Notes of Castillo & Operario (BMLS – 4A)

CLINICAL CHEMISTRY 3 FINALS

ADRENAL CORTEX
**review ADRENAL GLAND from adrenal medulla Adrenal Classification Major
− Structurally and functionally, they are two Cortex Hormone/s
glands in one:
Zona Mineralocorticoids Aldosterone
● Adrenal Cortex ( 80-90%) Glomerulosa
↳ glandular tissue derived from
embryonic mesoderm (mesenchymal) Zona Glucocorticoids Cortisol
Fasciculata
↳ located near the urogenital ridge Corticosterone
↳ appears yellow on gross sectioning
Zona Gonadocorticoids Dehydroepiandroste-
● Adrenal Medulla (10- 20%) Reticularis Androgens rone Sulfate (DHEAS)
↳ formed from neural ectoderm, can
Dehydroepiandrostene-
be considered a modified sympathetic
dione
ganglion (DHEA)
↳ appears dark mahogany on gross
sectioning

ADRENAL CORTEX
− Synthesizes and releases steroid
hormones (corticosteroids)
− Different corticosteroids are produced
in each of the three layers: (outermost **under certain pathologic & physiologic conditions, these
distinctions become blurred
to the innermost)
**CRH stimulates to release Corticotropin/ACTH
● Zona glomerulosa **Cortisol (hydrocortisone) is the main human endogenous GC
● Zona fasciculate and is secreted primarily in response to adrenocorticotropic
hormone (ACTH).
● Zona reticularis **Primary Mechanism (Aldosterone): RAAS (REVIEW)
Secretion of ACTH:
1. Action of corticotropin-releasing hormone (CRH) on
cells of the adrenal cortex.
2. CRH binds to membrane receptors (R), which are
coupled to adenylate cyclase (AC) by stimulatory G
proteins (Gs).
3. Adenylate cyclase is stimulated and cAMP rises in the
cell.
● cAMP activates protein kinase A (PKA),
which then phosphorylates proteins (P-
Proteins) involved in stimulating ACTH
secretion and the expression of the POMC
**In the broadest terms, each zone is responsible for (proopiomelanocortin) gene.
4. The proteolytic processing of POMC occurs in the
secretory granules where it is split into several
hormones, ACTH (adrenocorticotropic hormone) and
Beta-LPH (Beta-lipotropin).
**POMC cleavage enzymes may be responsible for the formation
of rare forms of isolated ACTH deficiency
STEROID HORMONES

the synthesis and secretion of a unique set of

hormones:
Notes of Castillo & Operario (BMLS – 4A)
CLINICAL CHEMISTRY 3 FINALS

**Cholesterol is the parent compound for all steroid hormones SYNTHESIS

which are modified by enzymes
− Steroids are derivatives of cholesterol
Sources of Cholesterol: which are from the lipid droplets in
- Cholesterol can be made within the cell cortical cells (cholesterol esters in LDL)
from Acetyl CoA (de novo synthesis) − Adrenal parenchyma is responsible for
↳ to ensure that adrenal steroidogenesis accumulating and storing LDL’s from
remains normal in patients with variable lipid circulation
disorders − Removed cholesterol is replenished by
↳ And patients on lipid-lowering agents
cholesterol in LDL in blood or
Hydroxymethylglu Co
Acetyl CoA synthesized from acetate
taryl / HMG A − Steroid hormones are synthesized and
Cholestero Mevalonat
secreted on demand (not stored)
l e − First and rate-limiting step (syn. of all
- Is also taken up by the cell in the form
steroid hormones): conversion of
of Low-Density Lipoproteins
Esterifi cholesterol to pregnenolone by the
L Free
ed enzyme cholesterol desmolase
D Chole
Choles
LDL ↳ 6 carbons are removed from cholesterol by
L terol
Rece sterol mitochondrial membrane cytochrome P450
ptor (CYP450) enzyme
− Newly synthesized steroid hormones
are rapidly secreted from the cell
− Following secretion, all steroids bind to
some extent to plasma proteins:
○ CBG/Cortisol binding
globulin/Transcortin
○ Albumin
**MEMORIZE!!
 Notes of Castillo & Operario (BMLS – 4A)
CLINICAL CHEMISTRY 3 FINALS
Clinical & Biochemical Features

PHYSIOLOGICAL EFFECTS OF STEROIDS

Representative Biological Effects

Hormone

Cortisol ↑Protein Nitrogen catabolism

as a representative
glucocorticoid Gluconeogenesis **Familiarize defective gene and effects to adrenal
- ↑Blood glucose conc. hormone synthesis
- ↓Glucose tolerance **CYP11B1 – specific gene for glucocorticoids; refer to
- ↑Liver glycogen & glycogenolysis
previous diagram
- ↓Peripheral uptake & utilization of glucose
**Lipid hyperplasia – most severe; total absence of
↓Synthesis of acid-sulfated mucopolysaccharides hormone synthesis
**Although the may be present on some but they have
Fat synthesis & redistribution diff. genes involved
**mas delikado and Lipid Hyperplasia due to StAR
Cellular or tissue effects (without it the synthesis of making the steroid hormone
- Antiinflammatory would decrease or di na talaga siya present)
- Dissolution of lymphoid tissue
- Lymphopenia [ MINERALOCORTICOIDS ]
- Eosinopenia
- ↑Erythropoiesis - Synthesized in zona glomerulosa
- Alteration of cellular permeability, esp.
↓membrane permeability to water
↳low N:C ratio, small nuclei with dense
- ↑Gastric (HCl & Pepsin) secretion chromatin with intermediate lipid
Aldosterone Electrolyte Regulation
inclusions
as a representative - Sodium Retention - Regulate the electrolyte concentrations
mineralocorticoid - Potassium excretion
- Water retention & expansion of extracellular fluid of extracellular fluids
volume

↑Blood pressure
Aldosterone
- chief mineralocorticoid (most important)
Androgens Protein Nitrogen Anabolism • Maintains Na+ balance by
as representative - Growth & maturation―osseous & muscular
sex hormones reducing excretion of sodium from
Body Hair (pubic & axillary) the body
• Stimulates reabsorption of Na+ &
Congenital Adrenal Hyperplasia water by the kidneys (helps to
− Collectives diseases which depends on maintain BP & tonicity) and K+
enzyme involved excretion
• Acid – Base homeostasis
Congenital Adrenal Hyperplasia:
- Secretion is stimulated by:
Notes of Castillo & Operario (BMLS – 4A)
CLINICAL CHEMISTRY 3 FINALS
• ↓blood volume/pressure ● Renin-angiotensin mechanism
(RAAS*) is the major stimulant - kidneys release renin, which is
• Low blood Na+ converted into angiotensin II
• Rising blood levels of K+ that in turn stimulates
• ACTH aldosterone release
• ANP ● Plasma concentration of sodium and
- Expression of Aldosterone potassium
- directly influences the zona
Synthetase/CYP11B2 (site specific) =
glomerulosa cells
syn. of aldosterone & its intermediary
● ACTH
18-hydroxylated metabolites (restricted - causes small increases of
to the zona. glomerulosa) aldosterone during stress
- Precursor molecules (similarly possess
● Atrial natriuretic peptide (ANP)
mineralocorticoid activity):
- inhibits activity of the zona
• 11-deoxycorticosterone/DOC
glomerulosa (↓ aldosterone =
• 11-deoxycortisol
↳ unlike aldosterone, they can be synthesized within
↑ ANP)
zona fasciculata, as well as in the zona glomerulosa,
which explains the hypertension & electrolyte
disturbances seen in some forms of congenital adrenal
hyperplasia
- Responds to acute changes in ACTH but
is mainly under control of the RAAS

- Cortisol is the key glucocorticoid,

○ regulating its own secretion
through neg. feedback on the
hypothalamic-pituitary-adrenal
axis***
○ needed in times of stress to
maintain BP & Blood Sugar, and
to prevent shock
- Both CRH & AVP/ADH are produced by
the parvocellular neurons of the
paraventricular nuclei (hypothalamus)
- ACTH secretion is stimulated by CRH &
AVP (lesser extent) which in turn ACTIONS OF ALDOSTERONE
stimulates the cortisol production by - Stimulates sodium reabsorption by
the adrenals distal tubule and collecting duct of the
- Corticosterone, most important
nephron and promotes potassium and
glucocorticoid, also possesses
hydrogen ion excretion
glucocorticoid activity
*Primary Mechanism; REVIEW siya ulit from CC2 / AUBF o Increases transcription of Na/K
**Glucocorticoids are 21-carvin steroid compounds with a
hydroxyl group on carbon 17, hence 17-
pump
Hydroxycorticosteroids/17-OHCS o Increases the expression of
***In result, inhibits ACTH release from the pituitary & CRH from apical Na channels and an
the hypothalamus
****Androgens (18-carbon steroids with saturated A rings) & Na/K/Cl cotransporter
Estrogens (17-carbon steroids with unsaturated A rings) are - Expands ECF volume
produced by the zona reticularis
MECHANISMS OF ALDOSTERONE SECRETION
Notes of Castillo & Operario (BMLS – 4A)
CLINICAL CHEMISTRY 3 FINALS

**TPR; total peripheral resistance

ALDOSTERONE ROLE IN DISEASES

- Complete failure to secrete aldosterone
leads to death (dehydration, low blood
volume)
- Hyperaldosterone states: Contribute to
hypertension associated with increased
blood volume

OVERPRODUCTION OF ALDOSTERONE
- primary causes, ie. Conn’s syndrome
↳ adenoma, nodular hyperplasia of zona
glomerulosa
- secondary
↳ cirrhosis, ascites, nephrotic syndrome
↳ origin may be from liver or kidneys
rather than from pituitary gland
- Signs & Symptoms:
○ headache
○ hypokalemia causing muscle
Dehydration, Sodium weakness
Deficient, or ○ hypernatremia
Hemorrhage ○ hypervolemia
↓ Blood
○ nocturnal polyuria
Volume
○ hand cramping
↓ Blood Pressure
CONN’S SYNDROME (1O HYPERALDOSTERONISM)
Juxtaglomerular
cells of kidneys Types:
Angiotensino ↑ - there is a unilateral adenoma (benign
gen Renin tumor) of the adrenal gland, causing a
↑ condition known as hyperaldosteronism
Angiotensin ○ 1 adrenal gland is defective
↑I - when both adrenal glands are making
AC
ACE*
E Angiotensin too much aldosterone, the condition is
*Angiotensin II
Vasoconstrict called bilateral adrenal hyperplasia
Converting
Enzyme ion of ○ 2 adrenal glands are defective
Arterioles
Notes of Castillo & Operario (BMLS – 4A)
CLINICAL CHEMISTRY 3 FINALS
UPRIGHT PA/PRA RATIO
- Treatment:
○ surgical for adenoma (for
unilateral only)
○ medical for hyperplasia with
Spironolactone (both uni and
bilateral)
DIAGNOSIS OF PRIMARY ALDOSTERONISM
- 25% HTN patients have ↓ renin
- Criteria :
● Plasma Aldosterone/Plasma
Renin Activity (PA/PRA) greater
than 25
● Low plasma renin that fails to
increase with volume depletion
● High aldosterone that fails to
decrease with saline or
angiotensin inhibition
LABORATORY DIAGNOSIS
URINARY POTASSIUM EXCRETION
- Screening test for aldosteronism
- 24 hr urine
- In patients with HTN and unprovoked
hypokalemia
● 30 mEq/day =
CAPTOPRIL SUPPRESSION
hyperaldosteronism
● < 30 mEq/day = increased renal
K+ retention (diuretic or GI loss)
o accdg. to Henry's:
▪ >30mmol/24hrs
in face of
hypokalemia &
>15mg/ 24hrs
aldosterone =
localization of
underlying
pathology to
adrenal
- a.k.a. Plasma aldosterone
concentration/ plasma renin activity
(PAC/PRA)
- PAC expressed in ng/dL; PRA in
ng/mL/hour
- Preferred screening (secondary) test
- Patient must be in an upright position
○ any change of position could
alter the results
- In a fluid-deprived patient (overnight
dehydration increases PRA)
- Distinguishing primary aldosteronism
from other causes
- Performed after patient has remained
upright for at least 2 hrs
- Stop spironolactone & eplerenone
intake for 4-6 wks and other diuretics
for at least 2 wks prior to testing
- Hypokalemia should be corrected as
well prior to test and should not be on
sodium-restricted diet
- Diagnosis is only supported when both
PAC/PRA are elevated, since lower limit
for PRA values differ for every lab
- Validated immunometric assays are
preferred in measuring PRA
- PAC/PRA is highly dependent on renin
concentration; important to use assays
with sufficient sensitivity to lower limits
- Following volume expansion (2 liters of
normal saline over 4 hours) –
suppresses aldosterone
● > 25 – primary aldosteronism
Notes of Castillo & Operario (BMLS – 4A)
CLINICAL CHEMISTRY 3 FINALS
- establish/exclude presence of a
unilateral adenoma or bilateral
hyperplasia.

**not discussed during lesson but a good

screening test according to Bishop. So yeah.

- Confirmatory
- Collect baseline blood for PAC/PRA &
cortisol
- Treatment for hypertension
- Within 3 hours – 50 mg of captopril (1
mg/kg) ; oral administration
- Patient compliance, presence of
uncontrolled hypertension, renal
insufficiency, congestive heart failure &
local expertise are factors that test
depends on
● High Aldosterone –
aldosteronism
↳ PA/PRA >25 before and
after test **not necessarily memorize but familiarize, esp. Bartter’s
syndrome & Liddle’s syndrome.
↳ Accdg to Henry's: PAC=
remains elevated; PRA=
suppressed ACTH (Lab Diagnosis)
● Suppressed – with other forms ● Pulsatile fashion:
of HTN - 2:00 am – 4:00 am
● Diurnal variation:
18-HYDROXYCORTICOSTERONE - Highest (4:00 am – 8:00 am)
- Precursor hormone of aldosterone - Lowest (10:00 pm – 12 mn)
- Moderate sensitivity and specificity for ● Protein-rich meals
adenoma but not for hyperplasia
● > 100 ng/dL
○ aldosterone-producing [ GLUCOCORTICOIDS ]
adenoma (APA) - Synthesized in zona fasciculata
○ Idiopathic ○ Cords of clear cells with high
hyperaldosteronism N:C ratio & lipids laden with
“foamy” cytoplasm
ADRENAL IMAGING - Generate androgen precursors such as
• CT scan or MRI DHEA
- still the best confirmatory test
- Done once diagnosis for primary
hyperaldosteronism is confirmed

ADRENAL VEIN SAMPLING

Notes of Castillo & Operario (BMLS – 4A)
CLINICAL CHEMISTRY 3 FINALS
Cortisol ○ probably serving as a reservoir
- Only feedback regulator of ACTH – for free cortisol
stimulated hormone production of - Protein binding also may protect
adrenal cortex cortisol from deactivation by the liver or
- Influences pain perception and sense of filtration by the kidney
well-being
- Secretion is in response to ACTH, a CIRCULATING CORTISOL
diurnal rhythm, and stress
- ACTH 39 amino acids acid residues 90% bound to serum protein
- Most important factors for secretion:
10 - 20%:
○ CRH & AVP - Loosely bound to albumin
- Other stimulators: 80%-90%:
○ ANF - bound to the glycoprotein
○ Angiotensin II transcortin (cortisol-
binding globulin)
○ IL 6
○ IL 1 10% Unbound, free hormone
○ TNF alpha **According to Henry’s

● Maintain blood glucose by lipolysis,

gluconeogenesis, and glycogenolysis
● Most tissues are the target cells

- ↓cortisol production = ↑ ACTH & CRH

secretion in an attempt to stimulate cortisol
levels and lead to adrenal
hyperplasia/overproduction of androgens,
depending on affected enzyme
- Only hormone that inhibits the
secretion of ACTH

**GR: glucocorticoid receptor;

**HSP: heat shock proteins
- Inactive receptor and ligand accessible;
**GRE: Glucocorticoid response element;
**Coactivator complex: unable to bind on gene itself
**AP-1: Activator protein 1
- Synthesizes mediators of inflammations
such as prostaglandins
- Involved in the transcriptional control of
many inflammatory mediators
- Functions of AP-1 as a regulator of cytokine
expression and an important modulator in
inflammatory diseases such as rheumatoid
arthritis, psoriasis and psoriatic arthritis.
**cortisol binds to GR to inactivate AP-1
**Corticoid receptor coactivator needs to be binded
with the complex in order to transcript
- Believed that only free cortisol is active,
and that the protein-bound fraction is
metabolically inert
Notes of Castillo & Operario (BMLS – 4A)
CLINICAL CHEMISTRY 3 FINALS
DISEASES ASSOCIATED
GR transrepression ADRENAL INSUFFICIENCY
- Anti-inflammatory effect
GR transactivation Addison’s Disease
- In relation to metabolic effect - Primary disease
- Destruction of 90% of the adrenal
Metabolic response to fasting: cortex
○ Low baseline cortisol levels: 8:00
- Gluconeogenesis from amino acids
AM, Supine
(increased expression of the enzymes)
- Secondary to ACTH deficiency
- Mobilization of stored fat and its use in
○ abnormality at the Hypothalamic-
β-oxidation and the production of ketone
Pituitary level (HPA)
bodies - Vague and misleading symptoms
ANTI-INFLAMMATORY EFFECTS resembling failure to thrive:
○ Weakness
- Glucocorticoids are used to alleviate ○ Anorexia
inflammation ○ Nausea
● Inhibit production of ○ Diarrhea
prostaglandins & leukotrienes ○ Abdominal pain accompanied by
(mediate inflammation) physical findings such as weight
● This occurs via stimulation of an loss
inhibitor of phospholipase A2, - Signs and Symptoms: (based on lecture)
which is needed for PG synthesis ○ Hyperpigmentation
- Glucocorticoids are used to alleviate ○ Weakness
○ Fatigue
inflammation
○ Anorexia
● Decrease the inflammation
○ Nausea
reaction by decreasing ○ Diarrhea
permeability of capillary ○ Weight loss
membranes, reducing swelling ○ Pain
● also reduce effects of histamine ○ Adrenal Calcification

FREQ. SYMPTOMS SIGNS

100% Weakness Weight Loss

Fatigue
Anorexia

90% Hyperpigmentation
(Primary hyposecretion)

50% Nausea
Diarrhea

10% Pain Adrenal Calcification

Primary Adrenal Insufficiency

CIRCADIAN RHYTHM OF CORTISOL SECRETION - 70% is due to Autoimmune adrenalitis

- Others:
○ Fungal infections
○ HIV
○ Tuberculosis
○ Bilateral adrenal hemorrhage
○ Adrenoleukodystrophy
○ Infiltrative processes

○ Metastasis
Secondary Adrenal Insufficiency
Notes of Castillo & Operario (BMLS – 4A)
CLINICAL CHEMISTRY 3 FINALS
● Tumors - most HPLC systems use reverse-
● Hemorrhage phase liquid chromatography with
● Infiltrative processes UV detection
● Developmental abnormalities - both highly sensitive & free from
● Malignancies many of the sources of
● Glucocorticoid therapy (most common) interference encountered in I.A.

TREATMENT Reference Values

Primary:
- synthetic steroids from G & R zone are
replaced
- G aldosterone:
○ Florinef (50-100 μg/day)
- F cortisol: (either)
○ Hydrocortisone (20-25 mg/day)
○ Prednisone (5 mg/day)
Secondary:
- hydrocortisone 300mg/day in divided doses
for significant stressors (ex. Surgery)
5-25 μg/dL (140-690 mmol/L) at 8-10 AM
3-12 μg/dL (80-330 mmol/L) by 4pm (dropped)
**Because of wide swings in basal cortisol resulting from its
diurnal & ultradian pattern of secretion, serum cortisol assays are
most useful when evaluated in the context of dynamic
manipulation (i.e., adrenal stimulation or suppression)
BASAL CORTISOL LEVEL
- Baseline Cortisol:
○ 8:00-9:00 am, supine
- Diagnosing feature:
○ <3μg/ dL (83 nmol/L)

LABORATORY TESTS RANDOM CORTISOL

● Baseline Cortisol - Diagnosing feature of Addison’s:
● ACTH ○ <10 μg/dL

● Cosyntropin Administration - Only useful when elevated (>20μg/dL)

SERUM CORTISOL LEVEL PLASMA ACTH

● Fluorometric Assay
- One of the earliest and simplest
methods used
- Developed by Nelson & Samuels
- Based on a technique first
developed by Porter & Silber
● Radioimmunoassay &
Chemiluminiscent Assay
● HPLC with Tandem Mass Spectrometry
- Two site immunoradiometric Assay
- Immunochemiluminometric assay
- Prechilled EDTA lavender top
and kept in an ice bath
- Normal range:
○ 2-12 pmol/L (9-52 pg/mL)
○ between 7 am to 10 am [peak]
Notes of Castillo & Operario (BMLS – 4A)
CLINICAL CHEMISTRY 3 FINALS
ACTH STIMULATION TEST
- Anytime of the day
- Baseline serum cortisol + administering
250 μg Cosyntropin (synthetic
stimulator of aldosterone & cortisol
secretion
- After 30 and 60 minutes collect serum
for cortisol quantitation
- Normal response: >18-20μg/dL at either
time point
- <18 μg/dL = impaired secretion in
adrenal cortex
OVERNIGHT METYRAPONE TEST
- Alternate diagnostic / confirmatory test
for central causes of adrenal
insufficiency
- Inhibits 11-β-hydroxylase
- Preventing the conversion of
11-deoxycortisol to cortisol
- 30 mg/kg orally at midnight
- Blood cortisol and 11-deoxycortisol
(8:00 AM)
- Normal: 11-deoxycortisol → 7 μg/dL
(200 nmol/L)
- Abnormal: <7μg/dL 11-deoxycortisol
- If suspected with central cause of
adrenal insufficiency, px should be
screened via MRI
CRH TEST
- Baseline ACTH and Cortisol
- IV 100μg oCRH ( ovine CRH)
- Collect blood every 15 minutes for 60-
90 minutes
- Normal response: cortisol >20 μg/dL
- Peak: 30-40 minutes post- injection
- Adrenal Insufficiency due to
hypothalamus: <20μg/dL (↓because it
is unaffected by ACTH cortisol)
HYPERCORTISOLISM
excess cortisol affects multiple mechanisms...
● Immune (suppression, poor healing)
● dermatologic (thin, friable tissue, wide
purple striae)
● vascular (vessel fragility, ecchymosis)
● adipose ( increase fat with distribution to
upper back and central area)
● muscle (wasting, proximal muscle
weakness, heart failure)
● bone (loss)
● neurologic (peripheral neuropathy,
autonomic dysregulation)
● renal (edema, HTN, calciuria)
● metabolic (hyperglycemia & insulin
resistance)
Cushing’s Syndrome
- A group of clinical and metabolic
disorders characterized by
adrenocortical hyperfunction
- Excess production of glucocorticoids
and androgens
- Signs:
● Fat is deposited in the body
trunk (central obesity)
● Buffalo hump
● Moon facies (subcutaneous fat
in cheeks and submandibular)
● purple striae
● ↑ Blood- glucose level (adrenal
diabetes)
● May cause death of beta cells
- Is a state of glucocorticoid excess
resulting from an ACTH- secreting
pituitary adenoma
- Most common cause = iatrogenic in
origin
- However, may be due to ectopic
production of CRH or ACTH by a tumor
or due to a primary adrenal malignancy
- COMMON CAUSE (from Bishop’s):
● 68%: ACTH secreting pituitary
adenoma
● 17%: autonomous cortisol production
from an adrenal tumor
● 15%: Ectopic(excess) ACTH or CRH
production (usually malignant)
DIAGNOSIS
URINE FREE CORTISOL
- Sensitive indicator for endogenous
cortisolism
- Common test
- When serum cortisol exceeds the
capacity of its carrier protein binding,
free cortisol levels rise rapidly,
Notes of Castillo & Operario (BMLS – 4A)
CLINICAL CHEMISTRY 3 FINALS
increasing the free cortisol filtered into Source/ Cause ACTH Cortisol
the urine
- Affected by hydration (3-5L/day) ACTH - Adrenal ↓ ↑
independent Cause <10pg/mL >25μg/dL
- patients drinking >5L/day will have 64% Cushing’s
Syndrome
increase in urine cortisol
ACTH - Pituitary/ ↑ ↑
URINE 17- HYDROXYCORTICOSTEROID (17- dependent Ectopic Source >10pg/mL >25μg/dL
Cushing’s
OHCS)
Syndrome
- 17 OHCS = metabolite of cortisol
- Excretion occurs at constant rate
- Not affected by volume changes

- Uncommon/ Not tested in lab

24-HOUR URINE CORTISOL
- 24 hr urine = best sample
- Measured by Tandem Mass
Spectroscopy
- Most sensitive (95-100%) and specific
(98%) for excess cortisol
- Collecting urine overnight (10 pm -
8am) factored by creatinine

- 24-47% of patients had at least 1

normal 24hr urine cortisol; hence,
patients with intermediate values
should be reevaluated 2-3 mos. Later.

DEXAMETHASONE SUPPRESSION TEST

- As cortisol substitute, suppressing ACTH
if the pituitary gland is not normal and
Cortisol secretion if adrenal gland is not
normal
- Common confirmatory test
- Overnight DST:
○ 1mg at 11 pm suppress the
early morning ACTH-stimulated
rise in cortisol
○ Suppressed free cortisol
(<3.6μg/dL) between 8-9 am =
NEGATIVE TEST
CRH STIMULATION TEST
- Helpful in distinguishing types of
Cushing's syndrome (central diseases vs
primary adrenal syndrome)
- 8:00 am - serum cortisol and ACTH level
is drawn following CRH injection
Androgens:
[ GONADOCORTICOIDS/ ANDROGENS ]
- Synthesized in zona reticularis
○ sharply demarcated with lipid-
deficient cords or irregular,
dense cells with lipofuchsin
deposits
○ DHEA and is sulfonated to
DHEAS by sulfotransferase
- Men:
○ <5% of testosterone of adrenal
origin
○ 95% from testes
- Women:
○ 40-65% of testosterone of adrenal
origin
○ almost all are converted to
estrogen
Notes of Castillo & Operario (BMLS – 4A)
CLINICAL CHEMISTRY 3 FINALS
● Androstenedione
● Testosterone
● 5-dihydrotestosterone (5-DHT)
● Androgens contribute to :
○ Onset of puberty
○ Appearance of secondary sex
characteristics
○ Sex drive

Estrogens:
● E1- ESTRONE :
- MENOPAUSAL women
***Andropause for Male
● E2 - ESTRADIOL :
- NON PREGNANT
● E3 - ESTROTIOL:
- PREGNANT

MALE SECONDARY SEX CHARACTERISTICS USUAL AGE RANGE

The testicles begin to enlarge, and the 10 - 13

scrotum turns darker and coarser

Pubic hair begins to grow 10 - 15

Body grows taller and heavier 10 - 16

Penis begins to grow longer and fuller

11 - 15
Voice begins to deepen

Boys become fertile (capable to ejaculate) 11 - 17

Hair begins to grow under the arms and on

the face
12 - 17
Glands in the skin & scalp begin to produce
more oil, which can cause skin blemishes

FEMALE SECONDARY SEX CHARACTERISTICS USUAL AGE RANGE

Breast begins to develop 7 - 13

Notes of Castillo & Operario (BMLS – 4A)
CLINICAL CHEMISTRY 3 FINALS
Pubic hair begins to grow 8 - 14 - decrease testes size

Vagina grows longer, & its outer lips (labia) 8- 15 Adrenal Androgens Excess in Females
become more pronounced
● Infertility
Body grows taller & heavier 9 - 14 ● Masculinizing effects
○ Hirsutism (excessive hair)
Menstruation begins 9 - 16
○ Acne
Hair begins to grow under the arms ○ Male pattern baldness
11 - 16 ○ Menstrual irregularities
Glands in the skin & scalp begin to produce
more oil, which can cause skin blemishes
○ Virility

Adrenal Androgens Excess in Males DIAGNOSIS

● Infertility ● Plasma DHEA
● Feminizing effects by inhibiting pituitary ● Plasma DHEAS
gonadotropins ● Urine 17- ketosteroids
● Lower testosterone
○ Hypogonadal symptoms
- loss muscle mass
- decreased hair growth