Lecture 18 (endocrine)-Exam 6 Flashcards
Thyroid Nodules
* What are the two types?
* Prevalence with what?
* When are they found?
Thyroid Nodules
* Clinical importance is primarily related to what?
* Order what?
- Clinical importance is primarily related to the need to exclude thyroid cancer, which accounts for 4 to 6.5 percent of all thyroid nodules
- Order I-123 scan/uptake to see if nodule is hot/cold
What are the benign causes of thyroid nodules?
What are the malignant causes of thyroid nodules?
kinda long-> flow chart
What is the work up for thyroid nodule?
Thyroid nodule dx:
* how do you dx it?
* The thyroid gland requires what to function? Why is this important?
- The radioactive iodine uptake test (RAIU) is also called a thyroid uptake.
- The thyroid gland requires iodine to function. This uptake of iodine is reflective of its function. If the thyroid gland is functioning normally, the quantity of iodine taken up should be within a particular range.
Diagnosis of thyroid nodule
* Radiotracer is either what? What happens to it?
* Radioactive emissions from the radiotracer are what?
* By using radioactive/radiotracer iodine, it is possible to determine what?
* If excessive amount of radioactive iodine is taken up by the gland, it indicates what? What happens if it is a little?
- inhaled as a gas and eventually accumulates in the organ or area of the body being examined.
- Radioactive emissions from the radiotracer are detected by camera and provides molecular information.
- By using radioactive/radiotracer iodine, it is possible to determine how much iodine the thyroid gland pulls in.
- If excessive amount of radioactive iodine is taken up by the gland, it indicates an overactive thyroid gland.
- If very little is taken up, it is indicative of hypothyroidism.
Diagnosis of thyroid nodule
* Radioactive iodine uptake is a measure of what?
* Scintigraphy, on the other hand, is the use of what?
- Radioactive iodine uptake is a measure of the rate of accumulation of radioactive tracer by the thyroid and the ability of it to trap that tracer.
- Scintigraphy, on the other hand, is the use of gamma cameras to capture emitted radiation from internal radioisotopes to create two-dimensional images.
Thyroid Scan: Palpable Nodules on NM scan
* Hot vs cold nodules?
* No uptake?
Hot Nodules
* Essentially always benign
Cold Nodules
* Usually benign but can be malignant
* Majority of nodules are cold (90%)
No uptake
* Infection
Fill in covered part
⭐️Know the most common⭐️
Thyroid Carcinoma
* What are the different types?
- Papillary Carcinoma (60%) ⭐️
- Follicular Carcinoma (20%)
- Anaplastic Carcinoma(1%)
- Medullary Carcinoma(5%)
- Lymphoma(1%)
Thyroid Carcinoma Txt:
* What usually just gets followed?
Patients with benign nodules (macrofollicular or adenomatoid/hyperplastic nodules, colloid adenomas, nodular goiter, and Hashimoto’s thyroiditis) are usually followed without surgery.
Thyroid Carcinoma Txt:
* What is the monitoring for the thyroid nodules that worrisome?
Periodic ultrasound monitoring of benign thyroid nodules initially at 12 to 24 months, then at increasing intervals (eg, two to five years), with the shorter intervals for large nodules or nodules with worrisome ultrasound features and the longer interval for smaller nodules with classic benign ultrasonographic features.
Thyroid Carcinoma US:
* Sonographic features favoring a malignant nodule?
- hypoechoic solid
- presence of microcalcifications: almost always warrants biopsy
- local invasion of surrounding structures
- taller than it is wide
- large size: the cutoff is often taken as 10 mm to warrant biopsy
- suspicious neck lymph nodes suggesting metastatic disease
- intranodular blood flow
Thyroid Carcinoma Treatment:
* Repeat the FNA within 12 months if what?
Repeat the FNA within 12 months if the initial ultrasound shows highly suspicious ultrasound features despite a benign biopsy
Thyroid Carcinoma Treatment:
* Repeat FNA is also warranted when there is what?
Repeat FNA is also warranted when there is substantial growth (more than a 50 percent change in volume or 20 percent increase in at least two nodule dimensions), there is the appearance of suspicious ultrasound features, or new symptoms are attributed to a nodule.
Thyroid Carcinoma Treatment:
* Patients with nodules that are suspicious for malignancy or malignant should be referred for what?
for biopsy vs. removal.
Follow-up and patient education of thyroid cancer
* What needs to be done?
* Need what?
* What type of referral?
- Serial Diagnostic tests as usual
- Need compliance!
- Endocrine referral
What is the pituitary gland anatomy?
Pituitary adenoma
Pituitary adenoma
* What is the mc mass? What is that?
* What is the mc tumor?
Most common Sellar Mass
* Sellar masses (SMs) are adenoma bodies that are typically located on or around the pituitary gland, specifically near the sella turcica. Sellar masses are known to account for approximately 10% to 15% of all intracranial neoplasms. and are responsible for a myriad of visual, neurological, and hormonal deficiencies
Most common pituitary tumor is prolactinoma
Adenoma can become what?
It is a lot-> flow chart
What are the pituitary mass effects?
Fill in for the causes of sellar masses
Fill in for the causes of sellar masses
Pituitary Adenoma
* What imaging can you do and what does it show?
- Coronal T1-weighted postcontrast MRI image shows a homogeneously enhancing mass (arrowheads) in sella turcica & suprasellar region compatible with a pituitary adenoma;
- Small arrows outline carotid arteries.
Clinical Presentation of pituitary adenoma
* What are the neuro sxs?
* What are the ophthalmological sign? ⭐️
Neurological Symptoms
* Headache and meningeal signs
* CN 3, 4, 6 dysfunction
* Temporal Seizures
Ophthalmological Signs
* Decreased visual acuity-> usually bitemporal hemianopia
* Rarely exophthalmos
*
Pituitary Adenoma
* What are the radiological signs?
* What are silent ones?
Radiological Signs
* Enlarged surface of sella turcica
* Combined clinical suspicion based on exam (Ex: acromegaly)
25-35% are clinically nonfunctioning or “silent”
* Therefore don’t produce hormone symptoms (normal cortisol, hGH, and prolactin), but present with mass effect type symptoms on the chiasm
Hormonal Evaluation of Pituitary Adenomas
* What do you need to test for? (3)
Hormonal Evaluation of Pituitary Adenomas
* Gonadotropins: test for what? (3)
* TSH: Test for what? (2)
Gonadotropins
* Test for hyperfunction -FSH, LH
* Test for deficiency testosterone in men; menstrual history in women
* In post-menopausal women, can test gonadotropin levels to look for hypopituitarism
TSH
* Test for hyperfunction -TSH, free T4
* Test for deficiency –TSH, free T4
⭐️
Pituitary adenomas
* how do you dx and tx?
Acromegaly/Gigantism
* Stemming from what?
* The most common cause of acromegaly is what?
* These adenomas account for what?
* Others are either what?
Stemming from excessive growth hormone (hGH) from pituitary adenoma
* The most common cause of acromegaly is a somatotroph (growth hormone [GH]-secreting) adenoma of the anterior pituitary.
* These adenomas account for approximately one-third of all hormone-secreting pituitary adenomas.
* Others are either central or peripheral ectopic adenomas (hypothalamic, bronchial, pancreatic, or thyroid)
Acromegaly/Gigantism
* Prominent where?
* What results in pituitary gigantism?
* What is the annual incidence?
* What is the mean age?
A lot-> flow chart
What is the pathogenesis and clinical findings of GH excess?
Acromegaly/Gigantism
* What is the clinical presentation?
Acromegaly/Gigantism
* What is going on here?
Note large head, forward projection of jaw & protrusion of frontal bone
How do you confirm diagnosis acromegaly? ⭐️
Confirm Dx by demonstrating failure of GH suppression to < 1ug/L within 1-2 h or a 75- g oral glucose load
* CHATGBT: Oral Glucose Tolerance Test (OGTT): This is the gold standard test for diagnosing acromegaly. In a healthy individual, GH levels should decrease following glucose ingestion. In patients with acromegaly, GH levels remain elevated or do not decrease appropriately after a glucose load.
What are the DDX for Acromegaly/Gigantism
Acromegaly/Gigantism
* What is the txt? ⭐️
Surgical therapy
* Preferred transsphenoidal resection
Acromegaly/Gigantism
* What is the txt if cannot do surgery?
Medical therapy
* If not a surgical candidate (unresectable, patient preference or medical comorbidities)
* Somatostatin analogs (Octreotide) adjunctive medical therapy that suppresses GH secretion with modest effects on tumor size.
* Pegvisomant is excellent for microadenomas if not amenable to surgery
Dwarfism
* What are the two types? Explain what they are and caused by?
Proportional
* Person is smaller than average all over
* Most commonly caused by hGH deficiency (atrophy or tumor of anterior pituitary)
Disproportional
* Some average-sized parts and some smaller than average
* Achondroplasia is the most common, causing a normal sized torso but short limbs
Achondroplasia
* What is the genetic component? What is it caused by? ⭐️
Achondroplasia is an Autosomal Dominant disorder caused by pathogenic variants in the fibroblast growth factor receptor 3 (FGFR3) gene interfering with normal longitudinal growth at growth plates.
Achondroplasia
* Most common what?
* What is more affected?
* WHat are common issues?
* Gender?
- It is the most common bone dysplasia in humans.
- Proximal extremities (humerus) are more affected than distal (forearm)
- Motor skills delay, hearing loss, crowding of teeth, early arthritis and scoliosis are common
- M=F across the races
achondroplasia
* What is the gene involved? What does it cause? ⭐️
* Who has achondroplasia?
- The FGFR3 gene makes a protein called fibroblast growth factor receptor 3 that is involved in converting cartilage to bone.
- All people who have only a single copy of the normal FGFR3 gene and a single copy of the FGFR3 gene mutation have achondroplasia.
achondroplasia management
* Surgical? Especially in who?
* Give what for porportional dwarfism?
- Surgical correction of orthopedic problems->Especially in disproportionate dwarfism
- Synthetic hGH in proportional dwarfism
achondroplasia management
* The overall prognosis for patients with achondroplasia is good unless what?
* A vigilant follow-up of what?
- The overall prognosis for patients with achondroplasia is good unless they are affected with spinal compression of the cervical medullary junction, which is the most significant cause of morbidity and mortality in achondroplasia.
- A vigilant follow-up of lumbar stenosis in older individuals is also required to avoid complications.
normal physiology of ADH
* ADH is produced by? Why?
* Vasopressin is then transported where? (2)
- Vasopressin (antidiuretic hormone/ADH) is produced by the hypothalamus in response to increased serum osmolality.
- Vasopressin is then transported to the posterior pituitary gland, where it is released into the blood.
- Vasopressin then travels to the kidneys where it binds to vasopressin receptors on the distal convoluted tubules.
Normal physiology of ADH
Normal physiology of ADH
* This binding causes aquaporin-2 channels to move how? What does this cause?
This binding causes aquaporin-2 channels to move from the cytoplasm into the apical membrane of the tubules:
* Aquaporin-2 channels allow water to be reabsorbed out of the collecting ducts and back into the bloodstream
* This results in both a decrease in volume and an increase in osmolality (concentration) of the urine being excreted
Normal physiology of ADH
* The extra water that has been reabsorbed re-enters and causes what?
* This reduction is caused by what?
- The extra water that has been reabsorbed re-enters the circulatory system, reducing serum osmolality.
- This reduction in serum osmolality is detected by the hypothalamus as negative feedback, resulting in decreased production of vasopressin.
Diabetes Insipidus
* Diabetes insipidus (DI) is a disease characterized by what?
* In some cases, the volume of urine produced can be as much as what? What does this cause?
- Diabetes insipidus (DI) is a disease characterized by the passage of large volumes (>3L/24hrs) of dilute urine (osmolality <300 mOsmol/Kg).
- In some cases, the volume of urine produced can be as much as 20 liters in a 24 hour period and therefore rapid dehydration can easily occur, leading to death if not managed appropriately
Diabetes Insipidus
* What are the two types? Why are they caused?
Central DI
* Deficiency of ADH production by hypothalamus (synthesized)-pituitary (released)
Nephrogenic DI
* Kidney resistance to ADH
*
Etiology of DI
* What are the causes of Central DI?(5)
DI-The most common causes of central diabetes insipidus (CDI), accounting for the vast majority of cases, are idiopathic/autoimmune (DI), primary or secondary tumors or infiltrative diseases (such as Langerhans cell histiocytosis), neurosurgery, and trauma
*
Whare the common causes of nephrogenic DI?(5)
Nephrogenic DI-The most common causes of ADH resistance severe enough to produce polyuria are hereditary nephrogenic DI in children, and chronic lithium ingestion and hypercalcemia in adults. Sjogren patients and those recovered from Acute Tubular Necrosis may develop DI.
*
Clinical Presentation and Diagnosis of DI
* What can be high or normal?
* What is the dx text?
* What may show lesions?
Serum Na+ can be normal or high depending upon fluid intake
Vasopressin Challenge Test
* Urine specific gravity increases and serum osmolality decreases in Central DI
* No response in nephrogenic DI
MRI of the pituitary, hypothalamus, and skull may show lesions
Clinical Presentation and Diagnosis of DI
* What are the sxs?
* What are the serum osm or urine osm?
Treatment-CDI
* Treatment of central diabetes insipidus is aimed at what?
* What are the two options? What does it do?
Treatment of central diabetes insipidus is aimed at decreasing the urine output
There are three major therapeutic options:
* Low-solute (sodium and protein) diet
* Desmopressin (dDAVP), an ADH analog
* The initial aim of therapy with desmopressin is to reduce nocturia, thereby permitting adequate sleep; after this is achieved, one aims for control of the diuresis during the day.
Treatment-CDI
* Besides low-solute diet and desmopressin, what can you give?
Other drugs, including thiazide diuretics . The choice of therapy varies with the severity of the polyuria.
Treatment-NDI
* What type of diet? What will it cause?
Low-sodium, low-protein diet
* The reduction in urine output will be directly proportional to the fall in solute excretion. As a result, the efficacy of solute restriction will depend directly upon patient compliance.
Treatment-NDI
* What are some other medications that can be used?
- Indomethacin may improve symptomatic polyuria, if there are no contraindications
- In patients with persistent symptomatic polyuria a trial of desmopressin may be used as last resort
*
Treatment-NDI
* What is the primary therapy in lithium induced DI patients?
Amiloride (K sparing diuretic) should be primary therapy in lithium-induced DI in patients in whom lithium is continued
Treatment-NDI
* In those with significant polyuria, what is done?
* In those with symptomatic polyuria persisting what?
* In children with polyuria due to congenital polyuric-polydipsic Bartter-like syndromes, what is the DOC?
- In those with significant polyuria, frequent and “double-voiding” to avoid bladder dilatation and dysfunction.
- In those with symptomatic polyuria persisting despite a low-solute diet, a thiazide diuretic
- In children with polyuria due to congenital polyuric-polydipsic Bartter-like syndromes, NSAIDs is the therapy of choice
Bartter syndrome
* What is it?
Bartter syndrome usually is seen in children and adolescents who also have stunted growth and complaints of polyuria, polydipsia, cramps, vomiting, dehydration, constipation, growth delays, and failure to thrive. Bartter syndrome (BS) is a rare inherited disease characterised by a defect in the thick ascending limb of the loop of Henle, which results in low potassium levels (hypokalemia),[2] increased blood pH (alkalosis), and normal to low blood pressure.
Adrenal Glands
* What is the anatomy of the gland?
Chronic Adrenocortical Insufficiency
* What is primiary and secondary?
- Secondary – failed ACTH secretion from pituitary (glucocorticoid use)
- Primary – Addison’s disease – adrenal destruction and gluco/mineralcorticoid deficiency despite normal or high ACTH
Chronic Adrenocortical Insufficiency
* What are the sxs?
*
primary Hypoadrenalism
* What is a disease?
* What are the causes?
Addison’s Disease – aka primary Hypoadrenalism
* 90% - adrenal cortex is destroyed due to tissue autoantibodies
* 10% - malignancy/hemorrhage/TB/drugs
What is the test done for Adrenocortical Insufficiency?
Rapid ACTH Stimulation Test
Involves assessing response to injection of synthetic ACTH (Cortrosyn)
* Baseline plasma cortisol sample collected & then 0.25 mg of Cortrosyn administered IM or IV
* Samples for plasma cortisol assay collected at 30 minutes & at 60 minutes
* Normal response is a one hour value of 18-20 mcg/100ml or above with a rise of more than 7 mcg/100ml of cortisol
* Positive test is no increase of cortisol following ACTH stimulation
Addison’s Disease
* What ist he primiary clinical sign?
* What are other sxs?
- Primary clinical sign – hyperpigmentation (they look very tanned) – due to increase in stimulation of melanocyte-stimulating hormone by ACTH
- Weakness, fatigue, anorexia, weight loss, nausea, abdominal pain, salt craving
*
Addison’s Disease
* Symptoms due to what?
* How do you dx? (3)
* What is the tx?(2)
- Symptoms due to lack of aldosterone & sex hormones
- DX – 8am ACTH, cortisol and renin levels
* Hyponatremia seen in ~90% - TX – Glucocorticoids, Mineralocorticoid
*
Addison’s Disease
* What do the labs show? (CMP and CBC)
* What does the plasma cortisol show? ACTH?
Diagnosis of Addison’s disease
* What test is dx? *
* What will be present in a lot of cases? What is seen in autoimmune addison’s disease?
* Serum DHEA levels ?
Adrenal Crisis/Addisonian Crisis
* What type of condition?
* What are the sxs?
- Emergent, life-threatening
- Hypotension
- Hypoglycemia
- +/- Hyperkalemia
Adrenal/Addisonian Crisis
* Acute what?
* Can be a sudden increase of what?
- Acute adrenocortical insufficiency
- Can be a sudden increase of symptoms or an undiagnosed chronic adrenal insufficiency induced by stress (surgery, trauma, MI, steroid withdrawal)
What are the sxs of adrenal crisis?
Adrenal/Addisonian Crisis
* What happens with clinical? (5)
* What do the labs show? (5)
* What is the txt?
- Clinical – Shock picture – hypotension, hypovolemia, hypoglycemia, fever
- Labs – Electrolytes, cortisol, aldosterone, ACTH, renin
- Don’t wait for labs – start TX
* TX – Normal saline (2-3L) or D5NS + IV hydrocortisone for Addison’s or IV Dexamethasone if undiagnosed
*
What happens with Na, K and glucose in Adrenal/Addisonian Crisis? Why does this happen?
- Hyponatremia
- Hyperkalemia
- Hypoglycemia
- All due to mineralocorticoid deficiency and decreased gluconeogenesis and glycogenolysis
*
Expected Labs in Adrenal/Addisonian Crisis
* What happens with ACTH, Ca, creatinine, renin, aldosterone?
- Low or low normal ACTH level in secondary adrenal insufficiency and high or high normal ACTH level in primary adrenal insufficiency.
- Hypocalcemia (due to hypovolemia)
- Prerenal failure with elevated creatinine level
- Hyperrenemia
- Low aldosterone ( due to mineralocorticoid deficiency in primary adrenal insufficiency)
Treatment Background of Adrenal/Addisonian Crisis
* What is the initaial replacement? How are the doses divided? What else can be used?
- Initiate replacement with hydrocortisone in two or three divided doses (total dose of 10 to 12 mg/m2/day) as the glucocorticoid of choice for the management of chronic primary adrenal insufficiency or with surgical procedures.
- A daily dose of dexamethasone or prednisone may also be used. A lowest glucocorticoid dose that relieves symptoms of glucocorticoid deficiency should be used
Treatment Background of Adrenal/Addisonian Crisis
* The vast majority of patients with primary adrenal insufficiency eventually require what?
* Initiate dehydroepiandrosterone (DHEA) therapy only in who?
- The vast majority of patients with primary adrenal insufficiency eventually require mineralocorticoid replacement with fludrocortisone. We suggest adjusting the fludrocortisone dose to lower the plasma renin activity to the upper normal range
- Initiate dehydroepiandrosterone (DHEA) therapy only in women with impaired mood or sense of well-being despite optimal glucocorticoid and, if needed, mineralocorticoid replacement.
Treatment Background of Adrenal/Addisonian Crisis
* What is not helpful in patients with secondary adrenal insufficiency ?
* In patients with primary adrenal insufficiency, measurement of what is not necessary?
* Measurement of what is not reliable to assist in txt?
- Measurement of early morning plasma corticotropin (ACTH) concentration is not helpful in patients with secondary adrenal insufficiency because values are expected to be low.
- In patients with primary adrenal insufficiency, measurement of early morning plasma ACTH concentration is not necessary for routine monitoring, but may detect over-replacement, in which case the value will be in the low normal range.
- Measurement of urine cortisol excretion is not completely reliable to assist in dose-titration of hydrocortisone
Follow-up, Referral and Patient Education in Adrenal/Addisonian Crisis
* Patients must be informed about what?
* What are the type of stressors and what do you treat them with?
* Medical _
* Normal what?
* What does happen?
Cushing Syndrome (Hypercortisolism)
* Characterized by what?
* Most common exogenous etiology?
* Most common endogenous etiology?
- Characterized by excessive levels of cortisol
- Most common exogenous and overall etiology – long term glucocorticoid use
- Most common endogenous etiology – tumors of adrenal gland causing increased cortisol production
Cushing Syndrome (Hypercortisolism)
* Syndrome is more common but less severe than what?
* What is cushing’s disease caused by?
* Both Disease and Syndrome are linked to what?
- Syndrome is more common but less severe than Cushing’s Disease
- Cushing’s Disease caused by pituitary tumor secreting ACTH
- Both Disease and Syndrome are linked to excess stress, depression, weight gain, eating disorders and higher amount of estrogen
Cushing Syndrome (Hypercortisolism)
* What are the sxs?(3)
Symptoms and Signs related to cortisol excess
* Abdominal fat with striae
* “Buffalo hump” at base of neck/suprclavicular fat pad
* “Moon Facies”
* *Next slide for complete list
What are the clinical sxs of cushing’s syndrome?
Cushing Syndrome – tumor(s) of Adrenal Glands
What is this?
adrenal tumor
What is this?
Pituitary tumor
Pathophysiology of cushing disease?
What is the patho difference between ACTH dependent CD and ACTH independent CS?
What are common causes of cushing syndrome?(3)
Ectopic ACTH syndrome – High association with pulmonary neuroendocrine tumors.
Adrenal tumors Adrenal carcinoma and adenoma.
Iatrogenic Cushing’s syndrome
* More than 10 million Americans receive pharmacologic doses of glucocorticoids each year.
* Therefore, iatrogenic Cushing’s syndrome must be more common than any other cause but is seldom reported.
*
What are the screen tests of cushing syndrome?(3)
*
Diagnosis Breakdown of cushing syndrome
* The low-dose dexamethasone suppression tests are used for what? What does it measure?
The low-dose dexamethasone suppression tests (DSTs; 1 mg overnight and two-day, low-dose) are used to differentiate patients with Cushing’s syndrome of any cause from patients who do not have Cushing’s syndrome.
* Measures response of adrenal glands to ACTH. Cortisol levels should decrease in healthy person. If cortisol elevated with low dose dexamethasone + one other positive test = Cushing’s syndrome
*
Diagnosis Breakdown of cushing syndrome
* What is used for the DDX of corticotropin (ACTH)-dependent Cushing’s syndrome?
The high-dose (8 mg) DSTs (HDDSTs)
Diagnosis Breakdown of cushing syndrome
* The HDDST may be used when?
* Simultaneous measure of serum dexamethasone concentration is very useful to do what?
* Because states of increased estrogen exposure (eg, pregnancy, oral contraceptives, and menopausal hormone therapy) may stimulate what?
- The HDDST may be used with caution when inferior petrosal sinus sampling for ACTH is not available.
- Simultaneous measure of serum dexamethasone concentration is very useful to ensure that the dexamethasone was taken, absorbed, and reached sufficient blood levels to exert glucocorticoid negative feedback.
- Because states of increased estrogen exposure (eg, pregnancy, oral contraceptives, and menopausal hormone therapy) may stimulate corticosteroid-binding globulin (CBG) production, results using serum cortisol as an endpoint may be falsely abnormal.
*
Treatment of cushing disease
* Resection of what? (2)
* What if not eligible for surgery?
* Taper what?
- Resection of pituitary tumor cures 75-90% (CD)
- Resection of adrenal tumor (CS)
- Pasireotide if not eligible for surgery
- Taper of glucocorticoids as adjunct
Follow-up, Referral and Patient Education
* prognosis for those with Cushing’s syndrome?
* Most cases of Cushing’s syndrome can be what?
* Many individuals with Cushing’s syndrome show significant improvement with what?
- The prognosis for those with Cushing’s syndrome varies depending on the cause of the disease.
- Most cases of Cushing’s syndrome can be cured (with surgery).
- Many individuals with Cushing’s syndrome show significant improvement with treatment, although some may find recovery complicated by various aspects of the causative illness. Some types of tumors may recur.
Pheochromocytoma
* What is it?
* Pheochromocytoma has serious and potentially lethal what?
- Pheochromocytoma is a rare neuroendocrine tumor, occurring in less than 0.2 percent of patients with hypertension.
- Pheochromocytoma has serious and potentially lethal cardiovascular complications due to the effects of secreted catecholamines.
Pheochromocytoma
* What are the two types?
* What is the mean age?
Adrenal type (85%)
* Adrenal medulla chromaffin cell tumor
* 10% are malignant
Extra-adrenal type (15%)
* 35% are malignant
Mean age of onset ~40yo
Pheochromocytoma-Pathophysiology
* What type of tumor?
* BP?
* Most common what?
- Catecholamine-secreting adrenal tumor.
- Rare- represents less than 0.1% of HTN patients
- The most common adrenal tumor in adults
Pheochromocytoma-Pathophysiology
* What does it secrete?
* What are the triggers?
- Secretes: norepinephrine, epinephrine and dopamine
- Triggers: meds (opiates, TCA, metoclopramide, glucagon, histamine)
*
Pheochromocytoma
* What is the classic traid of sxs?
The classic triad of symptoms in patients with a PHEochromocytoma consists of episodic Headache, Episodic sweating and tachycardia via Palpitations in association with HTN.
Pheochromocytoma
* What is the MC clinical sign?
* Should R/O what?
* Approximately one-half have what?
* Most patients with pheochromocytoma do not have what?
- Hypertension is the most common clinical sign
Should r/o hyperthyroidism and carcinoids - Approximately one-half have paroxysmal hypertension; most of the rest have either primary hypertension (formerly called “essential” hypertension) or normal blood pressure.
- Most patients with pheochromocytoma do not have the three classic symptoms, and patients with primary hypertension may have paroxysmal symptoms.
Pheochromocytoma dx
* 24 hour what?
* What needs to be drawn after 30 mins of supine position
* Urine what?
* Monitor what for disease progression and txt? ⭐️
* What are meanephrines?
- 24hr urine fractionated metanephrines and catecholamines
- Plasma fractionated metanephrines drawn after 30mins supine position
- Urine Vanillylmandelic Acid (metabolite of cathecholamines: NorEpi/Epi/Dopamine)
- Monitor concentration of Vanillymandelic acid in serum to monitor pheo disease progression and treatment success after surgical or medical repair.
- Metanephrines: NorEpi/Epi/Dopamine/normetanephrine/metanephrine
Pheochromocytoma dx
* 2-fold elevation of upper normal limits of metanephrine concentration in serum requires what? What are they (2)
* In approximately 60 percent of patients, the tumor is discovered how?
2-fold elevation of upper normal limits of metanephrine concentration in serum requires imaging localization (adrenal vs. extra-adrenal)
* MRI/CT of abdomen/Adrenal glands
* Alt: Iobenguane (I-123) scan or a FDG PET scan
In approximately 60 percent of patients, the tumor is discovered incidentally during computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen for unrelated symptoms
Pheochromocytoma
* What is the txt?
Pheochromocytoma Preoperative preparation
* All patients with pheochromocytoma need to undergo what?
* After adequate alpha-adrenergic blockade has been achieved, what is needed? Would should you never do?*
*
- What is the normal RAAS pahtophysiology?
Hyperaldosteronism (Conn’s Syndrome)
* Conn syndrome is what?
* Nonsuppressible or incompletely suppressible (primary) hypersecretion of aldosterone will coexist with what?
* Secondary hyperaldosteronism will coexist with what? why?
*
Hyperaldosteronism (Conn’s Syndrome)
* The classic presenting signs of primary aldosteronism are what?
* What is frequently seen?
- The classic presenting signs of primary aldosteronism are Hypertension ( via Na retention) and Hypokalemia, but potassium levels are often normal in modern-day series of aldosteronomas.
- Metabolic alkalosis is frequently seen.
Hyperaldosteronism (Conn’s Syndrome)-Etiology
* The most common causes of primary aldosteronism are what? (2)
* In rare cases?
- The most common causes of primary aldosteronism are aldosterone-producing adenomas (APAs) and bilateral adrenal hyperplasia;
- In rare cases, familial hyperaldosteronism (FH) type I (glucocorticoid-remediable aldosteronism [GRA]), type II, type III, or type IV.
*
Hyperaldosteronism (Conn’s Syndrome)
* What is the clinical presentation?
*
Hyperaldosteronism (Conn’s Syndrome)
* What is the screening test? What does it show?
Screening: Plasma renin and aldosterone levels and ratio: High aldosterone + low/normal renin = Primary hyperaldosteronism
* Hypokalemia on electrolyte panel with metabolic acidosis
* ECG may show signs of hypokalemia
Hyperaldosteronism (Conn’s Syndrome)
* What is used to confirm the dx?
To Confirm Diagnosis: Oral sodium loading test or Sodium infusion test – if urine aldosterone is high (i.e. no suppression of aldosterone) – it’s primary
Hyperaldosteronism (Conn’s Syndrome)
* What are some imaging?
* What can be draw? How does it occur?
Hyperaldosteronism (Conn’s Syndrome)
* If due to adrenal hyperplasia, what is the txt? (4)
* If due to adrenal tumor, what is the txt?(2)
- If due to adrenal hyperplasia – Spironolactone, ACE inhibitors, Calcium Channel Blockers and correct electrolyte abnormalities
- If due to adrenal tumor – surgical excision + Spironolactone
MEN syndrome (Multiple Endocrine Neoplasia)
* What is it?
* What are the three types?
MEN syndrome (Multiple Endocrine Neoplasia)
* Patients with MEN 1 have what?
* MEN 2A includes what?
* MEN2B is similar to what? What is the exception?
MEN Syndromes
* The multiple endocrine neoplasia (MEN) syndromes are rare, but recognition is what?
important both for treatment and for evaluation of family members
*
MEN Syndromes
MEN 1
* MEN1 is a rare genetic (AD) disorder classically characterized by what? (3)
MEN1 is a rare genetic (AD) disorder classically characterized by a predisposition to tumors of the
* Parathyroid glands (hypercalcemia and kidney stones)
* Anterior pituitary (prolactinomas and hGH hormone tumors)
* Pancreatic islet cells tumors (gastrinomas, insulinomas, VIPomas, and glucagonomas)
MEN 1
* What is the gene issue?
* Defined clinically as what?
- Menin Mutation of Chromosome 11-Menin is coded by the MEN1 gene and is a tumor suppressor gene.
- Defined clinically as the occurrence of two or more primary MEN1 tumor types, or the occurrence of one of the MEN1-associated tumors in family members of a patient with a clinical diagnosis of MEN1.
MEN 1
* Multiple parathyroid tumors causing what?
* Patients can also present with what?
- Multiple parathyroid tumors causing primary hyperparathyroidism are the most common component of MEN1, occurring in nearly all (>90%) of patients by age 50 years, and is the initial manifestation of the disorder in most patients.
- Patients can also present with peptic ulcers, hypoglycemia, or hyperglycemia (Zollinger-Ellison Syndrome).
MEN 2A
* What is the genetic issue?
* What gene is mutated?
- MEN2A is also Autosomal dominant know as Sipple’s Syndrome
- RET gene is a tyrosine kinase receptor on chromosome 10. It is an oncogene that develops a gain of function mutation in the MEN2A and MEN2B syndromes
MEN 2A
* 100% of patients have what? These are derived from what?
* 50% have what?
- 100% of patients have medullary thyroid carcinoma. These tumors derived from C cell or parafollicular cells and secrete calcitonin (produced by the medullary cell of the thyroid)
- 50% have pheochromocytoma. Triad of sxs: HTN, HA, episodic HA, and sweating and tachycardia
MEN 2A
* Only 10-25% have what?
Only 10-25% have parathyroid adenomas (leading to hypercalcemia and kidney stones)
* Of those that have PT adenomas, 50% do not develop hypercalcemia
MEN 2B
* What gene is involved? Occurs when?
* 100% of patients have what? What is it caused by?
AD RET gene is also involved
* Usually occur at a younger age and often have marfan-like or marfanoid body habitus
100% of patients have medullary thyroid carcinoma. These tumors derived from C cell or parafollicular cells and secrete calcitonin (produced by the medullary cell of the thyroid)
MEN 2B
* 50% have what?
* >95% of patient can have what?
- 50% have pheochromocytoma (increased catecholamines leading to HTN/palpitations/Headache/Sweating)
- > 95% of patient can have oral ganglioneuromatosis – Mucosal neuroma characteristically found in GI tract. Usually benign growth of ganglioma cells
Treatment of MEN?
Prognosis of MEN
* Average age of death? What do patient die from?
* 50% of pancreatic tumors (gastrinoma) become what? What is the life expectancy?
