Other Endocrine Diseases

Question 1

What are the associated neoplasias of MEN1?

Answer 1

Pituitary, parathyroid, pancreatic (3 Ps)

Question 2

What are the associated neoplasias of MEN2A?

Answer 2

Medullary Thyroid Ca, Pheochormocytoma, Parathyroid (2Ps, 1M)

Question 3

What are the associated neoplasias of MEN2B?

Answer 3

Medullary thyroid Ca, Marfanoid habitus/mucosal neuroma, Pheochromocytoma (1P, 2Ms)

Question 4

What are the genetics of the MEN1?

Answer 4

Autosomal dominant, MEN1 gene-11q, classic tumour suppressor, bi-allelic inactivation and LOH, mutations occur throughout MEN1 gene

Question 5

What are the genetics of MEN2?

Answer 5

Autosomal dominant, RET gene-10q, Classic proto-oncogene, activating mutations limited to specific codons

Question 6

Why is MEN1 important?

Answer 6

Premature morbidity and mortality-50% of affected individuals will die as a direct result of the disease. Considerable psychological burden

Question 7

What are the genetics of VHL syndrome?

Answer 7

Mutation in VHL gene-autosomal dominant

Question 8

What does the mutation in VHL syndrome lead to?

Answer 8

Accumulation of HIF proteins and stimulation of cellular proliferation

Question 9

What are the classic symptoms of NF1?

Answer 9

Axillary freckling, cafe au lait patches, neurofibromas

Question 10

What are some pitfalls in phaeochromocytoma diagnosis?

Answer 10

Catecholamines raised in heart failure, episodic catecholamine secretion , malignant/extra adrenal tumours less efficient at catecholamine synthesis

Question 11

What are the acute symptoms of hypercalcaemia?

Answer 11

Thirst, dehydration, confusion, polyuria

Question 12

What are the chronic symptoms of hypercalcaemia?

Answer 12

Myopathy, osteopaenia, fractures, depression, HT, abdo pain-pancreatitis, ulcers, renal stones

Question 13

What should you think to remind you of hypercalcaemia?

Answer 13

Stones, groans, bones, psychic moans

Question 14

What does hypercalcaemia with normal/low albumin with suppressed PTH and high phosphate indicate?

Answer 14

Bone pathology

Question 15

In hypercalcaemia caused by a bone pathology what does high alkaline phosphatase indicate?

Answer 15

Bone mets, sarcoidosis, thyrotoxicosis

Question 16

In hypercalcaemia caused by a bone pathology what does low alkaline phosphatase indicate?

Answer 16

Myeloma, vit D excess, mild-alkali syndrome (thyrotoxicosis, sarcoidosis, raised bicarb)

Question 17

In hypercalcaemia with normal/low albumin, PTH normal/high, phosphate low/normal and increased urine calcium what is the likely cause?

Answer 17

Primary/tertiary hyperparathyroidism

Question 18

In hypercalcaemia with normal/low albumin, PTH normal/high, phosphate low/normal and decreased urine calcium what is the likely cause?

Answer 18

FHH

Question 19

In hypercalcaemia with raised albumin and urea what is the likely cause?

Answer 19

Dehydration

Question 20

In hypercalcaemia what does a raised albumin but normal urea usually indicate?

Answer 20

Cuffed sample

Question 21

What are the causes of hypercalcaemia?

Answer 21

Primary hyperparathyroidism, malignancy, drugs:vit D, thiazides, granulomatous disease e.g. sarcoid, TB, FHH, high turnover (bedridden, thyrotoxic, pagets), tertiary hyperparathyroidism, others

Question 22

How is a diagnosis of primary hyperparathyroidism made?

Answer 22

Raised serum calcium, raised serum PTH (or inappropriately normal), increased urine calcium excretion

Question 23

How does hypercalcaemia occur due to malignancy?

Answer 23

Metastatic bone destruction, PTHrp from solid tumours, osteoclast activating factors

Question 24

How do you diagnosis hypercalcaemia of malignancy?

Answer 24

Raised calcium and ALP, X-ray, CT, MRI, isotope bone scan

Question 25

What is the treatment for acute hypercalcaemia?

Answer 25

Fluids-rehydrate with 0.9% saline 4-6l in 24hrs, consider loop diuretics once rehydrated, biphosphonates, steroids e.g. pred 40-60mg/day for sarcoidosis, chemo in malignant disease

Question 26

What is the management of primary hyperparathyroidism?

Answer 26

Surgery (but not always required) or nothing.

Question 27

What are the indications for parathyroidectomy?

Answer 27

End organ damage: bone disease (osteitis fibosa et cystica; brown tumours/pepper pot skull), gastric ulcers, renal stones, osteoporosis, very high calcium (>2.85mmol/l), under age 50, eGFR decreased

Question 28

What is secondary hyperparathyroidism?

Answer 28

Physiological response to low calcium

Question 29

What is tertiary hyperparathyroidism?

Answer 29

Parathyroid becomes autonomous after many years of secondary

Question 30

What are the biochemical features of Familial Hypocalciuric Hypercalcaemia?

Answer 30

Mild hypercalcaemia, reduced urine calcium excretion, PTH may be elevated

Question 31

What are the signs and symptoms of hypocalcaemia?

Answer 31

Paraesthesia-fingers, toes, perioral, muscle cramps, tetany, muscle weakness, fatigue, bronchospasm/laryngospasm, fits, chovsteks sign (tapping over facial nerve), trousseau sign (carpopedal spasm), QT prolongation

Question 32

What are the possible causes of hypocalcaemia?

Answer 32

Hypoparathyroidism, vitamin D deficiency (osteomalacia, rickets), chronic renal failure

Question 33

What is the treatment for acute hypocalcaemia?

Answer 33

Emergency: IV calcium gluconate 10ml,10% over 10 mins (in 50ml saline or dextrose), infusion (10ml 10% in 100ml infusate, at 50ml/h)

Question 34

What are some causes of hypoparathyroidism?

Answer 34

Congenital absence (DiGeorge syndrome), destruction (surgery, radiotherapy, malign), AI, hypomagnesaemia, idiopathic

Question 35

What is the long term management of hypoparathyroidism?

Answer 35

Calcium supplement, vitamin D replacement

Question 36

What is calcium release from cells dependent on?

Answer 36

Magnesium

Question 37

Is intracellular calcium low or high in magnesium deficiency?

Answer 37

High

Question 38

What changes to PTH sensitivity and release occur during hypomagnasaemia?

Answer 38

PTH release is inhibited, and skeletal and muscle receptors are less sensitive to PTH

Question 39

What are some of the causes of hypomagnasaemia?

Answer 39

Alcohol, drugs-thiazide, PPI, GI illness, pancreatitis, malabsorption

Question 40

What is pseudohypoparathyroidism?

Answer 40

Low calcium but PTH concentrations are elevated due to PTH resistance

Question 41

What is the genetic defect in pseudohypoparathyroidism?

Answer 41

Dysfunction of G protein (Gs alpha subunit) gene-GNAS 1

Question 42

How does pseudohypoparathyroidism present?

Answer 42

Bone abnormalities (McCune Albright), obesity, subcut calcification, learning disability, brachdactyly (4th MCP)

Question 43

What is pseudo-pseudohypoparathyroidism?

Answer 43

Like pseudohypoparathyroidism, but with normal calcium

Question 44

What is rickets and osteomalacia caused by?

Answer 44

Vit D deficiency due to malabsorption (gastric surgery, coeliac, liver disease, pancreatic failure), chronic renal failure, lack of sunlight, drugs e.g. anticonvulsants

Question 45

How does osteomalacia present?

Answer 45

Low calcium, muscle wasting-proximal myopathy, dental defects (caries, enamel), bone-tenderness, fractures, rib deformity, limb deformity

Question 46

What are looser zones?

Answer 46

Wide, transverse lucencies traversing part way through a bone, usually at right angles to the involved cortex and are associated most frequently with osteomalacia and rickets

Question 47

What is often seen in patients with chronic kidney disease?

Answer 47

Secondary hyperparathyroidism

Question 48

How will osteomalacia due to lack of UV exposure present?

Answer 48

Low calcium, low phosphate, high ALP, low vit D (25-OH), PTH-high

Question 49

What are long term consequences of vitamin D deficiency?

Answer 49

Demineralisation/fractures, osteomalacia/rickets, malignancy (especially colon), heart disease, diabetes etc.

Question 50

What is the treatment for chronic vitamin D deficiency?

Answer 50

Vit D tablets, or combined calcium + Vit D

Question 51

What is vitamin D-resistant rickets also known as?

Answer 51

X-linked hypophosphataemia

Question 52

What gene is mutated in vitamin D-resistant rickets?

Answer 52

PHEX gene mutation

Question 53

How do people with vitamin D-resistant rickets present?

Answer 53

Low phosphate, high vitamin D

Question 54

How is vitamin D-resistant rickets treated?

Answer 54

With phosphate and Vit D supplements (1,25-OH Vit D3) +/- Surgery