Transcript Lecture 17. The main methods in endocrinology

The main methods of
investigation in endocrinology
• Oral glucose tolerance test (OGTT)
Indications:
• borderline fasting or post-prandial
blood glucose
• persistent glycosuria
• glycosuria in pregnant women
• pregnant women with a family history
of diabetes mellitus and those who
previously had large babies or
unexplained fetal loss
Glucose tolerance test (GTT)
Fasting serum 2 hours after
glucose, mmol/l glucose loading,
mmol/l
Capillary blood
Health
3,3 – 5,5
<7,8
Impaired glucose
tolerance
5,6 – 6,1
7,8 – 11,1
Diabetes mellitus
> 6,1
> 11,1
Impaired fast
5,6 – 6,1
glucose tolerance
< 7,8
Screening for diabetes
•
•
•
•
•
with typical symptoms of diabetes
__ with a first-degree relative with diabetes
__ who are members of a high risk ethnic group
__ who are overweight (BMI ≥ 25.0 kg/m²)
__ who have delivered a baby >4.5 kg or had
GDM
• __ who are hypertensive (≥ 140/90 mmHg)
• __ with raised serum triglyceride and cholesterol
levels
• __ who were previously found to have IGT or
IFG
• The basic laboratory measures for
screening are:
• 1. Fasting capillary blood glucose
• 2. Glucosuria
• 3. HbA1c
• 4. OGTT
The thyroid hormones, thyroxine (T4) and triiodothyronine (T3)
Hypothalamus
TRH stimulation
inhibition
Pituitary
Free hormone
Liver
Thyroid
Binding
proteins
Bound hormone
T4
T3
TSH stimulation
Thyroid
are secreted under the stimulatory
influence of pituitary thyrotropin
(thyroid-stimulating hormone or
TSH). TSH secretion is primary
regulated by a dual mechanism:
• thyrotropin-releasing hormone
(TRH);
• thyroid hormone.
Thyroid hormone exits in circulation
in both free and bound forma. The
thyroid gland is the sole source of
T4 and only 20% of T3 is secreted
in the thyroid. Approximately 80%
of T3 in blood is derived from
peripheral tissue (mainly hepatic or
renal) deiodinatoin of T4 to T3.
Diagnosis of toxic diffuse goiter
I.
1.
2.
3.
II.
Laboratory findings.
(The diagnosis of hyperthyroidism is usually
straightforward and depends on careful clinical history and
physical examination, a high index of suspection, and
routine thyroid hormone determination).
In most patients serum total T3 and T4 concentrations, are
increased. Elevation of T3 - resin uptake is present.
TSN (serum thyroid stimulating hormone) may be
decreased, but it is not very sensitive assay in the
assessment of thyroid hyperfunction.
If the diagnosis of hyperthyroidism remains unclear after
these initial tests, more expensive, sophisticated and time –
consuming tests may be required, e.g. A TRH test
Ultrasonography,computed tomography, MRT
Diagnostic of hypothyroidism
1. Blood analysis: anemia; hypercholesterolemia
2. Levels of thyroid hormone: both serum T4 and T3
are decreased (but in 25% of patients with primary
hypothyroidism may be normal circulating levels of
T3), TSH hormone disturbances (in primary
hypothyroidism serum levels of TSH are very high
(feedback), low level of circulating TSH in
secondary)
3. ECG;
4. Examination of tendon reflexes
5. Ultrasonic examination
Subclinical laboratory
hypothyroidism
It is a state in which we can’t find clinical features of
hypothyroidism and euthyroidism is reached by
compensatory increasing of TSH secretion and that’s
why synthesis and secretion of such level of thyroid
hormone that will be enough for organism.
It is an asymptomatic state in which serum T4 and free
T4 are normal, but serum TSH is elevated.
Regulation of secretion
• glucocorticoids’
and androgens’
secretion is
regulated by
hypothalamic –
pituitary system
• mineralocorticoids
’ secretion is
regulated by the
renin –
angiotensin
system, the level
of Na+, K+ in
blood, and to a
lesser extent of
ACTH
1.
2.
•
•
3.
Laboratory findings in adrenal
insufficiency.
A low serum Na level and a high serum P level together
with a characteristic clinical picture suggest the possibility of Addison’s
disease.
Adrenal insufficiency can be specifically diagnosed by:
low levels of plasma glucocorticoids and
mineralocorticoids, or urinary 17 – hydroxycorticosteroid
(17 – OHCS) or 17 – ketogenic steroid (17 – KGS);
demonstrating failure to increase plasma cortisol levels,
or urinary 17 – OHCS or 17 – KGS excretion, upon
administration of ACTH (in patients with primary adrenal
insufficiency, those with secondary adrenocortical insufficiency will have a
significant increase in plasma cortisol or 24 - h urinary corticosteroid
levels.)
To distinguish between primary and secondary adrenal insufficiency, me
have to find the level of plasma ACTH: primary shows increased, and
secondary shows decreased level.
Instrumental findings.
1. The ECG may decreased voltage and
prolonged P – R and Q – T intervals.
2. The EEG shows alized slowing of the α –
rhythm.
Catecholamines are produced
from the tyrosine (organism takes it from the
meal or from the phenilalanine in the liver) →
dioxyphenilalanine (DOPHA) → dopamine (it
goes into blood only from some neurons of the
central nervous system) → norepinephrine
(noradrenaline) (it goes into blood only from
sympathetic teleneurons) → epinephrine
(adrenaline) (it goes into blood only from adrenal
medulla).
The principle urinary metabolic products of
epinephrine and norepinephrine are the
metanephrines and vanillylmandalic acid (VMA).
Investigations of
pheochromocytoma
1. An increased 3-h (24-h) urinary
excretion of epinephrine,
norepinephrine and their metabolic
products (VMA or metanephrines).
2. Increased plasma epinephrine,
norepinephrine.
3. CT scanning, MRI of the abdomen
for the localization of the tumor.
4. A scan with iodine I 131–labeled
metaiodobenzylguanidine (MIBG)
is useful for extra – adrenal
tumors.
The pituitary gland is the “master gland”, which lies in
a bony structure, the sella turcica, located at the base of the skull.
The gland is a small organ about I cm long; it weighs 500 mg and
is divided into two parts, anterior (adenohypophysis) and posterior
(neurohypophysis).
The anterior pituitary secretes
- corticotropin (ACTH)
- Prolactin
- Somatotropin (growth hormone (GH)
- gonadotropins [follicle-stimulating (FSH) and
luteinizing (LH) hormones]
- thyrotropin (TSH)
- melanocyte-stimulating hormones (MSH).
In the nerve endings of the posterior pituitary are
stored
- Vasopressin (antidiuretic hormone, ADH)
- Oxytocin
The hypothalamus plays an important role in hormone
regulation by secreting a series of small peptides which stimulate
or inhibit the synthesis and release of hormones by the anterior
pituitary
• First hypothalamic releasing
hormone identified in 1970 was
TRH by Schalli and Guilemin who
von Nobel prize in medicine for
their discoveries in1977
• Realising
Inhibiting
-
CRG
TRG
LGRG
FSRG
GRH
PRG
MRG
- GIH (somatostatin)
- PIF (dopamine)
- MIH
Regulation
• FEEDBACK:
Hormone secretion → delivery to target
cells → hormone recognition by receptors
in target cells → biologic effect →
hormone degradation → signal from target
cells to stop further hormone secretion
Diagnosis
of acromegaly :
-
Laboratory investigations:
The level of GH (0,5 – 5,0 ng/ml)
Somatomedin-C
Test with glucose suppression of
growth-hormone secretion
Test with TRH
GTT
3. Enlargement of the sella turcica
(90 % of patients) X-ray,
CT,MRT
4. Visual - field defects
(bitemporal hemianopsia)
Diagnosis of diabetes insipidus
Laboratory signs:
-
a specific gravity of less than 1,005
an osmolality of less than 100 mosmol/kg
serum osmolality is increased.
level of ADH can be decreased