Pituitary and adrenal development
Development of the pituitary and adrenal glands
Both glands are made of two different tissues that grow together: the pituitary from mouth ectoderm and brain, the adrenal from coelomic mesoderm and neural crest. The dual origin explains their separate blood supply and control, the tumours that arise from leftover embryonic tissue, and the large fetal adrenal that feeds the placenta's oestrogen production.
Pituitary: two origins
| Part | Embryonic origin | Adult parts | Hormones |
|---|---|---|---|
| Adenohypophysis | Rathke's pouch, an upgrowth of oral ectoderm from the roof of the stomodeum (week 3–4) | Anterior wall: pars distalis; posterior wall: pars intermedia; collar around the stalk: pars tuberalis | Makes GH, prolactin, ACTH, TSH, FSH, LH |
| Neurohypophysis | Infundibulum, a downgrowth of the floor of the diencephalon (neuroectoderm) | Pars nervosa, infundibular stalk, median eminence | Stores and releases ADH and oxytocin made in the supraoptic and paraventricular nuclei |
- Rathke's pouch meets the infundibulum, then loses its connection with the mouth; its stalk passes through the developing sphenoid.
- The posterior lobe makes no hormone of its own and contains glial pituicytes. Damage to the stalk or posterior lobe (head injury, surgery) gives diabetes insipidus.
- Because one lobe is brain and one is epithelium, the anterior lobe is controlled by blood (hypothalamic releasing hormones in the hypophyseal portal system) and the posterior lobe by nerve fibres.
Remnants of Rathke's pouch
- Residual lumen (Rathke's cleft): lies between pars distalis and pars intermedia; may form a Rathke cleft cyst lined by ciliated cuboidal epithelium. A cyst pressing on the stalk can raise prolactin by removing dopamine inhibition.
- Pharyngeal pituitary: rests along the path in the roof of the nasopharynx or the sphenoid; can give an ectopic adenoma with a normal sella.
- Craniopharyngioma: from squamous remnants of the pouch. Typically a child with headache, short stature (GH loss), diabetes insipidus and visual loss; imaging shows a calcified, cystic suprasellar mass; the cyst holds machinery oil fluid.
- Visual fields: the chiasm compressed from above (craniopharyngioma) gives bitemporal inferior quadrantanopia first; from below (pituitary adenoma), superior quadrants go first. Both end as bitemporal hemianopia.
GnRH neurons and the pituitary in pregnancy
- GnRH neurons arise in the olfactory (nasal) placode and migrate along olfactory nerve fibres into the hypothalamus. Failure gives Kallmann syndrome: anosmia, low FSH and LH and primary amenorrhoea; the pituitary still responds to pulsatile GnRH.
- In pregnancy, lactotroph hyperplasia enlarges the anterior pituitary. It depends on low-pressure portal blood, so severe postpartum haemorrhage can infarct it (Sheehan syndrome: failed lactation first, then amenorrhoea, hypothyroidism, adrenal insufficiency). The posterior lobe has a direct arterial supply and is usually spared.
Adrenal gland: two origins
| Part | Origin | Notes |
|---|---|---|
| Cortex | Coelomic (mesothelial) mesoderm of the posterior abdominal wall, next to the gonadal ridge, weeks 5–6 | First wave forms the large fetal cortex; a second wave forms the thin definitive (adult) cortex around it |
| Medulla | Neural crest cells that invade the cortex | Chromaffin cells, modified postganglionic sympathetic neurons, supplied by preganglionic splanchnic fibres |
- Shared mesoderm with the gonad explains adrenal rests (cortex only) in the broad ligament, ovary or testis; they enlarge under high ACTH in CAH.
- Neural crest origin explains neuroblastoma and extra-adrenal paraganglioma. The commonest extra-adrenal site is the organ of Zuckerkandl beside the aorta near the IMA origin; these tumours make mainly noradrenaline, because the enzyme PNMT needs the high cortisol of the adrenal portal blood.
The fetal adrenal and the placenta
- At term the adrenals are about one-third the size of the kidneys, mainly the fetal zone. It regresses in the first weeks after birth; large newborn adrenals on ultrasound are normal.
- The fetal zone makes DHEA-S, the main steroid of the fetal adrenal. The fetal liver 16-hydroxylates it and the placenta, which lacks 17-alpha-hydroxylase, converts it to oestriol: the fetoplacental unit.
- The fetal zone depends on fetal ACTH. In anencephaly there is no hypothalamic drive, so the adrenals are tiny and maternal oestriol is low; pregnancy may run past term.
- Fetal cortisol late in pregnancy matures the lungs (surfactant) and the gut.
- CAH (21-hydroxylase deficiency): low cortisol raises fetal ACTH, the cortex enlarges and diverts precursors to androgens, virilising a 46,XX fetus.
Zones after birth
| Zone | Main product | Timing |
|---|---|---|
| Glomerulosa | Aldosterone | Present at birth |
| Fasciculata | Cortisol | Present at birth |
| Reticularis | DHEA and DHEA-S | Forms in early childhood; rising output at about 6–8 years is adrenarche |
- Premature adrenarche: pubic hair and body odour with raised DHEA-S and normal 17-hydroxyprogesterone but no breast development, because the ovary is not active.
Remember Pituitary: anterior from the mouth, posterior from the brain. Adrenal: cortex from mesoderm, medulla from neural crest.
Exam trap The fetal adrenal is driven by fetal ACTH, not maternal ACTH; anencephaly gives small adrenals and low oestriol.
Exam trap Rathke's pouch is oral ectoderm from the stomodeum, not an outgrowth of the diencephalon; the diencephalon gives the posterior lobe.
Test yourself on this topic
5 of the 12 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A 9-year-old girl has headaches, falling school grades, short stature and bitemporal visual field loss. MRI shows a partly calcified cystic suprasellar mass; at surgery the cyst contains thick fluid like machinery oil. What is the most likely diagnosis?
Answer: Craniopharyngioma
Craniopharyngioma is the commonest suprasellar tumour of childhood. It arises from squamous epithelial remnants of Rathke pouch along the path of the pituitary stalk. It is typically cystic, calcified and filled with cholesterol-rich 'machinery oil' fluid, and it compresses the chiasm, pituitary and hypothalamus, causing visual loss, growth failure and diabetes insipidus. Pituitary adenomas are rare in children and seldom calcify.
Craniopharyngioma
- From Rathke pouch remnants
- Child: growth failure, bitemporal loss
- Calcified cyst on imaging
- Machinery oil fluid
Remember Calcified suprasellar cyst in a child.
Exam trap Calcification in a childhood suprasellar mass points away from adenoma.
Why the other options are wrong
- Pituitary macroadenoma Rare in children and rarely calcified.
- Optic pathway glioma Solid, non-calcified; often with neurofibromatosis.
- Intracranial germinoma Usually solid; often causes diabetes insipidus early.
- Rathke cleft cyst Simple non-calcified cyst, usually without symptoms.
A 34-year-old woman with mild hyperprolactinaemia has MRI showing a small non-enhancing cyst lying between the anterior and posterior lobes of the pituitary. Excision shows a cyst lined by ciliated cuboidal epithelium. What does this cyst represent?
Answer: Residual lumen of Rathke pouch
Rathke pouch grows up from the roof of the stomodeum. Its anterior wall forms the pars distalis, its posterior wall forms the pars intermedia, and the space between them, Rathke cleft, normally shrinks to a tiny residual lumen. If this lumen expands, it forms a Rathke cleft cyst lined by cuboidal or ciliated epithelium between the anterior and posterior lobes. Large cysts can compress the stalk and raise prolactin by blocking dopamine.
Rathke cleft cyst
- Anterior wall: pars distalis
- Posterior wall: pars intermedia
- Cleft between: residual lumen
- Cyst lies between the lobes
Remember Cyst between the lobes: Rathke cleft.
Exam trap A stalk-compressing cyst can raise prolactin without being a prolactinoma.
Why the other options are wrong
- Persisting infundibular recess The infundibular recess is part of the third ventricle.
- Remnant of the notochord Notochord remnants give chordoma of the clivus.
- Remnant of the thyroglossal duct Thyroglossal remnants lie in the neck.
- Arachnoid cyst of the suprasellar cistern Lined by arachnoid, not ciliated epithelium.
At autopsy, an anencephalic fetus delivered at 36 weeks has very small adrenal glands, with the fetal zone almost absent. Which of the following best explains the adrenal hypoplasia?
Answer: Lack of fetal ACTH stimulation
Growth and function of the fetal adrenal zone depend on ACTH from the fetal pituitary, driven by the hypothalamus. In anencephaly the hypothalamus is absent and fetal ACTH secretion is very low, so the fetal zone fails to grow, and DHEA-S output and maternal oestriol fall. The adrenal medulla, from neural crest, is not the main tissue affected. hCG helps early fetal zone growth but is present in normal amounts in anencephaly.
Adrenal in anencephaly
- Fetal zone needs fetal ACTH
- No hypothalamus: low ACTH
- Small adrenals
- Low maternal oestriol
Remember No brain drive, no big fetal adrenal.
Exam trap The fetal adrenal is mainly under fetal, not maternal, ACTH control.
Why the other options are wrong
- Absent placental hCG hCG is produced normally by the placenta.
- Excess maternal cortisol Placental 11β-HSD2 inactivates most maternal cortisol.
- Failure of neural crest migration Neural crest forms the medulla, not the large fetal zone.
- Absent ureteric bud induction Relates to the kidney, not the adrenal.
A 7-year-old girl has fine pubic hair and adult body odour but no breast development. Bone age is mildly advanced, DHEA-S is raised for age and 17-hydroxyprogesterone is normal. Which adrenal zone is the source of the rising hormone?
Answer: Zona reticularis
The zona reticularis matures in mid-childhood and produces adrenal androgens such as DHEA and DHEA-S; this is adrenarche, usually at 6–8 years. Early or exaggerated adrenarche causes pubic hair and body odour without breast development, which needs ovarian oestrogen. The fetal zone, which also makes DHEA-S, has regressed by early infancy. A normal 17-hydroxyprogesterone makes non-classic CAH unlikely.
Adrenarche
- Zona reticularis matures
- Makes DHEA-S
- Pubic hair, body odour
- No breasts: ovary not active
Remember Reticularis gives the hair, the ovary gives the breasts.
Exam trap Premature adrenarche is not true puberty; there is no breast or uterine growth.
Why the other options are wrong
- Zona glomerulosa Makes aldosterone.
- Zona fasciculata Makes cortisol mainly.
- Adrenal medulla Makes catecholamines.
- Fetal zone Regresses after birth.
A 28-year-old woman has paroxysmal hypertension and raised urinary normetanephrine, but both adrenals are normal on CT. A 3 cm mass lies beside the aorta near the origin of the inferior mesenteric artery. What is the tissue of origin?
Answer: Organ of Zuckerkandl
Neural crest cells that form the adrenal medulla also form clusters of chromaffin tissue along the aorta. The largest, the organ of Zuckerkandl, lies near the origin of the inferior mesenteric artery and is prominent in the fetus before regressing in childhood. It is the commonest site of extra-adrenal phaeochromocytoma (paraganglioma). Extra-adrenal tumours usually secrete noradrenaline because they lack the cortisol-induced enzyme PNMT.
Organ of Zuckerkandl
- Neural crest chromaffin tissue
- Near the IMA origin
- Commonest extra-adrenal phaeo site
- Secretes noradrenaline
Remember Phaeo outside the adrenal: look at the IMA origin.
Exam trap Extra-adrenal tumours make mostly noradrenaline, since PNMT needs high cortisol.
Why the other options are wrong
- Aortic body chemoreceptors Chemoreceptor paragangliomas are usually non-secretory and lie in the head and neck or arch.
- Para-aortic lymph node Not a source of catecholamines.
- Accessory adrenal cortex Cortical rests secrete steroids, not catecholamines.
- Coeliac ganglion neurons Postganglionic neurons do not form secreting tumours here.
Where this sits in the CPSP syllabus
- Obstetrics & Gynaecology, Paper 2: Embryology, Development of the pituitary and adrenal glands
Read next
Drug dose pages
Doses, cautions and practical tips for drugs in this chapter.