Hypothalamus and Pituitary BSC

Objectives

• Review case presentations related to ADH (antidiuretic hormone).

• Correlate signs and symptoms of hypopituitarism to deficiencies in pituitary hormones.

• Evaluate the causes of hyperprolactinemia.

• Correlate the metabolic functions of GH (growth hormone) to the clinical features of acromegaly.

• Differentiate between the actions of GH and IGF-I (insulin-like growth factor I) in acromegaly. Apply the characteristics of disease presentation to either GH or IGF-I effects.

• Describe appropriate screening tests, as well as identify the appropriate suppression or stimulatory tests for endocrine disorders (based on the physiology of feedback loops).

Physiology Knowledge Check

• Damage to the pituitary stalk may result in an increase in:

  • A. FSH (Follicle-stimulating hormone)

  • B. GH (Growth Hormone)

  • C. ACTH (Adrenocorticotropic hormone)

  • D. PRL (Prolactin)

  • E. TSH (Thyroid-stimulating hormone)

• During a fast, GH secretion is stimulated by:

  • F. Insulin

  • G. Glucagon

  • H. Ghrelin

  • I. Somatostatin

  • J. GnRH (Gonadotropin-releasing hormone)

• The pituitary cell that produces two hormones is:

  • K. Thyrotrope

  • L. Gonadotrope

  • M. Corticotrope

  • N. Somatotrope

• A 74-year-old patient presents with headaches, difficulty concentrating, impaired memory, muscle cramps, and weakness. Laboratory values report serum sodium of 120 mmol/L. Which would be compatible with a differential diagnosis of syndrome of inappropriate ADH secretion?

  • O. Low plasma AVP (Arginine vasopressin) levels

  • P. Serum osmolarity of 265 mOsm/L

  • Q. Plasma glucose 300 mg/dL

  • R. Urinary osmolarity <400 mOsm/L

Posterior Pituitary Clinical Correlations #1

• A 32-year-old patient post-concussion showed increased urine output with low urine osmolality 24 hours later.

• Diagnosis and hormone responsible:

  • Likely diagnosis: Diabetes insipidus.

  • Hormone responsible: ADH deficiency.

Posterior Pituitary Clinical Correlations #2

• A 56-year-old man with lung cancer and a grand mal seizure has:

  • Serum [Na + ]: 110 mEq/L (normal 140)

  • Urine Osmolarity: 650 mOsm/L (concentrated)

  • Diagnosis: Likely SIADH (Syndrome of Inappropriate Antidiuretic Hormone secretion).

• Treatment: Intravenous infusion of hypertonic NaCl and demeclocycline (ADH antagonist).

Posterior Pituitary Clinical Correlations #3

• A 27-year-old female developed hypernatremia and increased dilute urine output after head trauma.

• ADH levels: Decreased.

• Effects of decreased ADH levels: Increased serum osmolarity, decreased urine osmolarity.

Case #1: Mrs. Omaya

• Chief Complaint: Extreme fatigue since childbirth 9 months ago.

• Patient Profile: 25-year-old female, previous good health, problematic lactation post-delivery, amenorrhea, weight retention, changes in skin and voice, history of postpartum hemorrhage requiring transfusion.

• Vital Signs: T 37°C, BP 100/70 mmHg, P 60/min.

• Physical Exam: Coarse skin texture, otherwise normal.

Mrs. Omaya’s Symptoms/History

• Fatigue

• Unable to lactate

• Amenorrhea

• Weight retention

• Changes in skin and voice post-pregnancy

• History: Normal pregnancy, postpartum hemorrhage.

Mrs. Omaya’s Laboratory Values

Sheehan Syndrome

• Correlating Mrs. Omaya’s symptoms:

  • Inability to lactate → indicate prolactin deficiency.

  • Amenorrhea → due to insufficient LH and FSH.

  • Weight retention/skin changes → suggest cortisol deficiency.

  • Fatigue → linked to low thyroid hormones.

• Susceptibility of Pregnant Women to Pituitary Infarction: Increased blood supply during pregnancy can make pituitary tissue vulnerable.

• Posterior Pituitary Affected: Damage may not be uniform across pituitary; often anterior lobe is significantly affected.

Prolactin Regulation and Stimulation

• Hypothalamus: Prolactin induces dopamine synthesis.

• Dopamine: Main inhibitory factor limiting prolactin production.

• Thyrotropin-releasing hormone (TRH) stimulates prolactin release.

Stimulatory Factors

• Pregnancy (induced by estrogen)

• Breast-feeding

• Sleep

• Stress

• TRH

Inhibitory Factors

• Dopamine

• Dopamine antagonists (such as bromocriptine)

• Somatostatin

• Prolactin (negative feedback)

Causes of Hyperprolactinemia

• Physiologic Causes:

  • Pregnancy

  • Nipple stimulation

  • Stress

• Pathologic Causes:

  • Lactotroph adenomas

  • Decreased dopaminergic inhibition due to hypothalamic or pituitary diseases.

  • Drug use (e.g., antipsychotics).

• Other Causes:

  • Estrogen

  • Hypothyroidism

  • Chest wall injury

  • Chronic renal failure

  • Idiopathic hyperprolactinemia

  • Macroprolactinemia

  • Genetic causes.

Serum Prolactin Levels in Pregnancy and Breastfeeding

• During pregnancy, increased levels of prolactin serve to suppress GnRH.

• Serum prolactin levels change based on:

  • Pregnancy duration (higher in later months).

  • Lactation status postpartum.

Case #2: Eloise

• Chief Complaint: Amenorrhea for 3 months post-motorcycle accident.

• Patient Profile: 28-year-old female, has gained weight, drinks and urinates more than prior to the accident, reports galactorrhea.

• Vital Signs: T 36.5°C, P 84/min, BP 95/60, BMI 29.

Eloise’s Laboratory Values

Identifying the Cause of Hyperprolactinemia

• Likely condition based on history and symptoms:

  • Ischemic necrosis of the pituitary.

  • Traumatic damage to the pituitary stalk.

  • Prolactinoma (adenoma of lactotropes).

  • Increased prolactin due to dopamine antagonist use.

  • Hypothyroidism.

Case #3: Megan

• Chief Complaint: Irregular menses and missed periods.

• Patient Profile: 30-year-old female not on hormonal contraception, normal onset of menstruation.

• Physical Exam: Normal pelvic exam.

Megan’s Laboratory Values

Identifying Causes of Megan’s Hyperprolactinemia

• Likely causes:

  • Ischemic necrosis of the pituitary.

  • Hypopituitarism due to damage to the pituitary stalk.

  • Prolactinoma (adenoma of lactotropes).

  • Increased prolactin due to a dopamine antagonist.

  • Hypothyroidism.

Identifying the Cause of Low Gonadotropin Levels in Megan

• Causes of low LH and FSH:

  • Negative feedback due to high prolactin levels.

  • Negative feedback due to stress.

  • Loss of LH and FSH production due to lactotroph hyperplasia.

  • Negative feedback from elevated estrogen levels.

PRL Suppression of LH and FSH

• Illustration of hormone dynamics:

  • Normal hormone profiles show suppression of LH and FSH by elevated prolactin levels.

Growth Hormone

• Physiologic Role of GH varies with age; typically decreases with increasing age.

Correlation Between GH Levels and Age

• GH secretion patterns demonstrate a peak during ages 3-5 years, tapering off in adulthood,

• The clinical significance of GH levels includes growth velocity in children and impacts on metabolism in adults.

Clinical Cases of Acromegaly

• 34-year-old Man: Increased shoe size, altered facial features, high IGF-1 and GH levels leading to a diagnosis of acromegaly.

• 42-year-old Jeweler: Noted physical changes and bitemporal hemianopsia, MRI revealed macroadenoma with elevated GH levels.

Sam Atotrope - Findings

• Fasting GH level: 56 ng/ml (normal: 0-5 ng/ml).

• IGF-1: 988 ng/ml (normal: 90-360 ng/ml).

• Glucose suppression test showed slow suppression (persisted elevated levels).

Metabolic Dysregulation in Acromegaly

• Considerations for metabolic effects of excess GH:

• Changes in fat, protein, and glucose metabolism correlate with the clinical features of acromegaly (visual changes, fatigue, increased appetite).

Treatment of Acromegaly

• Treatment strategies include:

  • Surgical resection of the pituitary tumor.

  • Stereotactic radiotherapy.

  • Medical therapy with somatostatin analogues (e.g. octreotide) or GH receptor antagonists.

• Note that while some symptoms may improve, skeletal changes are typically irreversible.

Diagnosis of Acromegaly

1. Biochemical confirmation by measuring IGF-I levels.

2. Oral glucose tolerance test for GH measurement indicating insufficient suppression.

3. Follow-up with pituitary MRI.

Questions?