ENDOCRINE FUNCTION

THYROID
jueves, 12 de mayo de 2022 9:45 a.m.
 THYROID

Tyrosyl residue Tyrosine iodinase

 THYROID

• Thyroxine binding globulin (TBG)

• Thyroxine binding pre-albumin (TBPA)
• Albumin
 THYROID

• T4 is metabolized in the peripheral circulation to T3.

• Concentration of T4 is about 50 times greater than T3. T4 can
also be metabolized to reverse T3 (rT3).
• T4 is considered a prohormone for T3.
• T3 is the most active thyroid hormone and more potent than
T4.
• Almost all circulating T4 and T3 hormones are bound to
serum proteins.
• Only 0.03% of T4 and 0.3% of T3 are not bound to proteins.
These fractions free T4 (FT4) and free T3 (FT3) are the
physiologically actives portions of the thyroid hormones.
 THYROID METHODS

• Total T3 (triiodothyronine) y Total T4 (thyroxine).

• Métodos: INMUNOENSAYOS: basados en la técnica de
competencia por RIA o fluoroinmunoensayos,
• T4 es más estable por varios días pero se recomienda ponerlo en
nevera. Hemolisis y lipemia no crea problemas con la medida
(método).
 THYROID METHODS

• Triiodothyroxine uptake / thyroxine-binding globulin

(T3 uptake):
• método para medir indirectamente la concentración de
TBG. El suero del paciente es incubado con T3 marcado
con Iodo 125. Se añade un “binder” para que absorba el
T3 que no se pegó y ese es el que voy a medir. El
resultado es expresado en % del total añadido
originalmente (marcado). T3 uptake disminuido implica alta
concentración de TBG.
• T3 U (T3 uptake) = Contaje muestra del paciente
Contaje T3 uptake Standard X
%T3 uptake del Standard
 THYROID METHODS

• Free Thyroxine Index (FT4 I):

• es una manera indirecta de medir la concentración de hormona
libre y es basado en el equilibrio de la relación T4 unido y Free
T4 (FT4).
• FT4 I = T4 X T3 U ratio
• El T3 U ratio es un derivado de la composición del T3 U del
paciente en un suero normal.
• Ejemplo: T4 = 12 µg/dL
T3 U = 25 % ( normal 30%)
T3 U ratio = 25/30 = 0.83
FT4 I = 12 X 0.83
FT4 I = 10 (valor normal = 4.5-12)
 THYROID METHODS

• Reverse T3 ( rT3)= Todo el el rT3 viene de la

deionización del T4. Se utiliza para diagnóstico
de hypotiroidismo fetal. rT3 va a estar elevado en
liquido amniotico y estado tempranos del
embarazo.
• Metabolically inactive, also can be measured by
immunoassay. Ordered to help conflicting
laboratory results, NTI. Elevated at an early stage
of pregnancy, is useful in the diagnosis of fetal
hypotiroidism and thyroiditis.
 THYROID METHODS

• TSH: Three different generations of assay

• First generation- RIA (unable to detect levels associated with
hyperthyroidism
• Second generation- IRMA
• Third generation- chemiluminiscent with sensitive limits of
0.01mIU/L
 THYROID METHODS

• Anticuerpos contra la tiroide:

• Estos pueden actuar como bloqueadores o
estimuladores y son asociados con con hyper o hypo
tiroidismo. Estos incluyen:
• TSI (thyroid stimulating immunoglobulin, microsomal antibodies
y thyroglobulin antibodies).
• Include antibodies to Thyroperoxidase (TPO),
Thyroid Microsomal Antigen (Mic), Thyroglobulin
(Tg), Thyrotropin Receptor, Thyroid-Stimulating
Immnunoglobulins (TBII).
 THYROID METHODS

• FT4: can be measured directly or calculated indirectly

as the free thyroxine index (FTI). FTI= TT4XT-uptake.
Direct methods involve the measured of FT4 by add
anti-T4.
• TT4: is not recommended, TT4 is affected by both
changes in thyroid function and TBG, thus making the
diagnosis of thyroid disease difficult.
• T-Uptake: now considered obsolete test provide an
indirect estimation of TBG, or the number of TBG sites
available.
• TT3,FT3: is measure by immunometric techniques
similar to TT4.
 THYROID METHODS

• Laboratory Tests:
• For diagnosis of hypothyroidism TSH, FT4
• For diagnosis of hyperthyroidism TSH, FT4
 THYROID

• Thyroid diseases: classified into the categories of:

• hyperthyroidism (thyrotoxicosis),
• hypothyroidism
• nonthyroidal illness (euthyroid sick syndrome).
 THYROID

• Hyperthyroidism
• Clinical Syndrome caused by excess of circulating active thyroid hormone.
• Clinical features:
• weight loss, sweating, fatigue, sinus tachycardia or atrial fibrillation, angina,
general muscle weakness.
 THYROID

• Primary Hyperthyroidism:
• Toxic multinodular goiter
• Thyroid adenoma
• Thyroid carcinoma
• Secondary Hyperthyroidism:
• Increased TSH
• Graves disease
• Neonatal hyperthyroidism (mother with thyroid stimulating
immunoglobulin)
• Pituitary tumors
• Exogenous administration of excessive thyroid hormone
 THYROID

• Graves Disease:
• Immunological disorder in which serum antibodies bind to the
TSH receptors and thus stimulate production and release of
thyroid hormone. The auto-antibodies belong to the IgG group
and are collectively called Thyroid stimulating immunoglobulin
(TSI).
• Clinical findings:
• basic symptoms + protrusion of the eyeball (ophthalmopathy)
• Lab findings:
• High T3, T4 & Low TSH. Increased Thyroglobulins, and
increased TSI.
 THYROID
• Toxic Goiter:
• Normal thyroid tissues mixed with areas of hyperplasia. The
hyperplastic areas secrete excessive amount of thyroid
hormone.
• Clinical findings:
• Basic symptoms, ophthalmopathy is not seen.
• Lab findings:
• High T3, T4 & Low TSH
• Exophthalmic Goiter:
• Most common cause of hyperthyroidism.
• Clinical Findings: basic symptoms + ophthalmopathy.
• Lab findings: High T3, T4 & Low TSH
 THYROID

Thyroid Adenoma:

Benign tumor which can produce excess thyroid hormone. usually, most adenomas do not cause
hyperthyroidism, but it can.

Thyroiditis:

Inflammation of the thyroid gland. This condition can cause hyperthyroidism by releasing hormone from the
inflamed follicles.

Thyrotoxicosis:

This condition refers to the elevation of one or the other (T3 & T4) with the other not being elevated.
 THYROID

• Hypothyroidism:
• Clinical syndrome caused by insufficient amount of thyroid hormone.
• Clinical features:
• Lethargy, tiredness, cold intolerance, dryness and coarsening of skin and hair,
weight gain, slow relaxation of muscles and tendon reflexes.
 THYROID
• Primary causes:
• Atrophic hypothyroidism
• Autoimmune hypothyroidism (Hashimoto's Thyroiditis)
• Post surgery , Radioactive iodine, Antithyroid drugs (e.g.
Carbimazole)
• Congenital
• Secondary causes:
• Pituitary or hypothalamic diseases
• Iodine deficiency.
 THYROID
• Hashimoto's Thyroiditis:
• The most common cause of hypothyroidism. This condition is
an autoimmune disease where the thyroid is attacked by the
immune system. In this condition there is an Organification
defect and lymphocytic infiltration of the gland with loss of
thyroid tissues.
• Clinical Findings:
• Basic symptoms + Antithyroid antibodies are seen in the
serum.
• Lab Findings:
• Low T3, Low T4, Low fT4 .
• In primary hypothyroidism TSH is elevated.
 THYROID

• Nonthyroidal illness(NTI), (Euthyroid Sick Syndrome)-

Abnormal thyroid tests.
• Illness result in a decline in FT3 and TT3 (caused by decreased
conversion of T4 to T3).
• TSH abnormal, elevated or suppressed.
 ENDOCRINE

ADRENAL FUNCTION
jueves, 12 de mayo de 2022 1:55 p.m.
 ADRENAL GLANDS

• Adrenal glands are paired organs located one at the

upper pole of each kidney. Each gland consists of outer
cortex and inner medula.
• ADRENAL CORTEX: composed of 3 layers (steroids)
• Zona glomerulosa: Zone G, responsible for secretion of
mineralocorticoides(Aldosterone). (Impact on blood pressure,
electrolites)
• Zona fasciculata :Zone F, responsible for secretion of
glucocorticoides(Cortisol). (Impact on glucose levels)
• Zona reticularis : Zone R, responsible for secretion of sex
hormone (Androgens).
 ADRENAL GLANDS

• ADRENAL MEDULA : (neuropeptides)

• Cells are regulated by a sympathetic nervous system (part of the autonomic
nervous system)
• Secrete catecholamine (Epinephrine and Nor-epinephrine) or also known as
(Adrenaline and Nor-adrenaline)
 ADRENAL

• GLUCOCORTICOIDES:
• The principle glucocorticoide hormone is CORTISOL.
• Functions of cortisol:
• Anti-insulin.
• CHO, fat, and protein metabolism.
• Water and electrolyte balance.
• Suppression of inflammatory and allergic reaction.
 ADRENAL

• REGULATION OF CORTISOL:
• Cortisol is regulated by the pituitary gland through the ACTH
(Adreno cortico trophic hormone). Regulation take place through
the feedback mechanism.
• Corticotropin releasing factor (CRF) is secreted from the
hypothalamus
• This will stimulate ACTH secretion by the anterior pituitary gland
• ACTH stimulate the secretion of cortisol by the adrenal cortex.
 ADRENAL
• FEEDBACK MECHANISM:
• When the cortisol level increases in the serum it act in the
pituitary and hypothalamus to inhibit further production of
ACTH, Untill serum level of cortisol start to fall this inhibitory
effect start to diminishes, and ACTH is again
released(Negative feedback).
• CORTISOL
• Normal range: 8-20 g/dl
• In the plasma, approximately 90% of serum cortisol is bound
to carrier protein (Cortisol-binding globulin). when cortisol
production increase free cortisol increases.
• Since free cortisol is readily filtered and excreted by the
kidneys, urine free cortisol level are a sensitive indicator of
adrenal hyperfunction.
 ADRENAL-CORTISOL

• HYPERCORTISOLISM: (Cushing's syndrome) May result

from:
• Primary, Increase cortisol secretion due to ADRENAL adenoma.
• Secondary, Increase ACTH secretion due to PITUITARY
adenoma, Leading to adrenal hyperplasia.
• Diagnosis:
• Measue plasma ACTH.
• Dexamethasone suppression test:
 ADRENAL-CORTISOL

• HYPOCORTISOLISM: (Addison's disease)

• Decreased production of serum cortisol. May result from:
• Primary, adrenal disease
• Secondary to pituitary abnormalities.
• Diagnosis:
• Measure plasma ACTH
• ACTH stimulation test.(by administration of synthetic ACTH to
stimulate cortisol)
 LABORATORY METHODS:
• Porter-Silber: for measure 17,21 dihydroxy-20-ketone
(cortisol, cortisone, 11deoxycortisol and the
tetrahydroderivates).
• The method use phenylhydrazine in presence of alcohol and
sulfuric acid as reactive, absorption at 410nm. Use 24hrs
urine sample.
• Zimmermann Reaction: for measure compound that
can be oxidized to 17-ketostructures (cortisol,
cortisone, 11-deoxycortisol and the
tetrahydroderivates).
• To produce 17-ketosteroids uses sodium bismuthate as
oxidizer. The reaction also use m-dinitrobenzene to produce a
reddish-purple color with absorption at 520nm. Use 24hrs
urine sample
 LABORATORY METHODS
HYPERCORTISOLISM
• Overnight dexamethasone suppression test
• this test should be performed if the screening test for
urinary cortisol is elevated. Dexamethasone is an analog
of cortisol. Suppression ocurr in normal patients.
• Low-dose dexamethasone suppression test
(LDDS):
• this test should be performed if the cotisol levels is not
suppressed in overnight dexamethasone suppression test.
• High-dose dexamethasone suppression test
(HDDS):
• to identify the ethiology of hypercortisolism. Administration
of 2 mg of dexamethasone every 6 hours for 2 days.
 LABORATORY METHODS:
• Cushing’s disease
• suppress the urinary 17-OH too less than 35% of
the baseline level and the plasma cortisol is less
than 380 nmol/L.
• If the urinary 17-OH steroid and plasma cortisol are
not suppressed, adrenal tumor producing high
levels.
• Measurement of plasma ACTH:
• because of cortisol and ACTH interact in feedback
loop.
• ACTH stimulation test:
• this test should be performed in hypocortisolism.
250mg of tetracosactrin is administed. A normal
response is with rise in plasma cortisol. A person
with adrenal failure will not response.
 ADRENAL CORTEX

• Aldosterone:
• is the major adrenal mineralocorticoid hormone.
Maintain electrolyte balance and extracellular fluid
volume.
• Primary aldosteronism (excess of mineralocorticoids),
symptoms are hypertension, hypokalemia.
• Reabsorption of NA+and water and expense of k+ and
H+.
• The primary cause is adrenal adenoma (Conn’s
syndrome).
 MEDULA ADRENAL
DOPAMINE (DA), NOREPINEFHRINE(NE), EPINEPHRINE (EPI)
 MEDULA ADRENAL

• Medullary hyperfunction
• Pheochromocytoma > catecholamines, methaneprine,
VMA
• Catecholamine hormones:
• epinephrine, norepinephrine and dopamine are
produced by adrenal medulla.
• Functions as neurotransmitters. The catecholamines
are catabolized to methaneprine, normethaneprine
and vanillymandelic acid (VMA), which are excreted
into the urine.
 LABORATORY METHODS:

• Pisano Method:
• For measure catecholamines. 24hrs urine sample
are subjected to acid hydrolysis and absorbed on
ion-exchange resin (amberlite CG-50). After elution
with ammonium hydroxide, the compounds are
converted to vanillin (reacted withperiodate) and
spectrophotometrically measure at 360nm.
 Laboratory Methods
Adrenal Insufficiency

• Metyrapone:
• is used as an alternate diagnostic or confirmatory test for
central causes of adrenal insufficiency.
• Metyrapone administered orally at midnight
• in normal individuals, block 11β-hydroxylase ,
• increasing 11-deoxycortisol (11-DOC) (>7µg/dL) while
cortisol decreases (<5 µg/dL).
REPRODUCTIVE
FUNCTION
 ADRENAL ANDROGENS
• Adrogens Precursors:
• Dehydroepiandosterone (DHEA)
• Dehydroepiandosterone sulfate (DHEA-S)
• Active androgens
• Androstenedione
• Testosterone
• 5-dihydrotestosterone
• Estrogens
• Androgens Excess
• In men, converted to estrogen and cause infertility,
feminizing effects, lower testosterone
• In women, infertility, masculizing effect
 DIAGNOSIS

• Gonads produce 10% of DHEA-S and DHEA

• Adrenal causes of pathologic masculinization
(females) and feminization (males)
• Plasma DHEA-S, DHEA, or urinary 17-ketosteroids
viernes, 13 de mayo de 2022 1:21 p.m.
 THE GONADS

• The gonads are reproductive target organ.

• Reproductive hormones are employed to
evaluate are:
• Testosterone – hirsutism and virilization in females
and primary hypogonadism in males.
• Estradiol - amenorrhea, precocious puberty in girls,
follicular maturation in ovulation.
• Progesterone – ovulation detection and
confirmation, detection of luteal phase defect,
verification of the ovulation induction, monitoring
progesterone replacement therapy, evaluation of
patients at risk for early gestation abortion.
• hCG – detect pregnancy, to assess pregnancy
viability, evaluate a suspected ectopic pregnancy.
 OTHER HORMONES: GROWTH
HORMONE (GH) AND PROLACTIN
• GH:
• release from the anterior pituitary in response to
GHRH from hypothalamus.
• It affects metabolic process by stimulating protein
synthesis and fat and glucose metabolism. The
effects are exerted directly and indirectly through
insulin-like growth factors (somatomedins).
• Excess result in gigantism in children and
acromegaly in adults.
 OTHER HORMONES: GROWTH
HORMONE (GH) AND PROLACTIN
• Prolactin:
• acts directly without the production of target gland
hormone.
• It is responsible for initiation and maintenance of
lactation.
• Inhibits secretion of GnRH and positive feedback of
estradiol and LH release.
• Clinically serum prolactinis monitored to assess
infertility and diagnose and monitor prolactinomas.
 PANCREATIC AND
GASTROINTESTINAL
FUNCTION
viernes, 13 de mayo de 2022 2:19 p.m.
 PANCREATIC FLUID

• Pancreatic fluid has about the same concentrations

of potassium and sodium as serum
• The digestive enzymes:
• proteolytic enzymes:
• trypsin, chymotrypsin, elastase, collagenase, leucine
aminopeptidase, and some carboxypeptidases
• lipid-digesting enzymes:
• lipase and lecithinase;
• carbohydrate-splitting:
• pancreatic amylase
• several nucleases:
• (ribonuclease), which separate the nitrogen-containing bases from
their sugar-phosphate strands.
 PANCREATIC ACTION

• Pancreatic activity is under both nervous and

endocrine control.
• vagus nerve can cause a small amount of pancreatic fluid
secretion when food is smelled.
• Most of the pancreatic action, however, is under the
hormonal control of:
• Secretin (production of bicarbonate)
• cholecystokinin (CCK)(is produced by the cells of the intestinal
mucosa and is responsible for release of enzymes by the
pancreas into the pancreatic fluid.
 DISEASES OF THE PANCREAS

• Cystic fibrosis: is an inherited autosomal recessive

disorder characterized by dysfunction of mucous
and exocrine glands throughout the body
• 1 of 1,600 live births
• intestinal obstruction of the newborn, excessive pulmonary
infections in childhood.
• malabsorption in adults
• cystic fibrosis gene known as CFTR occurs on
chromosome 7, and more than 900 mutations
 DISEASES OF THE PANCREAS

• Pancreatic carcinoma:
• Pancreatic cell tumors: which overproduce gastrin, are called
gastrinomas; they cause Zollinger-Ellison syndrome and can be
duodenal in origin.
• These tumors are associated with watery diarrhea, recurring peptic
ulcer, and significant gastric hypersecretion and hyperacidity
• Pancreatitis: inflammation of the pancreas:
autodigestion of the pancreas as a result of reflux of
bile or duodenal contents into the pancreatic duct.
• Pancreatitis acute (no permanent damage to the pancreas),
• Pancreatitis chronic (irreversible injury).
 TESTS OF PANCREATIC FUNCTION
• The secretin/ CCK test: is a direct determination of
the exocrine secretory capacity of the pancreas.
• The test involves intubation of the duodenum without
contamination by gastric fluid. Performed after a 6-hour or
overnight fast.
• Pancreatic secretion is stimulated by intravenously
administered secretin in a dose varying from 2 to 3 U/ kg of
body weight, followed by CCK administration
• Pancreatic secretions are collected variously for 30, 60, or
80 minutes after administration of the stimulants.
• The pH, secretory rate, enzyme activities and amount of
bicarbonate are determined.
• The average amount of bicarbonate excreted per hour is
about 15 mmol/ L for men and 12 mmol/ L for women, with
an average flow of 2 mL/ kg.
 TESTS OF GASTRIC FUNCTION

• Measuring Gastric Acid in Basal and

Maximal Secretory:
• After an overnight fast, gastric analysis is usually
performed as a 1-hour basal test, followed by a 1-
hour stimulated test subsequent to pentagastrin
administration (6 µg/ kg subcutaneously)
• anacidity (e.g., in pernicious anemia) and the
extreme hypersecretion found in Zollinger-Ellison
syndrome.
 TESTS OF GASTRIC FUNCTION

• Measuring Gastric Acid:

• After intubation, the residual secretion is aspirated and
retained.
• Secretion for the subsequent 10 to 30 minutes is discarded
to allow for adjustment of the patient to the intubation
procedure.
• Specimens are ordinarily obtained as 15-minute collections
for a period of 1 hour.
• The total acid output in a timed interval is determined from
the titratable acidities and volumes of the component
specimens.
• intravenous secretin stimulation may be used to investigate
patients with mildly elevated serum gastrin levels
 TESTS OF GASTRIC FUNCTION

• Plasma Gastrin:
• Measurement of plasma gastrin levels is invaluable in
diagnosing Zollinger-Ellison syndrome,
• In fasting levels typically exceed 1,000 pg/ mL and can reach
400,000 pg/ mL, compared with the normal range of 50 to 150
pg/ mL.
• Gastrin is usually not increased in simple peptic ulcer
disease.
 TESTS OF INTESTINAL FUNCTION

• D-Xylose Absorption Test

• D-xylose: a pentose sugar ordinarily not present in blood
• Pentose sugars are absorbed unaltered in proximal small
intestine and do not require intervention of pancreatic lytic
enzymes.
• Ability to absorb D-xylose helps differentiate malabsorption of
intestinal etiology from that of exocrine pancreatic
insufficiency.
• Process
• After overnight fast, patient voids and drinks D-xylose
solution.
• Patient drinks equivalent amount of water during next hour.
• Urine is collected for 5 hours after ingestion; blood specimen
is collected at 2 hours.