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

Endocrine Pathology
Organs
Pituitary Thyroid Parathyroids Adrenals Endocrine pancreas

Diseases
Non-neoplastic

too much hormone too little hormone

Neoplastic

benign malignant

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

NEUROSECRETORY NEURONS
HYPOTHALAMUS

VASOPRESSIN OXYTOCIN

POSTERIOR PITUITARY

ANTERIOR PITUITARY

HYPOTHALAMUS AND ANTERIOR PITUITARY

NEUROSECRETORY NEURONS

HYPOTHALAMUS

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

Acidophilic, basophilic cells and chromophobes

Nerve endings

ANTERIOR PITUITARY

POSTERIOR PITUITARY

PITUITARY GLAND
Hypothalamic Releasing Hypothalamic Hormone

hormone

Corresponding Anterior PituitaryHormone(s) Pituitary hormone Luteinizing Hormone (LH) Follicular Stimulating Hormone (FSH) Growth Hormone (GH)

Cell type
Basophil

Cell type

Gonadotropin Releasing Hormone (GnRH)

Growth Hormone Releasing Hormone (GRH) Corticotropin Releasing Hormone (CRH) Thyrotropin Releasing Hormone (TRH) Dopamine

Acidophil

Adrenocorticotropic Hormone (ACTH) Thyroid Stimulating Hormone (TSH) Prolactin (PRL)

Basophil Basophil Acidophil

Green = stimulatory Red = inhibitory

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

Hyperpituitarism
Definition: too much anterior pituitary hormone(s)
Most common cause: Pituitary adenoma Other causes : Pituitary hyperplasia, carcinoma, hypothalamic disorders

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

Pituitary adenoma
* 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%

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

IGF 1

Functions of IGF 1: Stimulates growth of bone (linear and lateral) , cartilage and soft tissue

In children : Gigantism : due to increase in

linear growth

Clinical features

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

PITUITARY ADENOMA
GROSS MICROSCOPY

Well circumscribed lesionSmall 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

Summary : Functioning pituitary Adenomas

Prolactin Amenorrhea, galactorrhea, impotence Growth hormone Gigantism and acromegaly Corticotropin Cushings disease TSH - Hyperthyroidism

Hypopituitarism
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

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

ANTERIOR PITUITARY HYPOFUNCTION

Gonadotrophin deficiency
In children: Delayed puberty Adult femalies: Sec amenorrhoea In Males : impotence Gn RH stimulation test : No increase in FSH and LH

Growth hormone 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

TSH deficiency
-Cold intolerance, constipation TRH stimulation test: -No increase in TSH

ACTH deficiency
-Decreased cortisol -Hypoglycemia Metapyrone stimulation test: -No increase in ACTH

Sponge Bob, why is panhypopituitarism so rare?

Why, Clucky, its 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 Cannot concentrate urine

Polyuria and polydypsia Low

ADH Increased reabsorption of free water Cannot dilute urine

Oliguria High

Results in
Clinical manifestations Urine specific gravity

POSTERIOR PITUITARY SYNDROMES

ADH Deficiency (Diabetes Insipidus)

Inappropriate ADH Secretion (SIADH)

Serum Na levels

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

Hyponatremia (lifethreatening) : brain swelling MCC is ectopic ADH secretion by a small cell carcinoma of lung TB and pneumonia can cause ectopic ADH secretion Fluid restriction

Causes

Treatment

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 lumen contains machine oil like contents