Download Endocrine disease

Endocrine disease
Prepared by: Siti Norhaiza Binti
Hadzir
Introduction
• Endocrinology- the study of hormones,
which are secreted from specialized
glands into the blood to influence the
activity of cells at distance sites in the
body.
Types of Hormones
• Peptides or proteins- hypothalamic
factor (thyrotrophin releasing
hormones), and pituitary gonadotropin.
• Amino acid derivatives- e.g thyroid
hormones and adrenaline
• Steroid hormones- derivatives from
cholesterol (e.g estrogen)
Measurement of Hormones
• Radioimmunoassay
• Monoclonal antibodies
Endocrine Disease
• Described as over or under secretion of
hormones
• Failure of hormones responsiveness
Oversecretion
Cushing’s disease where a pituitary adenoma secretes
ACTH
Underscretion
Primary hypothyroidism where the thyroid gland is unable
to make sufficient thyroid hormone despite continued
stimulation by TSH
Failure of hormone responsiveness
Pseudohypoparathyroidism where pt become
hypocalcemic despite elevated plasma PTH concentration
because target organs lack a functioning receptor
signaling mechanism
Examples of Endocrine Disease
The Pituitary Gland
•
•
•
•
The location
Anterior pituitary-hormone secreted
Posterior pituitary-hormone secreted
Hypersecretion-tumours (prolactin
secreting adenoma the most common)
• Hypopituitarism-is uncommon; the clinical
presentation depends on the age, sex or
the person.
Growth disorders
• Growth in children can be divided into 3
i) rapid growth-1st 2 years –condition in
utero and nutrition
ii) Steady growth-around 9 years-mainly
controlled by GH
iii) puberty- sex hormones and GH
-Other hormones involve in growth
Growth hormone insufficiency
• Is a rare cause of impaired physical
growth.
• Test of GH insufficiency:
- serum GH in response to exercise,
nocturnal sample
- Stimulant (clonidine)
• Treatment: genetically engineered GH for
children
Excessive growth
• Extremely rapid linear growth (gigantism).
The condition is rare often due to pituitary
tumor.
• Other causes; congenital adrenal
hyperplasia, hyperthyroidism, inherited
disorders.
• ↑GH later in life-Acromegaly due to
pituitary adenoma
Diagnosis of Acromegaly
• OGTT- a normal person will suppress GH
in plasma in response to glucose load.
• Acromegaly-not suppress
• ↑ IGF 1
• Treatment-surgery, radiotherapy, drugs
(octreotide-somastostatin analogue) and
bromocriptine
The Thyroid Gland
• The location
• Thyroid hormone- thyroxine (T4) and triiodothyronine (T3).
• Most cells capable of taking up T4 and
deiodinating to the more biologically active T3.
• It is T3 which binds to receptors and triggers the
end-organ effects of the thyroid hormones.
• T4 can be metabolized to reverse T3 (inactive)
Thyroid Hormone Action
• Essential for the normal maturation and
metabolism of all the tissues in the body.
Plasma concentration
Total (nmol/L) free (pmol/L)
Extent of Half life
protein
(days)
binding
T4
60-144
9.0-26.0
99.98
6-7
T3
1.0-2.9
3.0-9.0
99.66
1-1.5
Thyroid hormones in blood
Regulation of thyroid hormones
_
Hypothalamus
TRH
+
Anterior pituitary
TSH
+
Thyroid
T4 + T3
_
Thyroid Function Test
•
•
•
•
•
•
•
TSH (thyroid stimulating hormone)
Total T4 (bound hormone + free)
Free T4
TBG level
Free T3
Total T3 (bound hormone + free)
Titre of auto-antibodies to thyroid tissue
antigens
TRH test
• Involves intravenous injection of TRH
and the measurement of pituitary TSH
secreted in response to the stimulation.
• Purposes:
i) Investigation of pituitary disorders
ii) Investigation of hyperthyroidism
Pituitary responses to TRH
TRH
TRH
Normal
response
TSH
Hyperthyroidism
20
Time (minutes)
60
Primary hypothyroid
TSH
Normal
response
Secondary (pituitary)
hypothyroid
20
Time (minutes)
60
Goitre
• A goitre is an enlarged thyroid gland.
• This may be associated with
hypofunction, hyperfunction or indeed
normal concentrations of thyroid
hormones in blood.
Hypothyroidism
• 90% of cases of hypothyroidism occur as
a consequence of:
- autoimmune destruction of the thyroid
gland (Hashimoto’s disease)
- radioiodine or surgical treatment of
hyperthyroidism
Diagnosis of Hypothyroidism
• Hypothyroidism is caused by a deficiency
of thyroid hormones.
• Primary hypothyroidism – failure of the
thyroid organ itself-elevated TSH
concentration is diagnostic
• Secondary hypothyroidism-failure of
pituitary to secrete TSH (less common).
• Treatment- thyroxine (tablet) therapy.
Non-thyroidal Illness
• In systemic illness the normal regulation of
TSH, T4 and T3 secretion and subsequently
metabolism of the thyroid hormones, is
disturbed.
• ↑ T4 are converted to the reverse T3.
• Reduction in thyroid hormone activity does
not result in an increased serum TSH
concentration.
• TSH secretion is suppressed→ ↓ T4 and T3.
• TBG decrease
Neonatal Hypothyroidism
• The failure of the thyroid gland to develop
properly during early embryonic growth.
• Children develop irreversible mental
retardation and characteristic feature of
cretinism.
• The screening test- ↑ blood TSH
concentration.
Hyperthyroidism
• Hyperthyroidism can be result from:
- Graves’ disease, diffuse toxic goitre
- Toxic multinodular goitre
- solitary toxic adenoma
- thyroiditis
- exogenously administered iodine and
iodine- containing drugs, e.g amiodarone
- excessive T4 and T3 ingestion
Graves’ disease
• An autoimmune disease in which
antibodies to the TSH receptor on the
surface of the thyroid cells appear to
mimic the action of the pituitary hormones.
• The normal regulatory controls on T4
synthesis and secretion are lacking.
• Pituitary secretion of TSH is completely
inhibited by the ↑ conc. of thyroid
hormones in the blood-eyelid retraction
Diagnosis
• Suppressed TSH concentration,↑ T4
and T3- primary hyperthyriodism
• Occasionally, biochemical confirmation
of suspected hyperthyroidism will prove
more difficult e.g in pregnancy.
Pt
T4
nmol/L
55-144)
T3
nmol/L
(0.9-2.8)
TSH
TBG mg/L
mU/L
(12-30)
(0.35-5.0)
Free
Comment
T4
pmol/L
(9-24)
1
130
2.0
3.4
25
18
Euthyroid
2
175
3.6
1.1
35
14
Euthyroid
3
190
5.0
<0.05
36
30
Hprthyroid
Thyroid hormone and binding protein results in
pregnancy
Treatment
• Anti-thyroid drugs (such as carbimazole
and propylthiouracil)- younger patient
• Radioiodine-therapy with sodium I131is
commonly used in older pt. Most will
require eventually require replacement
thyroxine.
• Surgery-thyroidectomy
Thank you