PHPT is common disease among adults. However it’s occurrence is very rare among children and adolescents with about 200 cases reported worldwide up to now [
1]. It’s incidence is estimated as 1 case per 300,000 live births [
2]. PHPT in children has a bimodal age distribution occurring in very young and older children. In neonates and infants it can be due to inactivating mutations of the calcium sensing receptor gene on chromosome 3q which is inherited as an autosomal dominant disorder [
3]. In older children it is caused by adenoma or hyperplasia of the gland and can be either familial (27–31%) or sporadic (65–70%).
The characteristic feature in older children is delayed presentation. Almost 80% of children are symptomatic and have end organ damage at the time of presentation [
2,
4]. This is in contrast to adults where most of the cases of PHPT are diagnosed by incidental detection of hypercalcemia during routine investigations in asymptomatic patients. Children can present with various non specific symptoms involving gastrointestinal, musculoskeletal, renal and neurological systems due to hypercalcemia. Our patient presented with genu valgum. Skeletal survey revealed bilateral SUFE with bilateral genu valgum, displacement of epiphysis of bilateral humeri, rugger jersey spine and sub periosteal bone resorption involving radial aspects of phalanges in hand. Genu valgum is a rare presentation in children with PHPT with only 10 cases reported in literature. These 10 cases are summarized in an article on Genu valgum and primary hyperparathyroidism in children by Ramkumar et al. [
5]. Most of these patients had genu valgum at presentation indicating an etiological link. All these patients had solitary parathyroid adenoma and none were reported vitamin D deficient. Genu valgum can also manifest in vitamin D deficiency which can also cause a similar clinical picture due to tertiary hyperparathyroidism. Our patient had biochemical evidence of vitamin D deficiency. However there were no other radiological features favoring vitamin D deficiency apart from bilateral SUFE which is known to occur in both vitamin D deficiency as well as hyperparathyroidism. Vitamin D deficiency alone is unlikely to cause genu valgum in children with PHPT. Adequate vitamin D supplementation resulted in worsening of hypercalcemia and failure of reduction in PTH levels. Tc 99 Sestamibi uptake scan demonstrated focal increase in uptake of tracer in the right inferior lobe of the thyroid for which she underwent surgery and removal of a parathyroid adenoma with clinical resolution. This was the case in the two patients encountered by Ramkumar et al. as well. The classic picture in the case of tertiary hyperparathyroidism would be parathyroid hyperplasia. Most of the cases of PHPT with genu valgum described so far have occurred in adolescence when a rapid growth spurt is expected. The exact mechanism of genu valgum in PHPT is unclear however it is postulated that PHPT has a direct effect on the growth plate during the pubertal growth spurt [
6]. Similar phenomenon occurs in SUFE which is displacement of the capital femoral epiphysis caused by shear stress on a vulnerable physis during rapid growth in adolescence [
7]. Although the exact pathogenesis is unclear many endocrine diseases such as hypothyroidism, administration of growth hormone, PHPT, panhypopituitarism and lately vitamin D deficiency have been contributory factors. These disorders result in abnormal growth and mineralization of cartilage thus predisposing to slippage of the vulnerable physis. Prevalences of these among 85 patients with SUFE were hypothyroidism in 40%, growth hormone deficiency in 25% and others in 35% [
8]. PHPT causing SUFE is extremely rare with only 9 cases reported worldwide [
9]. Madeira et al. reported the occurrence of genu valgum, SUFE and several painful skeletal manifestations in a teenager which was attributed to the rapid growth spurt during puberty [
10]. Further to the development of genu valgum and SUFE, our patient had radiological evidence of epiphyseal displacement of bilateral humeri as well. This most likely can be attributed to the same mechanism of the effect of excess parathyroid hormone on the bone and epiphysis in a child going through the pubertal growth spurt. However there is no literature published to date describing epiphyseal displacement of humerus in association with PHPT.
PHPT in our 12 year old patient was unmasked due to these skeletal deformities as she progressed through puberty. Apart from these she did not have any other clinical features suggestive of PHPT. Following excision of the parathyroid adenoma she developed biochemical resolution. However further surgeries will be required to correct the limb deformities.