Hypoparathyroidism

Inherited condition caused by a lack of parathyroid hormone resulting in hypocalcemia and hyperphosphatemia and their clinical manifestations.

Endocrine disorder of the parathyroid gland as a consequence of primary or secondary lack of parathormone secretion. Primary forms result from many rare diseases.

Primary hypoparathyroidism is rare; fewer than 1000 cases of the idiopathic form, familial or not, have been reported. Rare in children.

• Both autosomal dominant (gene map locus 3q13) and X-linked (also related to a mutation in the parathyroid hormone gene) forms of familial idiopathic hypoparathyroidism have been reported.
• X-Linked Agenesis of Parathyroid Gland: Gene map locus is Xq26-q27.
• Hypoparathyroidism-Retardation-Dysmorphism Syndrome (HRDS): Autosomal recessive.
• Sanjad-Sakati Syndrome (Congenital Hypoparathyroidism with Growth Retardation, Developmental Delay, and Dysmorphism): Gene map location is 1q42-43.

Primary and secondary hypoparathyroidism are conditions in which there is a deficiency of parathyroid hormone. This deficiency induces hypocalcemia and decreases calcium resorption from bone and calcium absorption from gastrointestinal tract by preventing synthesis of vitamin D. The lack of parathyroid hormone stops the osteolytic effect of vitamin D and results in a decrease in bone metabolism. The decreased calcium concentration in the motor plate induces neuromuscular hyperexcitability. A very sensitive extracellular calcium-sensing receptor, coupled to a G protein, has been isolated from parathyroid, kidney, and brain cells. Some autosomal dominant forms of hypocalcemia result from activating mutations of this extracellular calcium-sensing receptor, which inhibits parathyroid hormone exocytosis (mechanism is unknown).

In primary hyperparathyroidism, note hypocalcemia, hypomagnesemia, hyperphosphoremia, and low serum level of parathyroid hormone. Urinary excretion of calcium, phosphorus, and cAMP is decreased. Ellsworth Howard test (infusion of 200 IU of parathyroid hormone) induces an increase of cAMP and phosphaturia. Intracerebral calcifications on CT scan.

In neonates, the symptoms of hyperparathyroidism are respiratory distress, cyanosis, apnea, hypertonia, agitation, and tetany. In infants, the symptoms are seizures and tinnitus crisis with inspiratory stridor, laryngospasm, and unexplained tachycardia. In children, tinnitus is the most frequent sign, with seizures that can be typical or not. Hypocalcemia may be life-threatening and can cause nephrocalcinosis and renal lithiasis.

Primary forms are related to many rare diseases, mostly genetically inherited.

Autoimmune diseases: Type I autoimmune polyglandular syndrome (or HAM syndrome) results in primary hypoparathyroidism by 10 years of age as a result of destruction of the parathyroids. Other types of autoimmune hypoparathyroidism may exist alone, in sporadic or familial forms.

Congenital diseases and syndromeswith agenesis or hypoplasia of the parathyroid glands include the following:

• Isolated primary hypoparathyroidism
• X-linked primary hypoparathyroidism (band Xq26-Xq27)
• X autosomal recessive primary hypoparathyroidism
• Branchial dysgenesis (DiGeorge syndrome)
• Chromosomal defects dup(1q), del(5p), dup(8q), del(10q), del(22q)
• Monogenic hypoparathyroidism
• Isolated autosomal dominant conditions
• Isolated autosomal recessive conditions
• Velocardiofacial syndrome
• Zellweger syndrome
• Teratogenic effects
• Diabetic embryopathy
• Fetal alcohol syndrome
• Retinoid embryopathy
• CHARGE syndrome
• Kenny-Caffey syndrome
• Kearns-Sayre syndrome
• Barakat syndrome (i.e., primary hypoparathyroidism, nerve deafness, steroid-resistant nephrosis)
• Hypoparathyroidism with short stature, mental retardation, and seizures (hypoparathyroidism-retardation-dysmorphism Syndrome; Sanjad-Sakati syndrome; Kalam-Haafez syndrome)

Congenital diseases and syndromes without agenesis or hypoplasia of the parathyroid glands (functional mutations), including the following:

• Mutation of chromosome arm 3q
• Familial isolated hypoparathyroidism, which is a heterogenous mix of disorders including autosomal dominant and autosomal recessive abnormal preproparathyroid hormone allele

Secondary forms may result from several causes: ablation of parathyroid glands during thyroid or parathyroid surgery, radiotherapy, transitive neonatal hypoparathyroidism (maternal hyperparathyroidism during pregnancy), metal overload (iron overload in hemochromatosis and thalassemia, copper overload in Wilson disease, aluminum overload in hemodialyzed patients), or metal deficiency (hypomagnesemia), idiopathic.

Full history and evaluation of associated syndrome. Search for neuromuscular irritability indicating chronic hypocalcemia (Chovstek or Trousseau sign); if positive, calcium levels require correction. Electromyography (EMG), EEG, CT scan, ECG (prolonged QT). Ophthalmologic examination. Skeletal radiograph. Dosages of Ca+2, parathyroid hormone, cAMP. Correct calcemia: in acute hypocalcemia, calcium chloride or calcium gluconate 1 to 2 g IV; in chronic form, calcium carbonate 1 to 8 g per os with vitamin D. Correct associated electrolyte disturbances.

The risks are those of hypocalcemia: arrhythmia, acute hypocalcemia as a consequence of citrated blood transfusion. Monitoring of ECG preoperatively and postoperatively is highly recommended. Muscle relaxant must be controlled by nerve stimulator. Difficult tracheal intubation can occur in genetically inherited forms with associated facial malformations. For hypoparathyroidism in association with other syndromic conditions, refer to this syndrome for further information.

Avoid agents that can prolong QT, such as local anesthetics because of their quinidine-like action. Increased efficiency of muscle relaxants because of hypocalcemia.

Albright Hereditary Osteodystrophy: Heterogeneous group of disorders characterized by hypocalcemia, hyperphosphatemia, and increased serum concentration of parathyroid hormone. Caused by insensitivity to parathyroid hormone activity.