ENDOCRINE Flashcards
most common type of thyroid cancer radiation-induced
papillary.
Subsequent development of thyroid neoplasia is associated with a dose of 5 to 20 cGy.
The risk is lower with higher levels of radiation!
[ probably because of the cytotoxic effect of higher doses ]
The latency period has been reported to be as long as 40 years.
gold standard in initial evaluation and diagnostic tool for thyroid masses
Fine-needle aspiration biopsy (FNAB)
However, tissue diagnosis remains as the best predictor for surgical intervention. Majority of nodules sampled by
FNAD can be categorized as benign (65%), suspicious (20%), and malignant (5%).
management of thyroid Nodules in the suspicious category
SESAP is surgery siting 20-30% malignancy rate
SCORE says
a repeat biopsy or be subjected to other modes of characterization.
associated with production of calcitonin
Medullary thyroid carcinoma
parafollicular or C cells
The superior parathyroids are usually where give landmarks of nerve and thyroid gland where are ectopic sites
POSTERIOR and LATERAL to recurrent laryngeal nerve
1 cm above the junction of the nerve and the inferior thyroid artery
Embedded in fat along the posterior surface of the middle or upper portions of the thyroid lobes
Occasionally, a superior parathyroid may be found within the substance of the thyroid gland.
Other aberrant sites for the superior parathyroids include:
tracheoesophageal groove
retroesophageal space
posterior mediastinum
The inferior parathyroids are located
ANTERIOR and MEDIAL
to the recurrent laryngeal nerve
near the lower pole of the thyroid
or in the thyrothymic ligament
the most bioactive form of thyroid hormone.
T3
20% of T3 is secreted directly from the thyroid and
80% is derived by peripheral conversion from T4.
Renin is an enzyme secreted by
the juxtaglomerular cells of the kidney in response to decreased pressure in the renal afferent arterioles.
stimulation of Renin
Decreases in plasma sodium concentration sensed by osmoreceptors in the cells of the macula densa promote renin release as well.
Renin secretion is also stimulated by
hyperkalemia
HYPOnatriemia - which ultimately leads to release of angiotensin II that directly stimulates secretion of aldosterone.
inhibited by potassium depletion.
The major physiologic regulator of aldosterone secretion is
the renin–angiotensin system and angiotensin II directly stimulates secretion of aldosterone.
Somatostatin primary functions
Prolongs gastric emptying time.
decrease production of gastric acid
inhibit secretion of other peptide hormones including gastrin
Inhibits insulin secretion
most sensitive means to identify tumor recurrence in the thyroid bed or involvement of lymph nodes by metastatic disease during postoperative surveillance of patients with thyroid cancer.
Ultrasound!
roles of ultrasound for assessing thyroid mass
To preoperatively assess for evidence of tumor invasion into surrounding structures or for evidence of lymphadenopathy or abnormal-appearing lymph nodes!
To assess the thyroid gland and any nodules within it
As an adjunct to confirm needle placement during fine-needle aspiration of a thyroid nodule
Thyrotropin-releasing hormone is synthesized in the
hypothalamus
paraventricular nucleus of the hypothalamus.
It is a tropic hormone that stimulates the release of thyroid-stimulating hormone (TSH) and prolactin from the anterior pituitary gland.
management of indeterminate cytology on FNA of the thyroid nodule
“There is a 20% chance that an indeterminant specimen is actually a thyroid malignancy. “
Since there is no other test that would accurately determine the malignancy of the lesion, a thyroid lobectomy for diagnosis is the next most appropriate step in management.
If the lesion turned out to be a malignant thyroid neoplasm on final pathology, a reoperation for a completion thyroidectomy would be performed.
An alternative approach would be to offer a total thyroidectomy up front, which would eliminate the risk of reoperation but would require lifelong thyroid replacement therapy.
A thyroid lobectomy for diagnosis is considered the most appropriate management in this question scenario.
management of benign category FNA findings on thyroid nodule workup
Patients with a benign FNAB are recommended to undergo a repeat FNAB in 6 months.
If they continue to be asymptomatic, the nodule is unchanged, and the FNAB continues to be benign, they are recommended to continue with observation and yearly follow up.
external branch of the superior laryngeal nerve innervated
The cricothyroid muscle is innervated (CAREFUL-this is not cricopharyngeus)
functions to help maintain tension on the vocal cords.
arytenoids innervation and function
help form the intrinsic musculature of the larynx
innervated by the inferior laryngeal nerve,
which is the terminal branch of the recurrent laryngeal nerve.
intrinsic muscles of the larynx innervation
The are innervated by the recurrent laryngeal nerve.
Cricopharyngeus innervation and function
The cricopharyngeus is part of the inferior constrictor of the pharynx and is innervated by branches of the glossopharyngeal and vagus nerves
CAREFUL-this is not cricothyroid muscle innervated by the external branch the superior laryngeal nerve
Sternothyroid muscle location and innervation
one of the infrahyoid muscles of the neck,
all of which are innervated by upper cervical nerve fibers through the ansa cervicalis.
necessary for the induction of phenylethanolamine-N-methyltransferase activity, which catalyzes the conversion of norepinephrine to epinephrine.
Cortisol.
Catechol-o-methyl transferase (COMT)
the enzyme principally responsible for metabolism of the circulating catecholamines.
Catecholamine synthesis begins with
hepatic synthesis of tyrosine from phenylalanine and dietary sources.
most common cause of hypocalcemia after total thyroidectomy
Operative injury or excision of the parathyroid glands!!
The cause of the hypocalcemia is usually temporary, reversible ischemia of the parathyroid tissue, and hypocalcemia provides the maximum stimulus for the secretion of parathyroid hormone.
decision algorithm of treating a low serum calcium after total thyroidectomy
whether the patient has signs and symptoms of hypocalcemia,
such as paresthesias in the fingers, toes, or circumoral region; carpopedal spasm; agitation; laryngeal stridor; or a positive Chvostek’s sign.
If the patient is asymptomatic
and
calcium is >= 7.5 mg/dL,
simple monitoring of symptoms and calcium levels is the preferred method of management.
effective treatment for a symptomatic patient whose serum calcium is less than 7.5 mg/dL.
Intravenous or oral calcium
or
vitamin D
Oral calcium may be adequate for mild symptoms, but patients with severe symptoms such as carpal pedal spasm or laryngeal stridor 253should receive intravenous calcium, either as 10% calcium gluconate, which has a calcium content of 90 mg or 4.5 mEq, or 10% calcium chloride, which has a calcium content of 270 mg or 13.5 mEq.
VIP-secreting tumors are associated with
secretory diarrhea
and profound hypokalemia
Somatostatinoma are associated with
These include dyspepsia, mild diabetes mellitus, gallbladder disease, steatorrhea, and hypochlorhydria
Glucagonoma are associated with
frequently malignant pancreatic endocrine neoplasms characterized by elevated plasma glucagon levels that result in glucose intolerance and diabetes mellitus.
These patients also have a characteristic necrolytic migratory erythematous skin rash as well as weight loss and anemia.
Gastrinoma are associated with
Gastrinomas are associated with the development of virulent peptic ulcer disease and diarrhea (Zollinger-Ellison syndrome). Diabetes mellitus and skin rashes are not a part of this syndrome.
Pancreatic polypeptidoma are associated with
Pancreatic polypeptide secreting tumors of the pancreas are not associated with any identifiable clinical syndrome.
Excess iodide suppresses
both iodide transport and hormone synthesis
but does not affect peripheral conversion of T4 to T3.
Methimazole
Methimazole
member of the thionamide class of antithyroid drugs and inhibits thyroid hormone synthesis.
Dopamine effects on thyroid
inhibits pituitary secretion of TSH
Propranolol effects on thyroid
β-adrenergic receptor blocker,
controlling the peripheral manifestations of increased catecholamines sensitivity in patients with thyrotoxicosis.
It also has the effect of blocking peripheral conversion of T4 to T3, thereby slowing the metabolism rate of thyroid hormone.
Lithium effects on thyroid
Lithium inhibits the release of thyroid hormone
Verner-Morrison syndrome
is a secretory diarrhea, high levels of circulating VIP, and a pancreatic tumor.
99m technetium sestamibi, scanning
Preoperative imaging can help to localize a parathyroid adenoma and thereby guide a surgeon’s exploration.
preferential uptake in abnormally enlarged parathyroid glands.
It has a sensitivity of up to 80% but does not have good success in identifying small adenomas.
New thyroid nodules more likely to be malignant
New thyroid nodules at the extremes of age are more likely to be malignant than one that occurs in the third through seventh decade.
The risk of a solitary thyroid nodule in a child less than 14 years old being malignant
The risk of a solitary thyroid nodule in a child less than 14 years old being malignant may be as high as 50%.!
A new thyroid nodule after the age of 60 is more likely to be malignant in a man or a woman
MAN
Excess aldosterone leads to
sodium retention
and expansion of the extracellular fluid volume,
which feeds back on the renal juxtaglomerular cells and macula densa to shut off renin production.
Both potassium and hydrogen ions are excreted in the urine in exchange for sodium, which results in potassium depletion and alkalosis.
Movement of hydrogen ion into the cells to replace intracellular potassium also contributes to the alkalosis.
Mild glucose intolerance may accompany significant potassium depletion.
Renin secretion is stimulated and inhibited by what lytes
hyperkalemia stimulated
hypokalemia inhibited
Patients with primary aldosteronism will have what K finding
hypokalemic
where are cells that down regulate renin
renal juxtaglomerular cells and macula densa to shut off renin production
(in response to increase extracellular VOLUME expansion)
Aldosterone stimulates
renal tubular reabsorption of sodium in exchange for potassium and hydrogen ion with the net effect of fluid reabsorption and expansion of the intravascular volume.
where are cells that regulate renin and what effects them
Renin is secreted by the juxtaglomerular cells of the kidney
primarily in response to decreased pressure in the renal afferent arteroles.
Calcitonin is a polypeptide hormone secreted by
parafollicular, or C- cells, of the thyroid gland.
Calcitonin acts to
reduce serum calcium levels
opposes the actions of parathyroid hormone.
Its mechanism of action is through the inhibition of
1) osteoclast-mediated bone resorption,
2) absorption by the intestine,
3) resorption of calcium by the renal tubular cells.
Secretion of calcitonin is stimulated by
an increase in serum calcium, gastrin, or pentagastrin.
Calcitonin is often used as a post-operative marker to monitor for recurrence of
Medullary thyroid cancer arise from C-cells of the thyroid.
the most reliable test for distinguishing primary hyperparathyroidism from hypercalcemia of malignancy.
Measurement of intact PTH levels is
Patients with hypercalcemia of malignancy should have low levels of intact parathyroid hormone.
Nelson syndrome includes
INCR ACTH (rather than just incr cortisol in cushings)
progressive hyperpigmentation,
visual field loss,
amenorrhea
associated with elevated adrenocorticotropic hormone levels.
It was originally described in a patient who had a functional pituitary adenoma and who had undergone bilateral adrenalectomy for hypercortisolism.
This syndrome today generally represents a missed diagnosis of Cushing disease that has been treated with adrenalectomy.
Often these tumors are aggressive or occasionally malignant. Multiple endocrine neoplasia type 1 (Wermer syndrome) includes pituitary adenoma, hyperparathyroidism, and multiple pancreatic endocrine tumors.
Arteriography, venography, and selective venous sampling to work up adrenal
have become less popular as experience with other imaging techniques has become greater.
Invasive procedures with intravascular contrast agents have clear disadvantages.
Arteriography is especially dangerous in examinations of patients with pheochromocytoma.
Appropriate tests include screening for primary hyperparathyroidism
serum levels of calcium parathyroid hormone (PTH),
screening for pituitary adenoma with prolactin level, as this tumor is the most frequent functional pituitary tumor in the syndrome. (if suspect MEN)
differential diagnosis of hypocalcemia includes
DiGeorge syndrome causes hypocalcemia due to congenital absence of the parathyroids and the thymus.
DCR magnesium affects PTH secretion in a less potent, but qualitatively similar manner to calcium, severe hypomagnesemia paradoxically inhibits PTH secretion.
This occurs probably as a result of interference with intracellular secretory mechanisms. Hypocalcemia in patients with profound hypomagnesemia will not respond to calcium administration until the hypomagnesemia has been corrected.
Pseudohypoparathyroidism is a rare disorder characterized by target tissue resistance to PTH, hypocalcemia, and congenital defects in growth and skeletal development.
most common cause of hypocalcemia.
surgical removal or injury of the parathyroid glands
The best initial test to evaluate a patient with suspected Cushing syndrome is:
cortisol excretion in the urine over a 24-hour time period. Elevated levels are present in more than 90% of patients with Cushing syndrome.
The high-dose dexamethasone test has been used primarily to differentiate
pituitary from nonpituitary causes of ACTH-dependent Cushing syndrome. It is generally not used as an initial screening test for persons with suspected hypercortisolism.
Glasgow coma scale, pupillary function, and lateralized extremity weakness if present together is most often associated with what head trauma situation
a focal mass lesion, such as
subdural,
epidural
intracerebral hematoma.
Subdural hematoma
most common, occurring in 20% to 40% of severely head-injured patients.
The combination of progressive hypertension associated with bradycardia and a diminished respiratory rate (the Cushing response) strongly suggests a rise in intracranial pressure due to a mass lesion.
Glasgow coma scale abnormalities without pupillary change or lateralized extremity weakness may signify
diffuse brain injury, in particular, diffuse axonal injury, concussion, or hypoxemia.
subarachnoid characterized by
depressed level of consciousness,
severe headache,
photophobia.
Nasopharyngeal carcinoma
higher in Asians for reasons that are not fully understood.
adults, a neck mass that represents lymphatic spread of the tumor is the most frequent presenting sign.
The tumor has a variety of histologic patterns, including keratinizing squamous cell carcinoma, spindle cell carcinoma, round cell carcinoma, and mixed nonkeratinizing carcinoma.
Although epistaxis, hearing loss, nasal stuffiness, and cranial nerve palsy may all be part of the initial presentation, a painless neck mass is the most common.
Epistaxis is usually the result of erosion by the tumor of superficial mucosal blood vessels in the anterior nares. Hearing loss and nasal stuffiness occur secondary to obstruction of the choanae or the eustachian tubes by the tumor mass. Cranial nerve paralyses occur after bony erosion of the base of the skull.
The trigeminal, oculomotor, and abducens are the most frequent cranial nerves involved.
The standard compliance or volume-pressure curve is drawn by means of measuring
volume and pressure at stages of lung deflation after total inflation.
The decreased compliance in acute respiratory distress syndrome occurs because
the lung is smaller (from colapsed alveoli)
In acute respiratory failure, the cause of decreased compliance is almost always associated with a decrease in functional residual capacity.
The decreased functional residual capacity represents lost alveoli, which are either collapsed or filled with fluid but still perfused with blood.
All of the following serum tumor markers can be seen in seminoma except:
AFP! NOT in seminoma
BHCG rare in seminoma approximately 10–15% of classical seminomas.
Elevated alkaline phosphatase can be seen in the presence of seminoma.
Elevated lactate dehydrogenase can be elevated in the presence of seminoma.
Some cell surface markers are unique to a species
(xenospecific).
Some markers are unique to a group of individuals within a species
(allospecific).
Some markers are completely unique to the individual itself
(autospecific).
associated with the development of Kaposi sarcoma.
Herpesvirus type-8
associated with Burkitt lymphoma,
Epstein-Barr virus.
pseudohypoparathyroidism, associated findings include
target tissue resistance to parathyroid hormone (PTH),
low serum calcium,
elevated serum phosphate,
defect in skeletal growth and development.
rare familial disorder
parathyroid hormone function itself is normal, but the kidney cannot respond to PTH stimulation. This results in hypocalcemia and hyperphosphatemia.
he essential steps in the laboratory evaluation of patients with Cushing syndrome overview broad
documentation of excess adrenal cortisol production,
differentiation of ACTH-dependent from independent causes,
localization of the source.
used to differentiate adrenal causes from nonadrenal causes of Cushing syndrome.
Plasma ACTH levels are
Patients with cortisol-secreting adrenal tumors should have suppressed ACTH levels to less than 20 pg/mL.
differentiating pituitary from nonpituitary causes of ACTH-dependent Cushing syndrome.
Inferior petrosal sinus sampling for ACTH test
The metabolic actions of insulin include
Inhibition of lipolysis in adipocytes. to promote the storage of triglycerides, increase glucose transport into adipocytes, and inhibit lipolysis.
stimulates synthesis of proteins in liver and muscle and
stimulates the formation of very low-density lipoproteins.
Stimulates glycogen synthesis and storage and inhibits its breakdown.
Inhibition of gluconeogenesis with reduction in cellular catabolism in part by inhibiting hepatic gluconeogenesis and glycogenolysis.
the most common causes of Cushing syndrome
ACTH-secreting tumors of the pituitary also termed Cushing disease,
account for approximately 70% of all cases.
Primary adrenal tumors account for only 15% to 20% of cases of Cushing syndrome.
Ectopic ACTH-secreting tumors comprise approximately 15% of cases of Cushing syndrome. The most common ectopic ACTH-secreting tumors are small cell lung carcinomas.
The percentage of total plasma calcium that is protein bound is, however, affected by changes in
plasma pH, as hydrogen ion competes with calcium for the same binding site on plasma proteins.
This results in an increase in the percentage of ionized calcium in acidosis, whereas in alkalosis the proportion of ionized calcium ion is decreased.
Biochemical abnormalities that may accompany hypercalcemia in patients with primary hyperparathyroidism include
Elevation of the
chloride: phosphate ratio to greater than 33 is seen in many patients with HPT.
Metabolic acidosis (not alkalosis) is more commonly associated with primary hyperparathyroidism because of increased urinary excretion of bicarbonate.
Elevated alkaline phosphatase elevated in patients with bone disease from hyperparathyroidism due to an increase in osteoclastic bone resorption.
Hypophosphatemia due to the phosphaturic actions of PTH on the kidney.
Hyperchloremia - hyperchloremic metabolic acidosis from increased urinary excretion of bicarbonate.
Hypomagnesemia seen in approximately 5% to 10% of patients with primary hyperparathyroidism.
The organ of Zuckerkandl, located and function
adjacent to the origin of the inferior mesenteric artery, is a common site for extra-adrenal chromaffin tissue. It is the only chromaffin tissue outside the adrenal gland that contains the enzyme phenylethanolamine N-methyl transferase necessary for conversion of norepinephrine to epinephrine.
increase lower esophageal sphincter pressure
α-adrenergic neurotransmitters
or
beta-blockers
The hormones
gastrin
motilin
antacids,
cholinergic agonists,
metoclopramide,
decrease lower esophageal pressure
alpha-blockers and β stimulants
cholecystokinin, estrogen, glucagon, progesterone, somatostatin, secretin
Anticholinergics, barbiturates, calcium channel blockers, caffeine, diazepam, theophylline
Peppermint, chocolate, coffee, ethanol, fat
the most common neoplasm of the endocrine pancreas
Insulinoma
Insulinoma location
distributed equally in the head, body, and tail of the pancreas.
Insulinoma Preoperative localize success rate and first choice
Preoperative selective visceral angiography will localize more than 90% of solitary adenomas.
The diagnosis is most reliably established with a monitored fast.
Insulin and glucose levels are then obtained every four to six hours.
Normal persons have insulin/glucose ratios less than 0.3, whereas patients with insulinoma demonstrate insulin/glucose ratios greater than 0.4 following a prolonged fast.
Elevated levels of proinsulin and C peptide are also found in patients with insulinoma.
Intraoperative ultrasonography may eliminate the need for preoperative localization studies. This imaging technique can identify insulinomas with a sensitivity of 90% to 95%, and also characterizes the relationship of the tumor to the pancreatic duct and the vascular structures. (1995 SCORE refs)
PTH effect on Ca, phos, D, and bicarb at the kidney
increase reabsorption of
calcium
PTH stimulates the hydroxylation of 25-hydroxy vitamin D
and
inhibits the reabsorption of
phosphate.
bicarbonate
test is used to distinguish pituitary from nonpituitary causes of ACTH-dependent Cushing syndrome
high-dose dexamethasone
next test performed when 24 urine cortisol up and ACTH is up
supraphysiologic doses of glucocorticoids will SUPPRESS the hypothalamic-PITuitary axis in patients with a pituitary tumor
NO affect on cortisol production in patients with ECTOPIC ACTH-secreting tumors.
diagnostic categories for reporting thyroid cytopathology
Benign
Consistent with a benign follicular nodule (includes adenomatoid nodule, colloid nodule, etc.) Consistent with lymphocytic (Hashimoto’s) thyroiditis in the proper clinical context Consistent with granulomatous (subacute) thyroiditis
management of thyroid FNA when finding is: Nondiagnostic or unsatisfactory
Repeat FNA with ultrasound scan guidance
management of thyroid FNA when finding is: Benign
Clinical follow-up only
management of thyroid FNA when finding is: Atypia of undetermined significance or follicular lesion of undetermined significance
REPEAT! FNA
(CAREFUL, Atypia of undetermined significance or follicular only gets repeat FNA while, suspicious for a follicular neoplasm gets LOBECTOMY!!)
management of thyroid FNA when finding is: Follicular neoplasm or suspicious for a follicular neoplasm
Surgical lobectomy
management of thyroid FNA when finding is: Suspicious for malignancy
Near-total thyroidectomy or surgical lobectomy‡
management of thyroid FNA when finding is: Malignant
Near-total thyroidectomy
Thyroid storm
clinical manifestations are fever, sweating, and tachycardia and occasionally nausea, vomiting, and abdominal pain.
Congestive heart failure, pulmonary edema, restlessness, delirium, and psychoses may also develop.
coma occurs and death
Either PTU or methimazole should be administered to slow the release of thyroid hormone, unless the thyroid storm has occurred after thyroidectomy.
PTU inhibits peripheral conversion of T4 to T3, whereas methimazole does not and therefore is the preferred thionamide.
BETA-blockers such as propranolol are given to block the adrenergic effects continue until the morning of surgery and should not be stopped abruptly postoperatively.
Steroids such as dexamethasone may aid in inhibiting peripheral conversion of T4 to T3
Lugol’s solution can be administered as 5 to 10 drops three times daily for 2 weeks preoperatively to decrease vascularity
