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Investigation of endocrine disease

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Investigation of endocrine disease * * * * Cushing s Syndrome Diagnosis of Cushing s syndrome History Weight gain, fatigue Infertility, impotence, changes in ... – PowerPoint PPT presentation

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Title: Investigation of endocrine disease


1
Investigation of endocrine disease
2
Endocrinology is Easy
  • Diseases are due to
  • TOO MUCH hormone
  • TOO LITTLE hormone
  • Hormone levels vary physiologically
  • Testing needs to be dynamic
  • If the hormone is too high SUPPRESS IT
  • If the hormone is too low STIMULATE IT

3
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4
Pituitary Gland
  • Anterior hormone secretion of thyroid, adrenal
    cortex, gonads
  • Posterior water balance, salt balance

5
Two Major Divisions of Pituitary
Anterior Adenohypophysis
Posterior Neurohypophysis
  • Each has a distinct role to play in hormone
    regulation

6
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7
Diagnosis of PD by PH stimulation test
Hormone Test agent N response
G H I H test 0.1 uint L-dopa 250-500 Arginine 0.5 gm Clonidine test Glucagon test Serum GH gt 10ng/ml at any time
Prl TRH 100-500 metoclopramide Doubling of baseline
TSH TRH 500 ng Peak value gt5 mu/ml



8
Pituitary stimulation test 2
hormone Test agent N response
LH _at_FSH GnRH 100mmg IV Doubling of the base line LH_at_FSH
ACTH I H TEST (short ACTH stimulation test cosyntropin test) Metyrapone test 2-3 gm po Peak serum cortisol gt20 ng/dl Serum 11-deoxycortisol level gt8 ng/dl


9
Laboratory finding in acromegaly
  • Plasma glucose may be elevated
  • Increase serum insulin
  • Elevated serum phosphate
  • Hypercalciuria
  • Elevated GH

10
Diagnosis of acromegaly
  • Glucose suppression test
  • IGF-1
  • Tumor localization
  • MRI

11
Posterior pituitary hormone (ADH vasopressin)
  • ADH acts through tow receptors V1 _at_ V2
  • V1 receptors mediate vascular smooth muscle
    contraction _at_stimulate prostaglandin synthesis
  • V2 receptors produce renal action by increase the
    water permeability of the luminal membrane of
    collecting duct epithelium
  • In the absence of ADH permeability of the
    epithelium is decrease leading to polyuria

12
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13
Laboratory finding
  • A large urinary volume gt3 l /per day
  • Urine osmolality less than 200 mosm/kg
  • Slightly elevated plasma osmolality
  • Low serum ADH in CDI
  • High or normal ADH in NDI

14
Diagnosis of DI
  • Water deprivation test (method)
  • Deprivation from water for 4-18 hr
  • Hourly measurements of urine osmolality
  • Continues until urine osmolality of 3 consecutive
    sample varies by less than 30 mosml/kg
  • 5 unite of AVP or 1 mg of desmopression injected
    _at_ urine and plasma osml measure 30,60,120 m later

15
Interpretation of WDT
CDI NDI psychogenic
Urine osmol after wdt No change lt300 No change lt300 Increase gt750
Urine osmol after vasopressin increase No change increase
Plasma ADH low Normal or high low
16
Thyroid gland
17
Thyroid
  • Growth, development
  • Metabolic rate

18
Thyroid Function Tests
  • Free serum thyroxine (T4)
  • Free serum T3
  • TSH

19
Scans/Ultrasound
  • Radioiodine uptake (RAIU)
  • Thyroid Scan
  • Ultrasound
  • Fine needle Aspiration

20
Radioiodine Uptake
  • Useful in differentiating non-pituitary
    thyrotoxic states (i.e., low TSH, high free
    thyroxine)
  • No use in hypothyroidism
  • A set dose of radioactive iodine (usually I123)
    is given and 24hrs later a radiation detector is
    placed over the thyroid to determine of dose
    taken up by thyroid

21
RAIU
  • RAIU is increased in
  • Graves Disease
  • Hot nodules
  • Multi-nodular goiters
  • Toxic Solitary Nodule
  • hCG secreting tumors

22
RAIU
  • RAIU is decreased in
  • Amiodarone
  • Factitious Thyroiditis
  • Self limited thyroiditis-induced thyrotoxic state
  • Painless chronic thyroiditis
  • Postpartum thyroiditis
  • Subacute thyroiditis

23
Thyroid Scan
  • Also called scintiscan or radionuclide scan
  • A dose of radioiodine or Tc99m is given
  • Scintillation scanner produces a rough picture
    indicating how these isotopes localize in the
    thyroid
  • Thyroid scan is only used for nodular
    disease---useful for determining whether a nodule
    is hot or cold
  • Again---RAIU produces a number, scan produces a
    picture

24
Ultrasound
  • U/S can provide information about its size and
    texture
  • Used for determining whether a nodule is cystic
    or solid
  • Follow the size of a nodule or goiter over time.

25
Parathyroid gland
  • And calcium metabolisms

26
CALCIUM HOMEOSTASIS
DIETARY CALCIUM
THE ONLY IN
BONE
DIETARY HABITS, SUPPLEMENTS
ORGAN, ENDOCRINE
BLOOD CALCIUM
INTESTINAL ABSORPTION ORGAN PHYSIOLOGY ENDOCRINE
PHYSIOLOGY
KIDNEYS
ORGAN PHYS. ENDOCRINE PHYS.
URINE
THE PRINCIPLE OUT
27
VITAMIN D SYNTHESIS
SKIN
LIVER
KIDNEY
7-DEHYDROCHOLESTEROL
VITAMIN D3
25(OH)VITAMIN D
25-HYDROXYLASE
1a-HYDROXYLASE
h?
VITAMIN D3
25(OH)VITAMIN D
1,25(OH)2 VITAMIN D (ACTIVE METABOLITE)
TISSUE-SPECIFIC VITAMIN D RESPONSES
28
CALCIUM, PTH, AND VITAMIN D FEEDBACK LOOPS
BONE RESORPTION URINARY LOSS 1,25(OH)2 D
PRODUCTION
SUPPRESS PTH
RISING BLOOD Ca
NORMAL BLOOD Ca
FALLING BLOOD Ca
BONE RESORPTION URINARY LOSS 1,25(OH)2 D
PRODUCTION
STIMULATE PTH
29
Adrenal gland
30
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31
Synthesis of Adrenocortical Hormones
  • Zona glomerulosa aldosterone
  • Zona fasciculata glucocorticoids (cortisol)
  • Zona reticularis androgens (DHEA and
    androstenedione)

32
Regulation of Adrenocortical Hormones
  • Hypothalamus
  • CRH-containing neurons are stimulated
  • CRH delivered to anterior pituitary
  • CRH binds to receptors on corticotrophs, causing
    synthesis and secretion of ACTH

33
Pathways of Steroid Biosynthesis
34
Cushings Syndrome
  • Diagnosis of Cushings syndrome
  • History
  • Weight gain, fatigue
  • Infertility, impotence, changes in menstruation
  • Diabetes, polyuria, polydypsia
  • Depression, headache
  • Signs of underlying tumor (weight loss, appetite)
  • Physical exam
  • Obesity, fat distribution
  • Proximal muscle weakness/wasting
  • Palpation of abdominal mass

35
Cushings Syndrome
  • Diagnosis of Cushings syndrome
  • Labs
  • 24 hour urinary cortisol
  • 2-3 consecutive days
  • Verify with creatinine values
  • Spot AM/PM serum cortisol
  • Circadian variation
  • AM ACTH surge causes increased cortisol
  • PM should see at least 50 drop in cortisol level
  • Low-dose dexamethasone suppression test

36
Cushings Syndrome
  • Diagnose cause of Cushings syndrome
  • History (steroid use?)
  • Serum ACTH
  • Elevated Cushings disease, ectopic ACTH
  • Suppressed primary adrenal source
  • Correlate with cortisol levels
  • High-dose dexamethasone suppression test
  • Metyrapone test

37
Cushings Syndrome
  • Dexmethasone suppression test
  • Synthetic glucocorticoid (30x more potent as
    inhibitor)
  • Low dose
  • 0.5mg po q6 hours x48 hours
  • Measure cortisol, 17-hydroxycorticosteroid,
    creatinine
  • Fall in all steroid levels in pseudo-Cushing and
    normals
  • Differentiates presence/absence of Cushings
    syndrome
  • Alternative dosing
  • 1mg po at midnight and measure 8am cortisol
  • Much less sensitive

38
Cushings Syndrome
  • Dexmethasone suppression test
  • High Dose
  • 2mg po q6 hours x48 hours
  • Measure cortisol and urinary free cortisol
  • Ectopic ACTH and adrenal tumors- no suppression
  • Cushings disease- suppress to lt50 of baseline
  • Usually only used if ACTH/Cortisol assays
    unavailable or equivocal

39
Cushings Syndrome
  • Metyrapone test
  • Inhibits 11-B-hydroxylase
  • Blocks conversion of 11-deoxycortisol to cortisol
  • Plasma cortisol levels fall and ACTH increases
  • Marked increase in 17-hydroxycorticosteroid
    levels and 11-deoxycortisol levels
  • Cushings Disease- normal or supernormal increase
    in levels
  • Ectopic ACTH or adrenal sources- no response
  • Risks adrenal insufficiency

40
Cushings Syndrome
  • Petrosal vein sampling
  • Measure petrosal venous sinus ACTH level and
    correlate to plasma levels
  • Invasive with morbidity
  • Usually not used
  • Adrenal venous sampling
  • Measure cortisol and aldosterone
  • Not used anymore

41
Cushings Syndrome
  • Radiographic Localization
  • CT of sella turcica
  • Unenhanced and gadolinium enhanced MRI
  • Radionuclide imaging for somatostatin receptors
  • gt60 sensitive
  • 1st study if diagnosed with Cushings syndrome
  • CT of chest/abdomen with 3mm cuts through adrenal
  • Adrenal hyperplasia
  • Thickening and elongation of adrenal rami
    bilaterally
  • Multinodularity of cortex bilaterally

42
Cushings Syndrome
  • Radiographic Localization
  • CT of adrenal glands
  • Adenomas- usually gt2cm but lt5cm
  • Low attenuation (lipid content)
  • Atrophy of opposite gland
  • Carcinoma- indistinguishable from adenomas
  • gt5cm
  • Necrosis, calcifications, irregularity, invasion
  • MRI of adrenal- usually not needed
  • Signal intensity much higher than in spleen
    carcinoma
  • Adjacent organ and/or vascular involvement

43
Cushings Syndrome
  • Radiographic Localization
  • CT of adrenal glands
  • Adenomas- usually gt2cm but lt5cm
  • Low attenuation (lipid content)
  • Atrophy of opposite gland
  • Carcinoma- indistinguishable from adenomas
  • gt5cm
  • Necrosis, calcifications, irregularity, invasion
  • MRI of adrenal- usually not needed
  • Signal intensity much higher than in spleen
    carcinoma
  • Adjacent organ and/or vascular involvement

44
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45
DIAGNOSIS
  • Basal Cortisol Level
  • Avoid random level low sensitivity
  • Check morning cortisol
  • Greater than 18 µg/dL indicates an intact axis
  • Less than 3 µg/dL strongly suggests insufficiency
  • Intermediate values perform cosyntropin
    stimulation test

46
DIAGNOSIS
  • Low-Dose Cosyntropin Test
  • Cosyntropin doses as low as 0.5 to 1 ug will give
    a maximal response within 15 to 30 mins
  • Possibly superior to high-dose test for
    diagnosing secondary insufficiency because ACTH
    level closer to physiologic level
  • Normal response peak plasma cortisol level gt 18
    µg/dL
  • Like high-dose test, low sensitivity when ruling
    out mild or recent secondary insufficiency
    confirm with more sensitive tests (insulin
    tolerance, metyrapone)

47
DIAGNOSIS
  • Insulin Tolerance Test
  • Hypoglycemia induced by the IV injection of reg
    insulin stimulates the entire HPA axis.
  • Plasma glucose and cortisol are measured after
    injection of insulin.
  • Normal response cortisol increases to at least
    18ug per dL
  • Expensive and contraindicated in patients with
    coronary heart disease or seizures

48
DIAGNOSIS
  • Metyrapone Test
  • Metyrapone inhibits conversion of
    11-deoxycortisol to cortisol
  • Give at midnight and measure the concentration of
    11-deoxycortisol and cortisol at 8am
  • In normal subjects, the plasma 11-deoxycortisol
    concentration increases to at least 7ug per dL.
    In patients with adrenal insufficiency, the
    increase is smaller and is related to the
    severity of the corticotropin deficiency

49
Hyperaldosteronism
  • Causes
  • Adenoma (most common)
  • FgtM
  • 4th-5th decades of life
  • Bilateral adrenal hyperplasia
  • Adrenocortical carcinoma (rare)
  • Glucocorticoid remedial aldosteronism
  • Aldosterone producing adenoma
  • Responsive to renin

50
Hyperaldosteronism
  • Diagnosis
  • History, HTN, symptoms
  • Laboratory
  • Serum K (lt3.0)
  • Serum aldosterone
  • Salt load patients (suppresses aldosterone)
  • Level gt14 micrograms/d diagnostic of primary
    hyperaldosteronism
  • Serum renin
  • If gt1.0 then unlikely primary hyperaldosteronism

51
Pheochromocytoma, Diagnosis
  • 24hr urinary catecholamines (NE, Epi, Dop) and
    metabolites (metanephrine, normetanephrine, VMA)
  • Plasma catecholamine or metabolites during
    episode
  • Elevated serum epinephrine suggests pheo in
    medulla or Organ of Zukerkandl
  • NO FNA! (can precipitate hypertensive crisis)

52
Pheochromocytoma, Diagnosis
  • Localizing studies CT, MRI, MIBG scan
  • Thin cut CT detects most lesions 97
    intraabdominal
  • MRI 90 pheos bright on T2 weighted scan
  • MIBG used for extraadrenal, recurrent,
    multifocal, malignant disease
  • Malignant disease
  • Local invasion, disease outside of
    adrenal/paraganglionic tissue
  • No histological or clinical criteria can
    differentiate malignant disease
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