Endocrinology Flashcards
1
Q
What does your body have trouble moving if you have diabetes Mellitus? What is the result of this?
A
Has trouble moving glucose from the blood into cells
This results in high levels of glucose in your blood, and not enough of it in your cells results in energy depletion of cells.
2
Q
What hormones control how much glucose is in the blood relative to how much gets into the cell
A
Insulin: reduce blood glucose levels
Glucagon: Increase blood glucose levels
3
Q
Where are glucagon and insulin secreted from?
A
Islets of Langerhans within pancreas
Beta cells: insulin
Alpha cells: glucagon
REMEMBER Alpha = glucAgon
4
Q
How does insulin reduce the amount of glucose in the blood
A
Binds to insulin receptors embedded in the cell membrane of various insulin-responsive tissues like adipose tissue and muscle cells
When activated, the insulin receptors cause vesicles containing glucose transporter within the cell to fuse with the cell membrane allowing glucose to be transported into the cell
5
Q
How does glucagon increase the amount of glucose in the blood
A
Raises blood glucose levels by getting the liver to generate new molecules of glucose from other molecules and break down glycogen into glucose
6
Q
What is diabetes mellitus
A
A group of chronic disorders characterised by abnormal glucose metabolism resulting in elevated glucose levels
7
Q
Type 1 Diabetes vs Type 2 diabetes
A
Type 1 : Body doesnt produce insulin.Autoimmune destruction of beta cells in the pancreas
Type 2 : Makes insulin but the body doesnt respond to it. Insulin resistance followed by beta cell atrophy
8
Q
Classification of Type 1 Diabetes Mellitus
A
Type 1 diabetes is B-cell destruction leading to absolute insulin deficiency. It accounts for 5-10% of all diabetes. Type I diabetes is divided into two types: Immune-mediated and idiopathic. The traditional paradigm is of childhood-onset with acute symptoms of DKA.
Type 1A: immune-mediated diabetes
-Most common
-Autoimmune destruction of pancreatic beta-cells -> decrease in insulin
-Type IV hypersensitivity response
Type 1B: idiopathic diabetes
-No evidence of autoimmunity
-Varying degrees of low insulin, episodes of ketoacidosis
9
Q
Cause of Type 1 diabetes
A
Genetic abnormality causes a loss of self-tolerance among T cells that target beta-cell antigens. This means beta cells are attacked, and less insulin and glucose pile up in the blood because they can’t enter the body’s cells
10
Q
What is latent autoimmune diabetes
A
A progressive form of autoimmune diabetes
Onset is at >30 years old
11
Q
Risk factors of Type 1 diabetes
A
Genetic predisposition
Multiple gene polymorphisms associated with DM Type 1
12
Q
Diagnosis of Type 1 diabetes mellitus
A
The age of onset and rate of B-cell destruction is quite variable:
- Rapid in infants and children
- Slow in others (mainly adults), such as in Latent AutoimmunenDiabetes of Adulthood (LADA).
This influences clinical presentation and may confuse the diagnosis.
Diabetes:
Acute onset of hyperglycaemic symptoms with ketoacidosis:
- Random plasma glucose > 11.1 mmol/L consistent with diagnosis
- HbA1c is not used in diagnosis
Autoimmune markers are not routinely used but can include:
- Glutamic acid decarboxylase (GAD65)
- Insulin (IAA)
- Tyrosine phosphatases (IA-2 & IA-2B)
- ZnT8
Low or undetectable plasma C-peptide level supports the diagnosis.
13
Q
Latent autoimmune diabetes of adulthood
A
- A subtype of autoimmune Type 1 diabetes is sometimes misdiagnosed as T2D.
- Slowly progressive destruction of Beta cells.
- May appear to respond to oral agents initially.
- Less likely to have other features of metabolic syndrome (central obesity, HT, dyslipidaemia).
- More likely to have a history of other autoimmune diseases.
- Starting insulin early may help to preserve beta cell insulin production
Criteria to standardize the definition:
- Age of onset usually > 30y
- Positive titre for at least one T1D autoantibody
- Not treated with insulin within the first 6 months after diagnosis
14
Q
Complications of Type 1 diabetes
A
15
Q
What are the sign and symptoms of Type 1 diabetes (8)
A
16
Q
What are the management of Type 1 diabetes
A
17
Q
What is diabetic ketoacidosis
A
A condition resulting from deficient insulin availability, leading to lipid oxidation and metabolism rather than glucose metabolism. The insulin absence results in free fatty acid (FFA) released from adipose tissue and in unregulated hepatic FFA oxidation and ketogenesis.
18
Q
diabetic ketoacidosis characterised by?
A
severe hyperglycemia
accelerated ketogenesis.
19
Q
What is a serious complication of Type 1 diabetes
A
Diabetic ketoacidosis (DKA)
20
Q
Clinical Presentation of diabetes mellitus type 1
A
Signs of dehydration
* polyuria
* polydypsia
* weight loss
GI symptoms
Hyperventilation (↑Respiratory Rate - Kussmaul breathing)
True coma - 10% of cases)
Side Note Kussmaul breathing is air hunger, rapid deep breathing a sign of metabolic acidosis. This is different to Kusmaul’s sign looks at JVP relationship with breathing.
21
Q
DKA Aetiology (5I’s) + Initial Diagnosis
A
- Infection
- Infarction
- Insufficient insulin
- Intercurrent illness
- Inappropriate withdrawal of Insulin
- Initial Diagnosis
Remember Precipitating factors of DKA 5 I’s: Infection Ischemia Infarction Intoxication Insulin missed
22
Q
Investigations of DKA
A
23
Q
Complications of DKA
A
Cerebral oedema
* May be caused by very rapid reduction of blood glucose, use of hypotonic fluids and/or bicarbonate
* High mortality
* Treat with mannitol, oxygen
Acute respiratory distress syndrome
Thromboembolism
Disseminated intravascular coagulation (rare)
Acute circulatory failure
24
Q
Differential diagnosis of DKA- high blood glucose and coma
A
Head injury
Alcohol
Drug overdose
25
Risk Factors of DKA
Infection
Stress
Irregular insulin use
26
Diagnosis of DKA
Diagnosis of DKA
Hyperglycemia (>11.1mmol/L)
Metabolic acidosis (pH <7.3 or
27
Treatment for DKA
28
________ breathing presents as rapid, deep breathing and is seen in diabetic ketoacidosis
Kussmaul
29
What type of diabetes is more commonly associated with diabetic ketoacidosis?
Type 1 DM
30
What compound that gives patients with diabetic ketoacidosis a fruity odor to their breath
Acetone
31
In diabetic ketoacidosis, total body stores of potassium are (high/low)
Low
32
Diabetic ketoacidosis causes increased production of ketones such as
beta-hydroxybutyrate and acetoacetate.
33
Diabetic ketoacidosis causes a(n) (increase/decrease) _______ in epinephrine production
increase
34
Diabetes mellitus type (1/2) __ is caused by a type IV hypersensitivity reaction
1
35
The primary defect in diabetes mellitus type 1 is autoimmune destruction of the ____ of the pancreas
Beta cells
36
Type 1 diabetes is usually diagnosed (before/after) ___ the age of 30
Before
37
What is the primary defect of diabetes mellitus type 2
Increased insulin resistance
38
Risk Factors of type 2 diabetes
39
Signs and symptoms type II diabetes
Asymptomatic period
Infections
Fatigue
Blurred vision
4Ps
* Paresthesia
* Polydipsia
* Polyuria
* Polyphagia
40
Causes of Type 2 diabetes
41
Patients with diabetes mellitus type 2 have (high/low) __ insulin sensitivity
low
42
Risk Factors of DKA
Multifactorial; interaction between genetic, environmental, behavioural factors
43
Why is diabetes ketoacidosis rare in DM type 2?
As endogenous insulin prevents lipolysis
44
Diabetic Complications (advanced disease)
**Diabetic Retinopathy
Poor vision
**Diabetic Neuropathy**
Peripheral neuropathy
* pain
* loss of sensation
* dysaesthesia
* weakness
Autonomic neuropathy
* resting tachycardia
* orthostatic hypotension
* erectile dysfunction
* constipation
**Diabetic Nephropathy**
Oedema
Anaemia
Hypertension
Uremia
45
What is the most common intial manifestation of type 2 DM
elevated blood glucose with ketonemia.
46
What is the best pharmocological treatment for type 2 DM
Metformin
47
NICE provide guidelines on how drug therapy should be used in T2DM:
48
Table comparing T2DM medications
49
Investigations of Type 2 diabetes
50
Differential Diagnosis of Type 2 diabetes
51
How to differentiate Type 2 diabetes from Type 1
Type 2 diabetes differs from Type 1 in the following ways:
doesnt have autoantibodies
C peptide : normal/ elevated
52
Aetiology of type 2 diabetes
Genetic predisposition
Physical inactivity and being overweight contributes to insulin resistance.
53
Management of Type 2 diabetes
Management
54
Pharmacology for diabtes mellitus type II
Indications for Insulin
Acute metabolic complications
Perioperative in patients undergoing surgery
Severe infection
Pregnancy and lactation
Fasting plasma glucose >300mg/d
Failure of oral anti-diabetic agent/contraindication of oral anti-diabetic agents
55
Screening for Diabetic Complications
56
For which type of diabetes is Hyperosmolar Hyperglycaemic state more likely to occur?
Type 2
57
Complications and prognosis for diabetes mellitus type II
58
Type I vs Type II Diabetes
59
Hyperosmolar Hyperglyaecmic State
is a complication of type 2 diabetes. It involves extremely high blood sugar (glucose) levels without the presence of ketones.
Hyperosmolar Hyperglycaemia (HOH) state occurring primarily in type 2 diabetes and is characterised by marked hyperglycaemia and dehydration without ketoacidosis. The disturbance in consciousness in patients varies from drowsy to comatose. HOH is a more sinister complication than ketoacidosis with a mortality rate as high as 50%.
60
What does a hyperosmolar hyperglycemic state cause
increased plasma osmolarity due to extreme dehydration and concentration of the blood
61
Diagnosis of hyperglycaemic state
62
Pathophysiology hyperglycaemic state
This condition results from a combination of insulin deficiency and counterregulatory hormone excess. The insulin present stops ketone production but in insufficient quantities to prevent worsening hyperglycemia.
63
Management of hyperglycaemic state
64
complication of hyperglycaemic state
Venous thromboembolism
65
Hypoglycaemia
66
What is hyperthyroidism
denote conditions in which hyperfunction of the thyroid leads to thyrotoxicosis.
The most common cause of hyperthyroidism are Graves disease, multinodular goitre, an autonomously functioning thyroid nodule (adenoma) and subacute thyroiditis. Graves Disease is more common in women. Multinodular goitre is more common in the elderly. Graves disease typically manifests in middle aged women. Thyroid diseases are more common in women.
67
What is the hypothalamic-pituitary-thyroid axis
TRH (thyroid-releasing Hormone) stimulates the synthesis and secretion of TSH (thyroid-stimulating hormone)
TSH acts at the thyroid to stimulate all steps of thyroid hormone (T3 + T4) bio synthesis and secretion by binding onto TSH receptors
T3 + T4 inhibit TSH + TRH via negative feedback system
68
What does it mean for the hypothalamic-pituitary-thyroid axis with an individual diagnosed with hyperthyroidism
Elevated circulating T3 + T4
Since there is a negative feedback loop with TRH and TSH it means that there will be a decrease in those hormones
69
How are T3 and T4 (thyroid hormone) synthesised
1.TRH release from paraventricular nucleus from hypothalamus
2.Anterior pituitary to release from TSH
3.TSH stimulates follicle cells of the thyroid to synthesise thyroglobulin
4.Iodide trapping
5.Oxidation of iodide via thyroid peroxidase
6.Iodination of tyrosine amino acids
7.Couple of the DIT + MIT
8.Endocytosis of thyroglobulin with T3 + T4
9.Lysosomal enzymes cleave T3 + T4 out of thyroglobulin
10.Exocytosis of T3 + T4 into blood plasma
70
What does the Thyroid hormone do?
Promotes normal bone growth + maturation
Promotes muscular function and development
Increase basal metabolic rate/ O2 usage
Promotes normal C.O
Promotes an increase in synapses/myelinations/dendrites
Promotes G.I motility + secretions
Promotes normal hydration of skin
71
How is T3 + T4 made from tyrosine molecule
Tyrosine is broken down into T3 + T4 components via lysozyme enzymes
72
What makes up the thyroid hormone?
T4 thyroxine +
T3 triiodothyronine
73
What does thyroid peroxidase do?
Iodide oxidation: turns iodide ions into iodine
Iodination: puts I2 onto amino acids on tyrosine amino acids
Fuses DIT + DIT = T4 (Throxine)
Fuses MIT + DIT = triodothyronin
74
How does iodide enter from the blood into follicles of the thyroid gland
secondary active transport
75
Causes of hyperthyroidism
Graves disease: Most common
Toxic multinodular goitre: multinodular hyperplasia, <50% are thyrotoxic
Toxic adenomas: benign, solitary, discrete encapsulated nodules, usually non-toxic but can cause mild hyperthyroidism
Other causes: thyroiditis, carcinoma, TSH-secreting pituitary tumour, iatrogenic (iodine T4), choriocarcinoma, hydatidiform mole (rare)
76
Investigations to identify hyperthyroidism
TSH, free T3 & T4, Full Blood count, liver enzymes and erythrocyte sedimentation rate (ESR)
Thyroid antibodies (antithyroid peroxidase [TPO] or TSH-R antibodies)
Isotope scan (I123)
77
Clinical Presentation of hyperthyroidism
Hyperactivity, irritability, altered mood, insomnia
Heat intolerance, sweating
Palpitations
Fatigue, weakness
Dyspnea
Weight loss with increased appetite (weight gain in 10% of patients)
Pruritus
Increased stool frequency
Thirst and polyuria
Oligomenorrhea or amenorrhea; loss of libido
78
Clinical examination of hyperthyroidism
General: irritability, axious, weight loss, warm, moist skin, chorea, periodic paralysis (primarily in Asian males), psychosis (rare)
Hands: onycholysis, fine tremor
Face: Hair loss, Graves opthalmology
Cardiovascular: Sinus tachycardia, atrial fibrillation, palmar erythema, congestive (high-output) heart failure,
Neurological: hyperkinesia, hyperreflexia, muscle weakness and wasting
Legs: pretibial myxoedema
79
Features of Severe Hyperthyroidism
Atrial fibrillation
Heart Failure
Significant weight loss
Proximal myopathy
80
Graves Disease Additional Manifestation
Diffuse goiter
Ophthalmopathy
Localised dermopathy
lymphoid hyperplasia
Thyroid acropachy
81
Differential dioagnosis of hyperthyroidism
82
Investigations for hyperthyrodism
83
Causes of hyperthyroidism
84
Pathology of hyperthyroidism
85
Pathophysiology of hyperthyroidism
86
What treatment is given for indivualds with hyperthyroidism
Beta blockers: to treat immediate symptoms
Anti-thyroid drugs: block thyroid hormone production + release
Radioiodine therapy: partially or completely destroy thyroid function followed by replacement thyroid therapy
87
Complications of hyperthyroidism
Complications
Complications of thyroidectomy
Recurrent laryngeal nerve damage
Hypoparathyroidism
Thyroid crisis
Local hemorrhage, causing laryngeal edema
Wound infection
Hypothyroidism
Keloid formation
88
Thyroid storm
89
What is multinodular goitre
defined as an enlarged thyroid with multiple nodules that yields a hyperthyroid state.
90
Subacute granulomatous DeQuervain thyroiditis what is it?
type of thyroiditis that presents as a tender thyroid with transient episodes of hyperthyroidism.
91
What is Graves disease
Autoimmune disorder of the thyroid gland that causes hyperthyroidism
92
A characteristic sign of Graves' disease includes
pretibial myxedema
due to activation of dermal fibroblasts that express the thyroid stimulating hormone receptor.
93
Thyroid stimulating hormone levels are (increased/decreased) ___ in Graves' disease
decreased
94
What is a fatal complication of graves disease
thyroid storm
95
What is hypothyroidism
Variety of abnormalities that cause insufficient secretion of thyroid hormones. The most common cause is autoimmune thyroid disease
Primary hypothyroidism is decreased production of thyroid hormones because of thyroid gland disease (most common is hashimoto's thyroiditis). Secondary hypothyroidism is a problem in the Pituitary gland or hypothalamus resulting in ↓TSH leading to ↓Thyroid hormone production.
96
Primary causes of hypothyroidism
**-Autoimmune:**
Hashimoto's thyroiditis is characterised by lymphocytic infiltration of the gland and progressive destruction of functional thyroid tissue (goitre)
Primary atrophic hypothyroidism (no goitre)
**-Other causes**
Post-total or partial thyroidectomy or radioiodine treatment
Drug-induced with TSH receptor-blocking antibodies
Subacute thyroiditis (de Quervain's): after the hyperthyroid phase
Postpartum thyroiditis
Congenital (rare)
97
Secondary causes of hypothyroidism
Secondary to pituitary failure (reduced TSH production)
Iodine deficiency (commonest cause worldwide)
98
Risk factors for hypothyroidism
Iodine deficiency
Female sex
Middle age
Family History
Autoimmune disorders
Graves' disease
Post-partum thyroiditis
Turner's and Down's syndromes
Primary pulmonary HTN
Multiple sclerosis
Radiotherapy
Iodine deficiency
Amiodarone use and lithium use
99
Signs and symtpms of hypothyroidism
100
Differential diagnosis for hypothyroidism
Primary Hypothyroidism has many causes - identify the cause with investigations
Secondary Hypothyroidism
Pituitary adenoma
Malignancy of the hypothalamus
Depresssion
Alzhiemer's Dementia
Anaemia
101
Investigations for hypothyrioidism
102
Treatment for hypothyroidism
Mainstay of treatment is oral thyroxine; aim to restore TSH to normal with dose titrated according to age, gender and clinical status
103
Complications and porgnosis of hypothyroidism
104
Myoxedema coma
Myoxedema coma is a serious emergency, due to severe untreated hypothyroidism, and typically presents with impaired consciousness, hypoventilation and hypothermia. Hospitalizations is essential for initial treatment.
105
Hashimoto thyroiditis presents with an increased risk for
primary B-cell lymphoma.
106
What is Hashimoto thyroiditis
autoimmune cause of hypothyroidism that presents with a moderately enlarged, nontender thyroid.
107
How does amiodarone affect thyroid?
Amiodarone induces alterations in thyroid hormone levels by actions on thyroidal secretion, on the peripheral tissues, and on the pituitary gland.
These actions result in elevations in serum T4 and rT3 concentrations, transient increases in TSH concentrations, and decreases in T3 concentrations.
108
Complications of hyper/hypo thyroidism
Hyperthyroidism: thyroid storm
Hypothyroidism: myxedema, cretinism (infants, young children)
109
Types of thyroid cancers
-Papillary thyroid: most common, least agressive
-Follicular thyroid: 2nd most common
-Medullary thyroid carcinoma
-Anaplastic/undifferentiated carcinoma
110
Causes of thyroid cancer
Irradiation
Iodine - follicular carcinoma
Genetic syndrome (RET/PTC1, RET/PTC2 and RET/PTC3 TRK (less common)
Papillary microcarcinoma of the thyroid (PMC)
111
Risk factors of thyroid cancers
112
Signs and synptoms of thyroid cancers
113
Diagnosis of thyroid cancer
114
Treatment for thyroid cancer
Surgery
Thyroglobulin is the marker to measure thyroid cancer function post treatment
115
What is pituitary adenoma
Benign anterior pituitary tumour arising from specific cell types
116
Signs and symptoms of pituitary adenoma
Adjacent structure compression
-Visual changes (e.g diplopia, bitemporal hemianopsia), headache
117
Conditions which may be caused by pituitary adenoma
Cushing disease
Acromegaly
Prolactinoma
118
What are potential complications of pituitary adenoma if there is compression of the central satiety center of the hypothalamus
Hyperphagia and weight gain
119
What is a potential complications of pituitary adenoma if the oculomotor nerve (cranial nerve III) is compressed.
Oculomotor palsy
120
What is the most common pituitary adenoma
Prolactinoma
121
pituitary adenoma
122
What is Cushing disease defined as
ACTH-dependent syndrome is characterised by excess corticosteroid production from the adrenal glands. It is ACTH-dependent because an ACTH-secreting pituitary tumour triggers it. Cushing's syndrome is an overarching term to describe hypercortisolemia dependent of independent of ACTH. Adrenal Cushing's syndrome is different because it is hypercortisolemia independent of ACTH.
Is hypercortisolemia from an ACTH-secreting pituitary tumour (ACTH Dependent)
123
Cushing’s syndrome (CS)
Cushing’s syndrome (CS): is a disease complex that results from chronic hypercortisolemia of any cause. The causes may be classified as ACTH dependent and ACTH independent.
124
Serum adrenocorticotropic hormone levels are (increased/decreased) ____ in adrenocorticotropic hormone independent Cushing syndrome
decreased
125
Serum adrenocorticotropic hormone levels are (increased/decreased) _____ in adrenocorticotropic hormone dependent Cushing syndrome.
increased
126
Clinical features that best distinguish Cushing's syndrome
Clinical features that best distinguish Cushing's syndrome: Facial appearance: moon face and plethoric complexion, ecchymoses, Violaceous striae on abdomen, thighs and axillae, Proximal muscle weakness. In children, weight gain with decreased growth velocity. Early bone fractures, especially atraumatic rib or vertebral fractures
127
Differential Diagnosis and causes of Cushing’s syndrome
128
Investigations of cushing disease
129
Causes of cushings disease
The majority of endogenous Cushing’s syndrome is due to ACTH-secreting pituitary adenomas (Cushing’s disease).
Remember Cushing's Disease is ACTH dependent hypercortisolaemia. Most common cause is pituitary adenoma
130
Diagnosis of Cushings disease
Overnight dexamethasone suppression test (first line test)
-False positives (pseudo Cushing's) seen in depression, obesity, alcohol excess and inducers of liver enzymes (e.g phenytoin, rifampicin)
24-hour urinary free cortisol
48-hour dexamethasone suppression test
131
Management of cushings disease
132
Complications of cushings disease
133
Adrenal Insufficiency
134
How is acromegaly caused?
From hyposecretion of gonadotropin
Due to pituitary adenoma in 90% of cases. May also be from non-pituitary tumours of the pancreas, lungs and adrenal glands secondary to gonadotropin-releasing hormone (GnRH) secretion
135
Other complications of acromegaly
Diabetes
Congestive cardiac failure
Renal failure
Oligomenorrohoea/amenorrhoea
Impotence/erectile dysfunction
Obstructive sleep apnea
136
What is the cause of a prolactinoma
Benign lactotroph cell tumour in anterior pitiutary -> prolactin (PL) secretion, prolactinemia
137
What is Conn' s syndrome
also known as primary hyperaldosteronism, refers to the excessive secretion of the hormone aldosterone despite normal renin levels
138
Definiton and aetiology of Addisons disease
Primary adrenocortical deficiency results from destruction of the adrenal cortex, adrenal dysgenesis or impaired steroid genesis
-Glucocorticoid, mineralocorticoid and sex steroid levels are reduced
139
Causes of primary Addisons disease (hypoadrenalism)
Autoimmune adrenalitis (80%), TB, metastasis, HIV, amyloidosis, fungal infiltration, haemochromatosis, adrenoleucodystrophy, Waterhouse-Freiderichson syndrome
140
What is syndrome of inappropriate antidiuretic hormone secretion (SIADH)
141
Causes of SIADH
142
Signs and symptoms of SIADH
143
What is diabetes insipidus
Disorder resulting from deficiency of ADH or its action
Diabetes Insipidus (DI) is associated with inadequate arginine vasopressin (known as antidiuretic hormone) secretion or renal response to arginine vasopressin, resulting in hypotonic polyuria and a compensatory/underlying polydipsia. There are two main types of diabetes insipidus, central DI and nephrogenic DI
Triad Polyuria, dilute urine, and increased thirst are characteristic of DI
144
Pathophysiology of diabetes insipidus
Antidiuretic hormone is initially produced by the hypothalamus and then transported to the posterior pituitary gland via the pituitary stalk for storage.
When osmoreceptors sense hyperosmolarity in the blood it stimulates the posterior pituitary gland to release ADH into systemic circulation.
ADH acts on the kidneys and activates the arginine vasopressin 2 (AVP2) receptors of the renal collecting duct which increases the generation of aquaporin 2. Aquaporin 2 channels increases water retention
As a result, there is a net increase in water reabsorption in the collecting duct, leading to appropriate reservation of water and concentrating urine.
Think To little ADH or lack of response of the kidney to ADH means less water retention and more water output resulting in polyuria
145
Risk Factors of DI
146
Signs and symptoms of DI
147
Differential diagnosis of diabetes insipidus
Diabetes Mellitus Type I
Diabetes Mellitus Type II
Benign prostate hyperplasia
Excessive fluid intake
Pituitary adenoma
Craniopharyngioma
Psychogenic polydipsia
Hyperaldosteronism
Medications (Diuretics overdose)
Hypercalcaemia
Hyperosmolar hyperglycaemic state (HHS)
Urinary tract obstructions (prostatic hypertrophy, osmotic diuresis)
148
Investigations DI
149
Aetiology DI
Central DI (also known as neurogenic DI) caused by insufficient synthesis or release of ADH from the central nervous system
Nephrogenic DI caused by ineffective response to ADH in the kidneys, such as defective ADH receptors caused by genetic defects.
Dipsogenic DI (also known as primary polydipsia) results from excessive fluid intake practiced over an extended period. Sometimes not classified as a true diabetes insipidus.
Gestational DI During pregnancy, vasopressins are more readily metabolised peripherally by placenta hormones. Hence it can provoke transient "central DI" in some patients. Commonly, this condition resolves spontaneously upon delivery.
150
Pathophysiology of DI
**Central Diabetes Insipidus**
Traumatic or pathological damages affecting the hypothalamus or posterior pituitary gland causes cell death in hormone secreting cells in those areas, thus affecting the normal secretion and release of ADH. Without appropriate stimulation of ADH in the kidneys, renal collecting ducts lost its ability to perform adequate water reabsorption essential for volume maintenance of the body, resulting in a diuretic phenomenon.
**Nephrogenic Diabetes Insipidus**
Nephrogenic DI is caused by defective ADH receptors in the kidneys. Normally, two receptors AVPR1 and AVPR2 responds to increasing levels of ADH in the systemic circulation. AVPR1 is responsible for vasoconstriction and prostaglandin release, whereas the AVPR2 receptors mediated the antidiuretic response as well as certain coagulation factors (factor VIII and von Willebrand’s factor), hence unresponsive AVPR2 receptors in nephrogenic DI causes diuretic effects as well as mild coagulation defects.
151
Management of DI
152
Complications of DI
Hypernaturaemia
Growth retardation
Hydronephrosis
153
What is hyperparathyroidism
154
What are the types of hyperparathyroidism
Primary
Secondary
Tertiary
155
Differential diagnosis of hyperparathyroidism
156
Investigations for hyperparathyroidism
* PTH
* FBC
* EUC
* Vitamin D
* LFTs
* Thyroid Function test
* Urinary calcium
* Multiple Myeloma screening?
Once you have confirmed hyperparathyroidism (i.e. high PTH, high calcium, high urine calcium , low or normal phosphate, high ALP, more likely to be chronic, long standing, hypercalcaemia) then you can consider imaging:
* Bone Mineral Density Scan (DEXA) in primary hyperparathyroidism - Osteoporosis, osteopenia
* Renal imaging (abdo x-ray or U/S) - Nephrocalcinosis
157
causes of hyperparathyroidism
Primary hyperparathyroidism is caused by the inappropriate secretion of PTH, leading to hypercalcaemia. Causes:
* Parathyroid adenomas (85%)
MEN 1 and MEN 2 (15%)
Malignancy (<1%)
* External neck irradiation. Lithium therapy, often used to treat patients with bipolar disorder, can lead to the over-stimulation of parathyroid glands (rare)
Multiple Endocrine Neoplasia (MEN) are a group of familial endocrine diseases that affect multiple endocrine glands. There are two main types: MEN-1 and MEN-2.
158
Risk factors of hyperparathyroidism
Genetic mutations
-Multiple endocrine neoplasia (MEN) syndrome
159
complications for hyperparathyroidism
Post Surgery
* Haematoma
* Hypocalcaemia
* Larygneal nerve injury
* Pneumothorax
Osteoporosis
Bone Fractures
Nephrolithiasis
160
Signs and symptoms of hyperparathyroidism
161
Treatment for hyperparathyroidism
162
Pathology and causes of hypoparathyroidism
163
Causes of hypoparathyroidism
164
Signs and symptoms of hypoparathyroidism
165
What are the treatment for hypoparathyroidism
166
What is hypercalcemia?
Higher than normal calcium levels in the blood (over 10.5mg/dL)
One of the most common biochemical abnormalities in the body is elevated calcium levels in the blood, which is referred to as hypercalcaemia . Primary hyperparathyroidism and malignancy are the two most common causes of increased serum calcium levels. The presence of high or not adequately suppressed serum parathyroid hormone levels should point the diagnosis towards hypercalcaemia of parathyroid origins. Severe hypercalcaemia requires admission to hospital and treatment with aggressive intravenous hydration and bisphosphonates along with treatment of the underlying disease
167
Clinical Presentation of hypercalcaemia
"Bones, stones, thrones groans, moans”
Stones: nephrolithiasis
Bones: bone pain, myalgia, muscle cramps
Thrones: constipation, polyuria
Abdominal Groans: abdominal pain
Psychiatric Moans: anxiety, depression, memory loss, unsteady gait, poor sleep, parasthesia
168
What causes hypercalcaemia?
CHIMPS
C-Cancer
H-Hyperparathyroidism
I-Intoxication of vitamin D/Idiopathic
M-Milk alkali syndrome/Multiple myeloma
P-Paget's disease
S-Sarcoidosis
169
Calcium regulation
Calcium regulation is primarily controlled by the parathyroid hormone produced by the parathyroid gland. The parathyroid glands are tan-coloured, bean-shaped structures, about the size of a grain of rice. There are 4 parathyroid gland which lie on the posterior surface of the thyroid gland. Parathyroid gland main purpose is to synthesise and secrete parathyroid hormone (PTH). The parathyroid hormone does this in response to blood calcium levels.
* ↓Serum Ca2+ → Stimulates Parathyroidgland → Chief cells secrete PTH → ↑PTH aims to ↑Serum Ca2+
The normal range of serum calcium is 2.25-2.65mmol/L
Calcium is transported in blood bound to albumin. Some travel as free serum calcium.
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Timing and Severity of hypercalcaemia.
* Sudden = more likely malignancy
* Chronic = more likely hyperparathyroidism
* >3.7 really high = malignancy (parathyroid)
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Differential Diagnosis of Hypercalcaemia
* Hyperparathyroidism
* Malignancy
* PTH-like peptide
* Bone metastasis
* Sarcoidosis
* Dehydration and Prolonged immobilisation
* Hyperthyroidism
* Familial hypocalciuric hypercalcaemia
* Drugs
Remember 90% of hypercalcaemia cases are cause by primary hyperparathyroidism or by malignancy
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Approach to patient with hypercalcaemia (>2.65mmol/L)
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Hypocalcemia commonly presents with
convulsions, arrhythmias, tetany, and numbness.
Remember: without calcium, CATs go numb.
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Hyperkalemia is generally defined as serum potassium levels greater than
5.5 mEq/L
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Hypokalemia is generally defined as serum potassium levels less than
3.5 mEq/L
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↓↑Potassium (Hyperkalaemia and Hypokalaemia)
Overview Potassium (K+) is an important ion in the body. K+ is found mainly intracellularly (inside the cells) whereas sodium (Na+) is found extracellularly (outside the cells).
* Serum Potassium: 3.5mmol/L - 5.0mmol/L
* Serum Sodium:
Therefore:
* Hyperkalaemia: >5mmol/L
* Hypokalaemia: <3.5mmol/L
As the pH rises , K+ is shifted intracellularly and the serum levels falls; conversely when serum pH decreases, intracellular K+ shits extracellularly into the vascular space and so the serum level increases. This is because H+ and K+ are both positive and it is important to have normal +ions levels in the serum to maintain a gradient across the cell membrane to maintain the excitability of nerve and muscle cells, including the myocardium.
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Transcellular shifts as
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Causes of Hyperkalaemia
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Signs and symptoms hyperkalaemia
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Management hyperkalaemia
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MANAGEMENT OF HYPERKALAEMIA DEPENDING ON SEVERITY
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Complications of Hyperkalaemia
Cardiac arrest
Weakness
Paraesthesiae
Decreased reflexes
Ascending paralysis
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Signs and symptoms hypokalaemia
Generalised muscle weakness
Respiratory depression
Ascending paralysis
Ileus, constipation
Palpitations, Arrhythmia, Cardiac arrest
Nephrogenic diabetes insipidus (characterised by polyuria and polydipsia)
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Management hypokalaemia
Management - nonpharmacological
* ECG
* ABCD
* Check serum potassium
Management - pharmacological
* Chlorvescent - Given STAT
* Slow K
* Potassium Chloride (KCl) IV given in 10mmol in 100ml of normal saline
* Check serum potassium
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ECG findings hypokalaemia
Peaked P waves
T wave flattening and inversion
U waves
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↑↓Na (Hypernaturaemia and Hyponaturemia
Overview Hyponatremia is commonly defined as a serum sodium concentration below 130 mmol/L.
* Defined as a serum Na+ <130mmo/L
* It affects 1% of hospital in patients (on call book), 15% (BMJ)
* Most cases require no treatment.
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↑↓Na (Hypernaturaemia and Hyponaturemia) Classification
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Pseudohyponatraemia (arefactual)
Laboratory analysis technique
Hyponatraemia with normal serum osmolality
* Hyperlipidaemia, hyperproteinaemia
Hyponatraemia with increased serum osmolality
Hyperglycaemia, mannitol, excess urea
Toxic alcohols (ethanol, methanol, isopropyl alcohol, ethylene glycol)
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Hyponatreamia with high urinary Na+
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Hyponaturaemia with low urinary Na+
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Osmotic demyelination syndrome (central pontine myelonosis)
* Rapidly correcting hyponatraemia may produce permanent central nervous system injury, due to osmotic demyelination.
* Patients with chronic hyponatraemia (ie known duration more than 48 hours) are particularly at risk.
* Clinical manifestations typically delayed for 2-6 days.
Symptoms include dysarthria, dysphagia, paraparesis or quadriparesis, behavioural disturbances, movement disorders, seizures, lethargy, confusion, disorientation, obtundation, and coma. Severely affected patients may become "locked in"; they are awake but are unable to move or verbally communicate
Clinical Presentation
* Mild-moderate
Lethargy, weakness and ataxia
Nausea and vomiting
Headache
* Severe (<120mmols)
Confusion
Seizures and coma
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What is the common diagnostic of pheochromocytoma
An increase in 24-hour urine levels of metanephrines and catecholamines
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What is Pheochromocytoma
a tumor of the adrenal medulla that is associated with von Hippel-Lindau disease.
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he 5 presenting features of pheochromocytoma.
5 Ps of pheochromocytoma:
Pressure (episodic, elevated diastolic blood pressure)
Pain (pulsatile headache)
Perspiration
Palpitations (paroxysmal tachycardia)
Pallor
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Carcinoid syndrome results from
tumors associated with high levels of serotonin secretion.
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Carcinoid syndrome is associated with
flushing, wheezing, and diarrhea due to increased serotonin secretion
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The definitive treatment of carcinoid syndrome tumors is
surgical resection.
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Electrolyte disturbance Hypercalcaemia vs hyperkalaemia
