The anatomical evolution of the thyroid cartilage from childhood to adulthood: A computed tomography evaluation.

OBJECTIVE: To enhance knowledge and understanding of the laryngeal framework maturation in different age groups and genders. STUDY DESIGN: Cohort imaging study. SETTING: Tertiary academic referral center. METHODS: Computed tomography neck scans of 283 patients aged 8 to 20 years were studied. The interlaminae angle (ILA) of the thyroid cartilage at the level of the vocal folds, the anterior projection (angulation) of the thyroid cartilage (TC), and the degree of calcifications were evaluated and compared in sequential age groups of both genders. RESULTS: Neck scans of 171 males and 112 females were reviewed. The average ILA was 76.45° ± 14.2 and 94.25° ± 10.2 for males and females, respectively (P < 10-25). In the female group, the mean angle was relatively constant (91-970) in all age groups, whereas in the male groups the angle decreased with age (920-670) (r = -0.9, P < 0.005) The most significant decrease was measured in the 14- to 15-year age group. The thyroid prominence was significantly more anteriorly angulated in males. The angle in the female age groups was constant (170.1°), and the angle in males decreased with age (161.47°) (P = 0.000008). Calcifications were more prominent at the posterior portion of the cartilage in both genders and increased with age. CONCLUSION: Structural diversities of the TC begin in adolescent males because the thyroid cartilage grows anteriorly with a narrower ILA and with a greater anterior angulation. Our study shows that these changes, along with the degree of laryngeal cartilages calcification in both genders, occur as a continuum throughout puberty. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:E354-E358, 2017.

Different Patterns of Cartilage Mineralization Analyzed by Comparison of Human, Porcine, and Bovine Laryngeal Cartilages.

Laryngeal cartilages undergo a slow ossification process during aging, making them an excellent model for studying cartilage mineralization and ossification processes. Pig laryngeal cartilages are similar to their human counterparts in shape and size, also undergo mineralization, facilitating the study of cartilage mineralization. We investigated the processes of cartilage mineralization and ossification and compared these with the known processes in growth plates. Thyroid cartilages from glutaraldehyde-perfused male minipigs and from domestic pigs were used for X-ray, light microscopic, and transmission electron microscopic analyses. We applied different fixation and postfixation solutions to preserve cell shape, proteoglycans, and membranes. In contrast to the ossifying human thyroid cartilage, predominantly cartilage mineralization was observed in minipig and domestic pig thyroid cartilages. The same subset of chondrocytes responsible for growth plate mineralization is also present in thyroid cartilage mineralization. Besides mineralization mediated by matrix vesicles, a second pattern of cartilage mineralization was observed in thyroid cartilage only. Here, the formation and growth of crystals were closely related to collagen fibrils, which served as guide rails for the expansion of mineralization. It is hypothesized that the second pattern of cartilage mineralization may be similar to a maturation of mineralized cartilage after initial matrix vesicles-mediated cartilage mineralization.

Special pattern of endochondral ossification in human laryngeal cartilages: X-ray and light-microscopic studies on thyroid cartilage.

Endochondral ossification is a process that also occurs in the skeleton of the larynx. Differences in the ossification mechanism in comparison to growth plates are not understood until now. To get deeper insights into this process, human thyroid cartilage was investigated by the use of X-rays and a series of light-microscopic stainings. A statistical analysis of mineralization was done by scanning areas of mineralized cartilage and of ossification. We detected a special mode of endochondral ossification which differs from the processes in growth plates. Thyroid cartilage ossifies very slowly and in a gender-specific manner. Compared with age-matched women, bone formation in thyroid cartilage of men is significantly higher in the age group 41-60 years. Endochondral ossification is prepared by internal changes of extracellular matrix leading to areas of asbestoid fibers with ingrowing cartilage canals. In contrast to growth plates, bone is deposited on large areas of mineralized cartilage, which appear at the rims of cartilage canals. Furthermore, primary parallel fibered bone was observed which was deposited on woven bone. The predominant bone type is cancellous bone with trabeculae, whereas compact bone with Haversian systems was seldom found. Trabeculae contain a great number of reversal and arresting lines meaning that the former were often reconstructed and that bone formation was arrested and resumed again with advancing age. It is hypothesized that throughout life trabeculae of ossified thyroid cartilage undergo adaptation to different loads due to the use of voice.

The use of computed tomography in determining developmental changes, anomalies, and trauma of the thyroid cartilage.

Recognition of injury to the hyoid bone and thyroid and cricoid cartilages is intrinsic to post-mortem examination. Due to its increasing brittleness with age the thyroid cartilage is particularly susceptible to injury following neck trauma, although there is inconsistency in the patterns of injury reported. In this study computed tomography scans of the head and neck of 431 deceased persons (235 males and 196 females) between the ages of 1 day and 100 years (mean age 35.93 ± 24.15), and including 25 victims of hangings, were examined to reveal the pattern of age-related change and the types of injury that occurred. Thyroid cartilage anomalies likely to cause confusion and be misinterpreted as trauma-related are documented. Angulation of the thyroid cartilage horns was found to change with age, and it is suggested this may be a significant factor in traumatic neck injury. Unlike in previous reports, the average age of hanging victims with fractures to the thyroid cartilage was 34 years. The base of the superior horn was the most common fracture site and in 50 % of hanging cases was associated with a ligature positioned on the thyrohyoid membrane or thyroid lamina. Although an age-related relationship exists it was not possible to establish narrow age-prediction ranges from calcification of the thyroid cartilage.

Age-dependent structural and radiological changes in the larynx.

AIM: To define radiological physiological changes in the larynx by establishing an age-related scale. MATERIALS AND METHODS: The present retrospective study used radiological records of patients that had undergone lateral cervical imaging. Three hundred patients were included. Thyroid cartilage was divided into anatomical regions. The hyoid bone was evaluated as the body and greater horns. Cases were compared by grouping by age and gender. RESULTS: Thyroid tissue and cricoid cartilage only became visible after the second decade. Ossification in the thyroid cartilage began in the posterior inferior horn and progressed to the superior horn and central lamina. It also began in the posterior part of the cricoid cartilage and moved forward with age. In the first decade, the body and greater horn parts of the hyoid bone could be seen more distinctly, and after the third decade the hyoid bone appeared as a single bone. The hyoid bone was the only structure ossified in the laryngeal region below the age of 20 and formed an image on direct imaging. CONCLUSIONS: Age-related changes to the laryngeal tissues are evident on radiographs. Clinicians should bear this in mind when evaluating neck radiographs.

Laryngeal squamous cell carcinoma presenting as a prelaryngeal, air-filled structure (pseudolaryngocoele).

OBJECTIVE: We report a unique case of a squamous cell carcinoma of the larynx presenting as a large pseudolaryngocoele, arising through a thyroid cartilage defect. METHOD: Case report and review of the literature. CASE REPORT: A 47-year-old man presented with a two-month history of hoarseness and a large, midline neck swelling. Endoscopic examination revealed a transglottic carcinoma involving the anterior commissure. Fine needle aspiration of the neck mass showed it to be an air-filled structure which transiently collapsed but refilled within minutes. Subsequent computed tomography scanning and histopathological examination revealed that the air-filled mass was created by a defect in the thyroid cartilage, with formation of a pseudolaryngocoele. CONCLUSIONS: The anatomy of the anterior commissure region and its effect on the spread of laryngeal carcinoma is reviewed in order to explain the pathophysiology of this unusual presentation. We highlight the need for a high index of suspicion of malignancy if a laryngocoele or pseudolaryngocoele is detected clinically.

Gender-specific distribution of glycosaminoglycans during cartilage mineralization of human thyroid cartilage.

The role of glycosaminoglycans (GAG) in the process of cartilage mineralization, especially in the hypertrophic zone of growth plates, is not yet fully understood. Human thyroid cartilage can serve as a model to observe matrix changes associated with cartilage mineralization because the processes follow a distinct route, progress very slowly and show sexual differences. Histochemical staining for low sulphated GAG (chondroitin-4- and -6-sulphates) was decreased in the interterritorial matrix of thyroid cartilage starting at the beginning of the fifth decade, but not in the pericellular or territorial matrix of chondrocytes. Because cartilage mineralization progressed in the interterritorial matrix it seems likely that a decreasing content of chondroitin-4- and -6-sulphates is involved in the mineralization process. This hypothesis is supported by the observation that immunostaining for chondroitin-4- and -6-sulphates was weaker in mineralized cartilage areas than in unmineralized areas, whereas there was no difference in staining for keratan sulphate. In all life decades, female thyroid cartilages contained more chondrocytes with a territorial rim of chondroitin-4- and -6-sulphates probably preventing cartilage mineralization compared with age-matched male specimens. Taken together, the characteristic distribution pattern of chondroitin-4- and -6-sulphates being more concentrated in female than in male thyroid cartilages provided evidence that these macromolecules decrease in cartilage mineralization.

Biological repair of thyroid cartilage defects by osteogenic protein-1 (bone morphogenetic protein-7) in dog.

The efficacy of human recombinant osteogenic protein-1 (OP-1; bone morphogenetic protein-7) in regeneration of dog larynx was examined by treating thyroid cartilage defects (1.5 cm2) in dogs with thyroid allografts covered with host perichondrium or fascia. Prior to implantation allografts were frozen, thawed and demineralized. The treatment groups were as follows: I--Allograft control implant (n = 3); II--Implants coated with 500 micrograms OP-1 (n = 4); III--Implants coated with 100 micrograms OP-1 (n = 3); IV--Implants coated with 500 micrograms OP-1 and covered with neck fascia (n = 3); and V--Implants extracted with 1 M NaCl and guanidine hydrochloride, and coated with 500 micrograms OP-1 (n = 4). Dogs were sacrificed four months following surgery. Each larynx was removed, carefully dissected and a three-dimensional reconstruction of the defect area was performed on serial sections. The results revealed that the implants of control dogs remained intact with no apparent reduction in size and new tissue formation. OP-1 enriched thyroid allografts, dose dependently induced bone, cartilage and ligament-like structures comprising up to 80% of the total regenerated defect area. Boundaries of the defects healed by formation of new bone when bone resided within the old thyroid cartilage layers. Old cartilage not containing bone within its layers healed by complete integration with newly formed cartilage. Both new bone and cartilage were embedded into layers of new ligament-like tissue which expressed specific morphologic and molecular markers. The three newly formed tissues were tightly connected into a "bone-cartilage-ligament continuum" of tissues, suggesting that OP-1 served as a multiple tissue morphogen in this specific microenvironment.

Cartilage canals in human thyroid cartilage characterized by immunolocalization of collagen types I, II, pro-III, IV and X.

In this study the collagenous composition of cartilage canals in human thyroid cartilage, which are perichondral invaginations of blood vessels and connective tissue, and the surrounding cartilage matrix were investigated by immunolabelling with specific antibodies against type I, II, pro-III, IV and X collagen. During childhood and early adolescence no cartilage canals were detected in thyroid cartilage, and immunolabelling for type IV collagen was restricted to basal lamina components of blood vessels in the perichondrium. First immunolabelling for type IV collagen, belonging to blood vessels in cartilage canals, in both sexes was detected about the end of the second decade; it was localized in the dorsal part of the thyroid cartilage plate. At this time thyroid cartilage has already reached its final form and size. As revealed by von Kossa staining, vascularization preceded mineralization and ossification. In contrast to the male thyroid cartilage plate, no immunostaining for type IV collagen and no ossification was detected in the ventral half of female thyroid cartilage even in advanced age. The extracellular matrix of cells in cartilage canals showed positive immunostaining for collagen types I and pro-III as well as for collagen type II, indicating that the cells in the canal possess fibroblastic and chondrogenic properties. The extracellular matrix of hypertrophic chondrocytes adjacent to cartilage canals showed strong immunoreactivity for type X collagen. First mineralization was detected close to cartilage canals, suggesting that mineralization in human thyroid cartilage starts in the extracellular matrix adjacent to cartilage canals.

Estudo quantitativo do desenvolvimento da cartilagem tireóide fetal humana: III - 9ª à 38ª semanas pós-concepçäo / Quantitative study of the human fetal thyroid cartilage development: III - 9th to 38th weeks post-conception

Para o estudo quantitativo do crescimento da cartilagem tireóide durante o período fetal humano, aplicamos o método alométrico Log Y = k Log X + Logb. O peso da cartilagem tireóide (em gramas) foi correlacionado com o peso do feto (em gramas). Nossos resultados indicaram alometria negativa para o seu crescimento

Tracheal growth after resection and anastomosis in puppies.

Tracheal morphology, morphometric changes, and growth and histologic changes were studied in puppies submitted to tracheal resection and anastomosis. Fifteen mongrel puppies about 12 weeks old and weighing on an average 5.5 kg were operated under general anesthesia using fluothane. A median cervicotomy incision was made in ten puppies (experimental group, EG) and the proximal 14 tracheal rings were resected (average length 5.08 cm or about 35% to 38% of total tracheal length). One layer anastomosis was done using vicryl 4.0 maintaining the average tension of 1,450 g. Five puppies (control group, CG) were submitted to tracheal transection and anastomosis and the following parameters were studied. Tracheal morphology the trachea of the EG was a rounded triangle whereas in the CG it was oval in shape, there was increase in the intercartilageneous spaces in the EG, no granulation tissue was present, two mucous webs were seen in the EG and one in the CG. Morphometric changes average tracheal length EG 13 cm, CG 17.7 cm, intercartilagenous space EG 3.08 mm, CG 1.3 mm, intercricothyroid space EG 1.2 cm, CG 0.53 cm, sagittal and transverse tracheal thickness at the anastomosis EG 2.6 and 3.3 mm, CG 2 and 1.5 mm, sagittal and transverse diameter reduced on an average 2 mm in EG. Histology Moderate fibrosis was found at the level of anastomosis with no modification of chondrocytes at the cartilagenous rings in the EG. Even with high anastomotic tension, the dogs had normal tracheal growth without stenosis; the sagittal and transverse growth at the anastomosis in the EG was 90% and 85%, respectively, when compared with the CG.

Abnormal growth of the thyroid cartilage in the DiGeorge syndrome.

Larynges from 17 patients with DiGeorge syndrome (DGS) and from 14 patients with tetralogy of Fallot (TOF) (11 non-DGS and 3 possible but unproven DGS) were dissected, measured, and compared to a control population of comparable body length. The patients with DGS and the 3 patients with TOF suspected of having DGS showed the following: small thyroid cartilages with increased anterior angle, abnormally short superior cornua, low ratio of mean superior cornual length to distance between superior cornual tips, and delayed time of maximal rate of increase in superior cornual length relative to increase in body length. The hypoplasia, delayed maximal growth rate and persistent fetal shape of the thyroid cartilage (predominantly a derivative of the fourth branchial arch) in DGS, indicates that the causative process in the syndrome affects not only the third and fourth branchial pouches, but also, by a contiguous field defect, other derivatives than great vessels of the fourth-sixth branchial arches.

Androgen stimulation and laryngeal development.

Androgen-induced changes in laryngeal growth patterns were studied using a sheep animal model. Forty-eight lambs were divided into eight treatment groups. Lambs in seven of the groups were castrated at birth, while lambs in the eighth group served as an intact (noncastrated) control. Six groups were then treated with varying doses of testosterone and dihydrotestosterone, while the seventh served as a castrated, nontreated control. All animals were killed and gross dissections of the larynges were performed. Thirty-four linear and angular measurements were obtained from each larynx. The mean superior thyroid horn separation showed the most dramatic androgen-induced effect (p = 0.023). Laryngeal anterior-posterior diameter, superior thyroid horn height, posterior thyroid cartilage width, thyroid cartilage angle, and vocal process to arytenoid base distances all demonstrated positive dose-response relationships. Hypoandrogenic levels appeared to have an inhibitory effect upon laryngeal growth when compared to castrated controls.