1. Pathology of Endocrine Disease Department of Pathology
12/01/10
Pathology of Endocrine Disease
Adrenal glands
Dr. Arrigo Capitanio
Department of Pathology
05-11

2. Adrenal glands Anatomy and physiology Cortical pathology
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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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5. Adrenal cortex Composed of three zones: Zona glomerulosa
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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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8. Adrenal cortex – normal steroid synthesis
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Adrenal cortex – normal steroid synthesis
Normal adrenal steroid biosynthesis

9. Adrenal cortex Hyperadrenalism
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Adrenal cortex Hyperadrenalism
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

10. Primary Hyperaldosteronism
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Hyperadrenalisms
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
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. 10

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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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13. Secondary Hyperaldosteronism
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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)

14. 2. Adrenal cortex Cushing’s syndrome
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Hyperadrenalisms
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

15. Cushing’s syndrome - pathogenesis
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Cushing’s syndrome - pathogenesis
Slide 26.24

16. Cushing’s syndrome – adrenal adenoma and adrenal hyperplasia
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Adrenal hyperplasia causing Cushing’s syndrome
Adrenal adenoma – encapsulated tumour composed of cortical cells with little variation in size and shape. The residual cortex is atrophic. VS

17. Adrenal cortex Cushing’s syndrome – clinical features
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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

18. 3. Adrenal cortex Adrenogenital syndromes
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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%)

19. Congenital adrenal hyperplasia – 21-hydroxylase deficiency
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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 => 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

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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.

21. Adrenal cortex – hypoadrenalism Primary acute adrenal insufficiency
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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 – hypoadrenalism Primary 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

24. Adrenal cortex – hypoadrenalism Secondary adrenocortical 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

25. Adrenal medulla Most significant disorders are neoplasms
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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.

27. Adrenocortical adenoma
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Adrenocortical adenoma

28. Adrenocortical adenoma
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Adrenocortical adenoma

29. Adrenocortical carcinoma
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Adrenocortical carcinoma

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Phaeochromocytoma

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Phaeochromocytoma

32. Summarizing Adrenal glands
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Summarizing Adrenal glands
Anatomy and physiology
Cortical pathology
Hyper cortico-adrenalism
Hypo cortico-adrenalism
Medullary Pathology
Tumours