Hypoparathyroidism for the ABIM

Hypoparathyroidism for the American Board of Internal Medicine Exam

Hypoparathyroidism is a condition characterized by insufficient production or action of parathyroid hormone (PTH), leading to hypocalcemia, hyperphosphatemia, and disturbances in calcium-phosphate homeostasis.
Parathyroid Hormone (PTH): Normally regulates calcium levels by stimulating calcium release from bones, increasing renal calcium reabsorption, and activating vitamin D to increase gastrointestinal calcium absorption. In hypoparathyroidism, these processes are impaired, resulting in hypocalcemia.
Mechanisms:
Decreased PTH Secretion: Due to parathyroid gland dysfunction.
Resistance to PTH Action: Seen in some syndromes (e.g., pseudohypoparathyroidism).

Surgical Hypoparathyroidism: The most common cause, occurring after inadvertent damage or removal of the parathyroid glands during thyroid, parathyroid, or neck surgery.
Autoimmune Hypoparathyroidism: Autoimmune destruction of the parathyroid glands, often seen in association with polyglandular autoimmune syndromes (PGA).
Genetic Causes:
DiGeorge Syndrome (22q11.2 Deletion Syndrome): Congenital absence or hypoplasia of the parathyroid glands.
Familial Isolated Hypoparathyroidism (FIH): Rare inherited condition where hypoparathyroidism occurs without other endocrinopathies.
Infiltrative Diseases: Granulomatous diseases (e.g., sarcoidosis, tuberculosis) or metastatic cancer infiltrating the parathyroid glands.
Radiation-Induced Hypoparathyroidism: Following radiation therapy to the neck or head.
Magnesium Abnormalities: Severe hypomagnesemia can impair PTH secretion, while hypermagnesemia can inhibit PTH action.

Symptoms of Hypocalcemia: Primarily caused by low ionized calcium levels, which increase neuromuscular excitability.
Neuromuscular Symptoms:
Tetany: Muscle cramps, spasms, or prolonged muscle contractions, commonly in the hands, feet, and face.
Chvostek’s Sign: Twitching of facial muscles elicited by tapping the facial nerve.
Trousseau’s Sign: Carpal spasm elicited by inflating a blood pressure cuff above systolic pressure.
Paresthesia: Tingling or numbness in the fingers, toes, and around the mouth.
Seizures: Hypocalcemia can lower the seizure threshold.
Laryngospasm and Bronchospasm: Severe hypocalcemia can cause life-threatening airway spasms.

Cardiovascular Symptoms:
Prolonged QT Interval: Hypocalcemia can lead to a prolonged QT interval, increasing the risk of arrhythmias.
Hypotension: Due to the effects of hypocalcemia on smooth muscle and vascular tone.
Other Features:
Mental Status Changes: Depression, anxiety, irritability, and confusion.
Chronic Hypocalcemia: Can lead to calcification of the basal ganglia, contributing to movement disorders like Parkinsonism.

Laboratory Tests:
Serum Calcium: Low total and ionized calcium levels.
Serum Phosphate: Elevated due to decreased PTH-mediated renal phosphate excretion.
Serum PTH: Low or inappropriately normal in the setting of hypocalcemia, confirming the diagnosis of hypoparathyroidism.
Serum Magnesium: Hypomagnesemia can worsen hypocalcemia by impairing PTH secretion or action.
Vitamin D Levels: Should be assessed to rule out vitamin D deficiency as a contributing factor.
Electrocardiogram (ECG):
Prolonged QT Interval: Reflects hypocalcemia.
Imaging:
Head CT or MRI: May show basal ganglia calcifications in long-standing hypoparathyroidism.
Bone Densitometry (DEXA Scan): Assess for osteopenia or osteoporosis due to chronic calcium derangements.

Pseudohypoparathyroidism: A condition where PTH is elevated but tissues are resistant to its effects. This causes hypocalcemia and hyperphosphatemia similar to true hypoparathyroidism but with elevated PTH levels.
Vitamin D Deficiency: Can mimic some features of hypoparathyroidism by causing hypocalcemia and secondary hyperparathyroidism.

Acute Hypocalcemia:
Intravenous Calcium: Calcium gluconate is administered for acute, symptomatic hypocalcemia (e.g., tetany, seizures, or cardiac arrhythmias).
Monitoring: Continuous ECG monitoring is recommended during IV calcium administration due to the risk of arrhythmias.
Chronic Hypocalcemia:
Oral Calcium Supplements: Calcium carbonate or calcium citrate is given to maintain serum calcium in the low-normal range.
Vitamin D Supplementation:
Active Vitamin D (Calcitriol): Given in hypoparathyroidism due to impaired endogenous activation of vitamin D. Calcitriol enhances calcium absorption in the intestines.
Cholecalciferol or Ergocalciferol: Given if there is associated vitamin D deficiency.
Thiazide Diuretics: May be used to reduce urinary calcium excretion, thus lowering the risk of nephrolithiasis in patients on chronic calcium therapy.
Magnesium Supplementation: Correct hypomagnesemia if present to restore normal PTH function.
Recombinant Human PTH (rhPTH) Therapy:
Teriparatide (rhPTH 1-34) or Natpara (rhPTH 1-84): Can be used in patients with refractory hypocalcemia or those requiring high doses of calcium and vitamin D. It mimics endogenous PTH, improving calcium regulation.
Surgical Management: Rarely indicated, except in cases of hypoparathyroidism secondary to infiltrative diseases or tumors.

Hypocalcemic Crisis: Life-threatening tetany, laryngospasm, or cardiac arrhythmias due to severe hypocalcemia. Requires urgent IV calcium replacement.
Nephrocalcinosis: Chronic high-dose calcium therapy can lead to renal calcifications and kidney damage.
Ectopic Calcifications: In chronic hypoparathyroidism, calcium can deposit in soft tissues, including the kidneys (nephrocalcinosis) and basal ganglia (causing movement disorders).

Key Points

Hypoparathyroidism is characterized by inadequate PTH secretion, leading to hypocalcemia and hyperphosphatemia. The most common cause is post-surgical removal or damage to the parathyroid glands during neck surgery.
Clinical manifestations include neuromuscular excitability (tetany, muscle spasms), cardiovascular complications (prolonged QT, arrhythmias), and mental status changes (confusion, irritability).
Diagnosis is confirmed by low calcium, elevated phosphate, and low PTH levels. Serum magnesium should be checked, as hypomagnesemia can exacerbate hypocalcemia.
Management includes acute calcium repletion for severe symptoms and long-term oral calcium and vitamin D (calcitriol) supplementation for chronic management. Recombinant PTH therapy can be considered for refractory cases.
Complications include hypocalcemic crisis, nephrocalcinosis from chronic high calcium supplementation, and ectopic calcifications in the basal ganglia.