Endocrinology Flashcards
(500 cards)
1
Q
What is the endocrine function of the pancreas?
A
Release of insulin
2
Q
What is the exocrine function of the pancreas?
A
Release of lipid and protein digestive enzymes
3
Q
How is communication between glands and body achieved?
A
Secretion of hormone into blood stream and transport to target site
4
Q
What does anterior pituitary release?
A
ACTH which causes adrenal cortex to synth and release cortisol
5
Q
How is specificity of signalling achieved?
A
Chemically distinct hormones Specific receptorsDistinct distribution of receptors across target cells - like an address
6
Q
What are income of the overall functions of endocrine system?
A
Regulation of nutrient metabolism and h2o and electrolyte balance Enabling changes to stress - cortisol Promoting growth and development - growth factor Controlling reproduction Regulating rbc production (eg erythropoietin) Controlling and integrating GI system and cvs
7
Q
What is autocrine chemical signalling?
A
Specified cell(s) releases chemical which modifies THAT SAME CELL
8
Q
What is paracrine chemical signalling?
A
Specific cells release chemicals to adjacent cells (eg enterochromatin in stomach cells)
9
Q
What is endocrine chemical signalling?
A
Cells release hormone into bloodstream
10
Q
What are the three main classes of chem nature of proteins?
A
(Glyco) proteins and peptidesSteroids Tyrosine and tryptophan derivatives
11
Q
Outline (glyco) proteins and peptides -
A
Most diverse class, amino acids of different chain links, eg oxytocin and insulin - these contain disulfide bonds but they link different chains
12
Q
Outline steroids
A
Derive from cholesterol eg cortisol, testosterone All contain core steroid nucleus
13
Q
Outline tyrosine and tryptophan derivatives
A
Eg adrenaline, thyroid hormones, melatonin
14
Q
Outline synthesis, storage and release of amines
A
Tyrosine converted to adrenaline and stored in endocrine cell. Release is dependent upon calcium dependent exocytosis. They are presynthesised and stored in vesicles. Amines are hydrophilic
15
Q
Outline synth storage and release of peptides and proteins
A
Presynthesised, usually from longer precursors (by action of convertases), stored in vesicles, released in response to stimulation by Ca2+ dependent exocytosis. Peptides are hydrophilic and transported usually ‘free’
16
Q
Outline synth, storage and release of steroids
A
Synth and secreted on demand. Stimuli increase (i) cellular uptake and availability of cholesterol, (ii) rate of conversion of cholesterol to pregnenolone (rate limiting step). Steroids are insoluble (hydrophobic)-> transported in plasma mainly bound to plasma proteins -only ‘free’ is biologically active
17
Q
What do carrier proteins do?
A
Increase amount of insoluble steroids and thyroxine transported in blood. Prevent rapid excretion by preventing filtration of kidneys
18
Q
What does CBG do?
A
Binds cortisol selectively and also some aldosterone
19
Q
What does TBG do?
A
Binds thyroxine (T4) selectively and also some T3
20
Q
What does sex steroid binding protein do?
A
Binds mainly testosterone and estradiol
21
Q
What are some general protein carriers?
A
Albumin - binds many steroids And some thyroxine Transthyretin - binds thyroxine and some steroids
22
Q
What do circulating carrier proteins also do?
A
Act as buffers and reservoirs - maintain constant concentrations of free lipophilic hormone in blood - free and bound hormone are in equilibrium
23
Q
What is the conductor of the endocrine orchestra?
A
Pituitary gland
24
Q
What are some of the non specific symptoms of endocrine disease?
A
Tiredness, weakness, lack of energy, changes in appetite or thirst, changes in body size or shape, problems with libido and potency, problems with periods or sexual development, changes in skin (dry, greasy, acne, bruising, thinning or thickening) hair loss or excess
25
What should be included in a history of endocrine disease in patient?
Previous surgery or radiation involving endocrine glands, menstrual history, pregnancy and growth and development in childhoodA full drug history - including common iatrogenic endocrine problems FHx - autoimmune disease including tumours, diabetes, cardiovascular disease, knowledge of family members height, weight, body habitus, hair growth and age of sexual development,
26
What must be done in an endocrine examination?
Weight, height, bmi, BP, general body habitus, presence or absence of specific signs of deficiency or excess of individual hormone axes (signs of hypo- or hyper- thyroidism, acromegaly, cushings)
27
What should be checked in people with suspected pituitary disease?
Visual fields and adjacent cranial nerves
28
What should you check on examination of someone with suspected thyroid disease?
Thyroid eye disease, lid lag, goitre
29
What endocrine disease can be caused by using traditional anti-psychotics, oestrogens, dopamine-antagonist antiemetics?
Increase prolactin - causing galactorhhea and oligo-/amennorhea
30
What endocrine effect can occur after using iodine, amiodarone, immune-modulating drugs?
Hyperthyroidism (amiodarone can also cause hypothyroidism)
31
What can using lithium cause?
Hypothyroidism
32
What can chemotherapy cause?
Ovarian and testicular failure
33
What drugs can mimic thyrotoxicosis or phaeochromocytoma?
Sympathomimetics, amfetamines
34
What drugs can mimic hypoaldosteronism?
ACE inhibitors
35
What skin changes are significant in endocrine disease?
Pigmentation - Addison's and Nelson's Vitiligo - autoimmune endocrinopathies Acanthosis nigricans - PCOS and DM Skin thinning - cushings, hypogonadism Skin thickening - acromegaly, PCOS Bruising and striae - cushings
36
What do functional endocrine tumours cause?
Excess secretion of the relevant hormone
37
What is MEN?
Multiple endocrine neoplasia - these exist due to very specific mutations of a single gene such as the mutations of the RET proto-oncogene in MEN 2 or the MEN1 gene mutation in MEN1
38
What is an example of an enzyme deficiency disease?
Congenital adrenal hyperplasia
39
What is testicular feminization?
An example of a condition in which hormone secretion and control are normal (eg androgen) but the receptors are defective
40
Many hormones are bound to proteins within circulation so only the _______ hormone is available to the tissues and thus is biologically active
Free (unbound) (this binding works as a buffer to prevent very rapod changes in plasma conc of protein)
41
What might the binding result in problems clinically?
Many tests of endocrine function measure total rather than free hormone - can give rise to difficulties in interpretation when binding proteins are altered in disease states or by drugs
42
How do hormones act?
By binding to specific receptors in the target cell.
43
How are hormone receptors divided?
Cell surface or membrane receptors - typically transmembrane receptors with hydrophobic sections - they trigger internal cellular messengersNuclear receptors - typically bind hormones and translocate them to the nucleus
44
What is rabson mendenhall syndrome?
A rare autosomal recessive genetic trait - severe insulin resistance, hyperglycaemia and compensatory hyperinsulinaemia. Developmental abnormalities, acanthosis nigricans, fasting hypoglycaemia, DKA, SEVERE MUTATIONS IN INSULIN RECEPTOR
45
What do alpha cells in the pancreas secrete?
Glucagon
46
What do delta cells in the pancreas secrete?
Somatostatin
47
What do pancreatic PP cells secrete?
Pancreatic polypeptide
48
Outline the synthesis and structure of insulin
It is synthesised in RER of pancreatic beta cells as PREPROINSULIN.(pro insulin) Cleaved to form insulin, contains two polypeptide chains, joined by disulfide bonds. The C chain is cleaved off leaving a and b chains as active insulin
49
Pro insulin has how many chains?
3 - a chain, b chain and c chain.
50
Too much _______ will kill you.
LOVE. JK it's insulin :D
51
Are the insulins between species different?
There is v little variation between species, the differences do not affect bio activity however they become antigenic and induce antibody formation after a while
52
How does glucose enter beta cells?
Glucose enters Beta cells through GLUT2 glucose transporter and is phosphorylated by glucokinase
53
What happens to a change in glucose concentration?
A change in glucose conc can cause a dramatic change in glucokinase levels. Increased metabolism of glucose causes increased intracellular conc of ATP
54
Release of insulin is...
BIPHASIC
55
With increased ATP, what happens next?
ATP inhibits ATP sensitive K+ channel KATP. This leads to DEPOLARISATION OF CELL MEMBRANE. The Ca2+ channels open. There is increased internal calcium. This leads to fusion of secretory vesicles with cell membrane. This leads to RELEASE OF INSULIN.
56
Is all insulin readily available?
No, 5% insulin granules are available immediately! the reserve pool needs to undergo preparation rxns to be ready to be released
57
What is the KATP channel?
IT is made up of two proteins - pore subunit Kir6.1. A sulphonylurea receptor SUR1 - both are required to have a functional channel - channel exists as an optometric structure
58
KATP channel is directly inhibited by...
Sulphonylureas
59
KATP is stimulated by...
Diazoxide which then inhibits insulin secretion.
60
What can an over active KATP channel mean?
Neonatal DM
61
What can an inactive KATP Channel cause?
Hyperinsulinaemia
62
What do beta cells release in response to folbutamide?
Insulin
63
What does the pancreas contain?
Ductless endocrine glands
64
Where is the posterior triangle of the neck?
Anteriorly - posterior border of sternocleidomastoidLaterally - anterior border of trapezius Inferiorly - clavicle
65
What are some of the superficial swelling of the neck?
Sebaceous cysts LipomasNeurofibromas
66
What are some lumps that may occur in the midline of the neck ?
Thyroid related Thyroglossal cystDermoid cyst
67
What are some of the swellings that can occur at the anterior triangle ?
Lymph nodes, branchial cysts, salivary glands, carotid body tumour
68
What are some of the neck lumps that can occur in the posterior triangle ?
Lymph nodes Cystic hygroma
69
What should you always check for is someone has cervical lymohadenopathy ?
Other nodesLook for primary sites Look for hepatosplenomegaly Do a chest X-ray, ENT opinion, fine needle aspiration
70
What is a thyroglossal cyst?
It can arise anywhere in the Thyroglossal tract Contains lymphatics which may become infectedMoves with the tongue Usually presents in teenage years
71
What is a Dermoid cysts?
Rare congenital cystUsually presents in teenage years Soft, nonfluctuant
72
What is a branchial cyst ?
Persisting second brachial arch Arises in upper part of ant. Triangle Usually presents in teenage years "Half filled hot water bottle"Can fistulate
73
What is a cystic hygroma?
Majority present in the first year Can be large and cause pressure symptoms, lymph filled. Trans illuminate
74
What salivary gland swellings are there?
Submandibular - stone, pleomorphic adenoma Parotid - infective, pleomorphic adenoma, stone
75
What is the anterior triangle of the neck?
Superiorly - bounded by mandibleMidline - mediallyLaterally - anterior border of sternocleidomastoid
76
The human skeleton is composed of what type of bone?
20% trabecular (porous, sponge-like)80% cortical (dense material that provides stiffness and strength)
77
How much bone is remodelled each year?
Bout 10% of the adult skeleton
78
Which cells cause active resorption of bone?
Osteoclasts
79
Who is at risk of fragility fractures?
Previous fragility fractureCurrent or past use of oral glucocorticoidsHistory of fallsFamily history of hip fracture Other secondary causes of osteoporosisLow BM (4 units per day
80
If someone has had a previous colles fracture, what is the likelihood that they will have a hip fracture?
Their risk doubles
81
What are some secondary causes of osteoporosis?
Endocrine e.g. Hyperthyroidism, hyperparathyroidism, cushings disease, T1DMGI e.g. Coeliac, IBD, chronic liver disease, chronic pancreatitis Respiratory- e.g. CF, COPD Chronic kidney disease and WAAAY more
82
What is a direct effect on bone by corticosteroids ?
Reduce osteoblasts actvity and life span Suppress the replication of osteoblast precursor Reduce calcium absorption
83
What is an indirect effect on bone by corticosteroids ?
Inhibition of gonadal and adrenal steroid production
84
What is a DEXA scan ?
These scans report bone density with reference to the number of standard deviations from the mean
85
What does the T score mean?
Relates to young adult female population mean
86
What does the Z score relate to ?
Age-matched female population mean
87
What is a normal DEXA finding .
BMD within 1 SD of the young adult reference mean
88
What is osteopenia on a DEXA scan?
BMD >1SD below the young adult mean but <2.5SD from this value. Osteoporosis is worse than 2.5
89
What are some pieces of lifestyle advice given to people with osteoporosis ?
High intensity strength training Low impact weight bearing exercises Avoidance of smoking and excess alcoholLose weight Fall prevention
90
When should you treat osteoporosis?
Consider when T score is less than or equal to 2.5 or prolonged steroid use
91
What are the drug treatments for osteoporosis?
Calcium and vitamin D supplementation Bisphosphonate DenosumabStrontium ranelateHRTTestosterone
92
How much calcium should post menopausal women take?
1000mg per day and vitamin d supplementation is not required when you can go out and get sunshine
93
What are bisphosphonates?
Antiresorptive agents - alendronate and risedronate Prevent bone loss at all sites vulnerable to osteoporosis Reduce fracture risk
94
What do bisphosphonates do?
Analogues of pyrophosphate that adsorb onto bone within the matrix Ingested by osteoclasts leading to cell death thereby inhibiting bone resorption Filling of resorption sites by new bone increases BMD by 5-8%
95
What is strontium ranelate ?
Antiresorptive agent 3rd line agent as fracture risk reduction slightly less than bisphosopahate and many contraindications
96
What percentage of patient with a hip fracture will die within a year later?
About 20%
97
What are the causes of hypercalcaemia?
Primary hyperparathyroidismMalignancy Drugs: Vit d, thiazides Granulomatous disease e.g. Sarcoid, TB Familial hypocalciuric hypercalcaemia High turnover - bedridden, thyrotoxic, Paget's Tertiary hyperparathyroidism
98
How do you diagnose primary hyperparathyroidism?
Raised serum calcium Raised serum PTH or inappropriately normal Increased urine calcium excretion
99
What are the mechanisms of hypercalcaemia of malignancy?
Metastatic bone destructionPTHrp from solid tumours Osteoclast activating factors
100
How do you diagnose hypercalcaemia of malignancy?
Raised calcium and ALPX-ray, ct, MRI Isotope bone scan
101
How do you treat acute hypercalcaemia?
Fluids - rehydrate with 0.9% saline 4-6L in 24h Loop diuretics? (Avoid thiazides) Bisphosphonates - single dose will lower Ca over 2-3d, max effect at one week Steroids used occasionally e.g. Pred 40-60mg/day for sarcoidosis Chemo may reduce it in malignancy e.g. Myeloma
102
What are some indications for para thyroidectomy?
End organ damage: bone disease, gastric ulcers, renal stones, osteoporosis V high calcium (>2.85mmol/L) Under age 50eGFR < 60
103
What is primary hyperparathyroidism?
Primary overactivity of parathyroid e.g. Adenoma (PTH raised, Ca raised)
104
What is secondary hyperparathyroidism?
Physiological response to low calcium (Ca low and PTH high)
105
What is tertiary hyperparathyroidism?
Parathyroid becomes autonomous after many years of secondary (Ca raised and PTH raised too)
106
What is the screen for multiple myeloma?
Protein electrophoresis Benz jones Skeletal survey
107
What is hypocalciuric hypercalcaemia?
It is familial Autosomal dominant Usually benign/asymptomaticMild hypercalcaemia Reduced urine calcium excretion PTH may be slightly elevated
108
How does hypocalcaemia present?
Parasthesia - fingers, toes, perioralMuscle cramps, tetany Muscle weakness Fatigue Bronchospasm or laryngospasm Fits Chovsteks sign (tapping over facial nerve) Trousseau sign (carpopedal spasm) ECG - PROLONGED QT
109
What are the causes of hypocalcaemia?
HypoparathyroidismVitamin d deficiency - osteomalacia, rickets Chronic renal failure Others - pancreatitis, hyperventilation osteoblastic bone mets, rhabdomyolysis
110
How do you treat acute hypocalcaemia!
IV calcium gluconate (10ml, 10% over 10 mins) in 50ml saline or dextrose
111
What can cause Hypoparathyroidism?
Congenital absence (DiGeorge syndrome) Destruction (surgery, radiation, malign) AutoimmuneHypomagnesaemiaIdiopathic
112
What is the management for hypoparathyroidism!
Calcium supplement Vitamin d tablets
113
What is pseudohypoparathyroisism?
Genetic defect Low calcium but PTH is elevatedDue to PTH resistance Bone abnormalities ObesitySubcutaneous calcification Mental retardation Brachdactyly (4th metacarpal)
114
What is pseudo-pseudohypoparathyroidism?
All of pseudo but with normal calcium
115
How can one get vitamin d deficiency ?
Dietary deficiency Malabsorption- gastric surgery, coeliac, liver disease, pancreatic failureChronic renal failure Lack of sunlight Drugs eg anticonvulsants
116
What may you see clinically with osteomalacia?
Low calcium, proximal myopathy, dental defects, bone tenderness, deformity etc
117
What may you get with chronic renal disease (calcium wise) ?
Vit D deficiency Secondary hyperparathyroidism
118
Hat is the biochem with osteomalacia?
Low calcium Low phosphate High alk phos Low Vit D PTH high
119
What symptoms may someone have with Paget's disease?
Asymptomatic Bone painFracturesNerve compression - deafness, cord compression
120
How do you diagnose Paget's disease?
X raysRaised alk phos Isotope bone scan
121
What is the management for Paget's disease?
Oral bisphosphonate high dose Calcitonin
122
What are the symptoms of hypercalcameia?
Stones, groans, bones and psychic moans!Acute - thirst, dehydration, confusion polyuria Chronic - myopathy, osteopenia, fractures, depression, hypertension, abdo pain - pancreatitis, ulcers, renal stones
123
What is the target bmi for obese people ?
25
124
What is the target HbA1c?
7% or 75 mmol/L
125
What is the target BP for people with T2DM?
140/80 or lower for those with complications
126
What should their total cholesterol be?
Less than 5
127
What should their LDL cholesterol be?
Less than 3
128
What should their triglycerides be?
Less than 2.3
129
If someone has a bmi of less than 25 and they have T2DM, what drug?
Gliclazide up to 160mg bd
130
What do you give a person with a bmi above 25 who has t2dm ? Drug wise
Metformin 1g tds
131
If on someone is under 55, what is the first line anti hypertensive?and what if they are above?
ACEi or ARB But if they are over, calcium channel blocker
132
What is done at a diabetic review ?
General healthDiabetic understandingMedication review Smoking and alcohol Glycaemic control Symptoms of complications ICE, what does this mean to her? Compliance, concordance or adherence
133
What examinations should you do on a diabetic ?
Weight/BMIBPVisual acuityConsideration of retinopathy Consideration of foot care and neuropathy
134
What other investigations should you do on a diabetic?
Urinalysis for protein and consider screening for microalbuminuriaHbA1c U&Es Cholesterol and lipid profile
135
What is the stages of change model ?
Pre-contemplation ContemplationPreparationActionMaintenance
136
What is the oral glucose tolerance test?
It is a fasting plasma glucose tolerance test. No food or drink 8-12 hours prior to testBlood is drawn and glucose level is tested - high? Possible DMThen they drink glucose and two hours later blood is tested, high glucose = probably DM
137
What cells are inside the thyroid?
Follicular cellsColloid-tyrosine-containing thyroglobulin filled spheres enclosed by follicular cells Parafollicular cells -SECRETE CALCITONIN
138
What happens with iodine in the follicular cells?
They move in from capillary into cell where they then move into the colloid thyroglobulin. Attaches to tyrosine residues to form MIT and DIT. MIT + DIT = T3 DIT + DIT = T4 Stored in colloid thyroglobulin until required
139
What does carbimazole and propylthiouracil do?
They block the joining of iodine to tyrosine thus preventing the formation of MIT and DIT
140
Where is T4 converted to T3?
Liver and kidney
141
Which is more abundant t3 or t4?
T4 makes up 90% of thyroid hormones secreted And T3 the rest BUT T3 is the major biologically active one
142
How is thyroid hormone released and transported?
Secreted from the colloid via processing in the follicle cells t3 and t4 are hydrophobic/lipophilic so they bind to plasma proteins such as TBG and thyroxine binding prealbumin and albumin The unbound ones are the biologically active ones T4 needs to be converted to T3 in order to have an affect at the target cell
143
What do thyroid hormones do?
Increase BMR - increase no and size of mitochondria - increase oxygen use and rates of ATP hydrolysis - increase synthesis of respiratory chain enzymes Increases thermogenesis - 30% of our temperature regulation is due to thyroid hormone thermogenesis
144
What are some additional metabolic effects of thyroid hormone?
Carb metabolism - increase blood glucose due to stimulation of glycogenolysis and gluconeogenesis. Increase insulin dependent glucose uptake into cells Lipid metabolism - mobilise fats from adipose Increase fatty acid oxidation in tissues Protein metabolism - increase protein synthesis
145
What does the thyroid secrete?
Thyroxine (T4)Tri-iodothyronine (T3) Calcitonin
146
What are the next most common thyroid cancers?
Follicular, medullary, anaplastic, other
147
What is differentiated thyroid cancer?
Refers to papillary and follicular variants Differentiated refers to their histological appearance Most take up iodine and secrete thyroglobulin DTC are TSH driven!!!!Differentiated features mean good prognosis compared to other solid tumours
148
What is the incidence of DTC like?
Most commonly womenLower incidence in Afro AmericansStrong association with exposure to radiation
149
How does DTC present?
Most have palpable nodules and some are a chance finding
150
What is papillary thyroid cancer associated with?
Hashimoto's thyroiditis
151
How does papillary thyroid cancer spread?
Via lymphatics Haematogenous spread to lungs bone liver and brain
152
What is the prognosis like with papillary thyroid cancer ?
Generally very good with a 10 year mortality rate of less than 5%
153
How does follicular carcinoma spread?
Tends to spread haematogenously
154
How do you investigate DTC?
US guided FNA of lesion Can involve excision biopsy of lymph node No role for isotope thyroid scan No role for CT or MRI
155
What are some of the clinical predictors of malignancy?
New thyroid nodule in someone less than twenty or older than fifty MaleNodule increasing in sizeLesion greater than 4cm in diameter History of head and neck radiation Vocal cord palsy
156
What are the surgical options for DTC ?
Thyroid lobectomy with isthmusectomy Sub-total thyroidectomy Total thyroidectomy
157
What is the AMES system.
risk stratification A - age M - metastasis E - extent of primary tumour S - size of primary tumour
158
What is whole body iodine scanning L
Used in patients who have undergone total or sub total thyroidectomy Usually 3-6months post-opThey get an iodine capsule on Tuesday and they return for imaging on Friday and if uptake in thyroid bed >0.1% of ingested activity, patient undergoes thyroid remnant ablation on following Tuesday
159
What is thyroid remnant ablation?
Pt admitted to lead lined room with mains sewerage They get iodine capsule Few side effects - sore throat, sialadenitis Pt uses disposable cutlery, sheets and clothing until safe, little or no contact with nurses or visitors Discharged when count rate <500cps at 1m
160
Are there any long term effects of TRA?
Small but significant increase in incidence of acute myeloid leukaemia but that mostly happens in people with cumulative dosesNo evidence for increase in incidence of other solid tumours or infertility etc
161
How can recurrent disease be detected with DTC?
Can be detected clinically by rising Tg or by imaging Recurrence in cervical lymph nodes is commoner in papillary cancer Spread to lungs, bone, brain more common with follicular
162
What is the most common thyroid cancer?
Papillary (76%)
163
What is the target hba1c for children ?
Less than 58
164
How do you screen a child for congenital thyroid disease?
Guthrie test On day 5 of life Measures TSH and or T4 levels
165
What does the absence of thyroxine after three months of life lead to?
Permanent developmental delay - cretinism
166
What are the differentials when a child is born with ambiguous genitalia?
CAH or other steroid abnormalities Gene and or chromosomal abnormalities Congenital defects
167
How would a child with type one diabetes present.
Fasting blood glucose >7.0mmol/L and random blood glucose >11.0mmol/L Polyuria, polydipsia, weight loss, general malaise, nocturnal enuresis, constipation, blurred vision, oral or vulval candida and if untreated It will progress to DKA - vomiting, abdo pain, altered consciousness, acidotic, kussmaul breathing pH <7.3; urine ketones +++ Dehydrated Severe or untreated leads to coma and death
168
What are the causes of hyperthyroidism ?
GravesMulti-modular goitre Toxic nodule (adenoma) Subacute or postpartum thyroiditis Medication ie lithium, thyroxine, amiodarine
169
What does Graves' disease look like on scintigraphy?
High uptake, smooth symmetrical goitre
170
What antibodies may be present with Graves' disease ?
Anti-TPO in 70-80% (and in 95% of those with autoimmune hypothyroidism) Anti-thyroglobulin antibody in 30-50% graves and 60% of those with autoimmune hypothyroidism TSH receptor antibody in 70-100% (stimulating)of graves patients and in 10-20% of autoimune hypothyroidism (blocking)
171
How can you treat graves eye disease?
Lubricants, decompression surgery, radiotherapy, corrective surgery, stop smoking
172
What may you see on tests with multinodular goitre or a dominant nodule (toxic adenoma) ?
High T3/T4, low TSH Antibody negative ASSYMETRICAL GOITRE ESP SEEN ON SCINTIGRAPHY
173
When might someone get sub acute or de quervains thyroiditis?
Females more often than malesAge 20-50May be viral triggeredMay be associated with sore throat or fever, usualy self limiting
174
What are the tests like with sub acute or de quervains thyroiditis?
T4 is high in early stage, low in late and then normal TSH is low in early stage, high in late, then normal SCINTIGRAPHY - LOW UPTAKE
175
What is a thyroid storm?
MEDICAL EMERGENCY ABCDESevere hyperthyroidism Resp and cardiac collapseHyperthermiaExaggerated reflexes May require ventilation May be associated with underlying infection
176
With graves how do you treat?
Start with a high dose of carbimazole or ptu and reduce over 12-18 months and then stop
177
What are the symptoms of hyperthyroidism?
Cardiac - palpatations, AF, cardiac failure Sympathetic - tremor, sweating CNS - anxiety, nervousness, irritability, sleep disturbance GI - frequent, loose bowel movementsVision - lid retraction (all hyperthyroidism), double vision, exophthalmos Hair and skin - hair change - brittle hair, thinning hair, Reproductive - menstrual cycle changes, lighter bleeding etc Muscles - weakness esp on thighs and upper arms Metabolism - weight loss despite increased appetite Thermogenesis - intolerance to heat
178
What are some of the complications in the neonate of DM in pregnancy?
Respiratory distress - immature lungsHypoglycaemia - fits Hypocalcaemia - fits
179
What CNS defects can occur with DM in pregnancy ?
Anencephaly, spina bifida
180
What skeletal abnormalities can occur with DM in pregnancy ?
Caudal regression syndrome
181
What are some genital or GI complications that can occur with pregnancy DM ?
Ureteric duplication
182
What does maternal hyperglycaemia lead to?
Foetal hyperglycaemia which leads to foetal hyperinsulinaemia which leads to macrosomia and neonatal hypoglycaemia (insulin is major growth factor in third trimester)
183
How does a woman manage diabetes in pregnancy ?
Pre pregancy counseling - good sugar control pre conception, limit risk of congenital malformation Folic acid 5mg Consider changing from tablets to insulin for t2dm Regular eye checks - accelerated retinopathy Avoid ACEI, statin - for BP use labetalol, nifedipine, methyl dopa Diabetic diet Aim for good blood sugar control Monitor hba1c Monitor BP Maintain good blood glucose during labour (IV insulin and dextrose)
184
What is the treatment for MODY
Gilbenclamide
185
How do you ensure gestational diabetes has resolved ?
6 week post natal GTT
186
How does HCG from the pregnancy change thyroid tests?
It acts like TRH and there is sometimes a low TSH in pregancy (9%) fT4 is increased in 14% of pregnancies
187
What happens to the thyroid with hyperemesis gravidarum?
hCG high, 50-60% have abnormal TSH/T4
188
What does oestrogen do thyroid-wise in pregnancy?
Increases the thyroid binding globulin
189
What does a woman do if she has pre-existing hypothyroidism and gets pregnant ?
Increase thyroxine dose ASAPAs there is an increase in TBG but this plateaus at 20 weeks Check TFTs monthly for the first 20 weeks and then 22 monthly until term Average dose needs to increase by 50% by 20 weeks Aim for TSH <3
190
What are the risks of untreated hypothyroidism in pregnancy?
Increased abortion, pre eclampsia, abruption, postpartum haemorrhage, pre term labour Foetal neuropsychological development is often impaired Average Of 7 less iQ points in these children
191
What can cause thyrotoxicosis in pregnancy ?
Graves' disease TMNG, toxic adenoma Thyroiditis Gestational hCG - associated thyrotoxicosis - hyperemesis gravidarum -> increased hCG, less TSH Resolves by 20 weeks
192
What can hyperthyroidism result in in pregancy .,
InfertilitySpontaneous miscarriage Still birthThyroid crisis in labour Transient neonatal thyrotoxicosis
193
How do you manage hyperthyroidism in pregancy ?
Wait and see, hyperemesis will settle, graves should settle as it is autoimmuneB-blockers in early pregnancy Low dose anti thyroid drugs - PTU first trimester, carbimazole 2/3rd trimester
194
What is post partum thyroiditis?
Happens in 3-16% post partum women and 25% will already have t1DMUp to 1 year post partum Lymphocytic infiltration Post partum - exacerbation of all autoimmune Dx
195
What inhibits prolactin?
Dopamine
196
Wheat would the insulin stress test be used to test for?
Cortisol and GH response every 30 mins for 2-3 hours
197
What cranial nerves can be compressed by a non functioning pituitary adenoma.
3,4,6
198
What are the physiological causes of raised prolactin?
Breast feeding, pregnancy, stress, sleep
199
WHat drugs Can raise prolactin?
Dopamine antagonists e.g. MetoclopramideAntipsychotics e.g. PhenothiazinesAntidepressants e.g. TCA, SSRIs, Others such as estrogens, cocaine
200
What are some of the pathological causes of raised prolactin?
HypothyroidismStalk lesions-iatrogenic -road accident Prolactinoma
201
How may a woman present with a prolactinoma?
EARLY presentationGalactorrhea Menstrual irregularity Amenorrhea Infertility
202
How may a man present with a prolactinoma .
LATE Some get galactorrhea Visual field defects Headache Impotence Ant pit malfunction
203
How do you investigate a possible prolactinoma ?
Prolactin conc in blood MRI - look for a micro or macro, look at the stalk and optic chiasmVisual fields - bitemporal hemianopiaPituitary function test - look at other hormones affected
204
How do you treat a prolactinoma?
Dopamine agonists Bromocrptine, tds Quinagolide od Cabergoline twice a. Week - least side effects.
205
If GH is in excess before epiphyseal fusion, what happens?
The person gets gigantism
206
What other features are present with acromegaly ?
HT, cardiac failureThickened soft tissues - skin, large jaw, sweaty large hands HeadachesSnoring or sleep apnoea DMLocal pituitary effects - visual field etc Early CV death
207
How do you diagnose acromegaly?
IGF 1 - age and sex matched GTT - (75g oral: check GH 0, 30, 60, 90, 120 mins) - Normal - GH suppresses to <0.4micrograms/L after glucose - acromegaly - GH unchanged no suppression. Paradoxical rise, Other tests - visual field, ct or MRI pituitary, PFTs
208
How maya you reduce GH without surgery?
Somatostatin analogues Tumour shrinks Relieves headache in one hour pre op GH antagonist- pegvisomant. 85% response rate! binds to GH receptor
209
What side effects occur with somatostatin analogues?
Local stingingFlatulence Diarrhoea Abdo painsLong term - gallstones gastritis
210
What are some of the complications of diabetes in pregnancy ?
Congenital malformationPrematurityIntra uterine growth retardation--------------------------------------MacrosomiaPolyhydramniosIntra uterine death
211
What test is performed to diagnose cushings?
Dexamethasone suppression this leads to low cortisol but in cushings it will still be high (>100nmol/L)
212
What is the drug treatment for cushings ?
Metyrapone if other treatments fail, while waiting for radiotherapy to work KetoconazolePasireotide - new somatostatin analogue
213
What happens if pan hypopituitarism affects the anterior pituitary?
GH failureTSH suppression LH/FSH - hypogonadism ACTH- hypo adrenal Prolactin - none known
214
What happens if pan hypopituitarism affects the posterior pituitary?
Diabetes insipidus
215
What local brain tumours can cause hypopituitarism?
Pituitary ones, astrocytoma, meningioma, glioma
216
What are some symptoms and signs of anterior hypopituaitrism ?
Menstrual irregularity Infertility, impotenceGynaecomastiaAbdominal obesityLoss of facial hairLoss of axillary and public hair Dry skin and hair Hypothyroid faces Growth retardation in children
217
What does the growth hormone do in adults?
Improves well being and QOLDecreases abdominal fatIncreases muscle mass, strength, exercise capacity and stamina Improves cardiac function Decreases cholesterol and increases LDL Increases bone density Given by daily subcutaneous injection
218
How is testosterone replacement administered
IM injection every 3-4 weeks Or skin get Or a prolonged IM injection 10-14 weeks Oral tablets
219
What are the risks of testosterone replacement ?
Prostate enlargement- does not cause prostate cancer but it may make it grow, monitor PR exam and PSA Polycythaemia - monitor FBC Hepatitis (only for oral tablets) - monitor LFTs
220
What are some of the causes of cranial diabetes insipidus?
Familial AcquiredRare - tumour, sarcoid, ext radiation, meningitis
221
How do you treat diabetes insipidusL
Desmopressin oral, sublingual or injection or spray
222
How is cushings characterised?
Thin skin, prox myopathy, frontal balding in women, conjunctival oedema (chemosis), osteoporosis
223
Outline the regulation of cortisol/androgen production
Hypothalamus releases corticosteroid releasing hormone in response to stress, illness, time of day ---> goes into anterior pituitary which then releases ACTH to the adrenal cortex which then releases cortisol
224
What does angiotensin II do?
Vasoconstriction and indirect methods of BP elevation
225
What is the mechanism of action of corticosteroids?
They bind intracellular receptors Receptor/ligand complex binds DNA to affect transcription 6 classes of steroid receptors - glucocorticoid, mineralocorticoid, progestin, oestrogen, androgen, vitamin d
226
How does cortisol affect the CNS.
Involved with mood - euphoria, psychosis, decreased libido
227
How does cortisol affect bone or connective tissue?
Accelerates osteoporosis, low calcium, less collagen, less wound healing,
228
How does cortisol affect the immunological system?
Less capillary dilatation/permeabilityLess leucocyte migrationLess macrophage activity Less inflammatory cytokine production
229
What has cortisol got to do with the circulatory/renal system ?
Increases COIncreases BPIncreases renal blood flow and GFR
230
What has cortisol got to do with the metabolic system?
Increases blood sugarIncreases lipolysis, central redistribution Increases proteolysis
231
When are corticosteroids used clinically?
Suppress inflammation Suppress immune system Replacement treatment
232
What other autoimmune diseases are associated with Addison's disease?
T1DM, autoimmune thyroid disease, pernicious anaemia
233
How do you diagnose adrenal insufficiency?
Suspicious biochemistry - low Na, high K. Hypoglycaemia Short synACTHen test Raised ACTH Increased renin levels, low aldosterone Adrenal autoantibodies
234
What is the short synACTHen test?
Measure plasma cortisol before and 30 minutes after IV ACTH injection Normal: baseline >250nmol/L, post ACTH >480
235
What is the treatment for Addison's disease ?
Hydrocortisone 15-30mg daily in divided doses Try to mimic diurnal rhythm Fludrocortisone as aldosterone replacement - careful monitoring of BP and K Need to know sick day rules
236
What is secondary adrenal insufficiency?
Lack of CRH or ACTH Causes include: pituitary or hypothalamic disease, tumours, surgery, radiotherapy, trauma, exogenous steroid use,
237
What are the clinical features of secondary adrenal insufficiency?
Similar to Addison's disease BUT they have pale skin as they have no ACTH and aldosterone production is in tact
238
How do you diagnose Cushing's syndrome.
Overnight dexamethasone suppression test24 hour urinary free cortisol Late night salivary cortisolLow dose dexamethasone suppression test
239
Hypertension + hypokalaemia...
= primary aldosteronism
240
What is primary aldosterinism ?
Autonomous production of aldosterone independent of its regulators (potassium/angiotensin II)
241
How does aldosterone act on the cardiovascular system?
Increases cardiac collagen Increases BP, LVH, atheroma Sodium retention Increase sympathetic outflow
242
How do you diagnose primary aldosteronism?
Confirm excess - measure plasma aldosterone and renin and express as ratio (ARR-aldosterone to renin ratio) if ratio > 750 then investigate further with saline suppression test Step two - confirm subtype - adrenal ct ?adenoma
243
What is the commonest congenital adrenal hyperplasia?
21alpha hydroxylase deficiency Autosomal recessive
244
How does CAH present in males?
Adrenal insufficiency -often around two or three weeks oldPoor weight gainBiochemical pattern
245
How does CAH present in females.
Genital ambiguity
246
What are some clues to phaeochromocytoma?
Labile hypertension Postural hypotension Paroxysmal sweating, headache, pallor, tachy Or none!
247
What are some signs of phaeochromocytoma complications?
LVF, myocardial necrosis stroke, shock, paralytic ileus of bowel
248
What is the approach to phaeochromocytoma therapy?
Full alpha and beta blockade - phenoxybenzamine, atenolol or metoprololFluid and or blood replacement Careful anaesthetic assessment
249
What syndromes are associated with phaeo's?
MEN IIVon-Hippel-LindauSuccinate dehydrogenase mutations Neurofibromatosis Tuberose sclerosis
250
How is MEN II inherited.
Autosomal dominant.
251
What regulates aldosterone?
Renin - angiotensin system and plasma potassium
252
What are the Trophic hormones ?
TSH, ACTH, FSH, LH
253
What are the non Trophic hormones?
GH and prolactin
254
What does the posterior pituitary secrete?
ADH and oxytocin
255
Where does anterior pituitary come from?
Rathke's pouch
256
Where does the posterior pituitary come from?
Extension of neural tissue consists of modified glial cells and axonal processes
257
What cells are in the posterior pituitary ?
Non myelinated axons of neuro secretory neurons
258
What could hyper function of the anterior pituitary indicate?
Adenoma or carcinoma
259
What could hypo function of the anterior pituitary indicate.
Surgery/radiationSudden haemorrhage into gland Ischaemic necrosis - sheehans syndrome Tumours extending into sella Inflam conditions - e.g. Sarcoidosis
260
What disease affects the posterior pituitary ?
Diabetes insipidus - lack of ADH secretionSiadh - ectopic secretion of ADH by tumours
261
Briefly outline a pituitary adenoma
Derived from cells of anterior pituitary Sporadic or MEN1 Micro adenomas 1cm
262
How do you classify pituitary adenomas ?
By cell type or by what they are producing I.e. Prolactin (20-30%) They can produce more than one They can be hypo or non functional
263
What can large adenomas cause?
Visual field defects Pressure atrophy or surrounding normal tissue Infarction can lead to pan hypopituitarism
264
What does a prolactinoma cause?
Infertility, lack of libido, amenorrhea, galactorhea weight gain
265
What is the management for a prolactinoma?
Dopamine agonists are first line I.e. Bromocriptine Trans-sphenoidal surgery if this is not tolerated and if it is bigger it may need cut out then too
266
What can a growth hormone secreting tumour lead to?
Causes an increase in insulin like growth factor Stimulates growth of bone, cartilage and connective tissue Gigantism or acromegaly
267
What can an ACTH secreting tumour lead to?
Cushings It is usually a micro adenoma
268
What may cause pituitary hypofunction?
Primary or metastatic tumoursTraumatic brain injury Subarachnoid haemorrhage Surgery or radiationGranulomatous inflammationInfarction/haemorrhage I.e. Sheehans syndrome, apoplexy (EMERGENCY) Hypothalamic lesions
269
What is apoplexy?
Bleed within pituitary Causes headache, Diplopia, (pressure on CNIII) hypopituitarism, cardiovascular collapse and loss of consciousness
270
What is a craniopharyngioma?
Derived from the remnants of rathkes pouch Slow growing, often cystic, may calcify 5-15years of age and then 6th-7th decades of life Excellent prognosis ESP if less than 5cm Following radiation SCC may develop
271
What are the three zones of the adrenal cortex?
Zona glomerulosa, zone fasciculata, zone reticularis
272
What is produced in zona glomerulusa.
MineralocorticoidsAldosterone
273
What is produced in zona fasciculata?
GlucocorticoidsCortisol
274
What is produced in zona reticular is?
Sex steroidsGlucocorticoids
275
How is the adrenal medulla innervated?
By pre-synaptic fibres from the sympathetic nervous system
276
What do neuroendocrine/chromaffin cells secrete?
Catecholamines
277
What can cause hyper function of the adrenals ?
HyperplasiaAdenomaCarcinoma
278
What causes hypofunction of the adrenals?
Acute - Waterhouse friderichsen Chronic - Addison's
279
What is congenital adrenoxortical hyperplasia?
Groupmof autosomal recessive disorders There is a deficiency or lack of the enzyme required for steroid synthesis Leads to increased androgen production - masculinisation, precocious puberty Reduced cortisol stimulates ACTH release and cortical hyperplasia
280
What is acquired adrenocortical hyperplasia?
Endogenous ACTH production - pituitary adenoma, ectopic ACTH as a paraneoplastic syndrome from perhaps small cell lung carcinoma Bilateral adrenal enlargement Diffuse or nodular (diffuse is ACTH driven whereas nodular is usually indecent of ACTH )
281
How May an adrenocortical tumour present?
Mainly in adultsIncidentalHormonal effects Mass lesion Carcinomas with necrosis can cause fever
282
What is an adrenocortical adenoma like?
Well circumscribed, encapsulated lesionsUsually small -up to 2/3cm Yellow, yellow-brown Well differentiated, small nuclei, rare mitosesCan be functional but more likely not
283
What are adrenocortical carcinomas like?
Rare More likely to be functional and they are usually malignant Can closely resemble adenoma Local invasion - retroperitoneum, kidneyMetastasis is usually vascular 50% dead in two years
284
What factors may point towards carcinoma instead of adenoma?
Carcinoma - large, haemorrhage and necrosis, frequent mitoses, atypical mitoses, lack of clear cells, capsular or vascular invasion
285
What is primary hyperaldosteronism?
Conns syndrome Adenoma rarely carcinoma Usually associated with diffuse or nodular hyperplasia of both adrenal glands
286
What can cause primary adrenocortical insufficiency?
Acute - rapid withdrawal of steroids, infection, massive adrenal haemorrhage Chronic - Addison's: 3 common causes - autoimmune, infections (TB etc), metastatic malignancy
287
What are same symptoms seen with Addison's?
Weakness, fatigue, vomiting, weight loss, diarrhoea, pigmentation, hyponatraemia, hyperkalaemia, hypoglycaemia, hypotension
288
What are two adrenal medullary tumours ?
PhaeochromocytomaNeurobladtoma
289
When would someone often get neuroblastoma.
Usually diagnosed around 18months, 40% diagnosed in infancy
290
What type of cells make up neuroblastoma?
Composed of primitive appearing cells but they can show maturation and differentiation towards ganglion cells
291
Where does a phaeochromocytoma arise from?
A neoplasm derived from chromaffin cells of the adrenal medulla Secretes catecholamines Rare cause of secondary hypertension
292
How is phaeochromocytoma diagnosed?
Lab - detects urinary excretion of catecholamines and metabolites
293
What are the complications of a phaeochromocytoma?
Cardiac failure, infarction, arrhythmias, CVA
294
Why is phaeochromocytoma known as the '10%' tumour?
10% extra adrenal (called paragangliomas) 10% are bilateral 10% are biologically malignant 10% are NOT associated with hypertension(25% are familial)
295
What are the tumours associated with MEN2A?
TAPThyroid (medullary) carcinoma Adrenal phaeochromocytomaParathyroid hyperplasia
296
What are the tumours associated with MEN2B?
PhaeochromocytomaMedullary thyroidNeuromas or ganglioneuromasMarfanoid habitus
297
What are the tumours associated with MEN1?
Pituitary prolactinoma Pancreas Parathyroid 3 P's
298
What does the anterior pituitary secrete?
Trophic and non Trophic hormones
299
What are some examples of steroids with mineralocorticoid ?
Aldosterone (this is the main one) and cortisol and some others
300
What does too much mineralocorticoid activity do?
Leads to sodium retention and too little activity means sodium loss
301
What does sodium loss lead to?
WATER LOSS
302
Where is ADH or vasopressin released from?
By the posterior pituitary in response to osmotic and non osmotic stimuli
303
Where does ADH act.
On renal tubules to cause water resorption and thus anti diuretic effectIncreased ADH - concentrated urine Less ADH - dilute urine We assess this as urine osmolality
304
Why does Addison's lead to hyponatremia?
Adrenal insufficiency -> can't make enough steroids -> doesn't have enough mineralocorticoid activity -> can't retain enough sodium in kidneys -> loses sodium and water with it from ECF -> lower ECF volume means patient is clinically dehydrated
305
What can you attribute the symptoms of dizziness in Addison's to?
Low ECF gives hypotension
306
Why does someone with Addison's get excess pigmentation ?
Excess ACTH from pituitary
307
What is a typical presentation of diabetes insipidus?
Excess urine output Fluid requirement very large
308
What is the basic problem with diabetes insipidus ?
Disruption of pituitary or stalk -> so patient can't secrete ADH from posterior pituitary -> no ADH to act on kidneys to cause water to be reabsorbed -> so lots of pure water lost in urine -> patient has high sodium -> exogenous ADH can be given to replace
309
Hypovoleamia in hyponatremia indicates what?
Too little sodium
310
If you suspect adrenal insufficiency I.e. Addison's then what do you do?
Measure cortisol and ACTH but if they are very unwell don't wait just give them sodium replacement
311
How is sodium controlled?
Mineralocorticoid activity - which means sodium retention in exchange for potassium and or hydrogen ions
312
What are some of the macrovascular complications of DM?
Stroke, renovascular disease, limb ischaemia, most heart disease
313
What causes T1DM?
Insulin deficiency from autoimmune destruction of pancreatic beta cells
314
What is T1DM associated with?
Other autoimmune diseases (>90% carry HLA DR3 +/- DR4)
315
What is LADA?
Latent autoimmune diabetes of adults
316
T1DM - there is a higher prevalence in...
Asians, men, the elderly
317
What is the cause of t2dm?
Lower insulin secretion and increased insulin resistance - associated with obesity, lack of exercise, calorie and alcohol excess
318
What is IGT?
Impaired glucose tolerance, fasting plasma glucose 7.8 mmol/L but <11.1mmol/L (manage with lifestyle advice)
319
What is IFG.
Impaired fasting glucose. Fasting glucose >6.1mmol/L but <7 mmol/L (manage with lifestyle advice)
320
How do you perform an OGTT?
Fast overnight. Give 75mg of glucose in 300ml water to drink in the morning. Measure venous plasma glucose before and 2h after the drink
321
What can differentiate T2DM and T1DM?
T1DM - weight loss, persistent hyperglycaemia despite diet and medication, presence of autoantibodies, islet cell antibodies, GAD antibodies, ketonuria on dipstick
322
What other conditions can cause DM?
Steroids, anti-HIV drugs, newer antipsychotics, thiazides, pancreatitis, pancreatic cancer, surgery where 90% pancreas is removed, pancreatic trauma, pancreatic destruction (haemochromatosis, CF) cushings, acromegaly, phaeochromocytoma, hyperthyroidism, pregnancy, acanthosis nigricans, congenital lipodustrophy, glycogen storage diseases
323
Outline gestational diabetes
4% of pregnancies, risk increased if aged over 25, +ve FHx, fat, non-Caucasian, HIV+ve. Can cause increased birthweight, neonatal hypoglycaemia, sacral agenesis. Do another ogtt 6wks after birth (on mother)
324
What are some of the mechanisms of insulin resistance?
Obesity may cause insulin resistance by increased rate of release of non-esterified fatty acids, causing post-receptor defects in insulting action. Mutation of genes encoding insulin receptors. Circulating autoantibodies to the extracellular domain of the insulin receptor
325
What are some of the biological effects of insulin?
Amino acid uptake in the muscle, DNA synthesis, protein synthesis, growth responses, glucose uptake in muscles and adipose tissue, lipogenesis in adipose tissue and liver, glycogen synthesis in liver and muscle
326
With regards to severe insulin resistance, T2DM is...
Polygenic in nature, large environmental influences,
327
What is leprechaun-Donahue syndrome?
Rare autosomal recessive genetic trait. Mutations occur in the gene for insulin receptor causing severe insulin resistance - elfin features, growth retardation, absence of subcutaneous fat and decreased muscle mass.
328
What are the risk factors for T2DM?
Central obesity FHGestational DMAgeEthnicity (Asian, African, Afro-Caribbean)PHx of MI or stroke Medications like antipsychotics IGT/IFG
329
What are useful tests to distinguish between type one and type two DM.
GAD or anti-islet cell antibodies KetonesC-peptide (plasma)
330
What causes type three diabetes?
Pancreatic disease, other endocrine disease, drug induced (glucocorticoids etc), genetic diseases,
331
What is type four diabetes.
Gestational
332
What are the complications?
Heart disease and stoke Retinopathy nephropathy, neuropathy Psychiatry, psychology
333
How do you diagnose T1DM?
Fasting glucose >7Random >11.1 And symptoms
334
What HLA types are most susceptible to T1DM?
DR3-DQ2/DR4-DQ8
335
When would you suspect LADA ?
Occurs in young adults aged 25-40Male preponderanceUsually non-obeseAuto-antibody positive Associated autoimmune conditions Non insulin requiring at diagnosis
336
What is DIDMOAD or wolfram?
DIDMoptic atrophy DeafnessNeurological abnormalities
337
What is bardet-biedl syndrome ?
Often v obese Polydactyly HypogonadalVisual impairment Hearing impairment Mental retardationDiabetesConsanguineous parents
338
What other autoimmune conditions are associated with t1dm
Addison'sThyroidVitiligoCoeliac and some others
339
How is MODY inherited?
Autosomal dominant It is a non insulin dependent diabetes and age of onset is usually before age 25
340
What can cause MODY ?
Glucokinase mutations - onset at birth, stable hyperglycaemia, diet treatment Transcription factor mutations - adolescence, progressive hyperglycaemia, frequent complications (>75%) HNF mutationsResponds well to gliclazide
341
What insulin regime is recommended?
Basal bolus aims to mimic normal endogenous insulin production Rapid acting can be altered according to the amount and type of food intake
342
What is an insulin pump ?
A medical device - continuous administration of short acting insulin subcutaneously Delivers background insulin by basal rate Delivers manually insulin when meals are eaten
343
What is a DKA?
Am absolute or relative insulin deficiencyAccompanied by an increase in the counter regulatory hormones - I.e. Glucagon, adrenaline, cortisol and GH
344
What are some common precipitate to a dka ?
InfectionIllicit drugs and alcohol Non compliance with treatment Newly diagnosed DM
345
What are the three things needed to diagnose a dka ?
Ketonaemia - >3mmol/L or significant ketonuriaBlood glucose >11.0 or known DMBicarbonate <7.3
346
What may you see on biochem of someone with a dka?
High glucoseHyperkalaemia High creatinine Hyponatremia High lactate High ketones Bicarbonate low
347
Why does ketonuria persist after clinical improvement in a dka ?
Because ketones are being mobilised from fat tissue still
348
What is normal lactate range?
0.6 to 1.2 mmol/L
349
Where does lactate come from?
Red cellsSkeletal muscleBrain and renal medulla
350
What does clearance of lactate require?
Hepatic uptake and aerobic conversion to pyruvate and then glucose
351
How is lactic acidosis classified?
Type A - associated with tissue hypoxaemia: infarct end tissue e.g. Ischameic bowel, cardiogenic shock, hypovolaemic shock Type B - may occur in liver disease, ass with drug therapy I.e. Metformim
352
What may you see clinically with lactic acidosis?
HyperventilationMental confusionStupor or coma if severe
353
What are the lab findings with lactic acidosis ?
Reduced bicarbonateRaised anion Gap [(Na + K) - (HCO3 + Cl)] Absence of ketonaemia Raised phosphate
354
What features may you see with hyperglycaemic hyperosmolar syndrome?
Diabetes may be known, maybe not Usually older people or younger if not Caucasian
355
Hat is the biochemistry like with HHS?
Higher glucose than dka Significant renal impairment Sodium often raised on admissionSignificant elevation of osmolality Less ketonaemic or acidotic as compared to DKA
356
Why are fluids given slowly with HHS ?
To prevent cerebral oedema, insulin is also given slowly as they may be more sensitive
357
What are some of the microvascular complications of DM?
Retinopathy, nephropathy, neuropathy
358
When is bariatric surgery offered?
BMI>40 unless they have a co morbidity in which case it is bmi>35
359
What is a roux en y gastric bypas?
Duodenum is bypassed and the gastric pouch formed leads straight to the jejunum
360
What is an adjustable gastric band?
Creates a smaller stomach pouch, slows down food ingestion and causes satiety sooner.
361
What is vertical sleeve gastrectomy?
Some of he stomach is removed creating almost an entire tube
362
What is adaptive thermogenesis?
Means by which weight loss is hard to sustain - body sees drastic weight loss as a threat to survival so it causes you to eat more, lowers the bmr
363
What does oralistat do?
Inhibits action of lipase on fat molecules so that they can't be broken down and absorbed so up to 1/3 of all ingested fat is excreted into faeces causing steatorrhea
364
Give an example of a biguanide
Metformin
365
Give an example of a sulphonylurea
Gliclazide, gilbenclamide, gilmeparide,
366
Give an example of a thiazolidinedione
Pioglitazone, rosiglitazone
367
Name the ways in which therapies for T2DM act. State if they are insulin dependent or independent
Increasing insulin secretion - eg sulphonylureas, incretin mimetics, DPP-4 inhibitors (insulin dependent action) Decreasing insulin resistance and reducing hepatic glucose output- eg biguamides, tzds, - INSULIN DEPENDENTSlowing glucose absorption from GI tract - eg alpha glucosidase inhibitors - insulin independent action Enhancing glucose excretion by the kidneys - sglt2 inhibitors - insulin inhibitors
368
How do sulphonylureas act?
They act on SUR1 subunits of the KATP channel. They close the channel causing depolarization of the beta cell and insulin release independent of plasma glucose concentration.
369
Which other types of drugs act like sulphonylireas?
Glinides
370
How do incretin analogues work?
They mimic the action of GLP-1 but are longer lasting. Binds to GPCR GLP-1 receptors that increase intracellular cAMP concentration. Increases insulin secretion, slows gastric emptying, decreases appetite
371
The actions of GLP-1 and GIP are very rapidly terminated by what?
The enzyme DPP-4. Thus the action of DPP-4 inhibitors (eg sitagliptin)
372
How do alpha glucosidase inhibitors work?
Inhibiting the action of alpha glucosidase to break down dietary carb into absorbable glucose
373
How does metformin work?
Reduces hepatic gluconeogenesis, by stimulating AMP-activated protein kinase. Increases glucose uptake and utilization by skeletal muscle. Reduces carb absorption, increases fatty acid oxidation
374
What do TZDs do?
Enhance the action of insulin at target tissues. Act as exogenous agonists of PPARy which associates with RXR. PPARy is largely confined to adipocytes. This activated complex acts as transcription factor that binds to DNA and promotes the expression of genes encoding several proteins involved in insulin signalling.
375
What do sglt-2 inhibitors do?
Act to selectively block reabsorption of glucose by sglt2 in prox tubule to cause glucosuria. Causes decrease in blood glucose. Calorific loss.
376
Who should be given sulphonylureas as first line treatment?
In patients who are not overweight, who are intolerant of or have contraindications to metformin
377
When should pioglitazone not be used?
In pts with heart failure (also risk of fracture in female pts in the long term should be considered)
378
When should GLP-1 agonists be used?
To improve glycemic control in obese adults with type 2 diabetes who are already prescribed metformin and or sulphonylureas (usualy third lien)
379
Do you stop these drugs when insulin is initiated ?
Not when it is initiated should metformin and sulphonyoureas be stopped In this case once daily bedtime insulin is used
380
Give some examples of sulphonylureas?
Gliclazide, glibenclamide, glimeparide
381
What are some examples of TZDs?
PioglitazoneRosiglitazone
382
How is metformin given?
It comes from French lilacs! Usually start with 500mg od or bd
383
Can you sue metformin in pregnancy..
Yes
384
What are the adverse effects of metformin?
GI - anorexia, nausea, d and v, abdo pain, funny tasteInterference with vitamin b12 and folic acid absorption Lactic acidosis - can be fatal Liver failureRash
385
When should you be cautious with metformin ?
In pts with history of acute heart failure, sepsis, acute mi etc If EGFR <30 or serum creatinine is above 150 Half dose if EGFR is between 30 and 45 TEMPORARILY STOP IT IF IV CONTRAST IS BEING USED e.g. Angiography, CT scan Discontinue if advanced cirrhosis or liver failure, or if at risk if lactic acidosis
386
Which ones are the insulin "secretagogues" ?
Sulphonylureas
387
Do sulphonylureas prevent macrovascular complications?
No but they prevent the micro ones
388
What are the adverse effects of SUs?
Cause weight gain GI upset, headacheAVOID IN SEVERE RENAL OR HEPATIC FAILURE
389
What do TZDs do to someone's weight?
Increase is inevitable Due to an increase in subcutaneous not visceral fat and fluid retention this fluid retention doubles risk of having heart failure
390
What are incretin analogues ?
Intestinal secretion of insulin GIP from K cells and GLP-1 from L cells
391
What are the benefits of GLP-1 receptor agonists.
Promote insulin secretion from the pancreas without hypoglycaemiaSuppress glucagonDecrease gastric emptying - early satietyAct on hypothalamus - reduce appetite - resulting weight loss
392
What are the cons with GLP-1 receptor agonists?
Nausea, usualy resolves by 6-8 weeks Injectable Pancreatitis? Pancreatic cancer????
393
What are the '-gliptins'?
DPP-IV inhibitors
394
3 risks with sulphonylureas?
Potent Weight gainHypos
395
3 risks with TZDs
PotentWeight gainHeart failure, fractures
396
3 effects with DPP-IV inhibitors?
Weight neutralNo hypos??pancreatic cancer
397
3 effects with SGLT2 inhibitors?
Weight neutralNo hypos Thrush or UTI
398
Which drugs increase secretion of insulin?INSULIN DEPENDENT
Sulfonylureas, incretin analogues, glinides, DPP-4 inhibitors
399
Which drugs act to decrease insulin resistance and reduce hepatic glucose output ? INSULIN DEPENDENT
Metformin, TZDs
400
Which drugs act to slow glucose absorption in the GI tract? INSULIN INDEPENDENT
Alpha glucosidase inhibitors
401
Which drugs act to enhance glucose excretion by kidney?INSULIN INDEPENDENT
SGLT 2 inhibitors
402
When are glinides taken and why?
Taken before meals to reduce post prandial rise in blood glucose
403
What do GLP-1 and GIP do?
They are released from L cells in the ileum and K cells in the jejunum/duodenum They enter portal bloodThey enhance insulin release from pancreatic beta cells and delay gastric emptying They enhance glucose uptake and utilisation Decrease blood glucose (GLP-1s also decrease glucagon release from pancreatic alpha cells, decreased glucose production and thus decreased blood glucose)
404
What do incretin analogues do?
They mimic the action of GLP-1 but are longer lastingBinds to GPCR GLP-1 receptors that increase intracellular cAMP concIncrease insulin secretion, suppress glucagon secretion, slows gastric emptying, decreases appetite Reduces hepatic fat Admin subcutaneously
405
What terminates GLP-1 and GIP
DPP-4 enzyme
406
What do DPP-4 inhibitors do
They competitively inhibit the enzyme DPP four thus allowing GLP 1 and GIP to work more
407
What do alpha glucosidase inhibitors do?
They inhibit the enzyme alpha glucosidase which breaks down starch and disaccharides into absorbable glucose
408
How does metformin work?
Reduces hepatic gluconeogenesis and increases glucose uptake and utilisation by skeletal muscle Increases fatty acid oxidation
409
What are the main aims when treating T2DM?
Alleviate hyperglycaemic symptoms, improve glycemic control, minimise hypoglycaemia, minimise weight gain, increase weight loss, reduce micro and macrovascular complications
410
What must you do if you suspect an acute addisonian crisis?
Start treating immediately, (IV hydrocortisone, fluids and glucose)
411
Collapsing following 48h history of severe abdo pain, weakness and vomiting. Low BP, high RR, glucose low, HIGH POTASSIUM, LOW SODIUM?
Addisonian crisis. Can often be precipitated by an event such as acute concurrent illness (like the vomiting in the question) or stress, such as infection, trauma or surgery
412
What matters greatly when it comes to measuring basal blood levels?
Time, day and condition of measurement make great differences
413
When are basal levels particularly useful?
For systems with long half lives (e.g. T4 and T3, IGF-1, androstenedione, SHBG)
414
Why might measurement of stress related hormones prove difficult?
Patient may be stressed by hospitals or venepuncture
415
What is the indication for testing for short ACTH?
Diagnosis of Addison's disease, screening for ACTH deficiency
416
What are midnight salivary cortisol levels increasingly used to test for?
Cushings syndrome
417
How is endocrine function assessed - basically?
Measurement of hormone levels in blood (plasma or serum) and sometimes in other body fluids
418
What is the advice about diet?
Limit alcohol consumption - female -14 units. Male - 21 units. One unit is equal to half a glass of wine or a third of a pint of beer. Fewer if weight reduction is needed. Advise on a low fat/high fibre diet. Advise on a no added salt diet. Discourage consumption of low fat beers as they have a higher alcohol content.
419
What are the aims of dietary advice?
Provide knowledge of healthy eating, ensure optimal weight and reduce obesity, maintain blood glucose and lipids as near to normal as possible, to reduce the acute complications of DM ie hypo/hyper
420
What are the objectives of dietary advice.?
Tailor advice to suit needs taking into account eating habits, physique, occupation, culture, religion, To provide realistic advice, Provide dietary education, to allow patients to understand their diabetes and to achieve independence
421
What sort of advice could you give to the patient with their diet?
Have a look at the eat well plate. Take a look at the patient leaflet Encourage regular eating habits, Include low GI carb foods with each mealIncrease fruit and veg intake Reduce fat intake, replace saturated fat for unsaturated fat. Reduce salt, reduce sugar, safe and sensible alcohol consumption. Monitor weight.
422
How can weight loss improve prognosis in T2DM?
Improves insulin sensitivity and glucose tolerance Aim for weight loss of 5-10%
423
What can be done for people with BMI>30?
If they are motivated to address their weight then the tayside adult weight management service can help them (not diabetes specific)
424
Why does having three meals help?
Helps control appetitie and keeps blood glucose levels steady. If you need to eat between to maintain blood glucose levels then something like fruit, plain biscuits, scone or toast
425
What kind if carb should they have in every meal?
High fibre, low in fat, eg whole grain breakfast cereals like weetabux, potatoes, lentils, beans, broth, rice, pasta, whole grain bread.
426
Hat about sugar? What can they switch!
Have plain biscuits, diet coke etc low sugar foods
427
How much fruit and veg is recommended?
2-3 portions of veg or salad per day 2-3 portions of fruit per day
428
What is omega three good for?
Protects against heart disease. Found in oily fish like salmon, mackerel herring, fresh tuna.
429
Hat weight loss should they aim for?
Something realistic like 1-2lb per week
430
What can be done for smoking cessation?
Offer NRT - varenicline or bupropion (only sufficient prescription for two weeks after target stop date) don't offer within six months if it's failing and looks like it will continue to fail Target stop date Offer patches, gum, lozenge, inhaler
431
Will NRT work alone?
Most effective with behavioural therapy alongside
432
What are some of the cautions of NRT?
Severe CVD, recent cerebrovascular event, peripheral vascular disease, hyperthyroidism, DM, Phaeochromocytoma, Renal impairment, hepatic impairment, gastritis and peptic ulcers
433
What kind of advice can be given to T2DM?
DESMOND - diabetes education and self management for ongoing and newly diagnosed,
434
What can regular exercise help with?
Improves with insulin resistance and lipid profile (increases good cholesterol, lowers BP) 30 mins on at least five days of the week
435
What should be considered before they undergo exercise?
Consider insulin/oral hypoglycaemic therapy and meal schedule. Test BM before exercise, add snack if needed Autonomic neuropathy? - silent ischaemia, postural hypotensionPeripheral neuropathy?- numbness parasthesiae PVD - claudication, leg ulcers, Emphasise foot care
436
When is exercise contra indicated!
If there is active retinal haemorrhage or recent retinal photo coagulation
437
How would you manage the exercise?
Formal recording of levels, ID of new exercise opportunities, apt self monitoring, additional carb etc
438
When will changes in lifestyle be more likely to occur?
If the person is doing it with family or friends - has someone else to do it with
439
What is secondary adrenal insufficiency?
Most commonly due to a pituitary problem, a hypo functioning pituitary can result in a lack of ACTH production in turn resulting in a lack of drive for the adrenal glands to produce glucocorticoids and mineralocorticoids and adrenal atrophy
440
What is primary adrenal insufficiency?
Usually due to something like Addison's disease - autoimmune attack on the adrenal glands. Anti adrenal antibodies are usually elevated. This may also be caused by infective, structural and infiltrative conditions too such as TB, cancer, AIDS, amyloidosis, genetic defects
441
What are the signs of hypothyroidism?
The mnemonic BRADYCARDIC. B- bradycardiaR- reflexes relax slowlyA- ataxia (cerebellar)D- dry thin hair/skinY- yawning, drowsy, comaC-cold handsA- ascites and/or pitting oedema and or pericardial/pleural effusionR-round puffy face/double chin/obeseD- defeated demeanour I- immobile+/- ileusC-CCF Also - neuropathy, myopathy, goitre,
442
How is hypothyroidism diagnosed?
Increased TSHLow free T4Or in rare secondary hypothyroidism they are both low ie pituitary causes
443
What are the autoimmune causes of hypothyroidism?
Primary atrophic hypothyroidism - common, mostly women, diffuse lymphocytic infiltration of the thyroid, leading to atrophy - hence NO GOITREHashimoto's thyroiditis- goitre due to lymphocytic and plasma cell infiltrate, commoner in women aged 60-70, may be hypo thyroid or euthyroid- autoantibody titres are very high
444
What are some other cause of hypothyroidism?
Iodine deficiencyPost-thyroidectomy/radio iodine treatmentDrug inducedSubacute thyroiditis - temp hypothyroidism following hyper.Secondary - hypopituitarism
445
What drugs can induce hypothyroidism?
antithyroid drugs, amiodarone, lithium, iodine
446
What other illnesses are associated with hypothyroidism?
Turners, downs, CF, primary biliary cirrhosis, ovarian hyperstimulation, POEMS syndrome - Polyneuropathy, Organomegaly, Endocrinopathy, M-protein band, Genetic - dyshormonogenesis
447
What problems are associated with hypothyroidism and pregnancy?
Eclampsia, anaemia, prematurity, low birthweight, stillbirth, PPH(postpartum haemorrhage)
448
WHat is the treatment for hypothyroidism in young healthy people?
Levothyroxine (T4) - 50-100micrograms /24h PO review at 12 weeksAdjust 6 weekly by clinical state and to normalise, not suppress TSHOnce normal - check TSH annually
449
What is the treatment for hypothyroidism in the elderly or those with ischaemic heart disease?
Start with 25micrgrams levothyroxine /24h and increase dose by 25micrograms every 4weeks according to TSH
450
Why is caution advised with Levothyroxine and the elderly/ischaemic heart disease pts?
Thyroxine may precipitate an MI or angina
451
What is wrong with amiodarone thyroid wise?
Iodine rich drug structurally like T4 2% users get significant thyroid problems with it Hypothyroidism caused by toxicity from iodine excess which inhibits T4 release inhibitedA thyrotoxicosis may be caused by a destructive thyroiditis causing hormone release, radio iodine can be undetectable here and glucocorticoids might help. Get expert help.
452
What is myxedema?
THIS IS CONFUSING - either it is severe hypothyroidism e.g. Myxedema coma, OR an accumulation of hydrophilic mucopolysaccharides in the ground substance of the dermis and other tissues I.e. Pretibial myxoedena in GRAVES DISEASE IE, THYROTOXICOSIS
453
What would cause Goitrous hypothyroidism?
Hashimotos, iodine deficiency, drug induced
454
What would cause non Goitrous hypothyroidism?
Atrophic thyroiditis, post-ablative, post radiation
455
How can you confirm hashimotos?
Presence of thyroid peroxidase antibodies in blood T cell infiltrate and inflammation on microscopy
456
What may you see with myxoedema coma?
Bradycardia, heart block, t wave inversion, prolongation of QTT2 resp failure, hypoxia, hypercarbia, resp acidosis
457
How do you treat myxoedema coma?
Intensive carePassively reward Cardiac monitoring for arrhythmias Monitor BP, CVP oxygenation, urine output, blood glucose levels Fluids, fluid restrict, electrolyte balance Broad spec antibiotics Thyroxine cautious
458
What are the symptoms of hypothyroidism?
Tired, sleepy, lethargic, low mood, disliking the cold, weight gain, constipation, menorrhagia, hoarse voice, loss of memory, low cognition, dementia, myalgia, cramps, weakness
459
What are the two phases of the menstrual cycle?
Follicular phase and luteal phase
460
What is the follicular phase?
1st half Maturation of egg, ready for ovulation at mid cycle - ovulation signals end of follicular phase
461
What is the luteal phase?
2nd half of cycle Development of corpus luteum Induces preparation of reproductive tract for pregnancy if fertilisation occurs
462
HOw many eggs will be ovulated?
About 400
463
What does the corpus luteum secrete?
Progesterone (oestrogen is secreted in the follicular phase and progesterone is secreted in the luteal phase)
464
What signals the start of a new follicular phase ?
Degeneration of corpus luteum
465
What does the hypothalamus secrete with regards to ovulation? What happens with it?
It secretes GnRH which acts on the anterior pituitary. Which then secretes FSH and LH
466
WHat does FSH do?
Acts on ovary to stimulate development of follicles FSH and LH stimulate secretion of oestradiol and ovulation
467
What does LH do?
Acts on ovary Stimulates follicle maturation, ovulation and development of the corpus luteum
468
What does oestradiol do.
Thickens endometrium and thins cervical mucous
469
What does oestrogen suppress.
Suppresses FSH production by the anterior pituitary
470
What do the high levels of oestrogen at the mid cycle cause the hypothalamus to do?
Release GnRH
471
What do theca cells do?
They convert androgen to oestrogen
472
If pregnancy occurs, what does the developing embryo do?
Produces HCG (chorionic gonadotropin) which maintains the corpus luteum progesterone is also produced to support pregnancy and suppress ovulation
473
What does LH do with sperm?
LH stimulates testosterone secretion Testosterone decreases the release of GnRH and LH
474
When is a surgical sperm aspiration indicated.
For azoospermia
475
How long does oogenesis take?
Many years to complete, begins in utero and is suspended for many years begins again at puberty
476
What is secondary amenorrhea?
Cessation of periods for more than six months in a person who has previously menstruated
477
What syndromes could cause primary amenorrhea ?
Turners syndrome Kallmans syndrome
478
WHat is kallmans syndrome?
Failure to start puberty or failure to fully complete it Hypogonadotropic Hypogonadism Infertility Anosmia or hyposmia It occurs when the hypothalamic neurones responsible for releasing GnRH fail to migrate into the hypothalamus during embryonic development
479
What could cause secondary amenorrhea?
Ovarian problem - POF, Pcos Uterine problem - uterine adhesions Hypothalamic dysfunction - weight loss, over exercise, stress, infiltrativePituitary - high PRL, hypopituitarism
480
What would you like to establish in the history?
Symptoms of oestrogen deficiency - flushing, libido, dyspareuniaHypothalamic probs- exercise, weight loss, stress Features of pcos/androgen excess - hirsuitism/acne Anosmia? Kallmans?Symptoms of hypopituitarism/pituitary tumour including galactorrhea ?drugs associated with hyperprolactinaemia
481
What would you like to know in the examination ?
Body habitus ?turners Visual fields? Anosmia? Breast developmentHirsutism/acne/androgen excess
482
How should you investigate a pt with oligo/amenorrhea?
All should receive LH, FSH, oestradiol, TFTs, prolactin Additional investigation - ovarian ultrasound +/- endometrial thickness Testosterone if hirsutism Pituitary function tests + MRI pituitary if hypothalamic pituitary problems suspected Karyotype if primary amenorrhea or features of turners syndrome
483
How is female hypogonadism identified ?
Low oestrogen levels
484
What is primary hypogonadism?
Problem with the ovaries High LH/FSH - hypergonadotrophic hypogonadism E.g. POF
485
What is secondary hypogonadism?
Problem with hypothalamus or pituitary Low LH/FSH - hypogonadotrophic hypogonadism E.g. High PRL, hypopituitarism
486
What is POF ?
Amenorrhea, oestrogen deficiency, elevated gonadotrophins occurring <40years old as a result of loss of ovarian function Test FSH twice at least one month apart
487
What can cause POF?
Chromosomal abnormalities - turners syndrome, fragile XGene mutations. - e.g. FSH receptor, LH receptorAutoimmune diseases - e.g. Association with Addison's disease, thyroid, APS1/2 Iatrogenic - radiotherapy, chemotherapy
488
What can cause functional hypothalamic amenorrhea?
Weight change, stress, exercise, anabolic steroids, systemic illness, iatrogenic, recreational drugs, head trauma, infiltrative disorders e.g. Sarcoidosis
489
Briefly outline Kallmans syndrome ?
Genetic heterogeneity, normal MRI pituitary - absence of olfactory bulbs - 75% have a loss of smell. Normal remainder of pituitary function
490
What can cause loss of LH/FSH stimulation as a result of pituitary dysfunction?
Non functioning pituitary macroadenoma (pressure effects lead to hypopituitarism) Empty sella Pituitary infarction
491
What can cause hyperprolactinaemia as a result of pituitary dysfunction?
Micro or macro prolactinomaDrugs e.g. Dopamine antagonists
492
What is the Rotterdam criteria?
Any two of : menstrual irregularity, hyperandrogenism (hirsutism etc), polycystic ovaries Are needed to diagnose PCOS
493
What is congenital adrenal hyperplasia?
CAH is an inherited group of disorders charcterised by a deficiency in one of the enzymes necessary for cortisol synthesis - 90% due to 21alpha-hydroxylase deficiency, some autosomal recessive, varied presentation Classic CAH is typically diagnosed in infancy Non classic presents in adulthood or adolescence
494
What is the treatment for PCOS.
Oral contraceptive- regulates cycle, decreases ovarian androgens Anti-androgens - cyproterone acetate -dianette Local anti androgens - efflornithine cream Cosmesis - electrolysis, laser phototherapy
495
What is the treatment for late onset CAH?
Low dose glucocorticoid to suppress ACTH drive
496
What are some of the classics features of turners syndrome ?
Short stature, webbed neck, shield chest with wide spaced nipples, cubitus valgus CVS- coarctation of the aorta, bicuspid aortic valve, hypo plastic left heartGI - bleed (vascular malformation), increased crohns and UC Other - lymphoedema, 10-30% Al hypothyroidism, osteoporosis, scoliosis, otitis media, 1/3 have renal abnormalities
497
How many couples are affected by infertility?
App 20%
498
When does estradiol peak?
Before ovulation
499
When does progesterone peak?
Following ovulation
500
What is the progesterone challenge test ?
A menstrual bleed in response to a five day course of progesterone - this indicates oestrogen levels are normal Would be negative with hypothalamic pituitary failure
