Masafumi Kitaoka

Serial Evaluation of Parathyroid Size by Ultrasonography Is Another Useful Marker for the Long-Term Prognosis of Calcitriol Pulse Therapy in Chronic Dialysis Patients

To clarify whether the changes of parathyroid size have any correlations with the long-term prognosis of calcitriol pulse therapy, we examined the time course of serum levels of parathyroid hormone (PTH) and size of parathyroid glands in 14 chronic dialysis patients during and after the oral calcitriol pulse therapy. In 5 patients without any detectable glands, secondary hyperparathyroidism was easily controlled by calcitriol pulse therapy and then by conventional oral active vitamin D therapy. In 2 patients with detectable gland(s) in whom size of all parathyroid glands as well as PTH hypersecretion regressed to normal by calcitriol pulse therapy, secondary hyperparathyroidism could then remain controlled at least for 12 months after switching to conventional oral active vitamin D therapy. In contrast, in 7 patients in whom size of all parathyroid glands did not regress to normal by calcitriol pulse therapy, secondary hyperparathyroidism relapsed after switching to the conventional therapy, even if PTH hypersecretion could be controlled temporarily. Our findings suggest that the time course of parathyroid hyperplasia detected by ultrasonography is an important determinant of the efficacy and the prognosis of calcitriol pulse therapy. Thus, the change of parathyroid gland size as well as PTH hypersecretion should be taken into account for the management of secondary hyperparathyroidism.

Activin-A: A modulator of multiple types of anterior pituitary cells

When primary culture of rat pituitary cells were incubated with 1 nM activin-A for more than 24 hrs, activin-A significantly increased intracellular content of FSH without affecting the control of LH. Pretreatment of the cells with activin-A also enhanced LHRH-induced FSH release without affecting LH release. Furthermore, pretreatment of the cells with activin-A significantly reduced both GRF-mediated GH release and TRH-mediated PRL release. However, activin-A did not affect the response of ACTH and TSH to their releasing hormones. These results indicate that, in addition to the known action on gonadotrophs, activin-A also modifies the function of somatotrophs and lactotrophs.

Thyroid ultrasound findings in children from three Japanese prefectures: Aomori, Yamanashi and Nagasaki.

Due to the likelihood of physical and mental health impacts following the unprecedented accident at the Fukushima Dai-ichi Nuclear Power Plant, the Fukushima prefectural government decided to conduct the Fukushima Health Management Survey to assist in the long-term health management of residents. This included thyroid ultrasound examination for all children in Fukushima. For appropriate evaluation of ultrasound screening of the thyroid, it is important to understand its reference data of thyroid findings in children in general. In order to analyze the frequencies of specific thyroid findings, we conducted ultrasound screening of the thyroid by the same procedures as used in Fukushima in 4,365 children, aged 3 to 18 years, from three Japanese prefectures. Overall, thyroid cysts were identified in 56.88% and thyroid nodules in 1.65% of the participants. Thyroid cysts and nodules with a maximum diameter of more than 5 mm were identified in 4.58% and 1.01%, respectively, and age-adjusted prevalences were 3.82% and 0.99%, respectively. Although the prevalence of cysts and nodules varied among the examination areas, no significant differences were observed among the three examination areas in the prevalence of cysts and nodules with a maximum diameter of more than 5 mm. Also, the prevalence of thyroid cysts and nodules, especially those with a maximum diameter of more than 5 mm, significantly increased with age, and showed a female predominance. We also identified ectopic thymus (1.95%), diffuse goiter (1.40%), ultimobranchial body (0.73%), lymph node swelling (0.21%) and thyroid agenesis (0.05%). This is the first ultrasound description of the age-adjusted prevalence of thyroid cysts and nodules, or of the prevalence of abnormalities other than cysts and nodules, such as ectopic thymus, in relation to age, in the general Japanese child population. We contend that this can provide relevant information for the Fukushima Health Management Survey and future population studies.

Imaging of the parathyroid in chronic renal failure: diagnostic and therapeutic aspects.

&NA; On the basis of recent advances in our understanding of the pathogenesis of chronic renal failure, imaging of parathyroid hyperplasia in chronic dialysis patients has become a highly useful tool not only for identification, but also for evaluation of the nature of abnormal glands and for various intervention strategies. Rational imaging approaches, different from those used for primary hyperparathyroidism, should be established for secondary hyperparathyroidism.

Direct injections of calcitriol into enlarged parathyroid glands in chronic dialysis patients with severe parathyroid hyperfunction

Summary: Severe secondary hyperparathyroidism in chronic dialysis patients has been recently treated by supraphysiological concentration of calcitriol achieved through pulse therapy. However, there are many patients resistant to this therapy, who usually have larger parathyroid gland(s). to overcome this resistance, calcitriol was injected directly into the enlarged glands under ultrasonographic guidance. We injected 70–90% of the calculated gland volume of calcitriol solution (1 μg/mL) into the glands of 7 patients three times per week for 2 weeks. the parathyroid hormone (PTH) levels decreased significantly after 2 weeks of direct injections of calcitriol. Following a further 4 weeks of calcitriol pulse therapy, PTH levels remained suppressed and serum alkaline phosphatase activity and the volume of parathyroid glands also decreased. During the long‐term follow up, five patients remained well controlled with calcitriol pulse therapy, while two patients needed ethanol injections to control hyperparathyroidism. Although we could not completely rule out a toxic effect of the vehicle, direct injection of calcitriol into parathyroid glands may be another treatment option for chronic dialysis patients. Our data further support the important role of resistance of parathyroid cells to calcitriol in the pathogenesis of parathyroid hyper function in uraemic patients.

A stimulatory effect of somatostatin: Enhancement of activin A-mediated FSH secretion in rat pituitary cells

The interaction between somatostatin and activin A was studied in terms of FSH secretion in rat pituitary cells in primary culture. Incubation of pituitary cells with 1 nM activin A for 48 hrs resulted in an increase in FSH release into incubation medium. The effect of activin A was dependent on cell-density and the higher the density, the smaller the stimulatory action of activin A. Somatostatin, by itself, did not affect the FSH secretion. When 100 nM somatostatin was included together with activin A or the cells were pretreated with somatostatin for 2 hrs, the activin A-induced FSH secretion was enhanced. This potentiation effect of somatostatin was inversely dependent on the cell-density. These results indicate that somatostatin enhances, rather than inhibits, the activin A action in pituitary cells.

Stimulation of FSH release by erythroid differentiation factor (EDF)

The action of erythroid differentiation factor (EDF) on primary culture of rat anterior pituitary cells was examined. EDF stimulates FSH secretion in a dose dependent manner but not of LH secretion. ED50 of EDF for FSH secretion was 5 X 10(-10) M, while ED50 of LHRH for FSH secretion was 5 X 10(-9) M. These data indicate that EDF is a potent agonist for FSH secretion and the biological activity of EDF on anterior pituitary seems to be identical as that of FSH releasing protein (FRP).

Thyroid ultrasound findings in a follow-up survey of children from three Japanese prefectures: Aomori, Yamanashi, and Nagasaki

We conducted ultrasound thyroid screening in cohort of 4,365 children aged between 3 to 18 years in three Japanese prefectures (Aomori, Yamanashi, and Nagasaki) using the same procedures as used in the Fukushima Health Survey. Forty-four children had nodules ≥ 5.1 mm in diameter or cysts ≥ 20.1 mm in diameter detected at the first screening, and 31 of these children underwent the second follow-up survey. We collected information from thyroid ultrasound examinations and final clinical diagnoses and re-categorized the thyroid findings after the second examination. Twenty children had nodules ≥ 5.1 mm in diameter or cysts ≥ 20.1 mm in diameter at the second examination; of these, one child was diagnosed with a thyroid papillary carcinoma and the remaining 19 children were diagnosed with possibly benign nodules such as adenomas, adenomatous nodules, and adenomatous goiters. A further 11 children were re-categorized as “no further examinations were required.” Our results suggest that ultrasound thyroid findings in children may change with a relatively short-term passing period, and that thyroid cancer may exist at a very low but certain frequency in the general childhood population.

Effects of activin A and somatostatin on intact FSH secretion and intracellular Ca2+ concentration in human FSH-secreting pituitary adenoma cells.

Activin A stimulated synthesis and secretion of intact FSH in dispersed human FSH-secreting adenoma cells. Significant stimulation was observed after 24 hr. Activin A caused an increase in Ca2+ concentration ([Ca2+]i). This response occurred soon after the activin A action. These effects were blocked in Ca(2+)-deficient medium and by nitrendipine (5 microM). Somatostatin inhibited the activin A-induced intact FSH secretion and the [Ca2+]i response. These findings indicated that Ca2+ influx through voltage-gated Ca2+ channel was involved in the activin A induced synthesis and secretion of intact FSH.

Guanine nucleotides modify calcium entry induced by insulin‐like growth factor‐I

When calcium influx rate was measured in the cell suspension system instead of confluent monolayer culture, IGF‐I (1 nM) augmented calcium entry independent of the cell cycle. In a cell suspension system, NaF increased calcium entry in a dose‐dependent manner, which was sensitive to tetramethrin. When GTP‐γS was introduced into the cells by employing ATP4−, calcium influx rate was elevated whereas ATP‐γS was without effect. In cells loaded with GDP‐βS, IGF‐I did not stimulate calcium entry. These results suggest that a G‐protein is involved in the signal transduction of IGF‐I action.