuropathy) - can lead to ulcers/infections and may require amputation
- with neuropathy, the patient does NOT feel pain, so repetitive injuries go unnoticed and ultimately lead to non-healing wounds
- In addition, neuropathy may mask symptoms of PVD (claudication/rest pain). Also calcific medial artery disease is common and can cause falsely elevated BP readings in the LEs

Front 165

Increased susceptibility to infection in diabetic patients
- why does it occur?
- what infections are they are increased risk for?
- special concerns for ischemic foot ulcers?

Back 165

- this results from impaired WBC function, reduced blood supply, and neuropathy. Wound healing is impaired in diabetic patients and this can be a problem post-op
- diabetic patients are at an increased risk for the following infections: cellulitis, candidiasis, pneumonia, osteomyelitis, and polymicrobial foot ulcers
- infections of ischemic foot ulcers may lead to osteomyelitis and may require amputation

Front 166

Treatment of macrovascular disease in diabetic patients

Back 166

- risk factor reduction- BP reduction, lipid-lowering, smoking cessation, exercise, daily aspirin and strict glycemic control

Front 167

Treatment of nephropathy in diabetics

Back 167

ACE-inhibitors- may slow progression of microalbuminuria to proteinuria and slow the decline of GFR

Front 168

Treatment of retinopathy in diabetics

Back 168

refer to ophtho for photocoag if there is proliferative retinopathy - neovasc etc

Front 169

Treatment of diabetic neuropathy

Back 169

- treatment is complex.
- NSAIDS, tricyclics, and gabapentin
- for gastroparesis- promotility agent like metoclopramide can be helpful in addition to exercise and low-fat diet

Front 170

Diabetic Ketoacidosis - general characteristics
1. definition
2. pathogenesis
3. consequences

Back 170

1. an acute, life threatening medical emergency that can occur in both type I and type II - but is much more common in type I
2. secondary to insulin deficiency and glucagon excess, both of which contribute to accelerated hyperglycemia and ketogenesis. Severe hyperglycemia leads to osmotic diuresis, which causes dehydration and volume depletion
3. consequences include hyperglycemia, ketonemia, metabolic acidosis and volume depletion

Front 171

Precipitating factors of DKA

Back 171

- any type of stress or illness (infectious process, trauma, MI, stroke, recent surgery, sepsis and GI bleeding)
- Inadequate administration of insulin- missed dose
- drug use

Front 172

Clinical features of diabetic ketoacidosis (DKA)

Back 172

1. n/v
2. abdominal pain (more common in children- may mimic acute abd)
3. Kussmaul's respiration- rapid/deep breathing
4. "fruity" breath odor due to acetone
5. marked dehydration, orthostatic hypotension, tachycardia, volume depletion is always present
6. polydipsia, polyuria, polyphagia, weakness
7. AMS, drowsiness, frank coma
8. symptoms usually occurs rapidly - in less than 24 hours

Front 173

Diagnosis of DKA

Back 173

1. hyperglycemia: serum glucose is typically > 450 mg/dL and <850 mg/dL (although in certain conditions i.e. alcohol ingestion, the patient may be euglycemic
2. Metabolic acidosis - blood pH < 7.3 and serum HCO3- < 15 mEq/L
- increased anion gap- due to production of ketones (acetoacetate and beta-hydroxybutyrate)
3. ketonemia and ketonuria- although when DKA is complicated by circulatory collapse, serum and urine may be falsely negative for ketones. This is because lactate production results in less acetoacetate which is the only ketone measured standardly

D - Diabetes with sugar > 225 mg %
K - Ketosis
A - Acidosis ( pH < 7.2 + Anion Gap Wide)

Front 174

Other lab abnormalities in DKA

Back 174

1. hyperosmolarity
2. hyponatremia- serum sodium decreases 1.6. mEq/L for every 100 mg/dL increase in the glucose level because of osmotic shift from the ICF to ECF space. TOTAL BODY SODIUM is normal. Generally does not require treatment
3. hyper or hypokalemia- because of acidosis, hyperkalemia may be present initially, although TOTAL BODY POTASSIUM IS LOW. As insulin is given, it causes a shift of potassium into cells, resulting in hypokalemia. Be certain that the patient is not hypokalemic before giving insulin
4. phosphate and magnesium levels may also be low

Front 175

Treatment of DKA

Back 175

1. Give insulin immediately. Give a priming dose of 0.1 units/kg of regular insulin IV followed by an infusion of 0.1 units/kg per hour. This is sufficient to replace the insulin deficit in most patients. Make sure patient is not hypokalemic before you administer insulin
2. Continue insulin until the anion gap closes and metabolic acidosis is corrected-- then begin to decrease the insulin. Give subQ insulin once the patient is eating
3. Give fluids immediately. Add 5% glucose once the blood sugar reaches 250 mg/dL to prevent hypoglycemia
4. replace potassium prophylactically with IV fluids - initiate within 1-2 hours of insulin. Ensure adequate renal function before giving. Monitor potassium, magnesium and phosphate levels closely.
5. Bicarb replacement is controversial and usually not needed

Front 176

Hyperosmolar hyperglycemic nonketotic syndrome (HHNS) - general characteristics
1. definition, typical patient
2. pathogenesis

Back 176

1. a state of severe hyperglycemia, hyperosmolarity and dehydration that is typically seen in elderly type II diabetics
2. low insulin levels lead to hyperglycemia. Severe hyperglycemia causes osmotic diuresis and dehydration
3. ketogenesis is minimal because a small amount of insulin is released to blunt counterregulatory hormone release (glucagon)
4. ketosis and acidosis are typically absent or minimal
5. severe dehydration is due to continued hyperglycemic osmotic diuresis. The patient's inability to drink enough fluids (either due to lack of access in elderly/bedridden or due to inadequate thirst drive)

Front 177

Hyperosmolar hyperglycemic nonketotic syndrome - clinical features

Back 177

1. thirst, polyuria
2. signs of extreme dehydration and volume depletion- hypotension, tachycardia
3. CNS findings and focal neurologic signs are common-- seizures secondary to hyperosmolarity
4. lethargy and confusion may develop, leading to convulsion and coma

Front 178

Diagnosis of Hyperosmolar hyperglycemic nonketotic syndrome

Back 178

1. hyperglycemia- serum glucose is typically higher than that seen in DKA and is frequently > 900 mg/dL
2. hyperosmolarity- serum osmolarity > 320 mOsm/L
3. serum pH > 7.3 (no acidosis), serum bicarb > 15
4. BUN is usually elevated. Prerenal azotemia is common due to dehydration

Front 179

Treatment of Hyperosmolar hyperglycemic nonketotic syndrome

Back 179

1. Fluid replacement is the most important (normal saline). 1L in the first hour, another liter over the next 2 hours. Most patients respond well. Switch to 1/2 NS once the patient stabilizes.
2. glucose levels are lowered as the patient is rehydrated (but the patient still requires insulin)
3. when glucose levels reach 250 mg/dL give 5% dextrose (d5-1/2NS) to prevent hypoglycemia
4. very rapid lowering of blood glucose can lead to cerebral edema in children (just as in DKA)
5. In patients with cardiac disease or renal insufficiency, avoid volume overload as this can precipitate CHF-- although generous fluids are still needed
6. Insulin - An initial bolus of 5-10 units IV, followed by a continuous low-dose infusion of 2-4 units/hour is usually adequate

Front 180

What is the primary organ at risk during hypoglycemia?

Back 180

The brain. This is because the brain uses mainly glucose as its energy source (except when using ketones during fasting)
- Unlike other tissues, the brain cannot use free fatty acids as an energy source
- Hypoglycemia is really due to an imbalance between glucagon and insulin
- If there is NO correlation between symptoms and low glucose levels ( i.e. the patient is symptomatic when there glucose levels are normal), then it is unlikely that the patient has an underlying glucose metabolism disorder

Front 181

Causes of hypoglycemia

Back 181

1. Drug-induced- taking too much insulin-- a common in problem in diabetic patients attempting tight control of their disease
2. Factitious hypoglycemia- If the patient has surreptitiously taken insulin, they will have high insulin levels but low C-peptide levels. Endogenous insulin is always released with C-peptide. Also patients taking exogenous insulin will develop anti-insulin antibodies which can be measured. You may also check Sulfonylurea levels
3. Insulinoma
4. Ethanol ingestion - due to poor nutrition that leads to decreased glycogen. Metabolism of glucose lowers NAD levels and decreases gluconeogenesis
5. Post-operative complications after gastric surgery - due to rapid gastric emptyin
6. reactive hypoglycemia- occurs 2-4 hours after meals, and rarely indicates anything serious
7. Adrenal insufficiency
8. Liver failure
9. Critical illness
10. Disorders of carbohydrate metabolism (glycogen storage diseases)- usually diagnosed at young age

Front 182

Clinical features of hypoglycemia
1. when present?
2. symptoms and what are they due to?

Back 182

1. Symptoms occur at blood glucose levels of 40-50 mg/dL
2. Elevated epi/norepi levels lead to sweating, tremor, increased BP and pulse, anxiety and palpitations
3. Neuroglycopenic symptoms- decreased glucose for the brain (CNS dysfunction)- results in irritability, behavioral changes, weakness, drowsiness, headache, confusion, coma and even death

Front 183

What lab test should you order in a patient with hypoglycemia of unknown cause?

Back 183

1. plasma insulin level
2. c-peptide
3. anti-insulin antibodies
4. plasma and urine sulfonylurea levels

Front 184

Hypoglycemia unawareness

Back 184

- In diabetic patients, if there is severe neuropathy, the autonomic response (epinepherine) to hypoglycemia may not be activated. This leads to neuroglycopenic symptoms
- It is common for diabetic patients to become hypoglycemic with conventional therapy (insulin and oral hypoglycemics)
- With longstanding disease in which they lose their neurogenic symptom response to hypoglycemia, patients do not recognize the impending hypoglycemia and may even have a seizure or enter a coma

Front 185

Diagnosis of hypoglycemia

Back 185

1. Blood glucose level- symptoms generally begin when levels drop below 50 mg/dL. However, there is no cutoff value to define hypoglycemia
2. Whipple's triad- hypoglycemic symptoms brought on by fasting, blood glucose < 50 mg/dL during sx, glucose admin brings relief
3. Lab tests- serum insulin, c-peptide, and glucose when sx occur. Overnight fast may do this
4. 72-hour fast (24-hours is usually sufficient) used to diagnose insulinoma if suspected

Front 186

Treatment of hypoglycemia
1. acute treatment
2. underlying cause
3. reactive hypoglycemia
4. alcoholic patients

Back 186

1. If the patient can eat, give sugar-containing foods, if not give 1/2 to 2- ampules of d50W IV
- repeat administration of D50W as necessary but switch to D10W as clinical condition improves and glucose level is approx > 100 mg/dL
2. treat underlying cause (e.g. diabetes or insulinoma)
3. dietary interventions
4. if suspected alcoholic-- always give thiamine before a glucose load to prevent Wernicke's encephalopathy

Front 187

Insulinoma
1. what is it?
2. what is it associated with?
3. malignant vs benign?

Back 187

1. Insulin producing tumor of the beta cells of the pancreas
2. Associated with MEN I syndrome
3. usually benign - in up to 90% of cases

Front 188

Clinical features of an insulinoma

Back 188

1. sympathetic activation- diaphoresis, palpitations, tremor, high BP, anxiety
2. neuroglycopenic symptoms- HA, visual disturbances, confusion, seizures, coma

Front 189

Diagnosis of insulinoma

Back 189

1. 72-hour fast
a. the patient becomes hypoglycemic. Normally the insulin level should decrease as hypoglycemia develops
b. in persons with insulinoma, insulin does not respond appropriately to hypoglycemia. It may decrease or increase, or it may not change. However, it is still higher than it would be in a normal patient for the given glucose conc
2. Whipple's triad-- hypoglycemic symptoms brought on by fasting, blood glucose <50mg/dL during symptomatic attack, glucose administration brings relief of symptoms
3. elevate fasting serum insulin. C-peptide should also be elevated - distinguishes from exogenous insulin

Front 190

Treatment of insulinoma and success rate

Back 190

Surgical resection of tumor (up to 80-90% cure rate)

Front 191

Zollinger-Ellison Syndrome (Gastrinoma)
1. what is it?
2. benign vs malignant? where most often found?

Back 191

1. a pancreatic islet cell tumor that secretes high gastrin, which leads to profound gastric acid hypersecretion, resulting in ulcers
2. Up to 60% are malignant, 20% are associated with MEN I (80% are sporadic), 90% located in the gastrinoma triangle-- formed by cystic duct superiorly, junction of 2nd and 3rd portions of the duodenum inferiorly, and neck of the pancreas medially

Front 192

Complications and clinical features of ZES/gastrinoma

Back 192

- Complications- GI hemorrhage, GI perforation, gastric outlet obstruction/stricture, and metastatic disease (liver is the most common site)
- Clinical features- peptic ulcers, diarrhea, weight loss, abdominal pain

Front 193

Diagnosis of gastrinoma/ZES

Back 193

1. Secretin injection- this normally inhibits gastrin secretion, however in patients with ZES, gastrin levels increase substantially after being given secretin
2. Fasting gastrin level is elevated in patients with ZES
3. Normal basal acid output is <10 mEq/hr, in patients with ZES, it is >15 mEq/hr

Front 194

Treatment of ZES/gastrinoma

Back 194

- High dose proton-pump inhibitors (e.g. omeprazole)
- All patients with ZEs should undergo exploration to attempt a curative resection (20% of patients are cured by this). If it is widely metastatic or incurable, debulking and chemo should be considered

Front 195

Glucagonoma
1. what is it?
2. clinical features?
3. treatment

Back 195

1. a glucagon-producing tumor located in the head of the pancreas
2. necrotizing migratory erythema (usually below the waist), glossitis, stomatitis, DM (mild) and hyperglycemia (with low amino acid levels and high glucagon levels)
3. surgical resection

Front 196

Somatistatinoma
1. what is it?
2. prognosis?
3. triad of clinical features

Back 196

1. a rare, malignant pancreatic tumor (mets usually present at the time of diagnosis)
2. poor prognosis
3. classic triad of gallstones, diabetes, and steatorrhea

Front 197

VIPoma (Verner-morrison)

Back 197

1. a rare pancreatic tumor (>50% malignant)
2. clinical features include watery diarrhea (leding to dehydration, hypokalemia, and acidosis (loss of bicarb), achlorhydria (VIP inhibits gastric acid secretion), hyperglycemia and hypercalcemia
3. treatment - surgical resection

VIP= vasoactive intestinal peptide