Endocrinology Flashcards
1
Q
What is the most common cause for primary hypoadrenalism in the UK?
A
Addison’s disease
2
Q
What is Addison’s disease?
A
- Autoimmune destruction of the adrenal glands
- Results in low cortisol and aldosterone.
3
Q
What are the key features of Addison’s?
A
- lethargy, weakness, anorexia, nausea & vomiting, weight loss, ‘salt-craving’
- hyperpigmentation (especially palmar creases)
- vitiligo
- loss of pubic hair in women
- hypotension
- hypoglycaemia
- hyponatraemia and hyperkalaemia may be seen
- crisis: collapse, shock, pyrexia
4
Q
What are some primary causes of hypoadrenalism?
A
- Addison’s
- Tuberculosis
- Metastases (e.g. bronchial carcinoma)
- Meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
- HIV
- Antiphospholipid syndrome
5
Q
What are some secondary causes of hypoadrenalism?
A
- pituitary disorders (e.g. tumours, irradiation, infiltration)
- exogenous glucocorticoid therapy
6
Q
What are the investigations for Addison’s disease?
A
- Short synACTHen test
- Adrenal autoantibodies e.g. anti-21-hydroxylase may be present
- 9 cortisol if synacthen not available (<100 abnormal, 100-500 prompt further testing).
7
Q
What electrolyte abnormalities are associated with Addison’s?
A
Hyperkalaemia
Hyponatraemia
Hypoglycaemia
Metabolic acidosis
8
Q
What are some causes of Addisonian crisis?
A
-Sepsis or surgery causing an acute exacerbation of chronic insufficiency (Addison’s, Hypopituitarism)
-Adrenal haemorrhage eg Waterhouse-Friderichsen syndrome (fulminant meningococcemia)
-Steroid withdrawal
9
Q
What is the management of Addisonian crisis?
A
- Hydrocortisone 100mg IV/IM
- 1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic
- continue hydrocortisone 6 hourly until the patient is stable. No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action.
- oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
10
Q
What antibodies are typically associated with Graves disease?
A
TSH receptor antibodies
(present in 90-100% of cases)
11
Q
What antibodies are associated with Hashimoto’s disease?
A
Anti-TPO antibodies
(present in 90% of cases)
12
Q
What are the treatment options for thyrotoxicosis?
A
- Propranolol to control sx e.g tremor
- Carbimazole
- Radioiodine treatment
13
Q
What is the mechanism of action of carbimazole?
A
blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin → reducing thyroid hormone production
14
Q
What is an important side effect of carbimazole?
A
Agranulocytosis
15
Q
What is Cushing’s disease?
A
pituitary tumour secreting ACTH producing adrenal hyperplasia
16
Q
What is Cushing’s syndrome?
A
Disorder that occurs when the body produces too much cortisol
17
Q
What are some ACTH dependent causes of Cushing’s?
A
- Cushing’s disease (80%): pituitary tumour secreting ACTH producing adrenal hyperplasia
- ectopic ACTH production (5-10%): e.g. small cell lung cancer is the most common causes
18
Q
What are some ACTH independent causes of Cushing’s?
A
- iatrogenic: steroids
- adrenal adenoma (5-10%)
- adrenal carcinoma (rare)
- Carney complex: syndrome including cardiac myxoma
- micronodular adrenal dysplasia (very rare)
19
Q
How do you differentiate between Cushing’s syndrome and Pseudo-cushings?
A
insulin stress test
20
Q
What tests are used to confirm Cushing’s Syndrome?
A
- Overnight (low-dose) dexamethasone suppression test
(this is the most sensitive test and is now used first-line to test for Cushing’s syndrome
patients with Cushing’s syndrome do not have their morning cortisol spike suppressed) - 24 hr urinary free cortisol
(two measurements are required) - bedtime salivary cortisol
(two measurements are required)
21
Q
What would be the findings on a dexamethasone suppression test that indicate cushing’s disease?
A
Cortisol and ACTH suppressed
22
Q
What would be the findings on a dexamethasone suppression test that indicate ectopic ACTH syndrome?
A
Cortisol and ACTH not suppressed
23
Q
What would be the findings on a dexamethasone suppression test that indicate Cushing’s syndrome not caused by cushing’s disease or ectopic ACTH syndrome?
A
Cortisol not suppressed
ACTH suppressed
24
Q
When should a SGLT-2 inhibitor be introduced in a patient diabetes and cardiovascular disease?
A
As soon as develop CVD, are at high risk of CVD or have heart failure even if their sugars are well controlled
25
What is the mechanism of action of sulphonylureas?
Bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells
26
What are common side effects of sulphonylureas?
hypoglycaemic episodes (more common with long-acting preparations such as chlorpropamide)
weight gain
27
What condition may show raised total T3 and T4 but normal fT3 and fT4?
Normal pregnancy
28
What are the features of polycystic ovarian syndrome?
- subfertility and infertility
- menstrual disturbances: oligomenorrhoea and amenorrhoea
- hirsutism, acne (due to hyperandrogenism)
- obesity
- acanthosis nigricans (due to insulin resistance)
29
What investigations are indicated in PCOS?
- pelvic ultrasound: multiple cysts on the ovaries
- FSH, LH, prolactin, TSH, testosterone, sex hormone-binding globulin (SHBG) are useful investigations
raised LH:FSH ratio is a 'classical' feature but is no longer thought to be useful in diagnosis
prolactin may be normal or mildly elevated
testosterone may be normal or mildly elevated, however, if markedly raised consider other causes, SHBG is normal to low in women with PCOS
- check for impaired glucose tolerance
30
What criteria is used to diagnose PCOS?
Rotterdam
31
How is PCOS diagnosed?
If any 2 of the following 3 are present:
- infrequent or no ovulation (usually manifested as infrequent or no menstruation)
- clinical and/or biochemical signs of hyperandrogenism (such as hirsutism, acne, or elevated levels of total or free testosterone)
- polycystic ovaries on ultrasound scan (defined as the presence of ≥ 12 follicles (measuring 2-9 mm in diameter) in one or both ovaries and/or increased ovarian volume > 10 cm³)
32
What cancer can be caused by unopposed oestrogen?
Endometrial
33
Which medication is used in stress incontinence when pelvic floor training has failed?
Duloxetine
34
What is the mechanism of action of Gliptins (DPP-4 inhibitors)?
reduce the peripheral breakdown of incretins such as GLP-1
35
What medication can be added to T1 diabetics who have a BMI of >25?
Metformin
36
How do you differentiate MGUS from myeloma?
absence of complications such as immune paresis, hypercalcaemia and bone pain
37
What are some causes of hypercalcaemia?
- Primary hyperparathyroidism
- Malignancy: myeloma, squamous cell lung ca, bone mets
- Sarcoidosis
other causes of granulomas may lead to hypercalcaemia e.g. tuberculosis and histoplasmosis
- vitamin D intoxication
- acromegaly
- thyrotoxicosis
- Milk-alkali syndrome
- drugs: thiazides, calcium-containing antacids
- dehydration
- Addison's disease
38
What can be exacerbated when insulin is prescribed concomitantly with pioglitazone?
Peripheral oedema
39
What is the most common cause of primary hyperaldosteronism?
Bilateral idiopathic adrenal hyperplasia
40
What are the key features of primary hyperaldosteronism?
Hypertension
Hypokalaemia
Mild alkalosis
41
What level should a women with gestational diabetes keep her fasting glucose?
5.3 or less
42
What is Klinefelter's syndrome?
Chromosomal disorder associated with male infertility.
- karyotype 47, XXY
43
What are the features of Klinefelter's syndrome?
- often taller than average
- lack of secondary sexual characteristics
- small, firm testes
- infertile
- gynaecomastia - increased incidence of breast cancer
- elevated gonadotrophin levels but low testosterone
44
What are the features of MEN type 1?
MEN 1 gene
- Hypercalcaemia common presentation
- 3Ps - hyperparathyroidism, pituitary and pancreas (insulinomas/gastrinomas leading to peptic ulcers).
45
What are the features of MEN type 2a?
RET oncogene
- Medullary thyroid cancer
- 2Ps - Parathyroid and phaeochromocytoma
46
What are the features of MEN type 2b?
RET oncogene
- Medullary thyroid cancer
- 1P - phaeochromocytoma
- Marfanoid body habitus
- Neuromas
47
What is the first line anti-diabetic medication in gestational diabetes?
Metformin
48
What are the risk factors for developing gestational diabetes?
- BMI of > 30 kg/m²
- previous macrosomic baby weighing 4.5 kg or above
- previous gestational diabetes
- 1st degree relative with diabetes
- family origin with a high prevalence of diabetes (South Asian, black Caribbean and Middle Eastern)
49
how do you screen for gestational diabetes?
_ oral glucose tolerance test (OGTT) is the test of choice.
women who've previously had gestational diabetes: OGTT should be performed as soon as possible after booking and at 24-28 weeks if the first test is normal.
50
What are the diagnostic thresholds for gestational diabetes?
fasting glucose is >= 5.6 mmol/L
2-hour glucose is >= 7.8 mmol/L
51
How is gestational diabetes managed?
- Diet and exercise advice
- Metformin
- Add insulin (short acting) if still no improvement with combination of above.
- Commence insulin immediately if fasting glucose >7 at diagnosis or 6-6.9 with risk factors.
- Glibenclamide should only be offered for women who cannot tolerate metformin or those who fail to meet the glucose targets with metformin but decline insulin treatment.
52
What is the definitive management of primary hyperparathyroidism?
Total parathyroidectomy
53
Which steroid has the least mineralocorticoid action?
Dexamethasone
54
What are the endocrine side effects of glucocorticoids?
impaired glucose regulation
increased appetite/weight gain
hirsutism
hyperlipidaemia
55
What are the Cushing's side effects of glucocorticoids?
moon face
buffalo hump
striae
56
What are the MSK side effects of glucocorticoids?
osteoporosis
proximal myopathy
avascular necrosis of the femoral head
57
What are the psychiatric side effects of glucocorticoids?
insomnia
mania
depression
psychosis
58
What are the GI side effects of glucocorticoids?
peptic ulceration
acute pancreatitis
59
What are the ophthalmic side effects if glucocorticoids?
glaucoma
cataracts
60
What are some other side effects of glucocorticoids?
suppression of growth in children
intracranial hypertension
neutrophilia
61
What are the side effects of mineralocortioids?
fluid retention
hypertension
62
What is used first line for infertility in PCOS?
clomifene
63
What is Galactosaemia?
- rare autosomal recessive condition
- absence of galactose-1-phosphate uridyl transferase. This results in intracellular accumulation of galactose-1-phosphate
64
What are the features of Galactosaemia?
jaundice
failure to thrive
hepatomegaly
cataracts
hypoglycaemia after exposure to galactose
Fanconi syndrome
65
How is galactosaemia diagnosed?
urine reducing substances
66
What is the management of galactosaemia?
Galactose free diet
67
What is Penfred syndrome?
- autosomal recessive genetic disorder
- bilateral sensorineural deafness, with mild hypothyroidism and a goitre
- defect in the organification of iodine, leading to dyshormonogenesis
68
How is Penfred syndrome diagnosed?
genetic testing
MRI - 1 and half turns in cochlea rather than 2 and half.
audiometry
69
What is the treatment for Penfred syndrome?
Thyroid replacement and cochlear implants
70
Which anti-diabetic medication is associated with increased risk of severe pancreatitis and renal imapirment?
Exenatide
71
How does Cushing's syndrome cause metabolic alkalosis?
Increased cortisol - activates mineralocorticoid receptors in distal tubules - Increased reabsorption of Na and excretion of K and hydrogen ions.
72
What advice should you give someone taking iron and levothyroxine?
Take iron at least 4 hours apart from levothyroxine.
Iron reduces the absorption of levothyroxine.
73
What are the features of hypocalcaemia?
- tetany: muscle twitching, cramping and spasm
- perioral paraesthesia
- if chronic: depression, cataracts
- ECG: prolonged QT interval
74
What are the features of Kallmann's syndrome?
- 'delayed puberty'
- hypogonadism, cryptorchidism
- anosmia
- sex hormone levels are low
LH, FSH levels are inappropriately low/normal
- patients are typically of normal or above-average height
- Cleft lip/palate and visual/hearing defects are also seen in some patients.
75
What is the pathophysiology and inheritance pattern of Kallmann's syndrome?
- X-linked recessive trait
- failure of GnRH-secreting neurons to migrate to the hypothalamus
76
What is the management of Kallmann's syndrome?
- testosterone supplementation
- gonadotrophin supplementation may result in sperm production if fertility is desired later in life
77
What causes ketone production in DKA?
Low insulin levels stimulate Lipolysis, this produces ketone bodies, beta-hydroxybutyrate and acetoacetate which can be used as fuel.
78
What are the causes of raised prolactin?
- pregnancy
- prolactinoma
- physiological
- polycystic ovarian syndrome
- primary hypothyroidism
- phenothiazines, metoclopramide, domperidone
79
What is primary polydipsia?
- excessive consumption of fluid leading to the production of large volumes of dilute urine.
- high urine osmolality after fluid deprivation
80
What is the inheritance pattern of familial hypercholesterolaemia?
Autosomal dominant
81
What is the general HbA1c target in T1DM?
48mmol/mol
82
What are the characteristics of Type 1 renal tubular acidosis?
Distal tubule
- inability to generate acid urine (secrete H+) in distal tubule
- causes hypokalaemia
- complications include nephrocalcinosis and renal stones
- causes include idiopathic, rheumatoid arthritis, SLE, Sjogren's, amphotericin B toxicity, analgesic nephropathy
83
What are the characteristics of Type 2 renal tubular acidosis?
- Proximal tubule
- decreased HCO3- reabsorption in proximal tubule
- causes hypokalaemia
- complications include osteomalacia
- causes include idiopathic, as part of Fanconi syndrome, Wilson's disease, cystinosis, outdated tetracyclines, carbonic anhydrase inhibitors (acetazolamide, topiramate)
84
What are the characteristics of Type 3 renal tubular acidosis?
- Mixed distal and proximal
- extremely rare
- caused by carbonic anhydrase II deficiency
- results in hypokalaemia
85
What are the characteristics of Type 4 renal tubular acidosis?
- reduction in aldosterone leads in turn to a reduction in proximal tubular ammonium excretion
- causes hyperkalaemia
- causes include hypoaldosteronism, diabetes
86
What are some causes of raised ALP?
liver: cholestasis, hepatitis, fatty liver, neoplasia
Paget's
osteomalacia
bone metastases
hyperparathyroidism
renal failure
physiological: pregnancy, growing children, healing fractures
87
What is metabolic syndrome?
Group of health condition that increase your risk of insulin resistance and diabetes.
88
What are some examples of acute phase proteins?
CRP*
procalcitonin
ferritin
fibrinogen
alpha-1 antitrypsin
caeruloplasmin
serum amyloid A
serum amyloid P component**
haptoglobin
complement
89
What is androgen insensitivity syndrome?
X-linked recessive condition due to end-organ resistance to testosterone causing genotypically male children (46XY) to have a female phenotype.
90
What are the features of androgen insensitivity syndrome?
- 'primary amenorrhoea'
- little or no axillary and pubic hair
- undescended testes causing groin swellings
- breast development may occur as a result of the conversion of testosterone to oestradiol
91
How is androgen insensitivity syndrome diagnosed?
- buccal smear or chromosomal analysis to reveal 46XY genotype
- after puberty, testosterone concentrations are in the high-normal to slightly elevated reference range for postpubertal boys
92
What is the management of androgen insensitivity syndrome?
- counselling - raise the child as female
- bilateral orchidectomy (increased risk of testicular cancer due to undescended testes)
- oestrogen therapy
93
What is the most common cause of hypercalcaemia in malignancy?
parathyroid-hormone-related peptide release (80% cases)
94
What are the 4 phases of Subacute thyroiditis (de Quervain's)?
phase 1 (lasts 3-6 weeks): hyperthyroidism, painful goitre, raised ESR
phase 2 (1-3 weeks): euthyroid
phase 3 (weeks - months): hypothyroidism
phase 4: thyroid structure and function goes back to normal
95
What is the management of subacute thyroiditis?
- usually self-limiting - most patients do not require treatment
- thyroid pain may respond to aspirin or other NSAIDs
- in more severe cases steroids are used, particularly if hypothyroidism develops
96
What is the inheritance pattern of MODY?
Autosomal dominant
97
What are the features of MODY?
- mild non-ketotic hyperglycemia
-often normal weight and do not exhibit signs of insulin resistance.
- usually found incidentally
98
What are some drug causes of gynaecomastia?
- spironolactone (most common drug cause)
- cimetidine
- digoxin
- cannabis
- finasteride
- GnRH agonists e.g. goserelin, buserelin
- oestrogens, anabolic steroids
99
What are some non drug causes of gynaecomastia?
- physiological: normal in puberty
- syndromes with androgen deficiency: Kallman's, Klinefelter's
- testicular failure: e.g. mumps
- liver disease
- testicular cancer e.g. seminoma secreting hCG
- ectopic tumour secretion
- hyperthyroidism
- haemodialysis
100
What is a common complication of thyroid eye disease?
Exposure keratopathy
101
What is acromegaly?
Excess growth hormone secondary to a pituitary adenoma (95% cases) or ectopic GHRH or GH production by tumours e.g. pancreatic.
102
What are the features of acromegaly?
- coarse facial appearance, spade-like hands, increase in shoe size
- large tongue, prognathism (protrusion of mandible), interdental spaces
- excessive sweating and oily skin: caused by sweat gland hypertrophy
- features of pituitary tumour: hypopituitarism, headaches, bitemporal hemianopia
- raised prolactin in 1/3 of cases → galactorrhoea
- 6% of patients have MEN-1
103
What are some complications of acromegaly?
- hypertension
- diabetes (>10%)
- cardiomyopathy
- colorectal cancer
104
What is the 1st line investigation for acromegaly?
Serum IGF-1 levels with serial GH levels.
If IGF-1 levels raised then OGTT used to confirm diagnosis.
105
How is acromegaly managed?
Trans-sphenoidal surgery is 1st line in those with pituitary tumours.
If surgery unsuccessful/inoperable then:
- somatostatin analogues e.g. octreotide
- pegvisomant
- dopamine agonists e.g. bromocriptine
106
What are some examples of negative acute phase proteins?
albumin
transthyretin (formerly known as prealbumin)
transferrin
retinol binding protein
cortisol binding protein
107
Raised ALP and raised calcium suggests?
Bone mets
hyperparathyroididm
108
Raised ALP and low calcium suggests?
osteomalacia
renal failure
109
What is primary amenorrhoea?
failure to establish menstruation by 15 in girls with normal secondary sexual characteristics (such as breast development), or by 13 in girls with no secondary sexual characteristics.
110
What are some causes of primary amenorrhoea?
- gonadal dysgenesis (e.g. Turner's syndrome) - the most common causes
- testicular feminisation
- congenital malformations of the genital tract
- functional hypothalamic amenorrhoea (e.g. secondary to anorexia)
- congenital adrenal hyperplasia
- imperforate hymen
111
What is secondary amenorrhoea?
cessation of menstruation for 3-6 months in women with previously normal and regular menses, or 6-12 months in women with previous oligomenorrhoea
112
What are some causes of secondary amenorrhoea?
- hypothalamic amenorrhoea (e.g. secondary stress, excessive exercise)
- polycystic ovarian syndrome (PCOS)
- hyperprolactinaemia
- premature ovarian failure
- thyrotoxicosis*
- Sheehan's syndrome
- Asherman's syndrome (intrauterine adhesions)
113
How do you investigate amenorrhoea?
- exclude pregnancy
- gonadotropins (raised then ovarian, low then hypothalamic)
- prolactin
- androgens
- oestradiol
114
What is autoimmune polyendocrinopathy syndrome?
When Addison's disease is associated with other endocrine related conditions.
Type 1 and type 2.
115
What are the features of Autoimmune polyendocrinopathy syndrome type 2?
- polygenic inheritance and is linked to HLA DR3/DR4
- Addison's disease plus either:
type 1 diabetes mellitus
autoimmune thyroid disease
116
What are the features of Autoimmune polyendocrinopathy syndrome type 1?
Multiple Endocrine Deficiency Autoimmune Candidiasis (MEDAC).
- autosomal recessive disorder caused by mutation of AIRE1 gene on chromosome 21
- chronic mucocutaneous candidiasis (typically first feature as young child)
Addison's disease
primary hypoparathyroidism
- vitiligo can occur in both eyes.
117
What is Bartter's syndrome?
- autosomal recessive cause of severe hypokalaemia.
- associated with normotension.
118
What are the features of Bartter's syndrome?
- usually presents in childhood, e.g. Failure to thrive
- polyuria, polydipsia
- hypokalaemia
- normotension
- weakness
119
What is SIADH?
- hyponatraemia secondary to the dilutional effects of excessive water retention.
- typically euvolemic,
120
What are some causes of SIADH?
- Malignancy (small cell lung cancer, pancreas, prostate)
- Neurological (stroke, SAH, SDH, meningitis/abscess)
- Infections (TB, pneumonia)
- Drugs (SSRIs, sulphonylureas, TCA, carbamazepine, vincristine, cyclophosphamide)
-positive end-expiratory pressure (PEEP)
- porphyrias
121
What are the investigation findings in SIADH?
- high urine osmolality in relation to serum osmolality
- high urine sodium concentration
122
What is the treatment for toxic multinodular goitre?
Radioiodine
123
What is primary hyperparathyroidism?
- excess secretion of PTH resulting in hypercalcaemia
- 85% of cases a parathyroid adenoma is cause
124
What are the features of primary hyperparathyroidism?
'Bones, stones, pyschic moans and abdo groans'
- polydipsia, polyuria
- depression
- anorexia, nausea, constipation
- peptic ulceration
- pancreatitis
- bone pain/fracture
- renal stones
- hypertension
125
Which conditions are associated with primary hyperparathyroidism?
MEN I and II
Hypertension
126
What investigations would you carry out for primary parathyroidism?
- raised calcium, low phosphate
- high PTH or inappropriately normal
- technetium-MIBI subtraction scan
- x-ray findings: pepperpot skull, osteitis fibrosa cystica
127
What is the treatment for hyperparathyroidism?
Total parathyroidectomy
cinacalcet (calcimimetic)
128
What are some features of anaplastic thyroid carcinoma?
- Very rare
- Usually elderly females
- Local invasion is a common feature
- pressure sx e.g. hoarse voice, dyspnoea
- Treatment is by resection where possible, palliation may be achieved through isthmusectomy and radiotherapy.
- Chemotherapy is ineffective.
129
What are some causes of thyroid storm?
thyroid or non-thyroidal surgery
trauma
infection
acute iodine load e.g. CT contrast media
130
What are the features of thyroid storm?
- fever > 38.5ºC
- tachycardia
- confusion and agitation
- nausea and vomiting
- hypertension
- heart failure
- abnormal liver function test - jaundice may be seen clinically
131
What is the management for thyroid storm?
- symptomatic treatment e.g. paracetamol
- treatment of underlying precipitating event
- beta-blockers: typically IV propranolol
- anti-thyroid drugs: e.g. methimazole or propylthiouracil
- Lugol's iodine
- dexamethasone - e.g. 4mg IV qds - blocks the conversion of T4 to T3
132
What dietary advice should you give in T2DM?
- high fibre, low GI sources of carbohydrates
- include low-fat dairy products and oily fish
- control the intake of foods containing saturated fats and trans fatty acids
- limited substitution of sucrose-containing foods for other carbohydrates is allowable, but care should be taken to avoid excess energy intake
- discourage the use of foods marketed specifically at people with diabetes
- initial target weight loss in an overweight person is 5-10%
133
What are the HbA1c targets for those with T2DM?
Lifestyle - 48mmol
Lifestyle + metformin - 48mmol
Drug that may cause hypoglycaemia - 53
134
What is sick euthyroid syndrome?
non-thyroidal illness syndrome
found in critically ill patients.
- low T3 and T4
- low/normal TSH
135
What is premature ovarian insufficiency?
onset of menopausal symptoms and elevated gonadotrophin levels before the age of 40 years
136
What are some causes of premature ovarian insufficiency?
- idiopathic
- bilateral oophorectomy (hysterectomy with preservation of the ovaries has also been shown to advance the age of menopause)
- radiotherapy
- chemotherapy
- infection: e.g. mumps
- autoimmune disorders
- resistant ovary syndrome: due to FSH receptor abnormalities
137
What are the features of premature ovarian insufficiency?
- climacteric symptoms: hot flushes, night sweats
- infertility
- secondary amenorrhoea
- raised FSH, LH levels e.g. FSH > 30 IU/L
(elevated FSH levels should be demonstrated on 2 blood samples taken 4-6 weeks apart)
- low oestradiol e.g. < 100 pmol/l
138
What is the management of premature ovarian insufficiency?
hormone replacement therapy (HRT) or a combined oral contraceptive pill should be offered to women until the age of the average menopause (51 years)
139
Which condition is associated with thyroid lymphoma?
Hashimoto's thyroiditis
140
What are the features of papillary thyroid cancer?
Most common thyroid cancer
Usually young females
Excellent prognosis
-Usually contain a mixture of papillary and colloidal filled follicles
-Histologically tumour has papillary projections and pale empty nuclei
-Seldom encapsulated
-Lymph node metastasis predominate
-Haematogenous metastasis rare
141
What is the mechanism of action of SGLT-2 inhibitors?
reversibly inhibit sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule.
- reduce glucose reabsorption
- increase urinary glucose excretion
142
What are the adverse effects of SGLT-2 Inhibitors?
- urinary and genital infection (secondary to glycosuria). Fournier's gangrene has also been reported
- normoglycaemic ketoacidosis
- increased risk of lower-limb amputation: feet should be closely monitored
143
What is Gitelman's syndrome?
Defect in the thiazide-sensitive Na+ Cl- transporter in the distal convoluted tubule.
144
What are the features of Gitelman's syndrome?
- normotension
- hypokalaemia
- hypocalciuria
- hypomagnesaemia
- metabolic alkalosis
145
Which conditions can cause a lower than expected HbA1c?
Sickle-cell anaemia
GP6D deficiency
Hereditary spherocytosis
Haemodialysis
146
Which conditions can cause a higher than expected HbA1c?
Vitamin B12/folic acid deficiency
Iron-deficiency anaemia
Splenectomy
147
What are the features of uterine fibroids?
- may be asymptomatic
- menorrhagia (may result in IDA)
- bulk-related symptoms (lower abdominal pain: cramping pains, often during menstruation, bloating)
- urinary symptoms, e.g. frequency, may occur with larger fibroids
- subfertility
- rare features: polycythaemia secondary to autonomous production of erythropoietin
148
What is the treatment for acute, severe hyponatraemia?
Hypertonic saline (typically 3% NaCl)
149
What is the mechanism of action of carbimazole?
blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin → reducing thyroid hormone production
150
What causes ovulation?
Surge in LH
151
What are some adverse affects of Thiazolidinediones e.g. pioglitazone?
- weight gain
- liver impairment: monitor LFTs
- fluid retention - therefore contraindicated in heart failure. The risk of fluid retention is increased if the patient also takes insulin
- increased risk of fractures
- bladder cancer: recent studies have shown an increased risk of bladder cancer in patients taking pioglitazone (hazard ratio 2.64)
152
What are the risk factors for developing cervical cancer?
- HPV (16,18,33)
- smoking
- human immunodeficiency virus
- early first intercourse, many sexual partners
- high parity
- lower socioeconomic status
- combined oral contraceptive pill*
153
What is the primary pathophysiology in impaired fasting glucose?
Hepatic insulin resistance
154
What is hungry bone syndrome?
Can occur after parathyroidectomy.
Rapid fall in PTH levels causes osteoclast activity to decrease resulting in bone re-mineralising.
Can be painful and result in systemic hypoglycaemia.
155
What is Liddle's syndrome?
- Rare, autosomal dominant condition
- hypertension and hypokalaemic alkalosis.
- disordered sodium channels in the distal tubules leading to increased reabsorption of sodium.
- Treatment is with either amiloride or triamterene
156
What is Pendred's syndrome?
- Rare autosomal recessive disorder
- bilateral sensorineural deafness, with mild hypothyroidism and a goitre
- defect in the organification of iodine, leading to dyshormonogenesis.
157
What is pseudohypoparathyroidism?
End-organ resistance to parathyroid hormone (PTH) action, typically due to defects in the G protein signalling pathway.
- associated with low IQ, short stature, shortened 4th and 5th metacarpals, low calcium, high phosphate, high PTH
- dx is made by measuring urinary cAMP and phosphate levels following an infusion of PTH. In hypoparathyroidism this will cause an increase in both cAMP and phosphate levels. In pseudohypoparathyroidism type I neither cAMP nor phosphate levels are increased whilst in pseudohypoparathyroidism type II only cAMP rises.
158
What electrolyte disturbance is commonly seen in referring syndrome?
hypophosphataemia
159
What is diagnostic for Klinefelter's syndrome?
Karyotype
160
How is an insulinoma diagnosed?
Supervised fasting
161
Which antihypertensive should be started first in pheochromocytoma?
Phenoxybenzamine
162
What are some adverse effects of radio iodine treatment?
Hypothyroidism
Precipitates thyroid eye disease
163
What is the mechanism of action of Evolocumab?
Prevents PCSK9-mediated LDL receptor degradation.
164
What is the mechanism of action of meglitinides?
bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells
165
What may cause a decrease in libido in someone with Addison's disease?
Dehydroepiandrosterone deficiency
(most abundant adrenal steroid, may result in sx secondary to androgen deficiency)
166
What is the mechanism of action of pegvisomant?
Growth hormone receptor antagonist
Used in treatment of acromegaly
167
What is the genetic concordance of diabetes in identical twins?
Type 1 DM - 40%
Type 2DM - 100%
168
What is the management for subclinical hypothyroidism?
- Consider offering levothyroxine if the TSH level is > 10 mU/L on 2 separate occasions 3 months apart
- if < 65 years consider offering a 6-month trial of levothyroxine if:
the TSH level is 5.5 - 10mU/L on 2 separate occasions 3 months apart and there are symptoms of hypothyroidism.
- in older people (especially those aged over 80 years) follow a 'watch and wait' strategy is often used
- if asymptomatic people, observe and repeat thyroid function in 6 months
169
What medications can give a false negative renin:aldosterone ratio results impacting testing for primary hyperalodsteronism?
- ACEIs (e.g. ramipril or lisinopril).
- ARBs (e.g. losartan).
- Direct renin inhibitors (e.g aliskiren).
- Aldosterone antagonists (e.g. spironolactone or eplerenone).
170
What is the physiological response to hypoglycaemia?
- decreased insulin secretion (1st response).
- increased glucagon secretion (2nd response).
- Growth hormone and cortisol are also released but later.
sympathoadrenal response: increased catecholamine-mediated (adrenergic) and acetylcholine-mediated (cholinergic) neurotransmission in the peripheral autonomic nervous system and in the central nervous system
171
What are some causes of secondary hyperparathyroidism?
- occurs in chronic kidney disease typically
- can be secondary to vitamin D deficiency
PTH released due to low calcium, high phosphate and lack of vitamin D activation by diseased kidneys
PTH level high with calcium levels being low or normal
medical management primarily: phosphate binders, calcium and vitamin D supplementation
172
What are the features of secondary hyperparathyroidism?
- PTH released due to low calcium, high phosphate and lack of vitamin D activation by diseased kidneys
- PTH level high with calcium levels being low or normal
173
What is the management for secondary hyperparathyroidism?
- phosphate binders, calcium and vitamin D supplementation
174
What is the mechanism of action of orlistat?
Pancreatic lipase inhibitor
175
What are some potential complications of HRT?
- Increased risk of breast cancer
- Increased risk of endometrial cancer
- increased risk of VTE
- Increased risk of stroke
- increased risk of IHD if taken for 10yrs after menopause
176
Which cancer is associated with acromegaly?
Colorectal carcinoma
177
How is diabetes mellitus diagnosed?
fasting > 7.0, random > 11.1 - if asymptomatic need two readings
178
What rate should the insulin infusion be started at in DKA?
0.1unit/kg/hr
179
What secondary causes of hyperlipdaemia cause hypercholesterolaemia rather than hypertriglyceridaemia?
- nephrotic syndrome
- cholestasis
- hypothyroidism
180
Unapposed oestrogen increases the risk of which cancer?
Endometrial
181
What is the aim of statins in primary prevention of CVD?
a reduction in non-HDL cholesterol of > 40%
182
What are the features of gastroparesis in diabetes?
- Secondary to autonomic neuropathy
- erratic blood glucose control, bloating and vomiting
- management options include metoclopramide, domperidone or erythromycin (prokinetic agents)
183
What is the pathophysiological mechanism of Grave's Disease?
autoimmune condition caused by IgG antibodies to the thyroid-stimulating hormone (TSH) receptor
184
Which drug should be used for the treatment of thyrotoxicosis in the 1st trimester of pregnancy?
Propylthiouracil
185
What is the 1st line treatment in remnant hyperlipidaemia (dysbetalipoproteinaemia)?
Fibrates
186
What are some consequences of not treating subclinical hyperthyroidism?
Supraventricular arrhythmias
Osteoporosis
Increases likelihood of dementia
187
What is the treatment for myxoedemic coma?
hydrocortisone and levothyroxine.
188
What are the treatment options for hirsutism in PCOS?
1st - COCP
2nd - co-cyprindiol (anti-androgen)
3rd - Topical eflornithine
4th - spironolactone, flutamide and finasteride (specialist only).
189
What is the 1st line pharmacological treatment in MODY type 1?
Sulfonylureas
190
What are some causes of gynaecomastia?
- physiological: normal in puberty
- syndromes with androgen deficiency: Kallman's, Klinefelter's
- testicular failure: e.g. mumps
- liver disease
- testicular cancer e.g. seminoma secreting hCG
- ectopic tumour secretion
- hyperthyroidism
- haemodialysis
- drugs
191
What drugs cause gynaecomastia?
- spironolactone (most common drug cause)
- cimetidine
- digoxin
- cannabis
- finasteride
- GnRH agonists e.g. goserelin, buserelin
- oestrogens, anabolic steroids
192
Which gene is most commonly responsible for MODY?
HNF-1A (MODY3 which is most common type)
193
What is the most common ECG change in hypocalcaemia?
prolongation of the QTc interval
194
Which hormone is under continuous inhibition?
Prolactin
(primarily regulated by inhibition, most notably by dopamine)
195
What is the mechanism of action of metformin in PCOS?
Increases peripheral insulin sensitivity
196
What causes excessive sweating in acromegaly?
Sweat gland hypertrophy
197
What is the mechanism of action of mirabcgron?
Beta 3 agonist
198
What level of uptake does toxic multi nodular goitre have on ultrasound?
Patchy uptake
199
What is the single most useful way to monitor those with MEN type 1?
Serum calcium
200
What condition is an insulin stress test most useful for diagnosing?
Hypopituitarism
201
Which class of anti diabetic medication may result in DKA in those with T2DM?
SGLT-2 inhibitors
202
