Endocrine fifth yr Flashcards
Types of thyroid cancer
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
Management of papillary and follicular cancer
total thyroidectomy
followed by radioiodine (I-131) to kill residual cells
yearly thyroglobulin levels to detect early recurrent disease
What is acromegaly?
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
Features of acromegaly?
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
Ix for acromegaly?
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
Treatment for acromegaly?
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)
Summary of Kallman syndrome?
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
Summary of Klinefelter syndrome?
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
Summary of MEN type 1
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
Summary of MEN type 2a
2 P’s
Medullary thyroid cancer
Parathyroid - hyperparathyroidism
Phaeochromocytoma
RET oncogene
Summary of MEN type 2b
1 P
Medullary thyroid cancer
Phaeochromocytoma
Marfanoid body habitus
Neuromas
RET oncogene
Summary of prolactinoma
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
What is phaeochromocytoma?
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
Ix and Tx of phaeochromocytoma?
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
Causes of thyrotoxicosis?
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
Causes of hypothyroidism?
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
Summary of Graves disease?
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)
Summary of Hashimoto’s thyroiditis?
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
Summary of subacute (De Quervain’s) thyroiditis?
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
Summary of postpartum thyroiditis?
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
Summary of toxic multi nodular goitre?
number of autonomously functioning thyroid nodules resulting in hyperthyroidism
goitre with firm nodules. most patients >50
Scintigraphy reveals patchy uptake
Tx - radioiodine therapy
Summary of thyroid storm?
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
What is T1DM?
Autoimmune
Insulin-producing beta cells of Islets of Langerhans in pancreas are destroyed by immune system
What is T2DM?
Relative deficiency of insulin due to excess adipose tissue
What is MODY?
Maturity onset diabetes of the young (MODY)
AD condition
Younger patients with Sx similar to T2DM
What is LADA?
Latent autoimmune diabetes in adults (LADA)
Often misdiagnosed as T2DM
Other causes of DM?
Haemachromatosis
Chronic pancreatitis
Pancreatic cancer
S+S of DM?
Type 1:
WL
polydipsia/uria
Present with DKA
Type 2:
picked up incidentally
polydipsia and polyuria - due to osmotic effects of glycosuria
Ix of diabetes?
Pt. symptomatic - fasting glucose >7, random glucose >11
asymptomatic - same criteria but on 2 separate occasions
HbA1c - >48 is diagnostic of DM
What is prediabetes?
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
Ix for T1DM?
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
Management of T1DM?
HbA1c every 3-6m
Self-monitoring of BG - x4/d
Insulin - multi daily injection regiment, twice daily, insulin analogues
Metformin if BMI >25
T2DM managemnet?
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
