Pituitary Disorders

Question 1

What is the most common type of dwarfism?

Answer 1

The prototype chondroplasia is the most common non-lethal type.

Question 2

What causes achondroplastic dwarfism?

Answer 2

Results from the failure of cartilage to ossify

Question 3

What are the characteristics of dwarfism?

Answer 3

Dwarfs have short limbs, long and narrow trunks, large heads with mid-face hypoplasia and prominent brows. They have delayed motor milestones.

Question 4

What gene mutation is associated with dwarfism?

Answer 4

The achondroplasia group of disorders are all caused by mutations in the FGFR3 gene.

Question 5

Is there a treatment for dwarfism?

Answer 5

Surgical correction of orthopedic problems is indicated. No other treatment is available.

Question 6

How does growth hormone work?

Answer 6

GH exerts much of its growth promoting effects by stimulating the release of IGF-I from the liver and other tissues.

Question 7

What causes acromegaly? Where does it most likely occur?

Answer 7

Acromegaly is nearly always caused by a pituitary adenoma, particularly in the cavernous sinus. Most are macroadenomas.

Question 8

What is acromegaly?

Answer 8

The term means extremity enlargement

Question 9

What are the clinical findings of acromegaly?

Answer 9

Enlarged hands with a characteristic soft dough hand shake, Coarse facial features, prominent mandible, macroglossia, deep voice, HTN, and weight gain.

Insulin resistance is common and frequently causes DM (30%)

Question 10

What causes acromegaly?

Answer 10

Excessive release of GH causes tall stature and gigantism if it occurs in youth before the closure of the epiphyses. Afterward acromegaly develops.

Question 11

What are common laboratory and radiological findings in acromegaly?

Answer 11

For screening purposes a random IGF-I can be obtained, if it is normal for age, acromegaly can be ruled out.

MRI shows a pituitary tumor in 90% of patients. Radiography may also show tufting of the terminal phalanges of the fingers and toes.

Question 12

How is acromegaly treated?

Answer 12

Pituitary Microsurgery is the treatment of choice for patients with acromegaly. Other treatments include medications such as cabergoline suppress GH levels.

Question 13

What is a complication often seen in patients with acromegaly?

Answer 13

Patients with acromegaly have increased morbidity and mortality for CV disease and disorders and progressive acromegalic symptoms.

Question 14

What does the anterior lobe of the pituitary do?

Answer 14

Secretes hormones by negative feedback to adrenals, thyroid, and gonads. The anterior pituitary produces 6 major hormones: ACTH, TSH, LH, GH, FSH, and prolactin (PRL).

Question 15

What does the posterior lobe of the pituitary do?

Answer 15

Does not produce its own hormones but stores ADH (vasopressin) and oxytocin, which are made in the hypothalamus.

Question 16

What does the posterior pituitary secrete?

Answer 16

ADH and oxytocin

Question 17

Posterior Pituitary (Neurohypophysis)

Answer 17

Axons and nerve terminals of larger neurons that originate in the paraventricular and supraoptic nuclei of the hypothalamus terminate in the posterior pituitary and release vasopressin or ADH (Antidiuretic hormone) and oxytocin
ADH - acts on the kidneys to conserve water by acting on V2 receptors
ADH is also called ‘vasopressin’- acts on V1 receptors to increase vascular tone
Oxytocin –Causes uterine contraction during labor, and stimulates milk ejection during breast feeding

Question 18

Negative feedback mechanism

Answer 18

There is a negative feedback mechanism from the peripherally secreted hormones on the hypothalamus & the pituitary

Question 19

Sellar masses

Answer 19

Most common – pituitary adenomas
Other benign tumors include craniopharyngiomas, meningiomas, pituicytomas, cysts (Arachnoid, dermoid, epidermoid, Rathke’s)
Pituitary granulomas – sarcoidosis, histiocytosis X
Primary pituitary malignancy is very rare
Metastatic disease accounts for 1-2% of sellar masses
Lung ca and breast ca most common mets

Question 20

Pituitary adenomas

Answer 20

Benign tumors of the anterior pituitary account for 10% of all intracranial neoplasms
Microadenomas < 1 cm
Macroadenomas > 1 cm
Problems from adenomas – hormonal hypersecretion, hormonal hyposecretion or mass effect

Question 21

Clinical manifestations

Answer 21

Insufficient production
Hypopituitarism
Excessive production
Prolactinomas		Inc. prolactin
Cushing’s disease	Inc. ACTH
Acromegaly		Inc. GH after puberty
Gigantism		Inc. GH before puberty
Hyperthyroidism	Inc. TSH
Nonfunctional
Mass effect

Question 22

Mass effect

Answer 22

Headache
Visual field disturbances
Bilateral temporal hemianopsia occurs with tumor compression on the optic chiasm
Double vision (oculomotor palsies due to injury of CNs III, IV, and VI) from lateral expansion of the tumor to the cavernous sinus

Question 23

hypopituitarism

Answer 23

Etiology
Pituitary tumors
Surgery
Pituitary apoplexy
Sheehan’s syndrome
Infarction of the anterior pituitary gland during childbirth
Pituitary infiltrative diseases (less common)
Sarcoidosis, Hemosiderosis, Tuberculosis
Usually the patient has other organ involvement (lung, liver, pancreas, testicles)

Question 24

clinical features

Answer 24

GH deficiency:
Growth failure in children
Less dramatic effects in adults (decreased muscle and bone mass, fatigue)

Gonadotropin (LH/FSH) deficiency:
Amenorrhea & genital atrophy in women
Loss of libido and potency in males

TSH deficiency:
S&S of hypothyroidism

ACTH deficiency:
S&S of adrenal insufficiency

Prolactin deficiency:
Postpartum failure of lactation in Sheehan’s syndrome

Question 25

pattern of hormonal loss

Answer 25

GH and gonadotropin secretion occurs early, followed by TSH and finally ACTH
Do not forget to think of central cause for hormonal hypofunction!
Primary vs. secondary
Always think of feedback

Question 26

diagnosis

Answer 26

Clinical picture
Evaluation of target organ function
Measurement of pituitary hormone levels
			-TSH, total and free thyroid hormones
			-Prolactin
			-LH/FSH
			-Estradiol/Testosterone
			-Cortisol +/- ACTH
			-IGF-1

Question 27

hormone patterns

Answer 27

Target Gland Pituitary
T3, T4 (low) * TSH ( low, nl)
Cortisol (low) ** ACTH (low, nl)
Testosterone (low) LH/FSH (low, nl)

*secondary hypothyroidism
**secondary hypoadrenalism
Postmenopausal women with (low/Nl) FSH/LH suggest secondary hypogonadism
In all of these cases, the rest of the pituitary hormones need to be checked to R/O panhypopituitarism

Question 28

treatment

Answer 28

Treatment of the underlying pathology

Hormonal replacement

Question 29

growth hormone

Answer 29

Secreted from pituitary somatotrophs in a pulsatile fashion. Therefore a random GH level is not diagnostic
Its secretion is stimulated by hypothalamic GHRH and inhibited by hypothalamic somatostatin
Has a generalized anabolic effect
GH effect is exerted via production of IGF-1 by the liver, IGF-1 then binds to IGF receptors on most tissues

Question 30

GH hypersecretion

Answer 30

In children
Before the closure of the epiphysis:
“ GH secretion leads to Gigantism
” GH secretion leads to Dwarfism

In Adults
After the closure of the epiphysis
“ GH secretion leads to Acromegaly
” GH secretion leads to symptoms of GH deficiency

Question 31

acromegaly

Answer 31

Pituitary adenoma (usually a macroadenoma ) produces excess GH
Patients are usually diagnosed years later, when there is a mass effect present. Average delay in diagnosis of about 10 years

Question 32

clinical features

Answer 32

Enlargement of hands and feet
Increased ring, glove and shoe size
Coarsening of facial features
Enlargement of internal organs
CVS – HTN, LVH, cardiomyopathy
Metabolic – glucose intolerance
Sleep apnea
Increased incidence of colon polyps and cancer

Spacing of the teeth
Protrusion of the jaw - prognathism

Question 33

diagnosis

Answer 33

Clinical manifestations
Biochemical abnormalities
“ IGF-1
Diagnosis is confirmed by a GTT
Normally GH levels suppress after ingestion of 100 gm of glucose
Acromegaly-GH levels do not suppress

Question 34

treatment

Answer 34

Trans-sphenoidal resection of pituitary tumor
Trans-frontal resection (for severe invasion)
Conventional or Gamma knife radiotherapy
Medical treatment :
Somatostatin analog: Octreotide
DA agonist: Cabergoline
GH receptor blocker: Pegvisomant

Question 35

prolactin

Answer 35

Prolactin:
Secreted from pituitary lactotropes in a pulsatile fashion
Secretion rises with exercise, meals, intercourse, minor surgery, general anesthesia and acute stress
Release increases 10-fold during pregnancy and declines within 2 weeks after parturition
Inhibited by Dopamine secretion
Action: stimulates lobuloalveolar epithelium proliferation of breast, induces/maintains lactation, decreases reproductive function and suppresses sexual drive

Question 36

causes of hyperprolactinemia

Answer 36

Physiologic
Pregnancy, lactation, nipple stimulation

Prolactinomas

Damage to the hypothalamic pituitary stalk
(Interruption of the normal negative tonic effect of dopamine (from the hypothalamus) on lactotroph cells)
Surgery or trauma
Other pituitary or hypothalamic tumors

Drugs that inhibit dopamine secretion
Phenothiazides, TCA’s, Reglan, verapamil, etc.

Primary Hypothyroidism
Increased TRH stimulates prolactin secretion

Chronic renal failure/Liver cirrhosis
Decreased metabolic clearance of prolactin

Chest wall trauma (surgery, herpes zoster)

Seizures

Question 37

prolactinoma

Answer 37

Prolactin-secreting pituitary adenomas
Comprise one half of all functioning pituitary adenomas
More common in women
Tumor size generally correlates with hormonal levels
Generally are slow growing tumors
Men are usually diagnosed later

Question 38

clinical features

Answer 38

Amenorrhea, menstrual irregularities, infertility
Galactorrhea (80% women, uncommonly seen men)
Loss of potency and libido in men
Mass effect symptoms (visual loss, headaches)

Question 39

diagnosis

Answer 39

Prolactin level: Usually higher levels with larger tumors
25-100ug/L- microadenoma or stalk effect

MRI or CT of the pituitary

Question 40

treatment

Answer 40

Dopamine agonists (Bromocriptine or Cabergoline)
If the patient cannot tolerate D.A. or the tumor is not
responding to D.A. with compressive symptoms - trans-sphenoidal surgery
Radiation Therapy

Question 41

disorders of posterior pituitary

Answer 41

Diabetes Insipidus
Polyuria due to lack of ADH (anti-diuretic hormone)
 Divided into 2 categories
     Central DI 	
due to ADH deficiency

Nephrogenic DI
due to renal unresponsiveness to ADH

Question 42

causes of DI

Answer 42

Injury to the HPA axis
Head trauma
Primary brain tumors (pre or postoperative) esp. craniopharyngioma
Metastatic
Less common: encephalitis, sarcoidosis
Idiopathic

Question 43

clinical features

Answer 43

Polyuria
Urine output of 3-15 L/day
Thirst and polydipsia
A conscious patient with a normal thirst mechanism and free access to water will maintain hydration
In this case, this disease will be more an inconvenience rather than a life-threatening disorder

Question 44

important

Answer 44

Life-threatening dehydration in D.I. may occur:
An infant
Unconscious/confused adult
Abnormal thirst mechanism
Inability to gain access to water (restrained patient in N.H. or psych. Unit)

In uncompensated D.I:
hyperosmolality develops and patient have S&S of hypernatremia (lethergy, confusion) and in severe cases seizures and coma ensue

Question 45

laboratory eval

Answer 45

Check serum/urine osmolality and sodiums, urine specific gravity

Dilute urine
Osmolality < 300 mosm/Kg
Urine specific gravity < 1.010

In compensated DI
Plasma osmolality and serum Na are high normal or slightly elevated

In uncompensated DI
Serum Na is high (> 150 meq/L) and serum osmolality is high

Question 46

diagnosis

Answer 46

The gold standard is a Water Deprivation test

Should be done under direct medical supervision

Fluid intake is withheld until urine osmolality reaches a plateau

When Urine Osm is stable, dDAVP (synthetic analogue of vasopressin or ADH) is given to evaluate the increase in urine Osm.

Question 47

treatment

Answer 47

Desmopressin (dDAVP)
Synthetic analogue of vasopressin
Nasal spray, I.V. or tablets
In central D.I. (nephrogenic D.I. does not respond to dDAVP)
Correcting Hypernatremia quickly results in Cerebral edema
Chlorpropamide
Used in central D.I.
Potentiate the action of endogenous ADH
Can cause: hypoglycemia
Thiazide diuretics
Used in nephrogenic D.I.

Question 48

SIADH

Answer 48

Excess ADH Production

Causes
Pulmonary Diseases
Pneumonia, TB, small cell lung cancer
CNS disorders
Stroke, head trauma, encephalitis, ICH
Drugs that stimulate ADH secretion
Chlorpropamide, carbamazipine, narcotics, TCA’s, general anesthesia
Hormone deficiency
Hypothyroidism, hypoadrenalismOther causes include malignancy,major surgery and idiopathic

Question 49

pathophys

Answer 49

Normally, when serum osmolality decreases (associated with hyponatremia) ADH shuts off to allow excess free water diuresis and return of serum Na and osmolality to normal levels
SIADH: impaired ADH suppression despite hyponatremia and hypo-osmolality (ADH level is inappropriately normal or high despite low Na and low serum osmolality
Excess ADH causes water retention and ECFV expansion

Question 50

clinical features

Answer 50

Hyponatremia (Na < 135) with low serum osmolality
If Na level falls rapidly or it reaches a level < 125 meq/L, neurological symptoms manifest (lethargy, confusion, headache, nausea,vomiting)
Urine osmolality > serum osmolality
Euvolemia

Question 51

treatment

Answer 51

Fluid restriction (800-1000 ml/day)
This is the mainstay of treatment
If hyponatremia is severe, hypertonic saline (3%) should be used to raise the serum Na level to 120-125 meq/L
Serum Na should not be raised rapidly or CNS damage may result (Central Pontine Myelinolysis)
Rate of correction should be 10 meq or less per day
Salt tablets with fluid restriction, addition of loop diuretic may be tried
ADH receptor antagonists: Tolvalptan and Conivaptan
Demeclocycline