Pathology of the Endocrine System 3

Question 1

PARATHYROID HYPERFUNCTION

Answer 1

Hyperparathyroidism.
PRIMARY or
SECONDARY- Renal, nutritional or pseudohyperparathyroidism.

eg. Horse with primary hyperparathyroidism due to parathyroid adenoma. Presented with fracture- pathological due to weakened bones. Thickened mandible (‘big face’) seen due to bone resorption and replacement with fibrous connective tissue- FIBROUS OSTEODYSTROPHY.

Question 2

CALCIUM/PHOSPHATE REGULATION BY PTH/CALCITONIN AND VITAMIN D

Answer 2

Ca:P ratio is important- should be relatively high:relatively low.
Dietary Ca is reabsorbed from the intestinal lumen, aided by active Vitamin D (1,25-dihydrocholecalciferol, vitamin D3).
PTH aids activation of vitamin D and absorption of Ca from the gut.
It also promotes osteoclast activation and bone resorption of Ca, and renal tubule reabsorption of Ca/excretion of P/activation of vitamin D.
CALCITONIN has the opposite effect, inhibiting gut uptake of Ca, inhibiting osteoclast action and promoting Ca excretion in urine. It is released from the parathyroid glands in response to elevated serum Ca levels.

Question 3

RENAL SECONDARY HYPERPARATHYROIDISM

Answer 3

Secondary to CHRONIC RENAL FAILURE.
Decreased GFR- Lose Ca, retain P.
Decreased production of 1,25-diOHD3 (normally occurs in kidney).
Low Ca stimulates parathyroid glands (hyperplasia) -> increased PTH -> increased bone resorption -> increased circulating P/Ca.
P complexes with Ca in tissues, causing mineralisation/necrosis of lungs, kidney and stomach.
Uraemia.
Fibrous osteodystrophy eg. rubber jaw.

Tubular epithelial cells fail to respond to PTH, so P levels remain high -> relative hypocalcaemia- PTH continues to be produced, bone resorption etc. continue.

Question 4

RENAL SECONDARY HYPERPARATHYROIDSIM 2

Answer 4

Chronic renal disease- kidneys cannot respond to PTH.
-> phosphate retention continues, giving relative hypocalcaemia.
-> continues parathyroid stimulation (hyperplasia)-> continued bone resorption -> fibrous osteodystrophy/osteodystropha fibrosa.
Bone is replaced by fibroblastic tissue.
Bone remodelling increases size- periosteal new bone formation.
Bones are soft, rubbery and easily fractured.

Question 5

RELATIVE HYPOCALCAEMIA- NORMAL ANIMAL

Answer 5

In the normal animal, relative hypocalcaemia (low Ca:P ratio) would cause increased bone resorption, increased P excretion in kidney and increased Ca resorption in the kidney.

In chronic renal failure, increased P excretion and Ca absorption cannot occur, as the kidney is not functioning.
This is why bones are so severely affected (fibrous osteodystrophy).

Question 6

NUTRITIONAL SECONDARY HYPERPARATHYROIDISM

Answer 6

Dietary imbalance of calcium and phosphorous.
-Diets LOW in Ca (or HIGH in oxalate- chelates Ca)
-Diets HIGH in P (and normal or low in Ca)
-Occasionally seen with vitamin D deficiency.
PTH production is increased to try and resume normal CA:P ratio.
Seen more commonly in exotics- guinea pigs, reptiles.
-> Fibrous osteodystrophy in short bones.
->Osteopaenia in long bones- decrease in bone mass.
Histologically, periosteal new bone formation can be seen.

Question 7

PSEUDOHYPERPARATHROIDISM

Answer 7

HUMERAL HYPERCALCAEMIA OF MALIGNANCY- HHM.

• Tumours of non-endocrine origin eg. lymphoma, multiple myeloma, adenocarcinoma of glands of anal sac, also mammary/gastric adenocarcinomas.
• Produce PTHrP- parathyroid hormone-related protein.
• Increases circulating Ca- increased intestinal absorption, resorption from bone, decreased renal excretion.
• Atrophy of parathyroid glands- they are not needed to produce PTH, as the tumour is doing it instead.

Question 8

HYPERCALCAEMIA

Answer 8

Increased circulating Ca.
Has several possible causes: Humeral hypercalcaemia of malignancy, functional parathyroid neoplasm, chronic Johne’s disease…

Question 9

FUNCTIONAL PARATHYROID NEOPLASM

Answer 9

Primary hyperparathyroidism.
Increased PTH production
Increased intestinal absorption, bone resorption of Ca, decreased renal excretion of Ca.
-> hypercalcaemia.

Question 10

CHRONIC JOHNE’S DISEASE

Answer 10

Granulomatous inflammation of distal ileum causes macrophages to release a precursor of vitamin D.
-> hypercalcaemia -> mineralisation, especially in aorta.

Question 11

PANCREAS

Answer 11

Majority is exocrine tissue, producing and secreting digestive enzymes.
ENDOCRINE TISSUE- ISLETS OF LANGERHANS- comprised of ALPHA (a), BETA (B) and DELTA (d) cells.
-a cells- secrete GLUCAGON
-B cells- secrete INSULIN (made from proinsulin)
-d cells- secrete SOMATOSTATIN (Growth Hormone Inhibiting Hormone)

Question 12

NORMAL PANCREATIC ENDOCRINE TISSUE

Answer 12

Pale staining on H&E.

Triple staining can be used to visualise different cell types (a, B, d)

Question 13

PANCREATIC ISLET HYPOFUNCTION

Answer 13

Results in the clinical syndrome known as DIABETES MELLITUS.
Caused by damage to the pancreatic islets:
-Vacuolar degeneration
-Amyloidosis (cats)- pink, amorphous substance, accumulates in response to chronic inflammation.
-Immune mediated destruction (dogs)
-Secondary to pancreatitis- fibrosis decreases function.

Question 14

PANCREATIC ISLET HYPOFUNCTION- EFFECTS

Answer 14

DECREASED INSULIN PRODUCTION

• > glucose not converted to glycogen- HYPERGLYCAEMIA (increased circulating glucose)
• > glucosuria
• > inhibited renal tubular resorption -> PU/PD
• > less glucose biologically available -> weakness
• > increased glucose metabolised by sorbitol pathway (normally anaerobic glycolysis, but enzymes in this pathway have been overloaded by increased circulating glucose) -> accumulation of sugar alcohols in lens of eye -> cataracts.

Question 15

GLUCOSE RESORPTION BY PROXIMAL CONVOLUTED TUBULES

Answer 15

Normally relatively efficient.
Glucose transporters are SODIUM dependent.
Other ions are also resorbed.

Question 16

DIABETES MELLITUS

Answer 16

Common in dogs and cats (dogs more so).
Seen spontaneously in middle aged dogs (peak 7-9 years), 2x more likely in females than males.
Some small dog breeds show increased incidence- miniature poodles, dachshunds, terriers.
Dogs- INSULIN DEPENDENT (as in Type I in humans)
Cats- insulin dependent 50%- cell amyloidosis.
-insulin resistant 50%- as in Type II in humans. Multifactorial, often obese animals.

Question 17

DIABETES MELLITUS- CAUSES

Answer 17

eg. cat- chronic pancreatitis with nodular hyperplasia.
(nodular hyperplasia- ageing process, seen in spleen/liver also of middle aged animals)
Amyloid accumulation in islet cells in response to chronic inflammation- decreases function of islet cells.
The liver may also be affected- glycogen accumulation in hepatocytes due to abnormal metabolism- hepatic lipidosis. Pale, nucleated cells.
Cataracts are seen due to metabolism of glucose via the sorbitol pathway.

Question 18

PANCREATIC ISLET HYPERFUNCTION

Answer 18

Related to neoplasms- subclassified in to B cell type and non-B cell type.
TYPE DICTATES CLINICAL SIGNS.
Non-functional neoplasms and hyperplasia of the pancreas can still occur.

Question 19

PANCREATIC ISLET TUMOURS

Answer 19

• B CELL TUMOUR- INSULINOMA- causes severe hypoglycaemia.
• G CELL TUMOUR- GASTRINOMA- causes gastric hypersecretion, peptic ulcers.
• a CELL TUMOUR- GLUCAGONOMA- causes diabetes.
• d CELL TUMOUR- SOMATOSTATINOMA- diabetes, steatorrhoea.

Question 20

INSULINOMAS

Answer 20

Islet B cell tumours.
Adenomas- DOGS 40%, HUMANS 10%
Carcinomas- DOGS 60%, HUMANS 90%
Most are functional tumours.
Respond to provocative stimuli (glucose) to produce insulin.
Size of tumour does not necessarily indicate severity.
Diagnosis- PME and histopathlogy to confirm the tumour is not metastatic etc.
Metastasis can occur.

Question 21

INCREASED INSULIN

Answer 21

Seen with pancreatic islet hyperfunction.

• > hypoglycaemia (glucose all converted to glycogen)
• > decreased glucose bioavailability -> neurological signs- weakness, lethargy, collapse, nervousness, seizures.
• > adrenal medulla secretes catecholamines (in response to hypoglycaemia) -> increased blood pressure.

Question 22

GLUCAGONOMA

Answer 22

Glucagon secreting islet cell tumours (a cells).
Rare in dogs.
Insulin antagonising (glucagon converts glycogen to glucose)- causes DIABETES MELLITUS
Also causes- diarrhoea (altered water/electrolyte absorption), diffuse vacuolar hepatopathy, may cause superficial necrolytic dermatitis in cats.

Question 23

GASTRINOMA

Answer 23

Gastrin secreting islet cell tumours (G cells).
Rare in dogs and cats.
Zollinger-Ellison syndrome- hypersecretion of gastric acid, damages mucosal protection, leads to gastroduodenal ulceration.
Clinically presents as sudden extreme pain and collapse.
Infiltrative- metastases can be seen in regional lymph nodes and liver.

Question 24

GONADS- NORMAL FUNCTION

Answer 24

Hypothalamus secretes GnRH.
This acts on the pituitary, which releases FSH and LH.
These act on the gonads, which produce sex steroids, inhibin and activin.
Inhibin and activin exert negative feedback on the pituitary.
Sex steroids exert negative feedback on the pituitary and the hypothalamus.

Question 25

GONADAL HYPOFUNCTION

Answer 25

Usually associated with sub-fertility or infertility- important in breeding animals.
CAUSES:
-Hypoplasia- cryptorchid, disorder of sexual differentiation.
-Degeneration- secondary to trauma, neoplasia, inflammation etc.
-Secondary to other endocrine disturbances, or body weight.

Question 26

GONADAL HYPERFUNCTION

Answer 26

Almost always related to NEOPLASIA.
Ovaries can be hyperfunctional in older bitches that have never been bred from.
Clinical signs- often related to over production of hormone, but may just be limited to increased size of gonad (male) or tubular structure (female- cystic endometrial hyperplasia)

Question 27

OVARIAN HYPERFUNCTION

Answer 27

Several neoplasms can arise in the ovary, but only one is functionally significant: GRANULOSA CELL TUMOUR.
Clinical signs- Behavioural changes based on hormone production- TESTOSTERONE- aggression, stallion like behavious (horse), anoestrus.
OESTROGENS- nymphomania.

Question 28

TESTICULAR HYPERFUNCTION

Answer 28

3 main functionally significant neoplasms:
SEMINOMA- germ cell tumour
LEYDIG CELL TUMOUR- produces testosterone
SERTOLI CELL TUMOUR- often see bands of fibrosis.
Clinical signs vary with cell of origin.
Some types are more common in cryptorchid animal- SERTOLI cell tumour. Animal presents with feminisation.
Neoplastic testes are very yellow due to steroid production, and areas of haemorrhage are often seen.
Collision tumours- histologically distinct tumours occur in the same tissue eg. sertoli and leydig cell tumours at once.