ERS14 16 Pathology Of Endocrine Disorders I + II Flashcards
Basic ideas of Endocrine system
- Set of glands
- Maintain homeostasis by secreting hormones directly into blood to reach target organs
- Autocrine / Paracrine / Endocrine
Histology of Endocrine glands
- Similar normal histology (regardless of anatomical location)
—> similar arrangement + morphology - ***Nest / Packets of endocrine cells
- Granular cytoplasm with secretory granules
- ***Rich vasculature
Pathologies of Endocrine system
- Functional vs Non-functional
- Hyper / Hypo-function - Neoplastic vs Non-neoplastic
- Benign / Malignant
—> difficult to tell definitely benign / malignant by histology alone
—> integration of Clinical and Pathological findings to arrive diagnosis
Pituitary gland
Anterior lobe (Adenohypophysis) + Posterior lobe (Neurohypophysis) - Histologically distinct
Anterior lobe:
- Positive-acting releasing factors from Hypothalamus except for Prolactin
- ***Nest / Packets of endocrine cells
- Granular cytoplasm with secretory granules
- Rich vasculature
- Acidophils: Somatotroph, Lactotroph
- Basophils: Corticotroph, Thyrotroph, Gonadotroph
- Chromophobes
Posterior lobe:
- **Modified glial cells (Pituicytes) + **Nerve fibres from Hypothalamus
- Less capillaries
- ADH + Oxytocin
Pituitary disorders
- Hyper / Hypopituitarism
—> Hyper / Hypo excess secretion of adenohypophyseal hormones - Endocrine / Local mass effects
Pituitary adenoma (Hyperpituitarism)
- In Adults
- Benign
Classification: - Macroadenoma (> 1cm) / Microadenoma (< 1cm) - Histological cell type —> Lactotroph —> Galactorrhea, Menstrual disturbances —> Somatotroph —> Gigantism / Acromegaly —> Corticotroph —> Cushing’s disease —> Thyrotroph (rare) —> Gonadotroph (rare)
Gross appearance:
- In Sella turcica
- Well circumscribed
Histology:
- Uniform polygonal cells arranged in sheets / cords
- Rare mitosis
- Round regular nuclei
- Little polymorphism (Monotonous)
—> Immunostain: Synaptophysin (staining for endocrine differentiation)
Hypopituitarism
Loss of parenchymal tissue of Pituitary
Causes:
- Tumour / mass lesion (adjacent compression to structure)
- Surgery / radiation
- Trauma
- Ischaemic necrosis, Sheehan syndrome
- Infection / inflammation
Posterior pituitary: Oxytocin + ADH
Oxytocin:
- Contraction of uterine smooth muscle at pregnancy
- Contraction of smooth muscle around lactiferous ducts of mammary glands at lactation
ADH:
- ↓ BP / ↑ Plasma osmotic pressure (high salt) —> ADH release
- Converse water by restricting diuresis
- ↑ Permeability of renal collecting ducts
- ADH deficiency —> Diabetes insipidus
Case 1:
- 40 yo female
- past medical history endometriosis + haemorrhoids
- acromegalic features for 2 years
- coarsening of facial features + shoe size increase
Investigations:
1. P/E: large nose, spade-like hands
- Blood test (anterior pituitary):
- GH ↑
- TSH, Prolactin, LH, FSH, Cortisol normal - Skull X-ray:
- enlarged pituitary fossa - MRI brain:
- 1.2 cm hypo-enhancing nodule in right side of pituitary gland —> suggestive of pituitary adenoma - Transphenoidal (through sphenoid sinus) resection of pituitary tumour with intra-operative frozen section are arranged
- Toludine blue: stain chromosomes - Immunostain: Stain with GH Ab —> diffuse positive staining in cytoplasm
Diagnosis: Pituitary adenoma
Pancreas
Exocrine + Endocrine components
Endocrine components:
Islets of Langerhans
- β (Insulin), α (Glucagon), δ (Somatostatin), PP (pancreatic polypeptide) cells
- intermixed with exocrine components (acini)
Diabetes Mellitus
Abnormal metabolic state characterised by glucose intolerance due to inadequate insulin action
Biochemical features:
- Inability to utilise + overproduction of glucose
- ↓ Protein synthesis
- Lipolysis —> Hyperlipidaemia
Type 1:
- childhood
- inadequate insulin secretion
Type 2:
- middle age onset
- ↓ sensitivity to insulin
Histology:
- ***↓ Number + Size of islets
- ***Leukocytic infiltrate in islets (Insulitis) —> T cells + Eosinophils
- Amyloid deposition within islets, around capillaries / between cells (Type 2 DM)
Pancreas: Islet cell tumours
Functional / Non-functional (asymptomatic)
-
Functional:
1. Insulinoma —> Hypoglycaemia
2. Glucagonoma —> Secondary diabetes
3. Gastrinoma —> Severe peptic ulcer (Zollinger-Ellison syndrome) (G cells in pancreas secrete Gastrin)
4. VIPoma (**vasoactive intestinal peptide) —> Water diarrhoea
Histology:
- Arranged in ribbons + anastomosing trabeculae
- Richly vascularised
- Round nuclei, Fine chromatin, Eosinophilic cytoplasm (Monotonous cell)
***Adrenal glands
Cortex:
- derived from ***mesoderm
- Zona glomerulosa (closest to capsule) —> Mineralocorticoid
- Zona fasciculata —> Glucocorticoid
- Zona reticularis —> Sex steroids
Medulla:
- derived from ***neural crest, part of SNS
- Chromaffin cells (rich in Sympathetic nerve endings)
- Catecholamines (mainly E) synthesis + secretion
Adrenal gland Hypofunction
- Primary / Secondary:
Primary: Etiology in adrenal gland
Secondary: Etiology resides higher up in axis - Acute / Chronic
- Acute primary insufficiency (Waterhouse-Friderichsen syndrome):
- Overwhelming bacterial infection
- Rapidly progression to hypotension + shock
- DIC
- Massive adrenal haemorrhage - Chronic primary adrenocortical insufficiency (Addison’s disease):
Causes (destroy normal parenchyma of adrenal cortex):
- Autoimmune adrenalitis
- TB / other infections
- Amyloidosis
- Metastatic cancers
***Adrenal gland Hyperfunction
- Hyperplasia
- Cortical adenomas
- Phaeochromocytoma (tumour in adrenal ***medulla)
Example:
1. Cushing’s syndrome (Glucocorticoid hypersecretion)
- Central obesity, Hypertension, DM, Osteoporosis
- Causes:
—> Adrenal cortical neoplasm (e.g. adenoma)
—> Excess ACTH by pituitary —> Excess adrenal androgens —> Hirsutism
—> Iatrogenic effects (ACTH / steroid administration)
- Conn’s syndrome / Primary aldosteronism (Mineralocorticoid hypersecretion)
- Autonomous secretion of excess Aldosterone (Primary)
- Causes: Cortical adenoma - Secondary aldosteronism
- Causes: ↓ Glomerular perfusion (may due to ↓ CO)
—> Stimulation of RAAS system
—> ↑ Aldosterone secretion (try to conserve Na, H2O)
