Incidence,Risk Factors,and Clinical Implications of Delayed Hypoparathyroidism on Postoperative Day two Following Total Thyroidectomy for Papillary Thyroid Carcinoma

Objective: This study aimed to investigate the incidence rates, risk factors, and clinical implications of delayed hypoparathyroidism on postoperative day 2 (POD-2) after total thyroidectomy in patients with papillary thyroid carcinoma.Methods: This study included 410 patients with normal serum intact parathyroid hormone (iPTH) and calcium levels on postoperative day 1 (POD-1) who were classified into 2 groups according to the presence or absence of delayed hypoparathyroidism on POD-2.Results: Of the 410 patients, 98 experienced delayed hypoparathyroidism on POD-2 (23.9%). The significant risk factors for delayed hypoparathyroidism on POD-2 included female gender, age older than 45 years, central lymph node dissection, increased number of excised lymph nodes, and low POD-1 versus preoperative iPTH ratios. Additionally, delayed hypoparathyroidism on POD-2 was found to be a significant risk factor for hypocalcemia on POD-2 and permanent hypoparathyroidism.Conclusion: Prophylactic calcium supplementation and long-term surveillance for permanent hypoparathyroidism should be considered in patients with risk factors for delayed hypoparathyroidism on POD-2.Abbreviations: CI = confidence interval; iPTH = intact parathyroid hormone; OR = odds ratio; POD-1 = postoperative day 1; POD-2 = postoperative day 2; PTC = papillary thyroid carcinoma; ROC = receiver operating characteristic     

Surgeons and Patients Disagree on the Potential Consequences of Hypoparathyroidism

ObjectiveTo test the hypothesis that surgeons and their patients underestimate the potential negative impact that permanent hypoparathyroidism has on quality of life (QOL).MethodsWe used a modified SF-36 assessment tool to compare the perceptions of patients with permanent hypoparathyroidism to the perceptions of control subjects who were given a standardized preoperative statement about the complications of hypoparathyroidism. We also elicited the perceptions of endocrine surgeons regarding the QOL impacts of hypoparathyroidism using a subset of questions from the modified SF-36.ResultsA total of 340 postsurgical patients with permanent hypoparathyroidism, 200 controls, and 102 surgeons participated in the study. Both surgeons and controls underestimated the negative impact of hypoparathyroidism on QOL when compared to patients living with permanent hypoparathyroidism. Forty-seven percent of hypoparathyroid patients believed that their health was “much worse” than before surgery, compared with 16% of surgeons (P < .001) and 7% of controls (P < .001). Postoperative hypoparathyroid patients also reported far more negative effects on QOL, from interference with social activities, paresthesias, muscle cramping, and medications than were anticipated by surgeons or controls (P < .05 for all comparisons). In each of the 8 dimensions of QOL, including physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, and general health, hypoparathyroid patients reported a significantly lower mean score compared to the control group (P < .001 for all comparisons).ConclusionThe impact of postoperative hypoparathyroidism on patient QOL is consistently and significantly underestimated by surgeons and subjects receiving surgical consultation. (Endocr Pract. 2014;20:427-446)     

Prediction of the outcome of postoperative hypocalcemia in Graves' disease.

Symptomatic hypocalcemia sometimes follows subtotal thyroidectomy for Graves' disease. Irreversible damage to the parathyroids contributes to permanent hypocalcemia and the mechanism for a transient hypocalcemia is thought to be different from that of a permanent one. However, sensitive assays for parathyroid hormones (PTH), which had recently become available, revealed that levels of PTH decrease in patients with transient hypocalcemia. In order to differentiate a prolonged hypocalcemia from a transient one, calcium and inorganic phosphate concentrations in serum as well as in urine, and whole molecule-PTH levels were determined in 18 Graves' disease patients with postoperative hypocalcemia just after the initial symptoms for hypocalcemia appeared. In 13 patients, medication was withdrawn within one month since serum calcium levels had returned to normal (transient hypocalcemia). In five other patients, medication was required for six months or more to maintain normocalcemia (prolonged hypocalcemia). The same parameters were determined after surgery in eight Graves' disease patients without hypocalcemia. Urinary inorganic phosphate concentrations in patients with prolonged hypocalcemia (0.02 +/- 0.01 mmol/mmol Cr) were significantly lower (P less than 0.01) than those in patients with transient hypocalcemia (1.59 +/- 1.59 mmol/mmol Cr) or those in control patients (1.27 +/- 0.70 mmol/mmol Cr). Preoperative concentrations of calcium and inorganic phosphate in serum and urine, and serum alkaline-phosphatase activities were also determined. However, there were no significant differences in these parameters between patients with prolonged and those with transient hypocalcemia. It is concluded that prolonged hypocalcemia is discriminated from the transient type by determining the urinary inorganic phosphate at the time of appearance of the initial symptoms for hypocalcemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma human calcitonin (hCT) levels in normal and pathologic conditions, and their responses to short calcium or tetragastrin infusion.

Plasma hCT levels were less than 50 pg/ml in 50 normal subjects. In 16 patients with medullary carcinoma of the thyroid (MCT), plasma hCT levels were distinctively elevated and they fell significantly after total thyroidectomy, but in 11 of them plasma levels were still high, indicating the presence of metastases. In 74 patients with the other types of malignancy, plasma hCT levels were found to be high in 9 cases (3 oat cell carcinoma of the lung, 4 malignant carcinoids, one malignant pheochromocytoma and one acute myelocytic leukemia). Except for the leukemic case, all these tumors were derived from neural crest. In 12 patients with primary hyperparathyroidism, plasma hCT levels were less than 20 pg/ml. In 13 hypoparathyroid patients, two with pseudohypoparathyroidism and one with pseudoidiopathic hypoparathyroidism, plasma hCT levels were slightly elevated. Some patients with uremia had elevated plasma hCT levels, but there was no relation between plasma levels of hCT and those of PTH, urea nitrogen or creatinine. In response to Ca (4.5 mg/kg/10 min) or tetragastrin (4 mug/kg/5 min) infusion, a marked increase in plasma hCT was observed in all patients with MCT, but not in normal subjects. In 5 hypoparathyroid patients, a significant increase to both stimuli was also observed in all cases. Two patients with pseudopseudohypoparathyroidism responded to the Ca load. These results indicate that the determination of plasma hCT levels especially after a short Ca or tetragastrin infusion is important to study various pathological conditions.     

Hypoparathyroidism after surgery on thyroid cancer: is there a delayed chance for recovery after a prolonged period of substitutive therapy?

INTRODUCTION: Transient and persistent hypoparathyroidism (HPT) belong to the well known complications of total thyroidectomy performed because of thyroid carcinoma. The true frequency of persistent hypoparathyroidism is often higher than estimated in the reports published by the specialized centers with low rate of complications. THE AIM OF THE STUDY: Investigation whether the repeated check-up, performed over 2 years post thyroidectomy, reveals some cases of recovery in patients diagnosed with persistent HPT post thyroid cancer surgery. MATERIAL AND METHODS: In total, 115 patients were included into the study, all of them treated with vitamin D derivatives and calcium supplementation. In 17 of them a diagnosis of transient hypoparathyroidism was made on the basis of evaluation performed 6 months after surgery, the remaining 98 were diagnosed with persistent HPT. Parathyroid (PTH) function was reevaluated after withdrawal of active vitamin D derivatives for 10 days and of calcium carbonate for two days during the hospital stay in patients admitted for radioiodine scan, thus after thyroxine withdrawal. The control group consisted of 123 DTC (differentiated thyroid carcinoma) patients without parathyroid dysfunction. On the basis of intact PTH serum level and calcium and phosphorus estimations HPT was unequivocally confirmed in 49 patients (50%). The remaining 49 patients exhibited normal PTH level and in 43 (86%) of them Ca(2+) level was also within normal range, thus delayed, recovery from HPT was stated. RESULTS: Our results indicate that reevaluation of hypoparathyroidism post total thyreoidectomy is necessary, as delayed recover of parathyroid dysfunction is a frequent phenomenon. We also propose criteria of reevaluation of HTP in patients on chronic substitutive therapy.     

同型半胱氨酸及甲状腺功能在他汀致冠心病患者肝功能异常中的研究

目的:研究同型半胱氨酸及甲状腺功能与他汀致冠心病患者肝功能异常的相关性。方法:服用阿托伐他汀钙(20mg,1次/日)后1-3个月肝功能正常组(ALT和AST均正常者)300例;肝功能轻度异常组(ALT或/和AST升高3倍以下者)300例;肝功能重度异常组(ALT或/和AST升高3倍以上者)300例。在转氨酶重度升高组中选取停用他汀药观察组和加用CoQ10(20mg,3次/日)治疗组各100例,对比两组转氨酶下降情况。结果:PCI术后服用他汀类药物治疗1-3个月后出现肝功能异常的冠心病患者,同型半胱氨酸水平升高,甲状腺功能降低;肝功能的异常与年龄及饮酒有相关性。转氨酶重度升高患者中,加用CoQ10治疗组较仅停药组转氨酶显著下降。结论:阿托伐他汀钙引起的冠心病患者同型半胱氨酸水平升高及甲状腺功能下降与肝功能损伤有明显相关性。CoQ10可显著降低转氨酶水平。     

Prolonged Vitamin D Intoxication in a Patient with Hypoparathyroidism

Pitfalls in the management of hypoparathyroidism are illustrated by the case of a patient who developed hypervitaminosis D while receiving doses of calciferol and of calcium in amounts commonly recommended for treatment. Either the patient was very slow to obtain maximum vitamin D effect or else her sensitivity to vitamin D increased, because she did not become hypercalcemic until two years after treatment was started. The dose of vitamin D was halved to 50,000 units per day and the dose of calcium was lowered to 0.26 g. daily. She failed to remain under medical supervision for the next four years and presented with hypercalcemia and evidence of renal impairment. After vitamin D was discontinued she remained hypercalcemic for nine months.These findings are discussed in the light of current knowledge concerning the actions of parathyroid hormone and vitamin D. The influence of adrenocortical hormones on calcium metabolism is considered. The need to follow up hypoparathyroid patients closely, and to check the level of calcium in the serum, is emphasized.     

Effects of triiodothyronine treatments on body and organ growth and the development of immune function in dwarf chickens

The effects of triiodothyronine (T3) treatments on general body growth, long bone growth, primary lymphoid organ development, antibody production, and serum growth hormone (GH) and thyroid hormone levels were examined in two dwarf strains (sex-linked dwarf--SLD, and autosomal dwarf--ADW) and in a normal-growing control strain (K) of White Leghorn chickens. One-day-old male chicks from each of these strains were assigned to either an untreated control group or to one of the groups receiving a T3 supplement ranging from 0.01 to 1.0 ppm. General body growth and long bone growth were significantly (P less than 0.05) stimulated only within the SLD strain by the intermediate T3 dosages. The 1.0-ppm T3 dosage level resulted in depressed body weights within both the K and ADW strains but produced no significant changes within the SLD strain. Thymic growth was significantly stimulated due to treatments of 0.1 ppm T3 in the SLD strain (P less than 0.05) and 1.0 ppm T3 in both the SLD and ADW strains (P less than 0.001 and P less than 0.05, respectively). Bursal growth was significantly depressed (P less than 0.05) at all T3 dosage levels within the SLD strain while 0.01 and 0.1-ppm T3 treatments resulted in significant bursal growth stimulation in the K and ADW strains, respectively. Concomitant with the depressed bursal growth, antibody production was significantly depressed (P less than 0.05) within the SLD strain at the 1.0-ppm T3 dosage level. Antibody production was not significantly affected by any of the T3 treatments within the control K or ADW strains. Serum T3 levels were significantly increased in all strains by the T3 supplementation but thyroxine (T4) serum levels were affected only within the SLD strain. The 0.01-ppm T3 treatment resulted in a significant increase (P less than 0.05) in serum T4 levels within this strain and treatment group. The only increase (P less than 0.05) in GH levels due to T3 treatments occurred within the same SLD treatment group. The higher T3 treatments resulted in serum GH levels being severely depressed (P less than 0.01) in all strains.     

甲状腺全切除术与半切除术治疗甲状腺癌的临床效果分析

目的:比较甲状腺全切除术与半切除术治疗甲状腺癌的临床效果。方法:选取我院收治的90例甲状腺癌患者,对所有患者行甲状腺全切除术或近全切除术,同时应用I131以及甲状腺激素抑制治疗作为辅助治疗,并对所有患者进行随访。结果:两组患者的术中出血量、喉返神经显露率比较差异无统计学意义(P0.05),观察组的手术切口以及手术时间均明显长于对照组(P0.01),甲状旁腺显露率高于对照组(P0.01)。两组患者暂时性、永久性喉返神经损伤,暂时性、永久性甲状旁腺功能低下发生率比较差异无统计学意义(P0.05)。复发率为13.33%(6/45),观察组无复发,两组患者术后复发率比较差异具有统计学意义(P0.05)。结论:甲状腺全切除术治疗甲状腺癌的效果优于半切除术,且能够有效降低术后复发率。     

Postoperative hypoparathyroidism: risk of complications]

For assessing the risk of adverse complications of surgery the group of 130 patients with post-operational hypoparathyroidism was analysed. Surgical hypoparathyroidism has been diagnosed in 51% of operated on thyroid gland patients. Laryngeal nerves have been damaged in 46.6% of patients. The injury to laryngeal nerves has been irreversible in 2/3 of patients, and reversible in the remaining 1/3. Cataract, nephrolithiasis and vitamin D3 intoxication have been observed in some cases before surgery. Their incidence increased in severe surgical hypoparathyroidism. Osteoporosis of the spine has been diagnosed in 49% of patients including some with vertebral fractures. No correlation between the degree of spine osteoporosis and diagnosis before surgery, number of operations on thyroid gland, and type of therapy has been noted. The symptoms of hypercalcemia have been diagnosed in 5 patients out of which hypercalcemia has been transient in 2 patients, and lasted for 1-5 months in the remaining 3 patients. The results of 7,873 analyses of mineral metabolism have been assessed. Hypocalcemia has been found in 38.4%, hypercalcemia in 1.6%, hypomagnesemia in 25.7%, hyperphosphatemia in 41.5%, decreased alkaline phosphatase serum activity in 28.7%, and hypercalciuria in 22.4% of cases. Surgical hypoparathyroidism is frequently accompanied by surgical hypothyroidism and injury to the recurrent laryngeal nerves.     

Bone mineral density in hypoparathyroid women on LT4 suppressive therapy. Effect of calcium and 1,25(OH)2 vitamin D3 treatment

Our aim was to study the bone mineral density (BMD) of patients with chronic hypoparathyroidism (hypoPTH) after longterm calcium and vitamin D treatment. Twenty hypoPTH women (mean-/+SD, aged 50-/+15 years, IPTH 4-/+6 pg/ml) and 20 matched euparathyroid women (euPTH) after near total thyroidectomy for thyroid cancer, completed with I-131 ablation and on suppressive therapy with L-Thyroxine (LT(4)), were studied. In addition eight hypoPTH patients who were receiving LT(4) replacement therapy after surgery for compressive goiter were simultaneously studied. The hypoPTH patients were on calcium and 1,25(OH)(2) vitamin D(3) therapy to normalize serum calcium. Bone mineral density (BMD) (DXA, at the lumbar spine [L(2)- L(4), LS], femoral neck [FN] and Ward triangle [WT]), serum and urine calcium, serum phosphorus, TOTALALP and osteocalcin were measured. Patients with hypoPTH showed greater lumbar BMD than euPTH patients on suppressive therapy (Z-score; 1.01-/+1.34 vs. -0.52-/+0.70, p<0.05). Serum osteocalcin levels were higher in hypoPTH patients on suppressive therapy compared to hypoPTH patients on replacement therapy. The LS BMD from hypoPTH patients correlated with calcium supplements (r=0.439; p=0.02), 1,25(OH)(2)D(3) dose (r=0.382; p=0.04) and LT(4) dose (r=0.374; p=0.05). Our data suggest that long-term treatment with calcium and 1,25(OH)(2) vitamin D3 supplements in hypoPTH patients on suppressive LT4 therapy results in increased BMD when compared with patients with normal PTH levels.     

Effect of verapamil on CRF-induced abnormalities in phospholipid contents of brain synaptosomes

Chronic renal failure is associated with significant reductions in total phospholipids, phosphatidylinositol, phosphatidylserine, and phosphatidylethanolamine of brain synaptosomes. These derangements in synaptosomal phospholipid metabolism were attributed to the state of secondary hyperparathyroidism of chronic renal failure (CRF) and the parathyroid hormone-induced accumulation of calcium in synaptosomes. This study examined whether a calcium channel blocker, verapamil, would prevent this synaptosomal calcium accumulation and correct the abnormalities in synaptosomal phospholipids in CRF. Verapamil treatment of normal rats for 21 days did not affect synaptosomal content of calcium or phospholipids. CRF of 21 days' duration was associated with a significant (P less than 0.01) increase in synaptosomal calcium (10.2 +/- 0.5 vs 7.4 +/- 0.6 nmol/mg protein) and a significant reduction (P less than 0.01) in total phospholipids (397 +/- 12 vs 529 +/- 19 nmol phospholipid P/mg protein), phosphatidylinositol (2.7 +/- 0.22 vs 4.6 +/- 0.27 nmol phospholipid P/mg protein), and phosphatidylserine (37 +/- 1.9 vs 83 +/- 5.2 nmol phospholipid P/mg protein). Simultaneous treatment of CRF rats with verapamil for 21 days reversed the synaptosomal abnormalities in calcium and phospholipid contents. Our data support the notion that the effect of excess parathyroid hormone of CRF on synaptosomal phospholipids is mainly due to the parathyroid hormone-induced calcium accumulation.     

Thyrotropin measured by the immunoradiometric assay in low birth weight infants

In 37 infants, the blood levels of TSH were determined by the immunoradiometric assay (IRMA) and the relation between TSH and thyroid hormone was evaluated. The ranges of gestational age (weeks) and birth weight (g) of infants were 28-42 and 982-3,650, respectively. The birth weights of 19 infants were below 2,500 g. The free T4 levels in the low birth weight (LBW) infants were lower than those of the normal infants and significantly correlated to the birth weight (r = 0.64, P less than 0.01) and gestational age (r = 0.58, P less than 0.01). In addition, free T4 levels were significantly correlated to the levels of total T4 (r = 0.66, P less than 0.01). The concentrations of TSH measured by IRMA method were significantly correlated to those of free T4 (r = 0.51, P less than 0.01). From these data, we consider that the transient hypothyroxinemia observed frequently in LBW infants might be a physiological reaction regulated by hypothalamus and that thyroid hormone treatment should be avoided.     

Efficacy and safety of long term treatment of unresponsive hypoparathyroidism using multipulse subcutaneous infusion of teriparatide

Vitamin D nonresponsive hypoparathyroidism is uncommonly seen in the clinical practice. The use of new treatment modalities, including teriparatide administration, provides an alternative requiring its validation. We report the first case of hypoparathyroidism refractory to vitamin D that was successfully controlled for 5 years by teriparatide treatment. A 53-year-old woman presented severe hypoparathyroidism after thyroidectomy. No therapeutic response was obtained with oral and i. v. calcium and magnesium, or even with 5 μg calcitriol/day. Digestive disorders were ruled out and heterologous parathyroid transplant was ineffective. Subcutaneous (s. c.) recombinant human PTH 1-34 (rhPTH-teriparatide) plus oral calcitriol, calcium, and magnesium, were partially effective, but effectiveness of 20 μg teriparatide lasted less than 4 h and stable calcemia was not possible even with 4-6 injections/day. Multipulse s. c. pump driven infusion of teriparatide achieved complete normalization of serum calcium, phosphate, magnesium, calciuria, and magnesuria with relatively low teriparatide doses (25-35 μg/day) after the first day of treatment. Effectiveness of this treatment modality was maintained for 5 years. The only significant side effect observed during these years was the development of subcutaneous nodules with occasional insufficient control of calcemia. A gain in bone mineral density was observed after the first year of treatment, which had remained stable and within normal values, thereafter until now. No abnormalities in bone scintigraphy were detected in the follow-up. Vitamin D unresponsive hypoparathyroidism maybe safely and effectively controlled at long term by s. c. multipulse pump treatment recombinant human PTH.     

Amiodarone-induced changes in lipid metabolism

Hypothyroidism is a major cause of secondary hypercholesterolemia. Amiodarone treatment alters both the levels of serum lipids and thyroid hormones. We investigated whether the amiodarone-induced changes in lipid metabolism are related to the changes in thyroid hormone levels. Eighteen patients received amiodarone (31 +/- 3 g cumulative dose) for six weeks. Serum triglyceride, total-cholesterol, high density lipoprotein-cholesterol and its subfractions, apolipoproteins B and AI, and plasma post-heparin lipoprotein lipase and hepatic triglyceride lipase activities were determined. Amiodarone treatment caused significant increases in serum total-cholesterol (baseline 4.4 +/- 0.21 (SE), 6 weeks 5.12 +/- 0.26 mmol/l, P less than 0.01), in low density lipoprotein cholesterol (baseline 2.61 +/- 0.26, 6 weeks 3.36 +/- 0.21 mmol/l, P less than 0.05) and in apolipoprotein B (baseline 1.95 +/- 0.15, 6 weeks 2.26 +/- 0.13 mmol/l, P less than 0.01) concentrations. Serum high density lipoprotein and its subfractions, or apolipoprotein AI levels did not change. Plasma post-heparin lipoprotein lipase activity increased (baseline 137 +/- 21, 6 weeks 168 +/- 21 U/ml, P less than 0.01) while hepatic triglyceride lipase did not change. Amiodarone also caused an increase in serum thyroxine (baseline 110 +/- 8, 6 weeks 136 +/- 6 mmol/l, P less than 0.05), although values remained in euthyroid range. In summary, amiodarone therapy increased the concentrations of atherogenic lipoproteins in the serum similar to that seen in hypothyroidism. On the other hand the effect of amiodarone on lipoprotein lipase was opposite to that seen in hypothyroidism. Therefore, amiodarone-induced changes in lipid metabolism cannot be explained solely on the basis of the changes in circulating thyroid hormone levels.     

Permanent and Transient Congenital Hypothyroidism in Fayoum,Egypt: A Descriptive Retrospective Study

Background

Congenital hypothyroidism (CH) is one of the most common preventable causes of mental retardation. One important challenge in understanding the epidemiology of CH is that some newborns will have transient CH, a temporary depression of thyroid hormone concentrations that can last from several days to several months. Studies from other countries have reported that 10 to 15% of children treated for CH ultimately prove not to need treatment past 3 years of age to maintain normal hormone concentrations, and thus have transient hypothyroidism. The purpose of this study was to determine the prevalence of permanent and transient congenital hypothyroidism in Fayoum, Egypt.

Methods

Cases detected by Fayoum neonatal screening program (NSP) between January 2003 and December 2011, and followed up at health insurance center were included. Permanent or transient CH was determined using results of thyroid function tests.

Results

Of the 248 patients diagnosed primarily with CH by NSP; 204 (82.3%) patients were diagnosed to have permanent CH (prevalence 1/3587 live birth), and 44 (17.7%) patients were diagnosed to have transient CH (prevalence 1/16667 live birth). Initial TSH levels were higher in permanent CH cases than transient cases (p<0.004). Female to male ratio was 0.8 and 0.7 in permanent and transient CH respectively. 161 (65%) patients had thyroid dysgenesis (107 ectopic thyroid gland, 28 athyreosis and 26 thyroid hypoplasia). 87 (35%) patients had intact gland in thyroid scan and were considered to have dyshormonogenesis. Of these 87 patients 44 proved to have transient CH and 43 had permanent CH.

Conclusion

The preliminary data from our study revealed that the incidences of CH as well as the permanent form were similar to worldwide reports. Although the high incidence of transient CH in our study could be explained by iodine deficiency further studies are needed to confirm the etiology and plan the treatment strategies.     

1,25-Dihydroxyvitamin D production after stimulation with synthetic human parathyroid hormone (1-34) in hypoparathyroid and renal tubular disorders

1,25-dihydroxyvitamin D production in response to two successive infusions of synthetic active 1-34 fragment of human PTH [hPTH-(1-34)] was evaluated in order to develop an understanding of the vitamin D metabolism and the rationale of vitamin D therapy in calcium disorders. Five normal controls, six hypoparathyroid patients, two patients with hypophosphatemic vitamin-D-resistant rickets, one patient with Lowe's synd. and one patient with primary Fanconi's synd. were investigated, and the following results were obtained. All normal controls showed a significant increase in serum 1,25(OH)2D[43 +/- 3.8 (m +/- SEM, n = 5, basal), 53 +/- 4.3 (three hours after the first PTH infusion), 65 +/- 7.7 (six hours) and 66 +/- 4.4 (nine hours) pg/ml]. All patients with PTH-deficient hypoparathyroidism showed a significant increase in serum 1,25(OH)2D, and serum 1,25(OH)2D values were within the normal range after hPTH-(1-34) stimulation. Serum 1,25(OH)2D remained low after hPTH-(1-34) infusions in a patient with pseudohypoparathyroidism type I who showed a significant increase in this value after infusion of dibutyryl cyclic AMP. On the other hand, a patient with normocalcemic pseudohypoparathyroidism type I had a high basal 1,25(OH)2D value, which increased further after hPTH-(1-34) infusions. An almost normal increase in serum 1,25(OH)2D was observed in two patients with hypophosphatemic vitamin-D-resistant rickets, one with Lowe's syndrome and the other with primary Franconi's syndrome. We conclude that these results ae important in obtaining an understanding of calcium and vitamin D metabolism in these disorders and that this PTH stimulation test is a useful method to use in evaluating renal responsiveness in 1,25(OH)2D production to PTH in various calcium disorders.     

Optimum duration of antithyroid drug treatment determined by assay of thyroid stimulating antibody in patients with Graves' disease.

OBJECTIVE--To determine the optimal duration of antithyroid drug treatment by monitoring serum thyroid stimulating antibody values in patients with Graves'' disease. DESIGN--Prospective longitudinal trial of patients with Graves'' disease followed up for 24 months after withdrawal of treatment. SETTING--Tertiary referral centre. PATIENTS--A total of 64 consecutive patients with untreated Graves'' disease, eight of whom were subsequently excluded. Fifty six patients completed the study. INTERVENTIONS--All patients were treated initially with carbimazole 40 mg, then with decreasing doses that maintained a euthyroid state. Treatment was scheduled to continue for 18 months but was withdrawn earlier if serum thyroid stimulating antibody became undetectable. END POINT--Serum values of thyroid stimulating antibody (assayed by stimulation of human thyroid cells in vitro) and thyroid hormones and thyroid state every three months during treatment and afterwards every six months for 24 months. MEASUREMENTS AND MAIN RESULTS--In 44 patients serum thyroid stimulating antibody became undetectable during treatment and treatment was withdrawn (median duration of treatment nine months, range 3-18 months). In 12 patients the antibody could be detected during 18 months of treatment. Among the first group of 44 patients initial values of the antibody before treatment were significantly lower than in the second group of 12 patients (median 225% (range 138-1236%) v 570% (250-1480%), p less than 0.001); the incidence of relapse was also lower (41% v 92%, p less than 0.001); and among those who did relapse the disease free interval after treatment was longer (median 12 months v 1 month, p less than 0.001). Moreover, the initial median serum values of thyroid stimulating antibodies were not related to the occurrence of relapse or remission as these did not differ between patients who did and did not have a relapse (median 267% (range 139-1480%) v 220% (range 138-1236%). CONCLUSION--Monitoring of serum thyroid stimulating antibody was a good guide to the duration of treatment as it allowed the treatment period to be considerably shortened in a large group of patients with no loss of efficiency.     

Postoperative hypoparathyroidism: Direct para-operative period]

Surgical hypoparathyroidism is a severe complication of the operations on thyroid gland. Hundred thirty patients aged between 17 and 77 years have been analysed clinically. Group I involved 45 patients with surgical hypoparathyroidism of transient or partial character, group II involved 85 patients with severe irreversible surgical hypoparathyroidism. Hypocalcemia in postoperative period was significantly higher in group II than that in group I (p < 0.02), and negatively correlated with the maximal dose of vitamin D3 necessary to compensate calcemia (r = -0.42). Follow-up results indicate that the age and sex of patients, preoperative diagnosis, radiotherapy, and type of surgery have no effect on the degree of damage to parathyroid glands, tetany development rate, degree of hypocalcemia and hyperphosphatemia. High degree hypocalcemia diagnosed in the early postoperative period suggests irreversible injury to parathyroid glands. Management of patients with postoperative tetany requires a close cooperation of surgeon and endocrinologist.     

Negative impact of Crohn's disease on bone mineral mass

Prolonged chronic inflammation and corticosteroid therapy increase the risk of osteoporosis in patients with Crohn's disease. It has been estimated that 30% of these patients, who take steroids for prolonged periods, will suffer a vertebral fracture. Patients with Crohn's disease are difficult to wean from corticosteroids and therefore are at risk of developing bone complications. The purpose of this cross-sectional study was to examine the relationship between cumulative steroid dose, duration of the disease and the development of osteopenia in patients with Crohn's disease. We studied 28 patients (17 men, 11 women) with Crohn's disease: eight had one or more bowel resections and all the women were premenopausal. Serum calcium, phosphate, total alkaline phosphatase, immunoreactive parathyroid hormone (iPTH), 25(OH)Vitamin D(3) and 1,25 (OH)(2) Vitamin D(3) were measured by autoanalyser methods or radioimmunoassay. Bone mineral density (BMD) was studied using dual energy X-ray bone absorptiometry of the lumbar spine (L2-L4) and the femoral neck. Of these 28 patients, 27 received an average of 17.3 +/- 21.7 g (range 1 to 80) g of prednisone over a period of 4 to 216 months. Fourteen out of the 28 patients had mildly diminished bone density (z-score >-2.5 SD and < -1 SD) of the spine and 15/28 of the hip. We found a greater decrease in bone density (z-score < -2.5 SD) in 2 out of 28 patients at the spine and in 5 out of 28 at the femoral neck. Those in whom the duration of the disease was less than two years (12 patients) had significantly higher vertebral z-scores (-0.096 +/-0.91) than those who had the disease for over two years (-1.31 +/- 2.37), (p<0.05). We found no significant correlation between lumbar spine and femoral neck z-scores and cumulative steroid therapy. Six out of 28 patients (four women and two men), of mean age 47.2+/-11.7, had one vertebral fracture. The mean cumulative dose of steroids (prednisone or budesonide) in patients with vertebral fractures was higher but not significantly different from that in patients without fractures -20.1+/-18.2 versus 14.1+/-11.2 g of prednisone, respectively (p>0.05). No correlation was found between various serum hormones and other biochemical parameters of bone turnover or bone density. We conclude that a large proportion of patients with Crohn's disease have reduced bone mineral density (58% at the spine and 75% at the femoral neck). The pathogenesis of bone loss is probably multifactorial. Although steroid therapy might be an important contributory factor, we were unable to find a significant correlation between it and bone loss. On the contrary, we observed that the duration of the disease makes a significant contribution to bone loss.