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Laboratory Diagnosis of Endocrine Diseases and Hypersensitivity
Laboratory Diagnosis of Endocrine Diseases and Hypersensitivity
Laboratory Diagnosis of Endocrine Diseases and Hypersensitivity
Yanzi Chang
Lihuili hospital
Overview of endocrine system
• Including
- endocrine gland (e.g pituitary gland, thyroid, pancreas, adrenal
gland, gonad (testis and ovary))
- endocrine cells (distributed in gastrointestinal tract, heart, lung,
kidney, vessel)
• Mechanism of action
- Hormones combine with specific receptor on the cellular surface.
- A series of amplification effect in the cell.
• Range of action
- Specific e.g thyroid stimulating hormone(TSH), adrenocorticotrophic
hormone (ACTH)
- Extensive e.g thyroxine, growth hormone
Outline
• Laboratory diagnosis for endocrine diseases
- Pituitary hormone
- Thyroid hormone
- Adrenal hormone
- sex hormone
- Lab diagnosis for common endocrine diseases
• Laboratory diagnosis for hypersensitivity
- Categories of hypersensitivity
- Laboratory diagnosis for common hypersensitivity diseases
Pituitary hormone
• Anterior pituitary hormone
- Growth hormone (GH)
- adrenocorticotrophic hormone (ACTH)
- Thyroid stimulating hormone(TSH)
- Luteinizing hormone(LH)
- follicle stimulating hormone (FSH)
- Prolactin (PRL)
• Posterior pituitary hormone
- Antidiuretic hormone (ADH)
- Oxytocin
Growth hormone
• Secreted by anterior pituitary.
• Function: stimulate skeletal growth, promote protein
synthesis, gluconeogenesis, lipid peroxidation,
absorption of calcium and phosphorus.
• Regulated by growth hormone releasing hormone
(GHRH) and growth hormone releasing inhibitory
hormone (GHIH, also called somatostatin, SS).
Released in a pulsatile manner (one peak every 1 to 4h,
increase after sleep and reach peak 1h deep sleep
later).
• Half-value period: 20-30min, (difficult to detect)
IGF-I and IGFBP-3
• IGFs (Insulin-like growth factors), IGFBP-3(IGF binding
protein): GH dependent (synthetized by the liver after GH activates
liver cells). In blood, IGF-I (75%)combined with IGFBP-3.
• IGF-I:
- Half-value period: 2h
- relevant to age, and influenced by other hormone (e.g.
thyroxine and prolactin), nutrition intake.
• IGFBP-3:
- Reflects the total concentration of IGF-I and II.
- Not be influenced by age and nutrition intake.
• IGF-I and IGFBP-3 are the first selections in lab diagnosis for GH
disorder.
• Normal range:
- IGF-I:
Children: 31-160ug/L (1-2 years old)
Increase with the age, reach peak level in youthhood (11-16years
old).
Adults: decrease with the age.
- IGFBP-3
Newborn: 0.4-1.4mg/L, increase to 2-5mg/L in youthhood.
• Clinical significance:
- IGF-I and IGFBP-3 ↓↓, GH deficiency.
- IGF-I and IGFBP-3 ↑↑, gigantism in children or acromegaly in adults.
adrenocorticotrophic hormone (ACTH)
• Secreted by anterior pituitary.
• Function: Stimulate adrenal cortex
to secret glucocorticoids, hypothalamus
mineralocorticoid, androgen.
• Regulated by corticotropic hormone
releasing hormone (CRH) and by serum
cortisol concentration. Released in daily
rhythmicity (low in night, peak in the
morning)
• Clinical significance: differentiate the
hyperadrenocorticism, hypoadrenocorticism
• ↑seen in primary hypoadrenocorticism, congenital
adrenal cortex hyperplasia, ectopic ACTH syndrome,
ectopic CRH tumor.
• ↓anterior pituitary hypofunction, primary
hyperadrenocorticism.
Thyroid stimulating hormone, TSH
LH (IU/L) FSH(IU/L)
Males, 23-70 yr 1.2-7.8 1.4-15.4
Females
Follicular phase 1.7-15.0 1.4-9.9
Midcycle peak 21.9-56.6 0.2-17.2
Luteal phase 0.6-16.3 1.1-9.2
postmenopausal 14.2-52.3 19.3-100.6
• Clinical significance:
DIT: diiodotyrosine
T4 : tetraiodothyronine
TG: thyroglobulin
TBG: thyroxine binding
globulin
rT3 : reverse triiodothyronine
TT4, FT4 and TT3, FT3 , rT3
• TT4 and TT3 easily influenced by the quantity of
TBG. But FT4 and FT3 couldn’t be influenced by
TBG, so more susceptible and stable for
evaluating thyroid function.
estrogen intake.
• TG, thyroglobulin
• Synthetized in thyroid, combined with thyroxine for
storage.
• Mainly used to be a symbol for differentiating thyroid
carninoma (↑ ↑)from in thyroid adenoma, subacute
thyroiditis, hishimoto thyroiditis, Graves’ disease (↑)
Thyroid relevant protein and autoantibody
glomerulosa Mineralocorticoid(Aldo
sterone)
fasciculate Glucocorticoid
Adrenal cortex
(cortisol)
reticulary sex hormone, minor
cortisol
Adrenal medulla pheochromocyte Noradrenaline (90%)
Adrenaline (10%)
• Aldosterone, ALD
• Mineralocorticoid, secreted by adrenal glomerulosa.
Released in daily rhythmicity and influenced by body’s
position.
• Function: to act on the distal convoluted tubule, maintain
homeostasis (preserve sodium and eject potassium).
• Primary aldosteronism: caused by adrenal cortex
hyperplasia or tumor.
• Secondary aldosteronism: caused by effective blood
volume decrease, renal blood volume decrease, e.g
heart failure, nephrotic syndrome, hypertension, ascites
due to cirrhosis, long term low sodium diet.
Detection for adrenal cortex hormone
• ↑ seen in aldosteronism: primary aldosteronism
(most>500pmol/L), secondary aldosteronism
(most>1000pmol/L).
• ↓ seen in adrenal insufficiency, hypophyseal
insufficiency, high sodium diet…
Detection for adrenal cortex hormone
• Cortisol
• Urine 17-hydroxysteroid (17-OH)
• Urine 17-ketosteroid (17-KS)
Detection for adrenal cortex hormone
• Cortisol:
- Glucocorticoid, secreted by adrenal fasciculate and reticulary, in
daily rhythmicity.
- 90% cortisol binding with CBG (cortisol binding globulin), 5%-10%
free cortisol will be discharged in urine.
• Detection tests:
- Serum cortisol: 8am (Cmax), 2am (Cmin)
- 24h urine free cortisol (24hUFC): stable concentration, not be
influenced by daily rhythmicity.
- Serum cortisol and 24hUFC: first screening tests for dysfunction of
adrenal cortex.
Detection for adrenal cortex hormone
• Clinical significance:
- ↑ (Serum cortisol and 24hUFC) seen in adrenal hyperfunction,
bilateral adrenal hyperplasia or tumor, ectopic ACTH secretion, and
the increase lose daily rhythmicity.
- ↓ (Serum cortisol and 24hUFC) seen in adrenal hypofunction,
anterior pituitary hypofunction, but the decrease maintain daily
rhythmicity.
Detection for adrenal cortex hormone
• Urine 17-hydroxysteroid (17-OH)
- the metabolite of adrenal cortisol.
- Total level in 24h reflects the change of cortisol.
- ↑ seen in adrenal hyperfunction, e.g. Cushing syndrome,
ectopic ACTH secretion, primary adrenal tumor.
- ↓seen in primary hypofunction, e.g. Addison’s disease,
anterior pituitary hypofunction…
Detection for adrenal cortex hormone
• Progesterone
LH
• Clinical significance
- To evaluate placenta’s function, FSH
• Testosterone
• The most important male androgen. Secreted by testis in
daily rhythmicity. (peak time 8am)
• ↑male sexual precosity, congenital adrenal hyperplasia,
Adrenal cortical hyperfunction, Polycystic ovary
syndrome,
• ↓ primary small testopathy (klinefelter), testicular
development disorder, male Turner’s syndrome.
Detection for sex hormone
• Human chorionic gonadotropin, hCG
• One glycoprotein hormone produced by placental villi
tissue.
• Normal range: female: <=4U/L, male <=3U/L
• For diagnosis in pregnancy:
- 1w after pregnancy(menelipsis). hCG will increase one times every
two days.
- In the early 3 months, abnormal increase indicate Choriocarcinoma,
Hydatidiform mole, Multiple pregnancy.
- If decrease in early 3 months, indicate abortion, foetus death,
ectopic pregnancy.
• For diagnosis of other diseases:
- In non-pregnant female, increase seen in the tumors of germ cells,
ovary, bladder, pancreas, stomach, lung, liver, et al.
Outline
• Laboratory diagnosis for endocrine diseases
- Pituitary hormone
- Thyroid hormone
- Adrenal hormone
- sex hormone
- Lab diagnosis for common endocrine diseases
• Laboratory diagnosis for hypersensitivity
- Categories of hypersensitivity
- Laboratory diagnosis for common hypersensitivity diseases
Application of diagnostic test on common
endocrine diseases
• Dysfunction of GH
• Dysfunction of thyroid
• Cushing’s syndrome
• Adrenal insufficiency
Application of diagnostic test on common
endocrine diseases -Dysfunction of GH
• Growth retardation
- ↓ IGF-1, 96% sensitivity, 54% specificity.
- ↓ IGFBP-3, 97% sensitivity, 95% specificity.
• Acromegaly or Pituitary gigantism
- ↑ IGF-I
- ↑ IGFBP-3
Application of diagnostic test on common
endocrine diseases- Dysfunction of thyroid
• Hyperthyroidism
- Caused by Graves’ disease (85%), Nodular goiter with hyperthyroidism,
Subacute thyroiditis with hyperthyroidism.
• Hypothyroidism
- Primary hypothyroidism: caused by chronic thyroiditis, middle or late
period of subacute thyroiditis, Thyroid resection, anti-thyroid drug
treatment, Iodine deficiency
- Secondary hypothyroidism: TRH and (or) TSH release deficiency from
hypothalamus or pituitary damage caused by tumor, operation,
radiotherapy
Clinical suspicion of hyperthyroidism
Investigation of Primary
pituitary and hypothyroidism
adrenal function
Primary
Secondary Determinations of subclinical
hypothyroidism autoantibodies hypothyroidism
negative positive