Distinguish the pathophysiology of hypercalcemia for various clinical states. Also review the most important principles of endocrinology.

Explanation:

Commonest cause for  true high calcium is Primary hyperparathyroidism and its commonest presentation is asymptomatic. Gets discovered in a routine screening lab work-up. First test after finding a high calcium in such a patient  is PARATHORMONE level (provided the PO4 is low and you have corrected for albumin). Next step if PTH is elevated is NECK EXPLORATION by an EXPERIENCED surgeon.

I use the word true  when I talk about hypercalcemia because if a tourniquet is left  on the patient for a long time before blood is drawn then there is a falsely elevated Calcium level.

Secondary hyper parathyroidism is NOT A CAUSE OF HIGH CALCIUM. Seen in patients who have renal failure. Due to low Vit D3 there is low Ca in blood thus PTH level is elevated.

Tertiary hyperparathyroidism on the other hand is a cause of hypercalcemia. It is the conversion of a secondary hyperparathyroidism state of parathyroid to an autonomous state due to chronic stimulation by the low calcium.

NOTE(very important): IN ENDOCRINOLOGY FEEDBACK IS THE MOST IMPORTANT CONCEPT USED. For example if the calcium is high- the PTH should be very suppressed (if something other than PTH itself is causing the high Ca-for instance in hypercalcemia of malignancy). Therefore if PTH is anything other than very suppressed   then in such a patient it points to a diagnosis of Primary hyperparathyroidism -EVEN IF PTH IS IN THE NORMAL RANGE in a patient with high calcium-the diagnosis is hyperparathyroidism.

Other such feedback pairs are

• Thyroid hormones and TSH Therefore if thyroid hormones are high and TSH is in the normal range - the toxicosis is being driven by TSH

• Cortisol and ACTH Therefore if cortisol is high and ACTH is in the normal range - the hypercortisolism is being driven by ACTH

• Glucose and glucagon. Therefore if glucose level is high and Glucagon is in the normal range - the diabetes is being driven by a glucagonoma.

The following conditions cause hypercalcemia by mediators other than PTH thus PTH levels in them will be LOW

Myeloma- Hypercalcemia mediated via OAF(osteoclast activating factor)

SQUAMOUS cell cancer of Lung- Mediated via PTHrp(PTH related peptide) and also because of osteolytic metastases (commoner of the two).

Sarcoidosis- Via excess production of Vit D3(by alpha 1 hydroxylase) in the granulomas which also produce ACE(angiotensin converting enzyme)

Milk alkali syndrome- in a patient who has reflux disease and who thus consumes large amounts of antacids containing calcium or consumes a lot of milk to douse the heartburn.