22. Development of the endocrine glands. Malformations

Learning objectives

• Describe the development of the pineal gland
• Describe the development of the anterior lobe of the pituitary gland
• Describe the development of the thyroid gland
• Describe the development of the parathyroid glands
• Describe the development of the adrenal cortex
• Describe the development of the adrenal medulla
• What is craniopharyngioma, and where does it arise from?
• What is a thyroglossal cyst?
• Where can aberrant thyroid tissue be found?
• What is phaeochromocytoma and paraganglioma, and where do they arise from?

Development of endocrine glands

Pineal gland

The pineal gland develops from the roof plate of the diencephalon, meaning that it originates from neuroectoderm. The roof plate initially forms a hollow diverticulum, but the lumen of the diverticulum closes as cells of the walls proliferate.

The cells of the gland initially develop similarly as retinal photoreceptor cells. However, the cells of the pineal gland lose their photoreceptor functionality during foetal life, remaining only as producers of melatonin.

Anterior lobe of pituitary gland

The anterior lobe of the pituitary gland, also called the adenohypophysis, develops from the adenohypophyseal placode. This placode forms Rathke’s pouch, which migrates from the roof of the stomodeum and settles anteriorly to the neurohypophysis, which is an outgrowth of the diencephalon.

After settling the adenohypophysis gives an outgrowth superiorly, which forms the pars tuberalis around the infundibular stalk. The adenohypophysis initially has a lumen, but this lumen closes as endocrine cells proliferate. Some follicular structures remain in the pars intermedia of the adenohypophysis.

Thyroid gland

The thyroid gland develops from endoderm of the foregut. In the midline between the tuberculum impar and the copula cells start to proliferate and migrate inferiorly. As they migrate, they form a diverticulum with two lobes, and they form the foramen coecum of the tongue and the thyroglossal duct, which connects the foramen coecum to the thyroid gland.

The gland descends in front of the hyoid bone and laryngeal cartilages, eventually settling in its final position (in front of the trachea) in week 7. The thyroglossal duct later closes.

The parafollicular cells, or C cells, of the thyroid arise from the ultimobranchial body, which forms from the ventral wing of the fourth pharyngeal pouches. This body joins the thyroid gland as it descends.

Parathyroid glands

The parathyroid glands originate from the third and fourth pharyngeal pouches. The inferior parathyroid glands originate from the dorsal wing of the third pharyngeal pouch, while the superior parathyroid glands originate from the dorsal wing of the fourth pharyngeal pouch.

As the thymus descends, the inferior parathyroid glands are pulled with it, which is why they end up more inferiorly than the superior parathyroid glands. All four glands migrate inferiorly and settle on the posterior surface of the thyroid.

Adrenal cortex

The adrenal cortex originates from mesoderm. Mesothelial cells between the root of the mesentery and the developing gonad proliferate and penetrate the underlying mesenchyme. These cells form the primitive adrenal cortex, which will regress quickly after birth. The primitive adrenal cortex produces the hormone DHEA during foetal life.

However, shortly after the formation of the primitive adrenal cortex, a second wave of mesothelial cells proliferates and surrounds it. These cells form the definitive adrenal cortex and will differentiate into the three definitive layers of the cortex.

Adrenal medulla

The adrenal medulla originates from neural crest cells, which originate from ectoderm. These cells invade the primitive adrenal cortex as it develops.

Malformations

Craniopharyngioma

Craniopharyngioma is a brain tumour which arises from remnants of the Rathke’s pouch. It does not invade nearby tissues but can compress the pituitary, optic chiasm, and hypothalamus, causing various symptoms.

Thyroglossal cyst and fistula

A thyroglossal cyst is a remnant of the thyroglossal duct which can form if the duct does not obliterate. This cyst is usually detected in childhood and forms a painless, firm mass in the midline of the neck. It elevates when swallowing or protruding the tongue.

Sometimes, the cyst can have a connection with the outside of the neck, forming a thyroglossal fistula.

Aberrant thyroid tissue

Aberrant thyroid tissue can be present anywhere along the path of descent of the thyroid.

Phaeochromocytoma and paraganglioma

Phaeochromocytoma is a tumour of the chromaffin cells of the adrenal medulla. This tumour can suddenly release large amounts of epinephrine and norepinephrine, causing episodes of very high blood pressure.

Paraganglioma is the same tumour with the same properties, but it arises in other parts of the body, most commonly in the abdomen. It also arises from cells derived from the neural crest, which is why phaeochromocytomas and paragangliomas cause the same symptoms and have the same histology.

Summary

• Describe the development of the pineal gland
  • Neuroectoderm -> roof plate of diencephalon -> pineal gland
  • First it forms a hollow diverticulum, but the lumen later closes
  • The cells are similar to retinal photoreceptor cells but they lose their photoreceptor functionality during foetal life
• Describe the development of the anterior lobe of the pituitary gland
  • Ectoderm -> Adenohypophyseal placode -> Rathke’s pouch -> adenohypophysis
  • Rathke’s pouch migrates from the roof of the stomodeum and settles anteriorly to the neurohypophysis
• Describe the development of the thyroid gland
  • Thyroid develops from endoderm of foregut, in the midline between the tuberculum impar and copula
  • The thyroid migrates caudally and forms the thyroglossal duct, before it settles anteriorly to the trachea
  • The parafollicular cells of the thyroid originate from the ultimobranchial body, which arises from the ventral wing of the fourth pharyngeal pouches
• Describe the development of the parathyroid glands
  • Inferior PTH glands from dorsal wing of third pharyngeal pouch
  • Superior PTH glands from the dorsal wing of the fourth pharyngeal pouch
  • Inferior glands are pulled inferiorly as the thymus descends, settling inferiorly to the superior glands
  • All four glands settle on the posterior surface of the thyroid
• Describe the development of the adrenal cortex
  • Mesoderm -> mesothelial cells close to developing gonad penetrate underlying mesenchyme -> primitive adrenal cortex
    • The primitive adrenal cortex produces DHEA in foetal life but regresses after birth
  • More mesothelial cells penetrate underlying mesenchyme and surrounds the primitive adrenal cortex, forming the definitive adrenal cortex
• Describe the development of the adrenal medulla
  • Neuroectoderm -> neural crest cells -> adrenal medulla
  • Neural crest cells invade the primitive adrenal cortex as it develops
• What is craniopharyngioma, and where does it arise from?
  • It’s a brain tumour
  • It arises from remnants of Rathke’s pouch
• What is a thyroglossal cyst?
  • It’s a cystic remnant of the thyroglossal duct
  • It forms a painless, firm mass in the midline of the neck which elevates when swallowing
• Where can aberrant thyroid tissue be found?
  • Anywhere along the path of descent of the thyroid
• What is phaeochromocytoma and paraganglioma, and where do they arise from?
  • Phaeochromocytoma is a tumour of the chromaffin cells of the adrenal medulla
  • Paraganglioma is a tumour of other neural crest-derived cells
    • It arises elsewhere in the body, not in the adrenal medulla
  • Both tumours produce epinephrine and norepinephrine, causing episodes of very high blood pressure