Review of Endocrine Systems

Multiple endocrine glands throughout body

Pituitary Thyroid/Parathyroid Adrenal Pancreas (Liver & biliary tract lecture) Ovary and Testes (reproductive pathology lecture)

Endocrine glands

Hormones control many functions

Metabolism Reproduction Fluid and electrolyte balance Growth

Secrete hormones directly into blood; act at receptors (often on other endocrine glands)

 Produce a response

Hormone Actions
Oxytocin stimulates smooth muscle contraction ADH stimulates water absorption Prolactin stimulates lactation TSH stimulates thyroid hormone LH stimulates testosterone and progesterone ACTH stimulates cortisol

Stimulate an endocrine response

Negative feedback
Important aspect of hormone regulation May be exerted by another hormone
testosterone inhibits LH thyroxine inhibits TSH

May be exerted by a nonhumoral signal

Calcium inhibits PTH Glucose inhibits glucagon

Endocrine Disorders
Fall into 2 categories
Too much (hormone)
Often involves tumor May be ectopic

Too little (hormone)

Autoimmune response Overworked (no longer responds adequately)

1. Hormone deficiency 2. Hormone excess

Treatment

Hormone replacement Ex. Insulin for diabetes mellitus Inhibitory drug therapy
Bromocryptine for hyperprolactinemia Androgen antagonist for hirsutism (excess hair) Surgical removal of lesion, leaving gland intact

Ablation therapy

 Location: Sella turcica (close to optic chiasm). Divided into two lobes:
1. The adenohypophysis or anterior lobe. 2. The neurohypophysis or posterior lobe

Pituitary gland : Generalities

Role:
regulation of other endocrine glands (along with hypothalamus).

Posterior lobe = neurohypophysis

Anterior lobe = adenohypophysis

Intermediate lobe =parsintermedia

 Derived from Rathkes pouch. The hypothalamus: regulates the release of hormones from anterior pituitary by:
1. Hypothalamic releasing and 2. Inhibiting hormones

Anterior pituitary

Anterior pituitary: cell types On histological sections 3 cell types : Cells with
1. Eosinophilic cytoplasm=Acidophils 2. Basophilic cytoplasm= Basophils 3. Poorly staining cytoplasm=chromophobe

Basophils

Acidophils

Chromophobes

Normal microscopic appearance of adenohypophysis

The normal microscopic appearance of the adenohypophysis is shown here. The adenohypophysis contains three major cell types: acidophils, basophils, and chromophobes. The staining is variable, and to properly identify specific hormone secretion, immunohistochemical staining is necessary. A simplistic classification is as follows: The pink acidophils secrete growth hormone (GH) and prolactin (PRL) The dark purple basophils secrete corticotrophin (ACTH), thyroid stimulating hormone (TSH), and gonadotrophins follicle stimulating hormone-luteinizing hormone (FSH and LH) The pale staining chromophobes have few cytoplasmic granules, but may have secretory activity.

Pituitary hormones
Cell type Hormone secreted GH Prolactin TSH Stimulated by GHRH TRH TRH Inhibitor Somatotrophs Lactotrophs Thyrotrophs GIH Dopamine Thyroid hormone Glucocorticoids Sex steroids, FSH, Inhibin

Corticotrophs Gonadotrophs

ACTH LH,FSH

CRH GnRH

Posterior pituitary
Storage site for hormones produced by neurosecretory neurons. The two hormones are ADH and oxytocin. Antidiuretic hormone (ADH):
Promotes water retention through action on renal collecting ducts Induces uterine contraction and milk ejection.

Oxytocin:

Disorders of pituitary gland

1. Hyperpituitarism and Pituitary adenomas
a) b) c) d) Prolactinomas Growth hormone adenomas Corticotroph cell adenoma Other anterior pituitary neoplasms

2. Hypopituitarism 3. Posterior pituitary syndromes

Clinical manifestations of pituitary disease

Pituitary adenoma* Hyperplasia Carcinoma Ectopic secretion Hypothalamic disorders Ischemia* Surgery Radiation Inflammation Non functioning adenoma*

Local mass effects

Secretion of Trophic Hormone

Secretion of Trophic Hormones

Hyperpituitarism

Hypopituitarism

Radiological abnormalities Visual field defects S/S of Increased ICT Pituitary apoplexy

Pituitary adenoma

 CC: 42-year-old male, presented for evaluation of headache and "problems seeing." HOPI: Headache developed over past one year, worse while reclining.
In addition, noted the development of "blind spots" in his lateral fields of vision, particularly on the right side.

Case 1

Physical examination:
slight blurring of the optic discs. Asymmetric bitemporal visual field deficit.

 CT and MRI scans:

revealed a large midline mass associated with erosion of the sella turcica. The mass extended into the suprasellar space and into the right cavernous sinus.

Laboratory evaluation:
Prolactin level: 90 ng/mL (normal < 14 ng/mL).

 Peroperative findings: Mass

obliterated the diaphragma sella and the lateral walls of the sella turcica; compressed the optic chiasm superiorly and extended bilaterally into the cavernous sinuses.

Biopsy Specimen Of The Mass: consisted of soft, almost gelatinous, tan tissue. Histologic examination:
monomorphous population of cells with uniform, round-to-ovoid nuclei and amphophilic cytoplasm.

Management:
The mass was resected. The patient made an uneventful postoperative recovery

Diagnosis
Pituitary adenoma

 Most common cause: Pituitary adenomas:

Pituitary hyperfunction = hyperpituitarism

an adenoma arising in the anterior lobe of pituitary. Functional: associated with hormone excess and clinical manifestations. Non functional (Silent) : IHC demonstration of hormone, local pressure effects.

Prolactin cell (lactotroph) adenoma

Classification of pituitary adenomas

Growth hormone cell (somatotroph) adenoma Thyroid stimulating hormone cell (thyrotroph) adenomas ACTH cell (corticotroph) adenomas Gonadotroph cell adenomas Mixed GH-prolactin cell (mammosomatotroph) adenomas Other plurihormonal adenomas Hormone negative adenomas

 Most common type of adenoma Also the MC tumor of anterior pituitary. Clinical findings
Effects of increased prolactin levels:

Prolactinoma with hyperprolacteinemia

WOMEN:
secondary amenorrhea (Prolactin inhibits GnRH) and Galactorrhea (inappropriate milk secretion)

MEN:
Impotence Loss of libido and infertility due to decrease in testosterone No galactorrhea.

Morphology
Gross: could range in size from <1 cm to >1cm Microscopy: Composed of
Monomorphic polygonal cells arranged in sheets and cords.
Uniform nuclei Cytoplasm may be acidophilic, basophilic or chromophobic.

Microadenomas (<1cm) Macro adenomas (>1cm)

Undergo dystrophic calcification

Psammoma bodies

IHC: demonstrates prolactin.

The T1 weighted MRI scan in sagittal view here demonstrates a macroadenoma of the pituitary that is bright with gadolinium enhancement. Such an enlarging mass can produce the classic bitemporal hemianopsia by pressure effect on the optic chiasm superiorly.

Other causes of increased prolactin levels = hyperprolacteinemia:

1. Pregnancy 2. Drugs

Birth control pills (estrogen) Dopamine depleting (alpha methyl dopa, reserpine) Dopamine receptor antagonists
Phenothiazines, haloperidol

3. Hypothyroidism:
Low T4 increases TSH and TRH TRH is a stimulator for prolactin. Stalk transection

4. Damage to dopaminergic neurons

 Diagnosis:
Clinical suspicion: amenorrhea in women, impotence, infertility in men. Prolactin levels >100ng/mL suggest pituitary adenoma
Always exclude physiologic states, hypothyroidism, renal failure and medications.

Treatment:
Bromocriptine: dopamine receptor agonist (inhibits prolactin) Surgery

 Or simply GH adenoma Second most common type of pituitary adenoma Secrete growth hormone causing secondary hyper- production of somatomedins by the liver.
GH
Liver
Increased production and release of Acts on

Growth hormone cell) adenoma

(somatotroph

Somatomedins Especially IGF-1

 GH functions:
Increase amino acid uptake in muscle Gluconeogenesis Stimulates synthesis and release of IGF-1 in liver.

IGF-1 functions:
Linear and lateral bone growth Growth of soft tissues

 Causes gigantism in children :

Growth hormone excess : Clinical findings

increased linear bone growth (epiphyses are not fused) Tall stature and long extremities.

 Causes acromegaly in adults: Skeletal and soft tissue changes:

Growth hormone excess : Clinical findings

No linear growth in bones but increased lateral bone growth due to IGF-1 Enlargement of Hand and feet. Widening of Jaw (gaps in teeth) Enlargement of frontal sinuses : increases hat size Laryngeal hypertrophy and sinus enlargement lead to deep voice. Enlargenet of internal organs: (heart, lung, liver, kidneys) Cardiomyopathy: heart failure MC cause of death

Metabolic changes:
Impaired glucose tolerance, Diabetes

Change in the facial features of a patient with acromegaly over years.

Enlarged hands

Large feet

Glossomegaly

 Diagnosis:
Elevated growth hormone Elevated somatomedin C (IGF-1 = insulin like growth factor)

 Produce ACTH Increased ACTH Adrenal increased cortisol Cushing's disease/ Cushing syndrome. Cushing disease: Cushing syndrome:

Corticotroph cell adenoma

Refers to cortisol due to corticotropic adenoma of pituitary.

Refers to cortisol regardless of cause. May be of adrenal or ectopic origin

Refers to partial or complete loss of anterior pituitary function. Anterior pituitary hypofunction : causes Non-secretory pituitary adenomas *** Ischemic necrosis of pituitary: Sheehans post partum necrosis Ablation of pituitary by surgery or radiation Craniopharyngioma: (children+)**** Others: Sarcoidosis, TB etc Pituitary cachexia (Simmonds disease) Is generalized panhypopituitarism Is characterized by marked wasting Can result from any process that destroys the pituitary Most often caused by: Pituitary tumors Postpartum pituitary necrosis (Sheehan syndrome)

Hypopituitarism

 Nonfunctioning pituitary adenoma:

Most common cause of hypopituitarism in adults Associated with multiple endocrine neoplasia (MEN) I syndrome.

Anterior pituitary hypofunction

The adenoma expands causing

loss of trophic hormones and hypofunction of target organs. can also cause headache, visual field defects (bitemporal hemianopsia) and palsies (due to cranial nerve damage)

Lateral Ventricles Basal Ganglia Temporal lobes Anterior cerebral Art

Pituitary adenoma

ICA

Other causes of Anterior pituitary hypofunction Case 2 38 year old woman developed massive postpartum hemorrhage
Stabilized with multiple blood transfusions and crystalloids.

A few weeks later:

Not been able to lactate since birth of the baby Feels lethargic and weak and gets dizzy while standing up

Physical examination:
Axillary and pubic hair sparser than before.

Lab: markedly low serum levels of prolactin MRI: necrosis of anterior pituitary Diagnosis: Sheehans syndrome (or

Sheehans postpartum pituitary necrosis

Caused by ischemic necrosis of the pituitary gland Due to hypotension resulting from postpartum hemorrhage. Results in panhypopituitarism. Presentation: Sudden cessation of lactation Remember:
Normally pituitary doubles in size during pregnancy
Estrogen/progesterone inhibit lactation Delivery of placenta removes inhibition and lactation begins.

Other causes of Anterior pituitary hypofunction

Empty sella syndrome:
Refers to presence of an empty sella turcica that is not filled by pituitary. Two types:
Primary empty sella:
Due to compression and atrophy of pituitary because of herniation of CSF.

Secondary empty sella:

Due to surgical removal of an adenoma

Both result in hypopituitarism.

Craniopharyngioma(adamantinoma)

Most common cause of hypopituitarism in children Benign tumor derived from remnants of Rathkes pouch. Not a true pituitary tumor. Located superior to sella turcica; extends into sella turcica and destroys the pituitary gland.

Bimodal age distribution:

1st peak (5-15 yrs) 2nd peak (60-70 yrs)

Presentation
Children : endocrine deficiency

Gross:
3-4 cm in diameter.

Two variants:
1. Adamantinomatous CP 2. Papillary CP Microscopic features: Consists of nests and cords of stratified squamous epithelium or columnar cells embedded in a loose stroma (spongy reticulum). Compact keratin formation (wet keratin) is diagnostic feature. Often show cystic change: filled with fluid = machinery oil Often calcifies : helps in radiological detection.

Calcifications
Keratinizing squamous cells

Cholesterol crystals

Cysts: filled with fluid = machinery oil

 Decreased gonadotropins:
Adult woman:

Hypopituitarism: Clinical findings

Adult men: Children: Lab :

Secondary Amenorrhea Decreased libido Diminished sec. sex characteristics. Impotence (failure to sustain an erection) Diminished sec. sex characteristics. Growth and sexual maturation retardation Delayed fusion of epiphyses Low FSH and LH Low estradiol/ testosterone

 Growth hormone deficiency:

Adults:
no effect on growth hypoglycemia (GH is gluconeogenic)

Children:
pituitary dwarfism delayed growth and sexual maturation

TSH deficiency:
Secondary hypothyroidism Decreased serum T4 and TSH

ACTH deficiency:
Secondary adrenal insufficiency Hypoglycemia (cortisol is gluconeogenic)

Prolactin deficiency:
Failure of lactation in post-partum patients

Disorders of posterior pituitary

ADH and Oxytocin are synthesized in neurons of the supraoptic and paravenricular nuclei in the hypothalamus. Transported to posterior pituitary lobe to be stored and released.

 Syndrome associated with Excess secretion of ADH is k/a Syndrome of inappropriate ADH (SIADH) secretion:
Excess ADH resorption of excessive water and natriuresis.

Posterior pituitary hyperfunction

Clinical findings:
Water retention and extracellular fluid volume expansion Hyponatremia: key feature in SIADH, due to water retention and sodium loss.
Severe hyponatremia (Na <120) symptoms of cerebral edema prominent (irritability, confusion and seizures)

 Etiology:
Small cell carcinoma of lung (Ectopic ADH secretion)* MCC. Central nervous system injury Lung infection (e.g. tuberculosis). Drug use (e.g. chlorpropamide)

Diagnosis:
Hyponatremia (serum Na usually <120mEq/L

Treatment : restrict water

Posterior pituitary hypofunction

Deficiency of ADH: results in Central diabetes insipidus:
Lack of antidiuretic hormone (ADH) results in
Excessive urination (polyuria), increased thirst (polydipsia), hypernatremia and dehydration.

Etiology:
Hypothalamic disease (e.g. histiocytosis X and sarcoidosis) Transection of pituitary stalk (e.g. trauma) Posterior pituitary disease (e.g. metastasis)

Responds to ADH administration by increasing urine concentration (urine osmolality).

 Nephrogenic diabetes insipidus:

Collecting tubules refractory to ADH.

Caused by a lack of renal response to ADH Drug use (e.g. lithium), hypokalemia (vacuolar nephropathy) Excessive thirst, polyuria Does not respond to ADH administration; urine remains hypotonic. Hypernatremia and hypotonic urine.

Etiology:

Clinical findings:

Laboratory findings: