Hypoparathyroidism & Pseudohypoparathyroidism

Key Features

Essentials of Diagnosis

• Tetany, carpopedal spasms, tingling of lips and hands, cramps, irritability

• Chvostek sign and Trousseau phenomenon

• Hypocalcemia with low serum parathyroid hormone (PTH); serum phosphate high; alkaline phosphatase normal; urine calcium excretion reduced

• Serum magnesium may be low

General Considerations

• Acquired hypoparathyroidism

  • Most commonly caused by anterior neck surgery, occurring after total thyroidectomy in about 25% of patients transiently, and in about 4% of patients permanently

  • Risk is higher for patients undergoing total thyroidectomy (especially large goiters) or surgery for Graves disease, patients over age 50, and when fewer than 2 parathyroid glands are identified at surgery

  • Risk of permanent postoperative hypoparathyroidism can be reduced during thyroid surgery by taking parathyroid glands with suspected vascular damage and autotransplanting them into the sternocleidomastoid muscle

• Permanent hypoparathyroidism

  • May occur after the resection of multiple parathyroid adenomas

  • In cases of "hungry bone syndrome" (transient hypoparathyroidism after the surgical removal of a single parathyroid adenoma for primary hyperparathyroidism due to suppression of the remaining normal parathyroids and accelerated remineralization of the skeleton), hypocalcemia can be quite severe, particularly in patients with preoperative hyperparathyroid bone disease and vitamin D or magnesium deficiency

  • Neck irradiation is a rare cause

• Autoimmune hypoparathyroidism may be isolated or combined with other endocrine deficiencies

• Parathyroid deficiency may be caused by

  • Damage from heavy metals such as copper (Wilson disease) or iron (hemochromatosis, transfusion hemosiderosis)

  • Granulomas

  • Riedel thyroiditis

  • Tumors

  • Infection

• Magnesium deficiency causes functional hypoparathyroidism

• Hypomagnesemia

  • Most commonly caused by alcoholism, diuretics, intestinal malabsorption, and proton pump inhibitors

  • Can also be caused by

    • Certain antibiotics (aminoglycosides, amphotericin, and pentamidine)

    • Epithelial growth factor inhibitors (panitumumab, cetuximab) for colon cancer

  • Mild hypomagnesemia stimulates PTH secretion; however, more severe hypomagnesemia (< 1.2 mg/dL) inhibits PTH secretion

  • Also causes resistance to PTH in bone and renal tubules

• Symptomatic hypoparathyroidism may be precipitated by a proton pump inhibitor, since absorption of calcium decreases with reduced stomach acidity

• Congenital hypoparathyroidism

  • Causes hypocalcemia beginning in infancy; however, it may not be diagnosed for many years

  • Since hypoparathyroidism can be familial, screening is suggested for family members of any patient with idiopathic hypoparathyroidism

  • Genetic testing is suggested for the following

    • Early-onset idiopathic hypoparathyroidism

    • Hypoparathyroidism with a family history of idiopathic hypoparathyroidism

  • DiGeorge syndrome is another cause of congenital hypoparathyroidism, along with congenital cardiac and facial anomalies

Clinical Findings

Symptoms and Signs

• Manifestations of hypocalcemia vary from subtle to life-threatening

• Patients may complain of fatigue, irritability, depression, anxiety, cognitive impairment or "brain fog", lethargy, and paresthesias in the circumoral area, hands, and feet

• More severe manifestations include muscle weakness or cramps, carpopedal spasm, convulsions, tetany, laryngospasm, and stridor

• Brain calcifications in the basal ganglia and cerebral cortex can cause Parkinsonian symptoms or choreoathetosis

• Chronic hypocalcemia with hyperphosphatemia can cause ...