Cushings Testing

09 August 2010
11:38 AM

Cushings:

Screening tests:

Screening: 2/3 screening test positive

Confirmatory testing
Localisation testing

24 Hour Urine Collection: two samples measuring urine free cortisol

levels > 2x Upper limit of normal considered positive
confounders (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 measured
suppression below 50nmol/l considered normal
false 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 it
Bld drawn at -15min and 0mins for ACTH and cortisol. Pt given 1g/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 1g/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

Pituitary Function Testing Page 1

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 1g/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)

Pituitary Function Testing Page 2

Acromegaly:
09 August 2010
01:51 PM

Growth Hormone Suppression Test:

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

IGF -1:
Single blood test, Long half life, elevated level also confirm
diagnosis
But 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, 60mins
Normal 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 tumour
Often pancreatic source

Cure in Acromegaly:
Controlled acromegaly : suppressed GH levels during OGT and Normal IGF1 3-6/12 post neurosurgery
Pts on Somatostatin therapy random IGF1 and GH are sufficient for assessment
Discordant results: 30% of pts will have discordance between GH and IGF levels
mostly N GH with elevated IGF1
NOTE patients on Pegvisomant ==> monitor IGF1 levels only

Pituitary Function Testing Page 3

Prolactinoma
09 August 2010
02:33 PM

No provocative testing
Generally level corresponds to tumour size
Levels > 200 ng/ml ==> Macroadenoma
Levels< 100 ng/ml ==> microadenoma
Levels 100 - 200 ng/ml grey zone, could be either.
Note that levels > 100 unlikely to be stalk effect, interfering
Drugs or physiologcal But may be falsely low due to

Pituitary Function Testing Page 4

Pituitary Function Testing Page 5

Growth Hormone Deficiency

09 August 2010
02:57 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:

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):
1. height >2.25 SD below the mean for age or >2 SD
below the midparental height percentile;
2. growth velocity <25th percentile for bone age:
3. bone age >2 SD below the mean for age;
4. low serum insulin-like growth factor 1 (IGF-1) and/or
insulin-like growth factor binding protein 3 (IGFBP3);
5. other clinical features suggestive of GH deficiency.
Key elements that may indicate GH deficiency are:
1. Height more than 2 SD below the mean.
2. Neonatal hypoglycemia, microphallus, prolonged
jaundice, or traumatic delivery.
3. Although not required, a peak GH concentration after
provocative GH testing of less than 10 ng/ml.
4. Consanguinity and/or a family member with GH
deficiency.
5. Midline CNS defects, pituitary hypo- or aplasia,
pituitary stalk agenesis, empty sella, ectopic
posterior pituitary (bright spot) on MRI.
6. Deficiency of other pituitary hormones: TSH, PRL,
LH/FSH and/or ACTH deficiency.

Biochemical evaluation of GH deficiency:

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:
1. 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.
2. 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.
3. 24-hour or Overnight GH sampling: Blood sampling at frequent
intervals designed to quantify physiologic bursts of GH secretion.
4. 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).

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:
Pituitary Function Testing Page 6

 Insulin Hypoglycaemia test:

overnight fast, risk of seizure, need experienced personell, normal glucose at begin of test
Requirements: 10-25% dextrose infusion available, IV infusion with N/S at beginning, constant supervision, no Hx of hypoglycaemic seizures
Regular 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 mins
Glucose 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 mins
Oral 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)

Pituitary Function Testing Page 7

Diabetes Insipidus
10 August 2010
11:21 PM

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

Disorders of Water intake and Output

Polydypsia

1.
2.
3.

Hypothalamic Disease e.g. sarcoid

Drugs thiazides, chlorpromazine, anticholinergics

Vasopressin Deficiency

1.
2.

Psychogenic

Central DI
Drug inhibition of AVP ( opiate antagonists)

Nephrogenic DI

1.
2.

Congenital
Aquired
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

Prior to Water Deprivation testing, exclude treatable aquired causes of nephrogenic DI:
Hypokalaemia
Hypercalcaemia
Drugs: 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

Causes of Central DI

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

Pituitary Function Testing Page 8

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.

Inherited causes of Nephrogenic DI

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

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

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.

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

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 test
can 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.

Phase II: Once dehydration is achieved DDAVP (desmopressin) is given IM/IV (1g) or intra-nasally (10-20g) 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 DDAVPs renal actions can result in severe fluid
overload and reciprocal hyponatraemia.

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

Target Cutoff values for Dx of DI during water deprivation Testing

Initial S-Osm
Phase I

Final S-Na

Final S-Osm

U-Osm

% weight change

< 295 mOsm/kg 145 mmol/l 300 mOsm/kg < 650mOSM/kg 3%

plateau for >3hr

Phase 11 /

//

650 mOsm/kg

Pituitary Function Testing Page 9

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 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.

Pituitary Function Testing Page 10

GSH Chemical Pathology

Water Deprivation Test
Patient
sticker
Referring Dr
Date
Phase 1
Baseline 1hr

2hr

3hr

4hr

5hr

Phase 2
6hr

7hr

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

Pituitary Function Testing Page 11

8hr

30 min 60 min 90 min 120 min

Hypocortisolism
09 August 2010
11:39 AM

Synachten stimulation test:

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

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

Pituitary Evaluation:
Various tests available. Theory ==> in absence of regular stimulation by ACTH, adrenals atrophy so N
response to ACTH severely blunted
1g 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/l
True 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 Pituitary
30mg/kg Metyrapone given orally at midnight
measure 11 deoxycortisol level at 8am
Rise to > 0.2nmol/l (7g/dl) considered normal
Useful in borderline cases where ACTH stimulation equivocal
CRH Stimulation test:
CRH (ovine) given at 1g/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 levels
Secondary adrenal insufficiency: Absent ACTH response with
Tertiary (hypothalamic disease) Delayed peak in ACTH
but overlap in acth response of N pts with pts with secondary adrenal insufficiency

Adrenal Funtion Page 12

Phaeochromocytoma:
09 August 2010
04:21 PM

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
Catechola
mines

Metaneph
rines

NE

NMN

MN

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

+++

+++

a-Blockers (non-selective)
Phenoxybenzamine (Dibenzyline)

+++

+++

a-Blockers (a1-selective)
Doxazosin (Cardura), Terazosin
(Hytrin), Prazosin (Minipress)

-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

unknow
n

Monoamine oxidase inhibitors

Phenelzine (Nardil), tranylcypromine
(Parnate), Selegiline (Eldepryl)

+++

+++

Sympathomimetics
Ephedrine, Pseudoephedrine (Sudafed),
Amphetamines, Albuterol (Proventil)

++

++

++

++

Stimulants
Caffeine (coffee*, tea), Nicotine
(tobacco), Theophylline

++

++

unknown

unknow
n

Levodopa, Carbidopa (Sinemet)*

++

unknown

unknow
n

Cocaine

++

++

unknown

unknow
n

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).

Miscellaneous

Adrenal Funtion Page 13

Hyperaldosteronism:
09 August 2010
04:42 PM

Primary aldosteronism (PA) is a group of disorders

in which aldosterone production is inappropriately
high, relatively autonomous, and non-suppressible
by sodium loading.
Primary aldosteronism caused by adrenal adenoma,
adrenal hyperplasia and glucocorticoid remediable
aldosteronism

Adrenal Funtion Page 14

Aldosterone : renin ratio is gold standard screening test

Four testing procedures (oral sodium loading, saline
infusion, fludrocortisone suppression, and captopril
challenge) are in common use, and there is currently
insufficient direct evidence to recommend one over
the others.

Adrenal Funtion Page 15

Adrenal Funtion Page 16

Congenital Adrenal Hyperplasia

09 August 2010
05:09 PM

Who to test:
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

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 Postnat Diagno

Ambig
al
stic
uity
Virilizat Hormo
ion
nes

Treatment

I. 21-Hydroxylase
A. Classic
1. Salt wasting (SW)b

Yes

17OHP
4-A
Aldoster
one

HC, 10-15
mg/m2/day
orally (PO),
and 9FF,
0.05 - 0.2
mg/day PO

2. Simple virilizing (SV)

Yes

17-OHP,
4-A

HC (same);
addition of
9aFF (same) if

renin
B. Nonclassic (symptomatic and
asymptomatic)

No

Yes

17-OHP,
HC, 10-15
mg/m2/ day or
4-A
dex, 0.25-0.5
mg/day h.s.,
or prednisone
5-10 mg/day

Yes

17-OHP

II. 3-Hydroxysteroid dehydrogenaseb

A. Classic

Adrenal Funtion Page 17

HC and 9FF

A. Classic

M
(F)

Yes

17-OHP
5 17OHP
DHEA
4-A

HC and 9FF
as for SW 21OHD

B. Nonclassic

No

Yes

17-OHP
HC as for
DHEA
nonclassic 21OHD

A. Classic (hypertensive CAH)

Yes

DOC
S
4-A
PRA

HC, 10-15
mg/m2/day

B. Nonclassic

No

Yes

S
DOC

HC, dex, or
prednisone as
for
nonclassical
21-OHD

III. 17-Hydroxylase/ 17,20-lyase

No

DOC
B

HC, 10-15
mg/m2/daya

IV. Steroidogenic acute regulatory protein

(StAR; congenital lipoid hyperplasia)b

No

None

HC, 10-15
mg/m2/ day
9FF,
0.05-0.2
mg/daya

III. 11-Hydroxylase

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

4-Androstenedione; B: Corticosterone; S:
11-Deoxycortisol; DOC:
Deoxycorticosterone; DHEA:
Dehydroepiandrosterone; HC:
Hydrocortisone; 5 17-OHP: 17hydroxypregnenolone; 9FF:
fludrocortisone acetate; dex:
dexamethasone; PRA: Plasma renin
activity
a With addition of sex steroidreplacement
at puberty;
b Salt wasting is a risk

Diagnosis of Classical CAH

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

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

Adrenal Funtion Page 18

Adrenal Funtion Page 19

Polycystic Ovarian Syndrome:

09 August 2010
11:39 AM

Ovarian Function Page 20

Figure 7. Pathophysiologic mechanisms associated with PCOS that may help

Ovarian Function Page 21

Figure 7. Pathophysiologic mechanisms associated with PCOS that may help

explain the chronic anovulation.

Ovarian Function Page 22

Primary and Secondary Amenorrhoea

10 August 2010
09:53 PM

Ovarian Function Page 23

Alterations in SHBG
10 August 2010
09:54 PM

Ovarian Function Page 24

Hirsutism Evaluation
10 August 2010
10:30 PM

Who to Test

Ovarian Function Page 25

Ovarian Function Page 26

Primary and Secondary Hypogonadism

09 August 2010
11:39 AM

Testicular Function Page 27

Testicular Function Page 28

Gynaecomastia Investigation
10 August 2010
09:54 PM

Testicular Function Page 29

Table 2. Drugs that induce gynecomastia by known mechanisms

Estrogenlike, or
binds to
estrogen
receptor

Stimulate
estrogen
synthesis

Supply
Direct
aromatizab Testicular
le estrogen Damage
precursors

Block
Block
testosteron androgen
e synthesis action

Displace
estrogen
from SHBG

Estrogen
vaginal
cream

Gonadotro
pins

Exogenous Busulfan
androgen

Ketoconazo Flutamide
le

Spironolact
one

Androgen
Nitrosurea
precursors
(ie
androstene
dione and
DHEA)

Spironolact Bicalutami
one
de

Ethanol

Delousing
powder

Vincristine

Metronidaz Finasteride
ole

Digitalis

Ethanol

Etomidate

Estrogen- Growth
containing Hormone
embalming
cream

Cyproteron
e

Clomiphen
e

Zanoterone

Marijuana

Cimetidine
Ranitidine
Testicular Function Page 30

Ranitidine
Spironolact
one
Table 3. Drugs that cause gynecomastia by uncertain mechanisms:
Cardiac and antihypertensive medications:
1. Calcium channel blockers (verapamil, nifedipine, diltiazem)
2. ACE Inhibitors (captopril, enalapril)
3. b blockers
4. Amiodarone
5. Methyldopa
6. Reserpine
7. Nitrates
Psychoactive drugs:
1. Neuroleptics
2. Diazepam
3. Phenytoin
4. Tricyclic antidepressants
5. Haloperidol
Drugs for infectious diseases:
1. Indinavir
2. Isoniazid
3. Ethionamide
4. Griseofulvin
Drugs of Abuse:
1. Amphetamines
Others:
1. Theophylline
2. Omeprazole
3. Auranofin
4. Diethylpropion
5. Domperidone
6. Penicillamine
7. Sulindac
8. Heparin

Testicular Function Page 31

Ambiguous Genitalia Workup Algorithm

09 August 2010
11:40 AM

Ambiguous Genetalia Page 32

Ambiguous Genetalia Page 33

Hypoglycaemia Workup
09 August 2010
11:43 AM

Pancreatic Function Page 34

Pancreatic Function Page 35

Diabetes Diagnosis
10 August 2010
10:51 PM

2010 ADA Diagnostic Criteria

Pancreatic Function Page 36

Diabetes
guidelines ...

Pancreatic Function Page 37

Cardiovascular Autonomic Function Tests

09 August 2010
02:58 PM

Table 3. Diagnostic tests of cardiovascular

autonomic neuropathy
TEST

METHOD/ PARAMETERS

Resting heart rate

Beat-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 RR 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 intervals

Spectral 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
* 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 .

Autonomic Function Page 38

Using noninvasive laser Doppler measures of peripheral

sympathetic responses to nociception.