Endocrine Flashcards

Question

Differentiate Psychogenic Polydipsia and Diabetes Insipidus

Answer 1

Psychogenic Polydipsia: - Low sodium, normal glucose - Low plasma osmolality - Dilute urine with low osmol <100 - Low urine sodium <10 Diabetes Insipidus - High plasma osmolality - Low urine osmolality <300 - Normal or high urine sodium (So essentially in psychogenic polydipsia the kidney is trying to retain fluid, retaining sodium)

Answer 2

OGTT is gold standard, but best test now is IGF-1 → elevated = diagnostic

Answer 3

Surgical resection is first line, 80% success rate. IGF-1 levels for surveillance post op. Somatostatin analogues such as Octreotide if levels high post op or can't have surgery. Reduced GH release → reduce systemic symptoms and also reduce size of adenoma improving mass effect. RTx also for recurrence post op

Answer 4

Can cause tumour enlargement. This is because it doesn't target the tumour directly, but instead prevents the excess GH from binding to its target. Also means GH levels/ IGF-1 levels remain high. Second line agent after Octreotide. GH receptor antagonist.

Answer 5

High Risk: DR3, DR4 Protective: DR2

Answer 6

Glutamic Acid Decarboxylase Insulinoma Associated Ab Proinsulin Zinc Transport

Answer 7

Subtype of T1DM Initially responds to oral agents as Beta cells not yet depleted Criteria: - Age of onset ≥30 - Positive titre for a least one T1DM autoantibody - Not treated with insulin within the first 6 months

Answer 8

Autoimmune thyroid disease (27%) Coeliac Disease (12%)

Answer 9

Key benefit is lowering risk of severe hypoglycaemia. Also small HbA1c benefit

Answer 10

Reduces microvascular complications, particularly retinopathy and nephropathy. Increases risk of severe hypoglycaemia and weight gain. Benefits greater, and adverse effects lessened by insulin analogues compared to human insulin.

Answer 11

0.5U/kg/day Half given as basal Half split through day as bolus doses, guided by patient

Answer 12

ICR: grams or carbs/unit of insulin (around 500/total daily insulin) ISF: effect 1U rapid acting insulin will have over a couple of hours (around 100/total daily insulin requirement)

Answer 13

Not approved in Australia, but: - reduce HbA1c - Body weight reduction - Lower daily insulin requirement - Lower SBP - Increased risk of ketosis

Answer 14

Small reduction in weight and lipids No effect on HbA1c

Answer 15

Reduced time in hypoglycaemia without compromising HbA1c Improve time in target range Improve HbA1c

Answer 16

Reduced hypoglycaemic events without increasing HbA1c Improves Hb1c Reduced hospitalisation for hypoglycaemia and ketoacidosis Reduced work absenteeism Improved QOL

Answer 17

Adrenergic: Palpitations, tremor, anxiety/arousal, pallor Cholinergic: Sweating, hunger, paraesthesia Occur at BGL <4

Answer 18

Cognitive impairment Behaviour change Psychomotor abnormalities Seizures Coma Occur with BGL <3

Answer 19

Increasing age and long diabetes duration Aggressive glycaemic control Frequent hypoglycaemia Autonomic neuropathy Medications, e.g. beta blockers

Answer 20

Serum BGL >30 Serum Osmolality >320 Dehydration pH >7.3 Low ketones (<3) Altered level of consciousness

Answer 21

Microangiopathy of vasonervorum causes nerve ischaemia Length dependent sensory > motor neuropathy Paraesthesia most common symtpom Don't forget autonomic neuropathy

Answer 22

Retinopathy

Answer 23

Subclinical, normal vision. Microaneurysms, dilated venules, flame haemorrhages, cotton wool exudates, macular oedema

Answer 24

Small vessel damage → reduced blood flow → VEGF release → neovascularisation → new vessels fragile and prone to rupture Extensive neovascularisation Retinal ischaemia Fibrosis Vitreal haemorrhage Retinal detachment Management: laser photocoagulation, intravitreal anti-VEGF (Bevacizumab)

Answer 25

Loss of vibration (No. 1) Preulcerative lesions Peripheral arterial disease Previous ulcer Osteomyelitis High GDS

Answer 26

GLUT2 brings glucose into beta cells which drives Insulin release GLUT4 brings glucose into peripheral cells

Answer 27

Autosomal Dominant hereditary form of DM. MODY3: most common and most severe, due to mutations of hepatocyte nuclear transcription factor 1. Treat with Sulphonylurea MODY2: second most common, due to mutation of glucokinase. Mild hyperglycaemia, minimal treatment needed.

Answer 28

Loss of first phase insulin secretion → post prandial hyperglycaemia

Answer 29

General <7.0% New onset aim <6.0% Reduction improves microvascular outcomes Intensive control <6.5% increases mortality

Answer 30

Block glucose reabsorption in proximal convoluted tubule. Low risk of hypoglycaemia, but have risk of euglycaemic ketoacidosis and UTIs. Contraindicated in renal impairment (Empa <30, Dapa <25) Benefits. Reduced HbA1c Weight loss Reduced blood pressure Reduced MACE Reduced HF hospitalisation, Empa reduced HF mortality and all cause mortality Renoprotective

Answer 31

Inhibit hepatic gluconeogenesis, no risk of hypo, modest weight decrease. First line unless contraindicated. Severe renal impairment is key contraindication. Risk of lactic acidosis, GI side effects. Hold when unwell

Answer 32

Bind to ATP sensitive K channels on Beta cells → calcium influx → insulin secretion. High risk of hypoglycaemia which rises with age and renal/hepatic impairment. Lead to weight gain. Contraindicated in hypoglycaemia and pregnancy as well as CrCl <15. Not used much now. Gliclazide key example.

Answer 33

Inhibit DPP4 → reduced GLP-1 breakdown → Increased glucose dependent insulin secretion, slowed gastric emptying, inhibition of glucagon release, reduced appetite. No risk of hypo with monotherapy. Contraindicated in renal impairment, and can worsen CCF (esp Saxagliptin). Linagliptin can be used in any CrCl. End in "gliptin"

Answer 34

Increase GLP-1 activity which increases glucose dependent insulin secretion, slowed gastric emptying, reduced glucagon release, reduced appetite, reduced hepatic steatosis. Minimal hypoglycaemia risk, marked decrease in weight. Mortality benefit for Liraglitide. Others reduce MACE and stroke risk. Semaglutide slows CKD progression. Contraindicated in renal impairment, CrCl <30 (<15 for Dulaglutide)

Answer 35

Insulin secreting neuroendocrine tumour of the beta cells, most common neuroendocrine tumour and most common cause of endogenous hyperinsulinism. Mostly benign. 5% part of MEN1. Present with sympathetic symptoms then neuroglycopaenic symptoms. High C peptide and proinsulin. Tumour resection for localised disease. Octreotide can work while awaiting surgery.

Answer 36

Hypoechoic Height greater than width Irregular margins Calcification Increased vascularity Size >10mm

Answer 37

TFTs to ensure euthyroid Ultrasound then done Tc-99 scan can be done to further assess risk. Hot nodules typically benign, cold nodules concerning for malignancy Biopsy lesions >10mm with high risk features and all >20mm

Answer 38

Most common type of thyroid adenoma. 10-15% malignant but can't tell on FNA so need to excise. If surgical excisional biopsy shows cancer then completion thyroidectomy + adjuvant therapy indicated

Answer 39

Medullary: Calcitonin Follicular and Papillary: Thyroglobulin

Answer 40

Papillary (80%): young females, good prognosis Follicular (10%) Medullary (5%): part of MEN2 Anaplastic (1%): Worst prognosis

Answer 41

<1cm: Hemi or total thyroidectomy followed by surveillance >1cm: Total thyroidectomy, radioactive iodine treatment with TSH stimulation, annual screening (USS, Thyroglobulin)

Answer 42

Type 1: increased thyroid synthesis due to excessive iodine (from the Amiodarone), responds to antithyroid drugs, occurs early in course of treatment Type 2: Due to direct thyrocyte toxicity leading to inflammation. Typically self limiting, not responsive to antithyroid drugs. Responsive to steroids. More common Colour doppler reduced in type 2, as it Sestamibi scan/ When in doubt use both steroids and ATDs

Answer 43

Slows heart rate like other beta blockers, but also reduces peripheral conversion of T4 to T3.

Answer 44

Second line after antithyroid medications. Indicated in failed medical therapy or patients with contraindications to medical therapy

Answer 45

Antibodies to thyroid peroxidase drive CD8 T lymphocyte and Th1 lymphocyte response leading to thyroid gland destruction. Lymphocytic infiltrates, plasma cells, new germinal follicles, colloid atrophy present in histology. Collagen deposition is a marker of longstanding disease.

Answer 46

Coeliac Disease Type 1 Diabetes Mellitus Vitiligo

Answer 47

Iodine deficiency

Answer 48

Negative autoantibodies High TSH, low T3/T4 24 hour urinary iodine post oral iodine loading will be low (as iodine is retained rather than excreted)

Answer 49

Excessive replacement: hyperthyroidism (Jod-Basedow effect) Wolff-Chiakoff effect: worsening of hypothyroidism initially due to transient downregulation of iodine uptake in follicular cells due to sudden rise in iodine concentration.

Answer 50

Liver Kidneys Skeletal muscle

Answer 51

Alemtuzumab (Humanised anti CD52) Anti-retroviral therapy

Answer 52

Amiodarone (High TSH, high T4, low T3) Carbamazepine (low T4 and T3) Enoxaparin (High T4 and T3) Heparin (High T4 and T3) Phenytoin (Low T3) Biotin (High T4, low TSH)

Answer 53

Causes hypothyroidism with goitre. Due to reduced pinocytosis which impairs thyroglobulin release. Accumulates in cells and results in goitre formation. Not linked to therapeutic range/dose. More common in women, prolonged use, TPO antibodies.

Answer 54

PPI Antacid Calcium carbonate Alcohol Soy Milk

Answer 55

<1cm in diameter Monoclonal Majority are non functioning <5% enlarge Hypodense after gadolinium, due to reduced blood supply

Answer 56

>1cm in diameter To assess for function: Prolactin, TSH, fT4, Urinary Free Cortisol, IGF-1 Assess visual fields for mass effect

Answer 57

Macroadenoma

Answer 58

Metastasis - mets mainly spread to the posterior pituitary, so DI is classic of metastatic spread to the pituitary

Answer 59

GH, LH, FSH, TSH, ACTH

Answer 60

Embryonic remnants of Rathke's pouch BRAF V600E mutation Mostly in kids, but make up 1% of adult intracranial tumours Often calcified, with cystic component

Answer 61

HesX-1 Pit-1 (GH, TSH, Prolactin) Prop-1(Low GH, TSH, prolactin, FSH)

Answer 62

Generally due to haemorrhage. Don't bleed into normal pituitary Can mimic SAH Need to give steroid as acute ACTH deficiency can be life threatening Key indication for surgery is visual impairment

Answer 63

Usually quite delayed, minimal in first 3 years GH deficiency common, almost all at 5 years post Then LH/FSH, ACTH, TSH

Answer 64

Key cause of primary hypophysitis More common in women, and particularly during pregnancy or post partum. ACTH deficiency most commonly

Answer 65

CTLA-4 (Ipilimumab) (Some pituitary cells express CTLA-4) ACTH most affected (ACTH only in PD1, total anterior pituitary in CTLA-4) Visual field defects rare DI is rare

Answer 66

Somatostatin receptor SST2: Octreotide (GH) SST5: Likely to respond to Pasireotide (ACTH, GH) D2: Dopamine agonist

Answer 67

Asymptomatic don't need anything acute if non functioning and vision normal Transphenoidal pituitary surgery indicated if there are visual problems or enlarging 30% will regrow post surgery (more likely if silent corticotroph) Post op RTx if regrowing post surgery Medical therapy doesn't work well for mass effect (doesn't shrink tumour)

Answer 68

Compression of stalk → reduced dopamine flow to pituitary → reduced inhibition of prolactin secretion → hyperprolactinaemia

Answer 69

If no growth on repeat MRI at 1 year, and remains non functioning, no further monitoring required If any chiasmal compression or hypopituitarism

Answer 70

Reduces insulin and incretin levels → hyperglycaemia in 33% GLP agonists particularly effective in managing this

Answer 71

High Ki-67 index

Answer 72

IGF-1 is useful but not diagnostic, can be normal despite deficiency. The more other hormones are deficient, the more likely GH is to be deficient (3 deficient = 96% chance GH deficient) Stimulation testing: Glucagon response <3 (<1 if obese) diagnostic

Answer 73

Reduced cholesterol, improved cardiac function, improved quality of life, reduced body fat, improved insulin sensitivity. No impact on cancer risk Can increase conversion of cortisol to inactive form → may need glucocorticoid replacement Oral oestrogens (e.g. women taking the pill) are relatively resistant to oral GH

Answer 74

Macroprolactinaemia (prolactin bound together by Ig, increases half life in circulation) Pregnancy Drugs: Metoclopramide, Domperidone, Fluoxetine, Verapamil, Oestrogens If no clinical sequelae, not pregnant and not on any causative drugs, check macroprolactin levels.

Answer 75

Women present earlier as menstrual cycle far more sensitive than testicular axis to changes in prolactin levels, and thus develop symptoms earlier. Thus if men do present they typically present with a macroadenoma

Answer 76

Kisspeptin - inhibited by prolactin and thus reduces the usual pulsatile GnRH secretion → bloackade of oestrogen induced LH surge. Reduced gonadal steroid production results.

Answer 77

Prolactinoma 10% of prolactinomas are part of MEN1

Answer 78

Dopamine agonism key Bind to D2 receptor → increased dopamine → reduced prolactin synthesis and release Normalise prolactin levels and shrink tumour Cabergoline: more specific to D2 receptor than bromocriptine Can cause valvular heart fisease, so need TTE if higher doses Impulse control disorder is significant issue, need to screen Tumour shrinkage occurs within days so often can avoid surgery evenin in patients with visual field defects 20% can remain in remission after discontinuation of Cabergoline

Answer 79

Hypercalcaemia and hypokalaemia can down regulate AQP2 channels → clinical picture similar to nephrogenic DI

Answer 80

Also reduces peripheral conversion of T4 to T3

Answer 81

>40 years old Mild disease (fT4 <40) Low TRAB levels (<3x ULM) No goitre

Answer 82

Hepatotoxicity can be fulminant with PTU PTU can also induce an ANCA positive, Lupus like vasculitis Only times PTU us preferred: 1st trimester pregnancy, Thyroid storm Carbimazole can cause pancreatitis

Answer 83

Active Graves orbitopathy - radioactive iodine still stimulates TSH receptors, leading to worsening of gravers ophthalmopathy

Answer 84

Selenium 100mcg BD Other treatment for severe disease: - IV Methylprednisolone - Cyclosporin, RTX, Toci

Answer 85

Initially due to combination of genetic and environmental factors, typically relating to low iodine intake. Initially causes diffuse hyperplasia, but over time somatic mutations lead to focal epithelial proliferation and formation of nodules. These nodules may become hyper functioning (toxic) nodules which are autonomous → hyperthyroidism

Answer 86

Radioactive Iodine is treatment of choice, works very well Rates of post op hypothyroidism are low because the remainder of the thyroid doesn't take up the iodine due t low TSH

Answer 87

Thyroiditis, exogenous thyroid hormone excess, Iodine exposure

Answer 88

Inflammation leads to release of thyroid hormone stores. No overproduction of thyroid hormones

Answer 89

Expected response post iodine load - transient reduction in thyroid hormone production due to downregulation of sodium iodine transporter Euthyroid state returns within 24-48hr

Answer 90

Pathological response to exogenously administered iodine. Occurs in patients with impaired thyroid autoregulation Results in thyrotoxicosis as thyroid can take up iodine autonomously

Answer 91

Alemtuzumab: reconstitution syndrome → Graves ICI: Graves TKI: Hypothyroidism

Answer 92

Pregnancy <70 years of age and TSH >10 All other situations unclear Should send TPO antibodies - 60-80% actually have undiagnosed Hashimoto's

Answer 93

Mild: TSH 0.1-0.4; Severe <0.1 Increases risk of cardiac mortality and AF as well as fracture risk Treat if: TSH <0.1, also consider when mild if >65 or known cardiac disease

Answer 94

Impaired peripheral conversion of thyroxine, and reduced TSH, so everything usually low initially No treatment required, no evidence of benefit for thyroid replacement. Just repeat once well

Answer 95

Some increased demand, but also higher thyroid binding globulin, meaning more needed to saturate this and have normal functional free thyroid hormone

Answer 96

Respiratory failure

Answer 97

Autoimmune Adrenalitis >90% Key HLA: DR3-DQ2, DR4-DQ8 Driven by CD8+ T cells, reacting against 21-hydroxylase 60% is autoimmune polyendocrine syndrome AIRE gene mutation Accompanied by hypoparathyroidism, candidiasis (type 1) Autoimmune thyroid disease and T1DM (type 2)

Answer 98

Adrenoleukodystrophy

Answer 99

Loss of cortisol's inhibitory effect

Answer 100

Normal Synacthen, high ACTH, low Aldosterone, high renin, low DHEAS, 21-hydroxylase antibodies, Ab negative: check VLCFA in males, image adrenal for mets, TB, lymphoma, APLS Ab

Answer 101

Prolonged high cortisol, plus opioids and possibly steroid use lead to significant suppression of ACTH. Over time response blunted, can't then stimulate cortisol release Clinical diagnosis, no good testds

Answer 102

17-hydroxyprogesterone Mutation of CYP21A2 gene, leading to 21-hydroxylase deficiency Loss of cortisol and if severe aldosterone Can be salt wasting, and need mineralocorticoid replacement to manage this

Answer 103

Most common cause of secondary hypertension Increasess risk of: stroke, MI, CCF, AF, renal impairment Mx: Adrenalectomy for unilateral hyperaldosteronissm. MRA for bilateral forms Majority is bilateral hyperplasia Only 25% have hypokalaemia. If present need to correct before doing aldosterone:renin ratio, as hypokalaemia suppresses aldosterone production

Answer 104

Raised ratio = hyperaldosteronism Stop diuretics and spiro 6 weeks before testing Others 2-4 weeks prior Beta blockers: decrease renin (can cause false positive) ACEi: drop Aldosterone, increase Renin (false negative) Diuretics: increase renin (false negative) DHP CCB: decrease aldo, increase renin (false negative) So all cause false negatives except beta blockers Agents to use: non DHP CCB, Prazosin, Hydralazine, moxonidine

Answer 105

ARR has poor specificity, so confirmatory testing important Can skip if: hypokalaemia, undetectable plasma renin, plasam aldo >550 IV Saline test → Aldosterone >171 Captopril test: Aldosterone drops, renin rises, ARR reduced Then do CT: if unilateral adenoma and patient <35, presume functioning. Can identify carcinomas, and find hyperplasia which just needs medical mnagement. Adrenal venous sampling otherwise - gold standard for subtyping

Answer 106

Rare, but type 1 can be treated with dex, so important to be aware of Check if PA in very young patient CYP11B1, CYP11B2

Answer 107

Not used for secretory adenoma (Surgery better, though no mortality benefit). Aim for normal BP, normal K, normal plasma renin

Answer 108

Non functioning (75%) Of remaining functional, cortisol producing most common

Answer 109

Only time biopsy is indicated (once phaeo excluded) An adrenal mass found in a patient with history of malignancy will be a met in 20% of cases

Answer 110

Adrenalectomy usually Can do biopsy if high likelihood of met

Answer 111

TCAs, SNRI, MAOI, Levodopa, Methyldopa, CCB, Beta blockers, labetalol, Caffeine, Paracetamol, Mesalazine, Sulfasalazine If not >3x ULN with these medicatiosn avoided, do Clonidine suppression test

Answer 112

Normetanephrine higher when lesion is extra-adrenal. i.e. Paraganglioma

Answer 113

Surgery, but need to control hormones first to avoid haemodynamic instability. Give alpha blockade before beta blockade, but do give both To prevent unopposed alpha activity which can cause circulatory collapse Metastatic disease: chemotherapy or radiotherapy options

Answer 114

SDHB, SDHD, VHL, RET, NF1 Plus associated with MEN-2

Answer 115

High NPV, useful in shift workers, best test for cortisol secreting adrenal adenomas.

Answer 116

Pregnancy, on OCP, on Carbamazepine, Malabsorption

Answer 117

Desmopressin test: ACTH secreting adenomas express vasopressin V1b receptors, prodsucing an increase in plasma ACTH concentration after desmopressin injection

Answer 118

ACTH: High → image pituitary → inferior petrosal sinus sampling Low → image adrenals Can do CRH levels, Desmopressin test, etc. if MRI pituitary shows large mass, to confirm this is the cause

Answer 119

Neck and Chest mostly

Answer 120

Cushing's Disease: pituitary surgery → repeat surgery or medical therapy or radiotherapy Ectopic Cushing's: surgery if possible Adrenal adenoma: Adrenalectomy, unusual to recur unless carcinoma → poor prognosis

Answer 121

ABnormality of GnRH pulsatile release → Increased LH release → raised LH/FSH ratio Insulin resistance due to obesity Ovulatory dysfunction → hyperandrogenism, follicular arrest Low oestrogen, high testosterone is result Bloods: Raised testosterone, low SHBG, raised DHEAS, raised LH/FSH ratio, elevated AMH (this isn't in diagnostic criteria) OGTT is best test in PCOS for diabetes

Answer 122

CAH: 17OH progesterone (<6 = excluded) Hyperprolactinaemia Cushing's Syndrome, 24h UST, DST Acromegaly: IGF-1 Hypothyroidism Androgen secreting tumours: imaging

Answer 123

Letrozole (i.e. Aromatase Inhibitor)

Answer 124

Absence of menses due to stress, weight loss, xercise No identifiable anatomic/organic cause Under or normal weight GnRH pulsatility suppressed → high cortisol, low/N TSH, low T3, low IGF-1, low leptin, low FSH, low LH, low oestrogen Low bone density FGFR1 most common gene associated with risk Need to exclude pregnancy Check prolactin and pituitary function Provera challenge to exclude PCOS (get withdrawal bleed if PCOS), no bleed with FHA Weight gain is key management Calcium and Vit D for Osteoporosis

Answer 125

Essentially menopause early, <40 years of age Diagnosis: raised FSH in menopausal range (usually >40) on ≥2 occasions Most cases idiopathic/unknown, but can be induced by chemo, radiotherapy, Fragile X, autoimmune (autoimmune polyendocrine syndrome 1 and 2) Tests: raised FSH, low oestradiol, FMR-1 for Fragile X, Management: HRT, donor oocytes for fertility Spontaneous pregnancy can occur

Answer 126

Essentially should be male based on karyotype, but SRY gene on Y chromosome not working → female phenotype, but ovaries don't develop properly as need both X chromosomes for this → have female external genitalia but only gonadal streak Leads to primary amenorrhoea Gonadal streaks need to be removed High FSH and LH Low Oestradiol Normal testosterone Management: HRT → development of secondary female sex characteristics, remove streak gonads, assisted reproduction

Answer 127

Female external genitalia, but no internal structures as mullerian inhibitory factor present to block this. Testis present → tesotsterone aromatased → normal breast development 46XY karyotype, normal or high testosterone, LH normal or high

Answer 128

1:2500 live female births Loss of whole or part of X chromosome → 45X most common karyotype Short stature 90% have ovarian failure Oocytes lost rapidly, all lost by puberty → infertile Bicuspid aortic valve (16%), Coarctation of aorta (11%) 30% hypothyroidism Hypertension SNHL Renal tract abnormalities Diabetes Give GH, HRT

Answer 129

Is risk of breast cancer with long term use, as well as cardiovascular disease If used in patients <60 without history of CVD, Breast rCa, VTE → risks minimised Generally can use safely if within 10 years of menopause Need E and P to prevent endometrial cancer SSRIs can be useful

Answer 130

Hypogonadotrophic hypogonadism + anosmia Men ANOS1 or KAL1 X lnked recessive GnRH and Olfactory neurons don't work properly Presents at puberty Check for renal agenesis, SNHL lfactory bulkb/tract absent on MRI HRT with testosterone → induced puvberty Induction spermatogenesis Can recover spontaneously

Answer 131

47XXY, or 46XY/47XXY mosaic Tall, feminized physique, mild IQ impairment, poor beard growth, bresst development Raised FSH and LH, low testosterone Associated with T2DM, Osteoporosis, Thyroid disease, ILD, Breast cancer Mx: Testosterone, increased risk of chromosomal abnormalities in offspring

Answer 132

Prostate Cancer Doesn't increase risk of cardiovascular disease, but can cause polycythaemia

Answer 133

Median length 28 days Follicular phase: 1st day of menses to ovulation. Oestradiol levels secreted by developing follicles → stimulates LH surge → ovulation Ovulation Luteal phase: corpus luteum formed post ovulation, secretes progesterone which stimulates endometrial growth

Answer 134

Test 17-OH progesterone But 21 hydroxylase is what's lost → prevents conversion of 17-OH progesterone into cortisol and progesterone into aldosterone in most severely affected patients Steroid replacement for management

Answer 135

Passive paracellular reabsorption in PT and TAL (90%) - Calcium sensing receptor regulates calcium absorption in TAL - This reabsorption is tied to Mg reabsorption Active reabsorption in DCT (10%) - mediated by PTH

Answer 136

Inactivating mutation of Calcium Sensing Receptor → doesn't stop calcium reabsorption (in kidneys), doesn't turn of PTH production (in parathyroids) Leads to mild-moderate PTH dependent hypercalcaemia AD inheritance. CaSR gene, G alpha 11 gene Key for diagnosis: Inappropriately low urinary calcium excretion Hypermagnesaemia common Doesn't cause kidney stones or osteoporosis another key differentiator

Answer 137

Stimulates transcellular calcium reabsorption in DCT Phosphate excretion in PT Stimulates 1-alpha-hydroxylase → 1,25 Vit D synthesis

Answer 138

Key regulator of phosphate levels Levels rise when phosphate rises, blocking PT reabsorption, and downregulates bone resorption Decreases PTH synthesis Release stimulates by: PTH, phosphate levels, 1,25 Vit D

Answer 139

Parathyroid chief cells

Answer 140

Reduced fracture risk Reduced kidney stones Slows progression of CKD Indications: Renal involvement key, CRCl <60, nephrolithiasis, nephrocalcinosis

Answer 141

Ultrasound and Technetium 99 sestamibi to identify location of nodes and any enlargement

Answer 142

Bisphosphonates if only issue is reduced BMD. Improves BMD as much as PTx Cinacalcet for those unfit for surgery with severe/symptomatic hypercalcaemia. Doesn't improve BMD. Stimulates CaSR.

Answer 143

Inhibits sclerostin → increased bone formation, reduced resorption Contraindicated with history of MI/Stroke Used only when people have very poor BMD despite being on another antiresoprtive agent and still having fractures

Answer 144

Form bone, can be inhibited by high PTH levels ALso make hydroxyappatite, important for bone mineralisation

Answer 145

Osteoblasts initially, that get trapped in cortical bone and then become osteocytes At baseline secrete sclerostin, inhibiting bone formation (i.e. block Osteoblast activity). With mechanical stress to bone, sclerostin production stops → bone remodelling to respond to stress Produce RANKL which stimulates osteoclastogenesis and increases bone resorporption

Answer 146

Bone resorption Formation and activation stimulated by osteoblasts/osteoclasts via RANKL RANKL activity stimulated by PTH and Vitamin D RANK on osteoclasts precurors stimulated. Osteoprotegerin is a soluble decoy receptor for RANKL, so increased level blocks osteoclast activation (Denosumab mimics this)

Answer 147

Small benefit

Answer 148

T score < -2.5 Fracture of hip or vertebra regardless of T score Osteopaenia at femoral neck or total hip with 10 year FRAX risk ≥3% or MOF risk ≥20% Osteopaenia with other fragility fractures (wrist, pelvis, proximal humerus)

Answer 149

Assess actual microstructure of the bone, can adjust FRAX probability of fracture

Answer 150

For assessment of secondary causes of osteoporosis, by comparing to expected for age: If within 2 SD of expected, unlikely to have secondary osteoporosis

Answer 151

Crosslaps (CTX) should be low when on bisphosphonates Should be used to monitor effect Can use CTX, ALP, P1NP to monitor for wearing off of effect during bone holiday

Answer 152

Those on bisphosphonates, and those in RACF. Plus Vit D for those who are deficient in community, and calcium for those without adequatedietary calcium. But if levels normal, not required.

Answer 153

Inhibit osteoclast activity by inducing osteoclast apoptosis

Answer 154

Need to wait at least 2-3 years, otherwise won't necessarily have seen benefit

Answer 155

Bsiphosphonate fractures begin at lateral cortex Osteomalacia medial cortex

Answer 156

Osteonecrosis of jaw, atypical femoral fracture Cellulitis and Eczema are classic issues Rapid loss of BMD if stopped without replacement

Answer 157

Osteosarcoma

Answer 158

Binds to Wnt to block Osteoblast formation -> reduced bone formation

Answer 159

Inhibits sclerostin activity -> stimulates bone formation, inhibits bone resorption Possible increase in cardiovascular risk Used in patients with severe osteoporosis, still having fractures despite antiresorptive therapy Reduces risk of vertebral and hip fractures

Answer 160

Glucocorticoids inihibit osteoblastogenesis and also damage osteocytes -> reduced bone formation, and reduced remodelling in response to mechanical stress = poor quality bone So someone on steroids will have lower bone quality and strength than someone not on steroid with same BMD

Answer 161

Previous fracture OR age >70 OR Prednisolone dose >7.5mg/day If not previous fracture, age <70 or Pred dose <7.5mg/day, then treat if T score < -2.5, FRAX MOF >20% or Hip Fracture >3% Bisphosphonates first line, but Denosumab and Teriparatide also work

Answer 162

Testosterone treatment doesn't lower incidence of fracture compared to placebo

Answer 163

When patient is on a PPI. Carbonate required stomach acid to assist with absorption and should be taken with food.

Answer 164

Vitamin D promotes active transcellular absorption via TRPV channels in proximal small intestine

Answer 165

Consider with isolated ALP rise Only treat if symptomatic or in high risk location

Answer 166

Men: 102cm Women 88cm

Answer 167

Rising as weight increases, not decreasing. Makes up 50-70% of total daily energy expenditure

Answer 168

Secreted by white adipose tissue Low leptin drives appetite Overweight individuals are resistant to Leptin, so body thinks it has low levels

Answer 169

Orexogenic - released during fasting to stimulate appetite Released by Oxyntic glands in fundus and body of stomach Increases with fasting Increases gastric emptying

Answer 170

Anorexigenic - released post prandially and induce satiety Secreted by enteroendocrine L cells Release stimulated by presence of food in small intestine Stimulates insulin release, decreases gastric emptying and increases beta cell mass

Answer 171

Anorexigenic - released post prandially and induce satiety Secreted by Intestinal I cells when fat and protein in duodenum Also stimulates gall bladder contraction, slows gastric emptying and promotes pancreatic enzyme secretion

Answer 172

Anorexigenic - released post prandially and induce satiety Secreted by pancreatic F cells in presence of food, particularly high protein content Regulates pancreatic exocrine secretion, modules gastric acid release and GI motility

Answer 173

Key mechanism for effect - essentially get food into small intestine earlier = earlier release of satiety hormones