(53) Diseases of the endocrine system Flashcards
1
Q
What is the difference between endocrine, paracrine and autocrine?
A
endocrine = secrete into blood stream and act systemically
paracrine = act locally
autocrine = affects the cell secreting the protein
2
Q
Where is the pituitary gland situated?
A
in the sella turcica beneath the hypothalamus
- anterior (75%) and posterior parts (25%)
3
Q
What are the anterior and posterior parts of the pituitary also called?
A
anterior lobe = adenohypophysis (formed by outpouching of oral cavity)
posterior lobe = neuropophysis (formed by downgrowth of hypothalamus)
4
Q
What are the causes of anterior pituitary hypofunction?
A
- tumours (non-secretory adenoma, metastatic carcinoma)
- trauma
- infection
- inflammation (granulomatous, autoimmune, other infections)
- iatrogenic
5
Q
Describe the features of primary pituitary tumours
A
- vast majority are adenomas and benign
- may be derived from any hormone-producing cell
- effect secondary to hormone being produced
- local effects due to pressure on optic chiasma or adjacent pituitary
6
Q
Name 3 types of anterior pituitary adenoma
A
- prolactinoma
- growth hormone secreting
- ACTH secreting
7
Q
What is the commonest anterior pituitary adenoma?
A
Prolactinoma
8
Q
What do you get in prolactinoma pituitary adenomas?
A
Galactorrhoea and menstrual disturbance
9
Q
What is galactorrhoea?
A
Excessive or inappropriate production of milk
10
Q
What do you get in growth-hormone secreting pituitary adenomas?
A
Gigantism in children, acromegaly in adults
11
Q
What does an ACTH secreting pituitary adenoma cause?
A
Cushing’s syndrome
12
Q
Describe the anatomy of the thyroid
A
Bilobed, joined by isthmus, encased in thin fibrous capsule, located at level 5th/6th/7th vertebra in anterior neck, close to trachea
13
Q
Describe the anatomic relationships of the thyroid
A
- abuts thyroid cartilage of larynx
- recurrent laryngeal nerve located in tracheo-oesophgeal groove, close to posterior aspects of lateral lobes
14
Q
What is cretinism?
A
Severely stunted physical and mental growth due to untreated congenital deficiency of thyroid hormones (congenital hypothyroidism) usually due to maternal hypothyroidism
15
Q
What is the most common type of thyroid ectopia?
A
Lingual thyroid (usually at base of tongue)
16
Q
What occurs in most patients with lingual thyroid?
A
- over 75% have no other thyroid tissue
- 70% have hypothyroid
- 10% have cretinism
17
Q
Other than lingual thyroid, what are the other possible sites of ectopic thyroid?
A
- sella turcica
- larynx
- trachea
- aortic arch
- oesophagus
- heart
- pericardium
- liver
- gall bladder
- pancreas
- vagina
18
Q
Why do thyroglossal duct cysts occur?
A
Persistent track representing the embryological migratory path of thyroid anlage in the anterior neck
19
Q
Who do thyroglossal duct cysts occur in?
A
- most common in children and young adults
- 7% of adults
20
Q
What is the treatment for thyroglossal duct cysts?
A
Sistrunk procedure (with 4-6% recurrence rate)
21
Q
Where are the majority (75%) of thyroglossal duct cysts?
A
Anterior midline of neck or immediately below hyoid bone
- asymptomatic midline neck mass
22
Q
What is acute thyroiditis?
A
Acute inflammation of the thyroid parenchyma associated with local or systemic viral, bacterial or fungal infection
23
Q
Most cases of acute thyroiditis are due to what?
A
Generalised sepsis
24
Q
What are the symptoms of acute thyroiditis?
A
- fever
- chills
- malaise
- pain
- swelling of anterior neck
25
What does the prognosis of acute thyroiditis relate to?
The underlying condition
26
What is palpation thyroiditis?
Microscopic granulomatous foci centres on thyroid follicles - secondary to rupture of thyroid follicles due to palpation or surgery
27
Patients with palpation thyroiditis almost always have what?
A thyroid nodule
28
What is Riedel's thyroiditis?
A rare fibrosing form of chronic thyroiditis
- benign self-limited disease
- may be mistaken for malignant neoplasm
29
In Riedel's thyroiditis, the fibrosing disorder may also affect where?
- retroperitoneum
- lung
- mediastinum
- biliary tree
- pancreas
- kidney
- subcutis
30
How may patients with Reidel thyroiditis present?
- firm goitre
- dysphagia
- hoarseness
- stridor
31
What is Hashimoto's?
Chronic lymphocytic thyroiditis - autoimmune chronic inflammatory disorder associated with diffuse enlargement and thyroid autoantibodies
32
Who does Hashimoto's occur in?
- females much more common than males
| - peak age at 59 years
33
What do you get in Hashimoto's?
- diffusely enlarged non-tender gland
- serum thyroid antibodies elevated
- lymphocytic infiltration of thyroid parenchyma, often with germinal centre formation
34
Is Hashimoto's associated with hypothyroid or hyperthyroid?
Hypothyroid
35
What do patients with Hashimoto's (chronic lymphocytic thyroiditis) have an increased risk of?
- 80-fold increased risk of thyroid lymphoma
| - increased risk of papillary carcinoma of the thyroid
36
What is Grave's disease?
Au autoimmune process (activating antibodies to the TSH receptor) that results in diffuse hyperplasia of the thyroid and hyperthyroidism
37
What are the signs and symptoms of Grave's disease?
- symptoms of hyperthyroidism eg. irritability, muscle weakness, hair loss, tachycardia
- symptoms of autoimmune process eg. exophalmos, goitre, pretibial myxoedema
38
What are the hormone changes in Grave's disease (diffuse hyperplasia)?
- T3 and T4 elevated
| - TSH markedly suppressed
39
What are the autoantibodies in Grave's disease?
Thyroid stimulating immunoglobulins
40
What is a multinodular goitre?
Enlargement of thyroid with varying degrees of modularity
| - 1 or more thyroid nodules discovered by patient or doctor
41
Most patient with multi nodular goitre are euthyroid. What does this mean?
Have a normally functioning thyroid gland
42
What symptom may occur with multi nodular goitre?
- tracheal compression or dysphasia may occur with large nodules
- dominant nodule may be mistaken clinically for thyroid carcinoma
43
What is a follicular adenoma?
A benign encapsulated tumour with evidence of follicular cell differentiation
44
Who does follicular adenoma affect?
- females more than males
| - wide age range, usually 50-60
45
How does follicular adenoma present?
- painless neck mass, often present for years
- solitary nodule involving only one lobe
- usually cold nodule on radioactive iodine imaging
46
What is the commonest type of papillary carcinoma?
Papillary carcinoma (over 70%)
47
Who does papillary carcinoma affect?
Females 2.5:1
- mean 43 years
48
What is a papillary carcinoma?
A familial, autosomal dominant non-medullary thyroid carcinoma
49
Papillary carcinoma occurs as a result of what?
- radiation exposure
- FAP
- Cowden's syndrome
- therapeutic irradiation
50
What genetic alterations cause papillary carcinoma?
- activation of RET or NTRK1
- RAS mutations
- BRAF V600E mutation
- variety of chromosomal translocations or inversions
- fusion of RET tyrosine kinase regions with constitutively expressed thyroid proteins eg. PTC1 in inv(10)(q11;q21), PTC2 t(10;17)(q11;q21)
51
Describe the macroscopic appearance of papillary carcinoma
- ill-defined, infiltrative
- some encapsulated
- may be cystic
- granular
52
Name 3 types of follicular neoplasms
- follicular adenoma
- minimally invasive follicular carcinoma
- widely invasive follicular carcinoma
53
10-20% of all thyroid cancers are what?
Follicular carcinoma
54
How does follicular carcinoma present?
- 90% present with solitary nodule in thyroid
| - 10% present with distant metastasis
55
How do minimally invasive and widely invasive follicular carcinomas differ in terms of metastasis?
minimally invasive = less than 5% metastasis
widely invasive = over 60% metastasis
56
How do minimally invasive and widely invasive follicular carcinomas differ in terms of macroscopic and microscopic appearance?
minimally invasive = completely encapsulated, invasion only detectable histologically
widely invasive = macroscopic evidence of invasion, widespread invasion histologically
- minimally invasive but invades more than 4 capsular blood vessels
57
Hurthle cell carcinoma is a type of what?
Differentiated thyroid carcinoma
58
Describe the clinical behaviour of hurthle cell carcinoma
- significant cervical lymph node metastasis (unlike follicular carcinoma)
- common haematogenous sites = bone, liver, lung
59
Who does hurthle cell carcinoma occur in?
- median age = 53
| - f:m = 7:3
60
What is a better term for hurthle cell carcinoma?
Oncocytic carcinoma
61
Describe the features of insular carcinoma
- mean age = 58
- often locally advanced
- lymph node and distant metastases in 50%
- at least 60% will die of disease
62
Describe the features of anapaestic carcinoma
- mean age = 65
- rapidly enlarging thyroid mass
- may be preceded by longstanding goitre
- usually inoperable
- median survival = months
63
Describe the features of medullary carcinoma of they thyroid
- malignant tumour showing differentiation to parafollicular C cells
- 70-80% = sporadic
- 20-30% = autosomal dominant inherited
- MEN 2a and 2b
- familial MTC
- mutation in RET gene
64
What is primary thyroid lymphoma?
Primary lymphoma arising within thyroid gland, often associated with lymphocytic thyroiditis
- makes up about 2% of thyroid neoplasms
- mean age = 70s
65
Primary thyroid lymphoma may be of what 2 types?
- extranodal marginal zone type
| - diffuse large B cell type
66
Primary thyroid lymphoma are always what type of lymphoma?
Non-Hodgkin lymphoma
67
How does primary thyroid lymphoma present?
- mass in thyroid
- rapid enlargement, pain and dysphagia
- may have associated cervical lymphadenopathy
68
What is the prognosis for primary thyroid lymphoma?
Dependent on histologic type and stage, overall 60% survival
69
What are the possible metastatic tumours of the thyroid?
- renal cell carcinoma (differential diagnosis with primary clear cell thyroid tumours)
- melanoma
- small cell lung cancer
- neuroendocrine carcinoma (usually lung - differential diagnosis with medullary carcinoma)
- breast cancer
70
Which metastatic tumour would be part of the differential diagnosis of primary clear cell thyroid tumours?
Renal cell carcinoma
71
Which metastatic tumour would be part of the differential diagnosis of medullary carcinoma of thyroid?
Neuroendocrine tumour (usually lung)
72
What is primary hyperparathyroidism?
Excessive secretion of parathyroid hormone from one or more glands (PHPT)
73
What is secondary hyperparathyroidism?
Hyperplasia of glands with elevated PTH in response to hypocalcaemia (due to renal insufficiency, malabsorption, vitamin D deficiency etc)
74
What is tertiary hyperparathyroidism?
Adenoma in association with longstanding secondary hyperparathyroidism
75
What is the pathogenesis behind primary hyperparathyroidism?
- ageing, tumorigenesis in general
- association with ionising radiation
- MEN 2a
76
Describe the incidence of primary hyperparathyroidism
- 25/28 per 100,000
| - 60/190 per 100,000 in WHITE WOMEN
77
What are the potential symptoms/complications of PHPT?
- most asymptomatic
- arterial hypertension
- psychiatric problems
- hypercalcaemia
- decreased renal function
- osteoporosis
- hyperparathyroid bone disease
- hypercalcaemia symptoms
- urolithiasis
78
What are the 3 types of PHPT?
- single adenoma (most)
- diffuse chief or clear cell hyperplasia
- carcinoma (1%)
79
What is primary chief cell hyperplasia?
Non-neoplastic increase in parathyroid parenchymal cell mass within all parathyroid tissue without a known stimulus
- abnormalities in calcium metabolism
- peak age = 50-70
80
What are the symptoms of primary chief cell hyperplasia?
- fatigue
- lethargy
- anorexia
- weakness
- vomiting
81
What are the signs of primary chief cell hyperplasia?
- elevated calcium
- decrease in organic phosphorus
- increased parahormone levels
82
How is primary chief cell hyperplasia treated?
Surgery
83
What is parathyroid adenoma?
An encapsulated benign neoplasm of parathyroid cells
| - single enlarged parathyroid gland, remaining glands are suppressed and small
84
The symptoms of parathyroid adenoma are due to what?
Hypercalcaemia
85
Parathyroid adenoma is associated with which syndromes?
- MEN1 and MEN2 syndrome
| - hyperparathyroidism and jaw tumour syndrome
86
What are secondary and tertiary parathyroidism?
Non-neoplastic increase in parathyroid parenchymal cell mass within all parathyroid tissue WITH a known stimulus
87
Who is secondary and territory parathyroidism common in?
Patients with renal failure and on dialysis
88
Secondary and territory parathyroidism have identical pathologic features to what?
Primary hyperplasia
| - may be associated with massive gland enlargement
89
What is parathyroid carcinoma?
Malignant tumour derived from parathyroid parenchymal cells
| - less than 5% of primary hyperparathyroidism
90
How is parathyroid carcinoma treated?
Surgery
91
What is the prognosis for parathyroid carcinoma?
50% 10 year survival
92
The symptoms of parathyroid carcinoma are referable to what?
Excess calcium
- indolent with recurrence in about 50%
93
What are the layers of the adrenal glands?
- medulla
- reticularis
- fasciculata
- glomerulosa
= cortex
94
What do the adrenal glands secrete?
- catecholamines
- androgens
- cortisol
- aldosterone
95
What is adrenal congenital hypoplasia?
Reduced volume of adrenocortical tissue leading to adrenal cortical insufficiency (rare)
96
The clinical features of adrenal congenital hypoplasia are due to what?
Hypoadrenalism
97
How is adrenal congenital hypoplasia managed?
With glucocorticoid and mineralocorticoid replacement (mortality high if untreated)
98
What causes adrenal congenital hypoplasia?
- may be part of familial hereditary condition
| - male predominance, often X-linked
99
What is congenital adrenal hyperplasia?
Inherited disorder caused by deficiency of enzymes required for synthesis of glucocorticoids and mineralocorticoids
100
Lack of which enzymes causes congenital adrenal hyperplasia?
- 21 hydroxylase deficiency = more than 90%
- 11-beta-hydroxylase = 5%
Deficiencies of cortical and aldosterone secretion
101
Describe the signs/complications in congenital adrenal hyperplasia
- genital ambiguity in females, normal in males
- may be evidence of virilisation and hyperandrogenism
- advanced bone growth with premature epiphyseal maturation = short adult stature
102
What is virilisation?
Male-pattern hair growth and other masculine physical traits in women
- can be caused by hyperandrogenism
103
What is Addison's disease?
Primary adrenal cortical insufficiency caused by adrenal dysgenesis, adrenal dysfunction
104
What are the causes of Addison's disease?
- autoimmune against the adrenal cortex
| - TB infection (more common in developing countries)
105
What are the clinical features of Addison's disease?
- hyperpigmentation
- postural hypotension
- hyponatraemia
- fatigue
- weight loss
- increased thirst
- progressive anaemia
106
How is Addison's disease treated?
Long term steroid replacement
| - high mortality if not diagnosed
107
What are adrenal cortical nodules?
Benign non-functional nodules of adrenal cortex
108
Adrenal cortical nodules occur more in who?
- elderly
- hypotensive
- diabetic patients
109
What are the symptoms of adrenal cortical nodules?
- no clinical symptoms
- incidental discovery on radiographic studies
- no treatment required
110
What is adrenal cortical adenoma?
Benign neoplastic proliferation of adrenal cortical tissue
111
What are the symptoms of adrenal cortical adenoma?
Symptoms related to endocrine hyperfunction (hypertension, Cushing's syndrome, virilisation)
112
What do aldosterone-producing tumours cause?
Conn's syndrome
113
What do cortisol-producing tumours cause?
Cushing's syndrome
114
What is Conn's syndrome?
Excess production of the hormone aldosterone by the adrenal glands resulting in low renin levels
115
Describe an adrenal cortical adenoma
- unilateral solitary masses
- 2cm, less than 100g
- well-circumscribed yellow/brown nodules
- formed from lipid-filled adrenal cortical cells
116
What are the features of adrenal cortical carcinoma
- malignant counterpart of adrenal adenoma
- symptoms related to hormone excess
- abdominal mass
- prognosis is age and stage dependent
- 5 year survival about 70%
117
What is phaeochromocytoma?
Catecholamine-secreting tumour arising from adrenal medulla (10% bilateral, 10% extra-adrenal, 10% malignant, 10% familial, 10% children)
118
What is the prognosis of phaeochromocytoma?
- excellent prognosis when benign and properly managed surgically
- malignant tumour may pursue and aggressive course
119
What are the hormone changes in phaeochromocytoma?
Elevated urine catecholamines, adrenaline and noradrenaline
120
What are the causes of phaeochomocytoma?
Most are sporadic but may be due to familial syndromes MEN2a and 2b, von Recklinghausen's disease, von Hippel-Lindau disease
121
What are the symptoms of phaechromocytoma?
- hypertensions
- palpitations
- headaches
- anxiety
