Endocrine
Lec: 1
Dr. Mohammed Alhamdany
Functional anatomy and physiology:
Most hormone release from endocrine glands are under the control of pituitary
gland and hypothalamus except for example the adrenal zona glomerulosa
(regulated by the renin–angiotensin system), parathyroids (regulated by calcium
concentrations) and pancreas(regulated by glucose level).
Anterior pituitary hormone secretion is controlled in turn by substances
produced in the hypothalamus and released into portal blood, which drains
directly down the pituitary stalk. Posterior pituitary hormones are synthesized in
the hypothalamus and transported down nerve axons, to be released from the
posterior pituitary.
Hormone release in the hypothalamus and pituitary is regulated by numerous
stimuli and through feedback control by hormones produced by the target
glands which are either positive or negative feedback, this is called axes.
Paracrine is defined as hormone release from cell to affect adjacent cell such as
neurotransmitter, while autocrine define as hormone secrete from cell to affect
same cell.
The endocrine axes include:
1- Thyroid: thyrotrophin-releasing hormone TRH (in H.)
TSH (in anterior
P.)
T4 and T3 (in T. gland)
Metabolism.
Feedback: T3 can feedback TRH.
2- Sex hormone: GnRH (gonadotrophin-releasing hormone) in H
LH, FSH
( in anterior P)
Oestrogen, Progesterone, Androgen in Gonads: testes or
ovaries
Reproduction.
feedback: estrogen, Progesterone ,Androgen, Prolactin, Inhibin can feedback
GnRH.
3- Lactation: TRH and Dopamine (suppress)
Prolactin (ant. P)
Breast
Lactation.
Feedback: Estrogen and Stress can feedback Dopamine.
4- Growth: GHRH and Somatostatin
GH in (ant. P.)
IGF1 and
IGFBP3 (insulin like growth factor -1 and its binding protein (in the liver)
Growth, IGF-1 can feedback GHRH.
5- Adrenal: CRH in H
ACTH in ant. P.
Cortisol and Androgen in
Adrenal cortex
Stress.
Feedback: Stress and Cortisol can feedback CRH (which secrete in Circadian
rhythm).
6- Water balance: ADH in hypothalamus secrete to post. P. (also affect ACTH)
Distal nephron
Water balance.
Feedback: Osmolality and Intravascular volume can feedback ADH.
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7- Parturition and Lactation: Oxytocin in hypothalamus secrete to post. P.
Uterus and Breast
Parturition and Lactation
Endocrine pathology:
Classification of endocrine disease:
A-Hormone excess
1- Primary gland over-production
2- Secondary to excess trophic substance
B-Hormone deficiency
1- Primary gland failure
2- Secondary to deficient trophic hormone
C-Hormone hypersensitivity
1- Failure of inactivation of hormone
2- Target organ over-activity/hypersensitivity
D-Hormone resistance
1- Failure of activation of hormone
2- Target organ resistance
E-Non-functioning tumors: incidentinoma.
Pathology arising within the gland is often called ‘primary’ disease (for
example, primary hypothyroidism in Hashimoto’s thyroiditis), while abnormal
stimulation of the gland is often called ‘secondary’ disease (for example,
secondary hypothyroidism in patients with a pituitary tumour and thyroidstimulating hormone deficiency).
Principles of endocrine investigation:
Timing: Release of many hormones is rhythmical (pulsatile, circadian or
monthly), so random measurement may be invalid and sequential or dynamic
tests may be required.
Choice of dynamic biochemical tests
• Abnormalities are often characterized by loss of normal regulation of hormone
secretion.
• If hormone deficiency is suspected, choose a stimulation test.
• If hormone excess is suspected, choose a suppression test.
• The more tests there are to choose from, the less likely it is that any single test
is infallible, so avoid interpreting one result in isolation.
Imaging
• Secretory cells also take up substrates, which can be labelled
• Most endocrine glands have a high prevalence of ‘incidentalomas’, so do not
scan unless the biochemistry confirms endocrine dysfunction or the primary
problem is a tumour
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Biopsy
• Many endocrine tumors are difficult to classify histologically (e.g. adrenal
carcinoma and adenoma)
THE THYROID GLAND:
Diseases of the thyroid predominantly affect females and are common,
occurring in about 5% of the population. The thyroid axis is involved in the
regulation of cellular differentiation and metabolism in virtually all nucleated
cells.
The parafollicular C cells secrete calcitonin, which is of no apparent
physiological significance in humans. The follicular epithelial cells synthesize
thyroid hormones by incorporating iodine into the amino acid tyrosine on the
surface of thyroglobulin (Tg), a protein secreted into the colloid of the follicle.
Iodide is a key substrate for thyroid hormone synthesis; a dietary intake in
excess of 100 μg/day is required to maintain thyroid function in adults. The
thyroid secretes predominantly thyroxine (T4) and only a small amount of
triiodothyronine (T3); approximately 85% of T3 in blood is produced from T4
by a family of monodeiodinase enzymes. T4 can be regarded as a pro-hormone,
since it has a longer half-life in blood than T3 (approximately 1 week compared
with approximately 18 hours), and binds and activates thyroid hormone
receptors less effectively than T3. T4 can also be converted to the inactive
metabolite, reverse T3.
T3 and T4 circulate in plasma almost entirely (> 99%) bound to transport
proteins, mainly thyroxine-binding globulin (TBG).
A circadian rhythm of TSH secretion can be demonstrated with a peak at 0100
hrs and trough at 1100 hrs, but the variation is small so that thyroid function can
be assessed reliably from a single blood sample taken at any time of day and
does not usually require any dynamic stimulation or suppression tests.
Presenting problems in thyroid disease:
Thyrotoxicosis:
It's defined as clinical features arising from elevated circulating levels of thyroid
hormone.
The most common causes include:
1- Graves’ disease.
2- Multinodular goiter.
3- Solitary thyroid adenoma.
4- Thyroiditis: including Subacute (de Quervain’s) and Post-partum thyroiditis.
5- Iodide-induced include the Drugs induced eg: amiodarone, and Radiographic
contrast media.
Clinical feature: common:
1- Weight loss despite normal or increased appetite
2- Heat intolerance, sweating
3- Palpitations, tremor
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4- Dyspnoea, fatigue
5- Irritability, emotional lability.
Less common
1- Osteoporosis (fracture, loss of height)
2- Diarrhoea
3- Muscle weakness and Periodic paralysis
4- Amenorrhoea/oligomenorrhoea.
Common sign:
1- Weight loss.
2- Tremor.
3- Palmar erythema.
4- Sinus tachycardia.
5- Lid retraction, lid lag.
Less common
1- Goitre with or without bruit.
2- Atrial fibrillation( irregular irregularity).
3- Systolic hypertension/ increased pulse pressure.
4- Hyper-reflexia.
Sign specific to graves' disease as a cause of thyrotoxicosis:
1- Goitre with bruit.
2- periorbital oedema.
3- conjunctival irritation.
4- exophthalmos.
4- diplopia.
5- Pretibial myxedema.
6- Thyroid acropachy (periosteal hypertrophy, indistinguishable from finger
clubbing).
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