ENDOCRINE DISORDERS

The Players

The Endocrine System

Exocrine glands - transport their hormones to target

tissues via ducts.

Endocrine glands:

release their hormones directly into the blood

Organs

• Pituitary

• Thyroid

• Parathyroids

• Adrenals

• Endocrine pancreas

Diseases

Non-neoplastic

too much hormone

too little hormone

Neoplastic

benign

malignant

Endocrine Pathology

Pituitary gland

• “The Master Gland”

– Produces many hormones.

– Primary function is to control other glands & body systems

– Secretion is controlled by the hypothalamus

Pituitary

60 mg

Midline structure in sella turcica

Anterior and posterior lobes

Connected to the hypothalamus by a stalk

HYPOTHALAMUS AND POSTERIOR PITUITARY

HYPOTHALAMUS

NEUROSECRETORY

NEURONS

ANTERIOR

PITUITARY

POSTERIOR

PITUITARY VASOPRESSIN

OXYTOCIN

HYPOTHALAMUS AND ANTERIOR PITUITARY

HYPOTHALAMUS

NEUROSECRETORY

NEURONS

• TSH

•ACTH

•PROLACTIN

•GROWTH

HORMONE

•LH

•FSH

POSTERIOR

PITUITARY

ANTERIOR

PITUITARY

EMBRYOLOGY

• Anterior lobe (adenohypophysis) – Embryologically from Rathke pouch

– Histologic cell types = Eosinophilic cytoplasm (acidophil), basophilic cytoplasm (Basophil), or poorly staining cytoplasm (chromophobe) cells

• Posterior lobe (neurohypophysis) – Embryologically derived from an outpouching of the floor of the

third ventricle

– has nerve cell bodies in hypothalamic nuclei

PITUITARY GLAND

ANTERIOR PITUITARY POSTERIOR PITUITARY

Acidophilic, basophilic cells

and chromophobes Nerve endings

PITUITARY GLAND

Green = stimulatory

Red = inhibitory

AcidophilProlactin (PRL)Dopamine

BasophilThyroid Stimulating

Hormone (TSH)

Thyrotropin Releasing

Hormone (TRH)

BasophilAdrenocorticotropic

Hormone (ACTH)

Corticotropin Releasing

Hormone (CRH)

AcidophilGrowth Hormone (GH)Growth Hormone

Releasing Hormone

(GRH)

BasophilLuteinizing Hormone

(LH)

Follicular Stimulating

Hormone (FSH)

Gonadotropin Releasing

Hormone (GnRH)

Cell typeCorresponding Anterior

Pituitary Hormone(s)

Hypothalamic Releasing

HormoneHypothalamic

hormone Pituitary hormone Cell type

Pituitary hormones

– hormonal production is controlled predominantly by hypothalamus

– primary hypothalamic control of Prolactin secretion is inhibitory,

– while others have stimulatory effect

Negative feedback loops : control the secretion of pituitary hormones

Hypothalamus TRH

Pituitary TSH

Thyroid T3, T4

Disorders of Pituitary

Hyperpituitarism

Hypopituitarism

• Definition: too much anterior pituitary hormone(s)

• Most common cause: Pituitary adenoma

Other causes :

Pituitary hyperplasia, carcinoma, hypothalamic disorders

Hyperpituitarism

Pituitary adenoma

• Etiology is unknown

• 10-15% of all primary brain tumors

• 20-25% of pituitary glands at autopsy found to have adenomas

• 70% of adenomas secrete hormones

• 3% of those with MEN-I develop pituitary adenomas

Epidemiology

• Vary in size

• Microadenomas < 10 mm

• Macroadenomas > 10 mm – cause problems due to mass effect

Pituitary adenoma : Symptoms

– Functioning/ Non-functioning

– Mass effects:

– Earliest changes - radiographic abnormalities of the sella turcica

– visual field abnormalities- bitemporal hemianopsia

– Elevated intracranial pressure - headache, nausea, and vomiting

* FUNCTIONING : 70%

- Prolactin cell adenoma (Lactotroph adenoma / Prolactinoma ) : most common functioning pituitary adenomas : 30%

- GH ( Somatotroph ) adenoma : second most common

- ACTH producing (Corticotroph adenoma)

- FSH / LH-producing ( Gonadotroph adenoma)

- TSH-producing (Thyrotroph adenoma)

- Mixed ( plurihormonal ) adenoma

* NON-FUNCTIONING : 30%

Pituitary adenoma

Prolactinoma

In women

Secondary amenorrhoea : Prolactin inhibits

GnRH

Galactorrhoea

In Men Loss of libido

Labs: Prolactin levels > 200 ng/mL

Decreased FSH and LH

Treatment: Dopamine analogues/Surgery

Growth hormone adenoma

Functions of growth hormone:

• Stimulates liver synthesis of insulin growth factor 1(IGF-1)

• Stimulates gluconeogenesis and amino acid uptake in muscle

• Functions of IGF 1:

• Stimulates growth of bone (linear and lateral) , cartilage and soft tissue

IGF 1

Clinical features

In children : Gigantism : due to increase in

linear growth

In adults : Acromegaly Increase in lateral growth (as the

epiphyses have fused ) Prominent jaw, frontal bossing,

macroglossia Other findings

– diabetes mellitus – hypertension – Arthritis, generalised muscle

weakness – Congestive heart failure – gastrointestinal carcinoma

Labs: Increased GH and IGF1 : not suppressed by glucose TREATMENT: Surgery/Radiation

GIGANTISM ACROMEGALY

ACTH adenoma

• Leads to hypercortisolism : Cushings syndrome

• Cushings syndrome caused by excess secretion of ACTH by pituitary is called CUSHINGS DISEASE

GROSS MICROSCOPY

Well circumscribed lesion-

Small lesion : confined to the

sella tursica,

larger lesions extend beyond,

compress optic chiasma

Uniform cells in sheets, with

uniform nuclei,cytoplasm

acidophilic/basophilic/

chromophobic depending on the

cell type

PITUITARY ADENOMA

Summary : Functioning pituitary Adenomas

• Prolactin – Amenorrhea, galactorrhea, impotence

• Growth hormone – Gigantism and acromegaly

• Corticotropin – Cushing’s disease

• TSH - Hyperthyroidism

• Definition: too little anterior pituitary hormone(s) Many Causes:

• Empty sella syndrome: can occur from Surgery/Radiation

• Head trauma

– Pituitary destruction : due to a non – functioning pituitary adenoma / pituitary carcinoma / other tumor eg: Craniopharyngioma

– Ischemic necrosis (Sheehans syndrome)

– Hypothalamic lesions: tumors , both anterior and posterior hormone deficiency

Hypopituitarism

Sheehans Syndrome

- Postpartum necrosis of the anterior pituitary

– Most common form of clinically significant ischemic necrosis of the anterior pituitary

– During pregnancy anterior pituitary enlarges to almost twice its normal size not accompanied by an increase in blood supply

– relative anoxia of the pituitary is worsened by further reduction by obstetric hemorrhage or shock & precipitate infarction

Gonadotrophin deficiency

Growth hormone deficiency

TSH deficiency ACTH deficiency

- Children have

growth delay -

dwarfism

- Adults have

hypoglycemia

Arginine and sleep

stimulation test:

No increase in GH ,

normally GH is

released at 5 am

-Cold intolerance,

constipation

TRH stimulation

test:

-No increase in

TSH

-Decreased

cortisol

-Hypoglycemia

Metapyrone

stimulation test:

-No increase in

ACTH

ANTERIOR PITUITARY HYPOFUNCTION

In children:

Delayed puberty

Adult femalies:

Sec amenorrhoea

In Males :

impotence

Gn RH

stimulation test :

No increase in

FSH and LH

Sponge Bob, why is panhypopituitarism

so rare?

Why, Clucky, it’s because the pituitary has such a

big reserve!

Posterior pituitary syndromes

POSTERIOR PITUITARY SYNDROMES

ADH Deficiency (Diabetes Insipidus)

Inappropriate ADH Secretion (SIADH)

Due to ADH Decreased reabsorption of free water

ADH Increased reabsorption of free water

Results in

Cannot concentrate urine

Cannot dilute urine

Clinical manifestations

Polyuria and polydypsia Oliguria

Urine specific gravity

Low High

POSTERIOR PITUITARY SYNDROMES

Serum Na

levels

Hypernatremia

Hyponatremia (life-threatening) : brain swelling

Causes

Hypothalamic disease Transection of pituitary stalk ( as in trauma) Posterior pituitary lesions ( eg metastases)

MCC is ectopic ADH secretion by a small cell carcinoma of lung TB and pneumonia can cause ectopic ADH secretion

Treatment ADH administration Fluid restriction

ADH Deficiency

(Diabetes Insipidus)

Inappropriate ADH

Secretion (SIADH)

HYPOTHALAMIC SUPRASELLAR TUMORS

• CRANIOPHARYNGIOMA:

• Benign tumor derived from Rathkes pouch

• Extends into sella tursica and destroys the pituitary gland

• Common cause of hypopituitarism in children

• Can involve posterior pituitary also

• Pressure symptoms may be seen

Craniopharyngioma

Microscopy Gross

• Cystic structures lined by palisaded epitheium resembling tooth enamel

• Loose stellate reticulum

• Solid/cystic tumor with calcification

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