Other Endocrine Diseases Flashcards
What are the associated neoplasias of MEN1?
Pituitary, parathyroid, pancreatic (3 Ps)
What are the associated neoplasias of MEN2A?
Medullary Thyroid Ca, Pheochormocytoma, Parathyroid (2Ps, 1M)
What are the associated neoplasias of MEN2B?
Medullary thyroid Ca, Marfanoid habitus/mucosal neuroma, Pheochromocytoma (1P, 2Ms)
What are the genetics of the MEN1?
Autosomal dominant, MEN1 gene-11q, classic tumour suppressor, bi-allelic inactivation and LOH, mutations occur throughout MEN1 gene
What are the genetics of MEN2?
Autosomal dominant, RET gene-10q, Classic proto-oncogene, activating mutations limited to specific codons
Why is MEN1 important?
Premature morbidity and mortality-50% of affected individuals will die as a direct result of the disease. Considerable psychological burden
What are the genetics of VHL syndrome?
Mutation in VHL gene-autosomal dominant
What does the mutation in VHL syndrome lead to?
Accumulation of HIF proteins and stimulation of cellular proliferation
What are the classic symptoms of NF1?
Axillary freckling, cafe au lait patches, neurofibromas
What are some pitfalls in phaeochromocytoma diagnosis?
Catecholamines raised in heart failure, episodic catecholamine secretion , malignant/extra adrenal tumours less efficient at catecholamine synthesis
What are the acute symptoms of hypercalcaemia?
Thirst, dehydration, confusion, polyuria
What are the chronic symptoms of hypercalcaemia?
Myopathy, osteopaenia, fractures, depression, HT, abdo pain-pancreatitis, ulcers, renal stones
What should you think to remind you of hypercalcaemia?
Stones, groans, bones, psychic moans
What does hypercalcaemia with normal/low albumin with suppressed PTH and high phosphate indicate?
Bone pathology
In hypercalcaemia caused by a bone pathology what does high alkaline phosphatase indicate?
Bone mets, sarcoidosis, thyrotoxicosis
In hypercalcaemia caused by a bone pathology what does low alkaline phosphatase indicate?
Myeloma, vit D excess, mild-alkali syndrome (thyrotoxicosis, sarcoidosis, raised bicarb)
In hypercalcaemia with normal/low albumin, PTH normal/high, phosphate low/normal and increased urine calcium what is the likely cause?
Primary/tertiary hyperparathyroidism
In hypercalcaemia with normal/low albumin, PTH normal/high, phosphate low/normal and decreased urine calcium what is the likely cause?
FHH
In hypercalcaemia with raised albumin and urea what is the likely cause?
Dehydration
In hypercalcaemia what does a raised albumin but normal urea usually indicate?
Cuffed sample
What are the causes of hypercalcaemia?
Primary hyperparathyroidism, malignancy, drugs:vit D, thiazides, granulomatous disease e.g. sarcoid, TB, FHH, high turnover (bedridden, thyrotoxic, pagets), tertiary hyperparathyroidism, others
How is a diagnosis of primary hyperparathyroidism made?
Raised serum calcium, raised serum PTH (or inappropriately normal), increased urine calcium excretion
How does hypercalcaemia occur due to malignancy?
Metastatic bone destruction, PTHrp from solid tumours, osteoclast activating factors
How do you diagnosis hypercalcaemia of malignancy?
Raised calcium and ALP, X-ray, CT, MRI, isotope bone scan
What is the treatment for acute hypercalcaemia?
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
What is the management of primary hyperparathyroidism?
Surgery (but not always required) or nothing.
What are the indications for parathyroidectomy?
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
What is secondary hyperparathyroidism?
Physiological response to low calcium
What is tertiary hyperparathyroidism?
Parathyroid becomes autonomous after many years of secondary
What are the biochemical features of Familial Hypocalciuric Hypercalcaemia?
Mild hypercalcaemia, reduced urine calcium excretion, PTH may be elevated
What are the signs and symptoms of hypocalcaemia?
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
What are the possible causes of hypocalcaemia?
Hypoparathyroidism, vitamin D deficiency (osteomalacia, rickets), chronic renal failure
What is the treatment for acute hypocalcaemia?
Emergency: IV calcium gluconate 10ml,10% over 10 mins (in 50ml saline or dextrose), infusion (10ml 10% in 100ml infusate, at 50ml/h)
What are some causes of hypoparathyroidism?
Congenital absence (DiGeorge syndrome), destruction (surgery, radiotherapy, malign), AI, hypomagnesaemia, idiopathic
What is the long term management of hypoparathyroidism?
Calcium supplement, vitamin D replacement
What is calcium release from cells dependent on?
Magnesium
Is intracellular calcium low or high in magnesium deficiency?
High
What changes to PTH sensitivity and release occur during hypomagnasaemia?
PTH release is inhibited, and skeletal and muscle receptors are less sensitive to PTH
What are some of the causes of hypomagnasaemia?
Alcohol, drugs-thiazide, PPI, GI illness, pancreatitis, malabsorption
What is pseudohypoparathyroidism?
Low calcium but PTH concentrations are elevated due to PTH resistance
What is the genetic defect in pseudohypoparathyroidism?
Dysfunction of G protein (Gs alpha subunit) gene-GNAS 1
How does pseudohypoparathyroidism present?
Bone abnormalities (McCune Albright), obesity, subcut calcification, learning disability, brachdactyly (4th MCP)
What is pseudo-pseudohypoparathyroidism?
Like pseudohypoparathyroidism, but with normal calcium
What is rickets and osteomalacia caused by?
Vit D deficiency due to malabsorption (gastric surgery, coeliac, liver disease, pancreatic failure), chronic renal failure, lack of sunlight, drugs e.g. anticonvulsants
How does osteomalacia present?
Low calcium, muscle wasting-proximal myopathy, dental defects (caries, enamel), bone-tenderness, fractures, rib deformity, limb deformity
What are looser zones?
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
What is often seen in patients with chronic kidney disease?
Secondary hyperparathyroidism
How will osteomalacia due to lack of UV exposure present?
Low calcium, low phosphate, high ALP, low vit D (25-OH), PTH-high
What are long term consequences of vitamin D deficiency?
Demineralisation/fractures, osteomalacia/rickets, malignancy (especially colon), heart disease, diabetes etc.
What is the treatment for chronic vitamin D deficiency?
Vit D tablets, or combined calcium + Vit D
What is vitamin D-resistant rickets also known as?
X-linked hypophosphataemia
What gene is mutated in vitamin D-resistant rickets?
PHEX gene mutation
How do people with vitamin D-resistant rickets present?
Low phosphate, high vitamin D
How is vitamin D-resistant rickets treated?
With phosphate and Vit D supplements (1,25-OH Vit D3) +/- Surgery
