ENDOCRINE SYSTEM PATHOLOGY
PITUITARY HYPERFUNCTION
Associated with pituitary adenoma
Macroadenomas > 10 mm
Microadenomas < 10 mm
Small tumours – present due to excess hormone production
Large tumours – present due to pressure effects e.g. visual disturbances due to pressure on optic chiasm
Pituitary apoplexy – when haemorrhage into pituitary adenoma causes ↑ICP
Gigantism
↑ GH by acidophil adenoma
induces skeletal growth with normal shape and relative proportions i.e very long bones
Fusion of epiphysis is delayed = features of acromegaly:
Features of face coarsened: nose enlarged
Prognathic jaw (projecting)
Osteoarthritis due to irregular bone formation
Limbs enlarged
Pain due to nerve compression
Glucose tolerance diminished
10% develop DM
Hypertension
Cardiac hypertrophy
Extensive atheroma
Cardiac failure is common cause of death
2-3 fold increase in colonic ca.
HYPOPITUITARISM
Causes of failure of pituitary secretion:
Pituitary tumour
Pituitary surgery / cranial irradiation
Head injury
Hypothalamic dysfunction, including
Craniopharyngioma
Sheehan’s syndrome (NB where obstetric services are poor)
· Ischaemic necrosis of pituitary
· Post-partum haemorrhage
· Results depend on extent of necrosis:
§ ↓TSH = low BMR / features of hypothyroidism / sensitivity to cold / coarsening & loss of hair
§ ↓prolactin = failure of lactation & later breast atrophy
§ ↓ACTH = deficiency of glucocorticoids / weakness / low BP / hypoglycaemia
§ ↓ gonadotrophins / amenorrhoea / sterility / loss of libido /
§ Atrophy of peripheral endocrine organs
↓ GH in Childhood:
· dwarfism
· ↓ skeletal growth
· retarded sexual development
· normal intelligence
↓ GH in adults:
· lethargy
· diminished muscle mass
· obesity
· premature atheroma
HYPOTHYROIDISM
In children = CRETINISM
In adults = MYXOEDEMA
NB Clinical signs of myxoedema
§ ↓ BMR
§ weight gain
§ ↓ body temp. & cold intolerance
§ Lethargy (Abnormal drowsiness or stupor, a condition of indifference.)
§ Apathy (The lack of feeling or emotion, indifference.)
§ ↓ appetite
§ Constipation
§ ↓HR & ↓RR
§ ↓libido
§ Lack of ovulation
§ Skin thickened with non-pitting oedema due to ↑ mucopolysaccharide ground substance
§ Hair brittle dry and falls out
§ ↑ blood cholesterol
§ ↑ TSH
§ ↓T3 & T4 blood levels
Causes of myxoedema:
1. Autoimmune thyroiditis
a. Atrophic form / primary myxoedema
b. Goitrous form
Hashimoto’s disease
2. Severe iodine deficiency
3. Dyshormonogenesis – inborn errors in the formation of thyroid hormones
4. Anti-thyroid drugs e.g. lithium
5. Excessive surgical resection of thyroid gland
6. Treatment with radioiodine
7. Hypopituitarism → ↓TSH
Macroscopy of primary myxoedema:
Thyroid is shrunken
White
Firm
Microscopy of primary myxoedema:
Isolated islands of small follicles embedded in
Fibrous tissue
Lymphocytes
Plasma cells
Lack of colloid in follicles
Cretinism
Normal @ birth abnormality appears within weeks
Clinical Signs
Protruding tongue
Dwarf with short limbs
Coarse dry skin
Lack of hair & teeth
Mental deficiency
Pot belly with umbilical hernia
NB irreversible damage unless treatment is given early
Two clinical forms:
endemic
areas where iodine deficiency predominate
infantile thyroid is enlarged and nodular
hyperplastic foci containing colloid
iodine in salt reduced incidence
sporadic
congenital hypoplasia / absence of thyroid
deaf mutism
THYROID HYPERFUNCTION / HYPERTHYROIDISM
Thyrotoxicosis = ↑↑↑ thyroid hormone (T3 & T4
3 Lesions give rise to thyrotoxicosis
1. Grave’s disease (exopthalmic goiter) 80%
2. Toxic nodular goiter 10%
3. Toxic adenoma < 5%
Grave’s Disease
Clinical Signs
Exopthalmos
Prominent thyroid
↑ BMR
Skin warm & sweaty: heat intolerance
Weakness, hyperkinesias & emotional instability Loss of weight
↓ glucose tolerance with glycosuria
Rapid pulse
Cardiac arrhythmia / atrial fibrillation
↓ TSH
Macroscopy:
§ Diffusely enlarged gland
§ Pale pink in colour
Microscopy:
§ Hyperplastic
§ Numerous acini closely packed
§ Variable acinus size
§ Intra-acinar papilliform growths
§ Colloid absent
§ Cells columnar
§ Some cases thyroiditis (i.e. foci of plasma cells & lymphocytes)
Other changes:
Pre-tibial patches of myxoedema
Exopthalmos (auto-immune damage to eye muscle)
Aetiology:
Females (20 – 40 years peak)
More common with familial auto-immun pathology e.g. thyroiditis / pernicious anaemia
§ Stimulation of thyroid is due to autoantibody LATS
§ Long Acting Thyroid Stimulator IgG
§ Reacts with and activates the surface receptor for TSH on the thyroid epithelium
§ cAMP is formed and stim. Hyperplasia of thwe epithelium and increased formation of thyroid hormone
§ With increase TH the blood TSH falls
AUTOIMMUNE THYROIDITIS
Associated with:
Thyroid antibodies in blood
Inflammatory changes
Presence of lymphocytes and plasma cells
Three conditions additional to Grave’s disease are:
1. Hashimoto’s thyroiditis / lymphadenoid goitre
Microscopy:
· Lymphocytic infiltrate
· Germinal centres visible
· Multiple small acini
· Acini lined by Askanazy / Hürthle cells
· Plasma cells
· Nuclei large & irregular
Clinical effects:
· May be Euthyroid (A condition in which the thyroid gland is functioning normally, its secretion being of proper amount and constitution.)
· Middle aged female
· Develops hypothyroidism
· Surgical resection of thyroid results in hypothyroidism
2. Primary myxoedema
· Antibodies to thyroid hormones & epith.
3. Focal thyroiditis
· extremely common
· asymptomatic
· surgical interference may precipitate hypothyroidism
· low [antibody]
TUMOURS OF THYROID
Benign = Follicular adenoma
Single
Encapsulated
Compression of surrounding tissue
Degeneration with haemorrhage is common
Malignant = papillary carcinoma
60 – 70%
young women
small & multiple
metastasise readily to local LN
first clinical sign = enlarged cervical LN
Microscopy:
Small papillary structures
Uniform / optically clear nuclei / orphan annie
Psammoma bodies = concen tric calcification
Other malignancies:
Follicular carcinoma (15-20%)
Medullary carcinoma (5-10%)
Anaplastic carcinoma
B cell lymphoma
ADRENAL CORTEX HYPERACTIVITY
Cushing’s Syndrome
NB Clinical effects (12)
Clinical appearance:
Adiposity of face / neck & trunk tender & painful
Thin limbs
Striae
Causes:
· Excessive secretion of ACTH by pituitary adenoma (70%)
· Adenoma / carcinoma of adrenal cortex (20%)
· Bronchial ca. secreting ACTH = inappropriate secretion also pancreatic tumours
· Prolonged administration of glucocorticoids or ACTH as therapy
Conn’s Syndrome / primary hyperaldosteronism
Due to adenoma (>80%) / hyperplasia of zona glomerulosa
NB Effects of hyperaldosteronism (8)
ADRENAL CORTEX – HYPOFUNCTION
Due to panhypopituitarism / destruction 90% of the adrenal cortex
Acute adrenal failure is due to septicaemia / meningococcal (Waterhouse-Friderichsen Syndrome)
Causes of Chronic Hypofunction:
Addison’s disease (75%) a autoimmune adrenalitis
Tuberculous destruction of adrenals NB in developing countries
Pituitary failure
Associated diseases:
Diabetes
Thyroiditis
Parathyroiditis
Other features:
· Muscular weakness & wasting
· Weight loss
· Vomiting diarrhea
· Anaemia
· Pigmentation of exposed and pressure areas of skin (↑ MSH)
· Dehydration
· Crises with superimposed acute infection
Therapy = administer adrenal hormones = restoration to normal
ADRENAL MEDULLA
Phaeochromocytoma
§ Chromaffin cells
§ Over production of chatecholamine E & NE
§ Hypertension
§ ↑ BMR
§ hyperglycaemia
§ Tachycardia
§ Sweating
§ Cerebral haemorrhage
§ 10% familial
§ 10% bilateral
§ 10% malignant
ENDOCRINE PANCREAS
α CELLS – SECRETE GLUCAGON
§ glycogen converted to glucose and utilized by tissues
§ amino acids converted to glucose in liver
§ increased metabolism via citric acid cycle
§ increased conversion of fat to glucose
β CELLS - SECRETE INSULIN
§ glucose uptake and conversion to glycogen
§ uptake of amino acids and synthesis of protein
§ storage of fat in fat depots and conversion of glucose to fat
§ stimulates reabsorption of glucose from the renal glomerular filtrate
δ CELLS - SECRETE SOMATOSTATIN
§ Control hormone secretion of pancreas
DIABETES MILLETUS
Def: A metabolic abnormality in which there is an absolute or relative lack of insulin activity
CLASSIFICATION:
TYPE 1 – immune mediated β cell dysfunction
TYPE 2 – adult onset due to insulin resistance, relative insulin deficiency or from a secretory defect
TYPE 3 – a range of causes including genetic defects of β cell function and diseases of the exocrine pancreas.
TYPE 4 – Gestational diabetes
BIOCHEMICAL CHANGES & CLINICAL EFFECTS
1. Inability to control carbohydrate metabolism, causing
NB:
hyperglycaemia – ↑ plasma osmolarity & glycosuria – osmotic diuresis – hypovolaemia & loss of Na+ & K + - thirst - polydipsia
2. Increased fat catabolism
excess acetyl CoA – conversion to ketone bodies (acetone & hydroxybutyric acid) – ketoacidosis – acid excreted in combination with Na+ & K+ - further electrolyte depletion
3. Increased catabolism of amino acids
prevents proper protein synthesis and together with 1. & 2. leads to further electrolyte depletion
TYPES OF DIABETES
TYPE 1 due to destruction of β cells in Islets of Langerhans
Acute onset
Peak @ 13 years
Aetiology:
§ Associated with class II HLA antigens (DR3 & DR4)
§ Onset is commonest in autumn and winter
§ Cell mediated immunity and presence of auto-antibodies is against islet antigens is present in most cases
The theory of pathogenesis: NB multifactorial inheritance
+
Activation of autoimmunity = damage to β cells = TYPE 1
Diabetes may complicate:
1. A number of endocrine disease (acromegaly, Cushing’s syndrome, phaeochromocytoma)
2. Metabolic diseases (haemochromatosis)
3. Drug therapy (steroids, thiazide diuretics)
4. Pancreatic inflammation, etc. (chronic pancreatitis, mumps, cystitic fibrosis)
NB - COMPLICATIONS OF DIABETES
1. DIABETIC COMA (A deep prolonged unconsciousness where the patient cannot be aroused. This is usually as the result of a head injury, neurological disease, acute hydrocephaly, intoxication or metabolic derangement.)
keto-acidotic
hyperosmolar non-ketotic
2. HYPOGLYCAEMIC COMA
due to insulin excess
3. CARDIOVASCULAR LESIONS
atheroma
microangiopathy:
cardiac failure
retinopathy
neuropathy
gangrene of limbs
Kimmelstiel-Wilson lesions in kidney
4. RENAL FAILURE
glomerulosclerosis
pyelonephritis
renal papillary necrosis
5. INFECTIONS
sepsis
fungal infections
T.B.
6. NEUROPATHY
peripheral & autonomic (direct or microvascular)
HYPERPARATHYROIDISM
PRIMARY:
Adenoma (>80%) / hyperplasia (15%) & carcinoma (2%)
Blood calcium is raised
Effects:
§ Formation of renal calculi
§ Parathyroid bone disease
§ General muscle weakness
§ Metastatic calcification
SECONDARY
Parathyroid hyperplasia is a response to low blood calcium from a number of causes:
Chronic renal failure
Malabsorption syndromes
Vitamin D deficiency
HYPOCALCAEMIA
PARATHYROID HYPERLPASIA
HYPOPARATHYROIDISM
Occurs in three circumstances:
1. surgical removal
2. auto-immune disease
3. congenital deficiency (DiGeorge syndrome)
Effects:
↓ release of calcium from bones
↓ calcium absorption
↓ tubular reabsorption of calcium
hypocalcaemia
spasms & twitching = TETANY
MUTLIPLE ENDOCRINE NEOPLASIA SYNDROME (MENS)
Autosomal dominant inheritance
Multiple endocrine tumours
MENS 1 = parathyroid adenoma
Pancreatic cell tumour
Pituitary adenoma
MENS 2A = Medullary carcinoma of thyroid
Phaeochromocytoma
Parathyroid adenoma / hyperplasia
MENS 2B = medullary carcinoma of thyroid
Phaeochromocytoma
Mucosal ‘nueromas’
Ganglioneuromas of gut