11. • CORTISOL is formed in Zona Fasciculata.
• It has both glucocrticoid and
mineralocorticoid action
• It is converted to cortisone by 11B-
HYDROXISTEROID DEHYDROGENASE TYPE
2 enzyme which has only glucocorticoid
action
15. EFFECT ON FAT METABOLISM
• MIMIMAL LIPOLYSIS
• Increased FFA .
• Adipose tissue deposition present but more of
redistribution of body fat occurs leading to
• BUFFALO HUMP ,MOON facie ,central OBESITY
19. WORK UP
Screening test :
• 24-hour urinary cortisol: increased
• Spot Salivary cortisol: increased
• Overnight dexamethasone suppression test
20. Low-dose DX Suppression Test :
• 0.6mg . 6hr for 2 days
• A normal result is decrease in cortisol levels upon
administration of low-dose dexamethasone.
• Positive result suggests cushing syndrome
21. Large Dose DX Suppression Test
• D.X 2mg 6h .2 days
• Cortisol reduced : Cushing's disease (Pituitary adenoma)
• Cortisol still remains high :Adrenal tumor, carcinoma,
ectopic ACTH Syndrome
25. The remarkable anti inflammatory properties of
glucocorticoids have lead to their use in wide variety of
clinical condition
Equivalent doses of commonly used glucocorticoids…..
• hydrocortisone 20mg
• prednisolone 5 mg
• cortisone acetate 25 mg
• dexamethasone 0.5 mg
28. Adverse effect of glucocorticoids
Adverse effects are related to dose, duration and pre-existing conditions like DM and
osteoporosis.
• Diabetes mellitus
• Osteoporosis- fracture risk is increased. So whenever duration of steroid
therapy is >3 months, bone protective therapy should be considered.
• Weight gain
• Dyslipidemia
• Mood disturbance- depression, mania
• Insomnia
• Also increases WBC count – mainly neutrophils.
• Anti- inflammatory effect of glucocorticoids mask signs of disease.
• Lead to activation of latent TB, varicella zoster virus infection.
29.
30. Measures to reduce side effects of corticosteroid therapy:
By administering:
• Lowest required dose
• On alternate day.
• In the morning
• For the shortest duration
• Only under medical supervision.
• Use H2 blockers or PPI.
• Use bisphosphonates.
31. Management of glucocorticoid withdrawal
• Glucocorticoid therapy leads to HPA axis suppression.
• So if glucocorticoids have been administered for>3 weeks, then
withdrawal of treatment leads to adrenal insufficiency.
• c/f- anorexia, nausea, weight loss, emesis, fatigue, myalgia, arthralgias,
postural hypotension etc.
• For this, drug must be slowly withdrawn to allow adrenal glands to
resume cortisol production.
34. It Results From Inadequate Secretion Of Cortisol and/Or
Aldosterone.
Three types-
• Primary –failure of adrenal glands .
• Secondary- failure of HPA axis
Usually due to chronic exogenous glucocorticoid
administrartion.
Pituitary failure.
• Tertiary – hypothalamic dysfunction .
35. Primary adrenal insufficiency
Addison’s disease
1. Infections
• TB = infectious cause worldwide
• HIV = infectious cause
• CMV infection
2. Metastatic carcinoma
3. Bilateral adrenalectomy
38. Secondary adrenal insufficiency
• HPA AXIS FAILURE
deficiency of glucocorticoids and adrenal androgens and
mineralocorticoids are unaffected .
Most common cause – chronic exogenous glucocorticoid
therapy .
Less common causes – postpartum necrosis ( sheehan
syndrome)
Head trauma , adenoma , hemorrhage .
41. • Hyponatremia –
• Primary- lack of aldosterone and soidum wasting
• Secondary – due to vassopressin secrertion and
water loss
• Hyperkalemia – only in primary insufficiency with
metabolic acidosis .
42. Adrenal crisis
• Lifethreatening emergency .
• May be primary or secondary .
• Clinical presentation – hypotension resistatnt to
catecholamines and I v fluids .
• Abrupt adrenal failure usually from gland hemmorhage or
thrombosis – anticoagulation , DIC , sepsis ,
• Usually present with abdominal and flank pain .
47. • Glucocorticoid replacement
–oral hydrocortisone (cortisol) 15–20 mg daily in
divided doses, typically 10 mg on
–waking and 5 mg at around 1500 hrs.
48. • Mineralocorticoid replacement therapy
–Fludrocortisone (9α-fluoro-hydrocortisone) is
administered at the dose of 0.05–0.15 mg daily,
– and adequacy of replacement may be assessed by
measurement of blood pressure, plasma
electrolytes and plasma renin.
– It is indicated for virtually every patient with
primary adrenal insufficiency
49. • Androgen replacement
–Androgen replacement with DHEAS (50
mg/day) is occasionally given to women with
primary adrenal insufficiency
– side-effects such as acne and hirsutism.
50.
51. Incidental adrenal mass
• It is not uncommon for a mass in the adrenal gland to
be identified on a CT or MRI scan of the abdomen that
has been performed for another indication.
• Such lesions are known as adrenal ‘incidentalomas’.
52. Clinical assessment and investigations
• usually asymptomatic.
• However, clinical signs and symptoms of excess
glucocorticoids ,mineralocorticoids , catecholamines
and, in women, androgens should seen
53. Investigations
1.Dexamethasone suppression test,
2.urine or plasma metanephrines and
3. in virilised women, measurement of serum testosterone, DHEAS
and androstenedione.
4.Patients with hypertension should be investigated for
mineralocorticoid excess.
5.In bilateral masses consistent with adrenocortical lesions, 17-OH-
progesterone should also be measured.
6. CT and MRI
7. Biopsy
54. • CT and MRI are equally effective in assessing the
malignant potential of an adrenal mass, using the
following parameters:
• Size:-The larger the lesion, the greater the malignant
potential. Around 90% are over 4 cm in diameter.
• Configuration:-
• ++ Homogeneous and smooth lesions are more
likely to be benign.
• ++The presence of metastatic lesions elsewhere
increases the risk of malignancy.
55. • Presence of lipid:- adenomas are usually lipid-rich,
• resulting In an attenuation of below 10
Hounsfield units (HU)
• Enhancement:-
»Benign lesions demonstrate rapid washout
of contrast
» Malignant lesions tend to retain contrast.
56. Management
• In patients with radiologically benign, non-functioning
lesions of less than 4 cm in diameter, surgery is
required only if serial imaging suggests tumour growth.
• Functional lesions and tumours of more than 4 cm in
diameter should be considered for surgery.
59. Clinical features
• Individuals with primary hyperaldosteronism
are usually asymptomatic
• but may have features of sodium retention or
potassium loss.
• Sodium retention causes oedema
60. • Hypokalemia may cause
muscle weakness
polyuria (secondary to renal tubular damage,
which produces . nephrogenic diabetes insipidus) and
occasionally tetany (because of associated
metabolic alkalosis and low ionised calcium).
• Blood pressure is elevated but accelerated phase
hypertension is rare.
61. INVESTIGATIONS
• 1.Biochemical
• Routine blood tests may show a hypokalaemic alkalosis.
• Plasma renin and aldosterone
• The aldosterone : renin ratio (ARR) is employed as a screening
test for primary hyperaldosteronism in hypertensive patients.
Almost all antihypertensive drugs interfere with this ratio (β-
blockers inhibit while diuretics stimulate renin secretion)
62. • 2. Imaging
• CT scan
• MRI
• If the imaging is inconclusive then adrenal vein
catheterisation with measurement of aldosterone is
required.
63. MANAGEMENT
• Mineralocorticoid receptor antagonists (spironolactone and
eplerenone) are valuable in treating both hypokalaemia and
hypertension in all forms of mineralocorticoid excess.
• Up to 20% of males develop gynaecomastia on spironolactone.
• Amiliride (10–40 mg/day), which blocks the epithelial sodium
channel regulated by aldosterone, is an alternative.
65. Introduction
• These are rare neuro-endocrine tumours that may secrete
catecholamines.
• 80% of these tumours occur in the adrenal medulla
(phaeochromocytomas).
• 20% arise elsewhere in the body in sympathetic ganglia
(paragangliomas).
• Around 40% are associated with inherited disorders, including
neurofibromatosis von Hippel–Lindau syndrome MEN 2 and MEN 3.
• Paragangliomas are particularly associated with mutations in the
succinate dehydrogenase B, C and D genes.
66. Clinical features
• Hypertension (usually
paroxysmal; often postural drop
of blood pressure)
• Paroxysms of : Pallor
(occasionally flushing)
Palpitations, sweating Headache
Anxiety (angor animi)
• Abdominal pain, vomiting
• Constipation
• Weight loss
• Glucose intolerance
67. Investigations
• Plasma metanephrine is the most sensitive test.
• Chromogranin A: It is a major secretory protein present in
the soluble matrix of chromaffin granules and is elevated.
• Provocative (glucagon provocative test) and adrenolytic
(clonidine, phentolamine test) tests.
• CT scan: To localize tumor.
• Scintigraphy: Useful for localization of tumor and includes:
• – MIBG (meta-iodobenzyl guanidine) scintigraphy.
• – (18 F) flurodihydroxyphenylalanine (DOPA) PET scan.
68. Management
• In functioning tumours, medical therapy is required to prepare the
patient for surgery, preferably for a minimum of 6 weeks, to allow
restoration of normal plasma volume.
• Combined α + β-blockade to be given at least 2 weeks
preoperatively to control the hypertension.
• Antihypertensive agents used are: phenoxybenzamine, selective α1-
blocker (prazosin, terazosin, or doxazosin) and propranolol.
• The most useful drug in the face of very high circulating
catecholamines is the α-blocker phenoxybenzamine (10–20 mg
orally 3–4 times daily) because it is a non-competitive antagonist.
69. • During surgery, sodium nitroprusside and the short-
acting α-antagonist phentolamine are useful in
controlling hypertensive episodes.
• Management options for metastatic tumours include
debulking surgery, radionuclide therapy with 131I-MIBG,
chemotherapy and (chemo) embolisation of hepatic
metastases; some may respond to tyrosine kinase and
angiogenesis inhibitors.
70. Congenital adrenal hyperplasia
CAH is an inherited group of disorder characterized by a
deficiency of one of the enzyme necessary for cortisol
biosynthesis.
R NO 79 & 80
71. Pathophysiology:
• The most common enzyme defect is 21-hydroxylase
deficiency. This results in impaired synthesis of cortisol and
aldosterone, and accumulation of 17-OH-progesterone, which
is then diverted to form adrenal androgens.
72.
73. Types:
21-hydroxylase deficiency:
• Defective gene: CYP21A2
• Most common type of CAH
– Classic(neonatal): genital ambiguity in females, adrenal
insufficiency
– Non classic(late onset):presents later in life with androgen
excess signs
17-alpha hydroxylase deficiency:
• Defective gene:CYP17A1
• Steroid precursors to testosterone, cortisol synthesis shunted to
aldosterone
75. Clinical features:
21-hydroxylase deficiency
Varies by subtype
17-alpha hydroxylase deficiency
• Mineralocorticoid excess leads to secondary hypertension,
hypokalemic alkalosis
• Gonadocorticoid deficiency :males mildly underdeveloped
genitalia, hypergonadotropic gonadism, females: abnormal
pubertal sexual development, infertility
11-beta-hydroxylase deficiency
• Androgen excess leads to external genitalia virilization, sexual
ambiguity
• Biphasic mineralocorticoid balance leads to salt-wasting crisis in
early infancy, secondary hypertension and hypokalemia in
childhood and adult life.
76. • In about one-third of cases, this defect is severe and
presents in infancy with features of glucocorticoid and
mineralocorticoid deficiency and androgen excess, such as
ambiguous genitalia in girls.
• The other two-thirds, mineralocorticoid secretion is
adequate but there may be features of cortisol insufficiency
and/or ACTH and androgen excess, including precocious
pseudo-puberty, which is distinguished from ‘true’
precocious puberty by low gonadotrophins.
77. • Both 17-hydroxylase and 11β-hydroxylase deficiency may
produce hypertension due to excess production of 11-
deoxycorticosterone, which has mineralocorticoid activity
as it suppresses rennin/angiotensin system that leads to
low renin hypertension.
78. Investigations:
• Circulating 17-OH-progesterone levels are raised in 21-
hydroxylase
17-OH-progesterone can be routinely measured in
heelprick blood spot samples taken from all infants in the first
week of life.
In siblings of affected children, antenatal genetic diagnosis can
be made by amniocentesis or chorionic villus sampling
80. • Hydrocortisone is a good treatment option for the prevention of adrenal
crisis, but longer acting prednisolone may be needed to control androgen
excess.
• In children, hydrocortisone is given in divided doses at 1-1.5 times the
normal cortisol production rate (~10-13 mg/m2 per day).
• In adults, if hydrocortisone does not suffice, intermediate-acting
glucocorticoids (e.g., prednisone) may be given, using the lowest dose
necessary to suppress excess androgen production.
81. • For achieving fertility, dexamethasone treatment may be required but should
only be given for the shortest possible time period to limit adverse metabolic
side effects.
• The recent introduction of modified and delayed-release hydrocortisone,
which mimics the endogenous physiologic cortisol release pattern, is
promising , providing effective control of steroid precursor excess while the
daily hydrocortisone dose is lower than required for immediate- release
hydrocortisone.
82. • Biochemical monitoring should include androstenedione and testosterone,
aiming for the normal sex-specific reference range.
• 170HP is a useful marker of overtreatment, indicated by 170HP levels within
the normal range of healthy controls.
• Glucocorticoid overtreatment may suppress the hypothalamic-pituitary-
gonadal axis.
• Thus, treatment needs to be carefully titrated against clinical features of
disease control.
• Stress-dose glucocorticoids should be given at double or triple the daily dose
for surgery, acute illness, or severe trauma
83. • Poorly controlled CAH can result in adrenocortical hyperplasia, which gave
the disease its name, and may present as macronodular hyperplasia
subsequent to long-standing ACTH excess .
• The nodular areas can develop autonomous adrenal androgen production
and may be unresponsive to glucocorticoid treatment.
• The prevalence of adrenomyelolipomas is increased in CAH; these are
benign but can require surgical intervention due to lack of lself-limiting
growth.
84. • Mineralocorticoid requirements change during life and are higher in
children, explained by relative mineralocorticoid resistance that
diminishes with ongoing maturation of the kidney.
• Children with CAH usually receive mineralocorticoid and salt
replacement.
• How- ever, young adults with CAH should undergo reassessment of
their mineralocorticoid reserve. Plasma renin should be regularly
monitored and kept within the upper half of the normal reference
range.
