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Thyroid-stimulating hormone (TSH)
• Secreted in response to thyrotrophin-releasing
hormone (TRH).
• Stimulates thyroid secretion.
Follicle-stimulating hormone (FSH) and luteinizing
hormone (LH)
• Secreted in response to gonadotrophin-releasing
hormone (GnRH).
• Lead to stimulation of the male and female gonads.
Prolactin
• Secretion is controlled by the inhibitory action of dopamine. Factors that decrease dopamine lead to the release
of prolactin.
Growth hormone (GH)
• Secretion is stimulated by growth-hormone-releasing
hormone (GHRH) and inhibited by growth-hormoneinhibiting hormone (GHIH or somatostatin).
Posterior Pituitary Hormones
Oxytocin
• Produced by cells in the paraventricular nucleus in the
hypothalamus.
• Secretion is stimulated by sensory stimuli activating
mechanoreceptors in the breast during suckling.
• Also stimulates the ejection of milk and uterine
contractions.
Antidiuretic hormone
• Produced by cells in the supraoptic nucleus in the
hypothalamus.
• Release is stimulated by sensory input into osmoreceptors and cardiac stretch receptors (see section on uid
balance in Chapter 7).
Clinical Physiology
Pituitary Disorders
Increased hormone secretion
e clinical conditions seen as a result of excess hormone
secretion include:
• ↑ ACTH: Cushing’s disease (see below).
• ↑ Prolactin: hyperprolactinaemia occurs with pituitary
tumours (prolactinoma). Patients present with galactorrhoea, amenorrhoea, impotence, headaches and visual
eld defects. e eects on reproductive function are
via its inhibitory eect on GnRH production.
• TSH: TSH-secreting pituitary tumours can cause hyperthyroidism but they are exceedingly rare.
• GH: abnormal release of GH results in two disorders,
depending on the age at which it presents:
• ↑ in childhood results in gigantism (see below)
• ↑ in adult life results in acromegaly (see below).
CHAPTER 12 Endocrine System
• ↑ADH: elevated ADH leads to the syndrome of inappropriate antidiuretic hormone (SIADH). e condition is
diagnosed by ↓ Na+, ↓ plasma osmolarity, ↑ urine osmo-
larity, and urinary Na+ >30 mmol/L. Causes include:
• tumours, e.g. lung, pancreas, lymphomas
• TB
• lung abscess
• CNS lesions, e.g. meningitis, abscess, head injury
• metabolic, e.g. alcohol withdrawal
• drugs, e.g. carbamazepine.
241
Decreased hormone secretion
• Deciency of pituitary hormones can be isolated or
involve all hormones (panhypopituitarism).
• e eects of individual deciency include:
• ↓ ACTH: results in Addison’s disease (see below)
• ↓ TSH: results in hypothyroidism (see below)
• ↓ FSH and LH: leads to a failure in sexual function
and hypogonadism
• ↓ GH: leads to dwarsm (see below)
• ↓ ADH: results in diabetes insipidus (cranial), also
nephrogenic diabetes insipidus – this occurs due to
failure at the cell receptor level in the kidney. A deciency of ADH leads to an inability to concentrate
urine and the passage of litres of urine (polyuria).
• e causes of pituitary deciency include:
• rare congenital deciency, e.g. Kallman syndrome:
FSH and LH deciency
• infection: meningitis and encephalitis
• pituitary apoplexy: bleeding into a pituitary tumour
• Sheehan’s syndrome: infarction following post-par-
tum haemorrhage
• cerebral tumours
• radiation
• trauma, i.e. frontal skull
• sarcoidosis.
THYROID FUNCTION
Anatomy
• See Chapter 5.
• Microscopically, the thyroid is composed of follicles;
these consist of an outer layer of cuboidal epithelium
and are lled with colloid.
• e follicles are responsible for the production, storage
and secretion of thyroid hormone.
• Between follicles lie the parafollicular cells; these secrete
calcitonin (see Calcium and Phosphate Regulation
section).
242
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SECTION II Physiology
ColloidThyroid follicular cellPlasma
TPO
TG
Tyrosine
Lysosomes
–
I
MIT
DIT
MIT
DIT
I
2
TG
+
DIT
+
DIT
MIT
DIT
T
T
3
4
TG
–
I
T
3
T
4
Fig. 12.1 Production of T3 and T4 in the thyroid gland
(I− = iodide, I2 = iodine, TPO = thyroid peroxidase,
TG = thyroglobulin, MIT = monoiodotyrosine,
DIT = diiodotyrosine).
Synthesis of Thyroid Hormone (Fig. 12.1)
• Steps in the synthesis of thyroid hormones include:
• active pumping of iodide ions in from the extracellular space to the follicular epithelium
• iodide ions enter the colloid and are converted to
iodine
• iodine is combined with tyrosine.
• Two forms are produced: monoiodotyrosine (1 MT)
and diiodotyrosine (2 DT); these then combine to form
the two thyroid hormones:
• triiodothyronine (T3): MT + DT
• thyroxine (T4): × 2 DT.
• More T4 is produced but T3 is more biologically active.
• yroid hormones are stored in the colloid of the follicle
and released into the circulation as needed (the thyroglobulin is detached).
Clinical Physiology
Antithyroid Drugs
e drugs used in the treatment of hyperthyroidism include:
• ionamides, e.g. carbimazole and propylthiouracil:
this group of drugs competitively inhibits the peroxidase-catalysed reaction (iodide is converted to iodine).
ey also block the coupling of the iodotyrosine.
Propylthiouracil also inhibits the peripheral deiodination of T4.
• Anion inhibitors, e.g. perchlorate: competitively inhibits the uptake of iodine; discontinued as it can cause
aplastic anaemia.
• Iodide, e.g. Lugol’s solution: iodide is thought to work
by blocking the binding of iodine with tyrosine residues, inhibiting hormone release. It is also thought to
decrease the size and vascularity of the thyroid gland.
Secretion and Transport of Thyroid Hormone
• Hypothalamus releases thyrotrophin-releasing hormone (TRH). TRH is transported to the endocrine cells
of the anterior pituitary along the hypophyseal tract;
this stimulates the release of thyroid-stimulating hormone (TSH).
• TSH stimulates thyroid hormone production and
secretion.
• T3 and T4 have a negative feedback eect on TRH and
TSH.
• Cold stress stimulates thyroid hormone secretion.
• e majority of thyroid hormone in the circulation is
bound to thyroid-binding globulin (TBG); however,
only the free portion is biologically active.
Effects of Thyroid Hormone
• T3 and T4 cross the cell membrane via diusion; most of
the T4 is converted to T3 in the cell.
• yroid hormone then bonds to receptors and initiates
increased DNA transcription and protein production.
• e eects of thyroid hormone include:
• metabolic:
• ↑ basal metabolic rate: leading to ↑ O2 consumption and ↑ heat production
• ↑ absorption of glucose, glycolysis and gluco neogenesis
• ↑ catabolism of fatty acids
• ↓ cholesterol production
• ↑ synthesis and catabolism of protein
• cardiac:
• ↑ heart rate
• ↓ in peripheral vascular resistance (indirect, due
to increased metabolic rate in tissues)
• ↑ in cardiac output and pulse
• ↑ β-receptor production; facilitates activation and
increases the response
• promotes erythropoiesis
• respiratory:
• ↑ ventilatory rate
• gastrointestinal:
• ↑ motility and secretion
• CNS:
• ↑ CNS activity and alertness
• normal neuronal function
CHAPTER 12 Endocrine System
243
• growth and development:
• necessary for normal myelination and axonal
development
• stimulation of skeletal growth
• promotes bone mineralization.
Clinical Physiology
Thyroid Disorders
Hyperthyroidism
• Hyperthyroidism = ‘overactive’ thyroid.
• e causes of hyperthyroidism include:
• primary hyperthyroidism: this includes intrinsic
thyroid diseases:
• Graves’ disease: commonest cause, due to autoim-
mune IgG antibodies that bind to the TSH receptors and stimulate thyroid hormone production
• solitary toxic adenoma/nodule (Plummer’s disease)
• toxic multinodular goitre
• acute phase of thyroiditis – occurs in the early
phase of cell injury and is due to the release of
large amounts of stored thyroid hormone
• drugs, e.g. amiodarone.
• secondary hyperthyroidism: this includes causes of
hyperthyroidism extrinsic to the thyroid gland:
• pituitary/hypothalamic tumour secreting TSH/
TRH; very rare
• metastatic thyroid carcinoma: if well dierenti-
ated, may produce enough thyroid hormone to
produce symptoms of hyperthyroidism
• choriocarcinoma: this tumour usually produces
HCG; however, it can also produce a substance
similar to TSH
• ovarian teratoma: a particular specialized type of
teratoma – called struma ovarii – is composed of
mature thyroid tissue. is may overfunction and
lead to hyperthyroidism.
e clinical features of hyperthyroidism are shown in
Fig. 12.2.
Hypothyroidism
• Hypothyroidism = ‘underactive’ thyroid.
• e causes of hypothyroidism include:
• primary hypothyroidism: this includes diseases that
directly aect the thyroid gland; these include:
• autoimmune (atrophic): arises due to microsomal
antibodies that lead to destruction and atrophy of
the thyroid gland
• Hashimoto’s thyroiditis: an autoimmune inam-
mation of the thyroid gland; microsomal autoantibodies are also present. e condition is
associated with atrophy and regeneration of the
thyroid gland; this leads to goitre formation
• iodine deciency
• genetic defects: inherited defects in the enzymes
involved in the synthesis of thyroid hormones,
e.g. Pendred’s syndrome
• iatrogenic, e.g. post-thyroidectomy and -irradiation
• drugs, e.g. lithium
• neoplasia: inltration and destruction of the
gland secondary to a malignant neoplasm.
• secondary hypothyroidism: occurs due to pituitary
or hypothalamic disease:
• hypopituitarism
• isolated TSH deciency.
e clinical features of hypothyroidism are shown in
Fig. 12.3.
Sick euthyroid syndrome
• Acute illness from any cause can result in a number of
abnormalities in the markers of thyroid function without actually aecting thyroid function, i.e. the patient is
euthyroid. ese changes include:
• ↓ binding proteins
• ↓ anity of binding proteins
• ↓ peripheral conversion of T4 to T
• ↓ TSH.
• ese patients will thus have low T4/T3 levels, but levels
of TSH are also low.
3
CALCIUM AND PHOSPHATE REGULATION
Calcium
• Calcium is absorbed via the gut and is mainly excreted
in the urine.
• Calcium is stored in three ‘pools’:
• bone: 99% of total body calcium. Osteoclasts break
down bone to release Ca2+ (structural bone calcium)
and phosphate into the circulation; osteocytes are
also able to transfer Ca2+ into the circulation, but
do not aect the bone structure (exchangeable bone
calcium)
• intracellular: Ca2+ is an important mediator of intra-
cellular signals
• extracellular: normal levels are between 2.2 and
2.6 mmol/L. Approximately 50% is protein-bound,
only the free fraction is biologically active. e
extracellular pool is in constant ux with bone,
Ca2+ absorbed from the gastrointestinal tract, and
excreted in the urine.
• Calcium is important in a number of cellular processes:
• excitability of nerve and muscle: calcium level aects
the permeability of the Na+ channel; a low calcium level will lead to increased permeability and
increased Na+ inux, and will thus depolarize the
244
Osteoporosis
Oculomotor palsies
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SECTION II Physiology
Alopecia
Flushed
Sweating
Weight loss
Diarrhoea
Eye signs
Lid lag
Lid retraction
Exophthalmos
Tachycardia
Atrial fibrillation
Hyper-reflexia
Tremor
Thyroid
acropachy
Pretibial
myxoedema
Fig. 12.2 Features of hyperthyroidism.
cell towards threshold. If the Ca2+ level rises then Na+
permeability decreases, and the threshold will rise,
thus decreasing nerve and muscle activity
• muscle contraction: excitation–contraction coupling
in muscle (see Chapter 13) requires an inux of
calcium
• secretion processes: the products secreted from various glands is oen triggered by an inux of Ca2+ into
the cell
• clotting: Ca2+ is an essential blood-clotting factor; it
acts as a cofactor for several of the clotting factors
(see Chapter 20).
Parathormone
• PTH is an 84-amino-acid polypeptide released from
the parathyroid glands; these are found on the posterior
surface of the thyroid lobes.
• A fall in extracellular uid (ECF) Ca2+ stimulates the
release of PTH. It increases Ca2+ in several ways:
• stimulates Ca2+ release from bone; the initial rapid
phase of Ca2+ release is due to osteocytes mobilizing
the exchangeable bone calcium. Longer-term release
of PTH will stimulate osteoclasts to release Ca2+
from the structural bone pool
• increases the rate of Ca2+ uptake from the renal
tubules, therefore reducing urinary loss
Regulation of Calcium Balance
• e regulation of calcium is by two hormones (parathormone [PTH] and calcitonin) and vitamin D.
• stimulates urinary phosphate excretion
• stimulates the rate at which vitamin D is converted
to the biologically active 1,25 form in the kidney.
'Peaches and cream'
complexion
High blood pressure
CHAPTER 12 Endocrine System
Dry thin hair
Loss of eyebrows
Deafness
245
Obesity
Constipation
Bradycardia
Heart failure
Hyporeflexia
Cold
peripheries
Carpal tunnel
syndrome
Myopathy
Oedema
Fig. 12.3 Features of hypothyroidism.
Vitamin D
• Vitamin D is a fat-soluble vitamin, derived from two
sources:
• diet: vitamin D
• skin: UV radiation converts cholesterol to vitamin D3.
2
• Vitamin D (cholecalciferol) is converted to 1,25-dihydrocholecalciferol in two stages:
• converted to 25-hydroxycholecalciferol in the liver
• converted to 1,25-dihydroxycholecalciferol (the
most active form) in the kidney.
• PTH and low phosphate levels stimulate the conversion
steps for vitamin D.
• Vitamin D increases plasma Ca2+ by a number of
mechanisms:
• increases the rate of Ca2+ and phosphate uptake from
the gut
• increases renal tubular absorption of Ca2+ and
phosphate
• stimulates osteoclastic bone resorption
• promotes mineralization of osteoid.
Calcitonin
• Calcitonin is a 32-amino-acid polypeptide; it is secreted
by parafollicular C-cells within the thyroid gland.
• It acts to reduce the rate of Ca2+ release into the ECF by:
• decreasing Ca2+ and phosphate reabsorption from
the renal tubules
• stimulating osteoblasts to mineralize bone and thus
take Ca2+ from the circulation.
246
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SECTION II Physiology
• e action of calcitonin is thought to be signicant in
periods of hypercalcaemia, but plays little role in the
everyday regulation of Ca2+.
Regulation of Phosphate Balance
• e regulation of phosphate levels occurs in tandem
with Ca2+ regulation.
• PTH reduces phosphate levels (decreases renal tubular
absorption and thus increases urinary loss).
• 1,25-dihydroxycholecalciferol increases phosphate levels (increases renal tubular absorption).
• ↓phosphate stimulates the renal activation of vitamin D
to the 1,25 form.
Clinical Physiology
Disorders of Calcium and Phosphate Balance
Hypoparathyroidism
• Hypoparathyroidism is a rare cause of hypocalcaemia.
• Causes include:
• congenital, e.g. DiGeorge syndrome
• autoimmune
• iatrogenic: following total thyroidectomy or
parathyroidectomy
• hypomagnesaemia: low magnesium levels prevent
the release of PTH.
Hyperparathyroidism
• Hyperparathyroidism is a common cause of hypercalcaemia. ere are several dierent types:
• primary hyperparathyroidism. Causes include:
• single adenoma (>80%)
• multiple adenomas (<5%)
• parathyroid hyperplasia (<10%)
• parathyroid carcinoma (rare; <2%)
• secondary hyperparathyroidism: with prolonged ↓
Ca2+ the parathyroid glands hypertrophy. In these
instances, e.g. renal failure, the calcium level will be
low or normal, but the PTH level will be elevated.
• tertiary hyperparathyroidism: if secondary hyperpara-
thyroidism develops and the cause of the ↓ Ca2+ is not
treated, then tertiary hyperparathyroidism develops –
in this case the glands produce PTH autonomously
and the levels of both Ca2+ and PTH are elevated.
• ectopic PTH: this condition is very rare; it occurs
when tumours, e.g. squamous cell lung cancer, produce PTH-related peptide. is is a 141-amino-acid
protein that is similar to PTH and is thus able to
stimulate bone resorption and calcium release.
Vitamin D deficiency
• A lack of vitamin D leads to inadequate mineralization
of bone; in adults this leads to osteomalacia, in children
it leads to rickets.
• Causes of vitamin D deciency include:
• dietary insuciency: particularly common in vegans
• lack of sunlight: common in elderly patients and
Asian women
• malabsorption: particularly aer gastric surgery,
coeliac disease and disorders of bile salt production
• renal disease: leads to inadequate conversion to the
active form 1,25-dihydroxycholecalciferol
• hepatic failure
• Vitamin-D-resistant rickets: a familial condition
with hypophosphataemia, phosphaturia and rickets.
Hypocalcaemia
• Hypocalcaemia results in symptoms related to neuromuscular irritability, e.g. paraesthesia, numbness,
cramps and tetany. Neuropsychiatric disturbances may
also occur, e.g. anxiety and psychosis.
• Specic signs include Chovstek’s sign and Trousseau’s
sign.
• ECG may show a prolonged QT interval.
• Causes include:
• hypoalbuminaemia
• hypomagnesaemia
• hypophosphataemia
• hypoparathyroidism
• acute pancreatitis
• rhabdomyolysis
• sepsis
• massive transfusion (due to citrate binding)
• post-thyroid surgery
• vitamin D deciency
• osteoblastic metastases
• hypoventilation with respiratory alkalosis and reduc-
tion in ionized plasma calcium
• drugs, e.g. diuretics, aminoglycosides, bisphospho-
nates, calcitonin.
Hypercalcaemia
• Hypercalcaemia is more common than hypocalcaemia.
• Symptoms can be remembered by the rhyme, ‘stones,
bones, abdominal groans and psychiatric overtones’, i.e.
renal stones, bone pain, abdominal pain (due to peptic
ulceration in some cases) and depression.
• ECG may show a reduced QT interval.
• Causes include:
• excess PTH – primary and tertiary hyperparathy-
roidism, ectopic PTH secretion
• excess vitamin D
• sarcoidosis
• milk–alkali syndrome (excess calcium intake)
• drugs, e.g. thiazide diuretics
• malignancy.
• solid tumour with lytic bony metastases, e.g. carcinoma
of the breast, carcinoma of the bronchus
CHAPTER 12 Endocrine System
247
• solid tumour with humoral mediation, e.g. inappropriate PTH secretion with carcinoma of the bronchus,
carcinoma of the kidney
• multiple myeloma
• hyperthyroidism
• Addison’s disease
• prolonged immobilization
• Paget’s disease of bone
• familial hypocalciuric hypercalcaemia.
Hypophosphataemia
• Hypophosphataemia results in:
• confusion
• convulsions
• muscle weakness: acute hypophosphataemia can
lead to signicant diaphragmatic weakness and delay
weaning from a ventilator in patients in the intensive
treatment unit
• le shi of oxyhaemoglobin curve: this results in
decreased oxygen delivery to tissues and is due to the
reduction in 2,3-DPG.
• Causes include:
• hyperparathyroidism: PTH reduces renal tubule
absorption
• vitamin D deciency: vitamin D stimulates gut and
tubular absorption of phosphate
• total parenteral nutrition (TPN): refeeding with
carbohydrate aer fasting can result in hypo phosphataemia
• diabetic ketoacidosis
• alcohol withdrawal
• acute liver failure
• paracetamol overdose: phosphaturia.
Hyperphosphataemia
• Hyperphosphataemia is usually asymptomatic and no
treatment is required.
• Causes include:
• chronic renal failure: causes itching, hyperparathy-
roidism and deposition of calcium in the joints and
around vessels
• tumour lysis: occurs following radio- or chemotherapy
• myeloma.
ADRENAL FUNCTION
• e adrenal glands are located at the upper poles of both
kidneys (see Chapter 2).
• ey consist of an outer cortex and an inner medulla.
• e cortex secretes steroid-based hormones and is subdivided into three sections:
• zona glomerulosa: mineralocorticoids
• zona fasciculata: glucocorticoids
• zona reticularis: sex hormones.
• e medulla is part of the sympathetic nervous system;
it contains chroman cells; these are specialized sympathetic post-ganglionic neurons.
• Nerve bres from the splanchnic nerves innervate the
medulla; these release acetylcholine, which stimulates
hormone release.
• e chroman cells release a variety of hormones when
stimulated to do so; they are stored in granules and exit
the cells into the circulation via exocytosis.
• e adrenal medulla produces:
• epinephrine (adrenaline)
• norepinephrine (noradrenaline)
• dopamine
• β-hydroxylase (enzyme involved in catecholamine
synthesis)
• ATP
• opioid peptides (metenkephalin and leuenkephalin).
Cortex
Synthesis and Excretion
• Cholesterol is converted to pregnenolone in mitochondria; this provides the basic structure for the formation
of all other steroid hormones.
• Conversion products of pregnenolone are shown in
Fig. 12.4.
• Adrenal steroids are broken down by the liver and
excreted via the kidneys and in faeces.
Actions of the Adrenal Cortex Hormones
Aldosterone
• Aldosterone is a mineralocorticoid.
• Mineralocorticoids function to regulate ECF volume by
altering the rate of Na+ reabsorption.
• Glucocorticoids have a mild mineralocorticoid action.
• Aldosterone secretion is stimulated by a number of
factors:
• renin–angiotensin system: a reduction in the ECF
volume, blood pressure or Na+ concentration in
plasma (detected by the juxtaglomerular apparatus)
will lead to an increase in the secretion of renin from
the juxtaglomerular cells; this leads to the production of angiotensin II, which stimulates the release of
aldosterone
• ↑ K+ in plasma
• ACTH (does not play a role in the normal regulation
of aldosterone release).
• e actions of aldosterone include:
• stimulation of the reabsorption of Na+ from the dis-
tal convoluted tubule in the kidney
• secretion of K+ into the distal convoluted tubule
• secretion of H+ into the distal convoluted tubule.
248
Testosteron
Cholesterol
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SECTION II Physiology
ACTH control
PregnenoloneI7.OH pregnenolone
ProgesteroneI7.OH progesterone
e
II Deoxycortisol
CortisolOestradiol
Fig. 12.4 Scheme for the production of adrenal cortical hormones.
Cortisol
• e zona fasciculata releases several glucocorticoid hormones: cortisol or hydrocortisone (the main glucocorticoid), corticosterone and cortisone.
• Cortisol is bound to a specic binding protein called
transcortin (75%); approximately 15% is bound to albumin and only 10% is active or free.
• Cortisol secretion is stimulated by a number of factors:
• ACTH: released from the anterior pituitary (pro-
• cardiovascular eects: cortisol is necessary for vasopressors, e.g. epinephrine, to increase vascular tone.
In the absence of cortisol, blood vessels become
unresponsive to the eects of catecholamines
• CNS: cortisol produces euphoria
• anti-inammatory eects: the glucocorticoids have
profound anti-inammatory actions, which include:
• ↓ immunocompetent cells and macrophages
• stimulate synthesis of lipocortin in leukocytes.
moted by CRH released from the hypothalamus); it
binds to receptors in the adrenal glands and stimulates the release of cortisol. Cortisol levels then
inhibit CRH and ACTH release (negative feedback)
• circadian rhythm: cortisol levels are higher rst thing
in the morning (7–8 am) and fall to a lower level in
the middle of the night (1–2 am)
• stress
• trauma
• burns
• infection
• exercise
• hypoglycaemia.
• e actions of cortisol include:
• metabolic eects: the metabolic eects of cortisol
generally oppose those of insulin; they include:
• breakdown of protein to amino acids
• amino acids are then converted to glucose
(gluconeogenesis)
• storage of glucose as glycogen
• immunosuppressive eects: the immunosuppressive
eects of the glucocorticoids include:
• ↓ T-cell number and function
• ↓ B-cell clonal expansion
• ↓ basophils and eosinophils
• inhibit complement
• mineralocorticoid: the glucocorticoid hormones
have very mild mineralocorticoid activity
• permissive eects: this relates to the normal function
of other hormones in the face of normal cortisol levels; they include:
• vascular reactivity to catecholamines
• activity of aldosterone on renal tubules
• activity of ADH on the collecting ducts
• gluconeogenesis
• increases the eect of T3 in maintaining body
• lipolysis: mobilizes free fatty acids and glycerol;
these are then converted to glucose in the liver
• facilitates the action of growth hormone.
Corticosterone
Aldosterone
Under renin-angiotensin
control
is protein inhibits phospholipase A2 and thus
prevents formation of inammatory mediators
such as prostaglandins, leukotrienes and platelet
activating factor (PAF)
temperature
CHAPTER 12 Endocrine System
249
Androgens
• e zona reticularis produces sex steroids: androgens
in men, and oestrogen and progesterone in women; the
amount is insignicant in comparison with the amount
produced by the testes/ovaries.
• Secretion is stimulated by ACTH released from the
hypothalamus.
Medulla
• e adrenal medulla acts as an extension of the sympathetic nervous system. It contains chroman cells that
resemble the post-ganglionic cells in the sympathetic
nervous system. ey do not possess axons but are similar in the fact that they release a number of neurotransmitters from intracellular vesicles once stimulated.
• e main hormones secreted by the adrenal medulla
are epinephrine (adrenaline) and norepinephrine (noradrenaline); they are synthesized from the amino acid
tyrosine
• Epinephrine and norepinephrine released from the
adrenal medulla bind to α-receptors (mainly norepinephrine) and β-receptors (mainly epinephrine).
Binding to these receptors leads to the production of
second messengers such as cAMP; these second messengers lead to further intracellular reactions that ultimately alter cell function.
• e adrenal hormones are rapidly inactivated once
released, by the enzymes catechol-O-methyl-transferase and monoamine oxidase, present in the liver and
kidney.
e eects of epinephrine and norepinephrine are shown
in Box 12.1.
Clinical Physiology
Disorders of Adrenal Function
Addison’s disease
• Addison’s disease is caused by destruction of the adrenal
cortex; this produces a reduction in mineralocorticoid,
glucocorticoid and sex-hormone production.
• e causes of Addison’s disease include:
• primary hypoadrenalism: caused by destruction of
the adrenal cortex; causes include:
• autoimmune (>80%)
• TB (20%)
• haemorrhage, e.g. Waterhouse–Friderichsen syndrome in meningococcal septicaemia
• malignant inltration
• drugs
• secondary hypoadrenalism: due to pituitary disease and the resulting decrease in ACTH secretion;
production of mineralocorticoids is not aected as
BOX 12.1 Efficacy of Norepinephrine
(Noradrenaline) and Epinephrine
(Adrenaline) in Various Physiological
Processes
Norepinephrine >
Epinephrine
↑gluconeogenesis (α1) ↑glycogenolysis (β2)
↓insulin secretion (α2) ↑lipolysis (β3)
Vasoconstriction: ↑BP (α1) ↑insulin secretion (β2)
↑tone in GI sphincters (α1) ↑glucagon secretion (β2)
Bronchoconstriction (α1) ↑K+ uptake by muscle (β2)
Epinephrine >
Norepinephrine
↑heart rate (β1)
arteriolar tone in skeletal
muscle (β2)
↑cardiac contractility (β1)
bronchodilatation (β2)
stimulation is via angiotensin II; sex hormone secretion is also independent of pituitary function.
• e clinical features of Addison’s disease are shown in
Fig. 12.5.
• e clinical features of Addison’s disease are mainly
due to the deciencies in mineralocorticoid and
glucocorticoid:
• mineralocorticoid deciency: there is increased uri-
nary Na+ loss leading to dehydration, ↓ Na+, ↓ blood
pressure, K+ retention leading to hyperkalaemia, and
H+ retention leading to metabolic acidosis
• glucocorticoid deciency: this leads to nonspecic
symptoms such as weight loss, anorexia and lethargy.
Hypoglycaemia may occur during fasting, and there
is reduced resistance to trauma and infection.
Hyperaldosteronism
• Excess secretion of aldosterone may be primary or
sec ond ary.
• Primary hyperaldosteronism:
• a very rare cause of ↑ blood pressure (<1%); it is
caused by adrenal adenomas in 60–70% (Conn’s syndrome) and bilateral hyperplasia in 20–30%.
• Secondary hyperaldosteronism:
• results from excess secretion of renin, this stimulates
angiotensin II and thus aldosterone; causes include:
• renal artery stenosis
• congestive cardiac failure
• cirrhosis.
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Pigmentation
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SECTION II Physiology
Buccal
pigmentation
Postural
low blood
pressure
Weight loss
of scars
Fig. 12.5 Features of Addison’s disease.
• e eects of excess aldosterone secretion include:
• Na+ and water retention, leading to ↑ blood
pressure
• renal K+ loss, leading to hypokalaemia
• renal H+ loss, leading to metabolic alkalosis.
Cushing’s disease/syndrome
• Cushing’s disease/syndrome is due to excess glucocorticoid; this can occur in several situations:
• ACTH-dependent: there is increased ACTH, which
stimulates glucocorticoid secretion. e ACTH may
be from the pituitary (Cushing's disease) or by ectopic secretion from a tumour
• ACTH independent: this is caused by an excess of
glucocorticoid with suppression of ACTH; this can
result from:
• adrenal adenoma
Constipation
Loss of body
hair
• adrenal carcinoma
• glucocorticoid administration.
• e clinical features of Cushing’s syndrome are shown
in Fig. 12.6.
• e main eects of raised glucocorticoids include:
• hyperglycaemia
• muscle wasting due to protein breakdown
• osteoporosis
• striae (stretch marks)
• weight gain, partly due to a stimulation of appetite
but also due to abnormal fat deposition in the face
(moon face) and back (bualo hump)
• ↑ blood pressure, due to uid retention from the
mineralocorticoid activity of cortisol
• hirsutism and acne, due to the androgenic properties
of cortisol.
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