Endocrinology 06
Terms
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- Hypertension diagnosis
- systolic > 140 diastolic > 90 on 3 occasions
- __________ should be suspected in any patient with HTN associated with hypokalemia
- Primary hyperaldosteronism
- most cases of primary hyperaldosteronism are due to what?
- solitary, unilateral, adrenal adenomas
- 11-beta-steroid dehydrogenase enzyme
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located at the mineralocorticoid receptor
enzyme normal converts cortisol to cortisone which cannot beind to the mineralocorticoid receptor
if enzyme is deficient then cortisol can bind to the mineralocorticoid receptor and produce HTN and hypokalemia - glycericic acid
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found in black licorice and chewing tobacco
can inhibit the activity of 11-beta-steroid dehydrogenase - spironolactone
- mineralocorticoid receptor antagonist
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pheochromocytoma
- very general - catecholamine producing tumors of the adrenal medulla
- what is the triad of symptoms you usually see in pheochromocytoma?
- headache, palpitations, and diaphoresis
- clonidine suppression test
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clonidine is a centrally acting alpha adrenergic agonist that normally decreases catecholamine levels
failure of catecholamine levels to suppress after clonidine administration is consistent with pheochromocytoma - what is required preop for removal of pheochromocytoma?
- alpha-adrenergic blockade (phenoxybenzamine) as well as volume expansion is required
- what is the medical therapy that can be used for Cushings (where surgery didn't work or isn't an option) -- 5 choices
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(1) Ketoconazole
(2) Metyrapone
(3) Aminoglutethimide
(4) Mitotane
(5) RU 486 -
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Normal Parathyroid and Parathyroid Adenoma
An illustration of a 6-7 week embryonic pharynx and its derivatives. The parathyroid glands are derived from the III and IV pharyngeal pouches, also called brachial clefts. -
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Normal Parathyroid and Parathyroid Adenoma
Low power view of a normal parathyroid. -
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Normal Parathyroid and Parathyroid Adenoma
Higher power view of a normal parathyroid. -
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Normal Parathyroid and Parathyroid Adenoma
Low power view of parathyroid adenoma (left side) compressing normal parenchyma (right side). -
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Osteitis Fibrosa (Cystica) of Bone
Skeletal changes in hyperparathyroidism (von Recklinghausen's disease of the bone)
Gross photograph demonstrates advanced cystic rarefaction of the femur, due to a functioning parathyroid adenoma (primary hyperparathyroidism) -
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Osteitis Fibrosa (Cystica) of Bone
Skeletal changes in hyperparathyroidism (von Recklinghausen's disease of the bone)
Microscopic view of osteitis cystica. The slide shows zones of decalcification, increased numbers of osteoclasts with scalloped resorption of bone. -
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Nodular Goiter
Gross specimen of a nodular goiter. -
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Nodular Goiter
Microscopic section of a nodular goiter. -
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Adenoma of the Thyroid
Gross specimen of a nodular adenoma of the thyroid. The adenoma is the well circumscribed cream-colored nodular surrounded by normal tissue. -
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Adenoma of the Thyroid
Low power view of adenoma (left) compressing normal thyroid (right). -
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Adenoma of the Thyroid
High power view shows tumor (left) enclosed in a thin capsule. -
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Carcinoma of the Thyroid
Gross specimen of papillary carcinoma of thyroid. See arrow.
a. identify tumor and capsule
b. identify normal thyroid -
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Carcinoma of the Thyroid
Low power view of a papillary carcinoma of thyroid. -
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Carcinoma of the Thyroid
High power view of a papillary carcinoma. Notice "ground glass" nuclei. -
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Hashimoto's Thyroiditis
Low power view of a case of Hashimoto's thyroiditis. Notice lymphoid follicles. -
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Hashimoto's Thyroiditis
High power view of Hashimoto's thyroiditis showing lymphoid follicles within thyroid tissue. -
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Hyalinization of Islets of Langerhans
Low power view of islet hyalinization (diabetes). -
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Hyalinization of Islets of Langerhans
High power view of islet hyalinization (diabetes). -
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Diabetic Glomerular Nephropathy (Kimmelstiel-Wilson Lesion)
Low power view showing sclerosis of para-glomerular arterioles in kidney; another renal complication of diabetes. -
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Diabetic Glomerular Nephropathy (Kimmelstiel-Wilson Lesion)
High power view of diabetic glomerulopathy of Kimmelstiel-Wilson disease. - octreotide
- Octreotide is a somatostatin analogue. Many endocrine tumors such as carcinoids, insulinomas, pheo have somatostatin receptors and will "light" up in an octreotide scan.
- ambiguous genitalia
- any defect in external or internal genitalia that is more significant than simple isolated glandular hypospadius or unilateral undescended testis
- at what point does sexual differentiation direct along the male pathway?
- at 6-8 weeks gestation, once the embryonic testis develops
- what are the two critical hormones that determine sexual differentiation of the fetus?
- MIS and Testosterone (T)
- MIS
- induce regression of the mullerian structures: uterus, fallopian tubes and upper third of the vagina
- Testosterone
- induce ventral fusion of the external genital anlage, creating the scrotum and penile shaft with distal urethral opening
- what is the key gene initiator of testicular differentiation (and thus the key gene in sexual differentiation)
- SRY
- is production of gonadal steroids by the fetus controlled by the hypothalamic-pituitary-gonadal (HPGA) axis?
- No, it is controlled in the early testis by placental hCG
- what does INC leptin have to do with puberty?
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INC in serum leptin at onset of puberty
the earlier this happens, sooner puberty starts
may explain why obese girls start puberty earlier - precocious puberty
- sexual maturation beginning before 7 years in F (6 years for black girls) or before 9 years in males
- premature thelarche
- breast development without other signs of sexual maturation; usually seen in girls less than 3 years old; is benign and non-progressive
- premature adrenarche
- isolated growth of pubic hair < 7 yrs of age due to early INC adrenal androgen secretion
- central (true) precocious puberty
- early activation of the hypothalamic-pituitary-gonadal axis
- peripheral precocious puberty
- INC secretion of sex steroids NOT under influence of gonadotrophins
- what is the most common cause of primary (hypergonadotropic) hypogonadism in females?
- Turner syndrome
- Serum TRAb
- thyrotropin receptor antibody in patients with Graves' disease
- name three important factors that can inc TBG
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(1) pregnancy
(2) Estrogens (Birth Control Pills, BCPs)
(3) Acute Hepatitis - name one important factor that can dec TBG
- nephrotic syndrome
- does serum T3 measurement discriminate well between hyperthyroid and euthyroid? How about euthyroid and hypothyroid?
- discriminates well b/t hyper and eu, not so well b/t eu and hypo
- what is the DOC for hyperthyroidism in pregnancy and thyroid storm?
- PTU
- direct effect of PTH to INC blood calcium?
- inc bone resorption
- 1,25 vit D maintains normal calcium by which effect?
- INC absorption of Ca2+ in GI tract
- Low vit D produces what
- DEC serum calcium
- what is the most common cause of hypercalcemia?
- primary hyperparathyroidism
- does GH deficiency often present as amenorrhea in women?
- YES
- Vasopressin MOA
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binds to V2 receptors to activate cAMP in renal distal and collecting tubules --> inc synth and translocation of aquaporins to luminal surface of collecting tubules
secondary effect of vasopressin is vasoconstriction via binding to V1 receptors on vascular smooth muscle - 25-hydroxylation of vit D occurs where? regulated?
- occurs in the liver, is NOT regulated
- where does 1-hydroxylation of vit D occur? regulated?
- occurs in the kidney, IS regulated by PTH
- which portion of the kidney is responsible for the PTH-dependent excretion of calcium?
- distal tubule
- should you use thiazide diuretics in patients with hypercalcemia?
- NO --> dec sodium reabsorption and inc calcium reabsorption
- how does PTH effect phosphate levels and what is the significance on calcium levels of this change in phosphate?
- PTH acts to decrease the concentration of phosphate in the blood, primarily by reducing reabsorption in the proximal tubules of the kidney. The decreased phosphate enhances bone demineralization --> INC calcium
- how can lithium contribute to hypercalcemia?
- INC set point for inhibition of PTH secretion
- Sarcoidosis / Granulomatous disease -- what effect on calcium balance?
- granulomas have 1-hydroxylase activity --> inc levels of 1, 25 vit D --> inc Ca/phosphate (dec PTH)
- DiGeorge Syndrome
- genetic / embryologic abnormality of parathyroid gland formation
- does 1,25 OH vit D effect PTH secretion?
- 1,25 D directly inhibits PTH secretion
- Trousseau's Sign
- blood pressure cuff makes arm go funny --> sign of hypocalcemia
- Chvostek's Sign
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stroke cheek --> lip tremor
sign of hypocalcemia - Secondary Hyperparathyroidism
- Vitamin D deficiency
- are patients usually asymptomatic until the time of their first osteoporosis-related fracture?
- YES
- T/F measurement of bone mass provides the best prediction of future fracture risk.
- T
- T/F patients with higher rates of bone remodelling (bone turnover) have increased fracture risk.
- T
- what is the gold standard for the diagnosis of osteoporosis?
- DXA (dual energy X-ray absorptiometry)
- how does estrogen DEC bone resorption?
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estrogen DEC production of IL-6 (IL-6 itself INC bone resorption)
estrogen INC production of osteoprotegerin (OPG, which DEC bone resorption) - Raloxifene
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a Selective Estrogen Receptor Modulator (SERM)
an anti-estrogen analog that inhibits the action of estrogen on breast and uterine tissue ... BUT has estrogen-like effects on bone - bisphosphonates
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are ingested by osteoclasts, killing them
thus inhibit the resorption of bone - name two bisphosphonates
- Alendronate (Fosamax) and Risedronate (Actonel)
- Does PTH lead to bone resorption or anabolism?
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TRICK QUESTION -- it can be both
prolonged PTH --> resorption
intermittent PTH --> anabolic - can intermittent exposure to PTH restore some of the microarchitectural structure that is lost in patients with osteoporosis?
- YES!
- osteoporosis
- a skeletal disorder characterized by compromised bone STRENGTH predisposing to an increased risk of fracture
- In Graves' diesease, what is the cause of palpitations, stare, and lid lag?
- upregulation of beta-adrenergic receptors
- if T3RU is low, are thyroid hormone binding sites low or high?
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HIGH
T3RU is an inverse measurement of available thyroid hormone binding sites
low T3RU -- think INC TBG or hypothyroidism - what is the prognosis of medullary thyroid cancer compared with the other thyroid-associated cancers?
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prognosis for medullary thyroid cancer is poor
prognosis for papillary, follicular cancer good