endocrine testing protocols

Cushings:

Screening: 2/3 screening test positiveConfirmatory testingLocalisation testing

Screening tests:

24 Hour Urine Collection: two samples measuring urine free cortisollevels > 2x Upper limit of normal considered positiveconfounders (Obesity, Depression, Anorexia may increase levels slightly)

•

Diurnal rhythm: either salivary or serum cortisol level:midnight cortisol <50nmol/l (high sensitivity) but recent studies suggest cut off of <207nmol/l better specificity Salivary cortisol levels (<4nmol/l) considered normal

•

Low dose 1mg overnight dexamethasone suppression test:1mg Betamethasone given orally between 23:00 and 0:00 with serum 8:00am cortisol measuredsuppression below 50nmol/l considered normalfalse positives related to increased dexamethasone metabolism e.g. phenytoin, phenobarb, rifampicin), renal failure and depression

•

CONFOUNDERS: See table 3

Confirmatory tests:

Formal low dose 2mg 48hr Dexamethasone suppression test:pt given 0.5mg betamethasone (8 doses) every 6 hours starting at 12:00. Subsequent doses given every 6 hours (18:00, 0:00, 6:00, 12:00, 18:00, 0:00, 6:00) and serum cortisol at 8:00 taken

Suppression to <50nml/l considered normal and excludes cushings

•

Localizing tests:

Measure ACTH (EDTA tube on ice) levels <1.1pmol/l suggests ACTH independence

•

Levels >2.2pmol/l suggest ACTH dependence (note levels often much higher)

CRH Stimulation Test: very good to confrim cushings and localised itBld drawn at -15min and 0mins for ACTH and cortisol. Pt given 1µg/kg CRF iv. Blood taken at 15, 30, 60, 90, 120 mins for ACTH and Coritsol Interpretation: ACTH increase of >35% above basal in pts with Cushings disease but not in ectopic ACTH. Increase of cortisol by >20% at 30-45mins suggests cushings disease rather than ectopic secretion. (note poor discriminator of pseudocushings)

•

DEX-CRH test:improved diagnostic accuracy in confirming cushings and differential diagnosis:

•

Betamethasone 0.5mg given orally for as for 48hr dex suppression test: ==> pts with Cushings disease suppress by at least 50% (urinary cortisol / serum cortisol) whereas cushings syndrome does not (measured at 8:00) Basal ACTH and cortisol taken at -15mins and 0mins.Pt given 1µg/kg CRH ivi 2hrs (NBNB) after 8:00 cortisol and ACTH levels done at 15, 30, 60, 90, 120mins.Cortisol level > 38nmol/l at 15 mins post CRH suggests cushings disease

Inferior Petrossal Sinus Sampling:gold standard for diagnosing cushing's disease, but invasive and higher comlication rate.Catheters placed via left and right femoral veins into left and right inferior petrossal sinuses via xray screening. Peripheral large bore line placed to sample peripheral blood.Baseline samples for Prolactin (to confirm position in IPS) as well as Cortisol

•

Cushings Testing09 August 201011:38 AM

Pituitary Function Testing

Baseline samples for Prolactin (to confirm position in IPS) as well as Cortisol and ACTH obtained at -15, -10, -5 and 0 mins. CRH given ivi at dose of 1µg/kg via peripheral vein.Blood drawn for ACTH and Cortisol at 2, 5, 10 and 15 mins from all three catheters (L and R IPS and Peripheral line)


Growth Hormone Suppression Test:75g oral glucose load given in 300-500ml water ingested over 5 minsBlood for Glucose and GH taken at 0, 30, 60, 90, 120, 150 mins Levels of GH > 1ng/ml confirm acromegalyMeasure Prolactin and IFG-1 at basline also

IGF -1:Single blood test, Long half life, elevated level also confirm diagnosisBut levels fluctuate and affected by renal dysfunction and hepatic dysfunction, nutrition and DM

TSH Test: TRH inhibits GH release.TRH given 200mg IVI with GH measured at 0, 20, 60minsNormal response is a fall in GH concentration but in 60% of pts with Acromegaly have paradoxical rise in GH levels.

GHRH measurement:Done if MRI of pituitary shows no tumourOften pancreatic source

Cure in Acromegaly:

Pts on Somatostatin therapy random IGF1 and GH are sufficient for assessmentDiscordant results: 30% of pts will have discordance between GH and IGF levels mostly N GH with elevated IGF1NOTE patients on Pegvisomant ==> monitor IGF1 levels only

Controlled acromegaly : suppressed GH levels during OGT and Normal IGF1 3-6/12 post neurosurgery

Acromegaly:09 August 201001:51 PM


No provocative testingGenerally level corresponds to tumour sizeLevels > 200 ng/ml ==> MacroadenomaLevels< 100 ng/ml ==> microadenomaLevels 100 - 200 ng/ml grey zone, could be either.Note that levels > 100 unlikely to be stalk effect, interferingDrugs or physiologcal But may be falsely low due to

Prolactinoma09 August 201002:33 PM


Table 1. Guidelines for initial clinical evaluation of a

child with growth failure

Evaluation Key elements

Birth history Gestational age, birth weight and length, delivery type, birth trauma, hypoglycemia, prolonged jaundice.

Past medical

and surgical history

Head trauma, surgery, cranial radiation, CNS

infection.

Review of

systems

Appetite, eating habits, bowel movements.

Chronic

illness

Anemia, Inflammatory Bowel Disease,

cardiovascular disease, renal insufficiency, etc.

Family

history

Consanguinity, parents and siblings' heights,

family history of short stature, delayed puberty.

Physical examination

Body proportions (upper/lower segment ratios, arm span), head circumference, microphallus, dysmorphism, and midline craniofacial abnormalities.

Growth

pattern

Crossing of percentiles, failure to catch-up.

Screening

Tests

FBC, ESR, TFT's, UA, IGF1, IGFBP3, Bone age

(and a Karyotype for females)

Summary of diagnosis of GH deficiency:

height >2.25 SD below the mean for age or >2 SD

below the midparental height percentile;

1.

growth velocity <25th percentile for bone age: 2.bone age >2 SD below the mean for age; 3.low serum insulin-like growth factor 1 (IGF-1) and/or

insulin-like growth factor binding protein 3 (IGFBP3);

4.

other clinical features suggestive of GH deficiency. 5.

Children with severe GH deficiency can usually be

diagnosed easily on clinical grounds, and fail GH stimulation tests. Studies have shown that despite clinical evidence of GH deficiency, some children may pass GH

stimulation tests (11). In the case of unexplained short stature, if the child meets most of the following criteria, a trial of GH treatment should be initiated (1):

Height more than 2 SD below the mean. 1.Neonatal hypoglycemia, microphallus, prolonged

jaundice, or traumatic delivery.

2.

Although not required, a peak GH concentration after

provocative GH testing of less than 10 ng/ml.

3.

Consanguinity and/or a family member with GH

deficiency.

4.

Midline CNS defects, pituitary hypo- or aplasia,

pituitary stalk agenesis, empty sella, ectopic posterior pituitary (‘bright spot’) on MRI.

5.

Deficiency of other pituitary hormones: TSH, PRL,

LH/FSH and/or ACTH deficiency.

6.

Key elements that may indicate GH deficiency are:

Biochemical evaluation of GH deficiency:

Stimulation testing: GH provocation utilizing arginine, clonidine,

glucagon, L-Dopa, insulin, etc. This practice generally measures pituitary reserve-or GH secretory ability-rather than endogenous secretory status. Trained individuals should perform the GH

stimulation test according to a standardized protocol, with special care taken with younger children/infants.

1.

GH-dependent biochemical markers: IGF1 and IGFBP3: Values below

a cut-off less than -2 SD for IGF1 and/or IGFBP3 strongly suggest an abnormality in the GH axis if other causes of low IGF have been excluded. Age and gender appropriate reference ranges for IGF1 and

IGFBP3 are mandatory.

2.

24-hour or Overnight GH sampling: Blood sampling at frequent

intervals designed to quantify physiologic bursts of GH secretion.

3.

IGF generation test: This test is used to assess GH action and for the

confirmation of suspected GH insensitivity. GH is given for several days (3-5 days) with serum IGF-1 and IGFBP-3 levels measured at the start and end of the test. A sufficient rise in IGF-1 and IGFBP-3

levels would exclude severe forms of GH insensitivity (11, 21).

4.

As growth hormone is secreted in a pulsatile manner (usually 6 pulses in 24 hours and mainly during the night) with little serum GH at any given time, several methods have been recommended to assess the adequacy of GH secretion:

Diagnostic test for GH deficiency:

Need 2 different abnormal tests to diagnose GH deficiency as 10% of N children have abnormal response to single test•But rise of GH > 10ng/ml on any test excludes GH deficiency•

Screening test: GH level after 10 mins of vigorous exercise >10ng/ml (no guide what constitutes vigorous)•Insulin Hypoglycaemia test:•

Growth Hormone Deficiency09 August 201002:57 PM


Insulin Hypoglycaemia test:overnight fast, risk of seizure, need experienced personell, normal glucose at begin of testRequirements: 10-25% dextrose infusion available, IV infusion with N/S at beginning, constant supervision, no Hx of hypoglycaemic seizuresRegular insulin 0.075 - 0.1 U/kg in saline given as bolus. In 20-40 min a 50% drop in glucose levels occur. GH and cortisol and ACTH should increase (GH > 10ng/ml)Samples for GH and cortisol glucose taken at 0, 30, 45, 60, 75 and 90 minsGlucose should fall to <2.2mmol/l and cortisol should increase to >550mmol/l

•

Arginine infusion: 0.5g/kg infused over 30 mins ==> measure GH after 30 mins•Blood collected for GH at 0, 30, 60, 90 and 120 minsOral levodopa (125mg if <20kg and 250mg if >35kg and 500mg >35kg) measure GH •Clonidine Stimulation: (0.1-0.15mg/m2 given orally)•IGF 1 measurement and IGFBP3 are low in most with GH deficiency (but low in starvation, liver pathology and psychological deprivation)•


Water Deprivation Testing and a basic Approach to Polyuria.

C17/C20 Chemical Pathology: GSH

Definition: Polyuria is defined as > 2.5ml/kg/hour urine production in children or > 2500 ml/day in adults

Initial investigation = random S-Osm and U-Osm

1)- S-Osm > U-Osm

Psychogenic1.Hypothalamic Disease e.g. sarcoid2.Drugs – thiazides, chlorpromazine, anticholinergics3.

Polydypsia

Disorders of Water intake and Output

Central DI1.Drug inhibition of AVP ( opiate antagonists)2.

Vasopressin Deficiency

Congenital1.Aquired2.

Chronic renal disease (post ATN, transplant rejection, post obstructive uropathy)

Hypokalaemia ( incl aldosteronism)

Hypercalcaemia ( incl hyperparaT)

Drugs: Lithium, methoxyflurane, demeclocycline

Systemic disease: myeloma, sjogrens, amyloid, sickle cell anaemia

Nephrogenic DI

Prior to Water Deprivation testing, exclude treatable aquired causes of nephrogenic DI:HypokalaemiaHypercalcaemiaDrugs: Lithium/Diuretics

2) – S-Osm < U-Osm

Osmotic Diuresis

Glucose: DM

NaCl: Salt wasting renal disease e.g chronic pyelonephritis, Barters syndr, Fanconi syndr, diuretics, hypoaldosteronism

Urea: CRF, recovery phase of ATN

Other: mannitol

Surgery/trauma/infection/granuloma/infarction/tumor( craniopharyngiomas)

Causes of Central DI

Diabetes Insipidus10 August 201011:21 PM


Idiopathic : decreased ADH fibres present in adolescence, 40% have antibodies VS ADH neurons

Familial Central DI (AR and AD) have decrease ADH neurons: rare

DIDMOAD (Wolfram synr) = ADom, DI, DM, optic atrophy and deafness.

Placental vasopressinase may cause cause DI in pregnancy.

X linked Nephrogenic DI: boys, mutated V2 receptor and decreased adenylate cyclase activity

Mutations of the aquaporin II gene (boys and girls ) AR.

Inherited causes of Nephrogenic DI

Water deprivation Test:

Principle: The aim of water deprivation testing is to further investigate patients with polyuria/polydypsia and dilute urine with a low osmolality. It is used to differentiate primary polydypsia from DI in the first phase and then to distinguish AVP deficiency (Central DI) from AVP insensitivity (nephrogenic DI ) in phase II.

Phase I: Patients are kept NPO and if DI is present, they will continue to dehydrate beyond normal physiological set points. If a patient demonstrates significant dehydration as measured by a S-Na of > 145mmol/l, and/or a S-Osm of > 300 mOsm/kg (measured) and/or a >3% weight loss and a low Urine osmol within 8 hours of fasting they have an inability to retain water and have diabetes insipidus.

If they are able to concentrate their urine above 650mOsm/kg within 8 hours NPO and do not reach dehydration set points they most likely have primary polydypsia.

Some forms of partial DI take longer than 8 hours to reach dehydration end points. In these cases the first phase of the testcan be extended to12 - 18 hours before they reach dehydration targets.

Patients with primary polydypsia (psychogenic/drugs/thirst centre defects) initially produce dilute urine that gradually begins to concentrate as they fast. It can sometimes take longer than 8 hours for these patients to produce concentrated urine as their hypertonic renal medullary portal systems are often washed out and time is required for this to correct itself, they do not however reach dehydration set points even after 12 – 18 hours NPO.

Some patients yield equivocal results in phase I that are difficult to interpret. These patients can be given a therapeutic DDAVP trial under close supervision. Patients with central DI show an improvement, those with nephrogenic DI show none and those with primary polydypsia develop hyponatraemia; these patients must be watched closely.

Water deprivation should only be performed if the baseline S-Osm is < 295 mOsm/kg

In full blown DI patients, phase I can be extremely uncomfortable as thirst increases dramatically and patients must be kept away from fluids with vigilance. Blood and urine chemistry should also be measured rapidly and the results reported within a short time so as to minimize unnecessary prolongation of phase 1

Phase II: Once dehydration is achieved DDAVP (desmopressin) is given IM/IV (1µg) or intra-nasally (10-20µg) and free access to water is allowed. Central or cranial DI patients show a good response and are able to concentrate their urine and decrease the volume reaching a target U-Osm of 650 mOsm/kg within 2 – 4 hours. Patients with Nephrogenic DI demonstrate no response and continue to produce a large volume of dilute urine. (Note:-only DI patients go into phase II and get DDAVP). Please be careful when allowing central DI children free access to water after giving DDAVP, during phase I they become extremely thirsty and when allowed to drink they can take in too much water too soon and this, combined with DDAVP’s renal actions can result in severe fluid overload and reciprocal hyponatraemia.

Target Cutoff values for Dx of DI during water deprivation Testing

Initial S-Osm Final S-Na Final S-Osm U-Osm % weight change

Phase I < 295 mOsm/kg ≥145 mmol/l ≥300 mOsm/kg < 650mOSM/kgplateau for >3hr

≥3%

Phase 11 / / // 650 mOsm/kg /


Protocol:

Patients are allowed free fluids overnight and may take a light breakfast. Nicotine and caffeine are avoided.

Baseline bloods and a urine sample is obtained and the bladder voided. the patient is weighed after voiding urine

The patient is then kept NPO and blood and urine samples are collected every two hours, the patient is weighed and the urine volume over the preceding 2 hours measured and noted

Phase I continues until the dehydration cutoff values are achieved, in equivocal cases fasting is allowed for up to 18 hours.

If the patient does not achieve a dehydration cutoff and is able to achieve a U-Osmol of > 650 mOsm/kg within a maximum of 18 hours, a diagnosis of primary polydypsia is made and testing aborted

If dehydration targets are reached and urine osmol remains less than serum osmol. Phase II is begun

At the onset of phase II ,adult patients are given 1 ug DDAVP iv/sc/im and allowed free access to water

Urine osmol and volume is measured at ½ hourly intervals thereafter for 2-4 hrs. If an osmol of > 650 is achieved a diagnosis of central DI is made. If < 10% increase in U=Osm over 4 hours occurs, a diagnosis of nephrogenic DI is made. If the 4 hour U-Osm is < 650 but more than a 10% concentration in urine has occurred a diagnosis of partial nephrogenic DI is made.

Please arrange with C-17 core laboratory to have personnel available for stat serum and urine osmolarity measurements during testing

The S-Osm can be calculated initially to exclude an osmolar gap (ethanol)

After baseline measurements as per the accompanying table only S-Na, S-Osm and U-Osm need to be measured during the test. Results can be expressed graphically if the data sheet is filled in.


GSH Chemical Pathology

Water Deprivation Test

Patient

sticker

Referring Dr

Date

Phase 1 Phase 2

Baseline 1hr 2hr 3hr 4hr 5hr 6hr 7hr 8hr 30 min 60 min 90 min 120 min

Time

BP

Pulse

Weight(kg)

S-Li

S-Ca (corr)

S-urea

S-Na

S-K

S-gluc

S-creat

S-Osm:calc

S-Osm:meas

U-vol:ml

U-Osm:meas

Heparin

Clotting

Fluoride


Synachten stimulation test:

Use 1µg synacthen if testing for pituitary failureUse 250µg Synacthen if testing for primary adrenal failure

Adrenal evaluation:250µg given IVICortisol and ACTH measured prior to Synacthen and at 30mins Increase above 550mmol/l excludes addisons

1µg Synacthen test:Baseline ACTH and cortisol. Synacthen given and blood for cortisol taken at 30 mins post.Normal response if cortisol > 550mmol/l

•

Insulin Induced Hypoglycaemia test:See test for GH deficiency. Cortisol should be >550mmol/l in face of hypoglycaemia <2.2mmol/lTrue test of pituitary reserve to stress. Rarely performed due to risks.

•

Metyrapone stimulation test:Metyrapone inhibits 11 B Hydroxylase preventing cortisol formation ==> reduced negative feedback ==> rise in ACTH and ==> rise in cortisol precursor (11 deoxycortisol). Also true test of ACTH secretion be Pituitary30mg/kg Metyrapone given orally at midnightmeasure 11 deoxycortisol level at 8amRise to > 0.2nmol/l (7µg/dl) considered normal

Useful in borderline cases where ACTH stimulation equivocal

•

CRH Stimulation test:•CRH (ovine) given at 1µg/kg IVI provokes a peak ACTH response in 15 mins and peak cortisol response in 30-60 mins (measure at 15mins intervals)Different responses:Primary adrenal insufficiency: exaggerated ACTH response with elevated basal levelsSecondary adrenal insufficiency: Absent ACTH response with Tertiary (hypothalamic disease) Delayed peak in ACTHbut overlap in acth response of N pts with pts with secondary adrenal insufficiency

Pituitary Evaluation:Various tests available. Theory ==> in absence of regular stimulation by ACTH, adrenals atrophy so N response to ACTH severely blunted

Hypocortisolism09 August 201011:39 AM

Adrenal Funtion

24hr Urine fractionated Metanephrines (current gold standard for diagnosis)

•

Plasma free metanephrines if available has high sensitivity and specificity•MRI for localisation, Ideally not contrasted CT as can cause hypertensive crisis

•

Table 3. Drugs that may cause false positive elevations of plasma and urinary catecholamines or metanephrines

Catecholamines

Metanephrines

NE E NMN MN

NE, norepinephrine; E, epinephrine; NMN, normetanephrine; MN, metanephrine. +++, substantial increase; ++, moderate increase; +, mild increase if any; - , little or no increase; *, indicates a drug that can also cause direct analytical interference with some methods. Adapted from Eisenhofer and Pacak (88).

Tricyclic antidepressants

Amitriptyline (Elavil), Imipramine (Topfranil), Nortriptyline (Aventyl)

+++ - +++ -

a-Blockers (non-selective)

Phenoxybenzamine (Dibenzyline)

+++ - +++ -

a-Blockers (a1-selective)

Doxazosin (Cardura), Terazosin

(Hytrin), Prazosin (Minipress)

+ - - -

ß-Blockers

Atenolol (Tenormin), Metoprolol (Lopressor),

Propranolol (Inderal), Labetolol (Normadyne)*

+ + + +

Calcium channel antagonists

Nifedipine (Procardia), Amlodipine (Norvasc),

Diltiazem (Cardizem), Verapamil

+ + - -

Vasodilators

Hydralazine (Apresoline), Isosorbide

(Isordil, Dilatrate), Minoxidil (Loniten)

+ - unknown unknown

Monoamine oxidase inhibitors

Phenelzine (Nardil), tranylcypromine

(Parnate), Selegiline (Eldepryl)

- - +++ +++

Sympathomimetics

Ephedrine, Pseudoephedrine (Sudafed),

Amphetamines, Albuterol (Proventil)

++ ++ ++ ++

Stimulants

Caffeine (coffee*, tea), Nicotine

(tobacco), Theophylline

++ ++ unknown unknown

Miscellaneous

Levodopa, Carbidopa (Sinemet)* ++ - unknown unknown

Cocaine ++ ++ unknown unknown

Phaeochromocytoma:09 August 201004:21 PM

Adrenal Funtion

Primary aldosteronism (PA) is a group of disordersin which aldosterone production is inappropriatelyhigh, relatively autonomous, and non-suppressibleby sodium loading.Primary aldosteronism caused by adrenal adenoma, adrenal hyperplasia and glucocorticoid remediable aldosteronism

Aldosterone : renin ratio is gold standard screening testFour testing procedures (oral sodium loading, salineinfusion, fludrocortisone suppression, and captoprilchallenge) are in common use, and there is currentlyinsufficient direct evidence to recommend one overthe others.

Hyperaldosteronism:09 August 201004:42 PM

Adrenal Funtion

Adrenal Funtion

Figure 1. Clinical spectrum of steroid 21-hydroxylase deficiency

(from New MI, Dupont B Grumbach K, Levine LS. In: Stanbury JB, Wyngaarden JB. et al, eds. The Metabolic Basis of Inherited Disease, 5th ed. New York: McGraw-Hill, 1983:973-1000 with

permission).

Table 1. Clinical and Biochemical Features of Various Disorders of

Adrenal Steroidogenesis

Deficiency (Adrenal Disorder) Genital Ambiguity

Postnatal

Virilization

Diagnostic

Hormones

Treatment

I. 21-Hydroxylase

A. Classic

1. Salt wasting (SW)b F Yes 17OHP

4-A

Aldosterone

HC, 10-15 mg/m2/day orally (PO), and 9FF,

0.05 - 0.2 mg/day PO

2. Simple virilizing (SV) F Yes 17-OHP,

4-A

HC (same);

addition of 9aFF (same) if

renin

B. Nonclassic (symptomatic and

asymptomatic)

No Yes 17-OHP,

4-A

HC, 10-15

mg/m2/ day or dex, 0.25-0.5 mg/day h.s.,

or prednisone 5-10 mg/day

II. 3-Hydroxysteroid dehydrogenaseb

A. Classic M Yes 17-OHP HC and 9FF

Pts with ambiguous genitalia and 46XX karyotype•Apparent cryptorchid males•Infants present with shock hypoglycaemia and chemical findings compatible with CAH

•

Males and females with signs of virilisation before puberty•

Who to test:

Congenital Adrenal Hyperplasia09 August 201005:09 PM

Adrenal Funtion

A. Classic M(±F)

Yes 17-OHP

5 17-

OHPDHEA

4-A

HC and 9FF

as for SW 21-OHD

B. Nonclassic No Yes 17-OHPDHEA

HC as for

nonclassic 21-OHD

III. 11ß-Hydroxylase

A. Classic (hypertensive CAH) F Yes DOCS

4-A

PRA

HC, 10-15

mg/m2/day

B. Nonclassic No Yes SDOC

HC, dex, or prednisone as

for nonclassical

21-OHD

III. 17-Hydroxylase/ 17,20-lyase M No DOCB

HC, 10-15

mg/m2/daya

IV. Steroidogenic acute regulatory protein (StAR; congenital lipoid hyperplasia)b

M No None HC, 10-15 mg/m2/ day

9FF, 0.05-0.2

mg/daya

17-OHP: 17-Hydroxyprogesterone; 4-A:

4-Androstenedione; B: Corticosterone; S:

11-Deoxycortisol; DOC: Deoxycorticosterone; DHEA: Dehydroepiandrosterone; HC:

Hydrocortisone; 5 17-OHP: 17-

hydroxypregnenolone; 9FF:

fludrocortisone acetate; dex: dexamethasone; PRA: Plasma renin

activitya With addition of sex steroidreplacement

at puberty;b Salt wasting is a risk

17OH Progesterone levels > 242nmol/l in a random sample is diagnosistic of 21-Hydroxylase deficiency

•

If doubt use 250µg Synacthen test (gold standard in non classical CAH)Measure 17OH Progesterone at baseline and at 60 mins. Levels >45 nmol/l diagnostic of 21-Hydroxlase deficiency

•

Diagnosis of Classical CAH

Adrenal Funtion

Adrenal Funtion

Polycystic Ovarian Syndrome:09 August 201011:39 AM

Ovarian Function

Figure 7. Pathophysiologic mechanisms associated with PCOS that may help

Ovarian Function

Figure 7. Pathophysiologic mechanisms associated with PCOS that may help explain the chronic anovulation.

Ovarian Function

Primary and Secondary Amenorrhoea10 August 201009:53 PM

Ovarian Function

Alterations in SHBG10 August 201009:54 PM

Ovarian Function

Who to Test

Hirsutism Evaluation10 August 201010:30 PM

Ovarian Function

Ovarian Function

Primary and Secondary Hypogonadism09 August 201011:39 AM

Testicular Function

Testicular Function

Gynaecomastia Investigation10 August 201009:54 PM

Testicular Function

Table 2. Drugs that induce gynecomastia by known mechanisms

Estrogen-

like, or binds to estrogen

receptor

Stimulate

estrogen synthesis

Supply

aromatizable estrogen precursors

Direct

Testicular Damage

Block

testosterone synthesis

Block

androgen action

Displace

estrogen from SHBG

Estrogen

vaginal cream

Gonadotro

pins

Exogenous

androgen

Busulfan Ketoconazo

le

Flutamide Spironolact

one

Estrogen-

containing embalming cream

Growth

Hormone

Androgen

precursors (ie androstene

dione and DHEA)

Nitrosurea Spironolact

one

Bicalutami

de

Ethanol

Delousing

powder

Vincristine Metronidaz

ole

Finasteride

Digitalis Ethanol Etomidate Cyproteron

e

Clomiphen

e

Zanoterone

Marijuana Cimetidine

Ranitidine

Testicular Function

Ranitidine

Spironolact

one

Table 3. Drugs that cause gynecomastia by uncertain mechanisms:

Calcium channel blockers (verapamil, nifedipine, diltiazem) 1.ACE Inhibitors (captopril, enalapril) 2.b blockers 3.Amiodarone 4.Methyldopa 5.Reserpine 6.Nitrates 7.

Cardiac and antihypertensive medications:

Neuroleptics 1.Diazepam 2.Phenytoin 3.Tricyclic antidepressants 4.Haloperidol 5.

Psychoactive drugs:

Indinavir 1.Isoniazid 2.Ethionamide 3.Griseofulvin 4.

Drugs for infectious diseases:

Amphetamines 1.Drugs of Abuse:

Theophylline 1.Omeprazole 2.Auranofin 3.Diethylpropion 4.Domperidone 5.Penicillamine 6.Sulindac 7.Heparin 8.

Others:

Testicular Function

Ambiguous Genitalia Workup Algorithm09 August 201011:40 AM

Ambiguous Genetalia

Ambiguous Genetalia

Hypoglycaemia Workup09 August 201011:43 AM

Pancreatic Function

Pancreatic Function

2010 ADA Diagnostic Criteria

Diabetes Diagnosis10 August 201010:51 PM

Pancreatic Function

Diabetesguidelines ...

Pancreatic Function

Table 3. Diagnostic tests of cardiovascular autonomic neuropathy

TEST METHOD/ PARAMETERS

Resting heart rateBeat-to-beat heart rate

Variation*

>100 beats/min is abnormal.With the patient at rest and

supine (no overnight coffee or hypoglycemic episodes), breathing 6 breaths/min, heart rate monitored by EKG or

ANSCORE device, a difference in heart rate of >15 beats/min is

normal and <10 beats/min is abnormal, R-R inspiration/R-R expiration >1.17. All indices of HRV are age-dependent**.

Heart rate response to Standing* During continuous EKG monitoring, the R-R interval is measured at beats 15 and 30 after standing. Normally, a

tachycardia is followed by reflex bradycardia. The 30:15 ratio is normally >1.03.

Heart rate response to Valsalva maneuver* The subject forcibly exhales into the mouthpiece of a

manometer to 40 mmHg for 15 s during EKG monitoring. Healthy subjects develop tachycardia and peripheral

vasoconstriction during strain and an overshoot bradycardia

and rise in blood pressure with release. The ratio of longest R-R shortest R-R should be >1.2.

Systolic blood pressure response to standing Systolic blood pressure is measured in the supine subject. The

patient stands and the systolic blood pressure is measured after 2 min. Normal response is a fall of <10 mmHg, borderline is a fall of 10-29 mmHg, and abnormal is a fall of >30 mmHg

with symptoms.

Diastolic blood pressure response to isometric exercise

The subject squeezes a handgrip dynamometer to establish a maximum. Grip is then squeezed at 30% maximum for 5 min.

The normal response for diastolic blood pressure is a rise of >16 mmHg in the other arm.

EKG QT/QTc intervalsSpectral analysis

The QTc (corrected QT intevval on EKG) should be <440 ms.VLF peak

(sympathetic dysfunction)LF peak

(sympathetic dysfunction)HF peak

(parasympathetic dysfunction)LH/HF ratio

(sympathetic imbalance)

Neurovascular flow Using noninvasive laser Doppler measures of peripheral

sympathetic responses to nociception.

* These can now be performed quickly (<15 min) in

the practitioners' office, with a central reference laboratory providing quality control and normative

values. VLF,LF, HF =low, very low and high frequency

peaks on spectral analysis. These are now readily available in most cardiologist's practice.

** Lowest normal value of E/I ratio: Age 20-24:1.17,

25-29:1.15, 30-34:1.13, 35-30:1.12, 40-44:1.10, 45-49:1.08, 50-54:1.07, 55-59:1.06, 60-64:1.04,

65-69:1.03, 70-75:1.02 .

Cardiovascular Autonomic Function Tests09 August 201002:58 PM

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