Hypoparathyroidism Clinical Presentation

Updated: Aug 28, 2020
  • Author: Joseph Michael Gonzalez-Campoy, MD, PhD, FACE; Chief Editor: George T Griffing, MD  more...
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Presentation

History

Hypoparathyroidism results in hypocalcemia, which may be variably symptomatic. The history should focus on eliciting signs and symptoms of neuromuscular irritability, [11] including the following:

  • Paresthesias (involving fingertips, toes, perioral area)

  • Hyperirritability

  • Fatigue

  • Anxiety

  • Mood swings and/or personality disturbances

  • Seizures (especially in patients with epilepsy)

  • Hoarseness (due to laryngospasm)

  • Wheezing and dyspnea (due to bronchospasm)

  • Muscle cramps, diaphoresis, and biliary colic

  • Hypomagnesemia, hypokalemia, and alkalosis (eg, hyperventilation), which worsen signs and symptoms of hypocalcemia

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Physical

Physical findings may include the following:

  • Muscle cramps involving the lower back, legs, and feet are common in patients with hypoparathyroidism and hypocalcemia. Tetany develops if hypocalcemia is severe. In some patients, laryngospasm and bronchospasm may be life threatening.

  • Increased neuromuscular irritability from hypoparathyroidism-induced hypocalcemia may be demonstrated at the bedside by eliciting the following signs:

    • Chvostek sign: Facial twitching, especially around the mouth, is induced by gently tapping the ipsilateral facial nerve as it courses just anterior to the ear.

    • Trousseau sign: Carpal spasm is induced by inflating a blood pressure cuff around the arm to a pressure 20 mm Hg above obliteration of the radial pulse for 3-5 minutes.

  • Hypocalcemia of primary hypoparathyroidism may cause extrapyramidal choreoathetoid syndromes in patients with basal ganglia calcifications. [5]

  • Parkinsonism, dystonia, hemiballismus, and oculogyric crises may occur in approximately 5% of patients with idiopathic hypoparathyroidism. [6]

  • Spastic paraplegia, ataxia, dysphagia, and dysarthria have been documented in association with hypoparathyroidism-induced hypocalcemia. Severe hypocalcemia causes papilledema, which improves with treatment of the calcium derangement.

  • Emotional instability, anxiety, depression, confusion, hallucinations, and psychosis have been described in patients with hypoparathyroidism when the calcium level is low. Normocalcemia corrects these conditions.

  • Chronic hypocalcemia, as observed in primary hypoparathyroidism, is also associated with ocular cataracts, abnormal dentition, and dry, puffy, coarse skin. In severe hypocalcemia, a prolongation of the QT interval is observed on ECG, and congestive heart failure may develop. Correction of hypocalcemia reverses the cardiac effects of hypoparathyroidism.

  • In patients with autoimmune polyglandular syndrome, idiopathic hypoparathyroidism is associated with adrenal insufficiency and moniliasis. Moniliasis may affect the skin, nails, oral cavity, and vaginal cavity. It is frequently intractable. The underlying etiology is likely a defect in cellular immunity. Some authors advocate the term HAM syndrome, ie, hypoparathyroidism, Addison disease, and moniliasis (HAM), to denote these cases.

  • In a study of 33 patients with hypoparathyroidism, Rubin et al concluded that the disease causes bone to assume unusual structural and dynamic properties. [12] Examining biopsies of the iliac crest, the investigators found that, in comparison with biopsies from 33 patients with no known metabolic diseases, the individuals with hypoparathyroidism had greater cancellous bone volume, trabecular width, and cortical width. Moreover, the patients with hypoparathyroidism demonstrated profound suppression of dynamic skeletal indices, including mineralizing surface and bone formation rate.

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Causes

Most people have 4 parathyroid glands; consequently, primary hypoparathyroidism is uncommon. Hypocalcemia from hypoparathyroidism requires all 4 parathyroid glands to be affected. Primary hypoparathyroidism may be permanent or reversible. Permanent primary hypoparathyroidism may be congenital or acquired.

Iatrogenic causes

The most common cause of primary hypoparathyroidism is excision of all parathyroid glands via surgery in the treatment of thyroid, laryngeal, or other neck malignancy. [13] Patients with parathyroid hyperplasia, as observed in the multiple endocrine neoplasia (MEN) syndromes, are treated by surgical removal of the parathyroid glands. Attempts at restoring normal PTH levels and normocalcemia by autotransplantation [7] of a fraction of one of the parathyroid glands sometimes are effective, but many patients become hypoparathyroid. Repeated neck explorations for primary hyperparathyroidism caused by parathyroid adenoma may also cause hypoparathyroidism.

The risk of permanent hypoparathyroidism with ongoing hypocalcemia is 7.5% for patients who undergo bilateral near-total thyroidectomy, compared with 2.4% for those who undergo bilateral total thyroidectomy. [14]  Total or completion thyroidectomy resulting in a reduction in PTH levels of greater than 70% reliably predicts the occurrence of persistent hypoparathyroidism. [15]

Extensive irradiation to the face, neck, or mediastinum may cause destruction of all 4 parathyroid glands, with ensuing primary hypoparathyroidism and hypocalcemia.

The "hungry bone syndrome" develops after a parathyroidectomy for hyperparathyroidism. The body has been accustomed to high levels of PTH, causing hypercalcemia. Much of this hypercalcemic effect is because of resorption of bone. When the parathyroid gland or glands responsible for the hypersecretion of PTH are removed, the PTH level in the blood drops suddenly, and the patient experiences transient hypoparathyroidism. The bone, which has been starved of calcium, avidly retains it under the influence of osteoblasts. Without PTH and with bone now using calcium to remineralize, the ECF ionized calcium level falls. Postoperatively, patients require aggressive treatment with calcium for several hours to several days. Eventually, the hypoparathyroid state resolves, and calcium homeostasis is re-achieved.

Autoimmune causes

Type 1 autoimmune polyglandular syndrome (also referred to as HAM syndrome) includes primary hypoparathyroidism that is due to destruction of the parathyroid glands. On average, these patients develop primary hypoparathyroidism by age 10 years.

Autoimmune hypoparathyroidism may exist alone or in sporadic or familial forms. For patients with autoimmune primary hypoparathyroidism, the average age for development of hypocalcemia is 7 years, with a range of 6 months to 20 years. [16]

Congenital causes

Numerous conditions are described in the literature that result in congenital agenesis or hypoplasia and, therefore, can produce primary hypoparathyroidism with symptomatic hypocalcemia at birth or in the newborn period. These conditions, which are summarized from Goltzman and Cole (1996), are as follows: [17]

  • 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 (Shprintzen) syndrome (CATCH 22 [for cardiac, abnormal facies, thymic aplasia, cleft palate, and hypocalcemia with 22q deletion] is a mnemonic for the features of this syndrome.)

  • Zellweger syndrome

  • Teratogenic effects

  • Diabetic embryopathy

  • Fetal alcohol syndrome

  • Retinoid embryopathy

  • Associational arhinencephalia and/or DiGeorge syndrome and the coloboma, heart disease, choanal atresia, retarded growth and development, genital anomalies, ear anomalies (CHARGE) syndrome and/or DiGeorge syndrome

  • Cardiofacial–DiGeorge–Kenny-Caffey syndrome (ie, absent parathyroid tissue, growth retardation, medullary stenosis of tubular bones)

  • Kearns-Sayre syndrome (ie, mitochondrial myopathy, ophthalmoplegia, retinal degeneration, cardiac conduction defects, primary hypoparathyroidism)

  • Barakat syndrome (ie, primary hypoparathyroidism, nerve deafness, steroid-resistant nephrosis)

  • Hypoparathyroidism with short stature, mental retardation, and seizures

In addition to the above list, several other genetic defects cause primary hypoparathyroidism. As opposed to the conditions listed above, no agenesis or hypoplasia of the parathyroid glands occurs in these other genetic defects. These mutations are functional, not anatomic, and are listed as follows:

  • Mutation of chromosome arm 3q has been demonstrated to cause primary hypoparathyroidism in several kindreds because of activation of the parathyroid extracellular calcium-sensing receptor. These patients have mild-to-moderate hypocalcemia, urinary calcium excretion that is high relative to serum calcium (presumably the extracellular calcium-sensing receptor in the kidney contributes to this), and serum PTH concentration that is within the reference range (but is inappropriately low).

  • Familial isolated hypoparathyroidism is a heterogenous mix of disorders as follows: autosomal dominant abnormal prepro-PTH allele (C-to-T substitution in codon 18 of the prepeptide encoding region does not allow for cleavage to pro-PTH) and autosomal recessive abnormal prepro-PTH allele (C-to-G substitution in the first nucleotide position of prepro-PTH intron 2).

Causes related to metal overload (ion deficiency)

Hemochromatosis and thalassemia, both of which are associated with iron overload, may result in primary hypoparathyroidism.

Wilson disease, with copper overload, may also cause primary hypoparathyroidism.

Hypermagnesemia has been demonstrated to decrease PTH release. Correction of hypermagnesemia leads to correction of the primary hypoparathyroidism.

Aluminum deposition within the parathyroid glands may cause primary hypoparathyroidism in patients with end-stage renal disease who are on hemodialysis.

Hypomagnesemia causes reversible functional primary hypoparathyroidism.

Causes related to infiltration of the parathyroid glands

In addition to hemochromatosis and Wilson disease, parathyroid gland destruction has been reported as a result of metastatic disease, granulomatous disease, amyloidosis, syphilis, and progressive systemic sclerosis.

Of note, clinically significant hypocalcemia is not always apparent in these patients.

Neonatal causes

The unborn baby of a mother with hypercalcemia has chronic suppression of parathyroid gland function. In the worst circumstances, the parathyroid glands may become atrophic.

At birth, the maternal calcium excess is eliminated, and newborns are at risk of hypocalcemia caused by primary hypoparathyroidism.

Clinically significant hypocalcemia may develop within the first 3 weeks of life but may occur as late as 1 year after birth. The primary hypoparathyroidism in these patients is self-limited.

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