ENDO Flashcards
The 2 hormones stored in the posterior lobe are
ADH (antidiuretic hormone or vasopressin) and oxytocin
Microadenomas are defined as tumors ____ in diameter
<1 cm
Pituitary Adenomas by Function
Prolactin_____
Growth hormone (GH) _____
ACTH_____
Gonadotroph ____
50–60%
15–20%
10–15%
10–15%
Excess prolactin secretion is a common clinical problem in women and causes the syndrome of
galactorrhea-amenorrhea
Why is there amenorrhea in Prolactinemia
The amenorrhea appears to be caused by inhibition
of hypothalamic release of gonadotropin-releasing hormone (GnRH) with a decrease in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. Prolactin inhibits the LH surge that causes ovulation.
Prolactinemia
The most common presenting symptom in men is
erectile dysfunction and decreased libido.
Hyperprolactinemia can be seen in natural physiologic states such as
pregnancy, early nursing, hypoglycemia, seizure, exercise, stress, sleep, cirrhosis, nipple stimulation, and
chronic renal failure (due to PRL clearance).
Prolactinemia
They are usually _____ when they occur in women and ______ in men, usually presenting with visual field deficits, etc.
microadenomas
macroadenomas
Macroadenomas can obstruct the pituitary stalk, increasing prolactin release by
blocking dopamine transport from hypothalamus (stalk effect)
Hyperprolactinemia can also occur with decreased inhibitory action of dopamine.
This occurs with the use of drugs that
block dopamine synthesis (phenothiazines, metoclopramide) and dopamine-depleting agents (α-methyldopa, reserpine).
Always check _____in patients with elevated prolactin
TSH
Always exclude states such as_______
before starting the work-up of hyperprolactinemia
pregnancy, lactation, hypothyroidism and medications
Prolactinomas may co-secrete
growth hormone (GH)
Prolactin levels >100 ng/mL suggest probable
pituitary adenoma
For prolactinomas, initially treat with _____ both of which reduce prolactin levels in almost all hyperprolactinemic patients.
cabergoline or bromocriptine (a dopamine
agonist),
Surgery is reserved only for adenomas
not responsive to cabergoline or bromocriptine, or if the tumor is associated with significant compressive
neurologic effects.
T or F
Surgery is more effective for microadenomas than macroadenomas
T
About _____of patients treated with cabergoline have a drop in prolactin to <10% of pretreatment levels
90%
______ is used if drug therapy and surgery are ineffective in reducing tumor size and prolactin levels
Radiation therapy
______ is a syndrome of excessive secretion of growth hormone. In children this is called____
Acromegaly
gigantism
______ is an insidious, chronic debilitating disease associated with bony and soft tissue overgrowth, and increased mortality
Acromegaly
Acromegaly is caused by
pituitary adenomas, usually a macroadenoma in 75% of
the cases that produce growth hormone
Other SSX associated with acromegaly
Obstructive sleep apnea can also develop.
Interstitial edema, osteoarthritis, and entrapment neuropathy (carpal tunnel syndrome)
are seen
About 10-20% of patients develop cardiac anomalies such as hypertension, arrhythmias, hypertrophic cardiomyopathy, and accelerated atherosclerosis.
Metabolic changes asstd with acromegaly
impaired glucose tolerance (80%) and diabetes (13–20%).
Dx of Acromegaly
The best initial test is
IGF-1 level. A significantly elevated IGF level compared to
the average IGF-1 for age-matched equivalents is a positive screen for acromegaly
The most common cause of death in acromegaly is
_______
cardiovascular mortality.
Confirmatory test for acromegaly
Confirmatory testing involves the
measurement of GH after 100 g of glucose is given orally;
this test is positive if GH remains high (>5 ng/mL) and suggests acromegaly
Measurement of ______ and _______correlates with disease activity
insulin-like growth factor (IGF) or somatomedin
Goal of Tx for acromegaly
The objectives are to decrease GH levels to normal, stabilize or decrease tumor size, and preserve normal pituitary function
Mx of acromegaly for pit ad
Transsphenoidal surgery provides a rapid
response.
Mx of acromegaly
Drug of Choice (DOC)
______are the drugs of choice
Somatostatin analogues
Mx of acromegaly
__________ reduce GH values
in around 70% of patients and cause partial tumor regression in 20–50% of patients.
Octreotide and lanreotide
_____ is the best medical therapy for acromegaly
Octreotide
The main side effect of concern with
somatostatin analogues is
cholestasis, leading to cholecystitis.
_________ are used if surgery is not curative.
10% of patients respond to these drugs
Dopamine agonists such as bromocriptine and cabergoline
______is a growth hormone analogue that antagonizes endogenic GH by blocking peripheral GH binding to its receptor in the liver. It is a second- line agent.
Pegvisomant
Other complications of acromegaly include
cardiac failure (most common cause of death in acromegaly), diabetes mellitus, cord compression, and visual field defects.
Large pituitary tumors, or cysts, as well as hypothalamic tumors (craniopharyngiomas, meningiomas, gliomas) can lead to _______
hypopituitarism
______ are the most common cause of panhypopituitarism.
Pituitary adenomas
Hypopituitarism
_____ is a syndrome associated with acute hemorrhagic infarction of a preexisting pituitary adenoma, and manifests as severe headache, nausea or vomiting, and depression of consciousness. It is a medical and neurosurgical emergency
Pituitary apoplexy
Hypopituitarism
Vascular diseases such as ______ (initial sign being the inability to lactate) and infiltrative diseases including _____ and ________ may induce this
state as well
Sheehan postpartum necrosis
hemochromatosis and amyloidosis
1st hormone lost in panhypopit
________ can occur in women and lead to amenorrhea,
genital atrophy, infertility, decreased libido, and loss of axillary and pubic hair
Gonadotropin deficiency (LH and FSH)
1st hormone lost in panhypopit
In men, decreased ______ results in impotence, testicular atrophy, infertility, decreased libido, and loss of axillary and pubic hair
LH and FSH
2nd hormone lost in panhypopit
______ gives an asymptomatic increase in lipid levels and a decrease in muscle, bone, and heart mass. It also may accelerate atherosclerosis, and it increases visceral obesity
GH deficiency
3rd hormone lost in panhypopit
____ results in hypothyroidism with fatigue, weakness,
hyperlipidemia, cold intolerance, and puffy skin without goiter
Thyrotropin (TSH) deficiency
4th hormone lost in panhypopit
____ deficiency occurs last and results in secondary adrenal insufficiency caused by pituitary disease
Adrenocorticotropin (ACTH)
The first step in diagnosing pituitary insufficiency is to measure _____
GH, TSH, LH, and
IGF-1.
The most reliable stimulus for GH secretion is
insulin-induced hypoglycemia
How to Dx GH deficiency
After injecting 0.1 μ/kg of regular insulin, blood glucose declines to <40 mg/dL; in normal conditions
that will stimulate GH levels to >10 mg/L and exclude GH deficiency
Random _______
are not sensitive enough to diagnose GH deficiency.
GH and IGF levels
______can also stimulate growth hormone release. This is less dangerous because it does not lead to ____
Arginine infusion
hypoglycemia.
To diagnose ACTH deficiency,_______may be preserved (the problem could be only in response to stress).
basal cortisol levels
How to Dx ACTH deficiency
Insulin tolerance test is diagnostic and involves giving 0.05–0.1 U/kg of regular insulin and measuring serum cortisol; plasma cortisol should increase to ______
> 19 mg/dL.
A failure of ACTH levels to rise after giving ___would indicate pituitary insufficiency.
metyrapone (blocks cortisol production, which
should increase ACTH levels. )
_____may give abnormally low cortisol output if pituitary insufficiency has led to adrenal atrophy
Cosyntropin (ACTH) stimulation
To diagnose gonadotropin deficiency in women, measure _______.
In males, gonadotropin deficiency can be detected by measuring ______
LH, FSH, and estrogen
LH, FSH, and testosterone
To diagnose TSH deficiency, measure ______
serum thyroxine (T4) and free triiodothyronine (T3), which are low, with a normal to low TSH.
Management of hypopituitarism involves treating the underlying causes. Multiple hormones must be replaced, but the most important is______
cortisol replacement
____the sella has no bony erosion. It is caused by herniation of the suprasellar subarachnoid space
through an incomplete diaphragm sella. No pituitary gland is visible on CT or MRI
Empty Sella Syndrome (ESS)
MCC of Empty Sella Syndrome (ESS)
The syndrome can be primary (idiopathic) and is also associated with head trauma and radiation
therapy.
MC Sx of Pts with ESS
Most patients with these syndromes are obese, multiparous women with headaches;
30% will have hypertension; endocrine symptoms are absent
Vasopressin or ADH and oxytocin are synthesized in neurons of the _______ and _____, then transported to the posterior pituitary lobe to be released into the circulatory system
supraoptic and paraventricular
nuclei in the hypothalamus
The syndrome associated with an excess secretion of
ADH is called ______ and the syndrome associated with a deficiency of ADH is called ____
SIADH (syndrome of inappropriate secretion of ADH),
diabetes insipidus (DI).
____is a disorder of the neurohypophyseal system
caused by a partial or total deficiency of vasopressin (ADH), which results in excessive, dilute
urine and increased thirst associated with hypernatremia
Central diabetes insipidus (CDI)
_____ is caused by renal
resistance to the action of vasopressin.
Nephrogenic DI
The differential diagnosis of DI includes primary disorders of water intake _______ and hypothalamic diseases
(psychogenic polydipsia, drug-induced polydipsia from chlorpromazine, anticholinergic
drugs, or thioridazine)
For nephrogenic DI,_____ or ____ may be used, which enhances the reabsorption of fluid from the proximal tubule.
HCTZ or amiloride
SIADH SSx include
This includes adrenal insufficiency, excessive fluid loss, fluid deprivation, and probably positive-pressure respiration
The etiology of SIADH includes malignancies such as
1
2
3
small cell carcinomas, carcinoma
of the pancreas, and ectopic ADH secretion
Drugs such as _________ can induce SIADH
chlorpropamide clofibrate, vincristine, vinblastine, cyclophosphamide, and carbamazepine
The _____ and ______ both cause hyponatremia, which is a key feature in SIADH.
water retention
and sodium loss
Laboratory findings in diagnosis of SIADH include _____ and ______
hyponatremia <130 mEq/L, and Posm <270 mOsm/kg.
Other findings of SIADH are______
urine sodium concentration >20 mEq/L (inappropriate
natriuresis), maintained hypervolemia, suppression of renin–angiotensin system, and no equal concentration of atrial natriuretic peptide
Initial MX for SIADH
Fluid restriction to 800–1,000 mL/d should be obtained to increase serum sodium.
Mx of SIADH in chronic situations
_____ can be used in chronic situations when fluid restrictions are difficult to maintain.
Demeclocycline
Demeclocycline MOA________
inhibits ADH action at the collecting duct (V2).
_____ and _______ are V2 receptor blockers indicated for moderate to severe SIADH.
Conivaptan and tolvaptan
For very symptomatic patients (severe confusion, convulsions, or coma),_______ should be used.
hypertonic saline (3%) 200–300 mL intravenously in 3–4 h
The rate of correction should be between _______
0.5–1 mmol/L/h of serum Na.
The normal function of the thyroid gland is directed toward the secretion of_________), which influence a diversity of metabolic processes.
l-thyroxine (T4) and l-3,5,5′-triiodothyronine (T3
The most sensitive test in thyroid diseases is the _____
TSH.
T4 and T3 do not always reflect actual thyroid function. For example, increased TBG levels are seen in ________ This will increase total T4 but free or active T4 level is normal
pregnancy and the use of oral contraceptives.
Decreased TBG levels are seen in______ and the use of androgens. This will decrease total T4 but free or active T4 level is normal with the patient being euthyroid
nephrotic syndrome
Always check free ____to assess thyroid function.
T4
________ varies directly with the functional state of the thyroid
RAIU ( thyroid-reactive iodine uptake)
RAIU is increased in _____ or ______and decreased in thyroiditis or surreptitious ingestion of thyroid hormone.
Graves’ disease or toxic nodule
Other tests include______ and _______, which are detected in Hashimoto thyroiditis
antimicrosomal and antithyroglobulin antibodies
In Graves’ disease, ______
thyroid-stimulating immunoglobulin (TSI) is
found.
Serum________ concentration can be used to assess the adequacy of treatment and follow-up of thyroid cancer, and to confirm the diagnosis of thyrotoxicosis factitia
thyroglobulin
Graves’ causes the production of ______ which stimulate the thyroid to secrete T4 and T3.
antibodies (thyroid stimulating immunoglobulin [TSI]),
What condition
A toxic multinodular goiter non-autoimmune
disease of the elderly associated commonly with arrhythmia and CHF and sometimes the
consequence of simple goiter.
(Plummer disease),
Drugs such as _____, ______, and ______can induce thyrotoxicosis
amiodarone, alpha interferon, and lithium
Extrathyroid source of hormones include
thyrotoxicosis factitia and ectopic thyroid tissue (struma ovarii, functioning follicular carcinoma).
Graves’ disease
Patients with another autoimmune disease such as ______ and _______
are more likely to be affected
type 1 diabetes or pernicious anemia
Graves’ disease
_____causes increased risk of disease and may make the exopthalmos worse
Smoking
Graves
______ predominate in younger patients, whereas _______symptoms are more common in older patient
Nervous symptoms
cardiovascular and myopathic
Graves
Osteoporosis and hypercalcemia can occur from increases in ______
osteoclast activity.
Graves Tx
______ is preferred, as it has a longer half-life, reverses hyperthyroidism more quickly, and has fewer side effects
Methimazole
Methimazole requires an average of _______to lower T4 levels to normal and is often
given before radioactive iodine treatment; it can be taken 1x/ day
6 weeks
WHy is PTU CI in pregnancy?
is because there have been rare cases of liver damage in people taking propylthiouracil
For women who are nursing, ______ is probably a better choice than propylthiouracil (to avoid liver side effects).
methimazole
PTU and Methimazole can cause ______
agranulocytosis.
The most commonly used ‘permanent’ therapy for Graves’ disease is ______
radioactive iodine
Indications for RAI
- Large thyroid gland
- Multiple symptoms of thyrotoxicosis
- High levels of thyroxine
- High titers of TSI
Patients currently taking antithyroid drugs must discontinue the medication at least 2 days prior to taking
the radiopharmaceutical since_______
pretreatment with antithyroid drugs reduces the cure rate
of radioiodine therapy in hyperthyroid diseases.
Graves
______is indicated only in pregnancy (second trimester), in children, and in cases when the thyroid is so large that there are compressive
symptoms
Subtotal thyroidectomy (and rarely total thyroidectomy)
Thyroid storm
Therapy for hyperthyroidism is also used and includes first, ______.
Next,______ should be given to inhibit
hormone release.
This should be followed by ______.
Finally,___________is given to provide adrenal support
propylthiouracil
iodine
adrenergic antagonists (e.g., b-adrenergic blockers)
dexamethasone
Primary hypothyroidism can occur secondary to chronic thyroiditis (Hashimoto disease); this is the most common cause of goitrous hypothyroidism and is associated with _______
antimicrosomal antibodies
Drugs such as _______ can elicit primary hypothyroidism.
lithium and acetylsalicylic acid, Amiodarone, interferon, and sulfonamides
with the lower doses of amiodarone, incidence of thyroid
dysfunction is around______
4%
T or F
Amiodarone can both cause amiodarone- induced thyrotoxicosis or amiodarone-induced hypothyroidis
T
Amiodarone-induced thyrotoxicosis
Type 1________
Type 1 occurs in patients with underlying thyroid pathology such as autonomous nodular goiter or Graves’; treatment is anti-thyroid therapy
Amiodarone-induced thyrotoxicosis
Type 2________
is a result of amiodarone causing a subacute thyroiditis, with release of preformed thyroid hormones into the circulation; treatment is a trial of glucocorticoids
Amiodarone-induced hypothyroidism due to
inhibition of peripheral conversion of T4 to T3
Dx of Primary Hypothyroidism
↑ TSH, ↓ T4, ↓ FT4, T3 decreases in lesser extent
Dx of 2° or 3° Hypothyroidism
Normal or ↓ TSH, ↓ T4, ↓ FT4, Accompanied by decreased secretion of other hormones
The goal in management of hypothyroidism is to restore metabolic state with levothyroxine. This has to be done gradually in the _______ and ______
elderly and patients with coronary artery
disease.
If there is a strong suspicion of suprathyroid hypothyroidism of hypothalamic or pituitary
origin, give _________
hydrocortisone with thyroid hormones
In patients with suprathyroid hypothyroidism, _____ level rather than TSH is used to guide treatment
T4
Levothyroxine should be taken on an empty stomach with no other drugs or vitamins; multivitamins, including ______ and _____, can decrease its absorption
calcium and iron
Hypothyroidism during pregnancy should be treated with levothyroxine, with serum TSH goal to be _______
kept in the lower reference range
How to measure TSH during pregnancy
Serum TSH should be measured at 4−6 weeks’ gestation, then every 4−6 weeks until 20 weeks’ gestation
Myxedema coma is precipitated by
cold exposure, trauma, infections, and CNS depressants
Myxedema coma Tx
Treatment includes very high doses of T4 along with T3.
Subacute thyroiditis includes
granulomatous, giant cell, or de Quervain thyroiditis.
Labs of subacute thyroiditis
elevated erythrocyte sedimentation rate (ESR),
decreased radioactive iodine uptake,
initial elevation in T4 and T3 (caused by leak of hormone
from the gland), followed by hypothyroidism as the hormone is depleted.
Tx of subacute thyroiditis
Treatment is symptomatic with NSAIDs, prednisone, and propranolol
____ is a chronic inflammatory process of the thyroid
with lymphocytic infiltration of the gland, and is thought to be caused by autoimmune factors
Hashimoto thyroiditis
most common cause of sporadic goiter in children
Hashimoto Thyroiditis
SSx of Hashimoto Thyroiditis
Clinical findings include agoiter that is painless, which is the main feature of this disease. The goiter is rubbery and not always symmetrical. Hypothyroidism occurs
Hashimoto thyroiditis is managed by ____
replacement with l-thyroxine
______is a selflimiting episode of thyrotoxicosis associated with chronic lymphocytic thyroiditis
Lymphocytic thyroiditis
Labs of Lymphocytic thyroiditis
The thyroid is nontender, firm, symmetrical, and slightly to
moderately enlarged. T4 and T3 are elevated, RAIU is low, and ESR normal
Lymphocytic thyroiditis
This disease may last for ____ and be recurrent (as in postpartum thyroiditis)
2–5 months
_____results from intense fibrosis of the thyroid and surrounding structures (including mediastinal and retroperitoneal fibrosis).
Reidel thyroiditis
______ is the most common thyroid cancer. It is associated with history of radiation exposure
Papillary carcinoma
______ of all thyroid cancers are papillary
60–70%
Mx of papillary CA
The treatment is surgery when the tumor is small
and limited to a single area of the thyroid
____accounts for 15–20% of all thyroid cancers.
Follicular carcinoma
Follicular carcinoma spreads hematogenously with distant metastasis_______
to the lung and bone.
Mets of papillary CA
lymphatics
Mx of Follicular CA
Treatment requires near total thyroidectomy with postoperative radioiodine ablation
____ accounts for 1–2% of all thyroid cancer. It
occurs mostly in elderly patients
Anaplastic carcinoma
Anaplastic carcinoma Ssx
Anaplastic carcinoma is highly malignant with rapid and painful enlargement
Anaplastic CA
______of patients die within 1 year of diagnosis
Eighty percent
Anaplastic CA mets
This cancer spreads by direct extension
Medullary carcinoma accounts for___ of all thyroid cancers
5%
Medullary CA
This tumor arises from________ of the thyroid
and is more malignant than follicular carcinoma
parafollicular cells
Medullary carcinoma is the component of two types of MEN (multiple endocrine neoplasia).
In _______ pheochromocytoma, medullary thyroid carcinoma, and (in one-half of cases) parathyroid hyperplasia occur
type IIa (Sipple syndrome),
In MEN type IIb, ______, _______, _____ occur
pheochromocytoma,
medullary carcinoma, and neuromas
Medullary CA
The only effective therapy is ______
thyroidectomy
The only thyroid cancer with an elevated calcitonin level is __________
medullary cancer
Calcifications on x-rays such as psammoma bodies suggest ______ increased density is seen in
______
papillary carcinoma;
medullary carcinoma.
T or F
cancer is never hyperfunctioning
T
______ is the initial procedure of choice in the evaluation of most patients solitary nonfunctioning nodule
Fine-needle aspiration (FNA) for cytology
_____ of nonfunctioning thyroid nodules prove to be malignant
Five percent
The first test to do in a patient with a thyroid nodule is
____ if this is normal, then proceed to ____. U/S is useful to distinguish cysts from solid nodules.
TSH;
FNA
PTH acts directly on the ____ and indirectly on _____
(through its effects on synthesis of 1,25-dihydroxycholecalciferol [1,25(OH)2D3]) to increase
serum calcium.
bone and kidney,
intestine
PTH increases____ which releases calcium
osteoclast activity,
PTH also inhibits ______ in the kidney tubule.
phosphate reabsorption
PTH activates_____ which increases the GI absorption of calcium.
vitamin D,
Calcium is absorbed from the ______
proximal portion of the small intestine, particularly
the duodenum
Calcium
Of the 2% that is circulating in blood, free calcium is ___ protein bound is ____, with only ____ bound to citrate or phosphate buffers.
50%,
40%
10%
The most common cause of hypercalcemia is____
primary hyperparathyroidism
The hypercalcemia of malignancy is due to a PTH-like protein produced
by squamous cell carcinoma of the lung or metastatic disease to the bone
Neutrophils in granulomas have their own 25-vitamin
D hydroxylation, producing active ______
1,25 vitamin D.
Rare causes of hypercalcemia include 1 2 3 4 5
vitamin D intoxication, thiazide diuretics, lithium use, and Paget disease, as well as prolonged immobilization
______is associated with hypercalcemia because there is a partial effect of thyroid hormone on osteoclasts
Hyperthyroidism
_____ is a benign form of hypercalcemia. It presents
with mild hypercalcemia, family history of hypercalcemia, urine calcium to creatinine ratio <0.01, and urine calcium <200 mg/day (hypocalciuria).
Familial hypocalciuric hypercalcemia (FHH)
Familial hypocalciuric hypercalcemia (FHH) is associated with:
Most cases are associated with loss of function mutations in the CaSR gene, which encodes a calcium sensing receptor (expressed in kidney and parathyroid tissue).
Tx of FHH
none. they are asymptomatic
Why is there pancreatitis with hypercalcemia?
Pancreatitis occurs because of the precipitation of calcium in the pancreas.
Severe pancreatitis, however, is associated with
hypocalcemia because of_______
binding of calcium to malabsorbed fat in the intestine
Hypercalcemia results in polyuria and polydipsia because of the induction of ______
nephrogenic diabetes insipidus
Calcium also precipitates in the kidney, resulting in
both kidney stones as well as ______
nephrolithiasis
Hypertension occurs in 30–50% of patients with hypercalcemia. The EKG will show a _____
short QT
Severe, life-threatening hypercalcemia is treated first with
vigorous fluid replacement with normal saline or half-normal saline
_______ inhibit osteoclasts and stimulate osteoblasts
IV bisphosphonates such as zoledronate and
pamidronate
The maximum effect of bisphosphonates takes_____
2–3 days
Hyperparathyroidism
Etiology. It is most commonly due to ______ but hyperplasia of all 4 glands can lead to primary hyperparathyroidism (20%)
one gland adenoma (80%),
In MEN type I, _______, _______, _____are seen.
hyperparathyroidism, pituitary tumors (3 “Ps”), and pancreatic tumors
____ with hyperparathyroidism occurs because of increased rate of osteoclastic bone resorption and results in bone pain, fractures, swelling, deformity, areas of demineralization, bone cysts, and brown tumors (punched-out lesions producing a salt-and-pepper-like appearance).
Osteitis
fibrosa cystica
Dx of primary hyperparathyroidism
Diagnosis can be made by laboratory findings of serum calcium >10.5 mg/dL, with elevated PTH level.
A _______ can be used to localize the adenoma.
nuclear parathyroid scan (sestamibi)
The dietary calcium should be reduced to____ in pts with primary hyperparathyroidism
400 mg/d
In primary hyperparathyroidism, surgery is indicated if any of the following are present:
- Symptomatic hypercalcemia
- Calcium >11.5 mg/dL
- Renal insufficiency
- Age <50 years
- Nephrolithiasis
- Osteoporosis
_____ is hypocalcemia that occurs after surgical removal of a hyperactive parathyroid gland, due to increased osteoblast activity
Hungry bones syndrome
Hungry bones syndrome
It usually presents with :
rapidly decreasing calcium, phosphate, and magnesium 1–4 weeks post-parathyroidectomy
______ agent that has some effect in hyperparathyroidism by shutting off the parathyroids
Cinacalcet is a calcimimetic
Fn of Cinacalcet
This increases the sensitivity of calcium sensing (basolateral membrane potential) on the parathyroid
Cinacalcet is also indicated in:
It is also indicated for the treatment of hypercalcemia in patients with parathyroid carcinoma and in moderate-to-severe primary hyperparathyroidism unamenable to surgery.
________ results from a hyperfunction of the parathyroid glands themselves
Primary hyperparathyroidism
________ is due to physiologic (i.e., appropriate) secretion of PTH by the parathyroid glands in response to hypocalcemia (resulting vitamin D deficiency, chronic kidney disease, etc.)
Secondary hyperparathyroidism
_______is seen with long-term secondary hyperparathyroidism, which can
lead to hyperplasia of the parathyroid glands and a loss of response to serum calcium levels
Tertiary hyperparathyroidism
_____is most commonly caused by hypoparathyroidism, renal failure, hyperphosphatemia, and hypomagnesemia
Hypocalcemia
Drugs such as ________ will also lower calcium levels.
loop diuretics, phenytoin, alendronate, and
foscarnet
Renal failure causes hypocalcemia because of the _______
loss of
activated 1,25-dihydroxy-vitamin D.
_____ decreases free calcium levels by causing increased binding of calcium to albumin
Alkalosis
___ occurs with low albumin levels. The free calcium level
remains normal, while the total calcium level decreases
Pseudo hypocalcemia
Ca correction for hypoalb
To correct for albumin, add 0.8 to calcium level for every 1 gram below 4 of albumin
Hypocalcemia results in ________
increased neural hyperexcitability such as seizures,
tetany, circumoral numbness, and tingling of the extremities
Treatment of hypocalcemia is ________
IV or oral calcium replacement, and vitamin D replacement as necessary.
The most common cause of hypoparathyroidism is ______
surgical removal of the thyroid
_____ deficiency prevents release of PTH
from the gland.
Magnesium
Hypoparathyroidism
______ is seen, such as tetany, laryngospasm, cramping, seizures, and
impaired memory function
Neuromuscular irritability
Hypoparathyroidism eye findings
Ocular findings such as cataracts and soft tissue calcifications can occur.
Hyperventilation worsens symptoms of hypocalcemia
because the_________
alkalosis decreases free calcium levels
DX of hypoparathyroidism is made when?
Diagnosis is suggested when the serum calcium is low; it
Low calcium with high phosphorous can be due to______
renal failure, massive tissue destruction, hypoparathyroidism, and pseudohypoparathyroidism
Low calcium with low phosphorous is due to absent or ________
ineffective vitamin D
In the acute stage of hypocalcemia, _____can be given IV.
calcium gluconate
As many as _____ of diabetic patients can be kept off of medication with diet and exercise alone
25%
_____is the drug of choice and along with lifestyle intervention should be used in all newly diagnosed patients
Metformin
If a patient is initiated on metformin yet the diabetes does not become well-controlled, add a_______
sulfonylurea
If a patient is already taking both metformin and a sulfonylurea yet there is still poor glycemic control, then either switch to ________
insulin or add a glitazone
Glitazones can lead to ______
fluid retention.
If metformin cannot be used, use a new _____
glucagon-like peptide (GLP-1) agonist (exenatide
or liraglutide).
Sulfonylureas (glyburide, glipizide, glimepiride SE):
increase weight, cause hypoglycemia; sulfa drugs
Thiazolidinediones (rosiglitazone or pioglitazone): can worsen _______
CHF
Recent studies suggest pioglitazone may be linked to _______
bladder cancer
Augment the naturally occurring hormones that are secreted from the GI tract in response to food
Incretin mimetics (exenatide, liraglutide
Incretin is also called______
Also called gastric inhibitory peptide or glucose-dependent insulinotropic peptide (both abbreviated as GIP);
The “incretin mimetic” drugs exenatide and liraglutide are direct analogues of GIP and GLP, except that _______
their actions last much longer
Dipeptidyl peptidase IV (DPP-IV) inhibitors (sitagliptin, saxagliptin, linagliptin):
natural hormones which prevent the metabolism of the incretins GIP and GLP
The main problems in DKA stem from ______
acidosis with increased anion gap and dehydration
The adrenal cortex is divided into 3 areas, the outer zone (glomerulosa), which is the site of ______
the central zone (fasciculata), which is the site of __________;
and the inner zone (reticularis), which
is the site of ______
aldosterone synthesis;
cortisol synthesis
androgen biosynthesis
The etiology of Cushing syndrome includes ________. This can be secondary to pituitary ACTH production, which occurs in pituitary-hypothalamic dysfunction, and pituitary ACTH-producing adenomas (microadenoma, e.g., Cushing disease).
adrenal hyperplasia
Dx test for Cushing sundrome
The diagnostic tests used to establish the syndrome of cortisol excess are the:
1-mg overnight dexamethasone suppression test and the 24-hour urine-free cortisol
The tests used to establish a precise etiology of the cortisol excess are the
ACTH level, high-dose dexamethasone suppression test, CT and MRI scanning, and occasionally sampling of the petrosal venous sinus, which drains out of the pituitary
What is the normal result of the 1-mg overnight dexamethasone suppression test
If you give a milligram of dexamethasone at 11 p.m., the
cortisol level at 8 a.m. should come to normal if there is the normal ability to suppress ACTH production over several hours
False positive of the 1-mg overnight dexamethasone suppression test
Any drug that increases the metabolic breakdown of dexamethasone will prevent its ability to suppress cortisol levels.
Examples of drugs increasing the metabolism of dexamethasone are phenytoin, carbamazepine, and rifampin.
Stress increases glucocorticoid levels
An abnormality on the 1-mg overnight test should be confirmed with a ______
24-hour urine-free
cortisol
The ________is more accurate and is the gold standard for confirming or excluding Cushing’s syndrome.
24-hour urine-free
cortisol
A third screening test for Cushing is the ______
midnight salivary cortisol
The precise etiology of the Cushing syndrome is established by ______
using ACTH levels, sometimes in combination with high-dose dexamethasone suppression testing
ACTH levels are elevated with either a pituitary source of ACTH such as an _______
adenoma or with an ectopic source.
Highdose dexamethasone suppression testing can distinguish the difference between an adenoma or with an ectopic source.
The output of a pituitary adenoma will suppress with ______The output of an ectopic source will __________
high-dose dexamethasone.
not suppress with high-dose dexamethasone.
If the ACTH level is low, then the etiology is most likely from an adrenal tumor such as an ______
adenoma, cancer, or from adrenal hyperplasia
When there is a low ACTH level, the precise etiology is confirmed with a ________
CT scan of the adrenals.
When there is a high ACTH level, the precise etiology is confirmed with an ______
MRI of the pituitary looking for an adenoma or a CT scan of the chest looking for an ectopic focus
T or F
Single random cortisol levels are not reliable.
T
The normal function of aldosterone is to _______
reabsorb sodium and excrete potassium and acid (H+).
Hyperaldosteronism can be divided into the following:
- Primary aldosteronism,_______
- Secondary aldosteronism,_______
in which the stimulus for the excessive aldosterone production is within the adrenal gland
in which the stimulus is extraadrenal
The most common cause of primary hyperaldosteronism is a _______ (70%). _______ accounts for 25–30%.
unilateral adrenal adenoma
Bilateral hyperplasia
Primary hyperaldosteronism is characterized by _____ and ________
hypertension and low potassium levels.
Other Sx of Primary hyperaldosteronism:
muscle weakness, polyuria, and polydipsia, are
from the hypokalemia.
Metabolic alkalosis occurs because ______
aldosterone increases hydrogen ion (H+) excretion.
______is uncommon with primary hyperaldosteronism
because of sodium release into the urine
Edema
The preliminary screen for hyperaldosteronism is a _________
plasma aldosterone concentration (PAC) and plasma renin activity (PRA).
Hyperaldosteronism
Plasma aldosterone concentration (PAC) and plasma renin activity (PRA).
A positive screen is a PAC/PRA ratio ___ and a
PAC ______.
> 20:1
> 15
To confirm hyperaldosteronism, an ______ is required
This can be via normal saline, NaCl tabs, or fludrocortisone.
NaCl challenge
After an NaCl challenge, PAC should be_______
suppressed as in a normal individual. If PAC is still elevated, this confirms the diagnosis
Adrenal adenomas are removed surgically. Bilateral hyperplasia is treated with _______
spironolactone, which blocks aldosterone.
The exception of secondary hyperaldosteronism without edema or hypertension is________
Bartter syndrome
Bartter syndrome is caused by a defect in the __________This is like having a furosemide-secreting tumor.
loop of Henle in which it loses NaCl. This is due to a defect in the Na-K-2Cl cotransporter.
What are the problems in Bartters syndrome
juxtaglomerular hyperplasia, normal to low blood pressure, no edema, severe hypokalemic alkalosis, defect in renal conservation of sodium or chloride, and
renal loss of sodium, which stimulates renin secretion and aldosterone production
______ is a syndrome associated with increased adrenal androgen production because of enzymatic defects
Congenital adrenal hyperplasia
CAH
Enzymatic defects include ______ in 95% of all cases
C-21 hydroxylase
deficiency
C-21 hydroxylase deficiency is associated with _____
reduction in aldosterone secretion in one-third of patients
SSx of CAH from C-21 hydroxylase deficiency
Patients are female at birth with ambiguous external genitalia (female pseudohermaphrodism),
enlarged clitoris, and partial or complete fusion of the labia
Manifestations of C-11 hydroxylase deficiency in early infancy
In early infancy, despite having excessive mineralocorticoid hormones, patients sometimes present with relative ‘salt wasting’ (aldosterone deficiency).
This is because some infants have inefficient salt conservation as well as immature aldosterone
production.
During this phase, infants can present with hypotension and hyperkalemia (very similar to 21 hydroxylase deficiency).
Manifestations of C-11 hydroxylase deficiency Later in life (childhood and adulthood)
there is better ability to hold onto salt, so the patient develops the typical C-11 deficiency syndrome: hypertension and hypokalemia
C-17 hydroxylase deficiency can occur as well, and is characterized by hypogonadism, hypokalemia,
and hypertension resulting from increased production of ________
11-deoxycorticosterone
CAH should be considered in all infants exhibiting_______
failure to thrive, especially those with episodes of acute adrenal insufficiency, salt wasting, or hypertension
CAH
The most useful measurements are of _____
serum testosterone, androstenedione, dehydroepiandrosterone, 17-hydroxyprogesterone, urinary 17-ketosteroid, and pregnanetriol.
Tx of CAH
Treatment is glucocorticoid (hydrocortisone) replacement
Adrenal insufficiency can be divided into
1
2
primary adrenocorticoid insufficiency (Addison disease) and secondary failure in the elaboration of ACTH
MC etiology of Addison
Idiopathic atrophy is the most common cause of anatomic
destruction, and autoimmune mechanisms are probably responsible.
The clinical findings in Addison disease include :
weakness, paresthesias, cramping, intolerance to stress, and personality changes such as irritability and restlessness.
______ is characterized by fever and hypotension.
A low sodium with a high potassium level and mild acidosis are also present
Acute Addisonian crisis
The diagnosis of Addison disease is made through _______
rapid ACTH administration and measurement of cortisol
Lab findings of Addison disease
Laboratory findings include white blood cell count with moderate neutropenia, lymphocytosis, and eosinophilia; elevated serum potassium and urea nitrogen;
low sodium; low blood glucose; and morning low plasma cortisol
The definitive dx of Addison disease is:
cosyntropin or ACTH stimulation test.
Normal results of the cosyntropin or ACTH stimulation test.
A cortisol level is obtained before and after administering ACTH. A normal person should show a brisk rise in
cortisol level after ACTH administration.
The management of Addison disease involves
glucocorticoid, mineralocorticoid, and sodium chloride replacement, in addition to patient education.
Who may suffer adrenal crisis
• Previously undiagnosed patient with adrenal insufficiency who has undergone surgery,
serious infection, and/or major stress
• Bilateral adrenal infarction or hemorrhage
• Patient who is abruptly withdrawn from chronic glucocorticoid therapy
What is the rule of 10 for Phaeochrom
The rule of 10% applies in pheochromocytoma with 10% being extraadrenal, 10% malignant, 10% in children, and 10% bilateral or multiple (>right side).
Also, 10% are not associated with hypertension.
Familial pheochromocytoma occurs in 5% of cases, and is transmitted as an autosomal dominant trait alone or in combination with
MEN type II or III, von Recklinghausen neurofibromatosis, or von Hippel-Lindau retinal cerebellar hemangioblastomatosis.
In adults, _____ of pheochromocytomas occur as a unilateral solitary lesion with ___ being bilateral and ____ extraadrenal
80%
10%
10%
Extraadrenal pheochromocytomas are mostly located within the ______
abdomen and near the celiac, superior mesenteric, and inferior mesenteric ganglia
Clinical findings of pheochromocytoma include _____
paroxysms or crisis.
> 33% of pheochromocytomas cause death prior to diagnosis; death is often due to
cardiac arrhythmia and stroke
pheochromocytoma
__________are tests of choice.
Urinary-free catecholamines, urinary metanephrines, vanillylmandelic acid, and plasma catecholamines
pheochromocytoma
__________s are the best initial tests. Recently, plasma metanephrine levels have been used in conjunction with urinary tests
A 24-hour urinary VMA, metanephrines, and
free catecholamines
Overall, _______ are the most sensitive and specific
individual test
metanephrines
Failure of epinephrine levels to fall after _____
administration is highly suggestive of pheochromocytoma
clonidine
________ is used to locate a pheochromocytoma
not found on a CT scan.
MIBG (metaiodobenzylguanidine) scanning
1 2 3 , is required to control BP and prevent a hypertensive crisis, since high circulating catecholamine levels stimulate alpha receptors on blood vessels and cause vasoconstriction
Alpha-adrenergic blockade, phentolamine, and/or phenoxybenzamine
Phaechrom
______are not administered until adequate alpha blockade has been established, since unopposed alpha-adrenergic receptor stimulation can precipitate a hypertensive crisis.
beta blockers
Choice of BB in Phaeochrom
Noncardioselective beta blockers (propranolol, nadolol) are the usual choice, though cardioselective agents (atenolol, metoprolol) may be used
______has been associated with paradoxic episodes of hypertension thought to be secondary to incomplete alpha blockade.
Labetalol
