A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior), is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the pituitary gland (hypophysis). The anterior pituitary regulates several physiological processes including stress, growth, reproduction and lactation. Proper functioning of the anterior pituitary and of the organs it regulates can often be ascertained via blood tests that measure hormone levels.
The anterior pituitary contains five types of endocrine cell, and they are defined by the hormones they secrete: somatotropes (GH); prolactins (PRL); gonadotropes (LH and FSH); corticotropes (ACTH) and thyrotropes (TSH)
5. Pituitary Gland
• Located within the sella tursica
• Weight 600mg
• Contiguous to vascular and neurologic structures
• Cavernous sinuses
• Cranial nerves
• Optic chiasma
• Hypothalamic neural cells synthesize specific releasing and inhibiting hormones
• Secreted directly into the portal vessels of the pituitary stalk
• Blood supply derived from the superior and inferior hypophyseal arteries
8. Pituitary Gland
• Anterior pituitary gland
• Secrete various trophic hormones
• Disease in this region may result in syndromes of hormone excess or deficiency
• Posterior pituitary gland
• More of a terminus of axons of neurons in the supraoptic and paraventricular
nuclei of the hypothalamus
• Storehouse for the hormones
• The main consequence of disease in this area is disordered water homeostasis
9. Anterior Pituitary Gland
• Anterior Pituitary “Master gland”
• Major blood source: hypothalamic-pituitary portal plexus
• Allows transmission of hypothalamic peptide pulses without significant systemic dilution
• Consequently, pituitary cells are exposed to sharp spikes of releasing factors and in turn release
their hormones as discrete pulses.
• Production of six major hormones:
• Prolactin (PRL)
• Growth hormone (GH)
• Adrenocorticotropin hormone (ACTH)
• Luteinizing hormone (LH)
• Follicle-stimulating hormone (FSH)
• Thyroid-stimulating hormone (TSH)
10. Anterior Pituitary Gland
• Anterior Pituitary “Master gland”
• Secreted in a pulsatile manner
• Elicits specific responses in peripheral target tissues
• Feedback control at the level of the hypothalamus and pituitary
to modulate pituitary function exerted by the hormonal
products of the peripheral target glands
• Tumors cause characteristic hormone excess syndromes
• Hormone deficiency
• may be inherited or acquired
13. Adult Growth Hormone Deficiency
• First hormone to be affected
• Non functioning adenoma/ irradiation
• GH FSH/LH TSH ACTH
•
• Adults
• Often asymptomatic
• Fatigue
• Decreased exercise tolerance
• Abdominal obesity
• Loss of muscle mass
• Abnormal lipid profile
• Reduced BMD
• Atherosclerosis , LV dysfunction, increased fibrinogen
14. Treatment : GH replacement 0.1 – 0.3 mg/day
Maximum upto 1.25 mg/day
Women need higher doses than men
15. Gonadotropin Deficiency
Women
• Oligomenorrhea or amenorrhea
• Loss of libido
• Vaginal dryness or dyspareunia
• Loss of secondary sex characteristics
(estrogen deficiency)
Men
• Loss of libido
• Erectile dysfunction
• Infertility
• Loss of secondary sex characteristics
(testosterone deficiency)
• Atrophy of the testes
• Gynecomastia (testosterone
deficiency)
Most common presenting feature of adult hypopituitarism
17. ACTH Deficiency
• Most commonly due to glucocorticoid withdrawal
• Results in hypocortisolism
• Malaise
• Anorexia
• Weight-loss
• Gastrointestinal disturbances
• Hyponatremia, hypoglycemia
• Pale complexion
• No features of mineralocorticoid deficiency
• Aldosterone secretion unaffected
23. • Septo-Optic dysplasia
• Hypothalamic dysfunction and hypopituitarism
• may result from dysgenesis of the septum pellucidum or corpus callosum
• Affected children have mutations in the HESX1 gene
• involved in early development of the ventral prosencephalon
• These children exhibit variable combinations of:
• cleft palate
• syndactyly
• ear deformities
• hypertelorism
• optic atrophy
• micropenis
• anosmia
• Pituitary dysfunction
• Diabetes insipidus
• GH deficiency and short stature
• Occasionally TSH deficiency
24. •Kallman Syndrome
• Defective hypothalamic gonadotropin-releasing hormone (GnRH) synthesis
• Associated with anosmia or hyposmia due to olfactory bulb agenesis or
hypoplasia
• May also be associated with: color blindness, optic atrophy, nerve
deafness, cleft palate, renal abnormalities, cryptorchidism, and neurologic
abnormalities such as mirror movements
• GnRH deficiency prevents progression through puberty
• characterized by
• low LH and FSH levels
• low concentrations of sex steroids
25. •Laurence-Moon-Biedl Syndrome
• Rare autosomal recessive disorder
•Characterized by mental retardation; obesity; and
hexadactyly, brachydactyly, or syndactyly
• Central diabetes insipidus may or may not be associated
•GnRH deficiency occurs in 75% of males and half of
affected females
• Retinal degeneration begins in early childhood
• most patients are blind by age 30
•Renal abnormalities
29. •LYMPHOCYTIC HYPOPHYSITIS
• Etiology
• Presumed to be autoimmune
• Clinical Presentation
• Women, during postpartum period with hyperprolactinemia
• Mass effect (sellar mass)
• Deficiency of one or more anterior pituitary hormones
• ACTH deficiency is the most common
• Diagnosis
• MRI - may be indistinguishable from pituitary adenoma
• Elevated ESR +
• Treatment
• Corticosteroids
• Hormone replacement
33. •PITUITARY APOPLEXY
• Hemorrhagic infarction of a pituitary adenoma/tumor
• Considered a neurosurgical emergency
• Presentation:
• Variable onset of severe headache
• Nausea and vomiting
• Meningism
• Vertigo
• +/ - Visual defects
• +/ - Altered consciousness
• Symptoms may occur immediately or may develop over 1-2 days
Meningism is the triad of
nuchal rigidity (neck stiffness)
photophobia (intolerance of bright light)
headache
34. • Pituitary Apoplexy
• Diabetes
• Bleed into a pre existing adenoma
• Patients on warfarin
• Post partum ( sheehans)
• Hypertension
• Sickle cell anemia
• Shock
36. Apoplexy
•Usually resolve completely if treated correctly and early
•Diagnose with CT/MRI
•Differentiate from leaking aneurysm
•Treatment:
•Medical therapy – if symptoms are mild
• Corticosteroids – high dose glucocorticoids
• Surgical – Trans sphenoid decompression
• Visual defects and altered consciousness
38. Hypopituitarism
Diagnosis
• Biochemical diagnosis of pituitary insufficiency
• Demonstrating low levels of trophic hormones in the setting of low target
hormone levels
• Provocative tests may be required to assess pituitary reserve
40. Hormone Replacement
Trophic Hormone Deficit Hormone Replacement
ACTH Hydrocortisone (10-20 mg A.M.; 10 mg P.M.)
Cortisone acetate (25 mg A.M.; 12.5 mg P.M.)
Prednisone (5 mg A.M.; 2.5 mg P.M.)
TSH L-Thyroxine (0.075-0.15 mg daily)
FSH/LH Males
Testosterone enanthate (200 mg IM every 2 wks)
Testosterone skin patch (5 mg/d)
Females
Conjugated estrogen (0.65-1.25 mg qd for 25days)
Progesterone (5-10 mg qd) on days 16-25
For fertility: Menopausal gonadotropins, human chorionic gonadotropins
GH Adults: Somatotropin (0.3-1.0 mg SC qd)
Children: Somatotropin [0.02-0.05 (mg/kg per day)]
Vasopressin Intranasal desmopressin (5-20 ug twice daily)
Oral 300-600 ug qd
41. Take home points:
• Remember that the cause may be functional
• Treatment should be aimed at the underlying cause
• Not all KKK are hypopituitarism
• Hypopituitarism may present
• Acutely with cortisol deficiency
• After withdrawal of prolonged glucocorticoid therapy that has caused suppression of the HPA
axis
• Post surgical procedure
• TUBERCULOSIS
• DIABETES
• SYSTEMIC HYPERTENSION
• Post trauma
• Hemorrhage
44. Pituitary Tumors
•Microadenoma < 1 cm
•Macroadenoma > 1 cm
•Is the tumor causing local mass effect?
•Is hypopituitarism present?
•Is there evidence of hormone excess?
45. • Clinical presentation:
• Mass effect
• Superior extension
• May compromise optic pathways – leading to impaired visual acuity and visual
field defects
• May produce hypothalamic syndrome – disturbed thirst, satiety, sleep, and
temperature regulation
• Lateral extension
• May compress cranial nerves III, IV, V, and VI – leaning to diplopia
• Inferior extension
• May lead to cerebrospinal fluid rhinorrhea
46.
47. Pituitary Tumors
• Diagnosis
• Check levels of all hormones produced
• Check levels of target organ products
• Treatment
• Surgical excision, radiation, or medical therapy
• Generally, first-line treatment surgical excision
• Drug therapy available for some functional tumors
• Simple observation
• Option if the tumor is small, does not have local mass effect, and is nonfunctional
• Not associated with clinical features that affect quality of life
48.
49.
50.
51. Craniopharyngioma
• Derived from Rathke's pouch.
• Arise near the pituitary stalk
• extension into the suprasellar cistern common
• These tumors are often large, cystic, and locally invasive
• Many are partially calcified
• characteristic appearance on skull x-ray and CT images
• Majority of patients present before 20yr
• usually with signs of increased intracranial pressure, including
headache, vomiting, papilledema, and hydrocephalus
52. Craniopharyngioma
• Associated symptoms include:
• visual field abnormalities, personality changes and cognitive deterioration,
cranial nerve damage, sleep difficulties, and weight gain.
• Children
• growth failure associated with either hypothyroidism or growth hormone
deficiency is the most common presentation
• Adults
• sexual dysfunction is the most common problem
• erectile dysfunction
• amenorrhea
53. Craniopharyngioma
• Anterior pituitary dysfunction and diabetes insipidus are common
• Treatment
• Transcranial or transsphenoidal surgical resection
• followed by postoperative radiation of residual tumor
• This approach can result in long-term survival and ultimate cure
• most patients require lifelong pituitary hormone replacement.
• If the pituitary stalk is uninvolved and can be preserved at the time of
surgery
• Incidence of subsequent anterior pituitary dysfunction is significantly
diminished.
54. Prolactinoma
• Most common functional pituitary tumor
• Usually a microadenoma
• Can be a space occupying macroadenoma – often with visual field defects
• Although many women with hyperprolactinemia will have galactorrhea
and/ or amenorrhea
• The absence these the two signs do not excluded the diagnosis
• GnRH release is decreased in direct response to elevated prolactin, leading
to decreased production of LH and FSH
55. Prolactinoma
• Women
• Amenorrhea – this symptom causes women to present earlier
• Infertility
• Galactorrhea
• Men
• Impotence – often ignored
• Tend to present later
• Signs of mass effect
57. •If prolactin level > 200mcg/L, almost always a
prolactinoma (even in a nursing mother)
•Prolactin levels correlate with tumor size in
the macroadenomas
•Suspect another tumor if prolactin low with a
large tumor
58. Prolactinoma
•Diagnosis
•Assess hypersecretion
• Basal, fasting morning PRL levels (normally <20 ug/L)
•Multiple measurements may be necessary
• Pulsatile hormone secretion
• levels vary widely in some individuals with
hyperprolactinemia
•Hypothyroidism should be excluded by measuring
TSH and T4 levels
59. Prolactinoma
•Treatment
•Medical
• Cabergoline – dopamine receptor agonist
• Bromocriptine - dopamine agonist
• Safe in pregnancy
• Will restore menstruation
• Decreases both prolactin and tumor size (80%)
•Surgical
• Transsphenoidal surgery
• Irradiation
60. Quick Quiz!!!
• What type of tumors are most prolactinomas?
• Prolactin levels >200 almost always indicate what?
• Do prolactin levels correlate with tumor size?
61. Answer
• What type of tumors are most prolactinomas? Microadenomas
• Prolactin levels >200 almost always indicate what? Almost always
indicates prolactinoma
• Do prolactin levels correlate with tumor size? Yes, in macroadenomas
62.
63. Growth Hormone Tumors
• Gigantism
• GH excess before closure of epipheseal growth plates of long bones
• Acromegaly
• GH excess after closure of epipheseal growth plates of long bones
• Insidious onset
• Usually diagnosed late
64. Growth Hormone Tumors
• May have DM or glucose intolerance
• Hypogonadism
• Large hands and feet
• Large head with a lowering brow and coarsening features
• Hypertensive – 25%
• Colon polyps
• 3-6 more likely than general population
• Multiple skin tags
65. Growth Hormone Tumors
• Diagnosis
• Screen:
• Check for high IGF-I levels (>3 U/ml)
• Remember, levels very high during puberty
• Confirm:
• 100gm glucose load
• Positive: GH levels do not increase to <5ng/ml
• Treatment
• Surgical
• Radiation
• Bromocriptine - temporary measure
• May decrease GH by 50%
• Octreotide
• For suboptimal response to other treatment
68. Case 1
• 80-year-old man with history of hypertension (requiring three
antihypertensive agents) and type 2 diabetes mellitus (managed
with two oral hypoglycaemic drugs) was admitted with a fractured
neck of femur following a low-trauma fall.
• He was admitted to the orthopaedic ward to await fixation.
• However, he became hypotensive and required ionotropic support
and fluid resuscitation.
• His haemoglobin decreased (12.5 to 9.3 g/dl) and acute renal
dysfunction developed. The blood glucose was well controlled.
69. • Four days after admission the patient was considered fit for
hemiarthroplasty. Immediately postoperatively he became
hypoglycaemic and progressively drowsy, with no FND including visual
fields. Hyponatraemia and hypotension occurred.
• Full thyroid function testing showed hypothyroidism
• free T3 1.9 [3.4–5.6 pmol/L]
• free T4 6.4 [9–20 pmol/L]
• TSH 1.0 mU/L [0.3–5.5]
• Whats the diagnosis?
70. Case 2
• A previously healthy 64-year-old woman presented to the emergency room with a
three-day history of feeling generally unwell, drowsiness and acute onset, severe
headache.
• She had a decreased level of consciousness and a temperature of 39°C. No
ophthalmoplegia, visual field defect or other focal neurological signs were present.
She had a leucocytosis and raised C-reactive protein (CRP) with normal serum
sodium. The chest radiograph was unremarkable and computed tomography (CT) of
the brain was reported as showing involutional changes.
• Cerebrospinal fluid demonstrated
• 220 red cells per µL
• 408 white cells per µL (83% polymorphs, 17% lymphocytes)
• Proteins 1.7 g/L (NR 0.1–0.4)
• glucose 40 mg/dl
71. • The patient was presumed to have pneumococcal meningitis
• intravenous ceftriaxone was administered.
• No response
• Culture of CSF negative
• Hormone tests revealed panhypopituitarism
72. MRI brain showing a haemorrhagic lesion of the pituitary gland
extending to the optic chiasm causing displacement of the optic nerve,
consistent with pituitary macroadenoma
73. Diagnosis:
pituitary apoplexy related to haemorrhage with resultant
hypopituitarism
Hydrocortisone and thyroxine were commenced.
Mass reduced at 3 years of follow up