Anterior/Posterior Pituitary Disease

Question 1

What is the most common pituitary tumor?

Answer 1

The most common tumor of the pituitary is an adenoma.

Question 2

What is a prolactinoma and what does it do? Who gets it?

Answer 2

The most common functioning pituitary tumor, it presents at 20-40 years of age. It hypersecretes Prolactin (PRL)

Question 3

How does prolactinoma present and why?

Answer 3

Due to the high level of PRL, we get lactation but also inhibition of GnRH, which leads to decreases in FSH and LH, which in turn decrease progesterone and estrogen (testosterone in males), leading to amenorrhea/impotence.

In men we also see gynecomastia and in females we can see osteopenia due to the estrogen imbalance.

Finally, a classic finding is bitemporal hemianopsia due to superior growth of the tumor, leading to compression of the optic chiasm

Question 4

What can cause prolactinoma and an increase in PRL?

Answer 4

Dopamine inhibits PRL secretion so its depletion or pharmacologic antagonism disinhibits the anterior pituitary and PRL production. Excess PRL can arise from drugs that deplete or inhibit the synthesis/action of dopamine (reserpine, methyldopa, antipsychotics)

In hypothyroidism, elevated TRH stimulates the anterior pituitary to upregulate the PRL production.

Question 5

How do we treat prolactinoma?

Answer 5

1. Dopamine agonists like bromocriptine and cabergoline are first line and reduce size and secretion of the tumors making PRL
2. Transsphenoidal surgery is a secondary treatment.

Question 6

What does excessive GH lead to? What does it look like?

Answer 6

Gigantism in children and acromegaly in adults.

Gigantism refers to excess linear height of more than 2 SD above the mean for a person’s age, sex, and Tanner stage, where the epiphyseal plate does not close up.

Acromegaly is in adults and results from GH acting on fused growth plate cartilage. Presents with an enlarged jaw, hands, feet, facial features, prognathism (jaw that juts out)

Question 7

What commonly causes GH excess? Uncommonly?

Answer 7

Commonly, it is a pituitary adenoma composed of somatotroph cells.

Less common includes hypothalamic GHRH secretion or disruption of somatostatin tone.

Question 8

What condition that we have studied before is related to Gigantism?

Answer 8

Gigantism can be a secondary feature of McCune-Albright Syndrome.

Question 9

Besides the general MSK features of gigantism and acromegaly, what else can excessive GH lead to in the body?

Answer 9

• Cardiomyopathy - Enlarged liver and heart
• Peripheral neuropathies like carpal tunnel due to nerve compression
• Glucose intolerance and diabetes in 1/6 patients, tied with amenorrhea and impotence
• Headache and bitemporal hemianopsia due to mass effect on the optic chiasm

Question 10

What lab values help us diagnose excessive GH and why?

Answer 10

Elevated serum IGF-1 (GH increases IGF-1 secretion from the liver)
Oral glucose tolerance test - glucose normally decreases GH levels. If a bolus of glucose does not reduce the GH levels within 3 hours, you have a positive finding.

Question 11

How do we treat GH tumors?

Answer 11

Unlike with the pituitary tumors, like prolactinoma, our first line treatment is surgical, a transsphenoidal surgery, which can be followed by radiotherapy.

Drug therapy includes:

• octreotide, a long acting somatostatin analog that lowers GH levels
• Bromocriptine, a dopamine agonist that can work synergistically with octreotide
• Pegvisomant, a GH receptor antagonist

Question 12

What kills acromegaly patients?

Answer 12

The cardiac issues. They also suffer and increased risk of colon cancer and pituitary insufficiency.

Question 13

What is Sheehan Syndrome?

Answer 13

Ischemic necrosis of the pituitary.

Postpartum hemorrhage causing hypovolemic shock results in ischemic necrosis of the pituitary. This is due to the increase in size and blood demand of the pituitary during pregnancy

Question 14

What is panhypopituitarism? How does it present?

Answer 14

Reduction in release of all pituitary hormones. Patients can present with signs and symptoms of any or all pituitary deficiencies. The most life-threatening pituitary deficiency is ACTH.

Question 15

How do we treat panhypopituitarism?

Answer 15

Replacement of the missing hormones is required, the most important being cortisol. Because most of the anterior pituitary hormones are proteins or glycoproteins that induce the secretion of other hormones, the target gland hormone is often used as replacement rather than the pituitary hormone itself (i.e., TSH is replaced with T4, ACTH is replaced with hydrocortisone or another glucocorticoid, LH/FSH is replaced with testosterone, estrogen or progestin).

Question 16

What clinical findings would we see with hypopituitarism involving GH? As review, what does this hormone normally do?

Answer 16

Normally involves growth and glucose homeostasis.

Hormone deficiency leads to growth failure and dwarfism in children, and fatigue, osteoporosis, hypoglycemia (increased insulin sensitivity), increased LDL and fat mass, and decreased muscle mass in adults

Question 17

What clinical findings would we see with hypopituitarism involving Gonadotropin (LH/FSH)? As review, what does this hormone normally do?

Answer 17

Normally involved with the menstrual cycleand reproduction.

Deficiency causes amenorrhea, impotence, genital atrophy, infertility, decreased libido, decreased pubic hair

Question 18

What clinical findings would we see with hypopituitarism involving TSH? As review, what does this hormone normally do?

Answer 18

Normally stimulates T4 production from the thyroid gland.

Deficiency resembles primary hypothyroidism withou goiter (cold intolerance, lethargy)

Question 19

What clinical findings would we see with hypopituitarism involving ACTH? As review, what does this hormone normally do?

Answer 19

Normally stimulates glucocorticoid production from the adrenal gland.

Deficiency resembles primary adrenal insufficiency but without skin hyperpigmentation from MSH or volume depletion, hypokalemia, or salt craving since we still have an intact RAAS.

Question 20

What hormone is related to Diabetes insipidus (DI) and what is the story here?

Answer 20

DI is characterized by an ineffective ADH axis, resulting in inappropriately dilute urine. Vasopressin (ADH), synthesized by the supraoptic nucleus and stored in the posterior pituitary axon terminals, functions to concentrate urine and conserve water.

Question 21

What types of DI are there

Answer 21

Central DI - Absent or insufficient release of ADH from the posterior pituitary

Nephrogenic DI - Normal ADH secretion, but the kidneys are unresponsive (renal resistance to ADH)

Question 22

What is primary polydipsia?

Answer 22

A condition characterized by a marked increase in water intake, often seen in patients with psychiatric comorbidities, such as schizophrenia. It canalso develop in patients with lesions affecting the hypothalamic thirst center.

Question 23

How does DI present?

Answer 23

Excessive urination and thirst. In kids, DI can present with fever, vomiting and diarrhea as well. We see hypernatremia, which patients typically control with large water intakes to reduce the high osmolality.

Question 24

What causes the two types of DI?

Answer 24

Central - Idiopathic 50% of the time, but can be due to trauma, surgery, tumors, sarcoid and Hand-Schuuler-Christian disease

Nephrogenic - Caused by hypercalcemia, hypokalemia, and less often, medications, pyelonephritis, or V2/aquaporin gene mutations

Question 25

How do we distinguish between polydipsia alone and polydipsia with DI?

Answer 25

Low Urine osm and high plasma osmolarity in DI since the kidneys either don’t get ADH or can’t respond to it.

Low Urine osm and low plasma osm in primary polydipsia since the medullary gradient of the kidneys is washed out and dilute urine is produced.

Question 26

How do we treat DI?

Answer 26

• Vasopressin for central DI
• Chlorpropamide increases the release of ADH in partial ADH deficiency
• Thiazide diuretics like HCTZ or indomethacin are used for Nephro DI

Question 27

What is SIADH

Answer 27

Syndrome of inappropriate secretion of ADH

There is a net gain in free water over sodium, resulting in euvolemic hyponatremia. We see excess ADH in the absence of hyperosmolarity.

Question 28

Presentation of SIADH

Answer 28

Often asymptomatic if it is chronic. Acute usually presents with brain swelling - Lethargy, weakness, seizures, coma/death.

It causes volume expansion, but edema and hypertension are usually absent since we are excreting excess sodium in the urine.

Question 29

How do we make the diagnosis of SIADH?

Answer 29

Hypotonic hyponatremia in the presence of increased urine osmolarity.

BUN and uric acid also decreased reflecting the diluted fluid stores. Cr remains normal

Question 30

Problem with correcting hyponatremia too quickly?

Answer 30

Can lead to Central Pontine Myelinolysis

Question 31

Treating SIADH

Answer 31

Fluid restriction in mild cases , but if that isn’t working/not available, use conivaptan, a V2 receptor antagonist, or demeclocycline, which acts on collecting tubules to limit the response to ADH.

Hypertonic saline may be used if cerebral edema, convulsions, or coma develops.