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hypercalcemia and granulomatous diseases:

Macrophages and giant cells express high levels of 1α-hydroxylase, an enzyme that catalyzes the hydroxylation of 25-OH vitamin D to its active form, 1,25-(OH)2 vitamin D.

Granulomatous disorders (like sarcoidosis and TB) are characterized by the presence of granulomas which contain large numbers of macrophages and giant cells that lead to the overproduction of 1α-hydroxylase which is held responsible for the development of hypercalcemia in sarcoidosis patients.

Hyperparathyroidism (HPT) is divided to:

• Primary HPT: caused by excessive production of PT hormone from the PT gland. Most cases are due to a benign adenoma, only rarely it is caused by a malignant carcinoma.

• Secondary HPT: excessive PT hormone production in response to hypocalcemia (usually due to CKD, or vitamin D deficiency).

• Tertiary HPT: it's a result of long-standing secondary HPT in which the excessively high levels of PT hormone persist even after correcting the hypocalcemia.

This is caused by either of two mechanisms:

1. Humoral: in which the tumor (most commonly squamous cell, and renal carcinoma) produces something called parathyroid-related peptide (PTrP). You can guess what PTrP does from the name.

2. Bony metastasis: in which the cancer directly invades and erodes the bone (by producing osteoclast-activating factors) and thereby increasing the serum calcium levels.

To distinguish humoral hypercalcemia of malignancy (HHM) from HPT, all you need to do is to measure the level of PT hormone in the patient:

• if PT hormone is high, then it's HPT.
• if PT hormone is low or normal, then it's HHM (because HHM releases PTrP, not PT hormone).

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They are the most common cancers in infancy, and the most common extracranial cancers in childhood.
They are usually diagnosed before 5 years of age, and are classified into 3 subtypes:

• Neuroblastoma (malignant).
• Ganglioneuroblastoma (intermediate).
• Ganglioneuroma (benign).

MEN syndrome
(Multiple Endocrine Neoplasia syndrome)

MEN type-1

MEN type-2

MEN-2A

Familial thyroid medullary cancer

MEN-2B