Partial Hypoparathyroidism Research Articles

Long-Term Follow-Up and Treatment of Postoperative Permanent Hypoparathyroidism in Patients with Medullary Thyroid Carcinoma: Differences in Complete and Partial Disease.

This study aimed to identify factors influencing long-term outcome in complete or partial postoperative hypoparathyroidism (parathyroid hormone ≤10 or >10 ng/l, respectively) in medullary thyroid carcinoma (MTC). It was designed as retrospective, long-term follow-up with single-center outpatient visits. Quality of treatment, renal calcification, and function were evaluated. In 33 patients with MTC and postoperative hypoparathyroidism, current medication includes: calcium (73%), calcitriol (73%), alfacalcidol (6%), dihydrotachysterol (3%), and cholecalciferol supplements (21%). Mean hypoparathyroidism duration was 15.9±9.4 years. Initially, 15% of patients received high cholecalciferol dosages. Initial calcium dosages were higher (1 542±1 179 mg/day) than final dosages (1 188 ± 595 mg/day) (p<0.05); calcitriol dosages remained constant. Over the median observation period of about 12 years it was found that serum calcium was within the target range (2.0-2.3 mmol/l) in 63% of visits, decreased (<2.0 mmol/l) in 20.4%, high-normal (2.4-2.6 mmol/l) in 15.8%, and increased (>2.65 mmol/l) in 0.9% of visits. Calcitriol dosages were 0.73±0.22 μg/day and 0.47±0.20 μg/day in patients with complete (n=13) and partial (n=20) hypoparathyroidism, respectively (p=0.008). Renal function decreased slightly during follow-up (eGFR: 102±22 vs. 90±27 ml/min). eGFR was negatively correlated with hypoparathyroidism duration (r=-0.35, p=0.05). Of 9 patients with renal calcification, 5 had received high initial cholecalciferol doses. eGFR was lower in patients with than in those without calcification (77±17 vs. 95±29 ml/min) (p=0.07). At least one tetanic episode occurred in 60.6% of patients, and 9% had repeated tetanic complaints. In conclusion, severity of hypoparathyroidism affects treatment: Partial hypoparathyroidism required lower calcitriol dosages than complete hypoparathyroidism. Renal calcifications occurred more frequently in patients treated initially with high cholecalciferol dosages. Impaired renal function was related to hypoparathyroidism duration and renal calcification.

Post‐operative partial hypoparathyroidism: an under‐recognized disorder (Re: ANZ J. Surg. 2011; 81: 524–7)

Post‐operative partial hypoparathyroidism: an under‐recognized disorder (Re: <i>ANZ J. Surg.</i> 2011; 81: 524–7)

Practical Guidelines for Managing Patients with 22q11.2 Deletion Syndrome

A 12-year-old boy currently is followed by multiple sub-specialists for problems caused by the chromosome 22q11.2 deletion syndrome (22q11DS) (Figure). He was born via spontaneous vaginal delivery, weighing 3033 g, to a 31-year-old G3P3 mother after a full-term pregnancy complicated only by mild polyhydramnios. Family history was non-contributory. Apgar scores were 8 at 1 minute and 9 at 5 minutes. With the exception of a weak cry, the results of the infant’s initial examination were unremarkable, and he was moved to the well-baby nursery. Shortly thereafter, a cardiac murmur was noted, the cardiology department was consulted, and the child was transferred to a local tertiary care facility with a diagnosis of tetralogy of Fallot. Stable, he was discharged home at 3 days of life. Figure Mild dysmorphic facial features of a boy aged 11 years with 22q11.2DS, including a short forehead, hooded eyelids with upslanting palpebral fissures, malar flatness, bulbous nasal tip with hypoplastic alae nasi, and protuberant ears. At 5 days of life, he had jerky movements. On presentation to the local emergency department, his total calcium level was 4.7 mg/dL, and later partial hypoparathyroidism was diagnosed. At that time, a consulting geneticist suggested the diagnosis of chromosome 22q11DS. Weeks later, the family received a telephone call confirming the diagnosis with fluorescence in situ hybridization (FISH). No additional information about the diagnosis, prognosis, etiology, or recurrence risk was provided until the child was 5 months of age, when he underwent cardiac repair at a third hospital, where a comprehensive 22q11DS program was in operation. In the interim, the child had feeding difficulties requiring supplemental nasogastric tube feeds, nasal regurgitation, and gastroesophageal reflux, while the parents searched the internet for reliable information about their son’s diagnosis. Subsequent notable abnormalities and interventions included: recurrent otitis media with bilateral myringotomy tube placement at 6 months; angioplasty with left pulmonary artery stent placement after the identification of pulmonary artery stenosis with bilateral pleural effusions at age 6 years; chronic upper respiratory infections with significant T cell dysfunction requiring live viral vaccines to be held until age 7 years; velopharyngeal incompetence necessitating posterior pharyngeal flap surgery at 7 years; enamel hypoplasia and numerous caries resulting in 3 separate dental procedures under general cardiac anesthesia beginning at age 7 years; multiple cervical and thoracic vertebral anomalies with thoracic levoconvex scoliosis and upper lumbar dextroscoliosis requiring growing rod placement at age 11 years with subsequent rod extension at ages 11.5 and 12 years; postoperative hypocalcemia; short stature; constipation; and persistent idiopathic thrombocytopenia. Pertinent negative test results included normal renal ultrasound scanning and parental 22q11.2 deletion studies. On physical examination, the boy’s height and weight have consistently tracked just below the fifth percentile, with no evidence of growth hormone deficiency. His head circumference is within reference range at the 25th percentile. Dysmorphic features include: a low anterior hairline; hooded eyelids; malar flatness; normally formed but protuberant ears with attached lobes; a mildly deviated nose with a bulbous nasal tip and hypoplastic alae nasi; asymmetric crying facies with a thin upper lip; mild micrognathia; a sacral dimple; and soft tissue syndactyly of the second and third toes. Developmentally, the boy had mild delays in achieving motor milestones, sitting at 11 months and walking at 18 months. However, he exhibited significant delays in the emergence of language: he never babbled, spoke his first words at age 3 years, and only achieved full conversational speech at 7 years. However, he had relative strengths in receptive language and communicated appropriately by the use of sign language. Now quite conversant, he is mainstreamed in the seventh grade with resource room supports. Moreover, he is affable, but exhibits anxiety and perseverations. Lastly, despite numerous medical, academic, and social challenges, he participates in assisted athletics, is an avid wrestling fan, and enjoys travel. However, his exceptionally supportive parents, siblings, and extended family continue to worry about his long-term outcome and transition of care as he approaches adulthood. As demonstrated by this boy’s complicated course, practical multi-system guidelines are needed to assist the general practitioner and specialists in caring for patients with 22q11DS. Although still under-recognized, detection, including in the prenatal setting, is increasing. Moreover, the phenotypic spectrum is highly variable, and patients may present at any age. Thus, initial guidelines developed by an international panel of experts present the best practice recommendations currently available across the lifespan, with a major focus on the changing issues through childhood development.

Post‐operative partial hypoparathyroidism: an under‐recognized disorder

Permanent hypoparathyroidism is a well-recognized complication of total thyroidectomy, and a commonly reported clinical indicator of that procedure. However, a small number of patients still require ongoing calcium supplementation post-operatively in order to avoid the symptoms of hypocalcaemia, despite a normal serum parathyroid hormone level. The aim of this study was to characterize this disorder of post-operative partial hypoparathyroidism and to identify any risk factors. A retrospective study of patients undergoing a total thyroidectomy was performed. Patients with permanent hypoparathyroidism were excluded. Patients completed a telephone interview and had serum calcium and parathyroid hormone (PTH) measured. Patient demographics, operative indications and intervention, the number of parathyroid glands autotransplanted, the presence of ongoing symptoms and calcium requirements were documented. One hundred ninety-six patients participated. The overall rate of permanent hypoparathyroidism over the duration of the study was 0.77%. An additional 10 (5%) patients were identified with a normal PTH level but who were still requiring calcium supplementation to prevent the symptoms associated with hypocalcaemia and to maintain a normal serum calcium level. Nine patients were female with a mean age of 48.5 years. A mean of 1.4 parathyroid glands were autotransplanted and the mean PTH level was 3.95 pmol/L. This study demonstrates that in a small group of patients following total thyroidectomy, re-vascularization of parathyroid cells may be partial, with inadequate parathyroid reserve to avoid symptoms despite measurable PTH levels. This disorder of partial hypoparathyroidism has not been previously described and represents a small but important complication of total thyroidectomy.

Parathyroid Gland Dysfunction in 22q11.2 Deletion Syndrome

Background: 22q11 deletion syndrome (22q11DS) is characterized by conotruncal cardiac defects and hypoplasia of parathyroid glands and thymus, which result in variable hypoparathyroidism (HPT) and immune deficiency. Methods: To study the course of HPT and the spectrum of other associated manifestations we evaluated all patients with 22q11DS, confirmed by fluorescence in situ hybridization, and HPT who were under follow-up at the Calcium-bone clinic, The Hospital for Sick Children, Toronto. Patients were clinically assessed and their hospital records were reviewed. Results: Eighteen patients were included. At follow-up assessment at median age of 7.3 years HPT was judged complete in 11 (61%) and partial in 7 patients (39%). Patients with complete HPT presented with hypocalcemia later (median age at diagnosis 2.4 vs. 0.0 years) and more often with a hypocalcemic seizure than patients with partial HPT (73 vs. 29%). The spectrum of other associated manifestations did not differ between the groups. Conclusions: HPT in patients with 22q11DS is often partial. Many of the patients present with a hypocalcemic seizure which is predictive of complete HPT. Patients with complete and partial HPT do not differ in respect to their other associated features. Patients with features of 22q11DS should be actively screened for hypocalcemia to prevent development of symptomatic hypocalcemia.

Partial hypoparathyroidism associated with mitochondrial trifunctional protein deficiency

The mitochondrial trifunctional protein (MTP) catalyzes the last three steps in the long-chain fatty acid beta-oxidation pathway. We report herein a patient with an inherited MTP deficiency and hypoparathyroidism that were both revealed at 4 months of age. Although parathyroid function appeared to be normalized following nutritional management of the fatty acid beta-oxidation defect, persistent gland dysfunction was suggested by frequent mild episodes of hypocalcaemia without increase in plasma intact parathyroid hormone (iPTH) levels during recurrent fasting-induced episodes of rhabdomyolysis and by our finding of a bilateral cataract at 5 years of age. An acute provocation test conducted to stimulate iPTH release with sodium bicarbonate infusion resulted in a subnormal rise in iPTH release, which further supported a partial hypoparathyroidism. This case is the third report of inherited MTP deficiency associated with hypoparathyroidism, thus raising the possibility of a link between these two rare disorders.

Congenital Hypocalcemia: Transient or Persistent?-Reply

In Reply. —We thank Drs Liel and Harman-Baham for their comments regarding our article. 1 They draw attention to an editorial correspondence describing a child with Dubowitz syndrome associated with transient congenital hypoparathyroidism and subsequent overt hypoparathyroidism. 2 The course of that patient's disease is similar to the course we have observed in patients with partial hypoparathyroidism: transient neonatal hypocalcemia in the normal-weight newborn, a period of normocalcemia, development of mild hypocalcemia later in childhood, and an inappropriately low, but detectable, level of serum parathyroid hormone. This condition is probably more common than is recognized. We agree with Drs Liel and Harman-Baham that the true incidence of this disorder will be known only if serum calcium levels are measured regularly during childhood in all patients with transient congenital hypoparathyroidism.

Partial Hypoparathyroidism

We encountered three children who had neonatal hypocalcemia followed by a period of normocalcemia and recurrence of hypocalcemia later in childhood. They were full-term infants with normal birth weights who developed hypocalcemia within the first 48 hours after birth. The hypocalcemia resolved in 1 week, 3 months, and 14 months in the three patients. The recurrences of hypocalcemia occurred at 4, 7, and 12 years of age. Their plasma parathyroid hormone concentrations were consistently low but detectable. We suggest that partial hypoparathyroidism is the underlying abnormality in these patients and that neonatal hypocalcemia in otherwise healthy infants indicates the need for calcium measurements during childhood and adolescence.

Moderate hypocalcemia due to normal serum 1,25-dihydroxyvitamin D levels in an asymptomatic kindred with familial hypoparathyroidism

Hypoparathyroidism was diagnosed in nine members of a kindred of three generations. This study investigated why these persons were asymptomatic and without developmental abnormalities, in contrast to the common presentation of idiopathic hypoparathyroidism. In the hypocalcemic subjects, serum calcium level was 7.4 ± 0.8 mg/dl) mean ± SD) and ionized serum calcium level was 3.48 ± 0.21 mg/dl. Immunoreactive parathyrold hormone values were inappropriately low. Injection of EDTA in one patient lowered ionized calcium levels, but immunoreactive parathyroid hormone values did not rise. Serum levels of 1,25-dihydroxyvitamin D and other vitamin D metabolites were normal or elevated and substantially higher than in other hypoparathyroid states. The normally observed positive correlation between the fasting urinary calcium/creatinine ratio and serum 1,25-dihydroxyvitamin D that reflects the dependence of net bone resorption on 1,25-dihydroxyvitamin D was upheld in hypoparathyroid patients. It is proposed that the subjects with familial hypoparathyroidism in this kindred had moderate asymptomatic hypocalcemia without developmental abnormalities because normal or elevated serum 1,25-dihydroxyvitamin D levels enhanced intestinal calcium absorption. This may represent one point in the spectrum of idiopathic hypoparathyroidism. Alternately, both the moderate degree of hypocalcemia and the normal serum calcitriol values could have been related to mild, partial hypoparathyroidism, which could have been inherited in this kindred.

Idiopathic hypoparathyroidism presenting with seizures during infancy: X-linked recessive inheritance in a large Missouri kindred

HYPOCAI.CEMIA is most commonly encountered by pediatricians in neonates. ' Early neonatal hypocalcemia presents within the first two days of life and usually affects infants who are premature, are born of diabetic mothers, or have had anoxia, acidosis, or birth trauma. Late neonatal hypocalcemia is usually manifest at the end of the first week of life in infants who have been given feeding s with high phosphate content. Partial hypoparathyroidism appears to be important in the pathogenesis of both forms. This physiologic hypoparathyroidi sm is transient, i.e., usually lasts less than three to four weeks but occasionally as long as several months?, e Persistent idiopathic hypoparathyroidi sm is far less common. We report a large kindred in which IHP, presenting with hypocalcemia seizures in infant boys only, appears to be transmitted as an X-linked recessive trait.

Parathyroid response to EDTA in hypoparathyroidism and in tetany.

The parathyroid response to an EDTA infusion was measured in 11 patients with hypoparathyroidism and 22 patients with normocalcaemic tetany, and compared to that of normal controls and of 23 patients with primary hyperparathyroidism. Despite comparable basal PTH values, the patients with hypoparathyroidism and the normocalcaemic patients, with tetany following thyroid surgery, responded less than normals to EDTA, while normocalcaemic patients with tetany due to psychogenic hyperventilation responded more than normals. In hypoparathyroidism, mainly three types of results were observed: no response (total hypoparathyroidism), diminished or delayed response (partial hypoparathyroidism), and discrepant results using different antisera in cases of idiopathic hypoparathyroidism, suggesting the secretion of immunologically abnormal PTH. In tetany due to psychogenic hyperventilation, parathyroid hyperreactivity might be explained by repeated stimulation through respiratory alkalosis. Although the EDTA test rarely improved the diagnostic accuracy of basal PTH measurements in primary hyperparathyroidism, it was useful for differentiating between latent hypoparathyroidism and tetany due to psychogenic hyperventilation, both presenting with normal plasma calcium.