Subclinical Hypoparathyroidism Research Articles

Unique classification of parathyroid dysfunction in patients with transfusion dependent thalassemia major using Nomogram-A cross sectional study.

IntroductionHypoparathyroidism is a rare complication of iron overload in patients with transfusion dependent β thalassemia major (β-TM). We aim to determine the prevalence of parathyroid dysfunction in patients with β-TM.MethodsDiagnosed cases of transfusion dependent β-TM between 5 and 17 years of age were recruited from outpatient clinics of a non-profit organization in Karachi, Pakistan. Blood and urine samples were collected in fasting to determine Ca, P, Alb, Mg, Cr 25OHD and iPTH. Patients were grouped on the basis of upper and lower levels of Ca, 25OHD and iPTH for assessing parathyroid dysfunction into primary hypoparathyroidism [low calcium (Ca) & intact parathyroid hormone (iPTH)], sub-clinical hypoparathyroidism [low iPTH and 25 hydroxy vitamin D (25OHD), low/normal Ca], normal functioning parathyroid gland [Normal Ca, iPTH and 25OHD] and secondary hyperparathyroidism [high iPTH, low/normal Ca and/or 25OHD]. Using PTH nomogram subject specific expected PTH (maxPTH) was calculated. Difference between maxPTH and measured iPTH was determined to assess the utility of nomogram in identifying parathyroid gland dysfunction. The statistical analysis was performed using the Statistical Package of Social Sciences (SPSS) version 20.ResultsMedian age of patients was 11 years (13–7) with males being 54.2% (n = 205).Based on Ca, 25OHD and iPTH, primary hypoparathyroidism was identified in 3.4% (n = 13) [median iPTH 11.3 pg/ml (12.6–7)], 52.3% (n = 192) had subclinical hypoparathyroidism [iPTH 40.4 pg/ml (52.7–28.7)], and 34% (n = 125) were identified as secondary hyperparathyroidism [iPTH 88.6 pg/ml (116–74.7)]. Normal response to Ca & 25OHD was seen in 10.6% (n = 39) [iPTH 44.2 pg/ml (53.8–33.4)] patients. High phosphorous was present in all groups. Difference between maxPTH & iPTH was highest in primary hypoparathyroidism, followed by subclinical and secondary hyperparathyroidism.ConclusionNomogram by Harvey et al. identify low secretion capacity of parathyroid gland that correlated with biochemical classification of patients. It requires clinical validation before using in clinical practice for assessing parathyroid dysfunction.

Evaluation of Parathyroid Gland Function Using Sodium Bicarbonate Infusion Test for 22q11.2 Deletion Syndrome

Background/Aims: 22q11.2 deletion syndrome is a congenital malformation syndrome with hypoparathyroidism. The spectrum of parathyroid gland dysfunction ranges from severe neonatal hypocalcemia to subclinical hypoparathyroidism. The parathyroid hormone (PTH) secretory reserve is reduced in a significant number of 22q11.2 deletion syndrome patients with normocalcemia. The aim of this study was to investigate hypoparathyroid function using the bicarbonate infusion test for 22q11.2 deletion syndrome with normocalcemia. Methods: Sodium bicarbonate solution [7% (w/v); 40 ml/m² body surface area] was infused for 2 min, and blood samples for the determination of plasma ionized calcium and plasma intact PTH were serially obtained. The test was conducted on five 22q11.2 deletion syndrome patients with normocalcemia. Results: Two patients presented increments of intact PTH levels (peak value – basal value) of 70 pg/ml or higher during the test, whereas the remaining 3 showed PTH level increments of <30 pg/ml. The former 2 patients were diagnosed as having normal parathyroid gland function, and the latter 3 patients as having subclinical hypoparathyroidism. Conclusion: The bicarbonate infusion test may be a valuable method for the evaluation of residual parathyroid gland function in patients with 22q11.2 deletion syndrome. Screening of subclinical hypoparathyroidism should be considered in the regular follow-up of patients with 22q11.2 deletion syndrome, even in cases with normocalcemia.

Differences in the prevalence of growth, endocrine and vitamin D abnormalities among the various thalassaemia syndromes in North America

This study aimed to determine differences in the rates of growth, endocrine- and calcium-related abnormalities in the various thalassemia syndromes in North America treated with current therapies. Medical history, physical examinations and blood and urine collections were obtained from patients with all thalassemia syndromes age 6 years and older in the Thalassemia Clinical Research Network. 361 subjects, 49% male, mean age 23.2 years (range 6.1-75 years) were studied. Approximately 25% of children and adults, regardless of the thalassemia syndrome, had short stature. Overall growth in children was mildly affected. Final height was close to midparental height (z = -0.73 +/- 1.24). Patients with beta thalassemia major (TM) had higher rates of hypogonadism, multiple endocrinopathies, worse hyperglycaemia, subclinical hypoparathyroidism and hypercalciuria. Hypogonadism remained the most frequent endocrinopathy and was frequently under-treated. 12.8% of the subjects had 25 vitamin D concentrations less than 27 nmol/l and 82% less than 75 nmol/l, regardless of the thalassemia syndrome. Adolescents had lower 25 vitamin D levels than children and adults. Compared to patients with other thalassemia syndromes, those with beta TM suffered from higher rates of multiple endocrinopathies, abnormal calcium metabolism and hypercalciuria. Vitamin D abnormalities were high among adolescents.

Nocturnal calcium, phosphorus and parathyroid hormone in the diagnosis of concealed and subclinical hypoparathyroidism

Circadian rhythms of plasma parathyroid hormone (PTH) show peak values at night, whereas serum calcium levels peak in the evening and display a nadir at night. Subclinical hypoparathyroidism (HPT) can be detected by utilizing the knowledge of diurnal variations. Thalassemia major (TM) may provide a model system of subclinical HPT. Nocturnal plasma PTH and serum calcium values were determined in 13 TM patients with normal morning serum calcium levels as compared with the corresponding values in eight healthy control subjects. Six patients with TM presented a nadir serum calcium level of 8.3 mg/dl or lower (hypoCa TM) at 0200 h, whereas the remaining seven showed nadir levels of 8.4 mg/dl or higher (normoCa TM). Patients with hypoCa TM displayed a drop between peak and nadir of 1.2 +/- 0.5 mg/dl as compared with a considerably smaller fall of 0.3 +/- 0.7 mg/dl in control subjects (P < 0.05). NormoCa TM patients experienced comparable nocturnal variation to that of control subjects. Patients from both the hypoCa and normoCa TM groups presented significantly lower nocturnal PTH levels than those of control subjects and lost the nocturnal PTH variation characteristic of healthy subjects. A plot of all serum calcium against plasma PTH levels provides a clear distinction of the three groups. All 13 daytime normocalcemic TM patients presented a certain degree of HPT. The hypoCa TM group displayed a concealed HPT detected in all, except the morning sampling, whereas normoCa TM patients experienced sub clinical HPT observed in the absence of nocturnal HPT variation. Nocturnal measurements of serum minerals thus enhance the sensitivity of HPT diagnosis.

Idiopathic hypoparathyroidism and autoimmunity.

Only a small number of cases of idiopathic hypoparathyroidism linked to the presence of specific antibodies have been described until now. Serum antiparathyroid antibodies have been frequently discovered in the absence of overt parathyroid disease. This suggests either that this kind of antibody is only a marker of genetic predisposition to immunological disease or more probably that subclinical hypoparathyroidism does exist though we lack the sensitive laboratory tests to prove it.

854 STIMULATED NEPHROGENOUS CYCLIC AMP AS A PARATHYROID (PT) FUNCTION TEST IN THALASSEMIA MAJOR

As the detection of subclinical hypoparathyroidism in transfused thalassemic patients is hampered by assay insensitivity at low PTH levels, we used a provocation test as a dynamic measure of PT reserve. PTH response was assessed by using urinary cyclic AMP (cAMP) as a function of response. cAMP excretion correlates well with PTH activity, particularly when combined with plasma cAMP to calculate nephrogenous cAMP excretion. Eight patients aged 9-26 with thalassemia major and iron overload (ferritin 2-6 μg/ml vs normal <0.15),all with normal baseline serum calcium and phosphorus, and 4 young adult controls received 50 mg/kg disodium EDTA IV over 3 hours. Ionized calcium fell by 0.64 ± .33 mg% (controls 0.87 ± .33). Urinary cAMP rose by 1-5.2 nmol/100 ml glomerular filtrate (GF); control 1.2-5.1. In 4 patients nephrogenous cAMP rose 1.3-2.8 fold (controls 2.0-10.2 fold). The oldest patient showed the lowest rise in urinary cAMP (1.0 nmol/100 ml GF) and in nephrogenous cAMP (1.3 fold rise). We conclude that the response of the nephrogenous component of urinary cAMP to PT provocation with EDTA is a reliable, generally applicable test of PT reserve. The finding of well preserved PT function in at least 7 of our 8 patients is consistent with the clinical observation that overt hypoparathyroidism is a late and uncommon complication of thalassemia major. (Supported by Grant RR-125, GCRC Branch, NIH.)