Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MBChB - year 2 > Week 3 Endocrine Lectures > Flashcards

Week 3 Endocrine Lectures Flashcards

1
Q

What does prolactin do?

A

Stimulates lactation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Where is prolactin secreted?

A

Lactotrophs in the anterior pituitary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What does  Hyperprolactinemia lead to?

A

hypogonadotropic hypogonadism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is hypogonadotropic hypogonadism?

A

a form of hypogonadism that is due to a problem with the pituitary gland or hypothalamus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What can any drug that interferes with dopamine action cause?

A

Hyperprolactinemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What drugs can affect dopamine action (and therefor can cause hyperprolactinemia)

A
  • Antipsychotics – typical and atypical
  • Antiemetics – metoclopramide, domperidone
  • Antidepressants – SSRIs, MOA-I, TCA
  • Opiates
  • H2 receptor antagonists
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is a prolactinoma?

A

The commonest functioning pituitary tumour

  • Microprolactinoma <1cm
  • Macroprolactinoma >1cm
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the medical treatment of a prolactinoma?

A

Dopamine (D2) agonists
- Cabergoline – long half life, once/twice weekly dosing
• Quinagolide
• Bromocriptine – short half life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is vasopressin (ADH)?

A

A peptide hormone secreted from the posterior pituitary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

When is vasopressin (ADH) released?

A

In response to low plasma volume/increased serum osmolality

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

When does Diabetes insipidus occur?

A

When ADH no longer secreted (cranial) or kidneys unresponsive (nephrogenic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the effects of vasopressin (ADH)?

A

V1 receptors - in vascular smooth muscle —> vasoconstriction

V2 receptors - in distal tubule –> aquaporin channels reabsorb water

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the synthetic analogue of vasopressin (ADH)?

A

Desmopressin (DDAVP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the effects of desmopressin?

A

It is a synthetic analogue of vasopressin (ADH) without the vasoconstrictor effects and has a longer half life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is desmopressin used for?

A

Maintenance therapy for cranial diabetes insipidus.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

When is desmopressin usually prescribed for?

A

It is usually prescribed for morning and evening so people aren’t up through the night for the toilet

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What causes acromegaly?

A

Excess secretion of growth hormones stimulating IGF-1 due to pituitary adenoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the different manifestations of a pituitary adenoma?

A

If the long bones have fused then acromegaly

If long bones have not fused gigantism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is acromegaly?

A

Lots of soft tissue growth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the treatment options for a pituitary adenoma?

A

surgery, medical and radiotherapy (if surgery hasn’t been successful radiotherapy on pituitary gland)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are medical therapies for acromegaly?

A

Treatment aims to normalise IGF-1 (combination therapy may be required)

  • Somatostatin analogues
  • Dopamine agonist
  • GH receptor antagonist
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How are somatostatin analogues used?

A
  • short or long acting (short needs to be given multiple times a day, long just once a month)
  • Injection - subcut, IM or IV
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are potential side effects of somatostatin analogues?

A
  • Gallstones
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What do GH receptor antagonists do?

A

Block GH action at the receptor but do not decrease GH secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

When would GH replacement therapy be required in paediatrics?

A
  • Short stature
  • Isolated GH deficiency
  • Panhypopituitarism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is Panhypopituitarism

A

a condition of inadequate or absent production of the anterior pituitary hormones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

When would GH replacement therapy be required in adults?

A
  • GH deficiency following pituitary insult
  • Late effects of cancer treatment
  • Performance enhancing effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Describe the negative feedback loop of the thyroid gland?

A

Hypothalamus releases TRH –> acts on the pituitary causing it to release TSH –> acts on the thyroid causing the release of T3 (triiodothyronine) and T4 (thyroxine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What is levothyroxine metabolised to?

A

triiodothyronine (T3)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What do Thionamides do?

A

Cause reduced thyroid hormone synthesis:

  • Inhibit iodide oxidation
  • Inhibit iodination of tyrosine
  • Inhibit coupling of iodotyrosines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What are examples of Thionamides?

A

Carbimazole and propylthiouracil (PTU)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What are other treatments (not Thionamides) for hyperthyroidism?

A
  • Betablockers - propranolol
  • Potassium iodide
  • Radioactive iodine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Why are betablockers used to treat hyperthyroidism?

A

Reduce symptoms if sympathetic overactivity, do not affect hormone levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Why is potassium iodide used to treat hyperthyroidism?

A

Reduces thyroid hormone release acutely, used in thyroid storm and pre-operatively

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

How do Sulphonylureas work?

A

Bind to receptor on beta cells, inhibit KATP channels and permit increased insulin secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

How do Thiazolidinediones work?

pioglitazone, rosiglitazone

A
  • PPARγ agonists – increase transcription of insulin senstising genes
  • PPARγ is a nuclear receptor expressed in adipose tissue, muscle, liver
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What are the actions of insulin on the liver?

A
  1. Decrease gluconeogenesis

2. Increase glycogen synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What are the actions of insulin on skeletal muscle?

A
  1. Increased glucose transport via GLUT 4

2. Increase glycogen synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What are the effects of insulin on adipose tissue?

A
  1. Increased glucose transport via GLUT 4

2. Increase lipogenesis and decrease lipolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

How are glucocorticoid and mineralocorticoid release controlled?

A

The hypothalamus releases CRH —> acts on the pituitary causing it to release ACTH —> acts on the adrenal gland causing it to release cortisol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

How do steroid hormones travel through the body?

A

Bound to proteins in circulation (cortisol binding globulin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What are the systemic effects of glucocorticoids?

A
  1. anti-inflammatory by inhibiting transcription of genes for pro-inflammatory cytokines
  2. Reduced T-lymphocytes
  3. Counter-regulatory metabolic effects – gluconeogenesis, increase adiposity
  4. Improve alertness (circadian rhythm)
  5. Mineralocorticoid effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What is aldosterone?

A

A mineralocorticoid that is stimulated by angiotensin II, ACTH and potassium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What is the main action of aldosterone?

A

on Na/K pump—>sodium and water reabsorption, loss of potassium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Why can aldosterone not be given orally?

A

It is metabolised in the liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What can mineralocorticoid receptor antagonists be used for?

A

Primary aldosteronism, heart failure, hypertension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What are bisphosphonates used to treat?

A

Osteoporosis, Paget’s disease, metastatic bone disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What is the effect of bisphosphonates?

A

Reduce bone resorption. They bind to bone and inhibit osteoclast activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What are examples of bisphosphonates?

A

Alendronate, pamidronate, zolendronate, risedronate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What are examples of other (not bisphosphonates) treatments of osteoporosis?

A
  • Calcium + vit. D - Essential for bone formation
  • Denosumab
  • Teriparatide
  • Strontium ranelate
  • HRT
  • SERMS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

How does denosumab treat osteoporosis?

A

monoclonal antibody that inhibits RANK ligand which signals to osteoclasts, therefore reduces resorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

How does teriparatide treat osteoporosis?

A

recombinant parathyroid hormone, binds to osteoblasts to increase bone formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

How does Strontium ranelate treat osteoporosis?

A

stimulates osteoblasts and inhibits osteoclasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Why is HRT used in osteoporosis?

A

used for menopause related bone loss

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

How do SERMs treat osteoporosis?

A

bind to oestrogen receptor and decreases bone resorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

What hormones does the hypothalamus release?

A

GHRH, GnRH, CRH, TRH and dopamine

57
Q

What senses GH and IGF-1 for negative feedback?

A

Anterior pituitary and hypothalamus

58
Q

What is the pattern of GH secretion like?

A

Pulsatile, mainly overnight

59
Q

How does GH have its effects?

A

Either direct effects through surface receptor which is a tyrosine kinase receptor or via production of insulin-like growth factor-1 (IGF-1) from the liver

60
Q

What are the actions of GH on long bones?

A

promote cartilage growth (chondrocyte replications) also leads to local release of IGF-1 and IGF-1 receptor

61
Q

What are the actions of GH on liver?

A

generates IGF-1

62
Q

What are the actions of GH on muscle?

A

trophic hormone, promotes incorporation of amino acids and protein synthesis

63
Q

What are the actions of GH on adipose tissue?

A

promotes lipolysis and FFA release

64
Q

What is inhibin?

A

a peptide hormone produced by the ovary which exerts negative feedback on FSH secretion (produced in the late follicular phase).

65
Q

What two hormones does the posterior pituitary produce?

A

ADH and oxytocin

66
Q

When is oxytocin important?

A

Labour and breast feeding

67
Q

What does oxytocin do during labour?

A

Stimulates cervical dilatation and uterine contractions

68
Q

What does oxytocin do during breastfeeding?

A

‘let down’ reflex in mammary glands; suckling by the infant at the nipple is relayed by spinal nerves to the hypothalamus. The stimulation causes neurons that make oxytocin to fire action potentials in intermittent bursts; these bursts result in the secretion of pulses of oxytocin from the neurosecretory nerve terminals of the pituitary gland.

69
Q

What can functioning pituitary tumours cause?

A

Excess production of:

  • Prolactin
  • GH
  • ACTH
  • TSH
70
Q

Where does AVPR2 act?

A

The basolateral membrane of the kidney collecting ducts

71
Q

What is the function of AVPR2?

A

Inserts aquaporin channels to increase renal water absorption

72
Q

What does the binding of AVP (arginine vasopressin) to the V2 vasopressin receptor do?

A

stimulates a Gs-coupled protein that activates adenylyl cyclase, in turn causing production of cAMP to activate protein kinase A (PKA)

This pathway increases the exocytosis of aquaporin water channel–containing vesicles (AQMCV) and inhibits endocytosis of the vesicles, both resulting in increases in aquaporin 2 (AQ2) channel formation and apical membrane insertion. This allows an increase in the permeability of water from the collecting duct (CD).

73
Q

What are the clinical features of Diabetes Insipidus?

A

Polyuria, polydipsia, nocturia

this must exclude hyperglycaemia and hypercalcaemia

74
Q

What are the cranial causes of Diabetes insipidus?

A

o Deficiency of ADH
o Can be idiopathic or genetic (mutation in ADH gene)
o Trauma, tumours, infections, inflammatory conditions of the posterior pituitary

75
Q

What are the nephrogenic causes of Diabetes insipidus?

A

o Resistance to ADH
o Genetic (AVPR2 mutation)
o Or secondary to drugs (e.g. lithium), metabolic upset, renal disease

76
Q

What is the water deprivation test used for?

A

To test for diabetes insipidus

77
Q

What happens in the water deprivation test?

A
  • Deprive patients of fluid for 8h
  • Measure plasma and urine osmolality every 2-4h
  • Then give synthetic ADH (ddAVP) and reassess urine osmolality
78
Q

What is the treatment of cranial diabetes insipidus?

A
  • Desmopressin (vasopressin/ADH analogue)
  • Can be given orally/nasal spray/injection
  • Monitor plasma sodium and osmolality
79
Q

What is the treatment of nephrogenic diabetes insipidus?

A
  • Treat underlying cause

- High doses of desmopressin

80
Q

What is an incidentaloma?

A

A non-functioning pituitary adenoma that is asymptomatic and only picked up by accident or post-mortem.

81
Q

What is it important to check in non-functioning pituitary adenomas?

A
  • Hormone excess
  • Hypopituitarism
  • effect on visual fields
82
Q

How can pituitary tumours affect visual fields?

A

(Pituitary located just below optic chiasm and the tumour can expand upwards and push on chiasm causing loss of peripheral vision (‘bitemporal hemianopia’)

83
Q

What are the different types of secretory pituitary adenomas?

A 
- Prolactin- ‘Prolactinomas’
      •	Commonest; 30%
- ACTH- ‘Cushing’s Disease’
      •	20%
- Growth hormone - ‘Acromegaly’
      •	15%
- TSH – ‘TSHomas’
      •	Very rare, < 1%
84
Q

What are the clinical features of a prolactinoma?

A
  • Galactorrhoea
  • Menstrual disturbance and subfertility in women (more common in women)
  • Reduced libido/erectile dysfunction in men
85
Q

How is a prolactinoma managed?

A
  • Dopamine agonists (cabergoline)

- surgery if large tumour with visual field effects or if medication is not effective

86
Q

What causes acromegaly?

A

Excessive production of GH (and IGF-1) usually due to pituitary adenoma (often large)

87
Q

What are the signs and symptoms of acromegaly?

A

Sweats, headache, tiredness, increase in ring or shoe size, joint pains

Coarse facial appearance, Enlarged tongue, Enlarged hands and feet, Visual field loss

88
Q

What is acromegaly called in children?

A

Gigantism

89
Q

What are potential complications of acromegaly?

A

Hypertension, diabetes or impaired glucose tolerance, increased risk of bowel cancer, heart failure

90
Q

How is acromegaly diagnosed?

A
  • Glucose tolerance test - Glucose load fails to suppress GH and may reveal underlying DM or IGT
  • IGF-1 levels - long half-life and protein bound
  • Pituitary MRI - tumour usually large (macroadenoma, > 1 cm) and often extends into surrounding structures
91
Q

How is acromegaly managed surgically?

A

By trans sphenoidal route – up through the nose

Often not curative

92
Q

How is acromegaly managed medically?

A
  • Before and after surgery

* Somatostatin analogues to inhibit GH secretion

93
Q

How is pituitary radiotherapy used in acromegaly?

A
  • To treat residual tumour

* Risk of hypopituitarism and long-term problems

94
Q

What is hypopituitarism?

A

Failure of (anterior) pituitary function

95
Q

What affect does hypopituitarism have?

A

can affect single hormonal axis (FSH/LH most commonly) or all hormones (panhypopituitarism)
Leads to secondary gonadal/thyroid/adrenal failure – the issue is not with the gonad it isn’t being stimulated appropriately

96
Q

How is hypopituitarism treated?

A

Need multiple hormone replacement but cortisol can be given first if all axes are affected

97
Q

What can cause hypopituitarism?

A
  • Tumours
  • Radiotherapy
  • Infarction (apoplexy)
    • if post-partum then called Sheehan’s syndrome
  • Infiltrations (e.g. sarcoid)
    • Can affect posterior pituitary too
  • Trauma
  • Congenital
98
Q

What regulates anterior pituitary function?

A

The hypothalamus via the hypophyseal portal system

99
Q

How much does the thyroid concentrate iodine by?

A

20-50x

100
Q

What is the structure of the thyroid gland?

A

Two lobes on either side of the trachea

101
Q

What are the follicles of the thyroid gland made up of?

A

single layer of cells surrounding a lumen containing colloid (largely thyroglobulin)

102
Q

What happens when thyroid follicular cells are stimulated?

A

They become columnar and the lumen is depleted of colloid

103
Q

What happens when thyroid follicular cells are suppressed?

A

The cells become flat and colloid accumulates in the lumen

104
Q

What is necessary for thyroid hormone synthesis?

A

Iodine

105
Q

Where is iodine found in the diet and how much is required?

A

Fruit and vegetables - require 150-300µg daily

106
Q

Where is iodine deficiency more common?

A

Mainly in inland areas at high altitude

107
Q

What does iodine deficiency lead to?

A

endemic goitre (big neck – enlarged thyroid)

108
Q

What happens to oral iodine in the GI tract?

A

It is reduced to iodide and absorbed

109
Q

How has iodine deficiency been reduced?

A

By the iodine supplementation of salt

110
Q

How is iodide transported into follicular cells?

A

Actively against a chemical gradient by the sodium iodide transporter on the basolateral membrane

111
Q

what happens after iodide has been transported into the follicular cell?

A

It diffuses to apex of the cell and is transported into vesicles fused with the apical cell membrane

112
Q

What happens to iodide in the vesicles of the follicular cell?

A

It is oxidised to iodine and binds to tyrosine residues in thyroglobulin

113
Q

What catalyses the organification that takes place in the follicular cell?

A

Thyroid peroxidase

114
Q

How are T3/T4 formed after organification has just taken place?

A

Diodinated/monoiodinated tyrosine’s are formed which then combine to either make T3 or T4

115
Q

How are T3 and T4 released?

A

after droplets fuse with lysosome, thyroglobulin is hydrolysed and thyroid hormones reach the circulation

116
Q

Which is more active T3 or T4?

A

T3

117
Q

Which hormone is greater in quantity T3 or T4?

A

T4

118
Q

Where is T4 converted to T3?

A

The periphery

119
Q

How is the action of Thyroid hormones mediated?

A

By nuclear receptors

120
Q

How is production of thyroid hormones mediated?

A
  • TSH from anterior pituitary stimulates synthesis and secretion of T4 and secretion of T4 and T3
  • TSH secretion is inhibited by T4 and T3 (negative feedback)
  • TRH from HPS stimulates TSH secretion
121
Q

What are the clinical findings of primary hypothyroid?

A

High TSH low T4

122
Q

What are the clinical findings of secondary hypothyroid?

A

Low TSH and Low T4

123
Q

What are the clinical findings of primary hyperthyroid?

A

Low TSH high T4

124
Q

What is hyperthyroidism?

A

Excess of thyroid hormone

125
Q

What causes Hyperthyroidism?

A 
• Auto-immune
     o	Graves’ disease 
• Toxic adenoma 
• Multinodular goitre 
• Thyroiditis 
• Excess administration of thyroxine
126
Q

What are the symptoms of thyrotoxicosis?

A
  • Weight loss
  • Tachycardia
  • Tremor
  • Hypertension
  • Tremor
  • Hypertension
  • Heat intolerance
  • Palpitations
  • Diarrhoea
  • Sweating
127
Q

What happens in Ophthalmopathy

A
  • Lid retraction / lag and periorbital oedema
  • Proptosis (30%)
  • Diplopia (10%)
  • Nerve compression rare
128
Q

What are the treatment options for graves disease?

A
  • Antithyroid drugs
  • Surgery
  • Radio iodine
129
Q

What are the medication options for hyperthyroidism?

A
  • Carbimazole

- Propylthiouracil

130
Q

What are the potential complications from surgery to correct hyperthyroidism?

A 
- Haemorrhage
 0-1.3% 
- Rec laryngeal palsy 
0-4.5% 
- Permanent hypocalcaemia
0.6% 
- Hypothyroidism
131
Q

What are causes of hypothyroidism?

A 
- Autoimmune thyroid disease (Hashimotos) 
      •	Destruction of the thyroid gland (anti TPO antibody) 
      •	May be positive family history, more common in females 
- Thyroiditis 
      •	Viral and often painful 
- Thyroidectomy 
- Following radio iodine therapy 
- Drug-induced 
      •	Amiodarone, lithium, sunitinib 
- Pituitary disease 
      •	Secondary hypothyroidism 
- Severe iodine deficiency
132
Q

What are the signs and symptoms of hypothyroidism?

A 
- Symptoms of hypothyroidism 
      •	Weight gain 
      •	Depression 
      •	Lethargy
      •	Constipation 
      •	Cold intolerance 
      •	Poor concentration 
      •	Hoarseness 
      •	Menorrhagia
- Signs of hypothyroidism 
      •	Weight gain 
      •	Bradycardia 
      •	Dry skin 
      •	Coarse, thin hair 
      •	Anaemia 
      •	Slow relaxing reflexes 
      •	May have goitre
133
Q

What investigations are done for hypothyroidism?

A

Free T4 and TSH

134
Q

What are the T4 and TSH levels like in primary hypothyroidism?

A

High TSH and low T4

135
Q

What are the T4 and TSH levels like in secondary hypothyroidism?

A

Low TSH and low T4

136
Q

How is hypothyroidism treated?

A

The main treatment is levothyroxine
• Generally, need 1.7-2.0 micrograms / kg / day
• Best taken on an empty stomach
• Avoid taking with proton pump inhibitors, ferrous sulphate or calcium

137
Q

What are the long term treatment goals for hypothyroidism?

A

To make the patient euthyroid - resolve symptoms and normalise TSH

138
Q

What are the different types of Differentiated thyroid cancer?

A 
- Differentiated (good prognosis) 
      •	Papillary 17% 
      •	Follicular 13-20% 
      •	Mixed 50%
      •	Medullary Carcinoma of Thyroid 6%
139
Q

What are the different types of undifferentiated thyroid cancer?

A
  • Undifferentiated 15% (poorer prognosis)
    • Anaplastic
    • Small cell

MBChB - year 2 (25 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions