Endocrine Conditions Flashcards
1
Q
What is the pathophysiology of type 1 diabetes mellitus?
A
Autoimmune pancreatic beta cell destruction - Destruction proceeds symptoms for years (insulitis) and at 80% destruction hyperglycaemia occurs: unable to utilise glucose and counter hormones are secreted leading to ketogenisis
2
Q
What autoantibodies are involved in T1 diabetes?
A
insulin, islet-auto-antigen 2 and glutamic acid decarboxylase
3
Q
What genes are involved in T1 diabetes?
A
HLA-DR/DQ polymorphism
4
Q
What are risk factors for T1 diabetes?
A
Genetic predisposition, Infectious agents (may act as trigger), European
5
Q
What symptoms does T1 diabetes present with and what values are to be expected?
A
hyperglycaemia (plasma glucose above 11.1) polyuria, polydipsia and weight loss
fasting glucose above 7, HbA1c 48 or higher, presence of ketones, little to no C-peptide
6
Q
What tests should be ordered if T1 diabetes is suspected?
A
random plasma glucose, fasting plasma glucose and HbA1c (average blood glucose levels over the last 2 to 3 months)
Plasma or urine ketones and c-peptide
7
Q
What are differentials for T1 diabetes?
A
T2 diabetes, monogenic diabetes (MODY)
8
Q
What is MODY?
A
single gene mutation and responds to sulphonylureas such as gliclazide
9
Q
What are some consequences of T1 diabetes?
A
ketoacidosis, neuropathy (commonly feet), renopathy, hyperglycaemic coma, CV disease
10
Q
How do you treat T1 diabetes?
A
Basal-bolus insulin (i.e. determir + lispro), lifestyle modification, occasional metformin
11
Q
What is a downside of tight glycemic control?
A
Very strict management can lead to hypoglycaemia (trade off)
12
Q
what is Whipple’s triad?
A
Indicate hypoglycaemia
symptoms of low blood sugar, plasma glucose below 3 and symptoms resolved when corrected
13
Q
What is the pathophysiology of type 2 diabetes mellitus?
A
progressive disorder: combination of impaired secretion and insulin resistance - starts off with resistance and compensatory mechanisms may lead to beta cell failure
14
Q
What are some differences between T1 and T2 diabetes?
A
in T2 there is insulin detectable, which makes ketoacidosis and gluconeogenesis less likely. There is also no HLA link in T2.
T2 is more common.
15
Q
What are risk factors for T2 diabetes?
A
older age, overweight, family history, stress, gestational diabetes
16
Q
What symptoms does T2 diabetes present with and what values are to be expected?
A
Often starts asymptomatic and is caught in a screening: polyuria, polydipsia, skin infections, fatigue and blurred vision
fasting glucose above 7, Hb1Ac above 48, 2 hours after giving load glucose (75g oral glucose) glucose is above 11.1
High LDL can indicate dysplipidemia (same as high cholesterol or hyperlipidemia)
17
Q
What tests should be ordered if T2 diabetes is suspected?
A
fasting glucose, HbA1c, OGTT (oral glucose tolerance test), random plasma glucose
lipid profile, urine ketones, c-peptide
18
Q
What are differentials for T2 diabetes?
A
type 1 diabetes, gestational diabetes or pre-diabetes
19
Q
What are some consequences of T2 diabetes?
A
similar to T1: ketoacidosis, CV conditions, hyperosmolar hyperglycaemic state (very high blood glucose levels)
20
Q
How do you treat T2 diabetes?
A
initially with lifestyle changes and agree to a HbA1c target
Metformin, then dual therapy i.e. metformin and DPP4 inhibitor
If symptomatic consider insulin or sulfonylurea and review when control is achieved
in pregnancy give aspirin against preeclampsia
21
Q
What is Diabetic ketoacidosis (DKA) and what is its pathophysiology?
A
Complication of diabetes: Hyperglycaemia, ketosis and acidosis
hyperglycaemia is caused by inefficient insulin production (worsened by up regulation of counter-regulatory hormones)
ketones from FFA are produced and end up in blood causing acidosis
22
Q
What causes diabetic ketoacidosis?
A
mainly in T1 diabetes
infection, inadequate insulin treatment, drugs affecting carb metabolism,
23
Q
How does DKA present?
A
nausea and vomiting, abdominal pain, dehydration, reduced consciousness, acetone smell on breath
24
Q
What are the biochemical criteria for DKA?
A
hyperglycaemia (fasting glucose above 11), ketonanemia (above 3 or ketonuria) and blood pH below 7.3
25
What tests should be ordered if DKA is suspected?
venous blood gas, blood ketones, blood glucose, FBC
| urinalysis, ECG to look for cardiac trigger
26
What are differentials of DKA?
HHS, lactic acidosis or starvation ketosis
27
What consequences does DKA have?
hypokalaemia, hypoglycaemia, brain injury
28
How do you treat DKA?
- below 3.5 - IV fluids, potassium replacement and IV insulin
- above 3.5 - IV fluids and IV insulin
- If BP systole under 90 - fast fluid bolus otherwise just saline
29
when do you consider DKA to be resolved?
if blood pH is above 7.3, bicarbonate above 15 and ketones below 0.6
30
What is the pathology of Hyperosmolar hyperglycaemic state (HHS)?
Hyperglycaemia, hyperosmolality and volume depletion in the absence of ketoacidosis
results from relative insulin deficiency and up regulation of counter hormones - there is enough insulin to suppress lipolysis and therefore ketoacidosis
evolves over several days and leads to hypernatraemia
coupled with hyperglycaemia and inadequate water intake leads to hypovolaemia - a decline in eGFR aggravates this
31
what are differences between DKA and HHS?
HSS: slower onset, no ketones, increased mortality, some insulin present
32
What are some risk factors for HHS?
mostly T2, infection, postoperative, inadequate insulin, nursing home resident (more likely to be dehydrated)
33
How does HHS present?
- Presents with cognitive impairment, polyuria, polydipsia, nausea, weakness and dry mucus membranes
elevated glucose (30+), no ketones, mild acidosis, serum osmolality above 320
34
What are differentials to HHS?
DKA, lactic acidosis or alcohol ketoacidosis
35
what tests do you order if you suspect HHS?
blood glucose, ketones, venous gases, serum osmolality, Glasgow coma scale, urinalysis
36
What are some consequences of HHS?
hypoglycaemia after treatment, coma, stroke, death
37
How do you treat HHS?
IV fluids and insulin and potentially replace potassium
38
what is the pathophysiology of hypothyroidism?
Underproduction of T3 and T4 (triiodothyronine and thyroxine)
39
what are the two types of hypothyroidism?
Primary and central (secondary and tertiary)
40
Define primary hypothyroidism and its aetiology
TSH above range and T4 below
autoimmune (Hashimotos), destruction of gland, drugs
41
Define central hypothyroidism and its aetiology
insufficient stimulation from TSH
1. deficient synthesis and secretion
2. biologically ineffective TSH
pituitary mass lesions, other tumours, infection, trauma, genetic defect
42
what are RF for primary hypothyroidism?
iodine deficiency, female, autoimune conditions, lithium use
43
What are the RF for central hypothyroidism?
TBI, radiation
44
What symptoms does hypothyroidism present with?
non specific symptoms such as lethargy and weakness, cold intolerance, weight gain, menstrual irregularities, myxoedema coma, non-pitting oedema
Primary may present with a goitre
45
What are some differentials of hypothyroidism?
depression and iodine deficiency
46
What tests would you order for hypothyroidism?
TSH and serum T4
47
What lab results would you expect in primary hypothyroidism?
elevated TSH and reduced T4
| can have anti-TPO autoantibodies if hashimoto’s
48
What lab results would you expect in central hypothyroidism?
reduced T4 and normal or low TSH
| MRI may reveal lesions
49
How do you treat hypothyroidism?
levothyroxine
50
What is the pathology of Grave's disease?
Autoimmune thyroid condition associated with Hyperthyroidism
Infiltrating T-cells cause thyroid follicular cells to express HLA class 2 which causes an autoimmune cascade
TSH immunoglobulins bind to TSH receptors which stimulates T4
Negative feedback reduces TSH
51
What is the aetiology of grave's disease?
TSH receptor antibodies,
genetics,
potentially alemtuzumab treatment
52
What are the risk factors for Grave's disease?
female, 20-40 years old, HLA-DR3 polymorphism
53
What does Grave's disease present with and what lab results would you expect?
heat intolerance, weight loss, diffuse goitre, orbitopathy (wide open eyes), myxoedema
decreased TSH, increased T3 and T4, TSH receptor antibodies present (TRAb)
54
What differentials are there for Grave's disease?
toxic nodular goitre, gestational hyperthyroidism
55
What tests would you order if you suspect Grave's disease?
TSH, TSH receptor antibody, T3 and T4
56
What are complications of Grave's disease?
bone mineral loss, A.fib, congestive HF, thyroid storm
57
What is a thyroid storm and what does it present with?
Thyroid storm is untreated hyperthyroidism: tachycardia, fever, sweating, shaking and agitation
58
How do you treat a thyroid storm?
BB and reduce thyroid hormones: propylthiouracil
59
How do you treat Grave's disease?
with antithyroid drugs (carbimazole)
| surgery such as thyroidectomy or destroy gland with radioactive iodine
60
What is the pathology of Hashimoto's thyroiditis?
Destruction of thyroid cells causing hypothyroidism
autoimmune mediated lymphocytic inflammation destroys the thyroid cells (thyroiditis), which causes release of T4 and transient hyperthyroidism - followed by hypothyroidism
61
what genes is Hashimoto's associated with?
HLA-DR3 and DR5 genes
62
What are the RF for Hashimoto's?
female, postnatal period, autoimmune conditions and lithium therapy
63
What does Hashimoto's present with and what lab results would you expect?
cold intolerance, fatigue, dry skin, constipation and potentially an enlarged thyroid
TPO antibody positive, TRAb negative, low T3/T4, increased TSH
64
What are differentials for Hashimoto's?
Grave’s disease, toxic multi nodular goitre
65
What tests would you order if you suspect Hashimoto's?
TSH, T3+T4, TPO antibodies, TSH receptor antibodies , biopsy
66
What consequences can Hashimoto's have?
hyperlipidemia
67
How do you treat Hashimoto's?
levothyroxine
if symptoms are minimal then observe and monitor
if recurrent: ablation
68
what are the four types of thyroid cancer?
papillary, follicular, medullary and anaplastic
69
What are features of papillary thyroid cancer?
common, well differentiated and lymph node involvement
70
What are features of medullary thyroid cancer?
originates in thyroid parafollicular C- cells, sporadic, produces calcitonin
71
What are features of follicular thyroid cancer?
early forms are indolent then aggressive, direct haematogenous spread, hurtle cells
72
What are features of anaplastic thyroid cancer?
undifferentiated, vascular invasion, can intrude on recurrent laryngeal nerve, worse survival
73
What are RF of thyroid cancer?
head and neck radiation, female, family history
74
How does thyroid cancer present?
palpable thyroid nodule and hoarseness of voice
normal TSH, biopsy can reveal what type of cancer
high calcitonin in medullary cancer
75
What investigations would you order if you suspect thyroid cancer?
TSH, neck ultrasound, fine needle biopsy
| serum calcitonin, T4+T3
76
How do you treat thyroid cancer?
total thyroidectomy and levothyroxine
chemo for anapaestic types
77
What are DPP-4 inhibitors used for and how do they work?
Gliptins: inhibit the action of the enzyme DPP-4 which normally destroys the hormone incretin. Increatin helps the body to produce more insulin
Prescribed as a secondary line in T2D
78
Name some examples of DPP-4 inhibitors?
Alogliptin, Linagliptin and Sitagliptin
79
What do you use levothyroxine for?
Replacing thyroid hormones in an underachieve thyroid or after thyroid ablation
80
What do you use metformin for and how does it work?
Form of biguanide: lessens glucose absorption and makes body more sensitive to insulin
Type 2 diabetes (1st line) and sometimes T1D
81
What are contraindications of metformin?
diabetic ketoacidosis, eGFR below 30, AKI, conditions that can cause hypoxia and hepatic insufficiency
82
What enhances the effect of metformin?
Ace inhibitors
83
What reduces the effect of metformin?
diuretics, oestrogen or corticosteriods
84
What is Carbimazole and how does it work?
Antithyroid medication:
Carbimazole is a thionamide and reduces the amount of T4 released. It doesn't affect T4 that has already been made but reduces further production - it therefore takes 4-6 weeks to work
85
what is an alternative to carbimazole?
propylthiouracil which is also used in a thyroid storm
86
What are the contraindications of carbimazole?
severe blood disorders
87
What are SLGT-2 inhibitors and what are they used for?
- Sodium-glucose co-transporter-2 inhibitors: reduce the amount of glucose absorbed into the kidney and reduce the amount of glucose in blood
prescribed for T2D
88
What is a example of a SLGT-2inhibitor?
Dapagliflozin
89
what are sulphonylureas and what are they used for?
Stimulate the pancreas to make more insulin
Prescribed in MODY and T2 diabetes (if hyperglycaemic with symptoms or if metformin is contraindicated )
90
What are examples of sulphonylureas?
Glibenclamide or Gliclazide
91
What is Cushing's syndrome?
Clinical manifestation of hypercortisolism (any cause)
| Manifestations result from excessive exposure to cortisol (includes exogenous cortisol i.e. steroids)
92
What are the two types of Cushing's syndrome?
ACTH dependent: high ACTH levels cause excess cortisol, Cushing’s disease (pituitary related such as adenoma), secreting tumours
ACTH independent: excess cortisol despite surpassed ACTH, adrenal adenoma
93
What is Cushing's disease?
pituitary related causes of Cushing's syndrome
94
What is the aetiology of Cushing's syndrome?
corticosteroid treatment, ACTH-secreting pituitary adenomas
95
How does Cushing's syndrome present?
weight gain, dyslipidemia and glucose intolerance
more severe: facial plethora (swelling), increased subcutaneous fat, violaceous scarring and muscle weakness
96
what are differentials of Cushing's?
obesity and metabolic syndrome
97
What lab results would you expect in someone with Cushing's?
levated glucose, elevated cortisol, morning cortisol over 50 (dexamethasone suppression test)
98
What tests would you order if you suspect Cushing's?
erum glucose, late night salivary cortisol, dexamethasone suppression test (should suppress ACTH secretion and cortisol secretion), ACTH and imaging
99
What are some consequences of cushing's?
CV disease, HTN, diabetes and hypothyroidism
100
How do you treat cushing's?
Depends on the cause:
Cushing’s disease: transsphenoidal pituitary adenomectomy + Ketoconazale
Syndrome: Metyrapone for the management
Other: ablation of tumours or adrenalectomy
101
what is acromegaly and what is the pathology?
Chronic disease caused by excessive secretion of growth hormone
Tumours can release GH causing and excess - passes through blood and leads to IGF-1 secretion by the liver
GF acts directly on organs and indirectly through IGF-1 causing uncontrolled growth
102
What is the aetiology of acromegaly?
95% of cases are caused by pituitary adenomas, rarely endocrine tumours
(in 25% prolactin is co-secreted)
103
What are RF for acromegaly?
GPR101 over expression, carney complex, family history
104
How does acromegaly present?
coarse facial features (enlarged nose and jaw), macroglossia, soft tissue changes, carpal tunnel, joint pain
105
what lab results would you expect in acromegaly?
elevated IGF-1, lack of surpassed GH during oral glucose test, elevated prolactin
106
what is Pseudoacromegaly?
When IGF-1 is not elevated
107
What tests would you order for acromegaly?
IGF-1, OGTT (GH should be low but since secretion in independent it remains high), pituitary MRI, prolactin
108
Why is baseline serum GH not useful when testing for acromegaly?
baseline GH is not useful as it varies during the day (pulsatile release)
109
What are some consequences of acromegaly?
cardiac problems, HTN, sleep apnoea, diabetes
110
How do you treat acromegaly?
Treat depending on tumour:
pituitary: transphenoidal surgery and dopamine agonist (cabergoline)
unresectable: somatostatin (octreotide), dopamine agonist and debunking surgery
non-pituitary: somatostatin and surgery
111
What is Conn's syndrome and what is its pathology?
Primary aldosteronism: excessive aldosterone resulting in sodium reabsorption
Excessive aldosterone independent of angiotensin II causing excessive sodium reabsorption leading to hypertension and suppression of renin-angiotensin system
- Potassium is lost
112
What is the aetiology of conn's syndrome?
genetics, adrenal adenomas
113
How does conn's syndrome present and what lab results would you expect?
hypertension, nocturia, polyuria, lethargy, mood disturbances, difficulty concentrating
in 20% potassium is low, aldosterone/renin ration above 20
114
what are differentials of Conn's syndrome?
HTN, thiazide induced hypokalaemia
115
what tests would you order to test for conn's syndrome?
plasma potassium, aldosterone/renin ratio, adrenal CT
116
What are complications of Conn's syndrome?
HTN, hypokalaemia, stroke, MI, HF, impaired renal function
117
How do you treat Conn's syndrome?
surgically removing adenoma or with a aldosterone antagonist (spironolactone)
118
How does a pituitary adenoma form?
Hypermethylation of CDKI2A gene causes inactivation of it, leading to unregulated cell growth
119
what are the two types of pituitary adenoma's?
Functional: secreted hormones i.e. acromegaly or cushing’s disease
Non-functional (CNFPA): no hormone secretion, pituitary tumour transforming gene is over expressed in in CNFPA leading to cell growth and angiogenesis
120
How do CNFPA's present?
Symptoms are LT and progressive: headaches, erectile dysfunction, amenorrhea, infertility, fatigue, weight gain
121
What labs would you order for a CNFPA and what results can you expect?
Order prolactin, contrast enhanced CT and exclude functional adenoma
elevated prolactin, anaemia and mass seen on CT and MRI
122
what are consequences of CNFPA's ?
diabetes insipidus, meningitis, hypopituitarism, pituitary apoplexy (bleeding into the pituitary)
123
How do you treat CNFPA's?
observing and if its near the optic chasm: surgery and hormone replacement
124
what is Addison's disease?
Destruction of the entire adrenal cortex resulting in aldosterone, cortisol and androgen deficiencies
125
What causes Addison's disease?
autoimmune adrenalitis, TB, metastases, LT steroid use, adrenal haemorrhage
126
How does Addison's present?
Presents with lethargy, depression, weight loss, vitiligo, bronzed skin, skin pigmentation, impotence, hypotension
127
What tests would you order for Addison's and what results would you expect?
abdominal CT, serum cortisol, serum ACTH, electrolytes
decreased serum cortisol, increased ACTH, increased renin, hyponatraemia, hyperkalaemia
128
How do you treat Addison's?
lifelong gluticocorticoid replacement
129
How can you tell between Addison's and secondary adrenal insufficiency?
secondary has no skin pigmentation, low ACTH and mineralocorticoid production intact
130
What is SIADH?
syndrome of inappropriate ADH secretion: leading to an increase of water reabsorption, diluted blood leads to low sodium and less aldosterone to be released. This causes sodium to be excreted and water follows. We are now in a position where there is hyponatraemia.
131
What are the four types of SIADH
- Type A: erratic and independent of plasma osmolality, high ADH
- Type B: constant release of ADH
- Type C: baseline sodium concentration level is lower than normal
- Type D: ADH is normal but still high urine osmolality
132
what causes SIADH?
CNS disorders, ectopic ADH production (lung malignancies), medication, infection
133
How does SIADH present and what lab results would you expect?
headache, nausea, vomiting, cramps, tremor, neurological symptoms as cells swell
low blood sodium levels, high urine sodium, low blood osmolarity
134
How do you treat SIADH?
treat underlying cause and manage by restricting fluid intake and having a high salt diet
If severe: hypertonic UV fluids
135
what is diabetes insipidus?
Disorder of fluid balance i.e. large volumes of dilute urine
136
what are the two types of DI and their causes?
Neurogenic: caused by a decrease or absence of ADH
- idiopathic, congenital, genetic or damage to pituitary
Nephrogenic: Kidneys unresponsive to ADH secretion
- Causes include genetics, damage of renal tubules, lithium toxicity
137
How does DI present?
polyuria, nocturia, dehydration, lack of other pituitary hormones
138
what tests would you order to diagnose DI?
Cranial MRI, ADH levels, electrolytes, water deprivation test
139
How does a water deprivation test separate neurogenic and nephrogenic causes of DI?
if urine osmolality increases it confirms neurogenic cause and if there is no increase it confirms nephrogenic causes
140
How do you treat DI?
Treat depending on type:
- Neurogenic: desmopressin, chloropamide (increases renal response to low levels of ADH)
- Nephrogenic: NSAID’s, thiazide diuretics
141
What value classifies hypokalaemia?
below 3.5
142
How does hypokalaemia present?
mostly asymptomatic, if severe: constipation, muscle weakness, arrhythmia, polyuria
143
What causes hypokalaemia?
increased kidney excretion, vomiting, diarrhoea, sweating, drugs, low dietary intake, insulin
144
What can you see on an ECG in hypokalaemia?
flattened or inverted T waves, prolonged PR interval
145
How do you treat hypokalaemia?
replenishing potassium and magnesium
146
what classifies hyperkalaemia?
above 5.5.
147
What causes hyperkalaemia?
decreased excretion, trans cellular shift (uncontrolled T1D, acidosis, massive cell lysis), increased intake
148
How does hyperkalaemia present?
mostly asymptomatic, (remember MURDER) muscle weakness, urine, respiratory distress, decreased cardiac contractility, ECG changes, reflexes
149
what changes are seen on an ECG in hyperkalaemia?
prolonged PR interval, peaked T waves, widened QRS interval
150
How do you treat hyperkalaemia?
remember C BIG K DROP: calcium, beta 2 agonist, insulin and glucose, kayexalate (stops potassium from being absorbed), diuretics
