CALCIUM HOMEOSTASIS & PARATHYROID DISORDERS DR. MAHMUDUL HUQUE HOLY FAMILY RED CRESCENT MEDICAL COLLEGE

Calcium Homeostasis calcium homeostasis is the mechanism by which the body maintains adequate calcium levels. Derangements of this mechanism lead to hypercalcaemia or hypocalcaemia, both of which can have important consequences for health.

Normal range: 9–10.5 mg/dL or 2.2–2.6 mmol/L

Corrected Ca level Corrected calcium (mg/dL) = measured total Ca (mg/dL) + 0.8 X (4.0 - serum albumin [g/dL]

Hypercalcemia Polyurea, polydipsia Renal colic, lethargy Anorexia, nausea, dyspepsia Peptic ulcer, depression, drowsiness Impaired cognition Acute/chronic onset Malignant Hypercalcaemia Ca>12 mg/dl

Causes of Hypercalcemia Abnormal parathyroid gland function Primary or tertiary hyperparathyroidism Lithium induced familial hypocalciuric hypercalcaemia Malignancy Lungs, breast, renal, ovarian, colon, Thyroid malignancy. haematologic malignancy (multiple myeloma, Lymphoproliferative disorders)

Contd… Vitamin-D metabolic disorders hypervitaminosis D (vitamin D intoxication) elevated 1,25(OH)2D levels (e.g. sarcoidosis) Others Thyrotoxicosis – TSH, FT3, FT4 Thiazide use Paget's disease of the bone Addison’s disease severe secondary hyperparathyroidism milk-alkali syndrome

Treatment Hydrate with Normal saline: 4-6L deficient Diuretics: Look for K, Mg Salmon calcitonin: BD, 5-8 u/Kg, 3-4 days BISPHOSPHONATES: Pamidronate & Zoledronic acid Plicamycine / Gallium nitrate (toxic) Steroids: 40mg/day In granulomatous sarcoidosis Haemodialysis Treat cause

Hypercalcaemia Oral, perioral and acral paresthesias, tingling or 'pins and needles' sensation. This is often the earliest symptom of hypocalcaemia. Carpopedal Spasm and generalized tetany Latent tetany: Trousseau sign of latent tetany (eliciting carpal spasm by inflating the blood pressure cuff and maintaining the cuff pressure above systolic). Chvostek's sign (tapping of the inferior portion of the zygoma will produce facial spasms). Epilepsy, Psycosis Papilloedema Basal ganglia Calcification Metastatic calcification Severe Hypocalcaemia <6mg/dl

Causes of Hypocalcaemia Absent parathyroid hormone (PTH) Hereditary hypoparathyroidism Following parathyroidectomy Following thyroidectomy, the parathyroid glands are located very close to the thyroid and are easily injured or even accidentally removed during thyroidectomy In DiGeorge Syndrome, a disease characterized by the failure of the third and fourth pharyngeal pouches to develop, the parathyroid glands do not form and there is thus a lack of PTH. Storage – Al, Cu, Fe Trauma or vascular formation

Contd…. Alkalosis: Resp. + Metabolic CRF Vit. D deficiency, Malabsoption syndrome Pseudo hypoparathyroidism Acute pancreatitis Drug- Ca lowering drugs Massive Blood transfusion Osteoblastic metastasis

Treatment of Hypocalcaemia If alkalosis: Rebreath expired air or 5% CO2 in O2 . 10% Calcium gluconate slow IV to keep Ca >7mg/dl till relief. Oral Calcium: 1.5-3 gms elemental Ca, 500 mg of Ca tab. If serum Ca fall bellow 7mg/dl, give again after 6hrs Ca gluconate Upto 100mg/day. Tab. 1α in persistant hypo parathyroidism Magnesium (nalepsin) in calcium resistant persons

Hyperparathyroidism Primary: Single adenoma-90% Multiple adenoma-4% Nodular hyperplasia-5% Carcinoma-1% S. Ca PTH Secondary: CRF (specially) Malabsorption Osteomalacia & ricket S.Ca Tertiary: Esp. CRF

Contd…. Serum biochemical hyper and hypo calcaemia occupies the clinical spectrum of parathyroid disease. So are the features of hyper/hypo calcaemia.

Diagnosis Features of hypercalcaemia PTH radio-immuno assay 24 hr urinary calcium increased Radiology: Osteitis fibrosa cystica, Pepperpot skull, Bone cyst- brown tumour Tumour localisation by- Surgery, USG, CT, Neck catheterisation, PTH measurement, Technetium isotope imaging.

Treatment Manage hypercalcaemia Remove the tumour Tagging the remnant Transplant in symptomatic, young & progressive Secondary: Calcitriol to suppress PTH Tertiary: Remove

Hypoparathyroidism Hypocalcaemia, signs and symptoms of decreased Ca. Hyperphosphatemia Undetectable PTH Exclude serum Mg deficiency. If (+) Functional Hypoparathyroidism.

Hypoparathyroidism It is due to destruction, surgery, Vascular damage, or idiopathic as part of poly-glandular failure or agenesis (DiGeorge syndrome)

Pseudohypoparathyroidism Pseudohypoparathyroidism is a condition associated primarily with resistance to the parathyroid hormone. Patients have a low serum calcium and high phosphate, but the parathyroid hormone level (PTH) is actually appropriately high (due to the hypocalcaemia). Increased PTH + biochemically Low Ca and High PO4 + body stigma. Features: Short stature, obese with round face, short 4th and 5th metacarpal, mental retardation, defective teeth & bone formation

Short stature, obese with round face

blunting of the fourth and fifth knuckles of the hand Short 4th and 5th metacarpals blunting of the fourth and fifth knuckles of the hand

Pseudopseudohypoparathyroidism Pseudopseudohypoparathyroidism (pseudoPHP) is an inherited disorder, named for its similarity to pseudohypoparathyroidism in presentation. The term pseudopseudohypoparathyroidism is used to describe a condition where the individual has the phenotypic appearance of pseudohypoparathyroidism, but is biochemically normal. It is sometimes considered a variant of Albright hereditary osteodystrophy.

Young woman with short stature, disproportionate shortening of the limbs, generalized obesity, and round, flattened face. Radiograph of the hand showing the shortened 4th and 5th metacarpals

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