pathology of endocrine disease adrenal glands dr. arrigo capitanio department of pathology 05-11
TRANSCRIPT
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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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Normal adrenal steroid biosynthesis
Adrenal cortex – normal steroid synthesis
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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 (Conn’s
syndrome)
2. Cortisol – Cushing’s syndrome
3. Androgens – adrenogenital syndromes
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1. Adrenal cortex Primary
Hyperaldosteronism • Primary hyperaldosteronism – excess aldosterone
secretion which is independent of the renin-angiotensin system (Conn’s 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
Hyperadrenalisms
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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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1. 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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2. Adrenal cortex Cushing’s syndrome
• A chronic excess of cortisol• Pathogenesis:
– Prolonged treatment with glucocorticoids such as prednisolone
– Pituitary hypersecretion of ACTH (e.g. by adenoma) = Cushing’s
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
Hyperadrenalisms
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Cushing’s syndrome - pathogenesis
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Adrenal adenoma – encapsulated tumour composed of cortical cells with little variation in size and shape. The residual cortex is atrophic.
Cushing’s syndrome – adrenal adenoma and adrenal hyperplasia
Adrenal hyperplasia causing Cushing’s syndrome
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Adrenal cortex Cushing’s 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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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%)
Hyperadrenalisms
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21-hydroxylase deficiency may be mild or total and three syndromes are possible:
Salt-wasting adrenogenitalism – total deficiency => salt wasting, Na, K, acidosis, cardiovascular collapse, virilisation of female, precocious puberty in male.
Simple virilizing adrenogenital syndrome – subtotal deficiency => 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 => may be asymptomatic and only be diagnosed by genetic studies and demonstration of defects of steroidogenesis
Congenital adrenal hyperplasia – 21-hydroxylase deficiency
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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 – hypoadrenalism
Primary 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: Addison’s 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 – hypoadrenalism
Secondary 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 Addison’s 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).Clinically, 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 pathologyHyper cortico-adrenalism
Hypo cortico-adrenalism
• Medullary Pathology
Tumours