Pathology of endocrine disease

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Pathology of Endocrine Disease
Adrenal glands Dr. Arrigo Capitanio Department
of Pathology
05-11
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Adrenal glands

• Anatomy and physiology
• Cortical pathology
• Hyper cortico-adrenalism
• Hypo cortico-adrenalism
• Medullary Pathology

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Adrenal glands

• Adrenal glands are retroperitoneal structures
  located on the upper poles of the kidneys
• Combine two distinct endocrine systems
• Adrenal cortex derived from the mesoderm
• synthesises and secretes corticosteroid hormones
  produced from cholesterol
• Adrenal medulla derived from the neuroectoderm
• neuroendocrine component - synthesises and
  secretes the catecholamines adrenaline,
  noradrenaline and dopamine

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Adrenal cortex

• Composed of three zones
• Zona glomerulosa
• Outermost zone comprising 10 of the cortex and
  synthesising the mineralocorticoid aldosterone
  (regulated by plasma K and renin-angiotensin)
• Zona fasciculata
• Middle zone comprising 80 of the cortex and
  containing large amounts of relatively inactive
  cholesterol, on stimulation forms cells
  resembling the reticularis
• Zona reticularis
• Innermost zone which, with the zona fasciculata,
  synthesises glucocoticoids including cortisol and
  corticosterone, and androgens (under ACTH
  control)

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Zona glomerulosa
Zona fasciculata
Zona reticularis
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VS
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Adrenal cortex normal steroid synthesis
Normal adrenal steroid biosynthesis
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Adrenal cortexHyperadrenalism

• Excessive secretion of any one of the three basic
  types of corticosteroids gives rise to a distinct
  clinical syndrome
• 1. Aldosterone hyperaldosteronism (Conns
  syndrome)
• 2. Cortisol Cushings syndrome
• 3. Androgens adrenogenital syndromes

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Hyperadrenalisms

• Adrenal cortex
• Primary Hyperaldosteronism

• Primary hyperaldosteronism excess aldosterone
  secretion which is independent of the
  renin-angiotensin system (Conns syndrome)
• Causes
• Aldosterone secreting adenoma
• Bilateral hyperplasia of the cortex
• Rarely carcinoma
• Clinical features
• Hypertension, hypokalaemia, sodium retention,
  muscle weakness, paraesthesia, ECG changes,
  cardiac decompensation

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Renin-Angiotensin System renin, secreted by the
juxtaglomerular apparatus, activates the
precursor angiotensinogen. This liberates
angiotensin I, then angiotensin II, a
vasoconstrictor and stimulant to the secretion of
aldosterone.
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• Adrenal cortex
• Secondary Hyperaldosteronism

• Secondary hyperaldosteronism - adrenal response
  to increased levels of renin-angiotensin
• Causes
• Renal ischaemia
• Chronic oedema (Nephrotic syndrome, ascites)

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Hyperadrenalisms
2. Adrenal cortex Cushings syndrome

• A chronic excess of cortisol
• Pathogenesis
• Prolonged treatment with glucocorticoids such as
  prednisolone
• Pituitary hypersecretion of ACTH (e.g. by
  adenoma)
• Cushings disease
• Ectopic secretion of ACTH by a non-pituitary
  tumour small cell carcinoma of lung, medullary
  carcinoma of thyroid, carcinoid of
  bronchus/pancreas etc.
• Glucocorticoid hypersecretion by adrenal adenoma,
  hyperplasia or carcinoma

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Cushings syndrome - pathogenesis
Slide 26.24
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Cushings syndrome adrenal adenoma and
adrenal hyperplasia
Adrenal hyperplasia causing Cushings syndrome
Adrenal adenoma encapsulated tumour composed of
cortical cells with little variation in size and
shape. The residual cortex is atrophic.
VS
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Adrenal cortex Cushings syndrome clinical
features

• Obesity
• Moon facies
• Weakness and fatigability
• Hirsutism
• Hypertension
• Polycythaemia
• Glucose intolerance/diabetes
• Osteoporosis
• Abdominal striae
• Menstrual abnormalities
• Neuropsychiatric abnormalities

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Hyperadrenalisms
3. Adrenal cortex Adrenogenital syndromes

• Congenital adrenal hyperplasia a small group of
  congenital metabolic errors, each characterized
  by a deficiency or lack of a particular enzyme
  involved in the synthesis of cortical steroids
• Steroidogenesis is then channeled into other
  pathways, leading to increased production of
  androgens resulting in virilisation
• The deficiency of cortisol leads to increased
  ACTH secretion and thus adrenal hyperplasia
• Certain enzyme defects impair aldosterone
  secretion resulting in salt-wasting
• The most common defects are 21-hydroxylase
  deficiency (95) and 11 hydroxylase deficiency
  (3)

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Congenital adrenal hyperplasia 21-hydroxylase
deficiency
21-hydroxylase deficiency may be mild or total
and three syndromes are possible Salt-wasting
adrenogenitalism total deficiency gt salt
wasting, ?Na, ?K, acidosis, cardiovascular
collapse, virilisation of female, precocious
puberty in male. Simple virilizing
adrenogenital syndrome subtotal deficiency gt
reduced level of aldosterone but still sufficient
for salt resorption levels of glucocorticoid
insufficient to inhibit ACTH, therefore ?ACTH
(and adrenal hyperplasia). Nonclassic adrenal
virilism mild deficiency gt may be asymptomatic
and only be diagnosed by genetic studies and
demonstration of defects of steroidogenesis
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In newborn girls with this disorder, the clitoris
is enlarged with the urethral opening at the base
(ambiguous genitalia, often appearing more
male-like than female). The internal structures
of the reproductive tract (ovaries, uterus, and
fallopian tubes) are normal. As they grow
older, masculinization takes place deepening of
the voice, presence of facial hair, and failure
to menstruate.
In a newborn boy no obvious abnormality is
present, but after a few years, the child becomes
muscular, the penis enlarges, pubic hair appears,
and the voice deepens. He may appear to enter
puberty at 2-3 years of age. At puberty, the
testes are small.
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Adrenal cortex hypoadrenalismPrimary acute
adrenal insufficiency

• Clinical features
• Hypotension, hyponatraemia, collapse
• Causes
• Rapid withdrawal of long term steroid therapy
• Sepsis/stress in patients with chronic adrenal
  dysfunction
• Massive destruction of the adrenals
• Perinatal haemorrhagic necrosis
• Adrenal haemorrhage heparin/warfarin, DIC
• Post partum infarction
• Adrenal haemorrhage complicating bacteraemia (eg
  meningococcal) Waterhouse-Friderichson syndrome
• trauma

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Adrenal cortex hypoadrenalismPrimary chronic
adrenal insufficiency Addisons disease

• Clinical features
• Lethargy, depression, anorexia, weight loss
• Hypotension caused by salt and water loss
• Hyperpigmentation melanocytes stimulated by
  excess ACTH
• - ?Na, ?K, ?urea, ?glucose
• Causes
• Autoimmune
• Tuberculosis, metastases, amyloid,
  haemochromatosis, lymphoma

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Massive adrenal haemorrhage, resulting in primary
acute adrenal insufficiency
Metastatic breast carcinoma affecting the adrenal
gland and causing primary chronic adrenal
insufficiency
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Adrenal cortex hypoadrenalismSecondary
adrenocortical insufficiency

• Causes
• Any disorder of the hypothalamus or pituitary
  which results in a reduction in ACTH secretion
• Metastases, infection, infarction, irradiation
• Clinical features
• Similar to Addisons disease, but without
  hyperpigmentation (melanocytes not stimulated as
  no excess ACTH)
• Deficient cortisol and androgen output, but
  normal aldosterone (not ACTH dependent) and so no
  marked hyponatraemia or hyperkalaemia

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Adrenal medulla

• Most significant disorders are neoplasms
• Phaeochromocytoma
• Neuroblastoma
• Ganglioneuroma

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Phaeochromocytoma shown enclosed within an
attenuated cortex with residual adrenal
below. Originates from chromaffin cells of the
adrenal medulla (85) or other, extra-adrenal,
locations. 90 occur sporadiacally, 10 occur in
relation to other syndromes (MEN, von-Hippel
lindau, von Recklinghausen, Sturge-Weber). Clinica
lly, causes a catecholamine-induced hypertension
which can be cured by excision.
Residual adrenal
Electron micrograph of phaechromocytoma. The
tumour cells contain membrane-bound secretory
granules in which catecholamines are stored.
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Adrenocortical adenoma
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Adrenocortical adenoma
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Adrenocortical carcinoma
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Phaeochromocytoma
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Phaeochromocytoma
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Summarizing Adrenal glands

• Anatomy and physiology
• Cortical pathology
• Hyper cortico-adrenalism
• Hypo cortico-adrenalism
• Medullary Pathology
• Tumours