Endocrine System

• The ENDOCRINE SYSTEM includes all the glands (ductless

glands) of the body and the Hormones produced by those glands –
maintain Homeostasis
• Hormone (Greek. Hormaein - to excite/stir up): is a substance of
intense biological activity that is produced by specific cells in the
body and is transported through circulation to act on its target cells
• The endocrine system function is more generalized - In contrast,
ANS homeostasis links to specific target organs - (Circulation,
respiration, digestion, temperature regulation and some endocrine
secretion)
• Glands: Pituitary (anterior and posterior), Thyroid, Parathyroid,
Pancreas, Gonads
• Sites of action: (1) Cell membrane receptors - cAMP, IP3/DAG
generation, direct transmembrane activation of Tyrosine kinase; (2)
Cytoplasmic receptors; and (3) Nuclear receptors
c
CRH
C
C
 Hypothalamic Hormones – releasing or release inhibitory
HYPOTHALAMIC HORMONE
Thyrotropin-releasing hormone
(TRH)
Corticotropin-releasing hormone
(CRH)
Gonadrotropin-releasing hormone
(GnRH)
Growth hormone-releasing hormone
(GHRH)
Growth hormone-inhibiting hormone
(GHIH)
Prolactin-inhibiting hormone (PIH)
Vasopressin and Oxytocin
EFFECTS ON THE ANTERIOR
PITUITARY
Stimulates release of TSH
(thyrotropin)
Stimulates release of ACTH
(corticotropin)
Stimulates release of FSH and LH
(gonadotropins)
Stimulates release of growth
hormone
Inhibits release of growth hormone
Inhibits release of prolactin
 The Anterior pituitary hormones

Acidophils:

Somatotropes – GH
Latotropes – Prolactin

Basophils:

Gonadotropes- FSH & LH

Thyrotropes – TSH
Corticotrope - ACTH
Growth Hormone Physiological Role
Promotes Growth - Coordinated action of several hormones
• GH promotes growth of all organs by inducing hyperplasia – proportionate
increase in the size and mass of all parts – except brain and eye
– Retention of Nitrogen and other tissue constituents – more protoplasm
formation
– Positive Nitrogen balance – due to increase uptake of amino acids
– Promotes utilization of fats – spares glucose (muscles)
• Indirectly: Exerted mainly through Somatomedins or Insulin-like growth
factors (IGF-1 and IGF-2) – growth promoting, nitrogen retaining and
certain other metabolic events
• Direct effect: Lipolysis in adipose tissue, glycogenolysis in liver and
decreased glucose utilization in muscles and also direct effect on bone
growth - stimulating differentiation of chondrocytes
• IGF-I: produced by the liver and other tissues (Receptors are like Insulin)
• IGF-I also stimulates proliferation of chondrocytes (cartilage cells),
resulting in bone growth
Growth Hormone

• Receptors are JAK-STAT protein kinase type

• Regulation: Hypothalamus - secretes GHRH and also inhibitory GHIH
(Somatostatin – also in pancreas) – controls secretion (increasing or
decreasing cAMP) - all are GPCR
• GH secretion – high in children, reaches maximum level in adolescent and
decreases in age related manner - Occurs in irregular pulse, falls between
these pulses
• Amplitude of secretory pulses is maximum at night, shortly after onset of
deep sleep
• Secretory Stimuli: fasting, hypoglycaemia, stress, exercise etc.
• Inhibitory stimuli: Corticosteroids, free fatty acid etc.
• Human growth hormone is called hGH and are peptide hormones
GH
Acromegaly, Dwarfism and Gigantism
• GH deficiency produces dwarfism
• Excess GH before epiphysis closes –
Gigantism
• Excess GH after 18 years – Acromegaly
GH – Clinical Uses
• Natural GH not used due to rise of transmission of disease – lethal
infection (degenerative neurological disorder)
• Preparations: Somatropin is biosynthesis form made by recombinant
DNA technology - Somatrem is similar
1. GHRH: Diagnostic use
To differentiate dwarfism – pituitary (defect of somatrophs) or
hypothalamic (no production of GHRH) origin
Sermorelin (a synthetic material behaves like GHRH) is injected in
dwarfism
• Subsequently hGH level is estimated and If hGH level rises fault
lies in hypothalamus
2. hGH: Pituitary dwarfism
Somatropin is available for clinical use (rhGH) and obtained by
recombinant DNA technique
Dose: 0.03 to 0.07 mg/kg IM or SC 3 times a week
Start at the age of 3 and continued till 20-25 years
Should not administer to persons whose epiphyses are closed
IGF-1 appears in plasma following injection and remains detectable till 48
Hrs.
 Uses of GH
• Constitutional short stature in children
• Adult GH deficit – 150-300 mcg/day SC – mortality and morbidity
reduction
• Catabolic states – burns, renal failure, bed ridden patients and
osteoporosis etc.
• Renal failure in children
• AIDS – wasting (100 μgm/ kg)
• Abuse: Athlete abuse
• ADRs: Pain in injection site - lipodystrophy
– In first 8 weeks – intracranial hypertension, papilledema, visual
changes, headache, nausea and/or vomiting - Fundoscopic
examination at initiation of therapy and at periodic intervals
– Hypothyroidism, salt and water retention, myalgia, hand
stiffness
– Increase type 2 diabetes mellitus
 Somatostatin
• Somatostatin:14 amino acid peptide
• Produce mainly by hypothalamus and also in GIT
• Inhibits secretion of GH, TSH and prolactin by pituitary and insulin
and glucagon by pancreas and all GIT secretions (Gastrin, HCl)
• All GIT secretions are inhibited including HCl - Diarrhoea,
hypochlorhydria, nausea, dyspepsia etc. occurs
• Constrict hepatic, splanchnic and renal blood vessels
• Uses:
– Acromegaly: limited use due to short half-life (2-3 min)
– GI haemorrhages (250 mcg slow IV, 3 mg infusion for 12 Hrs)
– Pancreatic, biliary and intestinal fistulae – antisecretory effects
tumours producing excess HCl
– Diabetic ketoacidosis (inhibits glucagon and GH secretion)
• Drawbacks: Short duration (2-3 min) and rebound GH secretion
 Octreotide
• Synthetic analogue of Somatostatin and 40 times more potent
• Longer duration of action (t1/2 – 90 min)
• In acromegaly preferred - Injection octreotide (100 μg) s.c
thrice daily
• Monitor serum GH and IGF-1 levels to assess effectiveness
• Goal – decrease GH levels < 2ng/ml & IGF-1 levels within
normal range for age and sex
• Octreotide binds preferentially to receptors on GH secreting
tumors - decreases tumor size
• Octreotide inhibits TSH secretion and is treatment of choice in
thyrotrope adenoma that over secrete TSH and not good
candidate for surgery
Octreotide
• Other Uses:
– Secretory diarrhoeas associated with carcinoid, AIDS,
cancer chemotherapy or diabetes (100 mcg SC twice daily)
– benefits due to suppression of hormones which enhance
intestinal mucosal secretion
– Oesophageal bleeding (100 mcg followed by 25-50 mcg/hr
– Octreotide labeled with indium or technetium used for
diagnostic imaging of neuroendocrine tumors such as
pituitary adenoma and carcinoids
• Adverse effects: abdominal pain,diarrhoea and gall
stones
• Lanreotide and Pegyisomant (acromegaly)
 Prolactin brief
• Prolactin (PRL) causes synthesis of milk proteins and lactose by the
breast alveolar epithelium – proliferation of ductal and acinar cells
– After parturition – PRL induces milk secretion: inhibitory
influence of high Oestrogen and Progesterone withdrawn
– Oxytocin causes milk ejection
• Secretion: Very low in childhood, increases in girls at puberty, high
in adult females, progressive increase in pregnancy and peak at term

• PRL suppresses – hypothalamo-pituitary-gonadal axis : Inhibits

GnRH release - lactational ammenorrhoea, infertility etc. and loss
of libido, impotence in male

• Regulation of secretion: Under constant inhibition by PRIH

(dopamine) via D2 receptors
– DA agonists: DA, Bromocriptine, cabergoline
– DA antagonists: CPZ, haloperidol, Metoclopramide (TRH & VIP
– releases PRL)
• NO CLINICAL USE
Prolactin secretion
 Prolactin inhibitors - Bromocriptine
• Ergot derivative: 2-bromo-α-ergocryptine
– Potent dopamine agonist and also has weak alpha-adrenergic
blocking property
– Greater affinity for D2; partial agonist/antagonist at D1
• Pharmacological actions:
– Decrease in prolactin release – anti-galactopoietic
– Increases GH in normal persons but decreases in presence of
pituitary tumours (acromegally)
– Antiparkinsonian effects – like levodopa
– CTZ stimulation – nausea, vomiting
– Hypotension – postural reflex and alpha-blockade
– Decrease in GI motility
• Pharmcokinetics: Partially absorbed (1/3rd), high first pass
– reaches peak plasma concentration within 1-2 Hrs, crosses BBB,
metabolites are excreted in Bile, t1/2 - 3-6 Hrs
 Bromocriptine – contd.
• Mechanism of action:
– Prolactin is under constant inhibitory control of PRIH (Dopamine) –
acts on Pituitary lactotropes via D2 receptors
– Dopamine, Bromocriptine, cabergoline - act as agonist in D2
receptors – inhibitory to prolactin secretion
• Therapeutic uses:
1. Hyperprolactinemia: Due to Microprolactinomas causing
galactorrhoea, ammenorrhoea, infertility in female and impotence
and sterility in male- lower dose of 2.5 to 10 mg/day, response occurs
within weeks
• Should be stopped during pregnancy
• Lifelong therapy is required
2. Acromegaly: inoperable cases of pituitary tumors (5 – 20 mg/day)
3. Parkinsonism
4. Suppression of breast engorgement: neonatal death ?
5. Diabetes mellitus (D2 in hypothalaumus), hepatic coma
 Side effects: similar to levodopa – nausea, vomiting, constipation and
postural hypotension - Lately, behavioral alterations, hallucinations,
psychosis, mental confusions etc. – abnormal movements
 Cabergoline
• New D2 agonist
• More potent and more D2 selective
• Very long half life – 60 days or more
• Twice weekly dose
• Lesser nausea and vomiting
• Better patient compliance and tolerance
• Preferred for hyperprolactinemia and
acromegaly
 Gonadotropins – FSH and LH
Stimulates the gonads and promote gametogenesis and secretion of
gonadal hormones
• FSH: induces follicular growth, development of ovum and
secretion of Oestrogen. In male – spermatogenesis and trophic to
seminiferous tubules. Atrophy of ovary and testes in absence
• LH: Ripening of graafian follicles, triggers ovulation, rupture of
follicles and sustaining of corpus luteum. In male stimulates
testosterone secretion
• Receptors: GPCR – cAMP – gametogenesis – cholesterol to
pregnelone
• Regulation: GnRH (FSH/LH-RH) – single releasing factor for
both
– Secretes in pulses – high frequency, low amplitude and low
frequency, high amplitude
– Oestrogen and progesteron are feedback inhibitors
– Also Testosterone – weak inhibitor of FSH and LH secretion
– Inhibin – inhibits FSH and Dopamine inhibits LH
 Therapeutic Source of gonadotropins
• Preparations
– Urine of menopausal women (hMG) – Menotropin (FSH +
LH)
– Urofollitropin or pure menotropins (pure FSH)
– Placenta: human chorionic gonadotropin (hCG) – only LH
activity – urine of pregnant women
– Recombinant: rFSH and rLH
• Adverse effects: Ovarian bleeding, polycystic ovary, pain in
lower abdomen – due to hyper stimulation
– precocious puberty
– allergic reactions (skin test)
– Oedewma, headache, mood changes
 Therapeutic Uses
1. Amenorrhoea and infertility in low Gns patients (decreased
secretion from pituitary) to induce ovulation: Clomiphene
citrate failed cases Menotropins (75 IU FSH +75 IU LH)
IM daily for 10 days and followed by 10,000 units of hCG –
OVULATION
• Controlled ovarian hyperstimulation – suppression of
endogenous FSH/LH – by superactive GnRH/GnRH
antagonist
2. Hypogonadism in males: oligospermia, male sterility
– Sexual Maturation by Androgens – then Start with 1000-
4000 IU hCG IM 2-3 times a week – to stimulate
testosterone secretion
– FSH+LH (75 IU) after 3-4 months – spermatogenesis
3. Cryptorchism: undescended testes. Start between 1-7 years
of age with 1000-2000 IU 2-3 times a week. Stop if no result
in 2-6 weeks
4. In vitro fertilization: FSH and LH is used to induce
maturation of several ova and to precisely time the ovulation
such that harvesting can be done
 Gonadotropin Releasing Hormone
(GnRH)
• Synthetic GnRH – 100 mg IV – causes release of
FSH and LH
• Short plasma half-life: 4-8 minutes (rapid enzymatic
degradation)
• Used for testing pituitary gonadal axis in male and
female hypogonadism
• Pulsatile exposure to GnRH releases FSH/LH
– Desensitization of pituitary gonadotropes – loss of Gn
release – not used in treatment of hypogonadism
 Long-acting GnRH agonists
• GnRH analogs used clinically are Leuprolide, goserelin,
histrelin, triptorelin and nafarelin – Superactive GnRH

• 15-150 times more potent than natural GnRH – longer acting

(2-6 Hours) – high affinity to receptors and lack of enzymatic
hydrolysis

• MOA: Physiological release is pulsatile – but agonists act

continuously down regulation of GnRH receptors after 1-2
weeks (desensitization)
– Inhibition of FSH and LH – suppression of gonadal function –
suppression of ovulation and spermatogenesis
– Testosterone and oestrogen level falls to castration level
– Pharmacological Oophorectomy
 Nafarelin
• Long acting GnRH agonist and 150 times more potent than
GnRH - Plasma half-life 2 -3 hrs
• Peak down regulation of pituitary GnRH receptors – 1 month
• Uses: Assisted reproduction: 400 mcg BD intranasal
followed by 200 mcg BD when Menstrual bleeding occurs For
suppression of endogenous LH surge – matured oocyte can be
harvested
– Uterine fibroid: symptomatic relief 200 mcg BD
– Endometriosis: 200 mcg for 6 months
– Precocious puberty: 800 mcg BD nasal spray – arrest of
breast and genital development
• Goserelin: Long acting – in Ca Prostate, endometriosis etc. –
1-3 weeks earlier before ovulation
• Triptorelin – long acting (once a month): For regular release –
daily SC injection (female infertility). For long-term use – IM
injection monthly
• Leuprolide: Long acting IM/SC
 GnRH antagonists
• Inhibits Gn without initial stimulation
• Older ones - Reactions due to histamine release
• Newer – Ganirelix, cetrorelix
• Used in in vitro fertilization for suppression of LH surge
• Advantages:
– Quick – competitive antagonist
– Lower risk of ovarian hyperstimulation
– Complete suppression
 d
• Bromocriptine
• Octreotide

• Clinically used GnRH – decreases FSH

and LH secretion - after 2 weeks of
administration - Desensitization
Steroid Biosynthesis - contd.
 Regulation of Synthesis
1. Control by circadian
rhythm (Diurnal
rhythm) – morning rise
2. Stress: hypoglycaemia,
physical stress etc.
 Glucocorticoids - MOA
• Not stored:
– rate of synthesis = rate of release
• Synthesize rhythmically and controlled by irregular
pulses of ACTH, influenced by light and major pulses
occur early in the morning and after meals
• Glucocorticoids act via their receptors located in
nucleus (GR)
• GRs are widely distributed and located almost in all
cells of the body
• They are made up of almost 800 amino acids
 Glucocorticoids - MOA
• GR receptors are located in the cytoplasm
• One GR receptor has a DNA binding domain and a ligand
binding domain along with stabilizing proteins (HSP 90 and
HSP 70)
• This receptor is incapable of activating transcription
• Binding of free steroid molecule to GR forms an unstable
compound
• Therefore HSP and other proteins get dissociated
• The S+GR complex enters the nucleus and binds to
Glucocorticoids response element (GRE) on gene and regulate
transcription by RNA polymerase II and others
• The resulting mRNA is transported to cytoplasm for
production of protein and bring about final response
Glucocorticoids - MOA
 Actions
Numerous actions:
• Carbohydrate, lipid and protein metabolism
• Fluid and electrolyte balance
• Normal functioning of CVS, immune system, kidneys, skeletal
muscles and nervous system
• Provides resistance to stress and noxious stimuli and
environmental changes
• Permits and facilitates the actions of other hormones
• Direct Actions
• Permissive Actions
• Lipolytic effects
• Effect on BP
• Effect on bronchial muscles
• (e.g.,sympathomimetic amine)
 Actions of Corticosteroids -
Mineralocorticoid
• Aldosterone is the prototype of mineralocorticoid effects
• Acts on the distal tubule to enhance absorption of Na+
• Increase excretion of K+ and H
• Similar effects occur in colon, sweat gland and salivary gland
• Deficiency of mineralocorticoid action leads to – dilutional
hyponatraemia, hyperkalamia, acidosis, massive loss of Na+
and decreased EFC volume (essential for survival)
• Hyperaldosterinism: Positive Na+ balance, expansion of ECF,
increased plasma Na, hypokalaemia, alkalosis and progressive
rise in BP – hypertension, myocardial fibrosis etc.
 Glucocorticoid actions - Carbohydrate &
protein metabolism
• Profound effect on carbohydrate and protein metabolism –
aimed at protecting glucose dependent tissues (brain and heart)
• Promotes glycogen deposition in liver and stimulate it to form
glucose from amino acids – gluconeogenesis
• In peripheral tissues decreases utilization of glucose, increase
protein breakdown and activate lipolysis – form amino acids
and glycerol for gluconeogenesis
• All these results in -
– Diabetes like stat resistant to insulin – increased glucose release from
liver + decreased peripheral glucose utilization
– Negative Nitrogen balance (catabolic effect) – amino acid used up in
gluconeogenesis – increased urea production
– Mobilization of amino acids – muscles, thinning of bone and skin
Actions: Carbohydrate and protein metabolism

Negative nitrogen balance & hyperglycaemia

• Gluconeogenesis
– Peripheral actions (mobilize AA & glucose and glycogen)

– Hepatic actions

• Peripheral utilization of glucose

• Glycogen deposition in liver

(activation of hepatic glycogen synthase)
Fat Metabolism
• Redistribution of fats in different areas of the body
• Due to permissive facilitation of effects of other
agents – GH, glucagons, Adr, thyroxine and insulin
– Deposition of fats in face, neck and shoulder – moon
face/buffalo hump
– Glucocorticoids facilitated hormone sensitive lipolysis
action of GH and Adr. + Glucocorticoids mediated
increased insulin = net result is insulin mediated
lipogenesis and fat deposition
– Peripheral adipocytes are less sensitive to insulin, but in
face and neck predominant action – fat deposition
 Actions of Glucocorticoids
• Water excretion:
– Glucocorticoids play important role in maintaining normal GFR - in
adrenal insufficiency capacity to excrete water is lost – water
intoxication
• Calcium Balance:
– Decrease absorption of Ca++ in GIT and increased excretion – calcium
depletion - osteoporosis
• Skeletal muscle:
– Normal muscular activity needs Glucocorticoids at its optimum level
– Excess level leads to muscular weakness and wasting
– Muscular weakness occurs in both Hypocorticism (due to hypodynamic
circulation) and hypercorticism – due to hypokalaemia
• CNS:
– Euphoria – in pharmacological doses
– Addison's disease – apathy, depression and psychosis
– High doses – induce seizure
 Actions of Glucocorticoids
• CVS: Permissive role on pressor effect with Adr and angiotensin
– Maintain tone of arterioles and myocardial contractility
– Adrenal insufficiency leads to low cardiac output and arteriolar dilatation and
poor response to adrenaline
– Cardiovascular collapse – along with mineralocorticoids
• Blood and lymphoid tissues:
– Destruction of lymphoid tissue – modest in normal persons

– In presence of malignancy of lymphatic cells – lytic actions are significant

(apoptosis) – used in lymphomas (Basis of Use)

– Minor effects on haemoglobin and RBCs – protect against haemolysis of RBCs

– Increase in number of RBCs

– Decreases the numbers of circulating lymphocytes, monocytes, eosinophils and

basophils but increases Polymorphs
Glucocorticoids – anti-inflammatory and
immuno suppressive effects
• Suppress inflammatory response to all noxious stimuli:
Pathogens, chemical,physical and immune mediated stimuli,
hypersensitivity
• Underlying cause of disease is not corrected
• Reduction in cardinal signs of inflammation
• Anti-inflammatory effects are non—specific and covers all
components of inflammation:
– Effects on concentration, distribution and functions of peripheral
leukocytes – increased neutrophils & their activity
– In macrophages: reduction of arachidonic acid metabolites (mediators)
like PG, LT and PAF synthesis that results from activation of
phospholipase A2

Basis of exogenous use of most clinical uses

 Glucorticoids - Multiple Mechanisms
• Recruitment of WBC & monocyte - macrophage into
affected area & elaboration of chemotactic substances
• Lipocortin: decreased production of PG, LT and PAF
• Negative regulation of COX 2: inducible PG production
• Negative regulation of genes in cytokines of macrophages,
endothelial cells and lymphocytes:
production of IL (1, 2, 3, 6), TNFα, fibroblast
proliferation and T-lymphocyte function – interference with
chemotaxis
 Contd.
• In endothelial cells-Endothelial leucocyte adhesion molecule
(ELAM) and other – adhesion and localization of leucocytes
interfered
• Release of histamine from basophils is inhibited
• Decreased production of collagenase – prevention of tissue
destruction
• Decreased functioning of osteoblasts and increased activity of
osteoclastic activity - osteoporosis
• Decreased IgG production
• Decreased generation of induced nitric oxide
 Corticosteroids

Lipocortin
Phospholipids

Phospholipase A2

Arachidonic acids

lipoxygenase Cycylooxygenase

Prostaglandins,
Leukotriene Thromboxane
PAF by lipocortin Prostacyclins
 Immunosuppressive & anti-allergic actions

• Suppresses all types of hypersensitivity & allergic

phenomenon
• At High dose: Interfere with all steps of immunological
response
• Causes greater suppression of CMI (graft rejection & delayed
hypersensitivity)
• Transplant rejection: antigen expression from grafted
tissues, delay revascularization, sensitisation of T
lymphocytes etc.
Glucocorticoids – Anti-inflammatory and
Immunosuppressive effects
 Glucocorticoids - Pharmacokinetics
• Therapeutically given by various routes – orally, IM, IV,
topically
• Hydrocortisone undergoes high first pass metabolism
• Oral bioavailability of synthetic corticoids is high
• Both, endogenous and therapeutically administered GC are
bound to Corticosteroid Binding Globulin (CBG)
• Synthetic steroids have to undergo reduction in liver to active
compounds
• Metabolized in liver and excreted in urine
• Exogenously administered hydrocortisone has t1/2 of 1.5 Hrs
 Steroid Preparations
• An ideal GC should have no mineralocorticoid
activity
• Structural changes to the basic cortisol
molecule resulted in a number of compounds
with
– Minimal mineralocorticoid activity
– Greater potency
– Longer duration of action
 Important agents
• Injectable:
Betamethasone Dexamethasone
Prednisolone Methylprednisolone
Hydrocortisone Triamcinolone
• Oral:
Betamethasone Fludricortisone
Prednisolone Prednisone
Methylprednisolone
• Topical:
Betamethasone Clobetasol
Flucinolone Mometasone
• Inhalation:
Beclomethasone Budesonide
Flunisolode
 Chemical Structures
Pharmaceutical steroids are usually obtained from
“cholic acid” (obtained from cattle) or sapogenins found in
plants of Liliacaceae
Cyclopentanoperhydrophe Rings are labeled as A, B, C
nanthrene skeleton and D.

Numbering of each position

essentially follows a uniform
pattern except for the methyls.
 Therapeutic uses
• A number of diverse disease states respond to GCs
• Physiologic doses of Corticosteroids are used for
replacement therapy in primary and secondary
adrenal insufficiency such as Addison`s disease
• Supraphysiologic doses are used for their anti-
inflammatory effects in arthritis, asthma and
inflammatory bowel disease
• In organ transplant patients and those with
autoimmune disorders corticosteroids are used for
their immunosuppressive effects
 Replacement Therapy

• Adrenal insufficiency – acute/chronic

– Abrupt withdrawal of steroid therapy
– Chronic infections – Tuberculosis
– Autoimmune adrenal disease
– Surgery, Hemorrhage and AIDS
• Congenital adrenal hyperplasia
– Congenital disorder due to deficiency of 21-
hydroxylse enzyme – no cortisol but ACTH –
increased androgen production
 Replacement Therapy
• Acute adrenal insufficiency
– IV replacement of sodium chloride and fluid
– IV hydrocortisone 100 mg followed by100 mg every 8 Hrs
– maximal daily rate of secretion
(alternatively, dexamethasone can be used)
• Chronic adrenal insufficiency
– Hydrocortisone
– Prednisolone or dexamethasone – long acting
– Fludrocortisone for mineralocorticoid effects
• Congenital adrenal hyperplasia
– Hydrocortisone 0.6 mg/kg in divided doses – to maintain
feedback suppression
 Anti-inflammatory Uses
• For suppression of inflammatory components in –
– Rheumatoid arthritis – as adjuvant with NSAIDs in severe
cases
– Osteoarthritis – NSAIDs, intra-articular injection
– Rheumatic fever – severe cases with carditis and CHF
– Gout – NSAID failed cases and colchicine failed cases –
intra-articular injection
– Vasculitic disorders: Polyarteritis nodosa
 Autoimmune diseases

Autoimmune haemolytic anaemia

• Idiopathic thrombocytopenic purpura
• Active chronic hepatitis, alcoholic hepatitis
(Prednisolone 1-2 mg/kg/day given till remission
followed by gradual withdrawal or low dose
maintenance)
 Renal diseases
SLE

• Nephrotic syndrome in children

• Renal disease
• Renal sarcoidosis
• Glomerulonephritis – membranous type
(Life saving importance – usually given in large
doses followed by tapering to maintenance
dose)
 Organ Transplant
• Combined with other immunosuppressants –
cyclosporin, azathioprine
• For prolonged use:
• Prednisolone or methylprednisolone are used
– Intermediate duration of action
– Can be easily tapered
– Can be converted to an alternate regime
 Allergic Disorders
• Exhibit a delayed response in allergies (1-2 hrs even
in IV injection)
• In anaphylaxis, angioneurotic oedema and serum
sickness etc. – adrenaline is the choice
• Seasonal allergies, bee sting, drug allergies –
– Allergic reactions can be suppressed by corticosteroids as
supplements
• Intranasal administration in allergic rhinitis -
budesonide and flunisolide
 Bronchial Asthma
• The increased recognition of the immunological and
inflammatory nature of Bronchial asthma has led to the use
of corticosteroids
• In severe asthma attacks
IV hydrocortisone Methylprednisolone
Oral prednisolone
• Acute attacks:
*Inhaled beclmethasone, budesonide, flunisolide
alone or combined with beta-2 agonists/ipratropium
*Oral steroids
 Infectious Diseases
• Indicated only in severe infective diseases to
tide over crisis or prebent complictions
– AIDS and pneumocystis carinii pneumonia
– In haemophilus influenza meningitis to reduce
neurological complications
– Tubercular meningitis
– Lepra reaction
– Scepticaemia

Lepra reaction
 Ocular Diseases
• Important drug therapy for suppressing inflammation
in eye and preservation of sight
• Topical instillations are used for conditions of the
anterior chamber – allergic conjunctivitis, iritis,
iridocyclitis and keratitis etc.
• Systemic steroids for the posterior chamber
• Dexamethasone topical 0.1%
• Prednisolone oral
• Contraindicated in viral, fulminant bacterial
infections, fungal infections and injuries
 Skin Diseases

• The largest application of steroid therapy

• Topical forms are widely used in many
eczematous skin diseases
• Systemic therapy are also required and may be
life saving in
– Pemphigus vulgaris
– Exfoliative dermatitis
– Stevens-Johnson syndrome
GIT

• Inflammatory conditions of intestine like

– Ulcerative colitis
– Crohn`s disease
– Coeliac disease
(oral therapy or retention enema with hydrocortisone)
• May mask the major complications like perforation
and peritonitis
 Malignancy

Hodgkin`s lymphoma

• Essential for combined chemotherapy of

– Acute lymphatic leukemia
– Hodgkin's and other lymphomas
– Hormone responsive breast carcinoma
• Symptomatic relief in other advance
malignancies by improving appetite and
controlling secondary hypercalcaemia
 Cerebral Oedema
• Cerebral oedema due to tumors (neoplasms)
• Traumatic and poststroke oedema (?)
(Dexamethasone or betamethasone is preferred
because no Na+ retaining activity)
• Other CNS conditions - spinal chord injury,
Bell`s palsy and neurocysticercosis
• (Oral Prednisolone is the preferred drug)
 Other Uses

• Antiemetic – with ondansetron

• Acute mountain sickness
• Aspiration pneumonia, pulmonary oedema
from drowning
• Hyperthyroidism – thyroid storm
 Adverse Effects
• Two types:
– From abrupt withdrawal
– Chronic therapeutic use of high dose
• Withdrawal
– Flare up of underlying disease
– Suppression of HPA axis and acute adrenal
insufficiency
– Increased ICT and papilloedema
Adverse Effects

Cushing`s habitus
 Other Important Adverse Effects
• Fluid and Electrolyte Disturbance – Na and water retention
• Precipitation of Diabetes mellitus – hyperglycemia
• Increased susceptibility to infections – immune response
suppression
• Peptic ulceration – bleeding & perforation
• Osteoporosis – flat spongy bones
• Osteonecrosis – avascular necrosis of head of femur,
humorous etc.
• Myopathy – weakness of muscles
• Cataract – posterior sub capsular
• Glaucoma – prolonged topical therapy
• Growth retardation – in children
 Contraindications
• Say no to any drug formulation combined with
steroids
• Remember that STEROIDS are life saving drugs
• Note the following conditions where u have to be
extremely cautious:
– Peptic ulcer
– Hypertension and Diabetes mellitus
– Viral and fungal infections
– Tuberculosis and other diseases
– Osteoporosis
– Epilepsy and psychosis
– CHF and renal failure
 Choosing a Steroid
• Benefit/risk ratio is a major consideration
• Drugs with primary glucocorticoid activity are
used
• Minimal dose to achieve the desired effects is
chosen
• Topical or local therapy is preferred whenever
possible
 Choosing a Steroid – contd.
• Once daily dosing is usually
preferred for oral glucocorticoids
• Large steroid doses are
administered in divided doses to
reduce local GIT effects
• In order to mimic the normal diurnal
cycle and reduce the risk of
adrenal suppression, GCs should
be given in the morning between
6-10 AM
• Alternate day therapy allows the Single
dose
HPA axis to recover on off days Steroid
 Withdrawal of Steroid Therapy
• Taper the dose to reduce GC dose by 2.5-5 mg of prednisolone
equivalent daily
• Once the GC dose is reduced to 5 mg of prednisolone
equivalent, the patient may be switched to a shorter acting
agent for further tapering
• Intermediate acting corticosteroids allow for more flexible
dosing schedule
– Have potent glucocorticoid effects
– Causes lesser suppression of HPA axis
– Causes less GIT irritation
– Preferred for oral therapy
– Prednisolone, methylprednisolone and triacinolone have a half life of
12-36 Hrs, are available in a number of dosage forms
 Adrenocorticosteroid Inhibitors
• Metyrapone: 11 beta-hydroxylase enzyme inhibitor – used in
Cushing`s syndrome and test of pituitary efficiency

• Aminoglutethemide: Stops conversion of cholesterol to

pregnelone (Medical adrenalectomy) – Breast cancers

• Mifepristone: Progesterone antagonist

• Spironolactone: Aldosterone antagonist

• Ketoconazole: Inhibits synthesis of all hormones in testes

and adrenal cortex – used in Cushing`s syndrome and also in
hirsutism in female
 Glucocorticoids
• Promote normal intermediary metabolism:
Glucocorticoids-favor gluconeogenesis through increasing
amino acid uptake by the liver and kidney and elevating
activities of gluconeogenic enzymes. They stimulate protein
catabolism (except in the liver) and lipolysis, thereby
providing the building blocks and energy that are needed for
glucose synthesis.
• Increase resistance to stress: By raising plasma glucose
levels,glucocorticoids provide the body with energy to combat
stress caused by trauma, fright, infection, bleeding, or
debilitating disease.
• Alter blood cell levels in plasma: Glucocorticoids cause a
decrease in eosinophils, basophils, monocytes, and
lymphocytes by redistributing them from the circulation to
lymphoid tissue.
 C

• Have anti-inflammatory action: glucocorticoids are their potent anti-

inflammatory and immunosuppressive activities. These therapeutic effects
of glucocorticoids are the result of a number of actions. The lowering of
circulating lymphocytes is known to play a role. In addition, these agents
inhibit the ability of leukocytes and macrophages to respond to mitogens
and antigens. Glucocorticoids also decrease the production and release of
proinflammatory cytokines. They inhibit phospholipase A2, which blocks
the release of arachidonic acid (the precursor of the prostaglandins and
leukotrienes) from membrane-bound phospholipid. The decreased
production of prostaglandins and leukotrienes is believed to be central to
the anti-inflammatory action. Lastly, these agents influence the
inflammatory response by stabilizing mast cell and basophil membranes,
resulting in decreased histamine release.
Affect other systems: High levels of glucocorticoids serve as feedback
inhibitors of ACTH production and affect the endocrine system by
suppressing further synthesis of glucocorticoids and thyroid-stimulating
hormone. In addition, adequate cortisol levels are essential for normal
glomerular filtration. The effects of corticosteroids on other systems are
mostly associated with adverse effects of the hormones
 USES OF CORTICOSTEROIDS

• ANTI INFLAMMATORY
• Replacement therapy for primary adrenocortical
insufficienc(Addison disease):
• Replacement therapy for secondary or tertiary adrenocortical
insufficiency
• Diagnosis of Cushing syndrome
• Replacement therapy for congenital adrenal hyperplasia
• Relief of inflammatory symptoms
• Treatment of allergies
• Acceleration of lung maturation
 ADRENOCORTICOTROPIC HORMONE (ACTH, CORTICOTROPIN)

• ACTH promotes steroidogenesis in adrenal cortex by

stimulating cAMP formation in cortical cells (through specific
cell surface G protein coupled receptors) → rapidly increases
the availability of cholesterol for conversion to pregnenolone
which is the rate limiting step in the production of gluco,
mineralo and weakly androgenic steroids. Induction of
steroidogenic enzymes occurs after a delay. The stores of
adrenal steroids are very limited and rate of synthesis primarily
governs the rate of release. ACTH also exerts trophic influence
on adrenal cortex (again through cAMP): high doses cause
hypertrophy and hyperplasia. Absence of ACTH results in
adrenal atrophy. However, zona glomerulosa is little affected
because angiotensin II also exerts trophic influence on this
layer and sustains aldosterone secretion.
 Classification - Androgens
• Natural Androgens:
– From Testes:
• Testosterone (5-12 mg daily)
• Dihydrotestosterone (more active) by 5 α-reductase
– From Adrenal cortex: (weak androgens)
• Dehydroepiandrosterone
• Androstenedione
{Females testosterone: 0.25 – 0.5 mg/day (ovary + adrenals)}
• Androsterone – metabolite of testosterone
• Synthetic androgens: Submaximal andrgenic and Cholestatic
jaundice
– Methyltestosterone, Fluoxymesterone – 17-alkyl substituted derivatives
– Orally effective: Testosterone undecanoate and Mesterolone
– Lipid soluble esters: Propionate and enanthate salts
Testosterone

1 2 3

• Produced from cholesterol primarily by Leydig cells in testes

• Secreted at adult levels during 1st trimester1, during neonatal life2,
continually after puberty3
• Converted by 5 α-reductase to the more potent, 5α-
dihydrotestosterone (DHT), which is responsible for many of the
responses to testosterone in the urogenital tract (e.g. prostate gland
hyperplasia)
• Binds to and activates a single androgen receptor (AR)
• Androgen receptors are present in many tissues including
reproductive tissue, skeletal muscle, brain, kidney etc.
• All androgens contain a Testosterone structures
• Testosterone has 19-carbons and in general its a steroidal
structure

17-alkyl substitution Methyltestosterone

Testosterone

Fluoxymesterone
 Cholesterol ACTH

Oestriol
Pregnenolone 17-α- Hydroxy Dehydro-epi
pregnenolone androsterone

Progesterone 17- Hydroxy Andro-

Oestrone
progesterone stenedione

11-Desoxy- 21,β hydroxylase

corticosterone
11- Desoxy-
cortisol
Corticosterone
11,β hydroxylase
18-Hydroxy-
corticosterone

ALDOSTERONE CORTISOL TESTOSTERONE OESTRADIOL

 Regulation of Secretion

• Testosterone secretion - Leydig`s

cell of testes
• Pulsatile LH – Pituitary
• FSH – only Spermatogenesis
• High testosterone – inhibits LH
(atrophy)
• Oestrogen – feedback inhibition
• Inhibin – FSH inhibition

• Plasma level of Testosterone:

0.3 to 1 mcg/dl (male)
20 to 60 ng/dl (female)
 Pharmacological Actions -
Testosterone
Androgenic Effects:
• In the foetus, testosterone promotes development of male reproductive tract
– internal genitalia, vas deferens, epididymis and external genitalia (sex
differentiation)
• During puberty, testosterone promotes development of :
– primary sexual characteristics (e.g. enlargement of penis, scrotum and
testes)
– secondary sexual characteristics (e.g. male body shape, axillary/pubic
hair, deeper pitch of voice, thickening of skin – greasy, loss of
subcutaneous fat)
– Adulthood: Baldness, BHP, Prostatic cancer
Testes: Promotion of spermatogenesis and maturation of sperm
• Moderately high dose causes testicular atrophy by inhibiting Gn
secretion
• Higher doses: direct sustaining effect and less marked atrophy
 Testosterone – anabolic effects

• Pubertal spurt of growth at

puberty – both boy and girl
• Bone growth – thickness and
length
• Oestrogen from testosterone –
fuse of bones and mineralization
• Muscle building – if aided by
exercise
• Positive nitrogen, minerals and
water balance – increase in weight
• Increase in appetite
• Acceleration of erythropoiesis
Androgens – Targets of Action
 Mechanism of Action
Androgen receptor:
• Both, testosterone and DH testosterone – act via Androgen receptors (AR)
– nuclear receptor super family
• Ligand binding and DNA binding domains
• Mutations in AR: Incomplete sexual development
– Kennedy`s disease: in spinal and
bulbar muscle atrophy
Estrogen Receptor:
• Teststerone converts to
estrogen by CYP19
• Deficiency of CYP19 and
estrogen receptor – failure
to fuse long bones,
osteoporosis etc.
 cytoplasm Nucleus

T- R T- R

10%

90%
T DHT DHT- R

R
5-  reductase
 Androgen - Pharmacokinetics
• Absorption: undergoes high first pass metabolism.
Therefore IM injections or synthetic preparations are
used

• Transport: highly protein bound in plasma to albumin

& sex hormone binding globulin (SHBG)
(98%, SHBG, albumin)
• Metabolism:
– by liver enzymes : androsterone & etiocholanolone
– excretion by urine after conjugation
– small quantity of oestrogen also produced from
testosterone, but not from fluoxymesterone and
Dihydrotestosterone
 Therapeutic Uses of Androgens
• Androgen replacement therapy (ART)
• ART uses derivatives of testosterone, rather than synthetic
Androgens, because they are safe, effective and easy to monitor

1. Androgen deficiency: clinical diagnosis confirmed by hormone

assays
– is usually caused by
• underlying testicular disorders (high LH, but low
testosterone levels)
• hypothalamic-pituitary disorders (low LH and low
testosterone levels)
• Goal: Mimic the normal testosterone concentration as closely as
possible (serum concentration monitoring)
• If untreated, does not shorten life expectancy, but is associated with
significant morbidity (ambiguous genitalia, delayed puberty &
infertility)
• Treated by androgen replacement therapy (ART), usually for the
remainder of life. The aim is to restore tissue androgen exposure by
using the natural androgen testosterone
 Uses – contd.
2. Hypopituitarism
– Monitoring at anticipated time of puberty
3. AIDS related muscle wasting
4. Hereditary angioneurotic edema (methyltestosterone)
5. Ageing
Misuse: involves prescription with no acceptable medical
indication
• Examples of misuse include:
– male infertility
– male sexual dysfunction or impotence
– “male menopause” (andropause)
no convincing evidence that androgen therapy is either effective
treatment or safe for older men unless there is frank androgen
deficiency
Androgens – Adverse Effects
• Virilization:
– may occur in women receiving relatively high doses for prolonged
periods, such as for estrogen-dependent mammary carcinoma
• Cholestatic Jaundice
– may be produced by steroids possessing a 17-alkyl substituted group
• Priapism (sustained erection)
• Oligospermia
• Oedema--via promotion of salt and water retention
• Precocious puberty and short stature
• Acne
• Hepatic carcinoma`````
• Gynaecomastia
 Anabolic Steroids
• Synthetic androgens – higher anabolic but lower
androgenic activity (1: 3 ratio) – decreased virilizing
effect
• Similar anabolic effect, same receptors and same
androgenic effects
• Examples:
– Nandrolone propionate 10-25 mg/ml (10 – 50 mg
IM/week) – inj. Durabolin
– Nandrolone decanoate 25-100 mg/ml (25-100mg/week) –
inj. Decadurabolin
– Stanazolol (2 mg tablets (2-6 mg/day)
 Anabolic Steroids – Therapeutic uses
Catabolic states: Acute illness, severe trauma, major
surgery
1. Renal insufficiency
2. Osteoporosis
3. Suboptimal growth in boys
4. Anaemia: haemolytic and malignancy associated
5. Performance enhancement
 Anti-androgens
• Danazol
• Cyproterone acetate
• Flutamide
• Finasteride, Bicalutamide
Danazol

• Ethisterone derivative effective orally

• Weak androgenic, anabolic, progestational & glucocorticoid action
• Also Labeled as impeded/attenuated androgen:
– Induces some androgen specific mRNA production
• Prominent effect –
– suppression of Gn (FSH and LH) secretion from Pituitary -
FSH & LH release in both sexes decrease – inhibition of
testicular/ovarian function directly
– Directly by inhibition of steroidogenic enzymes
– Results in endometrial atrophy and ammenorrhoea
• Half life – 12-18Hrs
• Preparations:
– 50. 100 and 200 mg. tablets
– Dose is 200 – 600 mg/day
 Danazol – contd.
• Uses: • Side effects: Dose
– Endometriosis : 3-6 related
months course • Amenorrhea (High
– Menorrhagia doses)
– Fibrocystic breast • Androgenic effects -
disease Decreased breast size,
– Hereditary angioneurotic hirsutism, weight gain
oedema etc.
– Gynecomastia • Hot flashes, night
sweating, cramps
– Infertility
• Loss of libido in men
 Cyproterone acetate
• Direct antiantiandrogenic action
• Progesterone like activity – inhibits LH causing antiandrogenic
action
• Competes with dihydroteststerone for intracellular receptor
Uses:
• Precocious puberty in Boys
• Inappropriate sexual behaviour in men
• Virilization in women
• Limited use
 Flutamide
• Non-steroidal and no hormonal activity but specific
antiandrogenic action
• Active metabolite “2-hydroxyflutamide” causes competitive
block Androgen action – Accessory sex organs and Pituitary
• Increased LH secretion by blocking feedback inhibition
• Plasma testosterone level may increase – to overcome direct
antiandrogenic effect
• Uses:
– Cancer of prostate along with GnRH agonist
– Female hirusitism
• ADRs: Gynaecomastia and breast tenderness and also liver
damage
• Dose: 250 mg tds.
 Finasteride
• MOA: Competitive inhibitor of 5 α-reductase
– Selective of 5 α-reductase type-2 isoenzyme
– Mainly acts on urogenital tract (prostate) – DHT level lowered but
not plasma Testosterone level
• Uses:
1. Benign prostatic hypertrophy – decrease in prostate volume,
improved urinary flow, reversion of disease progression
– Withdrawal results in regrowth – prolonged therapy
2. Male pattern baldness
– Kinetics: effective orally, metabolized in liver (t1/2 – 4-6
hrs)
– Side effects: loss of libido, impotence, decreased ejaculation
– Doses: 5 mg OD (BHP) or 1 mg OD in baldness
Erectile Dysfunction Drugs
PDE-5 Inhibitors: Sidenafil, tadalafil
– Nitric oxide (NO) pathway
 Sidenafil
• Absorbed orally and half-life is 4 Hrs
• Inhibits PDE5 in the corpus cavernosa of the penis
• 50 mg 1 h before sexual activity
• Potentiate nitrate’s hypotension activity
• Ketoconazole, erythromycin, Verapamil increases its level – due to
CYP3A4 inhibition
• renal & hepatic disease increases its level
• Side effects:
– headache, flushing, dyspepsia, myalgia, loose motion
– Colour vision impairement (PDE6)
– Fall in BP and precipitation of MI
– Patient with Nitrates for angina
• Other Uses: Pulmonary hypertension
 Thyroid

• The thyroid gland facilitates normal growth and maturation

by maintaining a level of metabolism in the tissues that is
optimal for their normal function. The two major thyroid
hormones are triiodothyronine (T3; the most active form)
and thyroxine (T4). Inadequate secretion of thyroid
hormone
• (hypothyroidism) results in bradycardia, poor resistance to
cold, and mental and physical slowing. In children, this can
cause mental retardation and dwarfism. In contrast, excess
secretion of thyroid hormones
• (hyperthyroidism) can cause tachycardia and cardiac
arrhythmias, body wasting, nervousness, tremor, and heat
intolerance.
THYROID- SYNTHSIS
 Physiology
• half-life of 2 to 4 minutes
• Secretion mainly controlled by ionized
calcium levels via calcium sensing receptors (
CaSR)
• CaSR G protein coupled receptors present on
the chief cells
• is expressed on the surface of the parathyroid
cell and senses fluctuations in the
concentration of extracellular calcium
 Physiology
• Calcium binds on CaSR and reduces
intracelular c AMP decreases the PTH
secretion
• PTH secretion is also controlled by
catecholamine levels, magnesium levels
 Physiology
• PTH functions to regulate calcium levels via
its actions on three target organs, the bone,
kidney, and gut
 Regulation
The monocyte osteoclast precursor cells in the marrow near the bony surface are
activated to proliferate and fuse to form multinucleated osteoclasts. The osteoclast-
precursors express a ‘receptor for activation of nuclear factor-κ B’ (RANK) on their
surface. The osteoblasts on activation release a protein RANK-ligand (RANKL).
When RANKL is bound to RANK on the surface of osteoclast-precursors they are
transformed into mature osteoclasts and develop bone lysing ruffled surface. A bone
resorption pit is dug out by secretion of acid and proteolytic acid hydrolases.
Osteoblasts produce another protein osteoprotegerin (OPG) as well, which can bind
RANKL and prevent it from combining with RANK to activate osteoclasts. Thus,
osteoblasts by producing RANKL and OPG regulate bone resorption.
• After formation of the remodeling pit, preosteoblasts from bone marrow stem cells
proliferate, migrate to the base of the pit, transform into mature osteoblasts and
laydown new osteoid, which is later mineralized.
• Parathormone (PTH) acts on PTH-receptor located on the osteoblast membrane
and induces RANKL production— indirectly activating osteoclast differentiation
and function. Subsequently PTH promotes new bone formation as well.
• Calcitriol also induces RANKL in osteoblasts to indirectly activate osteoclasts.
Similarly, it promotes laying of osteoid as well as bone mineralization.
• Calcitonin directly inhibits osteoclast function and probably enhances osteoblastic
new bone formation.
 MAINTENANCE OF CALCIUM
AND PHOSPHATE HOMEOSTASIS
• It is dependent on  Na Cl and KCL
complete absorbtion at
– Intestinal intestine but CALCIUM
– Bone AND PHOSPHATE is
incomplete
– Renal function  * because of the
requirement for vitamin D
and formation of insoluble
salts like; Calcium
phosphate,calcium oxalate
and magnesium phosphate
at the intestinal lumen
 PARATHYROID GLANDS
Parathyroid hormone - protein

 Affects the metabolism of Са

and Р
- Promotes moving of Са2+
from bones into blood
- Inhibits reabsorption of Р in
kidneys (decreases the content
of Р in blood due to its
excretion with urine)
- Stimulates the absorption of
Ca in the intestine
PARATHYROID HORMONE
• A polypeptide secreted from the parathyroid
glands in response to a decrease in the plasma
concentration of ionized calcium
PTH increases Ca concentration
• 1. In the presenc e of by:
permissive amounts of
vitamin D it stimulates
bone resorptionrelease
of calcium phosphates
• 2. Enhances intestinal
Calcium and phosphate
absorption promotes
formation of vit D
• 3. It augments renal
calcium reabsorption
 PTH
• Regulation of Synthesis
– Biosynthesis is regulated by levels of calcium
– An acute decrease of Ca results in marked increase of
PTH mRNA increase of PTH synthesis
– Effects is at the level of gene transcription, MRNA
stability, mRNA translation
– Rate of degradation of PTH is low if low calcium and
high if calcium is high
– PTH synthesis can be enhanced by the size and number
of PTH producing chief cells in cases of prolonged
hypocalcemia
  Hypofunction
 Hyperfunction - hypocalciemia
(Recklinghausen’s - hyperphosphatemia
disease) - hypophosphaturia
- hypercalciemia - tetanus
- hypophosphatemia
- hyperphosphaturia
- osteoporosis
- Accumulation of Са in
tissues
Hyperparathyroidism: adenoma or
hyperplasia or ectopic
Hypocalcemia
 1,25 Vitamin D3
• Increases Ca++ uptake from the gut
– Increase transcription and translation of Ca++ transport proteins in gut
epithelium UV

Cholesterol precursor 7-dehydrocholesterol

Vitamin D3

25 Vitamin D3

1,25 Vitamin D3

Low plasma Ca++ increase kidney enzymes

 Vit D
• Vitamin D is the collective name given to
antirachitic substances synthesized in the body
and found in foods activated by UV radiation.D3
: cholecalciferol — synthesized in the skin
under the influence of UV rays. D2 :
calciferol—present in irradiated food—yeasts,
fungi, bread, milk. D1 : mixture of antirachitic
substances found in food—only of historic
interest.