At pathologically high levels, what does high levels of TRH stimulate the release of?

What condition commonly has this high level of TRH?

Prolactin

Hypothyroidism

A patient with a prolactinoma should NEVER be treated with what as a first line treatment?

What screening test and diagnostic can be done?

Never surgery as a first resort.

Screening=check blood prolactin levels.

Dx=Get an MRI.

Inhibits GH mostly, but also inhibits:

Insulin

Glucagon

Secretin

Vasoactive Inhibitory Peptide (VIP)

Thyriod Releasing Hormone (TRH)

Somatostatin can be used in medical imaging and the treatment of acromegaly.

Which of the hypothalamic hormones is NOT under stimulatory control?

What allows the release of this hormone?

Prolactin

Dopamine absence

Cushing's syndrome

iatrogenic Cushing's syndrome

What other autoimmune disease often presents with type 1 diabetes?

What percentage of T1DM patients have this disorder?

Hashimoto's Thyroiditis

30%

Abdominal girth greater than 40 inches in men, 35 in women.

Blood pressure higher than 130/80

Impaired fasting glucose

Triglycerides greater than 150.

HDL less than 40 in men, less than 50 in women.

Dx is made with 3 or more of the above criteria

What is the screening test used to assess if a patient has gestational diabetes?

 If the screening test is abnormal, what are the findings in a 3 hour oral glucose tolerance test (OGTT) that indicate diabetes in the mother?

50-gram 1-hour glucose challenge test (GCT). Should be less than 140mg/dl.

If the result on the GCT is abnormal, the patient undergoes a 100-gram 3-hour oral glucose tolerance test (OGTT).

Fasting blood sugar should be less than 105 mg/dl

1 hour blood sugar should be less than 190mg/dl

2nd hour blood sugar should be less than 165mg/dl

3rd hour blood sugar should be less than 145mg/dl

If 2 of the above are exceeded than the mother has gestational diabetes.

Which hormone in pregnant mothers is very similar to HGH?

What condition does this predispose pregnant mothers to?

Placental lactogen (used to modify maternal metabolism to support the fetus and to help develop things like breast tissue).

Gestational DM (like GH, increases blood sugar).

What signs of diabetes can be seen on the skin and in the eyes?

Which skin manifestation is almost pathopneumonic for diabetes?

Skin:

Acrochordons

necrobiosis lipoidica diabeticorum (almost pathopneumonic)

Eruptive xanthomas

Acanthosis nigracans

Eyes:

Cataracts

Cranial nerve palsies

Retinopathy

Rubeosis iridis

What is the most common cranial nerve palsy seen in a diabetic patient?

What is the most likely pathogenesis of cranial neuropathies, and of diabetic neuropathy?

3rd nerve palsy

Infarct of the vasa nervorum (small blood vessels which provide blood supply to larger nerves).

What therapies have been shown to be very effective in preserving the vision in diabetics experiencing retinopathy?

How does each help?

laser therapy-destroys the new vessels forming due to VEGF up regulation in the retina and prevents retinal detachment.

vetrectomy-use a needle to drain the vitreous humor and replace it with a synthetic vitreous.  This is important in that bleeding can opacify the vision in a diabetic, and to restore vision due to this problem this method can be used. ONLY HELPS WITH A HEALTHY RETINA, which may be hard to assess if the eyeball is opacified with blood.

Somatic: Peripheral loss of sensation and muscle tone.

Proximal neuromyopathy

Autonomic: Gastroparesis Diabeticum

Altered Heart Rate

Diarrhea

Impotence

Urinary retention

altered prespiration

Glargine (Lantus), Detemir (Levemir)

Consider the patients "morning glucose level" and adjust dosage to have this number below 120mg/dl

When considering insulin pumps, what is an example of a closed loop system?

Are these currently availible in the United States?

A pump which delivers insulin based on its own blood readings.  Current systems require user input.

This is not approved by the FDA yet.

Metformin; lowers hepatic gluconeogenesis.

Contraindicated in renal insufficiency

Stimulates acute phase release of insulin

Decreases glucagon release by alpha cells

Slows gastric emptying

Suppresses CNS appetite center

Exenatide (byetta) and Liraglutide (Victoza)

Mimic GLP-1

Inhibit the enzymatic degredation of GLP1; usually used as a conjunction therapy.

Sitagliptin (Januvia)

Always located midline and above where the gland should be

Always tethered to the tongue

Because they are tethered, they elevate when swallowing.

Iodide trapping

Iodidization of tyrosil residues

residue coupling

proteolysis

deidozation with reuse of I.

Deidozation of T4 to T3.

Describe the Wolf-Chaikoff effect.

Describe the Jod Basedow effect.

–Excess iodide

creates an inhibition of organification and

decreased hormonogenesis

-Excessive iodide induces hyperthyroidism.

More TBP due to pregnancy means less free thyroid hormone.

Need to increase her dosage of thyroid hormone as much as 50% during her pregnancy.

How can one distinguish primary from secondary hypogonadism?

Which remains infertile even with treatment?

Both have low testosterone, but:

Primary: Decreased TST with increased LH/FSH.

Secondary: Low TST with low or normal LH/FSH.

Primary

Orchiopexy – surgical placement of testis into scrotum

IM hCG or intranasal GnRH to promote descent

Spironolactone

Ketoconazole

Chemotherapy (alkylating agents)

EtOH

What makes the restoration of fertility in a male with hypogonadism more likely?

Less likely?

More likely to work if 

Hypogonadism acquired post-pubertal

Partial rather than complete

Secondary hypogonadism

Less likely if

Cryptorchidism

Primary testicular failure

What conditions are associated with MEN I (Werner's syndrome)?

Which is most common?

Pituitary adenoma

Parathyroid hyperplasia (hyperparathyroidism) MOST COMMON

Pancreatic tumor

"Pity Para Pan"

How is the diagnosis of a gastrinoma made?

How?

Diagnosis made with secretin stimulation test

Secretin stimulates gastrin secretion from gastrinomas but suppresses gastrin levels in normal tissue

Hyperparathyroidism

Pheochromocytoma

Medullary Thyroid Carcinoma

Pheochromocytoma

Medullary Thyroid Carcinoma

Mucosal Neuromas

Marfanoid Habitus

In pheochromocytoma:

10% bilateral

10% malignant

10% familial

10% in children

10% extra-adrenal

10% not associated with hypertension

Classic triad (need 2/3 for diagnosis)

Chronic mucocutaneous candidiasis

Autoimmune hypoparathyroidism

Primary adrenal insufficiency (Addison’s disease)

What is Chvostek’s sign?

What is it used for?

contraction of facial muscles elicited by tapping facial nerve 2cm anterior to earlobe

Used to screen for hypocalcemia as seen in hypoparathyroidism

What are the blood test signs common in Addison's disease?

What are the clinical signs?

Decreased cortisol and mineralocorticoids with increased ACTH

Weakness, fatigue, weight loss, hypotension, hyperkalemia, hyponatremia

Classic Triad (need 2/3 for diagnosis)

DM 1

Addison’s disease

Autoimmune thyroid disease

Anti-islet cell antibodies

Insulin autoantibodies

Glutamic acid decarboxylase (GAD) antibodies

What is the most potent treatment for osteoporosis and what is its mechanism of action?

What is the risk of overuse?

Forteo (teriparatide).

Stimulates PTH (synthetic PTH)

Sarcomas become a risk with 2 years of treatment.

Kidney failure

sarcoid and other granulomatous diseases because of their expression of 1 alpha hydroxylase (high active vitamin D)

Muscle spasms, specifically:

Laryngospasm

Arrhythmias

Seizures

What is another name of idiopathic PTH inactivity?

What is the etiology and clinical presentation of this disorder?

DiGeorge syndrome

associated with other developmental abnormalities in branchial pouches III-IV.

Thymic aplasia, aortic arch/vascular abn, mental retardation, craniofacial dysmorphism

Sporadic or autosomal dominant

Albright Hereditary Osteodystrophy (AHO)

Obesity, short stature, round face, short neck, shortening of 4th and 5th metacarpals and metatarsals

May see resistance to other hormones: Gn, glucagon, VP; deficiency TSH/PRL; deficient secretion insulin, thyroid hormone

How does a patient with Pseudo-Pseudo Hypo-Para present clincally?

Is there ususally a family history?

Physical stigmata of AHO but no hypocalcemia

Usually seen in family members of Pseudohypopara IA

A patient with a long Q-T interval would have what reading regarding their blood calcium?

What about with a short Q-T?

Low calcium

High calcium

Elevated calcium reading (1mg/dl higher than normal) with symptoms

Renal disease

Age less than 45 years old

Osteporosis on DEXA

A patient presents in the emergency room in a comatose state. After he is stabilized, He is noted to have a shortened Q-T interval, a normal PTH level, and normal levels of Ca in his urine.  After his family arrives, it is noted that his mother had problems with hypercalcemia.

What is the most likely diagnosis?

A patient with chronic renal failure has recently gone on to dialysis.  Before he was on dialysis, the patient had very elevated PTH levels and a short Q-T interval.  After his renal transplantation, the patient experiences severe hypercalcemia and enters a comatose state.

What is the most likely diagnosis and what is its etiology?

Tertiary hyperparathyroidism

Autonomous parathyroid glands due to their chronic overuse.

Could be a malignancy causing an excessive release of PTHrP.

Get a PTHrP assay as a followup.

Granulomatous disease

FHH

Milk-alkali syndrome

Medications such as lithium or thiazides

Adrenal insufficiency

hyperthyroidism

Hyperparathyroidism primary, secondary or tertiary.

MEN syndromes

What class of drugsinhibits PTH mediated bone resorption and has survival benefits in multiple myeloma?

What is the most commonly perscribed drug of this class?

bisphosphonates

Pamidronate

What percentage of patients with Cushing's syndrome have high blood pressure?

What percentage have diabetes or insulin resistance?

40%-60%

50%

What is the most significant clinical finding that is suggestive of Cushing's syndrome in a female?

What other two findings are generally very commonly found in Cushing's?

Severely irregular or absent menses.

Psychiatric disturbances and profound proximal myoneuropathy.

Why don't patients with ectopic ACTH secretion present like those who have Cushing's syndrome?

What common characteristics do these patients have?

They usually die before Cushing's symptoms present.

Hyperpigmentation (high MSH), cachexia, salt retention and hypokalemic alkalosis.

What can interfere with a baseline cortisol reading used in a dexamethazone test?

What should the morning cortisol readings be after a 1mg dexamethzone screening test?

What other conditions besides Cushings can cause a low or absent response to dexamethazone?

Birth control can artificially elevate cortisol levels.

Should be < 5 or < 50% of baseline

Obesity, ETOH abusers, and psychiatric patients may  not suppress

What are the ACTH levels in:

Cushing's patients

Ectopic ACTH tumor

Primary adrenal gland pathology

Normal to slightly high with Cushing’s disease

High to very high with

Ectopic ACTH

Low or nondetectable with

Primary adrenal gland pathology

What drug can be used to treat Cushing's disease without surgery, or in preparation for surgery?

After surgery, what will most patients require?

Cyproheptadine (a serotonin inhibitor)

Exogenous cortisol and/or mineralocorticoids (florinef)

What is the most common cause of adrenal insufficiency in the world?

What is this called?

What about in the united states?

TB infection

Addison's disease

Autoimmune

A child with a history of adrenal insufficiency presents with nausea, a headache and a slight fever.  On physical exam you also note purpura on his skin and low blood pressure. Blood tests show hyperkalemia and hyponatremia with a very slight leukopenia.  You suspect:

What causes this condition?

Waterhouse Friedrickson Syndrome

Infection of the adrenals with N. meningitidis

A 42 year old female on high anticoagulant therapy is noted to have large, dense adrenal glands on MRI.  An ACTH stimulation test shows a very minimal rise in blood cortisol levels. She also has psychiatric disturbances such as confusion and an impairment of consciousness.  Lastly, she has frequent headaches.

What is a likely diagnosis?

A 43 year old female patient presents with a loss of 15 pounds in 3 weeks, a "darker than normal" complexion, nausea and hypotension.

Blood tests reveal a potassium level of 6.2mEq/L, Na⁺ level of 89 mEq/L, blood glucose of 55mg/dL, Calcium level of 12.7 (albumin of 4 Gm/dL), azotemia, and a WBC of 8,500/mm3 with a eosinophil count of 8.8%.

This is most likely:

With secondary insufficiency:

No hyperpigmentation

Less hypotension

Na+ and K+ tend to be normal

What test can be used to assess for adrenal insufficiency?

What results from this test can differentiate primary from secondary insufficiency?

Rapid cosyntropin (semisynthetic ACTH) test

Baseline cortisol and aldosterone

Give 250mcg of drug

Check levels at 30 and 60 minutes

If both are low then primary 

If cortisol is low but aldosterone responds then secondary

Cortisol level should go above 21 ng/dl

Delta in cortisol should be at least 7 ng/dl

Aldosterone should delta 14ng/dl or more

What might a person have trouble with if they take exogenous steroids for more than 10-14 days?

What is a good clinical finding to check to see if a person has this problem?

What blood test can be used for this assessment?

How might a patient protect against this problem?

May not be able to adequately respond to stressful situations (cannot produce cortisol!) due to the inhibition of the stress axis and reversible ACI. This is called an adrenal crisis.

A proper response to hypoglycemia is usually a good sign.

Metapyrone test.

Increase dosage of their glucocorticoids by as much as 100-200% during stressful moments.  May also need a mineralocorticoid.  Try to mimic the diurinal pattern of cortisol (2/3 dose in AM, 1/3 in PM)

What is the clinical appearance of a patient with primary hyperaldosteronism?

What are the blood results?

None! Look normal.

Usually hypertensive

  K+ low

Renin levels very low (aldosterone:renin ratio as much as 20:1)

Aldosterone levels are high

20 to 1 ratio or more

Not edematous (some escape mechanism)

What is the most common cause of hyperaldosteronism?

What other types are possible?

A unilateral adrenal tumor (Conn's syndrome)

dexamethasone sensitive

idiopathic

Diagnostic tests

Aldo/renin ratio (>20:1)

MRI or CT of adrenals

Selective adrenal vein sampling for aldo (make sure the adrenal to be removed is really the problem adrenal!)

Treatment

Surgery for Conn’s syndrome

Steroid for dexa suppressible

spironolactone

What are the signs and symptoms of pheochromocytoma?

What diagnostic tests can be used?

How can this be treated?

Hypertension (sustained or episodic)

Headache

Tachycardia

Diaphoresis

Anxiety

T2 weighted image on MRI

MIBG scan

Plasma catecholamines (good first test)

Urinary metanephrines (good first test)

Selective adrenal drainage

Alpha blocker, then

Beta blocker, then

Resection

Probably a adrenal incedentaloma

Observe

What can accelerate the clearance or inhibit the absorbtion of L-thyroxine treatment?

What is a commonly missed substance which causes malabsorption?

Accelerated clearance

– Rifampin

– Dilantin/tegretol

• Malabsorption

– Surgery

– Medications

• Questran

• Carafate

• Iron

• aluminum

The calcium in multivitamins can cause malabsorption; often missed due to under-reporting taking multivitamins.

What should be measured in deducing if a patient has a thyroid condition?

What if the patient is pregnant?

Has undergone pituitary surgery?

Has or has had thyroid cancer?

• Ultrasensitive TSH assay

• Cascade/reflex to free T4

• Pregnancy --TSH + freeT4

• Pituitary surgery –freeT4 + T3

• Thyroid cancer –TSH + free T4 +

thyroglobulin

Thyroid

Eye

Shin region (Pre-tibial non pitting myxedema)

"Cold". Hot nodules almost never have cancer, they are just more efficient than other nodules.

What is a key differential in diagnosing DeQuervain's thyroiditis?

What would an I₁₂₃ scan show in this condition?

What results with this condition transiently?

Pain in the neck caused by thyroid inflammation.

Low uptake

Hyperthyroidism (usually resolves as the thyroid glands recover)

A 84 year old female in a nursing home has become less and less interested in social interation and prefers to stay in her room.  She was once quite social.  Blood tests reveal a TSH level of 0.9mIU/L, a total T₄ level of 10.8mIU/L and a total T₃ of 207mIU/L.  Her TSH level in the past has usually been around 3.7mIU/L

What is a likely diagnosis?

What pharmacological treatments can be used to treat hyperthyroidism?

When combined, what two treatments outweigh the risks of another treatment?

Methamiasole

PTU

Beta Blockers

Combined use of methamisole and beta blockers has the advandage of regulating blood pressure, preventing T4-T3 conversion in the periphery (B blocker effect), and preventing the formation of thyroid hormone.  This outweighs the risks of using PTU in patients (except in pregnant mothers)

A patient presents with a swelling in the knee region.  On palpation the area is non-pitting, and has an "orange peel" appearance.  This symptom is suggestive of:

What if the patient's knee WAS pitting?

Hyperthyroidism

Hypothyroidism

A pregnant mother presents with a total T₄ reading of 13.7mIU/L and a total T3 reading of 265mIU/L.  She is asymptomatic and has a TSH level of 3.2mIU/L

What is a likely explaination for this?

A 65 year old male has a palpable nodule in the right lobe of his thyroid gland.  His last check up a year ago did not have this.  Should this patient be worried about thyroid cancer?

What other risk factors would be important to consier?

Yes:

• Nodules appearing at the extremes of age

<20 or >60

• Males

• Rapid growth

• Exposure to external radiation

• Family Hx

• Local, asymmetric adenopathy

A I₁₂₃ scan of the thyroid is useful to detect hot nodules.

True or false: This scan is useful in detecting lobe areas which are cancerous.

What is the best way to visualize cold nodules after an I₁₂₃ scan?

If a node of concern is found, what is the most cost effective way to test to see if it is malignant?

False: This scan is used to detect areas that are NOT cancer!

After hot nodes are visualized on I₁₂₃ scan, do a ultrasound of the thyroid. This helps identify cold nodes.

A Fine-needle aspiration biopsy (guided with ultrasound usually)

What are the 4 types of thyroid cancer? Order them from least aggressive to most aggressive.

Which tend to spread?

Which tends to indicate cancer elsewhere due to probable oncogene problems?

Which tends to be familial?  What gene is involved?

Papillary (MC) (can indicate problems elsewhere)

Follicular (can spread to bone hemotogenously)

Medullary (familial, proto RET oncogene)

Anaplastic (can invasively spread to the trachea and other neck structures, also can be blood borne).

With a thyroid resin uptake test, would the T₃U value of a hyperthyroid patient be high or low?  Explain.

What about a hypothyroid patient?

What about a pregnant woman? What if she was hyper or hypothyroid? Explain.

High.  More binding of thyroid hormone to binding globulins in a hyperthyroid patient makes less sites availible for labeled thyroid hormone to bind; thus more is taken up by the resin.

Low; for the inverse reasoning.

A pregnant woman has more thyroid binding globulin, thus she will appear to have hypothyroidism.

A hypothyroidal pregnant woman would have the LOWEST value of T3U for the reasons above.

A hyperthyroidal pregnant woman may appear NORMAL for the reasons above.

Primary: A tumor causing hypersecretion of PTH, causing hypercalcemia.

Secondary: parathyroid gland over-secretion due to chronig hypocalcemia (low dietary intake, etc.) Can cause parathyroid gland hyperplasia.

Tertiary: as a result of chronic secondary hyperparathyroidism, the parathyroid glands may become autonomous and hyperplastic, oversecreting PTH.