Pseudohypoparathyroidism (PHP) encompasses a group of conditions that are characterized by parathyroid hormone resistance.
PHP may manifest in infancy or later with symptoms reflective of severe hypocalcemia. Signs can include paresthesias, tetany, cramps, and even seizures . Moreover, the physical exam is notable for findings such as Chvostek sign and Trousseau sign.
The constellation of PHP1a, also referred to as AHO, consists of short stature, round face, obesity , brachydactyly, brachymetacarpia, soft tissue ossification, dental hypoplasia, and possibly mental delay.
PHP1b   and PHP2  are characterized by PTH insensitivity without AHO. PHP1c is typified by both.
The clinical assessment consists of the patient's history, detailed physical exam, and relevant tests.
The biochemical studies are notable for hypocalcemia, hyperphosphatemia, and increased PTH levels. Since PHP is associated with various hormone deficiencies, further evaluation may include thyroid function tests, and measurements of the gonadotropin, estrogen or testosterone, growth hormone, and insulinlike growth factor-1 (IGF-1). Patients with infertility warrant a complete endocrine profile.
If hand x-rays are obtained, remarkable findings reveal a significantly shortened distal phalanx of metacarpals located on the thumb and digits three through five. Additionally, calcification and ossification may be apparent on radiography. Finally, a head computed tomography (CT) may show basal ganglia calcification.
The treatment objectives are to achieve control of the calcium and PTH levels and to manage any existing hormonal deficiencies.
Adults with profound hypocalcemia are treated with 100mg of intravenous (IV) elemental calcium at a duration of 10 to 20 minutes. If symptoms persist, additional calcium is administered while the patient undergoes calcium and heart monitoring. Children and infants are treated with 10% calcium gluconate at a dose of 0.5-1 mL/kg over a length of 5 minutes.
Patients with additional hormonal abnormalities should be treated accordingly.
If properly treated, patients are expected to have normal life expectancy.
The cause of PHP1a, PHP1b, and pseudopseudohypoparathyroidism (pseudo-PHP) is a mutation in the GNAS1 gene, which codes for the alpha subunit of the stimulatory G protein (Gsa) . Most cases of PHP1a are transmitted through an autosomal dominant pattern with parental imprinting. Maternal inheritance of this variant is associated with features of Albright hereditary osteodystrophy (AHO) and resistance to other hormones but the paternal expression does not produce the latter . PHP1b is inherited spontaneously in most cases. The etiology of PHP1c and PHP2 is unclear.
This rare condition exhibits a two-fold predilection for females.
PTH regulates the plasma calcium concentration through its effect on the kidneys and bone through PTHR1, which is a receptor coupled to Gsa  . In PHP, there is renal resistance to PTH at the level of the proximal tubule , which leads to less calcium reabsorption.
Biochemical surveillance should be performed every 3 months to track calcium levels and adjust treatment as needed.
Pseudohypoparathyroidism is a rare disorder defined by increased parathyroid hormone and low calcium levels. Signs may include short stature, round face, obesity, short bones in the hand, and mental delay. The disorder is diagnosed with a physical exam and laboratory tests. It is treated with calcium and vitamin D. The prognosis is generally good.