Endocrine system, pathophysiology, with it's management

Learning Objectives
 Define and use the key terms in endocrinology
 Identify features that characterize hormones.
 Discuss the role of the hypothalamic-pituitary axis in
regulating hormone levels.
 Identify pathways for mediating cell-to-cell
communication.
 Analyze the mechanisms of impairment that can lead to
altered hormonal and metabolic regulation.
 Discuss common measures to diagnose and treat
hormone dysfunction.

Hormones
 Are chemicals, formed originally in tissue or organs,
which effect the growth and/or function of other target
tissues or organs
 They have varied structures – simple single amino acid
(thyroid hormone) to complex lipids (cortisol)
 They have many important regulatory functions like
energy metabolism, growth & development, muscle &
fat distribution, fluid & electrolyte balance, sexual
development, reproduction and more importantly in
stress response

Regulating Hormones
Features common to all hormones includes;
 Control – control hierachy
 Patterns – predictable for secretion, metabolism and
elimination
 Feedbacks – both negative & positive FBM
 Action – acts on target organ to achieve an effect or to
a gland to produce another hormone
 Receptor binding – affinity and efficacy

The Hypothalamic – Pituitary Axis
Hypothalamus contains neurons that synthesize prolactin, Inhibiting hormones
and releasing hormones
Releasing Hormones
 Growth Hormone-Releasing Hormone (GHRH)
 Thyrotropin-Releasing Hormone (TRH)
 Corticotropin-Releasing Hormone (CRH)
 Gonadotropin-Releasing Hormone (GnRH)
Inhibiting Hormones
 Somatostatin (inhibits GH and TSH)
 Dopamine (inhibits prolactin)

HYPOTHALAMO-HYPOPHYSIO AXIS
Hypothalamohy
pophyseal
portal vessels
Adenohypophysis
Hormones
Neurohypophysis
Neuronses

Release of Hormones from the
Hypothalamus to the Anterior
Pituitary
Action 1
 The hypothalamus produces the hormone
 The hormone travels to the anterior pituitary.
 The hormone is released unchanged into the circulation
Example: prolactin
Action 2
 The hypothalamus produces a releasing hormone
 The releasing hormone travels to and acts upon the anterior pituitary
 The pituitary is stimulated to produce and release a different hormone
into the circulation.
Example: growth hormone

Release of Hormones from the
Hypothalamus to the Anterior
Pituitary
Action 3
 The hypothalamus produces a releasing hormone
 The anterior pituitary is activated to release a stimulating hormone
 The stimulating hormone acts on the gland to produce and secrete
a final hormone that is released into the circulation
Example: thyroid hormone

6 anterior pituitary hormones
 1-thyroid stimulating hormone -glycoprotein
 2-adrenocoticotrophic hormone-peptide
 3-lutenizing hormone-glycoprotein
 4-follicle stimulating hormone-glycoprotein
 5-growth hormone-peptide
 6-prolactin-peptide

2 Posterior pituitary
 Vasopressin (ADH)
 Oxytocin
NOTE
 Intermediate lobe
 Rudimentary in humans
 produces melanotropin

Functions of Select Hormones
Hormone Source Target Function
Androgens Testes Reproductive
organs
Control the development of
reproductive organs,
(testosterone) sperm
production, and secondary sex
characteristics and growth in
males
Antidiuretic
hormone
(ADH)
Hypothalam
us posterior
pituitary
Kidney Promotes water reabsorption
(retention of fluids)
Adrenocortic
ortopic
hormone
(ACTH)
Anterior
pituitary
Adrenal
cortex
Stimulates release of hormones
from the adrenal cortex
(primarily aldosterone and
cortisol)

Corticotrpin-
releasing
hormone (CRH)
Hypothala
mus
Pituitary gland Controls release of pituitary
hormones
Epinephrine and
norepinephrine
Adrenal
medulla
Sympathetic
nervous system
Transmits neural impulses

Estrogen Ovaries Reproductive
organs
Promotes development of
reproductive organs and
secondary sex characteristics
in women
Follicle-
stimulating
hormone (FSH)
Anterior
pituitary
Reproductive
organs
Stimulates growth of ovarian
follicle and ovulation in
women; stimulates sperm
production in men
Glucagon Pancreatic
islet cells
Blood glucose Stimulates glycogen
breakdown in the liver to
increase glucose in the blood

Glucocorticoids
(cortisol)
Adrenal
cortex
Multiple
targets
Affects metabolism of all
nutrients and growth;
regulates blood glucose
levels; has anti-
inflammatory properties
Gonadotropin-
releasinf
hormone (GnRH)
Hypothala
mus
hormones
Growth
hormone-
releasing
hormone (GRHR)
Hypothala
mus
hormones

Growth hormone
(GH)
Anterior
pituitary
Bone, muscle,
organs, and
other tissues
Stimulates growth, protein
synthesis, and fat
metabolism; inhibits
carbohydrates metabolism
Insulin Pancreatic
islet cells
Blood glucose Facilitates release of oocyte
and production of estrogen
and progesterone in women;
stimulates secretion of
testerone in men
Mineralocortico-
steroids
(aldosterone)
Adrenal
cortex
Kidney Increases sodium
reabsorption and potassium
loss

Oxytocin Hypothala
mus-
posterior
pituitary
Uterus and
breast
Stimulates contraction of
the uterus during labor and
milk release from the
breasts after childbirth
Parathyroid
hormone (PTH)
Parathyroi
d glands
Bone , blood Regulates calcium levels in
the blood
Progesterone Ovaries Reproductive
organs
Affects metabolic cycle;
increases thickness of
uterine wall;
supports/maintains
pregnancy

Thyroid hormones:
triiodothyronine
(T3) and thyroxine
(T4)
Thyroid
gland
Multiple
targets
Increases metabolic rate,
needed for fetal and infant
growth and development
Thyrotropin-
releasing hormone
(TRH)
Hypothala
mus
Pituitary
gland
Controls release of pituitary
hormones
Thyroid-stimulating
hormone (TSH)
Anterior
pituitary
Thyroid
gland
Stimulates synthesis and
secretion of thyroid
hormones (TH: T3 and T4)

Process of Altering Hormone
function
The following questions address the potential problems that can alter
hormone function:
1. Is there impairment of the hypothalamic-pituitary axis?
2. Is there impairment of the endocrine gland?
3. Is there too little or too much hormone that is being produced and
secreted?
4. Is the gland producing active hormone?
5. Is receptor biding adequate?
6. Is the target cell responding to the hormone?
7. Is hormone being produced ectopically?
8. Is hormone metabolism (inactivation) and elimination impaired?

DAMAGE TO THE HYPOTHALAMIC – PITUITARY AXIS
Damage to HPA leads to problems with production and secretion of multiple
hormones and can be due to;
1. Infections 2. Inflammation 3. Tumors
4. Degeneration 5. Hypoxia 6. Haemorrhage 7. Genetic defects
Hypopituitarism – Decreased secretion of one or more of pituitary
hormones
Hyperpituitarism – Excess of pituitary hormone secretion
Panhypopituitarism - Decreased secretion of all anterior pituitary hormones
may be congenital or may occur suddenly or slowly in an individuals life
time often from a pituitary tumour

DAMAGE TO ENDOCRINE GLANDS
Destruction of endocrine glands or lack of active hormone secretion can be
due to;
1. Genetic defects 2. Autoimmune conditions 3. Degeneration 4. Atrophy
5. Infection 6. Neoplastic growths 7. Hypoxia 8. Radiation 9. certain
medication 10. Other types of injuries
RESULT
1. Gland incapable of respondig to neuroendocrine messages
2. Hormone secretion is depressed or absent
3. Excessive stimulation of the gland leads to hyperplasia and
excessive hormone production and secretion
4. Secretion of hormone that has got no biological activity
necessary to elicit cellular response

DAMAGE TO CELL RECEPTORS
*A decreased number of receptors
*The lack of receptor sensitivity to hormone
*Impairment of FBM may be a problem of ectopically
produced hormone
*The presence of antibodies that block receptor sites
or occupy the receptor site and mimic the hormone
*The presence of tumor cells with receptor activity that
deprives the unaffected cells of the hormone

DAMAGE TO FEEDBACK MECHANISMS
*FBM may fail to respond to hormonal levels and continue to
suppress or stimulate hormone production and secretion
*This impairment can occur at any point along the HPA,
secreting gland, the receptor, or target tissues
*Some neoplasms are capable of producing and secreting
ectopic hormones and the tumor is NOT part of the negative
FBM
*Surgical removal of such tumors resolves hormone
hypersecretion
*ADH and ACTH are the most common ectopically produced
hormones.

DAMAGE TO METABOLISM AND ELIMINATION MECHANISMS
*This occurs with liver or kidney disease and results
in excess circulating hormone

GENERAL MANIFESTATIONS OF ALTERED HORMONE
FUNCTION
*HYPOPITUITARISM – Has gradual onset, and
clinical manifestations are NOT evident until most of
the pituitary gland has been destroyed.
Manifestations includes; fatigue, weakness,
anorexia, sexual dysfunction, growth impairment, dry
skin, constipation and cold intolerance
*HYPERPITUITARISM – Has a wide range of
manifestation depending on which hormones are
elevated (see details on the next slide)

General manifestations of Select Hormone
Excesses and Deficits
Hormone Excess Deficit
Antidiuretic
hormone
Fluid retention, low urine
output, and hyponatremia
Excessive water losses through the
urine, leading to nausea, vomiting,
fatigue, muscle thirst, dehydration,
can progress to shock twitching; can
progress to convulsions and death
Glucocorticoid
s (cortisol)
Truncal obesity, moon face,
buffalo hump, glucose
intolerance, atrophic skin,
striae, osteoporosis,
psychological changes, poor
wound healing, and
increased infections
Hypoglycaemia, anorexia, nausea,
vomiting, fatigue, weakness, weight
loss, and poor stress response

Growth
hormone
Before puberty (called
gigantism):excessive skeletal
growth. After puberty (called
acromegaly): bony proliferation
of spine, ribs, face, hands, and
feet; enlarged tongue, coarse
skin and body hair; pain,
weakness, and inflammation
related to excessive growth;
hypertension and left heart
failure may also occur.
Short stature, obesity, immature
facial features, delayed puberty,
hypoglycemia, and seizures in
children; obesity, insulin
resistance, and high circulating
lipids in adults.
Mineralocortico
ids
(aldosterone)
Hypertension, hypokalemia,
hypernatremia, muscle
weakness, fatigue, polyuria,
polydipsia, and metabolic
alkalosis
Weakness, nausea, anorexia,
hyponatremia, hyperkalemia,
dehydration, hypotension, shock,
and death

Thyroid
hormone
Hypermetabolism, weight loss,
diarrhea, exophthalmos, anxiety,
and goiter
Hypometabolism, weight gain,
constipation, goiter, dry skin, and
coarse hair
Parathyroid
hormone
Hypercalcemia, Excessive
osteoclastic activity and bone
reabsorption, pathologic
fractures, and formation of renal
calculi
Hypocalcemia, muscle spasms,
hyperreflexia, seizures, and bone
deformities

DIAGNOSING ALTERED HORMONE FUNCTION
*Complete patient history and Physical examination
• Measuring hormonal levels in the urine (over 24 Hrs) and
blood.
• Hormonal supression and stimulation tests to detect hormone
responses
• Serum electrolyte assay
• Imaging studies like Computed Tomography and MRI to R/O
tumors
• Genetic testing

TREATING ALTERED HORMONE FUNCTION
*Treatment depends on the cause:
• High (elevated) hormone levels requires eliminating the
cause eg surgical removal of the ectopically secreting tumor,
all or part of the corresponding endocrine gland or
administering the blocker of the hormone
• Low hormone levels requires life long replacement through
exogenous medication

SYNDROME OF INAPPROPRIATE
ANTIDIURETIC HORMONE (SIADH)

SYNDROME OF INAPPROPRIATE ANTIDIURETIC
HORMONE (SIADH)
*Due to excessive production and release of ADH despite
changes in serum osmolality and blood volume
• SIADH is commonly caused by tumor, some where in the
body, secreting ADH
• Water retention intracellularly alters cell function. CNS is most
sensitive
• Edema and fluid overload is uncommon since water initially
accumulates intracellularly
• The excess circulating fluid within cell increases TBW
concentration and eventually dilutes the sodium concentration
in the extracellular space
• Clinical manifestation: Related to hypotonic hyponatremia and
includes a decreased and concentrated urine output

SYNDROME OF INAPPROPRIATE ANTIDIURETIC
HORMONE (SIADH)
• Symptoms includes: anorexia, nausea, vomiting, headache,
irritability, disorientation, muscle cramps and weakness
(sodium levels less than 115 mEq/L)
• Psychosis, gait disturbances, seizure or coma (sodium levels
below110 mEq/L)
• DIAGNOSTIC CRITERIA: Based on the following lab findings:
Hyponatremia (below 135 mEq/L); Hypotonicity (Less than
280 mOsm/Kg plasma); Decreased urine volume; Highly
concentrated urine with high sodium content; Absence of
renal, adrenal or thyroid abnormalities
• TREATMENT: Removal of the cause; Water restriction;
Hypertonic saline (I.V) for severe hyponatremia; ADH
blockers

DIABETES INSIPIDUS (DI)
• Insufficient ADH hence inability of the body to concentrate or
retain water
• THREE MAJOR CAUSES: Insufficient production of ADH by
the hypothalamus or ineffective secretion by posterior
pituitary; Inadequate kidney response to ADH, also called
nephrogenic DI; Ingestion of extremely large volume of fluids
and decreasing ADH levels (Psychiatric problem)
• CLINICAL MANIFESTATIONS: Polyuria and excessive thirst;
Highly dilute urine with low specific gravity; Serum
hyperosmolality and severe dehydration; Shock and death if
untreated

DIABETES INSIPIDUS (DI)
DIAGNOSTIC CRITERIA:
Careful patient history and physical examination (recent
surgeries, tumors, head trauma, dehydration, bladder
enlargement)
Laboratory Tests: Serum Solute Concentration; ADH levels,
Urine-specific gravity (Urine-specific gravity below 1.005 and
osmolality below 200 mOsm/Kg)
TREATMENT
Hydration
I.V Hypotonic solution to quench the thirst
Pharmacologic treatment e.g; Desmopressin (synthetic
vasopressin analogue)

Thyroid hormones
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palliative care training-2010 may

SYNTHESIS
 The thyroid gland secretes 3 hormones- thyroxine (T4),
triiodothyronine (T3) and calcitonin.
 Essential for normal growth and development. Play a
role in energy metabolism.
 Thyroid hormone is synthesized from the aromatic
amino acid tyrosine (closely related to phenylalanine
and cathecholamine) in the thyroid gland.
 Iodine is an essential ingredient, and the conversion
from dietary inorganic iodide to iodinated thyroid
hormone is termed the organification of iodine.

Synthesis of thyroid hormones
1. Thyroglobulin synthesis
2. Iodide trapping
3. Oxidation of iodide
4. Transport of iodine into
follicular cavity
5. Iodination of tyrosine
6. Coupling reactions.
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• synthesis of thyroid hormones takes place in thyroglobulin, present in
follicular cavity.
• Iodine and tyrosine are essential for the formation of thyroid
hormones.
• Iodine is consumed through diet.
• It is converted into iodide and absorbed from GI tract.
• Tyrosine is also consumed through diet and is absorbed from the GI
tract.
• For the synthesis of thyroid hormones in normal quantities,
approximately 1 mg of iodine is required per week or about 50 mg per
year.
• To prevent iodine deficiency, common table salt is iodized with one
part of sodium iodide to every 100,000 parts of sodium chloride.
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 Thyroid hormones are avidly bound to plasma proteins-
only 0.03- 0.08% of T4 and 0.2- 0.5% of T3 are in the
free form.
 Almost all protein bound iodine (PBI) in plasma is
thyroid hormone. of which 90-95% is T4 and the rest T3
• Binding occurs to 3 plasma proteins in the following
decreasing order of affinity for T4
 (i) Thyroxine binding globulin (TBG)
 (ii) Thyroxine binding prealbumin (trans-thyretin)
 (iii) Albumin
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 Growth and
development
 Intermediary
metabolism
 Calorigenesis
 CVS: increase heart
rate, contractile and
output
 CNS
 Skeletal
 GIT increase peristalsis
 Kidneys
 Stimulate erythropoiesis
 reproduction
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 Thyroid secretes more T4 than T3, but in iodine
deficient state this difference is reduced.
 • T4 is the major circulating hormone because it is 15
times more tightly bound to plasma proteins.
 • T3 is 5 times more potent than T4 and acts faster.
Peak effect of T3 comes in 1- 2 days while that of T4
takes 6-8 days.
 • T3 is more avidly bound to the nuclear receptor than
T4 and the T4 -receptor complex is unable to
activate/derepress gene transcription.
 • About l /3 of T4 is converted to T 3 in the thyroid
cells, liver and kidney by type I deiodinase (DI) and
released into circulation.. 2/22/202
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 ln addition, T3 is generated within the target cells
(skeletal muscle, heart, brain, pituitary) by another
type (D2) of deiodinase.
 Thus, it may be concluded that T3 is the active
hormone, while T4 is mainly a transport fonn which
functions as a prohormone of Tr However, it may
directly produce some nongenomic actions
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HYPORTHYROIDISM
• Hypothyroidism – is a state of deficient thyroid hormone. It
can be congenital or acquired
• Congenital Hypothyroidism occurs during fetal
development and results in a lack of of thyroid gland
development, a lack of appropriate synthesis of thyroid
hormone, or problems with TSH secretion
• Cretinism refers to mental retardation in such born children
where there is lack of production and secretion of thyroxine.
NB/ Newborns appear normal

HYPORTHYROIDISM
• Acquired Hypothyroidism – results from; deficient thyroid
hormone synthesis, destruction of the thyroid gland or
impaired TSH or TSH secretion. The common causes
includes; autoimmunity, iodine deficiency, surgical removal of
or radiation therapy to the thyroid gland, medication that
destroys the thyroid gland and genetic defects that affect the
thyroid hormones.
• Hashimoto thyroiditis is an autoimmune hypothyroidism
that can result in total destruction of the thyroid gland
• Clinical manifestations are gradual and includes fatigue,
cold intolerance, weakness, weight gain, dry skin, coarse hair,
constipation, lethargy, impaired reproduction and memory.

HYPORTHYROIDISM
• Goiter – may arise due to overstimulation of the gland.
• Myxedema: Protein - carbohydrate complexes accumulates
in the extracellular matrix drawing water into the tissues,
resulting in boggy, nonpitting, edematous tissues, especially
on the face and mucous membranes, hand and feet
• Diagnosis Criteria: is based on the patient history and
physical examination, during which characteristic clinical
manifestations are noted. Laboratory studies includes; the
sensitive TSH assay, Free T4, total T4, and T3 uptake, thyroid
autoantibodies and antithyroglobulin tests to confirm
diagnosis and provide evidence to casuality

HYPORTHYROIDISM
• Treatment: Focuses on replacing the deficient hormone with
the goals of normalization of TSH, T4, and T3 levels, along
with alleviation of clinical signs and symptoms

HYPORTHYROIDISM
• Treatment: Focuses on replacing the deficient hormone with
the goals of normalization of TSH, T4, and T3 levels, along
with alleviation of clinical signs and symptoms
• L-thyroxine ( 25, 50, 100 micrograms)
Oral bioavailability of I-thyroxine is ~ 75%, but severe hypothyroidism can reduce
oral absorption.
It should be administered in empty stomach to avoid interference by food.
Sucralfate, iron, calcium and proton pump inhibitors also reduce I-thyroxine
absorption. CYP3A4 inducers like rifampin, phenytoin and carbamazepine
Increase metabolism. Dose may need adjustments.

HYPERTHYROIDISM
• Refers to excessive thyroid hormone due to excessive
stimulation of thyroid gland, diseases of the thyroid gland, or
excess production of TSH by a pituitary adenoma.
• GRAVES DISEASE – an autoimmune disease where IgG
antibodies binds to the TSH receptors on thyrocytes (Thyroid
cells) and stimulate excessive thyroid hormone secretion,
causing a state of thyrotoxicosis
• Chronic thyrotoxicosis – can be complicated by progressiv
e thyroid failure and result in hypothyroidism. Thyroid gland
undergoes hyperplasia due to excessive stimulation

HYPERTHYROIDISM
• Thyrotoxic storm – Also called Thyroid Storm, is a sudden,
severe worsening of hyperthyroidism that may result in death
• Major clinical manifestation - Are related to enlargement of
the thyroid gland and the excessive metabolic rate of the body
• Goiter - Enlargement of the thyroid gland may occur
because of follicular epithelial cell hyperplasia
• Exopthalmos – Protrusion of the eye-balls is also
characteristic of Graves disease. The protrusion occurs as a
result of interaction of TSH – sensitized antibodies interacting
with fibroblast antigens found in the extraocular muscle and
tissues.

HYPERTHYROIDISM
• Diagnosis Criteria: Graves disease diagnosis is based on
the patient history and physical examination
• Measurement of TSH level is useful screening test for the
presence of hyperthyroidism; however, the diagnosis of
hyperthyroidism must be confirmed by the measurement of
serum – free thyroxine
• In Thyrotoxicosis – serum levels of TSH are greatly reduced
via –veFBM loop
• Increased uptake of of radioactive iodine by the thyroid gland
confirms the diagnosis.

HYPERTHYROIDISM
• Treatment: aims at reducing thyroid hormone levels often
through gland destruction using radioactive iodine, medication
that block thyroid hormone production or, less commonly,
surgical removal of all or part of the gland (NB: Parathyroid
glands gets ablated altogether)
• Full ablation of the thyroid gland requires lifelong
supplementation with oral thyroid hormone replacement
therapy

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Thioamides
 Thioamides bind to the thyroid peroxidase and prevent
oxidation of iodide and iodotyrosyl residues, thereby;
 (i) Inhibit iodination of tyrosine residues in
thyroglobulin
 (ii) Inhibit coupling of iodotyrosine residues to form T3
and T4.
 Propylthiouracil also inhibits peripheral conversion of T4
to T1 by DI type of 5-Dl, but not by D2 type. This may
partly contribute to its antithyroid effects. Methimazole
and carbimazole do not have this action
 Carbimazole acts largely by getting converted to
methimazole in the body and is longer acting than
propythiouracil. 2/22/202
4

Iodine and iodides
 The response to iodine and iodides is identical, because
elemental iodine is reduced to iodide in the intestines.
 With daily administration, peak efTects are seen in 10-
15 days, after which 'thyroid escape' occurs and
thyrotoxicosis may return with greater vengeance.
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 All facets o f thyroid function seem to be affected, but
the most impo rtant action is inhibition ofhom1one
release-
 The mechanism of action is not clear.
 Excess iodide inhibits its own transport into thyroid
cells by interfering with expression of NIS on the cell
membrane.
 ln addition, it attenuates TSH and cAMP induced thyroid
stimulation.
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 Excess iodide rapidly and briefly interferes with
iodination of tyrosil and thyronil residues of
thyroglobulin (probably by altering redox potential of
thyroid cells) resulting in reduced T/ f 4 synthesis
(Wolff-Chaikoff effect).
 However, within a few days, the gland ' escapes' from
this effect and hormone synthesis resumes.
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Radioactive Iodide
 The stable isotope of iodine is 127 1.
 lts radioactive isotope of medicinal importance is: 131
I:
 physical half-life 8 days.
 The chemical behaviour of 1311 is similar to that of the
stable isotope.
 The thyroid follicular cells are affected from within,
undergo pyknosis and necrosis followed by fibrosis when
a sufficiently large dose has been administered, witho
ut damage to neighbouring tissues.
 With carefully selected doses, it is possible to achieve
partial ablation of thyroid. Radioactive iodine is
administered as sodium salt of 131 I dissolved in water
and taken orally
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ADRENERGIC BLOCKERS
 Propranolol (and other nonselective P blockers) have
emerged as an important form of therapy to rapidly
alleviate manifestations of thyrotoxicosis that are due
to sympathetic overactivity.
 E.g palpitation. tremor, nervousness, severe myopathy,
sweating. They have little effect on thyroid function
and the hypermetabolic state
 They are used in hyperthyroidism in the following
situations.
 (a) While awaiting response to carbimazole or IJ1! .
 (b) Along with iodide for preoperative preparation
before subtotal thyroidectomy.
 (c) Thyroid storm (thyrotoxic crisis)
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CUSHING SYNDROME
(Adrenal Cortical Excess)

Calcitonin role
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Parathyroid hormone
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Role of parathyroid hormone
 Bones – The parathyroid hormone (PTH) stimulates the release of
calcium from stores of calcium present in the bones into the
bloodstreams.
 Intestine – PTH increases the calcium absorption in the intestine by
food through its impacts and effects on the metabolism of vitamin D.
 Kidneys – PTH minimizes the calcium loss in the urine and also
stimulates active vitamin D formation in the kidneys.
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CUSHING SYNDROME
• Cushing syndrome refers to a condition of excess
glucocorticoids secreted from the adrenal cortex.
• Cushing disease is hypercorticolism specifically related to
pituitary cortisol-producing tumors.
• Glucocorticoids contribute to metabolic function, the
inflammatory and immune response, and the stress response

FUNCTIONS OF GLUCOCORTICOIDS
• Stimulate glucose production
• Decrease tissue glucose utilization
• Increase breakdown and circulation of plasma protein
• Increase mobilization of fats
• Prevents release of chemical mediators that triggers
inflammatory response
• Decrease capillary permeability and inhibit edema formation
• Inhibit the immune response
• Inhibit bone formation
• Stimulate gastric acid secretions
• Contributes to emotional behavios
• Contribute to an effective stress response

FOUR MAJOR PROCESSES THAT CAN LEAD TO CUSHING
SYNDROME
• Long-term administration of corticosteroids medications (such
as prednisone)
• Tumors of the pituitary gland that stimulates excess ACTH
production
• Tumor of the adrenal gland that stimulate excess cortisol
production
• Ectopic production of ACTH or CRH from tumor at distant site,
such as small cell carcinoma of the lung
• NB/ Effects of long term use of exogenous steroids

CUSHING SYNDROME
• Clinical manifestation: altered functions of glucocorticoids.
• Common is mobilization of fats and changes in fat metabolism
leading to obesity of the trunk, face and upper back referred
to ‘moon face’ and ‘buffalo hump’
• Overstimulation of adrenal cortex to overproduce cortisol
can also stimulate production of other adrenal cortex
hormones, primarily androgen and aldosterone. This may
lead to hirsutism and hypertension with hypokalemia
respectively
• NB/ Diagnostic criteria and treatment goals

ADDISON DISEASE
(Adrenal Cortical Insufficiency)

ADDISON DISEASE
• Adrenal cortical insufficiency may result from lack of
hormones secreted from the adrenal cortex
• Autoimmune destruction of the layers of the cortex is the
commonest cause
• Also Lack of ACTH production from pituitary gland
caused by pituitary gland destruction – Tumors,
haemorrhage, trauma, radiation or surgical removal
• This destruction leads to inability of adrenal gland to
produce any glucocorticoids, mineralocorticoids, or
androgens. As a result, ACTH levels are elevated to
increase secretion of these three major steroid hormones
from adrenal gland

ADDISON DISEASE
• CLINICAL MANIFESTATIONS: are based on the insufficient level
of the steroid hormone depicted.
• Glucocorticoids – Hypoglycemia, weakness, poor stress
response, fatigue, anorexia, nausea, vomiting, weight loss and
personality changes
• Mineralocorticoids – Dehydration, hyponatremia, hyperkalemia,
hypotension, weakness, fatigue and shock
• Androgens – sparse axillary and pubic hair in women
• NB/ Elevated ACTH stimulates melanocytes resulting in in
characteristic hyperpigmentation, or darkening of the skin and
mucous membrane

Endocrine system, pathophysiology, with it's management

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