Endocrine fifth yr

Question 1

Types of thyroid cancer

Answer 1

Papillary - Often young females - excellent prognosis - lymph node metastasis

Follicular - Usually present as a solitary thyroid nodule

Medullary - Cancer of parafollicular (C) cells, secrete calcitonin, part of MEN-2

Anaplastic - Not responsive to treatment, can cause pressure symptoms

Lymphoma - Not responsive to treatment, can cause pressure symptoms

Question 2

Management of papillary and follicular cancer

Answer 2

total thyroidectomy

followed by radioiodine (I-131) to kill residual cells

yearly thyroglobulin levels to detect early recurrent disease

Question 3

What is acromegaly?

Answer 3

clinical manifestation of excessive growth hormone

Growth hormone is produced by the anterior pituitary gland - commonly caused by pituitary adenoma. Less common - ectopic GHRH or GH from lung/pancreatic ca

Question 4

Features of acromegaly?

Answer 4

SOL - headaches, bitemporal hemianopia

Overgrowth of tissues - frontal bossing, macroglossia, prognathism, arthritis from imbalanced growth of joints

Organ dysfunction - hypertrophic heart, HTN, T2DM, colorectal ca

Development of new skin tags

Profuse sweating

Raised prolactin in 1/3 cases - galactorrhea

6% have MEN-1

Question 5

Ix for acromegaly?

Answer 5

Random GH level not helpful

Insulin-like growth factor 1 (IGF-1) is initial screening test

OGTT whilst measuring GH (glucose normally suppresses GH)

MRI brain

Refer to ophthalmology

Question 6

Treatment for acromegaly?

Answer 6

Trans-sphenoidal removal

Pegvisomant (GH antagonist given subcutaneously and daily)

Somatostatin analogues to block GH release (e.g. ocreotide)

Dopamine agonists to block GH release (e.g. bromocriptine)

Question 7

Summary of Kallman syndrome?

Answer 7

genetic condition causing hypogonadotrophic hypogonadism

X-linked recessive trait

thought to be caused by failure of GnRH-secreting neurons to migrate to the hypothalamus

causes failure to start puberty. Cryptochidism.

associated with reduced or absent sense of smell

Sex hormones low. LH/FSH inappropriately low/normal

Cleft lip/palate and visual/hearing defects are also seen in some patients

Tx - testosterone supplementation. Gonadotrophin supplementation may result in sperm production if fertility is desired later in life

Question 8

Summary of Klinefelter syndrome?

Answer 8

occurs when a male has an additional X chromosome, making them 47 XXY

Rarely people with Klinefelter syndrome can have even more X chromosomes, such as 48 XXXY or 49 XXXXY. This is associated with more severe features

patients with Kleinfelter syndrome appear as normal males until puberty - at puberty they can develop: taller height, wider hips, gynaecomastia, weaker muscles, small testicles, reduced libido, shyness, infertility, subtle learning difficulties

Tx:
Testosterone injections to improve Sx
IVF
Breast reduction surgery
SALT
OT
PT
Educational support

Life expectancy close to normal. Slight increased risk of: breast ca, osteoporosis, diabetes, anxiety and depression

Question 9

Summary of MEN type 1

Answer 9

3 P’s

Parathyroid - hyperparathyroidism due to parathyroid hyperplasia

Pituitary

Pancreas - insulinoma, gastrinoma (leading to recurrent peptic ulceration)

Also - adrenal and thyroid

MEN1 gene

Common presentation - hypercalcaemia

Question 10

Summary of MEN type 2a

Answer 10

2 P’s

Medullary thyroid cancer

Parathyroid - hyperparathyroidism

Phaeochromocytoma

RET oncogene

Question 11

Summary of MEN type 2b

Answer 11

1 P

Medullary thyroid cancer

Phaeochromocytoma

Marfanoid body habitus

Neuromas

RET oncogene

Question 12

Summary of prolactinoma

Answer 12

Type of pituitary adenoma -classified due to size (microadenoma <1cm, macro adenoma >1cm) and hormonal status (functioning/non functioning)

Feature - amenorrhoea, infertility, galactorrhea, osteoporosis, impotence, loss of libido, headache, visual disturbance (bitemporal hemianopia or upper temporal quadrantanopia), signs of hypopituitarism

Dx - MRI

Tx - symptomatic patients are treated medically with dopamine agonists (e.g. cabergoline, bromocriptine) which inhibit the release of prolactin from the pituitary gland.
trans-sphenoidal surgery

Question 13

What is phaeochromocytoma?

Answer 13

a tumour of the chromaffin cells that secretes unregulated and excessive amounts of adrenaline.

Adrenaline is a “catecholamine” hormone and neurotransmitter that stimulates the sympathetic nervous system and is responsible for the “fight or flight” response. In patients with a phaeochromocytoma the adrenaline tends to be secreted in bursts giving periods of worse symptoms followed by more settled periods.

Sx: Anxiety, Sweating, Headache, Hypertension, Palpitations, tachycardia and paroxysmal atrial fibrillation

Associated with MEN2, neurofibromatosis and von Hippel-Lindau syndrome

10% rule to describe the patterns of tumour:

10% bilateral
10% cancerous
10% outside the adrenal gland

Question 14

Ix and Tx of phaeochromocytoma?

Answer 14

24 hr urinary collection of metanephrines - 97% sensitivity - replaced: NOW
24 hour urine catecholamines
Plasma free metanephrines

Tx:
Alpha blockers (i.e. phenoxybenzamine)
Beta blockers once established on alpha blockers
Adrenalectomy to remove tumour is the definitive management

Question 15

Causes of thyrotoxicosis?

Answer 15

Graves’ disease
toxic nodular goitre
acute phase of subacute (de Quervain’s) thyroiditis
acute phase of post-partum thyroiditis
acute phase of Hashimoto’s thyroiditis (later results in hypothyroidism)
amiodarone therapy
contrast

Question 16

Causes of hypothyroidism?

Answer 16

F>M

Hashimoto’s thyroiditis
most common cause
autoimmune disease, associated with IDDM, Addison’s or pernicious anaemia
may cause transient thyrotoxicosis in the acute phase
5-10 times more common in women

Subacute thyroiditis (de Quervain’s)

Riedel thyroiditis

After thyroidectomy or radioiodine treatment

Drug therapy (e.g. lithium, amiodarone or anti-thyroid drugs such as carbimazole)

Dietary iodine deficiency

Secondary hypothyroidism - pituitary failure, associated conditions - Down’s, Turner’s, coeliac

Question 17

Summary of Graves disease?

Answer 17

most common cause of thyrotoxicosis. typically seen in women aged 30-50 years.

Signs of thyrotoxicosis.
Signs limited to Graves = eye signs (exophthalmos, ophthalmoplegia), pretibial myxoedema, thyroid acropachy (digital clubbing, soft tissue swelling of hands and feet, periosteal new bone formation)

Autoantibodies - TSH receptor stimulating antibodies, anti-TPO antibodies

Thyroid scintigraphy - diffuse, homogenous, increased uptake of radioactive iodine

Tx - propranolol to block adrenergic effects, carbimazole (usually for 12-18m, SE - agranulocytosis), radioiodine if resistant to medical Tx (CI = pregnant or <16)

Question 18

Summary of Hashimoto’s thyroiditis?

Answer 18

It is typically associated with hypothyroidism although there may be a transient thyrotoxicosis in the acute phase. It is 10 times more common in women

Sx - hypothyroidism, firm, non-tender goitre, TPO and anti-thyroglobulin antibodies

Question 19

Summary of subacute (De Quervain’s) thyroiditis?

Answer 19

thought to occur following viral infection and typically presents with hyperthyroidism.

There are typically 4 phases;
phase 1 (lasts 3-6 weeks): hyperthyroidism, painful goitre, raised ESR
phase 2 (1-3 weeks): euthyroid
phase 3 (weeks - months): hypothyroidism
phase 4: thyroid structure and function goes back to normal

Investigations
thyroid scintigraphy: globally reduced uptake of iodine-131

Management
usually self-limiting - most patients do not require treatment
thyroid pain may respond to aspirin or other NSAIDs
in more severe cases steroids are used, particularly if hypothyroidism develops

Question 20

Summary of postpartum thyroiditis?

Answer 20

Three stages
1. Thyrotoxicosis
2. Hypothyroidism
3. Normal thyroid function (but high recurrence rate in future pregnancies)

Thyroid peroxidase antibodies are found in 90% of patients

Management
thyrotoxic phase
propranolol is typically used for symptom control
not usually treated with anti-thyroid drugs as the thyroid is not overactive.
hypothyroid phase
usually treated with thyroxine

Question 21

Summary of toxic multi nodular goitre?

Answer 21

number of autonomously functioning thyroid nodules resulting in hyperthyroidism

goitre with firm nodules. most patients >50

Scintigraphy reveals patchy uptake

Tx - radioiodine therapy

Question 22

Summary of thyroid storm?

Answer 22

Thyrotoxic crisis

more severe presentation of hyperthyroidism with pyrexia, tachycardia, delirium, HTN, HF, abnormal LFTs

Precipitating events: thyroid or non-thyroidal surgery, trauma, infection, acute iodine load e.g. CT contrast media

It requires admission for monitoring and is treated the same way as any other presentation of thyrotoxicosis, although they may need supportive care with fluid resuscitation, anti-arrhythmic medication and beta-blockers. dexamethasone - e.g. 4mg IV qds - blocks the conversion of T4 to T3

Question 23

What is T1DM?

Answer 23

Autoimmune

Insulin-producing beta cells of Islets of Langerhans in pancreas are destroyed by immune system

Question 24

What is T2DM?

Answer 24

Relative deficiency of insulin due to excess adipose tissue

Question 25

What is MODY?

Answer 25

Maturity onset diabetes of the young (MODY)

AD condition

Younger patients with Sx similar to T2DM

Question 26

What is LADA?

Answer 26

Latent autoimmune diabetes in adults (LADA)

Often misdiagnosed as T2DM

Question 27

Other causes of DM?

Answer 27

Haemachromatosis

Chronic pancreatitis

Pancreatic cancer

Question 28

S+S of DM?

Answer 28

Type 1:
WL
polydipsia/uria
Present with DKA

Type 2:
picked up incidentally
polydipsia and polyuria - due to osmotic effects of glycosuria

Question 29

Ix of diabetes?

Answer 29

Pt. symptomatic - fasting glucose >7, random glucose >11

asymptomatic - same criteria but on 2 separate occasions

HbA1c - >48 is diagnostic of DM

Question 30

What is prediabetes?

Answer 30

HbA1c 42-47
Fasting glucose 6.1-6.9

Impaired fasting glucose - due to hepatic insulin resistance - fasting glucose 6.1-6.9, offer OGTT to rule out diabetes

impaired glucose tolerance - due to muscle insulin resistance - fasting glucose <7, but OGTT >7.8 but <11

Question 31

Ix for T1DM?

Answer 31

urine dipstick - glucose and ketones

fasting and random glucose

HbA1c isnt as useful for T1DM

If T1DM suspected but atypical features (>50, BMI >25, long prodrome):

C- peptide LOW

Diabetes specific autoantibodies - anti-GAD, ICA, IAA, IA-21

BMI - recent WL typical

Question 32

Management of T1DM?

Answer 32

HbA1c every 3-6m

Self-monitoring of BG - x4/d

Insulin - multi daily injection regiment, twice daily, insulin analogues

Metformin if BMI >25

Question 33

T2DM managemnet?

Answer 33

Dietary - high fibre, low GI carbs, lower fats, WL of 5-10%

HbA1c every 3-6m until stable, then 6m
Targets:
lifestyle - 48
lifestyle and metformin - 48
with drugs that may cause hypo - 53
add second drug if >48

Metformin - first line

SGLT-2 - in addition to metformin if ^ CVD - metformin established first

If metformin CI’ed, no CVD - DPP-4 inhibitor, pioglitazone, sulfonylurea

If triple therapy not effective - consider switching 1 drug for GLP-1 mimetic if BMI >35

Risk factor modification - HTN > ACEi/ARB