128; GEN Endocrine Flashcards
What cells secrete PTH?
Chief Cells of the parathyroid glands
What is the function of PTH?
- Increase tubular reabsorption of Ca
- VitD production
- Osteoclast mediated bone resorption
What is the most common cause of Hypercalcaemia?
- Primary hyperparathyroidism
- Malignancy
Less common
Milk-alkali syndrome
Diet
Thiazide diuretics
Sarcoid
Familial Benign Hypocalciuric Hypercalcaemia
What are the biological effects of PTH excess in Serum and urine tests?
Serum
- ↑Calcium
- ↑ PTH
- ↑Alkaline phosphatase
- ↑Chloride
- ↓Bicarbonate
- ↓Phosphorus
Urine
- ↑Calcium
- ↑Phosphorus
- ↑cAMP
WHat are the causes of primary Hyperparathyroidism?
Parathyroid
- Adenoma
- Carcinoma
- Hyperplasia
What are the causes of secondary hyperparathyroidism?
- Hypocalcaemia
What are the causes of tertiary Hyperparathyroidism?
Autonomous secretion of PTH following long-term hypocalcaemia
(Autonomous- not sensitive to Ca levels any more although they may be raised)
What would would a symptomatic Pt with Primary hyperparathyroidism present with?
Stones
- Kidney stones, nephrocalcinosis
Groans
- Bone pain, fractures, proximal myopathy
Thrones
- Polyuria, Constipation, N&V
Psychiatric Overtones
- Depression, confusion, tiredness
Cardiac
- Bradycardia, Heart block
What is the epidemiology of primary hyperparathyroidism?
Men >50
Female post-menopausal
What are the familial causes of Hyperparathyroidism?
Multiple endocrine nepolasia (MEN) 1
MEN 2a
Familial hyperparathyroidism
Familial hyopcalciuric hypercalcaemia
What investigations would be done for hyperparathyroidism?
Serum
- Calcium
- Phosphate
- U&E
- PTH
- VitD
Urine
- 24H urinary calcium
Imaging
- Chest Xray
- Bone density
- US kidneys
What is the treatment for Hyperparathyroidism?
Conservative
- Hydration, avoid diuretics, diet
Surgical
- Adenoma; unilateral removal of PTHyroids
- Hyperplasia; total PTHyroidectomy, forearm transplantation, Thymus removal
- Carcinoma; Removal and thymectomy
What are the most common malignancies associated with hypercalcaemia?
Lung 35%
Breast 25%
Blood (myeloma, lymphoma) 14%
Head & neck 6%…
What is the mechanism behind Malignant Hypercalcaemia?
**Increased osteoclast bone resorption **
- Tumour secrete osteoclast stimulating factors:
- cytokines; interleukins, chemokines
- PTH-related peptide from squ. cell cancers and breast cancer
- Ectopic PTH production (rare)
What are the signs and symptoms of severe hypercalcaemia?
Serum Calcium > 3.5mmol/l
Reduced GFR & impaired renal calcium clearance
Impaired renl tubular reabsorption
Extracellular volume depletion
Elevated PTHrP levels
What is the treatment fpr severe hypercalcaemia?
- Tumour ablation
- IV fluids
- Diuretics; frusemide with care
- Bisphosphonates
- Glucocorticoids
- Calcitonin
What are the causes of hypocalcaemia?
Hypoparathyroidism
Target organ resistance
VitD related disorders;
Diet, malabsorption
Liver, kidney disease
Drugs
Target organ resistance
What are the clinical presentations of hypocalcaemia?
Chvostek’s sign (hyperexcitability of facial nerve)
Trousseau’s sign (BP cuff, spasm of hand and forearm)
ECG; prolonged QT
Laryngeal spasm
Tetany
What is the treatment of Hypocalcaemia?
IV calcium infusions
IV Mg infusions
Oral Calcium carbonate
Oral magnesium
Oral VitD (or parenteral)
What are the causes of Hypoparathyroidism?
- Post surgical, transient or permanent
- Post radioactive iodine
- Polyendocrine deficiency syndromes
- Idiopathic
- Hypomagnaesaemia
- Metastases, haemochromotosis, chemotherapy
- Di George Syndrome
- Biologically inactive PTH
- Resistance to PTH, pseudo hypoparathyroidism
What would be the plasma profile in HypoPTH?
Low Ca
High PO4
Low/normal PTH?
Low Mg?
What is the aetiology for HypoPTH?
- Neck scar
- Coincidental autoimmune disease, monoliasis, family history
- Coincidental disease, malignancy
- Serum magnesium level
- Alcoholism, drug therapy
- Albright’s Hereditary Osteodystrophy (AHO)
- Neonatal hyperparathyroidism
What are the causes of PseudoHypoPTH?
Deficient G subunit in PTH receptor
Hormone resistance including TSH, FSH, LH
Albright’s hereditary Osteodystrophy
- Short stature
- Round face
- Short 4th metacarpal
- Obesity
- Subcutaneous calcification
How does PTH affect Ca and PO4 secretion in urine?
PTH:
- Increases phosphaturia
- Decreases Calciuria
What is PseudoPseudoHypoParathyroidism?
- Phenotypic appearance of pseudoHypoPTH, but biochemically normal -ish
- 1st degree relative with PseudoHypoPTH
- Variant of Albright’s Hereditary Osteodystrophy
