Calcium-mediated parathyroid hormone suppression test in uraemic secondary hyperparathyroidism.

AIM: The present study aimed to investigate the value of calcium-mediated parathyroid hormone (PTH) suppression test in evaluating the autonomic secretory function of parathyroid, and the management of uraemic secondary hyperparathyroidism (SHPT). METHODS: Calcium-mediated PTH suppression test was performed in dialysis with SHPT, who were candidates for parathyroidectomy from June 2017 to December 2019 in our hospital. The PTH inhibition rate (PTH-IR) was calculated, and the correlation between PTH-IR and clinical indicators was explored. RESULTS: Fifty-one subjects were included. PTH-IR was negatively correlated with baseline PTH (r = -0.35, P = .012), it was also correlated with dialysis years, coronary artery calcification score (CACS) and parathyroid mass (r = -0.397, P = .004; r = -0.327, P = .028; r = -0.363, P = .015), which were not found for baseline PTH. Forty-four patients underwent surgical treatment. According to the histological results, 26 patients presented with parathyroid non-nodular hyperplasia, and 18 patients presented with parathyroid nodular hyperplasia. The mass of parathyroid of patients with nodular hyperplasia was higher than that of patients with non-nodular hyperplasia (ρ = 0.01). The difference of the PTH-IR was not found between the two groups (ρ = 0.296). During the test, the highest serum calcium was 2.9 ± 0.4 mmol/L, which dropped to normal at the end of the test. CONCLUSION: Parathyroid hormone inhibition rate might be a useful indicator in evaluating the autonomic secretory function of parathyroid and the progression of SHPT on top of intact PTH. Calcium-mediated PTH suppression test was safe in uraemic SHPT patients, but need to monitor for transient hypercalcaemia.

[THYROID SURGERY WITH ELECTRIC WELDING OF BIOLOGICAL TISSUE: COURSE OF THE EARLY POSTOPERATIVE PERIOD].

The experience of performing surgery on the thyroid gland (TG) in 205 patients was generalised, including the use of electric welding of biological tissue technologies (EST) ­ at 95. We used the apparatus for electric welding and high frequency surgical coagulator EK300­M1 and EKVZ­300 "Patonmed" as well as the original adaptive bipolar coagulation instruments. Operations carried out under endotracheal anesthesia "open" process, completed their stratified overlay nodal joints and vacuum­suction drainage. To assess the effectiveness of EST in thyroid surgery were analyzed during the early postoperative period. The positive impact of technology EST not only on surgical tactics, but also course of the early postoperative period. Recommended use of EST as a standard for surgical interventions on the thyroid.

Cardiac dysrhythmia complicating total parotidectomy.

Sudden severe dysrhythmias during anaesthesia can be life- threatening for the patient. We describe a case in which ventricular dysrhythmias and severe bradycardia occurred during dissection and mobilization of the deep lobe of the parotid gland during total parotidectomy under general anaesthesia. We believe that these dysrhythmias were caused by a trigemino- vagal reflex similar to the oculocardiac reflex, but with afferent innervation from mandibular division of the trigeminal nerve. The case report is presented to illustrate a possible existence and importance of reflex bradycardic responses that may occur during surgical procedures involving the parotid gland.

The motor fibers of the recurrent laryngeal nerve are located in the anterior extralaryngeal branch.

OBJECTIVE: This study aimed to establish the prevalence of extralaryngeal bifurcation of the recurrent laryngeal nerve (RLN) and investigate the location of the motor fibers to the intrinsic muscles of the larynx within the branches of the RLN. SUMMARY OF BACKGROUND DATA: Recognition of extralaryngeal branching of the RLN is important, because inadvertent division of a branch may lead to significant vocal cord palsy despite the operator believing the nerve was preserved. METHODS: Prospective operative data on branching of the RLN were collected in 579 patients undergoing thyroidectomy or open parathyroidectomy over a 3 year period and nerve integrity monitoring was utilized to document the position of the motor fibers of the last 176 RLNs. Adduction of the vocal cords was detected by the electromyography-endotracheal tube and abduction by finger palpation of muscle contraction in the posterior cricoarytenoid. RESULTS: A total of 838 RLN were studied (right--432, left--406). Bifurcations occurred on the right in 111 (25.7%) and left 93 (22.9%). Bilateral bifurcation occurred in 23 (8.9%) of bilaterally dissected nerves. Overall 176 RLNs in 118 patients were assessed by the nerve integrity monitoring. Of these 41 (23.3%) were bifid RLN. In all 41 (100%) cases of bifid RLN, motor fibers for both adduction and abduction of the vocal cords were located exclusively in the anterior branches of RLN, and none in the posterior branches. CONCLUSION: Extralaryngeal bifurcation of RLN is a common anatomical variant. The motor fibers of RLN are located in the anterior branch, for both adduction and abduction. Great care is therefore required following the presumed identification of the RLN to ensure there is no unidentified anterior branch.

Nerve fibres in the parathyroid gland of the golden hamster (Mesocricetus auratus): immunohistochemical and ultrastructural investigations.

We investigated the morphology and the distribution of the nerve fibres in golden hamster (Mesocricetus auratus) parathyroid glands using antibodies to calcitonin gene-related peptide (CGRP) and substance P, and electron microscopy. CGRP-immunoreactive nerve fibres were densely distributed in the interstitial tissues and the capsules of the hamster parathyroid glands. Some nerve fibres were detected in close proximity of the parathyroid chief cells. The distribution pattern for substance P-immunoreactive nerve fibres was roughly the same as for CGRP-immunoreactive fibres. Ultrastructurally, we found numerous nerve fibres joining the blood vessels. Axon bundles were located adjacent to the smooth muscle cells of the arterioles. The axons formed structurally specialized neuromuscular junctions with the vascular smooth muscle cells. Some axons were in close vicinity to the parathyroid chief cells. These findings indicate that the hamster parathyroid gland contain CGRP and substance P, which may regulate the blood flow and the secretory activity of the gland.

[Adrenergic regulation of the structure and function of the parathyroid glands]. / Adrenergicheskaia reguliatsiia struktury i funktsii okoloshchitovidnykh zhelez.

In this review the current concepts on the sources of sympathetic innervation of the parathyroid glands (PTG) of mammals are systematized; morphological and histochemical characteristics of intraorganic sympathetic nerves are described. The influence of experimental sympathetic denervation and pharmacological modulation of adrenoreceptors on secretory and proliferative activity of parathyrocytes was analyzed. The main mechanism of influence of catecholamines released from the nerve endings and transported from the blood, on parathyrocytes is their diffuse action on cell receptor apparatus, mostly on beta-adrenoreceptors located in plasma membrane. In physiological regeneration conditions, catecholamines are able to increase secretory and mitotic activity of pararthyroid epithelium. In reparative regeneration of the PTG, chemical sympathetic denervation and pharmacological modulation of beta-adrenoreceptors lead to a decrease in the expression and duration of parathyrocyte proliferative response; at the organ level this resulted to in the appearance of the tendency towards development of focal-type proliferative reaction instead of diffuse ones.

Surgical anatomy of the thyroid and parathyroid glands.

From a surgical viewpoint there are several critical anatomic structures that lie in close proximity to the thyroid gland. These critical structures include the recurrent laryngeal nerves, the superior laryngeal nerves, and the parathyroid glands. Successful thyroid surgery depends on the technical skill of the surgeon to identify and preserve these vital structures.

Autotransplantation of rat parathyroid glands: a study on morphological changes.

BACKGROUND: Autotransplantation of parathyroid glands in man is performed to preserve parathyroid function after surgery. In a rat model, we performed autotransplantation into the renal subcapsular space to examine reinnervation and changes in cell activity in the transplanted glands. METHODS: Parathyroids grafted for 1-20 weeks were examined immunocytochemically for general and specific neuroendocrine markers to visualize nerve fibers and glandular cells and for bromodeoxyuridine to determine cell proliferation. In situ hybridization was used to localize and quantitate chromogranin A and parathyroid hormone (PTH) mRNA expression. RESULTS: Reinnervation was observed as early as 1 week after transplantation in that nerve fibers containing the general neuronal marker protein gene product 9.5 appeared along blood vessels. During the following 20 weeks, the nerve fiber density increased gradually. One week after transplantation, the immunoreaction intensity for PTH, chromogranin A, and pancreastatin was lower than in control glands. Bromodeoxyuridine-labeled cells were fewer than in control glands at 1 week and at 5-10 weeks after transplantation. The density of PTH mRNA labeling was lower than in control glands during the whole time period studied and reached a minimum after 10 weeks. The density of chromogranin A mRNA labeling was unaffected at 1 and 3 weeks after transplantation and then decreased to a minimum at 10 weeks after transplantation; at 20 weeks, the chromogranin A mRNA labeling had again reached the level in control glands. CONCLUSION: The changes in PTH and chromogranin A immunoreaction intensity and mRNA density indicate reduced hormone production for several weeks after transplantation. Our results using transmitter-specific markers indicate a rapid ingrowth of mostly sympathetic nerve fibers, preferentially around blood vessels. Later on, parasympathetic and sensory nerve fibers reached the grafts. The parathyroid innervation may be of importance for parathyroid hormone regulation, and the finding of an early reinnervation could be of clinical importance.

Developmental expression of neuronal and endocrine markers in the parathyroid glands of the rat.

The parathyroid glands of the adult rat harbor a number of neuroendocrine markers, biologically active peptides and "classical" neuromessengers in addition to parathyroid hormone (PTH). Their appearance during parathyroid development is, however, not known. In the present study we have examined several neuroendocrine markers and neuromessengers in the parathyroid glands of the developing rat [embryonic stage 21(E21), newborn, 1, 2, 3, 4 week old, and adult rats] using immunocytochemistry. Chromogranin A- and PTH-mRNA were also examined by in situ hybridization and the mRNA levels were quantitated by computerized image analysis. Protein gene product 9.5- and synaptophysin-containing nerve fibers appeared already before birth and then gradually increased in number postnatally, and at the age of 4 weeks the nerve fibers were moderate in number to numerous. Nerve fibers containing calcitonin gene-related peptide, neuropeptide Y and vasoactive intestinal polypeptide also increased gradually in number, while galanin-, substance P- and tyrosine hydroxylase-containing fibers remained few throughout development. The glandular cells expressed chromogranin A, pancreastatin and PTH already before birth. The levels of chromogranin A- and PTH-mRNA were low at E21 and increased markedly at birth; chromogranin A mRNA levels had increased even more at 1 week postnatally. Three to 4 weeks after birth the levels of PTH- and chromogranin A mRNA again increased, then stabilized at a slightly lower level in the adult rat. Our findings demonstrate that the parathyroid glands of rat are already innervated and express PTH and chromogranin A before birth and that the density of peptide-containing nerve fibers changes during development. The stepwise increases of PTH- and chromogranin A mRNAs during development indicate marked changes in parathyroid activity occurring at birth and at weaning.

Peptide-containing nerve fibres in normal human parathyroid glands and in human parathyroid adenomas.

There are only a few studies on the innervation of the human parathyroid glands and the content of neurotransmitters. We therefore studied the occurrence and distribution of peptide-containing and adrenergic nerve fibres and the coexistence pattern of neuromessengers by immunocytochemistry in normal (unaffected) and adenomatous parathyroid glands from patients undergoing surgery for parathyroid adenoma. The unaffected parathyroid glands had a moderate-to-rich supply of nerve fibres and terminals containing two general neuronal markers, protein gene product 9.5 (PGP 9.5) and synaptophysin, neuropeptide Y (NPY) and tyrosine hydroxylase (TH). They were seen close to blood vessels and, occasionally, among the endocrine cells. Only a few nerves contained calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), substance P (SP) and pituitary adenylate cyclase-activating peptide (PACAP). The general density of innervation, using PGP 9.5 and synaptophysin as markers, varied greatly among the different adenomas examined. This applied also to the density of fibres and terminals containing specific types of messengers. Some of the tumours had a rich supply of TH- and NPY-containing nerve fibres, while others contained only few scattered fibres. The CGRP-containing fibres varied from moderate in number to no detectable fibres. The PACAP-, SP- and VIP-containing fibres were always very few or not detectable. It is not inconceivable that the wide variation in general density of the innervation and frequency of peptide-containing nerves among individual parathyroid adenomas is of significance for their hormone secretory behaviour.

Innervation of the chicken parathyroid glands: immunohistochemical study with the TuJ1, galanin, VIP, substance P, CGRP and tyrosine hydroxylase antibodies.

The innervation of the chicken parathyroid glands was studied by immunohistochemistry using various antibodies. The parathyroid glands, as well as the carotid body and ultimobranchial gland, received branches originating from the vagus nerve. Numerous nerve fibers immunolabeled with the monoclonal antibody (TuJ1) against neuron-specific class III beta-tubulin isotype were found in the connective tissue capsule and septa penetrating into the parathyroid parenchyma. They were also prominent in the wall of blood vessels. Peptidergic nerve fibers immunoreactive for galanin, vasoactive intestinal polypeptide (VIP), substance P and calcitonin gene-related peptide (CGRP) were densely distributed in the capsule, septa and blood vessel walls of the parathyroid glands. In addition, some TuJ1-, substance P- and CGRP-immunoreactive fibers were detected in close association with the parenchymal cells of parathyroid glands. Tyrosine hydroxylase-immunoreactive fibers were concentrated around blood vessels and also in connective tissue stroma.

Accessory carotid body within the parathyroid gland III of the chicken.

In the chicken, the cranial and caudal parathyroid glands (parathyroid gland III and IV), which are connected to each other, are located adjacent to the carotid body. In the present study, we found that a mass of glomus cells surrounded by a thick layer of connective tissue was frequently distributed within the parathyroid gland III. The glomus cells in the parathyroid III, as well as those of the carotid body, expressed intense immunoreactivity for serotonin, chromogranin A, and tyrosine hydroxylase but no immunoreactivity for neuropeptide Y. The cells possessed long cytoplasmic processes containing dense-cored vesicles of 70-220 nm in diameter, and were in close association with sustentacular cells. In and around the glomus cell clusters of the parathyroid III, dense networks of varicose fibers showed immunostaining with the monoclonal antibody TuJ1 to a neuron-specific class III beta-tubulin isotype, c beta 4. Furthermore, the distribution was also detected of numerous galanin-, vasoactive intestinal peptide (VIP)-, substance P-, and calcitonin gene-related peptide (CGRP)-immunoreactive fibers.

Peripheral neuroendocrinology of the cervical autonomic nervous system.

1. The sympathetic superior cervical ganglia (SCG) provide innervation to the pineal gland and median eminence through the internal carotid nerve and to the thyroid and parathyroid glands through the external carotid nerve. 2. Postsynaptic activation in median eminence nerve endings shortly after superior cervical ganglionectomy (SCGx) was accompanied by a depression of LH and FSH release and by a 3-5 day delay in rat estrous cyclicity. A decrease in TSH and GH release and an increase in ACTH and prolactin release were also found. These effects were accompanied by a) an increase in medial basal hypothalamic (MBH) LHRH, TRH and GHRH, b) a decrease in MBH somatostatin, AVP and CRH, and c) a normal adenohypophyseal response to hypophysiotropic hormones. Neurohypophyseal AVP release decreased during degeneration of sympathetic nerve terminals in the neurohypophyseal lobe after SCGx. The effects were generally mediated by alpha 1-adrenoceptors and were pineal gland. 3. In thyroid and parathyroid tissue the following events were observed during the wallerian degeneration phase after SCGx: a) alpha 1-adrenoceptor inhibition of thyroxine (T4) release, b) alpha 1-adrenoceptor inhibition, together with beta-adrenoceptor stimulation, of calcitonin release, and c) alpha 1-adrenoceptor inhibition of parathyroid hormone release. Thyroid sympathetic nerves also modulate slow phenomena such as compensatory thyroid growth after partial thyroidectomy. 4. In rats subjected to cholinergic decentralization of the thyroid gland, a decrease of plasma T4 and an increase of plasma TSH, as well as an impaired goitrogenic and thyroid compensatory response were detectable. The calcitonin and PTH response to changes in calcium levels increased after regional parasympathetic denervation. 5. The results indicate that cervical autonomic nerves constitute a parallel pathway through which the brain communicates with the endocrine system.

Peripheral neuroendocrinology of the cervical autonomic nervous system

1. The sympathetic superior cervical ganglia (SCG) provide innervation to the pineal gland and median eminence through the internal carotid nerve and to the thyroid and parathyroid glands through the external carotid nerve. 2. Postsynaptic activation in median eminence nerve endings shortly after superior cervical ganglionectomy (SCGx) was accompanied by a depression of LH and FSH release and by a 3-5 day delay in rat estrous cyclicity. A decrease in TSH and GH release and an increase in ACTH and prolactin release were also found. These effects were accompanied by a) an increase in medial basal hypothalamic (MBH) LHRH, TRH and GHRH, b) a decrease in MBH somatostatin, AVP and CRH, and c) a normal adenohypophyseal response to hypophysiotropic hormones. Neurohypophyseal AVP release decreased during degeneration of sympathetic nerve terminals in the neurohypophyseal lobe after SCGx. The effects were generally mediated by alpha 1-adrenoceptors and were pineal gland. 3. In thyroid and parathyroid tissue the following events were observed during the wallerian degeneration phase after SCGx: a) alpha 1-adrenoceptor inhibition of thyroxine (T4) release, b) alpha 1-adrenoceptor inhibition, together with beta-adrenoceptor stimulation, of calcitonin release, and c) alpha 1-adrenoceptor inhibition of parathyroid hormone release. Thyroid sympathetic nerves also modulate slow phenomena such as compensatory thyroid growth after partial thyroidectomy. 4. In rats subjected to cholinergic decentralization of the thyroid gland, a decrease of plasma T4 and an increase of plasma TSH, as well as an impaired goitrogenic and thyroid compensatory response were detectable. The calcitonin and PTH response to changes in calcium levels increased after regional parasympathetic denervation. 5. The results indicate that cervical autonomic nerves constitute a parallel pathway through which the brain communicates with the endocrine system

Peptide-containing nerve fibers in the parathyroid glands of different species.

Several neuropeptides, calcitonin gene-related peptide (CGRP), galanin, neuropeptide Y (NPY), pituitary adenylate cyclase activating peptide (PACAP), substance P (SP), vasoactive intestinal polypeptide (VIP), the noradrenergic marker dopamine beta-hydroxylase (DBH) and the general neuroendocrine marker PGP 9.5 were localized by immunocytochemistry in the parathyroid glands of chicken, rat, guinea-pig, cat, dog and sheep. The general density of innervation varied markedly among the species. Nerve fibers storing CGRP, NPY, PACAP, SP and VIP were present in all species examined. Galanin-containing fibers occurred in all species except guinea-pig and adrenergic (DBH-containing) fibers in all species except chicken and guinea-pig. Generally, the nerve fibers were distributed around blood vessels, in the parenchyma as single scattered fibers, and often also within the capsule. Coexistence studies were performed in cat and sheep. CGRP and SP invariably coexisted in the same nerve fibers. Further, CGRP partially coexisted with PACAP, NPY was observed in the same nerve fibers as DBH. A small population of NPY-containing fibers also seemed to contain galanin (cat only). VIP and NPY coexisted in a population of nerve fibers in the parenchyma. A population of VIP-containing fibers also seemed to contain PACAP. The results indicate the presence of several neuropeptides in the parathyroid glands. As judged by their distribution patterns they may regulate both secretory activity and blood flow, some of them possibly in a cooperative manner.

Influence of the autonomic nervous system on calcium homeostasis in the rat.

The local surgical manipulation of sympathetic and parasympathetic nerves innervating the thyroid-parathyroid territory was employed to search for the existence of a peripheral neuroendocrine link controlling parathyroid hormone (PTH) and calcitonin (CT) release. From 8 to 24 h after superior cervical ganglionectomy (SCGx), at the time of wallerian degeneration of thyroid-parathyroid sympathetic nerve terminals, an alpha-adrenergic inhibition, together with a minor beta-adrenergic stimulation, of hypercalcemia-induced CT release, and an alpha-adrenoceptor inhibition of hypocalcemia-induced PTH release were found. In chronically SCGx rats PTH response to EDTA was slower, and after CaCl2 injection, serum calcium attained higher levels in face of normal CT levels. SCGx blocked the PTH increase found in sham-operated rats stressed by a subcutaneous injection of turpentine oil, but did not affect the greater response to EDTA. The higher hypocalcemia seen after turpentine oil was no longer observed in SCGx rats. The effects of turpentine oil stress on calcium and CT responses to a bolus injection of CaCl2 persisted in rats subjected to SCGx 14 days earlier. Interruption of thyroid-parathyroid parasympathetic input conveyed by the thyroid nerves (TN) and the inferior laryngeal nerves (ILN) caused a fall in total serum calcium, an increase of PTH levels and a decrease of CT levels, when measured 10 days after surgery. Greater responses of serum CT and PTH were detected in TN-sectioned, and in TN- or ILN-sectioned rats, respectively. Physiological concentrations of CT decreased, and those of PTH increased, in vitro cholinergic activity in rat SCG, measured as specific choline uptake, and acetylcholine synthesis and release. The results indicate that cervical autonomic nerves constitute a pathway through which the brain modulates calcium homeostasis.

Immunohistochemical identification of calcitonin gene-related peptide and substance P in nerves of the bovine parathyroid gland.

Although peptide neurotransmitters have been shown to modulate hormone secretion in many glands, there are very few studies of neurotransmitters in the parathyroid gland. Bovine parathyroid glands were collected at a local abattoir, fixed with paraformaldehyde, sectioned using a cryostat, and stained by indirect immunohistochemistry for calcitonin gene-related peptide and substance P. We were able to positively identify both neuropeptides. Nerve fibres containing calcitonin gene-related peptide and substance P were identified in contact with the tunica media of arteries and arterioles and dispersed throughout the stroma of the gland. While many of the fibres encircled parenchymal lobules, no intimate contact with the peripheral chief cells was observed. All immunoreactive fibres were found to contain both neuropeptides. Since calcitonin gene-related peptide and substance P are vasodilators, they may increase blood flow within the gland. In addition, the neuropeptides may diffuse from perilobular nerve fibres into the parenchyma, thereby modulating secretion of parathyroid hormone.

Studies on localization of calcitonin gene-related peptide (CGRP) in the thyroid-parathyroid complex.

Calcitonin gene-related peptide (CGRP) was localized by an immunocytochemical technique in the thyroid-parathyroid complexes of rat, guinea pig, rabbit, and in normal human thyroids and parathyroids. Human medullary carcinomas and parathyroid adenomas were also studied. In man and all animal species examined CGRP was present in the parafollicular cell, however, in guinea pigs only in small amounts. Except in rabbits, presence of CGRP was demonstrated in nerves of the thyroid and parathyroid capsule as well as in the nerve fibers of the capsular blood vessels. In the thyroid of guinea pigs CGRP was also noted in nerve fibers and in blood vessel walls between follicles. CGRP was also present in the parathyroid glands of rat and man, in nerve fibers localized between parathyroid cells. In rabbit the parafollicular cells between parathyroid cells also expressed CGRP immunoreactivity. No CGRP was noted in the parathyroids of the guinea pig. The proximity of parathyroid cells and CGRP containing tissue structures suggests a role for CGRP in the modulation of parathyroid hormone secretion. The importance of these regulatory mechanisms appear to be different in individual species.