Download - Pathology of Endocrine Disease Adrenal glands Dr. Arrigo Capitanio Department of Pathology 05-11
Pathology of Endocrine Disease
Adrenal glands
Dr. Arrigo Capitanio
Department of Pathology
05-11
Adrenal glands
• Anatomy and physiology
• Cortical pathology– Hyper cortico-adrenalism– Hypo cortico-adrenalism
• Medullary Pathology
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
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)
Zona glomerulosa
Zona fasciculata
Zona reticularis
VS
Normal adrenal steroid biosynthesis
Adrenal cortex – normal steroid synthesis
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
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
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.
1. Adrenal cortex Secondary
Hyperaldosteronism • Secondary hyperaldosteronism - adrenal
response to increased levels of renin-angiotensin– Causes
• Renal ischaemia
• Chronic oedema (Nephrotic syndrome, ascites)
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
Cushing’s syndrome - pathogenesis
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
VS
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
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
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
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.
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
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
Massive adrenal haemorrhage, resulting in primary acute adrenal insufficiency
Metastatic breast carcinoma affecting the adrenal gland and causing primary chronic adrenal insufficiency
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
Adrenal medulla
Most significant disorders are neoplasms
– Phaeochromocytoma– Neuroblastoma – Ganglioneuroma
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.
Adrenocortical adenoma
Adrenocortical adenoma
Adrenocortical carcinoma
Phaeochromocytoma
Phaeochromocytoma
Summarizing Adrenal glands
• Anatomy and physiology
• Cortical pathologyHyper cortico-adrenalism
Hypo cortico-adrenalism
• Medullary Pathology
Tumours