Endocrine pathology

Question 1

in the thyroid, what do parafollicular or C cells produce?

Answer 1

Calcitonin

Question 2

what ar ethe effects of the thyroid hormones?

Answer 2

upregulation of CHO, lipid metabolism and protein synthesis + an increase in metabolic rate, critical role in brain development

Question 3

What are the main causes of HYPERTHYROIDISM?

Answer 3

Graves Disease (20-40yo, F)- > autoimmune resulting from the brak down of self tolerance of thyroid autoantigens (TRAB), importantly the TSH receptors , which results in : diffuse toxic hyperplasia, infiltrative opthalmopathy, localised dermopathy known as myoedema.

• Hyperfunctioning toxic multinodular goitre
• hyperfunctioinig toxic adenoma
• Iodine induced hyperthryoidism
• Neonatal thyrotoxicosis assoc. with maternal graves disease.
• hyperfunctioning thyroid carcinoma
• TSH secreting pituiitary adenoma (rare)

Question 4

What are some causes of HYPERTHYROIDISM where you WOULDNT see low TSH levels?

Answer 4

• Subacute granulomatous thyroiditis (de Quervain’s)- painful thyroiditis : 40-50 yo F, post viral infection. Pain and transient hyperthyroidism
• Subacute lymphocytic thyroiditis:painless thyroiditis : anti-TPO positive-
• Struma ovarii (ovarian teratoma with ectopic thyroid)
• Factitious thyrotoxicosis (exogenous thyroxine intake)

Question 5

What are the causes of hypothyroidism? PRIMARY

** associated with goitre

Answer 5

Hashimoto’s Thyroiditis: autoimmune (45-65, F), autoimmune destruction of the thyroid gland characterised by a lymphocytic infiltrate, autoantibodies to thyroglobulin and thyroid peroxidase (anti-TPO)
- Iodine deficiency **
- Post ablative surgery, radioiodine surgery, external radiation
- drugs (lithium)
- Developmental
Congenital **

• Drugs (lithium, iodides, p-aminosalicylic acid);
• Developmental (thyroid dysgenesis: PAX-8, TTF-2, TSH-receptor
mutations);
• Thyroid hormone resistance syndrome (TRβ mutations);
• Congenital biosynthetic defect (dyshormonogenetic goitre)
Secondary: Pituitary failure, Tertiary: hypothalamic failure
**These can be associated with goitre (please also see “causes of goitre” below)

Question 6

What are secondary causes of hypothyroidism

Answer 6

Pituitary failure

Question 7

What are tertiary causes of hypothyroidism

Answer 7

hypothalamic failure

Question 8

What are the causes of goitre?

Answer 8

either diffuse or multinodular, endemic or sporadic.

Question 9

cuases of endemic goitre

Answer 9

endemic goitre?: characterised by low intake of iodine, and sometimes the intake of goitrogens that interfere with thyroid synthesis
Iodine deficiency is a common but preventable health problem. It leads to impairment of thyroid hormone synthesis and increase in TSH causing hypertrophy of the follicular cells.
The resultant increase in the mass of the thyroid overcomes the hormone deficiency, but not always and the patient may become hypothyroid.

Question 10

Causes of Sporadic goitre

Answer 10

SPORADIC GOITRE: has a female preponderance and a peak incidence at puberty or early adult life. Note that goitre may be physiological in adolescence and pregnancy. Sporadic goitre has many causes that include ingestion of substances that interfere with thyroid hormone synthesis, autosomal recessive conditions- dyshormonogenetic goitre or is idiopathic. Most simple goitrous presentations are euthyroid.

Question 11

Causes of Multinodular goitre

Answer 11

Is caused by recurrent episodes of hyperplasia and involution that produce irregular enlargement of the thyroid.
All simple types of goitre can convert into multinodular goitre
The dominant clinical features are mass effects including superior vena caval syndrome.
Most multinodular presentations are euthyroid or have subclinical hyperthyroidism.
Some may develop an autonomous nodule and produce hyperthyroidism. The incidence of malignancy in long-standing goitres is <5%.

Question 12

What features would you see on a HYPERPLASTIC THYROID?

Answer 12

Scalloping of coloid
Papillary folding
Loss of coloid ! relative icnrease in the number of cells at the expense of colloid
cells lining the coloid appear low columnar or cuboidal (instead of squamous)

Question 13

What would you see in a MULTINODULAR thyroid?

Answer 13

• variably sized and shape follicles form irregular nodules
• follicles are distended with colloid
• cuboidal cells show regular nuclei
• haemociderin laden macrophages
• fibrosis

Question 14

HASHIMOTO’s

Answer 14

• Atrophied follicles
• intense inflammatory cell infiltrate (germinal cells, lymphocytes, plasma cells) replacing follicles
• groups of HURTHLE CELLS

Question 15

What would you see in an adenoma?

Answer 15

regular round nuclei and granular cytoplasym

Question 16

What is the most common primary benign neoplasm of the thyroid?

Answer 16

Primary adenoma

Question 17

what are some primary malignant thyroid neoplasms?

what is the most common

Answer 17

Papillary carcinoma (75% to 85% of cases)

Follicular carcinoma (10% to 20% of cases) – often appear the same as adenoma but show capsular invasion.
Medullary carcinoma (5% of cases) – MEN2
Anaplastic carcinoma (<5% of cases)

Question 18

WHAT IS A GOOD WAY OF EVALUATING A THYROID NODULE?

Answer 18

FNA BIOPSY

Question 19

What does papillary carcinoma of the thyroid look like microscopically?

Answer 19

unencapsulate
papillary structures with a branching pattern
ground glass bodies 
PSAMMOMA BODIES- bright red
infiltrating nests of tumour cells

Question 20

What are the causes of primary hyperparathyroidism?

Answer 20

Parathyroid adenoma 80-85%
Parathyroid hyperplasia 15% (Note the association with MEN I and 2 ) and
rarely parathyroid carcinom

Question 21

wht is the commmonest tumour of the pituitary gland?

Answer 21

Pituitary adenoma
• Commonest tumour of the pituitary gland
• 10% of all intracranial neoplasms
• 25-35% invade local tissue without the capacity to metastasize
• Young to middle aged adults
• Functioning or non-functioning determines clinical presentation
• If non-functioning macroadenoma >10mm
– visual field defects and HYPOPITUITARISM
• If functioning usually a microadenoma <10mm

Question 22

In functioning adenoma’s what are common pathologies which can occura as a consequence?

Answer 22

– GH-gigantism or acromegaly
– TSH- hyperthyroidism
– Prolactin-galactorrhoea, amenorrhoea, infertility
– FSH/LH-ovarian cysts, oligomenorrhoea, amenorrhoea, endometrial
hyperplasia
– ACTH-Cushing’s disease

Question 23

Describe CUSHING’s Syndrome

Answer 23

Caused by any condition that produces elevated glucocorticoid levels (cortisol).
Aetiology:
exogenous: Most commonly iatrogenic glucocorticoid administration

Endogenous :
ACTH-dependent
• Cushing disease– pituitary adenoma (70%)
• Ectopic ACTH/CRH from tumour (for example lung cancer) (10%)
ACTH-independent
• Adrenal adenoma (10%)
• Adrenal carcinoma (5%) Rarer causes
• Macronodular hyperplasia
• Primary pigmented nodular adrenal disease
• McCune-Albright syndrome

Question 24

What is CONN’s Syndrome?

Answer 24

HIGH BP caused by excessive production of aldosterone (mineralocorticoid)
Aetiology
– Adrenal adenoma 40%
– Bilateral hypertrophy of the zona glomerulosa cells* 60%
– Glucocorticoid-remediable aldosteronism (Autosomal Dominant where
aldosterone secretion is under the control of ACTH)
– Adrenal Carcinoma

Question 25

What is Addison’s disease

Answer 25

Primary chronic adrenal hypofunction
Uncommon but can be life threatening. Caused by progressive destruction of the adrenal cortex. Manifestions do not appear until at least 90% of the adrenal cortex has been compromised.
Clinical features of progressive weakness and easy fatiguability, gastrointestinal disturbance, hyperpigmentation of the skin due to elevated POMC (pro-opiomelanocortin), which is a precursor for ACTH and MSH (melanocyte stimulating hormone).
Decreased mineralocorticoid leads to hyperkalaemia, hyponatremia, volume depletion and hypotension.
Hypoglycaemia may occur due to glucorticoid deficiency and impaired gluconeogenesis. People with adrenal hypofunction are at risk of an adrenal crisis, particularly when they have intercurrent illness - this may present as intractable vomiting, abdominal pain, hypotension, vascular collapse and coma.

Question 26

What are the causes of Addisons

Answer 26

progressive destruction of the adrenal cortex is caused by:
– Autoimmune adrenalitis (can be part of autoimmune polyendocrine syndrome type 1 or 3)
– Tuberculosis
– AIDS (complication from infection CMV, MAC or Kaposi sarcoma)
– Metastatic cancers (breast and lung more commonly)

Question 27

What is acute adren-cortical insufficiency, and what are the causes

Answer 27

– Adrenal crisis in patients with chronic adrenocortical insufficiency
– Withdrawal of glucocorticoid treatment without recovery of adrenal function
– Massive adrenal haemorrhage (called Waterhouse-Friderichsen syndrome
when associated with a bacteremic infection)

Question 28

What is secondary adreno-cortical insufficiency?

Answer 28

Secondary Adrenocortical Insufficiency
Any pathology that reduces output of ACTH (not associated with hyperpigmentation). Includes hypothalamic and pituitary pathology.

Question 29

what is phaeochromocytoma

Answer 29

• Tumours secrete catecholamines and can present as a rare but treatable cause of hypertension
Rule of 10s:
• 10% are not associated with HTN (in the 90% that are, it may be
paroxysmal HTN)
• 10% can be found in extramedullary tissue (in the paraganglia they are called paragangliomas and are more likely to be malignant).
• 10% sporadic adrenal phaeochromocytomas are bilateral
• 10% are malignant
- Up to 25% may have inherited germline mutations- MEN2A and 2B, Neurofibromatosis 1, Von Hippel Lindau, Familial paraganglioma (1,3 and 4) (and have additional features to phaeochromocytoma and/or paraganglioma).
Note that the adrenal gland produces oestrogens and androgens and these may contribute to the clinical presentation of adrenal disease