Block 6: DKA, Hypoparathyroidism, Hyperparathyroidism, bones Flashcards
1
Q
Further points for DKA management
A
- Both the ketonaemia and acidosis should have been resolved within 24 hours. If this hasn’t happened the patient requires senior review from an endocrinologist
- If the above criteria are met and the patient is eating and drinking switch to subcutaneous insulin
- The patient should be reviewed by the diabetes specialist nurse prior to discharge
2
Q
DKA complications
A
- Arrhythmias secondary to hyperkalaemia/iatrogenic hypokalaemia
- Iatrogenic due to incorrect fluid therapy: cerebral oedema, hypokalaemia, hypoglycaemia
- Acute respiratory distress syndrome
- Acute kidney injury
- Gastric stasis
- Thromboembolism
- Cerebral oedema
3
Q
Primary hyperparathyroidism
A
High Ca+ levels due to high circulating PTH. Causes bone breakdown to release Ca+ and excess reabsorption in the kidney
4
Q
Symptoms of Hypercalcaemia
A
- Thirst, polyuria, renal stones
- Weakness, myalgia, bone pain
- Anorexia, vomiting, constipation
- Mood change, depression, confusion
5
Q
Causes of Hypercalcaemia
A
- High PTH is primary or Tertiary Hyperparathyroidism, low PTH is cancer or other PTH independent causes
- If cancer its majority Humoral hypercalcaemia and sometimes osteolytic metastasis
6
Q
Investigations for Hypercalcaemia 1
A
- Diagnosed by measuring serum adjusted calcium and parathyroid hormone (PTH) levels at same time
- 24-hour urinary calcium to exclude familial hypocalciuric hypercalcaemia where its low
- CT/MRI to identify lesion if suspected
- Estimated glomerular filtration rate (eGFR) and creatinine to assess hydration status, risk of acute kidney injury and presence of chronic kidney disease
7
Q
Investigations for Hypercalcaemia 2
A
- Serum and urine protein electrophoresis, including testing for urine Bence-Jones protein to exclude myeloma
- Full blood count (FBC) to exclude haematological malignancy
- Liver function tests (LFTs) to exclude liver metastasis and some systematic diseases
- Dual energy x-ray absorptiometry (DEXA) to assess bone health and risk of osteopenia/osteoporosis
8
Q
Primary Hyperparathyroidism epidemiology
A
- More female, peaks 50-70yrs
- Family history
- Benign solitary parathyroid adenoma-85%
- ‘4-gland’ parathyroid hyperplasia-15%
- Parathyroid carcinoma <1%: majority is benign
9
Q
Inherited forms of primary Hyperparathyroidism- accounts for 15%
A
- Multiple endocrine neoplasia (MEN)
- Hyperparathyroidism jaw tumour syndrome
- Familial isolated primary hyperparathyroidism
10
Q
Biochemistry of primary Hyperparathyroidism
A
- Hypercalcaemia with low serum PO43-
- Raised or high-normal PTH
- Elevated Bony alkaline phosphatase
- Urinary calcium elevated or high normal
11
Q
Complications of primary Hyperparathyroidism
A
- Kidney stones, renal impairment
- Osteoporosis at Wrist and Hip
- Osteitis fibrosa cystica: periosteum of fingers and long bones is eroded
- Brown tumours of bone: accumulation of osteoclasts
- Corneal calcification: calcium deposited on the cornea, on the lateral and medial position. Appears white
- ?Hypertension
12
Q
Management of primary Hyperparathyroidism
A
- Surgical neck exploration: If patient has symptoms or Complications (renal stones) of hypercalcaemia
- Conservative management with regular monitoring: Only if asymptomatic (majority)
- Calcimimetic drugs (calcium receptor agonists): Cinacalcet, reduces renal stimulation- excrete more in the kidneys
- Bisphosphonates (anti-resorption therapy): Preserve bone density (monotherapy if conservative risk)
13
Q
Malignant Hypercalcaemia
A
- Median life expectancy of 6 weeks
- Humoral hypercalcaemia of malignancy (80%): PTHrP related release from tumour- normally released when a baby
- Bone erosion (20%): Diffuse bony disease, Focal osteolytic metastasis
- Rare causes: cancer which release 1,25(OH)2D3 and ectopic PTH
14
Q
Humoral hypercalcaemia of malignancy (HHM)
A
- Squamous cell carcinomas: Lung, Breast, Oesophagus, Cervix, Skin, Renal, Bladder, Ovary, Vulva
- Clinically obvious tumour mass
- Excess production of PTHrP from tumour cells which acts on PTH receptors
- Suppressed PTH and 1,25(OH)2D3
- Patients not at high risk of pathological fracture: not one a specific bony lesion that might fracture
15
Q
Myeloma
A
- 30% of myeloma patients get hypercalcaemic
- Myeloma sits in bone marrow causes osteolyses by cytokine release
- Diffuse osteolysis due to local cytokines (IL6)
- Causes renal impairement
- Typical biochemical features: Phosphate may be elevated, Alkaline Phosphatase- normal
- Hypercalcaemia is steroid responsive
16
Q
Hyperparathyroidism: focal osteolytic metastasis
A
- Lung, breast, prostate
- Direct invasion of the bone by malignancy: seen on plain X-ray
- Local pain
- High risk of pathological fracture
17
Q
Other causes of Hypercalcaemia
A
- Drugs (thiazide diuretics, lithium): High PTH
- Vitamin D intoxication: low PTH
- Milk-Alkali Syndrome: increased calcium ingestion and reduced excretion. Normally due to PPI or anti-indigestion meds: low PTH
- Sarcoidosis- increased hydroxylation of vitamin D
- Renal failure: high PTH
- Familial Benign Hypocalciuric Hypercalcaemia: mutation in Ca+2 receptor: High PTH
- Immobility with high bone turnover (astronauts- or teenagers who break their leg): Low PTH
- Endocrine Probs: Hyperthyroidism, Addison’s disease, Phaeochromocytoma
18
Q
Management of severe hypercalcaemia
A
- Baseline PTH if first presentation
- Surgery: Parathyroidectomy with primary hyperparathyroidism
- Ca+2 causes nephrogenic DI: Treat dehydration with IV N/Saline (6L/24hrs)
- Specific treatments (next day): IV bisphosphonates (zolendronic acid) if primary hyperparathyroidism. If myeloma give steroids
- Takes 72hrs to normalise calcium:
- SC denosumab if renal impairment
- Calcitonin: reduced calcium concentration by inhibiting kidney and bone reabsorption
- Cinacalcet: reduces serum calcium without affecting bone density or urinary calcium
19
Q
Parathyroidectomy is indicated:
A
- Symptomatic disease: Symptoms ofhypercalcaemia, Osteoporosis and/or fragility fractures, Renal stones or nephrocalcinosis
- Age <50 years
- Serum adjusted calcium of 2.85 mmol/L or above
- Estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m
20
Q
Complications of Hyperparathyroidism
A
- Osteoporosis and fragility fractures
- Kidney stones and kidney injury
- Hypertension and heart disease
- Numerous gastrointestinal disorders including peptic ulcer disease, pancreatitis and gall stones
21
Q
Hypopituitarism
A
Deficiency of one or more hormones produced by the anterior pituitary or released from the posterior pituitary. Clinical manifestation depends on the hormone affected
22
Q
Posterior pituitary
A
Produces oxytocin and ADH. Released neuronally by nerve signals from the Hypothalamus
23
Q
Hypopituitarism: most common causes
A
- Pituitary adenoma and other tumours
- Previous surgery/radiotherapy
- Trauma
- Apoplexy
- Hypophysitis: inflammation
- Infiltrative: hemochromatosis, lymphoma
24
Q
Hypopituitarism effects and mechanism
A
- Adrenal: Central adrenal insufficiency (CAI), lack of ACTH release.
- Thyroid
- Prolactin
- Gonadal
- Somatotropic
- DI
Hypopituitarism mechanism: Normal progression of symptoms GH -> FSH/LH -> TSH -> ACTH +/- DI
25
Q
Diagnosing CAI
A
- Basal cortisol <100nmol/L: AI
- Basal cortisol 100-400nmol/L: Do Corticotropin (Synathen test), if cortisol <500nmol/L at 30 or 60 minutes indicates AI
- Basal cortisol >400 nmol/L: excludes AI
- ACTH: low can be inappropriately normal (if low cortisol you expect ACTH to be high)
- Other stimulation tests: Insulin tolerance test, Glucagon stimulation test, Short syncathen (corticotropin) test.
26
Q
CAI treatment
A
Hydrocortisone in divide doses, more in the morning. Fludrocortisone is not required
27
Q
Central Hypothyroidism
A
- Reduced TSH.
- Bloods: low T4/T3 and high TRH, low/inappropriately normal TSH
- Treatment: thyroxine- adjust dose with T4/T3 levels (not TSH)
- If concerned they have low cortisol start them on steroids before thyroid replacement
28
Q
Hypopituitarism: prolactin
A
- Increased prolactin: Pituitary stalk compression (stops dopamine inhibition by tumour). Prolactinoma (pituitary adenoma with over production of prolactin). Can cause hypogonadism (low FSH/LH)
- Prolactin deficiency: Marker of severe pituitary hypofunction
- Deficit: Dopamine/prolactin
- Treat only if prolactinoma (tumour that is over producing prolactin): Dopamine agonists
- Dopamine from the Hypothalamus inhibits prolactin release
29
Q
Symptoms of Hypogonadism
A
Oligo/amenorrhea, erectile dysfunction, low libido, hot flashes, infertility, vaginal dryness, fatigue, weakness.
30
Q
Diagnosing Hypopituitarism (Hypogonadism): men
A
- Low or inappropriately normal FSH and LH
- Low total testosterone
- Low free testosterone- available one (calculated using SHBG)
31
Q
Treating Hypogonadism men
A
- Testosterone replacement (sc or topical): improved CV health, prostate and Hb
- Fertility treatment when required
32
Q
Diagnosing Hypogonadism men
A
- Low or innapropiately normal FSH and LH
- Low estrogens
- Rule out other causes of amenorrea including pregnancy and hyperprolactinemia
33
Q
Treating Hypogonadism women
A
- Estrogen replacement in premenopausal
- Fertility treatment when required
34
Q
GH pathophysiology
A
GH is released from the pituitary and travels to the liver where its metabolised to IGF-1 which is the active form
35
Q
Hypopituitarism (GH deficiency): diagnosis
A
- GH release in pulses therefore single sample does not reflect GH activity. Test IGF-1 and GH stimulation test.
- Stimulation test: administer insulin and sample blood at-30, 0, 30, 60, 120 min for GH and glucose
- Glucose should drop to 2.2mmol/L, otherwise not valid.
- GH deficiency: <3-5. cut offs for GH response are BMI related
- Indications: previous GH deficiency during childhood, evidence of pituitary damage. Don’t do if elderly
- GH increases in stress, gives energy, helps with growth
36
Q
Hypopituitarism (GH deficiency): monitoring and treatment
A
- Monitor every 6 months: IGF-1, BMI, Metabolic profile (glucose and lipids), QoL, other deficits
- Diagnosis: low IGF-1 and low GH after stimulation test
- Treatment: GH injection
37
Q
Hypocalcaemia causes
A
- Vitamin D deficiency: most common cause
- Hypoparathyroidism
- Drugs, Gd contrast (MRI)
- Renal failure
- PTH or vitamin D resistance syndromes
- Severe illness: Acute pancreatitis, Acute rhabdomyolysis
- Psuedohypoarathyroidism: resistance to PTH
38
Q
Symptoms of Hypocalcaemia
A
- Paraesthesia of mouth & fingers: symmetrical numbness or tingling
- Muscular twitching and leg cramps: evening and night
- Laryngeal stridor
- Carpopedal spasm (tetany)
- Seizures
- Papilloedema
- Prolonged QTc
- Chvostek’s sign: tap on parotid gland get involuntary twitching
- Trousseau’s sign: inflate BP cuff for 1 min above systolic BP hands spasm
- Hyperreflexia
- Long term: extrapyramidal symptoms, cataracts and calcification of the basal ganglia
39
Q
Hypoparathyroidism causes
A
- Post-surgical (thyroidectomy)
- Congenital absence of parathyroid gland: DiGeorge syndrome, GCMB mutation
- Autoimmune (with candidiasis & Addison’s)
- Reset PTH setpoint (calcium receptor)
- Tissue resistance to PTH: pseudohypoparathyroidism
- Infiltration of parathyroid gland
- Defective PTH molecule
40
Q
Biochemistry of Hypoparathyroidism
A
- Low serum calcium
- High serum PO43-
- Low- undetectable circulating PTH (can be inappropriately normal)
- Normal renal function
- Low Urine calcium excretion
41
Q
Pathophysiology of Hypoparathyroidism
A
Calcidiol cant be converted to calcitriol in the liver because 1 alpha hydroxylation is PTH dependent. Therefore active vitamin D isnt produced
42
Q
Treatment of Hypoparathyroidism
A
- Activated vitamin D: 1-Alfa calcidol (1 – 2.5 mcg daily), Calcitriol
- Calcium (1–3 g daily): Effervescent solution “Sandocal”, Chalky tablets Adcal or Calcichew
- Give both activated vitamin D and Calcium
- In rare cases IV calcium
43
Q
Other causes of Hypocalcaemia
A
- Drug induced hypocalcaemia: PO4, Bisphosphonates, Chemotherapy
- Hypomagnesaemia: induced hypocalcaemia by inhibiting PTH release and peripheral action
- Renal failure: Hypocalcaemia due to phosphate retention due to tubule damage. And failure of 1a hydroxylation of Vit D as it occurs in the kidneys. State of secondary hyperparathyroidism
44
Q
Parathyroid hormone acts to raise blood calcium levels by
A
- Increasingosteoclastactivity in bones (reabsorbing calcium from bones)
- Increasingcalcium reabsorptionin the kidneys (less calcium is lost in urine)
- Increasingvitamin Dactivity, resulting in increasedcalcium absorptionin theintestines
45
Q
Calcium homeostasis
A
- Drop in calcium is sensed by a calcium sensing receptor on the parathyroid cell and in the distal tubule
- The Parathyroid cell releases more PTH
- Acts on PTH receptor in renal tubule, bones and Duodenal lumen. Causes activation of vitamin D. Increased calcium absorption in the renal tubule, release of calcium from bone
46
Q
Vitamin D metabolism
A
- Synthesised by sunlight: 7-dehydrocholesterol turns into previtamin D. Then turns to vitamin D3
- Vitamin D3 turns into calcidol in the liver and into calcitrol in the kidney
- Calcitriol is the active vitamin D hormone and effects calcium and skeletal homeostasis
47
Q
Sources of vitamin D
A
- 90% from sunlight UVB exposure (April-October in the UK): 15 mins outside at midday
- Coleocalciferol from oily fish (egg yoke, meat)
- Ergocalciferol from yeast/mushrooms
- UK has profound vitamin D deficiency
48
Q
Bone structure
A
- Inert mineral (chalky): hydroxyapatite-Ca10(PO4)6(OH)2)
- Osteoid (flexible): Type 1 collagen (fibres), Chondroitin (matrix)
- Cellular component (5%): Osteoblasts: bone forming cells. Osteoclasts (from monocytes): bone resorbing cells. Osteocytes & haematopoetic tissue
49
Q
Osteoporosis vs osteomalacia
A
- Osteoporosis: proportional reduction in solid components (osteoid)- increase in living cellular component of bone. Causes fractures
- Osteomalacia: reduction in mineralised component (increased osteoid). Causes Bend
50
Q
Bone remodelling cycle
A
- Resorption: multinucleated osteoclasts adheres to bone and secretes acid reabsorbing the bone
- Osteoid formation: Osteoblasts are signalled to reform eroded bone, form osteoid which is mineralised
- Lining cells lie on the top of the bone protecting it from osteoclasts
