The Endocrine System pathology and anatomy

Pathology of endocrinology

1. The Endocrine System -I
DrA. Rapsang

2. •Anatomically, the endocrine system consists of 6
distinct organs:
–Pituitary
–Adrenals
–Thyroid
–Parathyroids
–Gonads
–Pancreatic islets

3. Human hormones are divided into 5 major classes
which can interact with either cell membrane or
nuclear receptor
•Amino acid derivatives
–Thyroid hormone
–Catecholamines. •Small neuropeptides
–Gonadotropin-releasing hormone (GnRH)
–Thyrotropin-releasing hormone (TRH)
–Somatostatin
–Vasopressin.
These interact with cell-surface membrane receptors

4. •Large proteins
–Insulin
–Luteinisinghormone (LH)
–Parathormone
•Steroid hormones
–Cortisol
–Estrogen. •Vitamin derivatives
–Retinol (vitamin A)
–Vitamin D.
These interact with intracellular nuclear receptors

5. Synthesis of hormones and their precursors
Takes place through a prescribed genetic pathway th at
involves:
Transcrip.on → mRNA → protein synthesis →
posttranslational
protein processing → intracellular sor.ng/ membrane
integra.on → secre.on.

6. Major functions of hormones
•Growth and differentiation of cells:
by pituitary
hormones, thyroid, parathyroid, steroid hormones.
•Maintenance of homeostasis:
thyroid (by regulating
BMR), parathormone, mineralocorticoids,
vasopressin, insulin.
•Reproduction:
sexual development and activity,
pregnancy, foetaldevelopment, menopause etc.

8. Hyperfunction:
•Results from excess of hormone secreting tissues
–Hyperplasia
–Tumours(adenoma, carcinoma)
–Ectopic hormone production
–Excessive stimulation from inflammation (often autoimmune)
–Infections
–Iatrogenic (drugs-induced, hormonal administration).
Hypofunction:
•Deficiency of hormones occurs from destruction of
hormone-forming tissues from
–Inflammations (often autoimmune)
–Infections
–Iatrogenic (e.g. surgical removal, radiation damage)
–Developmental defects and genetics
–Haemorrhageand infarction (e.g. Sheehan’s syndrome),
–Nutritional deficiency (e.g. iodine deficiency).

9. PITUITARY GLAND

10. •The pituitary gland weighs about 500 mg and is
slightly heavier in females.
•It is situated at the base of the brain in a hollow
called sellaturcicaformed out of the sphenoid bone.
•The gland is composed of 2 major anatomic
divisions:
–Anterior lobe (adenohypophysis)
–Posterior lobe (neurohypophysis).

11. Anterior lobe (adenohypophysis).
Composed of
•Chromophilcells
–Somatotrophs(GH cells) -produce growth hormone (GH).
–Lactotrophs(PRL cells) -produce prolactin (PRL).
–Cells containing both GH and PRL called mammosomato trophs
are also present
•Chromophilcells with basophilic granules
–Gonadotrophs(FSH-LH cells)
–Thyrotrophs(TSH cells)
–Corticotrophs(ACTH-MSH cells) -produce ACTH, melanoc yte
stimulating hormone (MSH), β-lipoprotein and β-endor phin.
•Chromophobecells without visible granules
–Sparsely granulated corticotrophs, thyrotrophsand
gonadotrophs.

12. Posterior lobe (neurohypophysis).
Contain granules of neurosecretorymaterial made up
of 2 octapeptides
•Vasopressin or antidiuretic hormone (ADH)
–Causes reabsorption of water from the renal tubules
–Essential for maintenance of osmolality of the plasma.
–Deficiency results in diabetes insipidus
•Oxytocin
–Causes contraction of mammary myoepithelialcells
resulting in ejection of milk from the lactating breast
–Causes contraction of myometrium of the uterus at term.

13. •Diseases of the pituitary gland
–Hyperpituitarism
–Hypopituitarism
–Pituitary tumours

14. HYPERPITUITARISM
•Hyperpituitarismis characterisedby oversecretionof
one or more of the pituitary hormones.
•Due to diseases of the anterior pituitary, posterio r
pituitary or hypothalamus. Hyperfunctionof Anterior Pituitary •Three diseases
–Gigantism and acromegaly.
–Hyperprolactenemia
–Cushing’s disease

15. Gigantism and acromegaly. -Sustained excess of GH,
most commonly by GH-secreting adenoma.
•Gigantism.
–When GH excess occurs prior to epiphyseal closure
–Occurs in prepubertalboys and girls
–There is excessive and proportionategrowth of the
child.

16. •Acromegaly.
–Overproduction of GH in adults following cessation of bone
growth
–More common than gigantism.
–The term ‘acromegaly’ means increased growth of extremities
(acro=extremity).
–There is
•Enlargement of hands and feet
•Coarseness of facial features with increase in soft tissues, prominent
supraorbital ridges and a more prominent lower jaw
•Protrusion of the lower teeth in front of upper tee th (prognathism).
•Enlargement of the tongue and lips
•Thickening of the skin
•Kyphosis.
–Associated features
•TSH excess - thyrotoxicosis
•Gonadotropin insufficiency - amenorrhoeain the femal es and
impotence in the male

17. Hyperprolactinaemia.
•Excessive production of prolactin (PRL), most
commonly by PRL-secreting adenoma, also called
prolactinoma.
•Can also result from hypothalamic inhibition of PRL
secretion by certain drugs (e.g. chlorpromazine,
reserpine and methyl-dopa).
•Females
–Amenorrhoea-galactorrhoea-infertility and expression of
milk from breast, not related to pregnancy
•Male
–Impotence or reduced libido.
Cushing’s syndrome.
•Results from ACTH excess.
•Most frequently, caused by ACTH -secreting adenoma.

18. Hyperfunctionof Posterior Pituitary and Hypothalamu s Inappropriate release of ADH.
•Excessive secretion of ADH
–Passage of concentrated urine -due to increased reabsorption
of water and loss of sodium in the urine
–Consequent hyponatraemia, haemodilutionand expansion of
ICF and ECF volume.
•Occurs most often in paraneoplastic syndrome e.g. i n oat
cell carcinoma of the lung, carcinoma of the pancre as etc
•Other causes
–Trauma
–Haemorrhage
–Meningitis
–Pulmonary diseases - tuberculosis, lung abscess,
pneumoconiosis, empyema and pneumonia (rarely)

19. Precocious puberty.
•A tumourin the region of hypothalamus or the
pineal gland may result in premature release of
gonadotropins causing the onset of pubertal changes
prior to the age of 9 years.
–Premature development of genitalia both in the male
and in the female
–Growth of pubic hair and axillary hair.
–In the female -breast growth and onset of
menstruation.

20. HYPOPITUITARISM
•There is usually deficiency of one or more of the
pituitary hormones affecting either anterior pituit ary,
or posterior pituitary and hypothalamus.
Hypofunctionof Anterior Pituitary •Due to destruction of the anterior lobe of more tha n
75%
–Anterior pituitary lesions
–Pressure and destruction from adjacent lesions.
•Two diseases
–Pituitary dwarfism
–Panhypopituitarism

21. Panhypopituitarism.
•Three most common causes of panhypopituitarism are
–Adenoma
–Sheehan’s syndrome and Simmond’sdisease
–Empty-sellasyndrome.

22. Sheehan’s syndrome and Simmond’sdisease. •Pituitary insufficiency occurring due to postpartum
pituitary (Sheehan’s) necrosis is called Sheehan’s
syndrome, whereas occurrence of similar process
without preceding pregnancy as well as its
occurrence in males is termed Simmond’sdisease.
•Usually due to enlargement of the pituitary followe d
by hypotensive shock precipitating ischaemic
necrosis of the pituitary.
–Failure of lactation following delivery (deficiency of
prolactin. )
–Loss of axillary and pubic hair
–Amenorrhoea, sterility and loss of libido.
•Concomitant deficiency of TSH and ACTH may result
in hypothyroidism and adrenocortical insufficiency.

23. Empty-sellasyndrome. •Characterisedby the appearance of an empty sella
and features of panhypopituitarism .
•Usually due to herniation of subarachnoid space int o
the sellaturcicadue to an incomplete diaphragma
sellacreating an empty sella.
•Other causes
–Sheehan’s syndrome
–Infarction and scarring in an adenoma
–Irradiation damage
–Surgical removal of the gland.

24. Pituitary dwarfism.
•Severe deficiency of GH in children before growth i s
completed results in retarded growth and pituitary
dwarfism.
•Mostly due to a genetic cause
•Other causes
–Pituitary adenoma or craniopharyngioma
–Infarction and trauma to the pituitary.
•Clinical features
–Proportionate retardation in growth of bones
–Normal mental state for age
–Poorly-developed genitalia
–Delayed puberty
–Episodes of hypoglycaemia.

25. Hypofunctionof Posterior Pituitary and Hypothalamus •Causes ADH deficiency - diabetes insipidus.
Diabetes insipidus.
•The causes of ADH deficiency are:
–Inflammatory and neoplastic lesions
–Destruction of neurohypophysisdue to
•Surgery
•Radiation
•Head injury
–Idiopathic.
•The main features of diabetes insipidus are
–Excretion of a large volume of dilute urine
–Polyuria
–Polydipsia.

26. PITUITARY TUMOURS

28. Pituitary Adenomas
•Adenomas are the most common pituitary tumours.
•They are conventionally classified according to the ir
H & E staining characteristics of granules
–Acidophil
–Basophil
–Chromophobeadenomas.
•Classification of pituitary adenomas based on
functional features are more accurate.
Morphologic features.
•Grossly
–Range in size
–They are spherical, soft and encapsulated.

29. •3 types of patterns:
•Diffuse pattern -
composed of polygonal
cells arranged in sheets
with scanty stroma.
•Sinusoidal pattern -
consists of columnar or
fusiform cells with
fibrovascularstroma
around which the tumour
cells are arranged
•Papillary pattern -
composed of columnar or
fusiform cells arranged
about fibrovascular
papillae.

30. •Pituitary adenoma may also occur as a part of
multiple endocrine neoplasia type I (MEN -I) in which
adenomas of pancreatic islets, parathyroidsand the
pituitary are found
•Clinically, the patients are characterisedby
combination of features of
–Zollinger-Ellison’s syndrome
–Hyperparathyroidism
–Hyperpituitarism.

31. ADRENAL GLAND

32. •The adrenal glands lie at the upper pole of each ki dney.
•Each gland weighs approximately 4 gm in the adult
•On sectioning, the adrenal is composed of 2 parts:
–Outer yellow-brown cortex
–Inner grey medulla.
Adrenal cortex.
•It is composed of 3 layers:
–Zona glomerulosa -outer layer responsible for the
synthesis of mineralocorticoids, the most important of
which is aldosterone, the salt and water regulating
hormone.
–Zona fasciculata-middle layer whose cells are precu rsors
of various steroid hormones such as glucocorticoids (e.g.
cortisol) and sex steroids (e.g. testosterone).
–Zona reticularis-inner layer for synthesis and secr etion of
glucocorticoids and androgens

33. Hypothalmus
↓corticotropin-releasing factor
ACTH release
↓
Hypothalamus-anterior pituitary.
↓
Synthesis of glucocorticoids and adrenal androgens
•Release of
aldosterone
is independentof ACTH control
and is largely regulated by
–Serum levels of potassium
–Renin-angiotensin mechanism

34. Adrenal medulla.
•Major function is synthesis and secretion of
catecholamines(epinephrine and norepinephrine).
•Also secrete various other peptides
–Calcitonin
–Somatostatin
–Vasoactive intestinal polypeptide (VIP)
•The major metabolites of catecholaminesare
–Metanephrine
–Nor-metanephrine
–Vanillylmandelicacid (VMA)
–Homovanillicacid (HVA).

35. Disorders of the adrenal cortex •Adrenocortical hyperfunction
–Hyperadrenalism
•Adrenocortical insufficiency
–Hypoadrenalism
–Adrenocortical tumours
Diseases of the adrenal medulla
•Medullary tumours

36. ADRENOCORTICAL HYPERFUNCTION
(HYPERADRENALISM)

37. •Cushing’s syndrome caused by excess of
glucocorticoids (i.e. cortisol)
; also called chronic
hypercortisolism.
•Conn’s syndrome caused by oversecretionof
mineralocorticoids (i.e. aldosterone)
; also called
primary hyperaldosteronism.
•Adrenogenitalsyndrome characterisedby excessive
production of
adrenal sex steroids (i.e. androgens);
also called adrenal virilism .
•Mixed forms of these clinical syndromes may also
occur.

38. Cushing’s Syndrome (Chronic Hypercortisolism ) Etiopathogenesis. Pituitary Cushing’s syndrome. •Excessive secretion of ACTH due to a lesion in the
pituitary gland
•Characterisedby
–Bilateral adrenal cortical hyperplasia
–Elevated ACTH levels.
•These cases show therapeutic response on
administration of high doses of dexamethasone
which suppresses ACTH secretion and causes fall in
plasma cortisol level.

39. Adrenal Cushing’s syndrome. •Caused by disease in one or both the adrenal glands .
–Adrenal cortical adenoma
–Carcinoma
–Cortical hyperplasia.
•Characterisedby low serum ACTH levels and absence o f
therapeutic response to administration of high dose s of
glucocorticoid.
Ectopic Cushing’s syndrome. •ACTH elaboration by non-endocrine tumours.
–Oat cell carcinoma of the lung
–Malignant thymoma
–Pancreatic tumours
•The plasma ACTH level is high in these cases and co rtisol
secretion is not suppressed by dexamethasone
•administration.

40. Iatrogenic Cushing’s syndrome. •Prolonged therapeutic administration of high doses
of glucocorticoids or ACTH
–Organ transplant recipients
–Autoimmune diseases.
•Generally associated with bilateral adrenocortical
insufficiency.

41. Clinical features.
•More often in the age of 20-40 years
•Women:men= 3:1
•Central or truncalobesity
–Thin arms and legs
–Buffalo hump -due to prominence of fat over the shoulders
–Rounded oedematousmoon-face.
•Increased protein breakdown
–Wasting and thinning of the skeletal muscles
–Atrophy of the skin and subcutaneous tissue
–Formation of purple striaeon the abdominal wall
–Osteoporosis
–Easy bruisabilityof the thin skin to minor trauma.

42. •Systemic hypertension
–Due to retention of sodium and water.
•Impaired glucose tolerance and diabetes mellitus
•Amenorrhoea
•Hirsutism
•Infertility
•Insomnia
•Depression
•Confusion
•Psychosis.

43. Conn’s Syndrome (Primary
Hyperaldosteronism)
•Occurs due to overproduction of aldosterone, the
potent salt-retaining hormone.
Etiopathogenesis.
•Adrenocortical adenoma, producing aldosterone.
•Bilateral adrenal hyperplasia, especially in childr en
(congenital hyperaldosteronism ).
•Adrenal carcinoma.

44. •Primary hyperaldosteronismfrom any of the above
causes is associated with
low plasma renin levels
.
•Secondary hyperaldosteronismoccurs in response to
high plasma renin level
due to overproduction of
renin by the kidneys such as in
–Renal ischaemia
–Reninoma
–Edema.

45. Clinical features.
•More frequent in adult females.
•Hypertension
•Hypokalaemia
–Associated muscular weakness
–Peripheral neuropathy
–Cardiac arrhythmias.
•Retention of sodium and water.
•Polyuria and polydipsia due to reduced concentratin g
power of the renal tubules.

46. AdrenogenitalSyndrome (Adrenal Virilism )
Etiopathogenesis.
•In children
–Congenital adrenal hyperplasia
•In adults
–Adrenocortical adenoma
–Carcinoma.
•Cushing’s syndrome is often present as well.

47. Clinical features.
•Depend upon the age and sex of the patient.
•In children
–Distortion of the external genitalia in girls
–Precocious puberty in boys.
•In adults
–Females
•Virilisation
–Hirsutism
–Oligomenorrhoea
–Deepening of voice
–Hypertrophy of the external genitalia
–Males
•Feminisation.

48. ADRENOCORTICAL INSUFFICIENCY
(HYPOADRENALISM)

49. •Adrenocortical insufficiency may result from
–Deficient synthesis of cortical steroids from the
adrenal cortex
–Secondary to ACTH deficiency.
•Three types of adrenocortical hypofunctionare
distinguished:
–Primary adrenocortical insufficiency
-caused by the
disease of the adrenal glands.
•Acute or
‘adrenal crisis’
•Chronic or ‘
Addison’s disease’.
–Secondary adrenocortical insufficiency
-resulting
from diminished secretion of ACTH.
–Hypoaldosteronism
-deficient secretion of
aldosterone.

50. PRIMARY ADRENOCORTICAL INSUFFICIENCY
•Primary adrenal hypofunctionoccurs due to defect in
the adrenal glands and normal pituitary function .
•Primary Acute Adrenocortical Insufficiency (Adrenal
Crisis)
•Sudden loss of adrenocortical function
•Etiopathogenesis.
–Bilateral adrenalectomy
–Septicaemia
–Rapid withdrawal of steroids.
–Any form of acute stress in a case of chronic insufficiency
i.e. in Addison’s disease.

51. Clinical features •Deficiency of mineralocorticoids (i.e. aldosterone
deficiency)
–Salt deficiency
–Hyperkalaemia
–Dehydration.
•Deficiency of glucocorticoids (i.e. cortisol defici ency)
–Hypoglycaemia
–Increased insulin sensitivity
–Vomiting

52. Primary Chronic Adrenocortical Insufficiency
(Addison’s Disease)
•Progressive chronic destruction of more than 90% of
adrenal cortex on both sides results Addison’s
disease.
•Etiopathogenesis.
•Any condition which causes marked chronic adrenal
destruction
–Tuberculosis
–Autoimmune or idiopathic adrenalitis
–Histoplasmosis
–Amyloidosis
–Metastatic cancer
–Sarcoidosis
–Haemochromatosis.

53. Clinical features. -Develop slowly •Asthenia - progressive weakness, weight loss and
lethargy
•Hyperpigmentation
•Arterial hypotension.
•Vague upper gastrointestinal symptoms –loss of
appetite, nausea, vomiting and upper abdominal pain .
•Lack of androgen causing loss of hair in women.
•Episodes of hypoglycaemia.
•Biochemical changes
–Reduced GFR
–Acidosis
–Hyperkalaemia
–Low levels of serum sodium, chloride and bicarbonate.

54. SECONDARY ADRENOCORTICAL INSUFFICIENCY •Adrenocortical insufficiency resulting from deficie ncy
of ACTH
•Etiopathogenesis.
•Selective ACTH deficiency due to prolonged
administration of high doses of glucocorticoids.
–Leads to suppression of ACTH release from the pituitary
gland and selective deficiency.
•Panhypopituitarism
•Clinical features.
•Similar to Addison’s disease except the following:
–No hyperpigmentation
–Plasma ACTH levels are low-to-absent in secondary
insufficiency but are elevated in Addison’s disease.
–Aldosterone levels are normal due to stimulation by renin.

55. HYPOALDOSTERONISM
•Isolated deficiency of aldosterone with normal
cortisol level and low renin level
•Etiopathogenesis.
•Congenital defect
•Prolonged administration of heparin.
•Certain diseases of the brain.
•Excision of an aldosterone-secreting tumour.

56. •Clinical features. •Usually patients already have mild renal failure an d
diabetes mellitus.
•The predominant features are
–Hyperkalaemia
–Metabolic acidosis.

57. TUMOURS OF ADRENAL GLANDS

58. ADRENOCORTICAL TUMOURS
Cortical Adenoma
•A cortical adenoma is a benign and slow -growing
tumour.
•It is usually small and nonfunctional.
•Large adenomas may produce excess of cortisol,
aldosterone or androgen.
•Association with systemic hypertension
•Cortical adenoma may be a part of multiple
endocrine neoplasia type I (MEN -I)

59. Morphologic features.
•Grossly
–Usually a small, solitary, spherical and encapsulated
–Well-delineated from the surrounding normal adrenal
gland.
•Cut section
–Typically bright yellow .
•Microscopically
–Tumourcells are arranged in trabeculae

60. MEDULLARY TUMOURS
Pheochromocytoma(ChromaffinTumour)
•Pheochromocytoma(meaning dusky brown tumour)
is generally a benign tumourarising from the
chromaffincells of the adrenal medulla.
•May occur at any age but most patients are 20-60
years old.
•Mostly slow-growing and benign
•5% of the tumoursare malignant, invasive and
metastasising.
–Associated with MEN syndrome
•Bilateral
•Association with medullary carcinoma of the thyroid,
hyperparathyroidism, pituitary adenoma etc

61. Clinical features
•Predominantly due to secretion of catecholamines-
epinephrine and norepinephrine.
•The most common feature is
hypertension
.
•Other manifestations due to sudden release of
catecholaminesare
–Congestive heart failure
–Myocardial infarction
–Pulmonary oedema
–Cerebral haemorrhage
–Death.
Diagnosis
•Measuring 24-hour urinary catecholaminesor their
metabolites such as metanephrineand VMA.

62. Pheochromocytomaof the
adrenal medulla.
Grossly
•Compressed kidney at the
lower end
•Upper end shows a large
spherical tumour
separate from the kidney.
Cut surface
•Cystic change while solid
areas show dark brown,
necrotic and
haemorrhagictumour.

63. Adrenal
pheochromocytoma.
•The tumourhas typical
nested pattern.
•The tumourcells are
large, polyhedral and
pleomorphic having
abundant granular
cytoplasm

65. Assignment
•Classify hormones and their major functions
•Define hyperfunctionand hypofunctionof hormones.
•Name the hormones secreted by pituitary gland
•Short notes on
–Hyperpituitarism
–Hypopituitarism
•Anatomy of adrenal gland
•Name the hormones secreted by adrenal gland
•Short notes on
–Conn’s syndrome
–Adrenal crisis
–Addison’s disease
–Pheochromocytoma