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Toronto Notes 2019 Calcium Homeostasis
Investigations
• MENI
■ laboratory
◆ may consider genetic screening for MEN-1 mutation in index patients – if a mutation is identified, screen family members who are at risk
◆ gastrinoma: elevated serum gastrin level (>200 ng/mL) after IV injection of secretin
◆ insulinoma: reduced fasting blood glucose (hypoglycemia) with elevated insulin and C-peptide
levels
◆ glucagonoma: elevated blood glucose and glucagon levels
◆ pituitary tumours: assess GH, IGF-1, and prolactin levels (for over-production), TSH, free T4, 8
AM cortisol, LH, FSH, bioavailable testosterone or estradiol (for underproduction due to mass
effect of tumour)
◆ hyperparathyroidism: serum Ca2+ and albumin, PTH levels; bone density scan (DEXA)
■ imaging
◆ MRI for pituitary tumours, gastrinoma, insulinoma
• MENII
■ laboratory
◆ genetic screening for RET mutations in all index patients
– if a mutation is identified, screen family members who are at risk
◆ calcitonin levels (MTC); urine catecholamines and metanephrines (pheochromocytoma); serum Ca2+, albumin, and PTH levels (hyperparathyroidism)
◆ pentagastrin ± calcium stimulation test if calcitonin level is within reference range
◆ FNA for thyroid nodules-cytology ■ imaging
◆ CT or MRI of adrenal glands, metaiodobenzylguanidine (MIBG) scan for pheochromocytoma ◆ octreoscan and/or radionuclide scanning for determining the extent of metastasis
Treatment
• MENI
■ medical
◆ proton pump inhibitor (PPI) for acid hypersecretion in gastrinoma
◆ cabergoline or other dopamine agonists to suppress prolactin secretion ◆ somatostatin for symptomatic carcinoid tumours
■ surgery for hyperparathyroidism, insulinoma, glucagonoma, pituitary tumours (if medical treatment fails for the latter)
◆ trans-sphenoidal approach with prn external radiation
• MENII
■ surgery for MEN IIa with pre-operative medical therapy
◆ prostaglandin inhibitors to alleviate diarrhea associated with thyroid cancer ◆ α-blocker for at least 10-21 d for pheochromocytoma pre-operatively
◆ hydration, calcitonin, IV bisphosphonates for hypercalcemia
Calcium Homeostasis
• normal total serum Ca2+: 2.2-2.6 mmol/L
• ionic/free Ca2+ levels: 1.15-1.31 mmol/L
• serum Ca2+ is about 40% protein bound (mostly albumin), 50% ionized, and 10% complexed with PO43-
and citrate
• regulatedmainlybytwofactors:parathyroidhormone(PTH)andvitaminD
• actions mainly on three organs: GI tract, bone, and kidney
Endocrinology E37
Table 28. Major Regulators in Calcium Homeostasis
Primary Hyperparathyroidism
Increased PTH secretion commonly due to parathyroid adenoma, lithium therapy; less often due to parathyroid carcinoma or parathyroid hyperplasia
Secondary Hyperparathyroidism Partial resistance to PTH action leads to parathyroid gland hyperplasia and increased PTH secretion, often in patients with renal failure and osteomalacia (due to low or low normal serum calcium levels)
Tertiary Hyperparathyroidism Irreversible clonal outgrowth of parathyroid glands, usually in long-standing inadequately treated chronic renal failure on dialysis
Net Effect
 Ca2+
 Cacitriol
 PO43-  Ca2+  PO43-
Ca2+ (in pharmacologic doses)  PO43-
Cofactor for PTH secretion  Ca2+
Major Regulators
PTH
Calcitriol (1,25-(OH)2D3)
Calcitonin
Mg2+ PO43-
Source
Parathyroid glands
Dietary intake of cholecalciferol (D3) or ergocalciferol (D2) OR
Synthesized from cholesterol: UV light on skin makes cholecalciferol (D3). Liver then coverts it to calcidiol (25- (OH)D3) and kidneys convert it to calcitriol
Thyroid C cells
Major intracellular divalent cation Intracellular anion found in all tissues
Regulation
Stimulated by low serum Ca2+ and high serum PO43- Inhibited by high serum Ca2+, high calcitriol, FGF23, and chronic low serum Mg2
Stimulated by: Low serum PO43 High PTH
Inhibited by:
High serum PO43
Low PTH
Calcitriol (negative feedback) FGF23
Stimulated by:
Pentagastrin (GI hormone) and high serum Ca2+; inhibited by low serum Ca2+
See Serum Magnesium, NP15 See Serum Phosphate, NP14